Search results for: gene expression profiles

Authors: Akanksha Bhatnagar, Sandhya Kortegare, Felice Elefant

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Context: Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by progressive cognitive decline and memory loss. The cause of AD is not fully understood, but it is thought to be caused by a combination of genetic, environmental, and lifestyle factors. One of the hallmarks of AD is the loss of neurons in the hippocampus, a brain region that is important for memory and learning. This loss of neurons is thought to be caused by a decrease in histone acetylation, which is a process that regulates gene expression. Research Aim: The research aim of the study was to develop mall molecule compounds that can enhance the activity of Tip60, a histone acetyltransferase that is important for memory and learning. Methodology/Analysis: The researchers used in silico structural modeling and a pharmacophore-based virtual screening approach to design and synthesize small molecule compounds strongly predicted to target and enhance Tip60’s HAT activity. The compounds were then tested in vitro and in vivo to assess their ability to enhance Tip60 activity and rescue cognitive deficits in AD models. Findings: The researchers found that several of the compounds were able to enhance Tip60 activity and rescue cognitive deficits in AD models. The compounds were also developed to cross the blood-brain barrier, which is an important factor for the development of potential AD therapeutics. Theoretical Importance: The findings of this study suggest that Tip60 HAT activators have the potential to be developed as therapeutic agents for AD. The compounds are specific to Tip60, which suggests that they may have fewer side effects than other HDAC inhibitors. Additionally, the compounds are able to cross the blood-brain barrier, which is a major hurdle for the development of AD therapeutics. Data Collection: The study collected data from a variety of sources, including in vitro assays and animal models. The in vitro assays assessed the ability of compounds to enhance Tip60 activity using histone acetyltransferase (HAT) enzyme assays and chromatin immunoprecipitation assays. Animal models were used to assess the ability of the compounds to rescue cognitive deficits in AD models using a variety of behavioral tests, including locomotor ability, sensory learning, and recognition tasks. The human clinical trials will be used to assess the safety and efficacy of the compounds in humans. Questions: The question addressed by this study was whether Tip60 HAT activators could be developed as therapeutic agents for AD. Conclusions: The findings of this study suggest that Tip60 HAT activators have the potential to be developed as therapeutic agents for AD. The compounds are specific to Tip60, which suggests that they may have fewer side effects than other HDAC inhibitors. Additionally, the compounds are able to cross the blood-brain barrier, which is a major hurdle for the development of AD therapeutics. Further research is needed to confirm the safety and efficacy of these compounds in humans.

Keywords: Alzheimer's disease, cognition, neuroepigenetics, drug discovery

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Authors: Louise H. Gracioso, Marcela P.G. Baltazar, Ingrid R. Avanzi, Bruno Karolski, Luciana J. Gimenes, Claudio O. Nascimento, Elen A. Perpetuo

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Introduction: Higher copper concentrations promote a selection pressure on organisms such as plants, fungi and bacteria, which allows surviving only the resistant organisms to the contaminated site. This selective pressure keeps only the organisms most resistant to a specific condition and subsequently increases their bioremediation potential. Despite the bacteria importance for biosphere maintenance, it is estimated that only a small fraction living microbial species has been described and characterized. Due to the molecular biology development, tools based on analysis 16S ribosomal RNA or another specific gene are making a new scenario for the characterization studies and identification of microorganisms in the environment. News identification of microorganisms methods have also emerged like Biotyper (MALDI / TOF), this method mass spectrometry is subject to the recognition of spectroscopic patterns of conserved and features proteins for different microbial species. In view of this, this study aimed to isolate bacteria resistant to copper present in a Copper Processing Area (Sossego Mine, Canaan, PA) and identifies them in two different methods: Recent (spectrometry mass) and conventional. This work aimed to use them for a future bioremediation of this Mining. Material and Methods: Samples were collected at fifteen different sites of five periods of times. Microorganisms were isolated from mining wastes by culture enrichment technique; this procedure was repeated 4 times. The isolates were inoculated into MJS medium containing different concentrations of chloride copper (1mM, 2.5mM, 5mM, 7.5mM and 10 mM) and incubated in plates for 72 h at 28 ºC. These isolates were subjected to mass spectrometry identification methods (Biotyper – MALDI/TOF) and 16S gene sequencing. Results: A total of 105 strains were isolated in this area, bacterial identification by mass spectrometry method (MALDI/TOF) achieved 74% agreement with the conventional identification method (16S), 31% have been unsuccessful in MALDI-TOF and 2% did not obtain identification sequence the 16S. These results show that Biotyper can be a very useful tool in the identification of bacteria isolated from environmental samples, since it has a better value for money (cheap and simple sample preparation and MALDI plates are reusable). Furthermore, this technique is more rentable because it saves time and has a high performance (the mass spectra are compared to the database and it takes less than 2 minutes per sample).

Keywords: copper mining area, bioremediation, microorganisms, identification, MALDI/TOF, RNA 16S

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Authors: Maisa Haj-Tas, Jehad Alaraifi

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The significance of the study: This retrospective study examined the speech and language profiles of patients who received clinical services at the University of Jordan Hearing and Speech Clinic (UJ-HSC) from 2009 to 2014. The UJ-HSC clinic is located in the capital Amman and was established in the late 1990s. It is the first hearing and speech clinic in Jordan and one of first speech and hearing clinics in the Middle East. This clinic provides services to an annual average of 2000 patients who are diagnosed with different communication disorders. Examining the speech and language profiles of patients in this clinic could provide an insight about the most common disorders seen in patients who attend similar clinics in Jordan. It could also provide information about community awareness of the role of speech therapists in the management of speech and language disorders. Methodology: The researchers examined the clinical records of 1140 patients (797 males and 343 females) who received clinical services at the UJ-HSC between the years 2009 and 2014 for the purpose of data analysis for this study. The main variables examined in the study were disorder type and gender. Participants were divided into four age groups: children, adolescents, adults, and older adults. The examined disorders were classified as either speech disorders, language disorders, or dysphagia (i.e., swallowing problems). The disorders were further classified as childhood language impairments, articulation disorders, stuttering, cluttering, voice disorders, aphasia, and dysphagia. Results: The results indicated that the prevalence for language disorders was the highest (50.7%) followed by speech disorders (48.3%), and dysphagia (0.9%). The majority of patients who were seen at the JU-HSC were diagnosed with childhood language impairments (47.3%) followed consecutively by articulation disorders (21.1%), stuttering (16.3%), voice disorders (12.1%), aphasia (2.2%), dysphagia (0.9%), and cluttering (0.2%). As for gender, the majority of patients seen at the clinic were males in all disorders except for voice disorders and cluttering. Discussion: The results of the present study indicate that the majority of examined patients were diagnosed with childhood language impairments. Based on this result, the researchers suggest that there seems to be a high prevalence of childhood language impairments among children in Jordan compared to other types of speech and language disorders. The researchers also suggest that there is a need for further examination of the actual prevalence data on speech and language disorders in Jordan. The fact that many of the children seen at the UJ-HSC were brought to the clinic either as a result of parental concern or teacher referral indicates that there seems to an increased awareness among parents and teachers about the services speech pathologists can provide about assessment and treatment of childhood speech and language disorders. The small percentage of other disorders (i.e., stuttering, cluttering, dysphasia, aphasia, and voice disorders) seen at the UJ-HSC may indicate a little awareness by the local community about the role of speech pathologists in the assessment and treatment of these disorders.

Keywords: clinic, disorders, language, profile, speech

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Authors: M. G. Murtaza, E. E. Tzirtzilakis, M. Ferdows

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The mixed convective flow of MHD incompressible, steady boundary layer in heat transfer over a curved stretching sheet due to temperature dependent thermal conductivity is studied. We use curvilinear coordinate system in order to describe the governing flow equations. Finite difference solutions with central differencing have been used to solve the transform governing equations. Numerical results for the flow velocity and temperature profiles are presented as a function of the non-dimensional curvature radius. Skin friction coefficient and local Nusselt number at the surface of the curved sheet are discussed as well.

Keywords: curved stretching sheet, finite difference method, MHD, variable thermal conductivity

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Authors: Yusuf E. Mustapha, Inioluwa A Akindoyeni, Oluwatoyin G. Ezekiel, Ifeoluwa O. Awogbindin, Ebenezer O. Farombi

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Background: Parkinson's disease (PD) is the most prevalent motor disorder. Available therapies are palliative with no effect on disease progression. Kolaviron (KV), a natural anti-inflammatory and antioxidant agent, has been reported to possess neuroprotective effects in Parkinsonian flies and rats. Objective: The present study investigates the neuroprotective effect of KV, focusing on the DJ1/Nrf2 signaling pathway. Methodology: All-trans retinoic acid (ATRA, 10 mg/kg, i.p.) was used to inhibit Nrf2. Murine model of PD was established with four doses of MPTP (20 mg/kg i.p.) at 2 hours interval. MPTP mice were pre-treated with either KV (200 mg/kg/day p.o), ATRA, or both conditions for seven days before PD induction. Motor behaviour was evaluated, and markers of oxidative stress/damage and its regulators were assessed with immunofluorescence and ELISA techniques. Results: MPTP-treated mice covered less distance with reduced numbers of anticlockwise rotations, heightened freezing, and prolonged immobility when compared to control. However, KV significantly attenuated these deficits. Pretreatment of MPTP mice with KV upregulated Nrf2 expression beyond MPTP level with a remarkable reduction in Keap1 expression and marked elevation of DJ-1 level, whereas co-administration with ATRA abrogated these effects. KV treatment restored MPTP-mediated depletion of endogenous antioxidant, striatal oxidative stress, oxidative damage, and inhibition of acetylcholinesterase activity. However, ATRA treatment potentiated acetylcholinesterase inhibition and attenuated the protective effect of KV on the level of nitric oxide and activities of catalase and superoxide dismutase. Conclusion: Kolaviron protects Parkinsonian mice by stabilizing and activating the Nrf2 signaling pathway. Thus, kolaviron can be explored as a pharmacological lead in PD management.

Keywords: Garcinia kola, Kolaviron, Parkinson Disease, Nrf2, behavioral incompetence, neurodegeneration

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Authors: Passkorn Khanthongthip, John T. Novak

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Many studies have been reported that the nZVI and MgO NPs were often found in waste activated sludge (WAS). However, little is known about the impact of those NPs on WAS stabilization. The aims of this study were to investigate the effects of both NPs on WAS anaerobic digestion for methane production and to examine the change of metanogenic population under those different environments using qPCR. Four dosages (2, 50, 100, and 200 mg/g-TSS) of MgO NPs were added to four different bottles containing WAS to investigate the impact of MgO NPs on methane production during WAS anaerobic digestion. The effects of nZVI on methane production during WAS anaerobic digestion were also conducted in another four bottles using the same methods described above except that the MgO NPs were replaced by nZVI. A bottle of WAS anaerobic digestion without nanoparticles addition was also operated to serve as a control. It was found that the relative amounts, compared to the control system, of methane production in each WAS anaerobic digestion bottle adding 2, 50, 100, 200 mg/gTSS MgO NPs were 98, 62, 28, and 14 %, respectively. This suggests that higher MgO NPs resulted in lower methane production. The data of batch test for the effects of corresponding released Mg2+ indicated that 50 mg/gTSS MgO NPs or higher could inhibit methane production at least 25%. Moreover, the volatile fatty acid (VFA) concentration was 328, 384, 928, 3,684, and 7,848 mg/L for the control and four WAS anaerobic digestion bottles with 2, 50, 100, 200 mg/gTSS MgO NPs addition, respectively. Higher VFA concentration could reduce pH and subsequently decrease methanogen growth, resulting in lower methane production. The relative numbers of total gene copies of methanogens analyzed from samples taken from WAS anaerobic digestion bottles were approximately 99, 68, 38, and 24 % of control for the addition of 2, 50, 100, and 200 mg/gTSS, respectively. Obviously, the more MgO NPs appeared in sludge anaerobic digestion system, the less methanogens remained. In contrast, the relative amount of methane production found in another four WAS anaerobic digestion bottles adding 2, 50, 100, and 200 mg/gTSS nZVI were 102, 128, 112, and 104 % of the control, respectively. The measurement of methanogenic population indicated that the relative content of methanogen gene copies were 101, 132, 120, and 112 % of those found in control, respectively. Additionally, the cumulative VFA was 320, 234, 308, and 330 mg/L, respectively. This reveals that nZVI addition could assist to increase methanogenic population. Higher amount of methanogen accelerated VFA degradation for greater methane production, resulting in lower VFA accumulation in digesters. Moreover, the data for effects of corresponding released Fe2+ conducted by batch tests suggest that the addition of approximately 50 mg/gTSS nZVI increased methane production by 20%. In conclusion, the presence of MgO NPs appeared to diminish the methane production during WAS anaerobic digestion. Higher MgO NPs dosages resulted in more inhibition on methane production. In contrast, nZVI addition promoted the amount of methanogenic population which facilitated methane production.

Keywords: magnesium oxide nanoparticles, methane production, methanogenic population, nano zerovalent iron

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Authors: Hamsa T. Tayeb, Mohammad A. Arafah, Dana M. Bakheet, Duaa M. Khalaf, Agnieszka Tarnoska, Nduna Dzimiri

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Background: CYP2D6 is a member of the cytochrome P450 mixed-function oxidase system. The enzyme is responsible for the metabolism and elimination of approximately 25% of clinically used drugs, especially in breast cancer and psychiatric therapy. Different phenotypes have been described displaying alleles that lead to a complete loss of enzyme activity, reduced function (poor metabolizers – PM), hyperfunctionality (ultrarapid metabolizers–UM) and therefore drug intoxication or loss of drug effect. The prevalence of these variants may vary among different ethnic groups. Furthermore, the xTAG system has been developed to categorized all patients into different groups based on their CYP2D6 substrate metabolization. Aim of the study: To determine the prevalence of the different CYP2D6 variants in our population, and to evaluate their clinical relevance in personalized medicine. Methodology: We used the Luminex xMAP genotyping system to sequence 305 Saudi individuals visiting the Blood Bank of our Institution and determine which polymorphisms of CYP2D6 gene are prevalent in our region. Results: xTAG genotyping showed that 36.72% (112 out of 305 individuals) carried the CYP2D6_*2. Out of the 112 individuals with the *2 SNP, 6.23% had multiple copies of *2 SNP (19 individuals out of 305 individuals), resulting in an UM phenotype. About 33.44% carried the CYP2D6_*41, which leads to decreased activity of the CYP2D6 enzyme. 19.67% had the wild-type alleles and thus had normal enzyme function. Furthermore, 15.74% carried the CYP2D6_*4, which is the most common nonfunctional form of the CYP2D6 enzyme worldwide. 6.56% carried the CYP2D6_*17, resulting in decreased enzyme activity. Approximately 5.73% carried the CYP2D6_*10, consequently decreasing the enzyme activity, resulting in a PM phenotype. 2.30% carried the CYP2D6_*29, leading to decreased metabolic activity of the enzyme, and 2.30% carried the CYP2D6_*35, resulting in an UM phenotype, 1.64% had a whole-gene deletion CYP2D6_*5, thus resulting in the loss of CYP2D6 enzyme production, 0.66% carried the CYP2D6_*6 variant. One individual carried the CYP2D6_*3(B), producing an inactive form of the enzyme, which leads to decrease of enzyme activity, resulting in a PM phenotype. Finally, one individual carried the CYP2D6_*9, which decreases the enzyme activity. Conclusions: Our study demonstrates that different CYP2D6 variants are highly prevalent in ethnic Saudi Arabs. This finding sets a basis for informed genotyping for these variants in personalized medicine. The study also suggests that xTAG is an appropriate procedure for genotyping the CYP2D6 variants in personalized medicine.

Keywords: CYP2D6, hormonal breast cancer, pharmacogenetics, polymorphism, psychiatric treatment, Saudi population

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Authors: Csaba Tóth, Éva Lakatos, László Pethő, Seoyoung Cho

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The temperature effect on asphalt pavement structure is a crucial factor at the design stage. In this paper, by applying the German guidelines for temperature along the asphalt depth is estimated. The aim is to consider temperature profiles in different seasons in numerical modelling. The model is built with an elastic and isotropic solid element with 19 subdivisions of asphalt layers to reflect the temperature variation. Comparison with the simple three-layer pavement system (asphalt layers, base, and subgrade layers) will be followed to see the difference in result without temperature variation along with the depth. Finally, the fatigue life calculation was checked to prove the validity of the methodology of considering the temperature in the numerical modelling.

Keywords: temperature profile, flexible pavement modeling, finite element method, temperature modeling

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Authors: Oindrila Nath, S. Sridharan

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Long-term (2002-2012) temperature and ozone measurements by Sounding of Atmosphere by Broadband Emission Radiometry (SABER) instrument onboard Thermosphere, Ionosphere, Mesosphere Energetics and Dynamics (TIMED) satellite zonally averaged over 10°N-15°N are used to study their long-term changes and their responses to solar cycle, quasi-biennial oscillation and El Nino Southern Oscillation. The region is selected to provide more accurate long-term trends and variabilities, which were not possible earlier with lidar measurements over Gadanki (13.5°N, 79.2°E), which are limited to cloud-free nights, whereas continuous data sets of SABER temperature and ozone are available. Regression analysis of temperature shows a cooling trend of 0.5K/decade in the stratosphere and that of 3K/decade in the mesosphere. Ozone shows a statistically significant decreasing trend of 1.3 ppmv per decade in the mesosphere although there is a small positive trend in stratosphere at 25 km. Other than this no significant ozone trend is observed in stratosphere. Negative ozone-QBO response (0.02ppmv/QBO), positive ozone-solar cycle (0.91ppmv/100SFU) and negative response to ENSO (0.51ppmv/SOI) have been found more in mesosphere whereas positive ozone response to ENSO (0.23ppmv/SOI) is pronounced in stratosphere (20-30 km). The temperature response to solar cycle is more positive (3.74K/100SFU) in the upper mesosphere and its response to ENSO is negative around 80 km and positive around 90-100 km and its response to QBO is insignificant at most of the heights. Composite monthly mean of ozone volume mixing ratio shows maximum values during pre-monsoon and post-monsoon season in middle stratosphere (25-30 km) and in upper mesosphere (85-95 km) around 10 ppmv. Composite monthly mean of temperature shows semi-annual variation with large values (~250-260 K) in equinox months and less values in solstice months in upper stratosphere and lower mesosphere (40-55 km) whereas the SAO becomes weaker above 55 km. The semi-annual variation again appears at 80-90 km, with large values in spring equinox and winter months. In the upper mesosphere (90-100 km), less temperature (~170-190 K) prevails in all the months except during September, when the temperature is slightly more. The height profiles of amplitudes of semi-annual and annual oscillations in ozone show maximum values of 6 ppmv and 2.5 ppmv respectively in upper mesosphere (80-100 km), whereas SAO and AO in temperature show maximum values of 5.8 K and 4.6 K in lower and middle mesosphere around 60-85 km. The phase profiles of both SAO and AO show downward progressions. These results are being compared with long-term lidar temperature measurements over Gadanki (13.5°N, 79.2°E) and the results obtained will be presented during the meeting.

Keywords: trends, QBO, solar cycle, ENSO, ozone, temperature

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Authors: Nurjannatul Naim Kamaruddin, Tengku Sifziuzl Tengku Muhammad, Aina Farahiyah Abdul Manan, Habsah Mohamad

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Atherosclerosis which leads to cardiovascular diseases such as myocardial infarction, unstable angina (ischemic heart pain), sudden cardiac death and stroke is the principal cause of death worldwide. It has been a very critical issue as current common drug treatment, statin therapy has left bad side effects like rhabdomyolysis, atrial fibrillation, liver disease, abdominal and chest pain. Interestingly, the discoveries of proprotein convertase subtilisin-kexin type 9 have paved a new way in the treatment of atherosclerosis. This serine protease is believed to involve in the regulation of LDL- uptake by LDL-receptor. Therefore, this study was conducted to evaluate the potential of Acanthaster plancii fractions to reduce the transcriptional activity of the PCSK9 promoter. In this study, the marine organism which is Acanthaster plancii has been used as the source for marine compounds in inhibiting PCSK9. The cytotoxicity activity of ten fractions from the methanol extracts of Acanthaster plancii was investigated on HepG2 cell lines using MTS assay and dual glo luciferase assay was carried out later to analyses the effects of the samples in reducing the transcriptional activity of the PCSK9 promoter. Both assays used fractions with five different concentrations, 3.13µg/mL, 6.25µg/mL, 12.5µg/mL, 25µg/mL, and 50µg/mL. MTS assay indicated that the fractions are non-cytotoxic towards HepG2 cell lines as their IC50 value is greater than 30µg/mL. Whilst, for the dual glo luciferase assay, among all the fractions, Enhance Fraction 2 (EF2) showed the best potential in reducing the transcriptional activity of the PCSK9 promoter. The results indicated that this EF2 gave the lowest PCSK9 promoter expression at low concentration which is 0.2 fold change at 6.25µg/mL. This finding suggested that further analysis should be done to validate the potential of Acanthaster plancii as the source of anti-atherosclerotic agent.

Keywords: Acanthaster plancii, atherosclerosis, luciferase assay, PCSK9

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Authors: Nuha Mansour Alhazmi, Magda Mohamed Aly, Fardus M. Bokhari, Ahmed Bahieldin, Sherif Edris

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Out of 30 fungal isolates, 2 new isolates were proven to degrade poly-β-hydroxybutyrate (PHB). Enzyme assay for these isolates indicated the optimal environmental conditions required for depolymerase enzyme to induce the highest level of biopolymer degradation. The two isolates were basically characterized at the morphological level as Trichoderma asperellum (isolate S1), and Aspergillus fumigates (isolate S2) using standard approaches. The aim of the present study was to characterize these two isolates at the molecular level based on the highly diverged rRNA gene(s). Within this gene, two domains of the ribosome large subunit (LSU) namely internal transcribed spacer (ITS) and 26S were utilized in the analysis. The first domain comprises the ITS1/5.8S/ITS2 regions ( > 500 bp), while the second domain comprises the D1/D2/D3 regions ( > 1200 bp). Sanger sequencing was conducted at Macrogen (Inc.) for the two isolates using primers ITS1/ITS4 for the first domain, while primers LROR/LR7 for the second domain. Sizes of the first domain ranged between 594-602 bp for S1 isolate and 581-594 bp for S2 isolate, while those of the second domain ranged between 1228-1238 bp for S1 isolate and 1156-1291 for S2 isolate. BLAST analysis indicated 99% identities of the first domain of S1 isolate with T. asperellum isolates XP22 (ID: KX664456.1), CTCCSJ-G-HB40564 (ID: KY750349.1), CTCCSJ-F-ZY40590 (ID: KY750362.1) and TV (ID: KU341015.1). BLAST of the first domain of S2 isolate indicated 100% identities with A. fumigatus isolate YNCA0338 (ID: KP068684.1) and strain MEF-Cr-6 (ID: KU597198.1), while 99% identities with A. fumigatus isolate CCA101 (ID: KT877346.1) and strain CD1621 (ID: JX092088.1). Large numbers of other T. asperellum and A. fumigatus isolates and strains showed high level of identities with S1 and S2 isolates, respectively, based on the diversity of the first domain. BLAST of the second domain of S1 isolate indicated 99 and 100% identities with only two strains of T. asperellum namely TR 3 (ID: HM466685.1) and G (ID: KF723005.1), respectively. However, other T. species (ex., atroviride, hamatum, deliquescens, harzianum, etc.) also showed high level of identities. BLAST of the second domain of S2 isolate indicated 100% identities with A. fumigatus isolate YNCA0338 (ID: KP068684.1) and strain MEF-Cr-6 (ID: KU597198.1), while 99% identities with A. fumigatus isolate CCA101 (ID: KT877346.1) and strain CD1621 (ID: JX092088.1). Large numbers of other A. fumigatus isolates and strains showed high level of identities with S2 isolate. Overall, the results of molecular characterization based on rRNA diversity for the two isolates of T. asperellum and A. fumigatus matched those obtained by morphological characterization. In addition, ITS domain proved to be more sensitive than 26S domain in diversity profiling of fungi at the species level.

Keywords: Aspergillus fumigates, Trichoderma asperellum, PHB, degradation, BLAST, ITS, 26S, rRNA

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Authors: Halima Albalushi, Mohadese Boroojerdi, Murtadha Alkhabori

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Introduction: Maintenance of stem cell properties during culture necessitates the recreation of the natural cell niche. Studies reported the promising outcome of mesenchymal stem cells (MSC) properties maintenance after using extracellular matrix such as CELLstart™, which is the recommended coating material for stem cells cultured in serum-free and xeno-free conditions. Laminin-521 is known as a crucial adhesion protein, which is found in natural stem cell niche, and plays an important role in facilitating the maintenance of self-renewal, pluripotency, standard morphology, and karyotype of human pluripotent stem cells (PSCs). The aim of this study is to investigate the effects of Laminin-521 on human umbilical cord-derived mesenchymal stem cells (UC-MSC) characteristics as a step toward clinical application. Methods: Human MSC were isolated from the umbilical cord via the explant method. Umbilical cord-derived-MSC were cultured in serum-free and xeno-free conditions in the presence of Laminin-521 for six passages. Cultured cells were evaluated by morphology and expansion index for each passage. Phenotypic characterization of UC-MSCs cultured on Laminin-521 was evaluated by assessment of cell surface markers. Results: Umbilical cord derived-MSCs formed small colonies and expanded as a homogeneous monolayer when cultured on Laminin-521. Umbilical cord derived-MSCs reached confluence after 4 days in culture. No statistically significant difference was detected in all passages when comparing the expansion index of UC-MSCs cultured on LN-521 and CELLstart™. Phenotypic characterization of UC-MSCs cultured on LN-521 using flow cytometry revealed positive expression of CD73, CD90, CD105 and negative expression of CD34, CD45, CD19, CD14 and HLA-DR.Conclusion: Laminin-521 is comparable to CELLstart™ in supporting UC-MSCs expansion and maintaining their characteristics during culture in xeno-free and serum-free culture conditions.

Keywords: mesenchymal stem cells, culture, laminin-521, xeno-free serum-free

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Authors: Ripon Sarkar, Kabita Chaterjee, Ananya Barui

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Smoking is one of the leading causes of oral cancer. Cigarette smoke affects various cellular parameters and alters molecular metabolism of cells. Epithelial cells losses their cytoskeleton structure, membrane integrity, cellular polarity that subsequently initiates the process of epithelial cells to mesenchymal transition due to long exposure of cigarette smoking. It changes the normal cellular metabolic activity which induces oxidative stress and enhances the reactive oxygen spices (ROS) formation. Excessive ROS and associated oxidative stress are considered to be a driving force in alteration in cellular phenotypes, polarity distribution and mitochondrial metabolism. Noninvasive assessment of such parameters plays essential role in development of routine screening system for early diagnosis of oral cancer. Electrical cell-substrate impedance sensing (ECIS) is one of such method applied for detection of cellular membrane impedance which can be correlated to cell membrane integrity. Present study intends to explore the alteration in cellular impedance along with the expression of cellular polarity molecules and cytoskeleton distributions in oral epithelial cells of habitual smokers and to correlate the outcome to that of clinically diagnosed oral leukoplakia and oral squamous cell carcinoma patients. Total 80 subjects were categorized into four study groups: nonsmoker (NS), cigarette smoker (CS), oral leukoplakia (OLPK) and oral squamous cell carcinoma (OSCC). Cytoskeleton distribution was analyzed by staining of actin filament and generation of ROS was measured using assay kit using standard protocol. Cell impedance was measured through ECIS method at different frequencies. Expression of E-cadherin and protease-activated receptor (PAR) proteins were observed through immune-fluorescence method. Distribution of actin filament is well organized in NS group however; distribution pattern was grossly varied in CS, OLPK and OSCC. Generation of ROS was low in NS which subsequently increased towards OSCC. Expressions of E-cadherin and change in cellular electrical impedance in different study groups indicated the hallmark of cancer progression from NS to OSCC. Expressions of E-cadherin, PAR protein, and cell impedance were decreased from NS to CS and farther OSCC. Generally, the oral epithelial cells exhibit apico-basal polarity however with cancer progression these cells lose their characteristic polarity distribution. In this study expression of polarity molecule and ECIS observation indicates such altered pattern of polarity among smoker group. Overall the present study monitored the alterations in intracellular ROS generation and cell metabolic function, membrane integrity in oral epithelial cells in cigarette smokers. Present study thus has clinical significance, and it may help in developing a noninvasive technique for early diagnosis of oral cancer amongst susceptible individuals.

Keywords: cigarette smoking, early oral cancer detection, electric cell-substrate impedance sensing, noninvasive screening

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Authors: Flóra Karsai-Rektenwald, Khongorzul Odgerel, Vanda Villányi, Zoltán Gábor Tóth, Zsófia Bánfalvi

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GIGANTEA (GI) is a plant-specific, circadian clock-regulated, nuclear protein involved in diverse processes from flowering to stress responses. In the obligate short-day tuberising Andigenum Group potatoes, GI is indirectly involved in determination of the time of tuber initiation. The goal of our study was to get information on the function of GI in the day-length independent tuberising commercial potato cultivar ‘Désirée’, a tetraploid plant carrying two GI genes, one on chromosome 4 (GI.04) and another one on chromosome 12 (GI.12). Functional analysis of the two GI genes was attempted by targeted mutagenesis using the CRISPR-Cas9 system. Two sets of mutants were generated. The mutations were mapped at nucleotide level and the plants grown in a greenhouse. GI is located in the nucleus and interacts with at least five proteins. Three out of them, two photoreceptors and FKF1, bind on GI close to the nuclear localisation (NLS) signal to the so called LOV domain. In Andigenum Group potatoes, FKF1 interacts not only with GI but form a triplex with CDF1, a positive regulator of tuberisation, and transport it to proteasomes, where CDF1 is degraded. Three GI.04 and three GI.12 null mutants were selected from the first set of mutagenesis. Although, the deletions did not reach the NLS and LOV domain in any of the six mutants all GI. 04 and two GI.12 mutants were shorter than the control suggesting that both GIs are involved in vegetative growth regulation and the deleted region might be important in terms of conformation or stability of the proteins. From the second set of mutagenesis, three null mutants carrying mutations in one of the two GI genes and three mutants carrying mutations in both GI genes were selected for detailed analysis. Deletions in the GI mutants of this set disrupted the NLS and extended to the LOV domain. Nevertheless, none of the single GI gene mutations influenced the time of tuberisation or the tuber number and yield, whereas one of the GI.04 and all GI.12 mutants were shorter than the ‘Désirée’ control. Furthermore, all GI.12 mutants showed early senescence. The early senescence of mutants carrying mutations in both GI genes was even more pronounced, resulting in substantial yield loss in one of the double mutants. These results raise the possibility that the two GI genes can substitute each other in term of tuberisation or they are not involved in it, the yield loss is due to the early death of the plants. To distinguish between the two possibilities yeast two-hybrid experiments were initiated to detect the interaction between the GI proteins and FKF1 and between FKF1 and CDF1 originated from ‘Désirée’.

Keywords: gene editing, tuberisation, senescence, Solanum tuberosum

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Authors: Yazhi Huang, Jing Yang, Dingge Ying, Yan Zhang, Vorasuk Shotelersuk, Nattiya Hirankarn, Pak Chung Sham, Yu Lung Lau, Wanling Yang

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Human leukocyte antigen (HLA) typing from next generation sequencing (NGS) data has the potential for applications in clinical laboratories and population genetic studies. Here we introduce a novel technique for HLA typing from NGS data based on read-mapping using a comprehensive reference panel containing all known HLA alleles and de novo assembly of the gene-specific short reads. An accurate HLA typing at high-digit resolution was achieved when it was tested on publicly available NGS data, outperforming other newly-developed tools such as HLAminer and PHLAT.

Keywords: human leukocyte antigens, next generation sequencing, whole exome sequencing, HLA typing

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Authors: Efe Gumuslu, Guclu Insel, Gülten Yuksek, Nilay Sayi Ucar, Emine Ubay Cokgor, Tuğba Olmez Hanci, Didem Okutman Tas, Fatoş Germirli Babuna, Derya Firat Ertem, Ökmen Yildirim, Özge Erturan, Betül Kirci

Abstract:

Although water reclamation and reuse are inseparable parts of sustainable production concept all around the world, current levels of reuse constitute only a small fraction of the total volume of industrial effluents. Nowadays, within the perspective of serious climate change, wastewater reclamation and reuse practices should be considered as a requirement. Industrial sector is one of the largest users of water sources. The OECD Environmental Outlook to 2050 predicts that global water demand for manufacturing will increase by 400% from 2000 to 2050 which is much larger than any other sector. Metal finishing industry is one of the industries that requires high amount of water during the manufacturing. Therefore, actions regarding the improvement of wastewater treatment and reuse should be undertaken on both economic and environmental sustainability grounds. Process wastewater can be reused for more purposes if the appropriate treatment systems are installed to treat the wastewater to the required quality level. Recent studies showed that membrane separation techniques may help in solving the problem of attaining a suitable quality of water that allows being recycled back to the process. The metal finishing factory where this study is conducted is one of the biggest white-goods manufacturers in Turkey. The sheet metal parts used in the cookers production have to be exposed to surface pre-treatment processes composed of degreasing, rinsing, nanoceramics coating and deionization rinsing processes, consecutively. The wastewater generating processes in the factory are enamel coating, painting and styrofoam processes. In the factory, the main source of water is the well water. While some part of the well water is directly used in the processes after passing through resin treatment, some portion of it is directed to the reverse osmosis treatment to obtain required water quality for enamel coating and painting processes. In addition to these processes another important source of water that can be considered as a potential water source is rainwater (3660 tons/year). In this study, process profiles as well as pollution profiles were assessed by a detailed quantitative and qualitative characterization of the wastewater sources generated in the factory. Based on the preliminary results the main water sources that can be considered for reuse in the processes were determined as painting and styrofoam processes.

Keywords: enamel coating, painting, reuse, wastewater

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Authors: M. Bhattarai, B. B. Rana, M. Kamimukai, I. Takamure, T. Kawano, M. Murai

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The sd1-d allele at the sd1 locus on chromosome 1, originating from Taiwanese variety Dee-geo-woo-gen, has been playing important role for developing short-culm and lodging-resistant indica varieties such as IR36 in rice. The dominant allele SD1 for long culm at the locus is differentiated into SD1-in and SD1-ja which are harbored in indica and japonica subspecies’s, respectively. The sd1-d of an indica variety IR36 was substituted with SD1-in or SD1-ja by recurrent backcrosses of 17 times with IR36, and two isogenic tall lines regarding the respective dominant alleles were developed by using an indica variety IR5867 and a japonica one ‘Koshihikari’ as donors, which were denoted by '5867-36' and 'Koshi-36', respectively. The present study was conducted to examine the effect of sd1-d on yield and related traits as compared with SD1-in and SD1-ja, by using the two isogenic tall lines. Seedlings of IR36 and the two isogenic lines were transplanted on an experimental field of Kochi University, by the planting distance of 30 cm × 15 cm with two seedlings per hill, on May 3, 2017. Chemical fertilizers were supplied by basal application and top-dressing at a rate of 8.00, 6.57 and 7.52 g/m², respectively, for N, P₂O₅ and K₂O in total. Yield, yield components, and other traits were measured. Culm length (cm) was in the order of 5867-36 (101.9) > Koshi-36 (80.1) > IR36 (60.0), where '>' indicates statistically significant difference at the 5% level. Accordingly, sd1-d reduced culm by 41.9 and 20.1 cm, compared with SD1-in and SD1-ja, respectively, and the effect of elongating culm was higher in the former allele than in the latter one. Total brown rice yield (g/m²), including unripened grains, was in the order of IR36 (611) ≧ 5867-36 (586) ≧ Koshi-36 (572), indicating non-significant differences among them. Yield-1.5mm sieve (g/m²) was in the order of IR36 (596) ≧ 5867-36 (575) ≧ Koshi-36 (558). Spikelet number per panicle was in the order of 5867-36 (89.2) ≧ IR36 (84.7) ≧ Koshi-36 (79.8), and 5867-36 > Koshi-36. Panicle number per m² was in the order of IR36 (428) ≧ Koshi-36 (403) ≧ 5867-36 (353), and IR36 > 5867-36, suggesting that sd1-d increased number of panicles compared with SD1-in. Ripened-grain percentage-1.5mm sieve was in the order of Koshi-36 (86.0) ≧ 5867-36 (85.0) ≧ IR36 (82.7), and Koshi-36 > IR36. Thousand brown-rice-grain weight-1.5mm sieve (g) was in the order of 5867-36 (21.5) > Koshi-36 (20.2) ≧ IR36 (19.9). Total dry weight at maturity (g/m²) was in the order of 5867-36 (1404 ) ≧ IR36 (1310) ≧ Kosihi-36 (1290). Harvest index of total brown rice (%) was in the order of IR36 (39.6) > Koshi-36 (37.7) > 5867-36 (35.5). Hence, sd1-d did not exert significant effect on yield in indica genetic background. However, lodging was observed from the late stage of maturity in 5867-36 and Koshi-36, particularly in the former, which was principally due to their long culms. Consequently, sd1-d enables higher yield with higher fertilizer application, by enhancing lodging resistance, particularly in indica subspecies.

Keywords: rice, dwarfing gene, sd1-d, SD1-in, SD1-ja, yield

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Authors: Eryati Darwin, Arina Widya Murni, Adnil Edwin Nurdin

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Background: Functional dyspepsia (FD) is a highly prevalent and heterogeneous disorder. Most patients with FD complain of symptoms related to the intake of meals. Psychological stress may promote peptic ulcer and had an effect on ulcers associated Hp, and may also trigger worsen symptoms in inflammatory disorders of the gastrointestinal. Cells in mucosal gastric stimulate the production of several cytokines, which might associated with Helicobacter pylori infection. The cascade of biological events leading to stress-induced FD remains poorly understood. Aim of Study: To determine the prion-flammatory cytokine IL-6, and Helicobacter pylori activity on mucosal gastric of FD and their association with psychological stress. Methods: The subjects of this study were dyspeptic patients who visited M. Djamil General Hospital and in two Community Health Centers in Padang. On the basis of the stress index scale to identify psychological stress by using Depression Anxiety and Stress Scale (DASS 42), subjects were divided into two groups of 20 each, stress groups and non-stress groups. All diagnoses were confirmed by review of cortisol and esophagogastroduodenoscopy reports. Gastric biopsy samples and peripheral blood were taken during diagnostic procedures. Immunohistochemistry methods were used to determine the expression of IL-6 and Hp in gastric mucosal. The data were statistically analyzed by univariate and bivariate analysis. All procedures of this study were approved by Research Ethics Committee of Medical Faculty Andalas University. Results: In this study, we enrolled 40 FD patients (26 woman and 14 men) in range between 35-56 years old. Cortisol level of blood FD patients as parameter of stress hormone which taken in the morning was significantly higher in stress group than non-stress group. The expression of IL-6 in gastric mucosa was significantly higher in stress group in compared to non-stress group (p<0,05). Helicobacter pylori activity in gastric mucosal in stress group were significantly higher than non-stress group. Conclusion: The present study showed that psychological stress can induce gastric mucosal inflammation and increase of Helicobacter pylori activity.

Keywords: functional dyspepsia, Helicobacter pylori, interleukin-6, psychological stress

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Authors: Rasha Ali Dheyab

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In today's increasingly interconnected and technologically-driven world, communication has evolved beyond traditional verbal exchanges. This paper delves into the fascinating realm of multimodal communication, a dynamic field at the intersection of linguistics, gesture studies, and technology. The study of how humans convey meaning through a combination of spoken language, gestures, facial expressions, and digital platforms has gained prominence as our modes of interaction continue to diversify. This exploration begins by examining the foundational theories in linguistics and gesture studies, tracing their historical development and mutual influences. It further investigates the role of nonverbal cues, such as gestures and facial expressions, in augmenting and sometimes even altering the meanings conveyed by spoken language. Additionally, the paper delves into the modern technological landscape, where emojis, GIFs, and other digital symbols have emerged as new linguistic tools, reshaping the ways in which we communicate and express emotions. The interaction between traditional and digital modes of communication is a central focus of this study. The paper investigates how technology has not only introduced new modes of expression but has also influenced the adaptation of existing linguistic and gestural patterns in online discourse. The emergence of virtual reality and augmented reality environments introduces yet another layer of complexity to multimodal communication, offering new avenues for studying how humans navigate and negotiate meaning in immersive digital spaces. Through a combination of literature review, case studies, and theoretical analysis, this paper seeks to shed light on the intricate interplay between language, gesture, and technology in the realm of multimodal communication. By understanding how these diverse modes of expression intersect and interact, we gain valuable insights into the ever-evolving nature of human communication and its implications for fields ranging from linguistics and psychology to human-computer interaction and digital anthropology.

Keywords: multimodal communication, linguistics ., gesture studies., emojis., verbal communication., digital

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Authors: Elmo Thiago Lins Cöuras Ford, Valentina Alessandra Carvalho do Vale, Rubens Maribondo do Nascimento, José Ubiragi de Lima Mendes

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Given the unquestionable need of environmental preservation of discarded industrial residues, The scrape of tires have been seen as a salutary alternative for addictive in concrete, asphalt production and of other composites materials. In this work, grew a composite the base of scrape of tire as reinforcement and latex as matrix, to be used as insulating thermal in "cold" systems (0º). Analyzed the acting of the material was what plays the thermal conservation when submitted the flow of heat. Verified the temperature profiles in the internal surfaces and it expresses of the composite as well as the temperature gradient in the same. As a consequence, in function of the answers of the system, conclusions were reached.

Keywords: cold system, latex, flow of heat, asphalt production

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Authors: Faizan Tariq, Moayid Ali Zaidi

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Facial emotion recognition algorithms are expanding rapidly now a day. People are using different algorithms with different combinations to generate best results. There are six basic emotions which are being studied in this area. Author tried to recognize the facial expressions using object detector algorithms instead of traditional algorithms. Two object detection algorithms were chosen which are Faster R-CNN and YOLO. For pre-processing we used image rotation and batch normalization. The dataset I have chosen for the experiments is Static Facial Expression in Wild (SFEW). Our approach worked well but there is still a lot of room to improve it, which will be a future direction.

Keywords: face recognition, emotion recognition, deep learning, CNN

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Authors: Bahar Salavati Vie Le Sage, Ismaïl Ben Hariz, Flavien Viguier, Sirine Noura Kahil, Audrey Jacquin, Maxime Convert

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The ballast layer plays a key role in railroad maintenance and the geometry of the track structure. Ballast also holds the track in place as the trains roll over it. Track ballast is packed between the sleepers and on the sides of railway tracks. An imbalance in ballast volume on the tracks can lead to safety issues as well as a quick degradation of the overall quality of the railway segment. If there is a lack of ballast in the track bed during the summer, there is a risk that the rails will expand and buckle slightly due to the high temperatures. Furthermore, the knowledge of the ballast quantities that will be excavated during renewal works is important for efficient ballast management. The volume of excavated ballast per meter of track can be calculated based on excavation depth, excavation width, volume of track skeleton (sleeper and rail) and sleeper spacing. Since 2012, SNCF has been collecting 3D points cloud data covering its entire railway network by using 3D laser scanning technology (LiDAR). This vast amount of data represents a modelization of the entire railway infrastructure, allowing to conduct various simulations for maintenance purposes. This paper aims to present an automated method for ballast volume estimation based on the processing of LiDAR data. The estimation of abnormal volumes in ballast on the tracks is performed by analyzing the cross-section of the track. Further, since the amount of ballast required varies depending on the track configuration, the knowledge of the ballast profile is required. Prior to track rehabilitation, excess ballast is often present in the ballast shoulders. Based on 3D laser scans, a Digital Terrain Model (DTM) was generated and automatic extraction of the ballast profiles from this data is carried out. The surplus in ballast is then estimated by performing a comparison between this ballast profile obtained empirically, and a geometric modelization of the theoretical ballast profile thresholds as dictated by maintenance standards. Ideally, this excess should be removed prior to renewal works and recycled to optimize the output of the ballast renewal machine. Based on these parameters, an application has been developed to allow the automatic measurement of ballast profiles. We evaluated the method on a 108 kilometers segment of railroad LiDAR scans, and the results show that the proposed algorithm detects ballast surplus that amounts to values close to the total quantities of spoil ballast excavated.

Keywords: ballast, railroad, LiDAR , cloud point, track ballast, 3D point

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Authors: Mladen Milicevic

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In this paper, subjective film sound will be addressed as it gets represented in narrative cinema. First, 'meta-diegetic' sound will be briefly explained followed by transition to “oneiric” sound. The representation of oneiric sound refers to a situation where film characters are experiencing some sort of an altered state of consciousness. Looking at an antlered state of consciousness in terms of human brain processes will point out to the cinematic ways of expression, which 'mimic' those processes. Using several examples for different films will illustrate these points.

Keywords: oneiric, ASC, film, sound

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Authors: Fatemeh Elmi, Zahra Etemadifar

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Improvement of soil mechanical properties is crucial before its use in construction, as the low mechanical strength and unstable structure of soil in many parts of the world can lead to the destruction of engineering infrastructure, resulting in financial and human losses. Although, conventional methods, such as chemical injection, are often utilized to enhance soil strength and stiffness, they are generally expensive, require heavy machinery, and cause significant environmental effects due to chemical usage, and also disrupt urban infrastructure. Moreover, they are not suitable for treating large volume of soil. Recently, an alternative method to improve various soil properties, including strength, hardness, and permeability, has received much attention: the application of biological methods. One of the most widely used is biocementation, which is based on the microbial precipitation of calcium carbonte crystalls using ureolytic bacteria However, there are still limitations to its large-scale use that need to be resolved before it can be commercialized. These issues have not received enough attention in prior research. One limitation of MICP (microbially induced calcium carbonate precipitation) is that microorganisms cannot operate effectively in harsh and variable environments, unlike the controlled conditions of a laboratory. Another limitation of applying this technique on a large scale is the high cost of producing a substantial amount of bacterial culture and reagents required for soil treatment. Therefore, the purpose of the present study was to investigate soil improvement using the biocementation activity of poly-extremophile, calcium carbonate crystal- producing bacterial strain, Bhargavaea cecembensis N1, in whey as an inexpensive medium. This strain was isolated and molecularly identified from sandy soils in our previous research, and its 16S rRNA gene sequences was deposited in the NCBI Gene Bank with an accession number MK420385. This strain exhibited a high level of urease activity (8.16 U/ml) and produced a large amount of calcium carbonate (4.1 mg/ ml). It was able to improve the soil by increasing the compressive strength up to 205 kPa and reducing permeability by 36%, with 20% of the improvement attributable of calcium carbonate production. This was achieved using this strain in a whey culture medium. This strain can be an eco-friendly and economical alternative to conventional methods in soil stabilization, and other MICP related applications.

Keywords: biocementation, Bhargavaea cecembensis, soil improvement, whey culture medium

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Authors: Sumeet Rai, Anuj Tyagi, B. T. Naveen Kumar, Shubhkaramjeet Kaur, Niraj K. Singh

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Since their discovery, indiscriminate use of antibiotics in human, veterinary and aquaculture systems has resulted in global emergence/spread of multidrug-resistant bacterial pathogens. Thus, the need for alternative approaches to control bacterial infections has become utmost important. High selectivity/specificity of bacteriophages (phages) permits the targeting of specific bacteria without affecting the desirable flora. In this study, a lytic phage (Ahp1) specific to Aeromonas hydrophila subsp. hydrophila was isolated from finfish aquaculture pond. The host range of Ahp1 range was tested against 10 isolates of A. hydrophila, 7 isolates of A. veronii, 25 Vibrio cholerae isolates, 4 V. parahaemolyticus isolates and one isolate each of V. harveyi and Salmonella enterica collected previously. Except the host A. hydrophila subsp. hydrophila strain, no lytic activity against any other bacterial was detected. During the adsorption rate and one-step growth curve analysis, 69.7% of phage particles were able to get adsorbed on host cell followed by the release of 93 ± 6 phage progenies per host cell after a latent period of ~30 min. Phage nucleic acid was extracted by column purification methods. After determining the nature of phage nucleic acid as dsDNA, phage genome was subjected to next-generation sequencing by generating paired-end (PE, 2 x 300bp) reads on Illumina MiSeq system. De novo assembly of sequencing reads generated circular phage genome of 42,439 bp with G+C content of 58.95%. During open read frame (ORF) prediction and annotation, 22 ORFs (out of 49 total predicted ORFs) were functionally annotated and rest encoded for hypothetical proteins. Proteins involved in major functions such as phage structure formation and packaging, DNA replication and repair, DNA transcription and host cell lysis were encoded by the phage genome. The complete genome sequence of Ahp1 along with gene annotation was submitted to NCBI GenBank (accession number MF683623). Stability of Ahp1 preparations at storage temperatures of 4 °C, 30 °C, and 40 °C was studied over a period of 9 months. At 40 °C storage, phage counts declined by 4 log units within one month; with a total loss of viability after 2 months. At 30 °C temperature, phage preparation was stable for < 5 months. On the other hand, phage counts decreased by only 2 log units over a period of 9 during storage at 4 °C. As some of the phages have also been reported as glycerol sensitive, the stability of Ahp1 preparations in (0%, 15%, 30% and 45%) glycerol stocks were also studied during storage at -80 °C over a period of 9 months. The phage counts decreased only by 2 log units during storage, and no significant difference in phage counts was observed at different concentrations of glycerol. The Ahp1 phage discovered in our study had a very narrow host range and it may be useful for phage typing applications. Moreover, the endolysin and holin genes in Ahp1 genome could be ideal candidates for recombinant cloning and expression of antimicrobial proteins.

Keywords: Aeromonas hydrophila, endolysin, phage, narrow host range

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Authors: Oluwafunmibi Omotayo Fasanya, Augustine Kena Adjei

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Diabetic nephropathy (DN) is a major complication of diabetes, with fibrosis and propionate metabolism playing critical roles in its progression. Identifying biomarkers linked to these pathways may provide novel insights into DN diagnosis and treatment. This study aims to identify biomarkers associated with fibrosis and propionate metabolism in DN. Analyze the biological pathways and regulatory mechanisms of these biomarkers. Develop a machine learning model to predict DN-related biomarkers and validate their functional roles. Publicly available transcriptome datasets related to DN (GSE96804 and GSE104948) were obtained from the GEO database (https://www.ncbi.nlm.nih.gov/gds), and 924 propionate metabolism-related genes (PMRGs) and 656 fibrosis-related genes (FRGs) were identified. The analysis began with the extraction of DN-differentially expressed genes (DN-DEGs) and propionate metabolism-related DEGs (PM-DEGs), followed by the intersection of these with fibrosis-related genes to identify key intersected genes. Instead of relying on traditional models, we employed a combination of deep neural networks (DNNs) and ensemble methods such as Gradient Boosting Machines (GBM) and XGBoost to enhance feature selection and biomarker discovery. Recursive feature elimination (RFE) was coupled with these advanced algorithms to refine the selection of the most critical biomarkers. Functional validation was conducted using convolutional neural networks (CNN) for gene set enrichment and immunoinfiltration analysis, revealing seven significant biomarkers—SLC37A4, ACOX2, GPD1, ACE2, SLC9A3, AGT, and PLG. These biomarkers are involved in critical biological processes such as fatty acid metabolism and glomerular development, providing a mechanistic link to DN progression. Furthermore, a TF–miRNA–mRNA regulatory network was constructed using natural language processing models to identify 8 transcription factors and 60 miRNAs that regulate these biomarkers, while a drug–gene interaction network revealed potential therapeutic targets such as UROKINASE–PLG and ATENOLOL–AGT. This integrative approach, leveraging deep learning and ensemble models, not only enhances the accuracy of biomarker discovery but also offers new perspectives on DN diagnosis and treatment, specifically targeting fibrosis and propionate metabolism pathways.

Keywords: diabetic nephropathy, deep neural networks, gradient boosting machines (GBM), XGBoost

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Authors: Hasti Abbasi

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Creative writers have long followed the tradition of romantic exile, looking inward in an attempt to construct new viewpoints through the power of imagination. The writer, who attempts to resist uncertainty and locate her place in the new country through writing, resists creativity itself. For a writer, certain satisfaction can be achieved through producing a creative art away from the anxiety of the sense of dislocation. Dislocation, whether enforced or self-inflicted, could in many ways be a disaster but it could also cultivate a greater creative capacity and be a source of creative expression. This paper will investigate the idea of the creative writer as exiled self through reflections on the relationship between dislocation and writing.

Keywords: dislocation, creative writing, remaking identity, exile literature

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Authors: O. O. Sufyani, M. E. Oraiby, S. A. Qumaiy, A. I. Alaamri, Z. M. Eisa, A. M. Hakami, M. A. Attafi, O. M. Alhassan, W. M. Elsideeg, E. M. Noureldin, Y. A. Hobani, Y. Q. Majrabi, I. A. Khardali, A. B. Maashi, A. A. Al Mane, A. H. Hakami, I. M. Alkhyat, A. A. Sahly, I. M. Attafi

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According to the Food and Agriculture Organization (FAO) Pesticides Use Database, pesticide use in agriculture in Saudi Arabia has more than doubled from 4539 tons in 2009 to 10496 tons in 2019. Among pesticides, pyrethroids is commonly used in Saudi Arabia. Pesticides may increase susceptibility to a variety of diseases, particularly among pesticide workers, due to their extensive use, indiscriminate use, and long-term exposure. Therefore, analyzing blood chemo-profiles and evaluating the detected substances as biomarkers for pyrethroid pesticide exposure may assist to identify and predicting adverse effects of exposure, which may be used for both preventative and risk assessment purposes. The purpose of this study was to (a) analyze chemo-profiling by Gas Chromatography-Mass Spectrometry (GC-MS) analysis, (b) identify the most commonly detected chemicals in a time-exposure-dependent manner using a Venn diagram, and (c) identify their associated disease among pesticide workers using analyzer tools on the Comparative Toxicogenomics Database (CTD) website, (250 healthy male volunteers (20-60 years old) who deal with pesticides in the Jazan region of Saudi Arabia (exposure intervals: 1-2, 4-6, 6-8, more than 8 years) were included in the study. A questionnaire was used to collect demographic information, the duration of pesticide exposure, and the existence of chronic conditions. Blood samples were collected for biochemistry analysis and extracted by solid-phase extraction for gas chromatography-mass spectrometry (GC-MS) analysis. Biochemistry analysis reveals no significant changes in response to the exposure period; however, an inverse association between the albumin level and the exposure interval was observed. The blood chemo-profiling was differentially expressed in an exposure time-dependent manner. This analysis identified the common chemical set associated with each group and their associated significant occupational diseases. While some of these chemicals are associated with a variety of diseases, the distinguishing feature of these chemically associated disorders is their applicability for prevention measures. The most interesting finding was the identification of several chemicals; erucic acid, pelargonic acid, alpha-linolenic acid, dibutyl phthalate, diisobutyl phthalate, dodecanol, myristic Acid, pyrene, and 8,11,14-eicosatrienoic acid, associated with pneumoconiosis, asbestosis, asthma, silicosis and berylliosis. Chemical-disease association study also found that cancer, digestive system disease, nervous system disease, and metabolic disease were the most often recognized disease categories in the common chemical set. The hierarchical clustering approach was used to compare the expression patterns and exposure intervals of the chemicals found commonly. More study is needed to validate these chemicals as early markers of pyrethroid insecticide-related occupational disease, which might assist evaluate and reducing risk. The current study contributes valuable data and recommendations to public health.

Keywords: occupational, toxicology, chemo-profiling, pesticide, pyrethroid, GC-MS

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Authors: A. Bajek, J. Skopinska-Wisniewska, A. Rynkiewicz, A. Jundzill, M. Bodnar, A. Marszalek, T. Drewa

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Traumatic injury and age-related degenerative diseases associated with cartilage are major health problems worldwide. The articular cartilage is comprised of a relatively small number of cells, which have a relatively slow rate of turnover. Therefore, damaged articular cartilage has a limited capacity for self-repair. New clinical methods have been designed to achieve better repair of injured cartilage. However, there is no treatment that enables full restoration of it. The aim of this study was to evaluate how collagen gel with bone marrow mesenchymal stem cells (MSCs) and collagen gel alone will influence on the hip cartilage repair after injury. Collagen type I was isolated from rats’ tails and cross-linked with N-hydroxysuccinimide in 24-hour process. MSCs were isolated from rats’ bone marrow. The experiments were conducted according to the guidelines for animal experiments of Ethics Committee. Fifteen 8-week-old Wistar rats were used in this study. All animals received hip joint surgery with a total of 30 created cartilage defects. Then, animals were randomly divided into three groups and filled, respectively, with collagen gel (group 1), collagen gel cultured with MSCs (group II) or left untreated as a control (control group). Immunohistochemy and radiological evaluation was carried out 11 weeks post implantation. It has been proved that the surface of the matrix is non-toxic, and its porosity promotes cell adhesion and growth. However, the in vivo regeneration process was poor. We observed the low integration rate of biomaterial. Immunohistochemical evaluation of cartilage after 11 weeks of treatment showed low II and high X collagen expression in two tested groups in comparison to the control one, in which we observed the high II collagen expression. What is more, after radiological analysis, we observed the best regeneration process in control group. The biomaterial construct and mesenchymal stem cells, as well as the use of the biomaterial itself was not sufficient to regenerate the hip cartilage surfaces. These results suggest that the collagen gel based biomaterials, even with MSCs, are not satisfactory in repar of hip cartilage defect. However, additional evaluation is needed to confirm these results.

Keywords: collafen gel, MSCs, cartilage repair, hip cartilage

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Authors: Inmaculada Yuste Martinez

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Since July 5, 2014, Abubaker al Bagdadi, leader of the Islamic State since 2010 climbed the pulpit of the Great Mosque of Al Nuri of Mosul and proclaimed the Caliphate, the number of fighters who have travelled to Syria to join the Caliphate has increased as never before. Although it is true that the phenomenon of foreign fighters is not a new phenomenon, as it occurred after the Spanish Civil War, Republicans from Ireland and the conflict of the Balkans among others, it is highly relevant the fact that in this case, it has reached figures unknown in Europe until now. The approval of the resolution 2178 (2014) of the Security Council, foreign terrorist fighters placed the subject a priority position on the International agenda. The available data allow us to affirm that women have increasingly assumed operative functions in jihadist terrorism and in the activities linked to it in the development of attacks in the European Union, including minors and young adults. In the case of Spain, one in four of the detainees in 2016 were women, a significant increase compared to 2015. This contrasts with the fact that until 2014 no woman had been prosecuted in Spain for terrorist activities of a jihadist nature. It is fundamental when we talk about the prevention of radicalization and counterterrorism that we do not underestimate the potential threat to the security of countries like Spain that women from the West can assume to the global jihadist movement. This work aims to deepen the radicalization processes of these women and their profiles influencing the female inmate population. It also wants to focus on the importance of creating de-radicalization programs for these inmates since women are a crucial element in radicalization processes. A special focus it is made on young radicalized female inmate population as this target group is the most recoverable and on which it would result more fruitful to intervene. De-radicalization programs must also be designed to fit their profiles and circumstances; a sensitive environment will be prisons and juvenile centers, areas that until now had been unrelated to this problem and which are already hosting the first convicted in judicial offices in Spanish territory. A qualitative research and an empirical and analytical method has been implemented in this work, focused on the cases that took place in Spain of young women and the imaginary that the Islamic State uses for the processes of radicalization for this target group and how it does not fit with their real role in the Jihad, as opposed to other movements in which women do have a real and active role in the armed conflict as YPJ do it as a part of the armed wing of the Democratic Union Party of Syria.

Keywords: caliphate, de-radicalization, foreign fighter, gender perspective, ISIS, jihadism, recruitment

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