Search results for: autosomal recessive genetic disorder (ARGD)

Authors: Sina Mahdavi

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Background and Objective: Multiple sclerosis (MS) is the most common inflammatory autoimmune disease of the central nervous system (CNS) that affects the myelination process in the CNS. Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially Epstein-Barr virus (EBV) and MS, is one potential cause that is not well understood. In this study, we aim to summarize the available data on EBV infection in MS disease progression. Materials and Methods: For this study, the keywords "Multiple sclerosis," "Epstein-Barr virus," and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2016 and 2022 were searched, and 14 articles were chosen, studied, and analyzed. Results: Demyelinated lesions isolated from MS patients contain EBNAs from EBV proteins. The EBNA1 domain contains a pentapeptide fragment identical to B-crystallin, a heat shock peptide, that is increased in peripheral B cells in response to B-crystallin infection, resulting in myelin-directed autoimmunity mediated by proinflammatory T cells. EBNA2, which is involved in the regulation of viral transcription, may enhance transcription from MS risk loci. A 7-fold increase in the risk of MS has been observed in EBV infection with HLA-DR15 synergy. Conclusion: EBV infection along with a variety of specific genetic risk alleles, cause inflammatory cascades in the CNS by infected B cells. There is a high expression of EBV during the course of MS, which indicates the relationship between EBV and MS, that this virus can play a role in the development of MS by creating an inflammatory state. Therefore, measures to modulate the expression of EBV may be effective in reducing inflammatory processes in demyelinated areas of MS patients.

Keywords: multiple sclerosis, Epstein-Barr virus, central nervous system, EBNAs

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Authors: Abdolrasoul Daneshjoo

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The purpose of this research was to study the effect of aerobic exercises with 75% heart beats on the amount of urea, uric acid and creatine in blood of Iranian soccer national U-23 players. 27 players were selected according to the following demographic specifications: age: 21.4±1.60 years old; weight: 68±9.4 kg; height: 174.2±8.6 cm. Urea, uric acid and creatine in blood are considered as dependent variations where as 40 minutes running on a track with maximum 75% heart beats are independent variations. Heart beat and blood pressure in rest time, age, height, and weight are considered as the controlled variations. Maximum heart beats are recorded under maximum exercises (8 minutes and 150-250 watt energy) on ergo meter. Then, in order to determine independent variations, 75% maximum heart beats are considered for each player. Blood is taken twice (before and after determining independence variation). Moreover, the players are given a few instructions to be fulfilled 24 hours before the main exercises. Laboratory analysis method for blood urea sample is deacetyl ammoniom, for uric acid Karvy test and for creatine pyric acid. 'T' formula is applied for analyzing statistical data in dependent groups with degree of freedom 7 (d.f=7) urea and uric acid contain P>0.01 and P>0.05 for creatine. 1. Aerobic exercise can effect on the concentration of urea of blood as well as uric acid and creatine in blood serum and increase the amount of them. 2. Urea of blood serum increases from 26.75±2.59 to 28.9±2.67 (25%) with 40 minutes running and 75% heart beat. 3. Aerobic exercise causes uric acid increase 12.5% from 5.7±0.52 (before exercise) to 6.1±0.71 (after exercise). Creatine of blood serum increases from 1.36±0.27 (before exercise) to 1.85±0.49 (after exercise). We came to this result that during aerobic exercise catabolism of protein substrate increases. Moreover, augmentation of urea, uric acid and creatine in blood serum as metabolic poisons causes disorder in kidney. Also, tendons and joints are affected by these poisons. Appropriate diet and exercise can prevent production of these poisons resulted from heavy exercise.

Keywords: aerobic exercise, urea, uric acid, creatine, blood, soccer national players

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Authors: T. Marinaci, C. Venuleo

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Different conceptualizations of disease affect patient care. This study aims to address this gap. It explores how health professionals conceptualize gambling problem, addiction and the goals of recovery process. In-depth, semi-structured, open-ended interviews were conducted with Italian psychologists, psychiatrists, general practitioners, and support staff (N= 114), working within health centres for the treatment of addiction (public health services or therapeutic communities) or medical offices. A Lexical Correspondence Analysis (LCA) was applied to the verbatim transcripts. LCA allowed to identify two main factorial dimensions, which organize similarity and dissimilarity in the discourses of the interviewed. The first dimension labelled 'Models of relationship with the problem', concerns two different models of relationship with the health problem: one related to the request for help and the process of taking charge and the other related to the identification of the psychopathology underlying the disorder. The second dimension, labelled 'Organisers of the intervention' reflects the dialectic between two ways to address the problem. On the one hand, they are the gambling dynamics and its immediate life-consequences to organize the intervention (whatever the request of the user is); on the other hand, they are the procedures and the tools which characterize the health service to organize the way the professionals deal with the user’ s problem (whatever it is and despite the specify of the user’s request). The results highlight how, despite the differences, the respondents share a central assumption: understanding gambling problem implies the reference to the gambler’s identity, more than, for instance, to the relational, social, cultural or political context where the gambler lives. A passive stance is attributed to the user, who does not play any role in the definition of the goal of the intervention. The results will be discussed to highlight the relationship between professional models and users’ ways to understand and deal with the problems related to gambling.

Keywords: cultural models, health professionals, intervention models, problem gambling

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Authors: Thomas Heffernan, Nick Neave, Colin Hamilton, Gill Case

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Hoarding is the acquisition of and failure to discard possessions, leading to excessive clutter and significant psychological/emotional distress. From a cognitive-behavioural approach, excessive hoarding arises from information-processing deficits, as well as from problems with emotional attachment to possessions and beliefs about the nature of possessions. In terms of information processing, hoarders have shown deficits in executive functions, including working memory, planning, inhibitory control, and cognitive flexibility. However, this previous research is often confounded by co-morbid factors such as anxiety, depression, or obsessive-compulsive disorder. The current study adopted a cognitive-behavioural approach, specifically assessing executive deficits and working memory in a non-clinical sample of hoarders, compared with non-hoarders. In this study, a non-clinical sample of 40 hoarders and 73 non-hoarders (defined by The Savings Inventory-Revised) completed the Adult Executive Functioning Inventory, which measures working memory and inhibition, Dysexecutive Questionnaire-Revised, which measures general executive function and the Hospital Anxiety and Depression Scale, which measures mood. The participant sample was made up of unpaid young adult volunteers who were undergraduate students and who completed the questionnaires on a university campus. The results revealed that, after observing no differences between hoarders and non-hoarders on age, sex, and mood, hoarders reported significantly more deficits in inhibitory control and general executive function when compared with non-hoarders. There was no between-group difference on general working memory. This suggests that non-clinical hoarders have a specific difficulty with inhibition-control, which enables you to resist repeated, unwanted urges. This might explain the hoarder’s inability to resist urges to buy and keep items that are no longer of any practical use. These deficits may be underpinned by general executive function deficiencies.

Keywords: hoarding, memory, executive, deficits

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Authors: A. Ferasat, S. Rostampour Yasouri

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Seasonal flu is a highly contagious infection caused by influenza viruses. These viruses undergo genetic changes that result in new epidemics across the globe. Medical attention is crucial in severe cases, particularly for the elderly, frail, and those with chronic illnesses, as their immune systems are often weaker. The purpose of this study was to detect new subtypes of the influenza A virus rapidly using a specific RT-PCR method based on the HA gene (hemagglutinin). In the winter and spring of 2022_2023, 120 embryonated egg samples were cultured, suspected of seasonal influenza. RNA synthesis, followed by cDNA synthesis, was performed. Finally, the PCR technique was applied using a pair of specific primers designed based on the HA gene. The PCR product was identified after purification, and the nucleotide sequence of purified PCR products was compared with the sequences in the gene bank. The results showed a high similarity between the sequence of the positive samples isolated from the patients and the sequence of the new strains isolated in recent years. This RT-PCR technique is entirely specific in this study, enabling the detection and multiplication of influenza and its subspecies from clinical samples. The RT-PCR technique based on the HA gene, along with sequencing, is a fast, specific, and sensitive diagnostic method for those infected with influenza viruses and its new subtypes. Rapid molecular diagnosis of influenza is essential for suspected people to control and prevent the spread of the disease to others. It also prevents the occurrence of secondary (sometimes fatal) pneumonia that results from influenza and pathogenic bacteria. The critical role of rapid diagnosis of new strains of influenza is to prepare a drug vaccine against the latest viruses that did not exist in the community last year and are entirely new viruses.

Keywords: influenza, molecular diagnosis, patients, RT-PCR technique

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Authors: Shantanu Arya, Sachin Sakhuja, Gunjan Mehta, Sanjay Munjal

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Stuttering may be defined as a speech disorder affecting the fluency domain of speech and characterized by covert features like word substitution, omittance and circumlocution and overt features like prolongation of sound, syllables and blocks etc. Many etiologies have been postulated to explain stuttering based on various experiments and research. Moreover, Breathlessness has also been reported by many individuals with stuttering for which breathing exercises are generally advised. However, no studies reporting objective evaluation of the pulmonary capacity and further objective assessment of the efficacy of breathing exercises have been conducted. Pulmonary Function Test which evaluates parameters like Forced Vital Capacity, Peak Expiratory Flow Rate, Forced expiratory flow Rate can be used to study the pulmonary behavior of individuals with stuttering. The study aimed: a) To identify speech motor & physiologic behaviours associated with stuttering by administering PFT. b) To recognize possible reasons for an association between speech motor behaviour & stuttering severity. In this regard, PFT tests were administered on individuals who reported signs and symptoms of stuttering and showed abnormal scores on Stuttering Severity Index. Parameters like Forced Vital Capacity, Forced Expiratory Volume, Peak Expiratory Flow Rate (L/min), Forced Expiratory Flow Rate (L/min) were evaluated and correlated with scores of Stuttering Severity Index. Results showed significant decrease in the parameters (lower than normal scores) in individuals with established stuttering. Strong correlation was also found between degree of stuttering and the degree of decrease in the pulmonary volumes. Thus, it is evident that fluent speech requires strong support of lung pressure and requisite volumes. Further research in demonstrating the efficacy of abdominal breathing exercises in this regard is needed.

Keywords: forced expiratory flow rate, forced expiratory volume, forced vital capacity, peak expiratory flow rate, stuttering

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Authors: Adar Pelah, Avraham Adelman, Amanda Balash, Jake Mitchell, Mattan J. Pelah, Viswadeep Sarangi, Xin Chen Cai, Zadok Storkey, Gregg B. Fields, Ximena Levy, Ali A. Danesh

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Introduction: Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 infection (PASC), or Long COVID, while primarily a respiratory disorder, can also include dizziness, lasting weeks to months in individuals who had previously tested positive for COVID-19. This study utilized gait analysis to assess the potential vestibular effects of PASC on the presentation of gait anomalies. Materials and Methods: The study included 11 participants who tested positive for COVID-19, a mean of 2.8 months prior to gait testing (PP=11), and 8 control participants who did not test positive for COVID-19 (NP=8). Participants walked 7.5m at three self-selected speeds: ‘slow,’ ‘normal,’ and ‘fast.’ Mean walking speeds were determined for each speed and overall range from four laps on an instrumented walkway using video capture. Results: A Z-test at 0.05 significance was used for speed range, ‘normal’ and ‘fast’ at the lower tail, and for ‘slow’ at the higher tail. Average speeds (m/s) were: ‘slow’ (PP=0.709, NP=0.678), ‘normal’ (PP=1.141, NP=1.170), ‘fast’ (PP=1.529, NP=1.821), average range (PP=0.846, NP=1.143). Significant speed decreases between PP and NP were observed in ‘fast’ (-17.43%) and average range (-29.86%), while changes in ‘slow’ (+2.44%) and ‘normal’ (-4.39%) speeds were not significant. Conclusions: Long COVID is a recognized disability (Americans with Disabilities Act), and although it presents variably, dizziness, vertigo, and tinnitus are not uncommon in COVID-19 infection. These results suggest that potential inner-ear damage may persist and manifest in gait changes even after recovery from acute illness. Further research with a larger sample size may indicate the need for providers to consider PASC when diagnosing patients with vestibular dysfunction.

Keywords: gait analysis, long-COVID, vestibular dysfunction, walking speed

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Authors: Manish Madappa, Madhavi Gayathri Raman

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The primary vehicle of human communication is language. A breakdown occurring in any aspect of communication may lead to frustration and isolation among the learners and the teachers. Over seven percent of the population in the world currently experience limitations and those children who exhibit a deviant/deficient language acquisition curve even when being in a language rich environment as their peers may be at risk of having a language disorder or language impairment. The difficulty may be in the word level [vocabulary/word knowledge] and/or the sentence level [syntax/morphology) Children with SLI appear to be developing normally in all aspects except for their receptive and/or expressive language skills. Thus, it is utmost importance to identify children with or at risk of SLI so that an early intervention can foster language and social growth, provide the best possible learning environment with special support for language to be explicitly taught and a step in providing continuous and ongoing support. The present study looks at Kannada English bilingual children and works towards identifying children at risk of “specific language impairment”. The study was conducted through an exploratory study which systematically enquired into the narratives of young Kannada-English bilinguals and to investigate the data for story structure in their narrative formulations. Oral narrative offers a rich source of data about a child’s language use in a relatively natural context. The fundamental objective is to ensure comparability and to be more universal and thus allows for the evaluation narrative text competence. The data was collected from 10 class three students at a primary school in Mysore, Karnataka and analyzed for macrostructure component reflecting the goal directed behavior of a protagonist who is motivated to carry out some kind of action with the intention of attaining a goal. The results show that the children exhibiting a deviation of -1.25 SD are at risk of SLI. Two learners were identified to be at risk of Specific Language Impairment with a standard deviation of more the 1.25 below the mean score.

Keywords: bilingual, oral narratives, SLI, macrostructure

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Authors: Sumeeta Khurana, Kirti Megha, Amit Gupta, Rakesh Sehgal

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Background: Amoebic keratitis is a painful vision threatening infection caused by a free living pathogenic amoeba Acanthamoeba. It can be misdiagnosed and very difficult to treat if not suspected early. The epidemiology of Acanthamoeba genotypes causing infection in our geographical area is not yet known to the best of our knowledge. Objective: To characterize Acanthamoeba isolates from amoebic keratitis patients. Methods: A total of 19 isolates obtained from patients with amoebic keratitis presenting to the Advanced Eye Centre at Postgraduate Institute of Medical Education and Research, a tertiary care centre of North India over a period of last 10 years were included. Their corneal scrapings, lens solution and lens case (in case of lens wearer) were collected for microscopic examination, culture and molecular diagnosis. All the isolates were maintained in the Non Nutrient agar culture medium overlaid with E.coli and 13 strains were axenised and maintained in modified Peptone Yeast Dextrose Agar. Identification of Acanthamoeba genotypes was based on amplification of diagnostic fragment 3 (DF3) region of the 18srRNA gene followed by sequencing. Nucleotide similarity search was performed by BLAST search of sequenced amplicons in GenBank database (http//www.ncbi.nlm.nih.gov/blast). Multiple Sequence alignments were determined by using CLUSTAL X. Results: Nine out of 19 Acanthamoeba isolates were found to belong to Genotype T4 followed by 6 isolates of genotype T11, 3 T5 and 1 T3 genotype. Conclusion: T4 is the predominant Acanthamoeba genotype in our geographical area. Further studies should focus on differences in pathogenicity of these genotypes and their clinical significance.

Keywords: Acanthamoeba, free living amoeba, keratitis, genotype, ocular

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Authors: Carolina V. Viegas, Monique Gonçalves, Gisel Chenard Diaz, Yordanka Reyes Cruz, Donato Alexandre Gomes Aranda

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To develop the massive cultivation of microalgae, it is necessary to isolate and characterize the species, improving genetic tools in search of specific characteristics. Therefore, the detection, identification and quantification of the compounds that compose the Scenedesmus sp. were prerequisites to verify the potential of these microalgae. The main objective of this work was to carry out the characterization of Scenedesmus sp. as to the content of ash, carbohydrates, proteins and lipids as well as the determination of the composition of their lipid classes and main fatty acids. The biomass of Scenedesmus sp, showed 15,29 ± 0,23 % of ash and CaO (36,17 %) was the main component of this fraction, The total protein and carbohydrate content of the biomass was 40,74 ± 1,01 % and 23,37 ± 0,95 %, respectively, proving to be a potential source of proteins as well as carbohydrates for the production of ethanol via fermentation, The lipid contents extracted via Bligh & Dyer and in situ saponification were 8,18 ± 0,13 % and 4,11 ± 0,11 %, respectively. In the lipid extracts obtained via Bligh & Dyer, approximately 50 % of the composition of this fraction consists of fatty compounds, while the other half is composed of an unsaponifiable fraction composed mainly of chlorophylls, phytosterols and carotenes. From the lowest yield, it was possible to obtain a selectivity of 92,14 % for fatty components (fatty acids and fatty esters) confirmed through the infrared spectroscopy technique. The presence of polyunsaturated acids (~45 %) in the lipid extracts indicated the potential of this fraction as a source of nutraceuticals. The results indicate that the biomass of Scenedesmus sp, can become a promising potential source for obtaining polyunsaturated fatty acids, carotenoids and proteins as well as the simultaneous obtainment of different compounds of high commercial value.

Keywords: microalgae, Desmodesmus, lipid classes, fatty acid profile, proteins, carbohydrates

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Authors: Hagos Abraham, Solomon Gizaw, Mengistu Urge

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A sound breeding objective is the basis for genetic improvement in overall economic merit of farm animals. Begait goat is one of the identified breeds in Ethiopia, which is a multipurpose breed as it serves as source of cash income and source of food (meat and milk). Despite its importance, no formal breeding objectives exist for Begait goat. The objective of the present study was to identify breeding objectives for the breed through two approaches: using own-flock ranking experiment and developing deterministic bio-economic models as a preliminary step towards designing sustainable breeding programs for the breed. In the own-flock ranking experiment, a total of forty five households were visited at their homesteads and were asked to select, with reasons, the first best, second best, third best and the most inferior does from their own flock. Age, previous reproduction and production information of the identified animals were inquired; live body weight and some linear body measurements were taken. The bio-economic model included performance traits (weights, daily weight gain, kidding interval, litter size, milk yield, kid mortality, pregnancy and replacement rates) and economic (revenue and costs) parameters. It was observed that there was close agreement between the farmers’ ranking and bio-economic model results. In general, the results of the present study indicated that Begait goat owners could improve performance of their goats and profitability of their farms by selecting for litter size, six month weight, pre-weaning kid survival rate and milk yield.

Keywords: bio-economic model, economic parameters, own-flock ranking, performance traits

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Authors: José Eduardo García-Mendiola

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In this work, a phenomenological approach to computational modeling of analogy processing is carried out. The paper goes through the consideration of the structure of the analogy, based on the possibility of sustaining the genesis of its elements regarding Husserl's genetic theory of association. Among particular processes which take place in order to get analogical inferences, there is one which arises crucial for enabling efficient base cases retrieval through long-term memory, namely analogical transference grounded on familiarity. In general, it has been argued that analogical reasoning is a way by which a conscious agent tries to determine or define a certain scope of objects and relationships between them using previous knowledge of other familiar domain of objects and relations. However, looking for a complete description of analogy process, a deeper consideration of phenomenological nature is required in so far, its simulation by computational programs is aimed. Also, one would get an idea of how complex it would be to have a fully computational account of the analogy elements. In fact, familiarity is not a result of a mere chain of repetitions of objects or events but generated insofar as the object/attribute or event in question is integrable inside a certain context that is taking shape as functionalities and functional approaches or perspectives of the object are being defined. Its familiarity is generated not by the identification of its parts or objective determinations as if they were isolated from those functionalities and approaches. Rather, at the core of such a familiarity between entities of different kinds lays the way they are functionally encoded. So, and hoping to make deeper inroads towards these topics, this essay allows us to consider that cognitive-computational perspectives can visualize, from the phenomenological projection of the analogy process reviewing achievements already obtained as well as exploration of new theoretical-experimental configurations towards implementation of analogy models in specific as well as in general purpose machines.

Keywords: analogy, association, encoding, retrieval

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Authors: Fumio Kasai, Noriko Hirayama, Jorge Pereira, Azusa Ohtani, Masashi Iemura, Malcolm A. Ferguson Smith, Arihiro Kohara

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The VERO cell line was established in 1962 from normal tissue of an African green monkey, Chlorocebus aethiops (2n=60), and has been commonly used worldwide for screening for toxins or as a cell substrate for the production of viral vaccines. The VERO genome was sequenced in 2014; however, its cytogenetic features have not been fully characterized as it contains several chromosome abnormalities and different karyotypes coexist in the cell line. In this study, the VERO cell line (JCRB0111) was compared with one of the sublines. In contrast to 59 chromosomes as the modal chromosome number in the VERO cell line, the subline had two peaks of 56 and 58 chromosomes. M-FISH analysis using human probes revealed that the VERO cell line was characterized by a translocation t(2;25) found in all metaphases, which was absent in the subline. Different abnormalities detected only in the subline show that the cell line is heterogeneous, indicating that the subline has the potential to change its genomic characteristics during cell culture. The various alterations in the two independent lineages suggest that genomic changes in both VERO cells can be accounted for by progressive rearrangements during their evolution in culture. Both t(5;X) and t(8;14) observed in all metaphases of the two cell lines might have a key role in VERO cells and could be used as genetic markers to identify VERO cells. The flow karyotype shows distinct differences from normal. Further analysis of sorted abnormal chromosomes may uncover other characteristics of VERO cells. Because of the absence of STR data, cytogenetic data are important in characterizing animal cell lines and can be an indicator of their quality control.

Keywords: VERO, cell culture passage, chromosome rearrangement, heterogeneous cells

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Authors: T. A. Rosy, M. R. I. Talukdar, N. S. Juyena, F. Y. Bari, M. N. Islam

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The ovarian follicular dynamics, vaginal electrical resistance (VER) and progesterone (P4) and estrogen (E2) profiles were investigated during estrus cycle in four indigenous ewes. Daily VER values were recorded with heat detector. The follicles were observed and measured by trans-rectal ultrasonography. Blood was collected daily for hormonal profiles. Results showed a significant variation in VER values (P<0.05) at estrus in regards to ewes and cycles. The day difference between two successive lower values in VER waves ranged from 13-17 days which might indicate the estrus cycle in indigenous ewes. Trans-rectal ultrasonography of ovaries revealed the presence of two to four waves of follicular growth during the study period. Results also showed that follicular diameter was negatively correlated with VER values. Study of hormonal profiles by ELISA revealed a positive correlation between E2 concentration and development of follicle and negative correlation between P4 concentration and development of follicle. The concentrations of estradiol increased at the time of estrus and then fall down in a basal level. Development of follicular size was accompanied by an increase in the concentration of serum estradiol. Inversely, when follicles heed to ovulation concentration of progesterone starts to fall down and after ovulation it turns its way to the zenith and remains at this state until next ovulatory follicle comes to its maximum diameter. This study could help scientists to set up a manipulative reproductive technique for improving genetic values of sheep in Bangladesh.

Keywords: ovarian follicle, hormonal profile, sheep, ultrasonography, vaginal electrical resistance

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Authors: Dona Pamoda W. Jayatunga, Veer Bala Gupta, Eugene Hone, Ralph N. Martins

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Being a neurodegenerative disorder, Alzheimer’s disease (AD) affects a majority of the elderly demented worldwide. The key risk factors for AD are age, metabolic syndrome, allele status of APOE gene, head injuries and lifestyle. The progressive nature of AD is characterized by symptoms of multiple cognitive deficits exacerbated over time, leading to death within a decade from clinical diagnosis. However, it is revealed that AD originates via a prodromal phase that spans from one to few decades before symptoms first manifest. The key pathological hallmarks of AD brains are deposition of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFT). However, the yet unknown etiology of the disease fails to distinguish mitochondrial dysfunction between a cause or an outcome. The absence of early diagnosis tools and definite therapies for AD have permitted recruits of nutraceutical-based approaches aimed at reducing the risk of AD by modulating lifestyle or be used as preventive tools during AD prodromal state before widespread neurodegeneration begins. The objective of the present study was to investigate beneficial effects of luteolin, a plant-based flavone compound, against AD. The neuroprotective effects of luteolin on amyloid beta (Aβ) (1-42)-induced neurotoxicity was measured using cultured human neuroblastoma BE(2)-M17 cells. After exposure to 20μM Aβ (1-42) for 48 h, the neuroblastoma cells exhibited marked apoptotic death. Co-treatment of 20μM Aβ (1-42) with luteolin (0.5-5μM) significantly protected the cells against Aβ (1-42)-induced toxicity, as assessed by the MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2(4sulfophenyl)-2H-tetrazolium, inner salt; MTS] reduction assay and the lactate dehydrogenase (LDH) cell death assay. The results suggest that luteolin prevents Aβ (1-42)-induced apoptotic neuronal death. However, further studies are underway to determine its protective mechanisms in AD including the activity against tau hyperphosphorylation and mitochondrial dysfunction.

Keywords: Aβ (1-42)-induced toxicity, Alzheimer’s disease, luteolin, neuroblastoma cells

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Authors: Haiyoung Jung, Mi Joung Leem, Sun Hwa Lee

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Background & Objective: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a genetic abnormality that results in an inadequate amount of G6PD, leading to increased susceptibility of red blood cells to reactive oxygen species and hemolysis. The present study aimed to evaluate the careSTARTTM S1 analyzer for measuring G6PD activity to hemoglobin (Hb) ratio. Methods: Precision for G6PD activity and hemoglobin measurement was evaluated using control materials with two levels on five repeated runs per day for five days. The analytic performance of the careSTARTTM S1 analyzer was compared with spectrophotometry in 40 patient samples. Reference ranges suggested by the manufacturer were validated in 20 healthy males and females each. Results: The careSTARTTM S1 analyzer demonstrated precision of 6.0% for low-level (14~45 U/dL) and 2.7% for high-level (60~90 U/dL) control in G6PD activity, and 1.4% in hemoglobin (7.9~16.3 u/g Hb). A comparison study of G6PD to Hb ratio between the careSTARTTM S1 analyzer and spectrophotometry showed an average difference of 29.1% with a positive bias of the careSTARTTM S1 analyzer. All normal samples from the healthy population were validated for the suggested reference range for males (≥2.19 U/g Hb) and females (≥5.83 U/g Hb). Conclusion: The careSTARTTM S1 analyzer demonstrated good analytical performance and can replace the current spectrophotometric measurement of G6PD enzyme activity. In the aspect of the management of clinical laboratories, it can be a reasonable option as a point-of-care analyzer with minimal handling of samples and reagents, in addition to the automatic calculation of the ratio of measured G6PD activity and Hb concentration, to minimize any clerical errors involved with manual calculation.

Keywords: POCT, G6PD, performance evaluation, careSTART

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Authors: Hasan AL-Khshemawee, Manjree Agarwal, Xin Du, Yonglin Ren

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The possibility use of stable isotopes to study Medfly mating and life history were investigated in these experiments. 13C6 glucose was incorporated in the diet of the Mediterranean fruit fly Ceratitis capitata (Diptera: Tephidae). Treatments included labelling and unlabelled of either the media or adult sugar water. The measured started from egg hatching till the adults have died. After mating, the adults were analysed for 13C6 glucose ratio using Liquid chromatography-mass spectrometry LC-MS in two periods of time immediately and after three days of mating. Results showed that stable isotopes were used successfully for labelling Medfly in laboratory conditions, and there were significant differences between labelled and unlabelled treatment in eggs hatching, larval development, pupae emergence, survival of adults and mating behaviour. Labelling during larval development and combined labelling of larvae and adults resulted in detectable values. The label glucose in larvae stage did not effect on mating behaviour, however, the label glucose in adults’ stage was affected by mating behaviour. We recommended that it is possible to label adults of Mediterranean fruit fly C. capitata and detected the label after mating. This method offers good tools to study mating behaviour in Medfly and other types of insects and could be providing useful tools in genetic studies, sterile insect technique (SIT) or agricultural pest management. Also, we recommended using this technique in the field.

Keywords: stable isotope, sterile insect technique (SIT), medfly, mating behaviour

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Authors: Katalin Gocze, Vanda A Nemes, Charlotte Briest

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Introduction: Premenstrual syndrome (PMS) is a psychoneuroendocrinological disorder adversely affecting life-quality for over 80% of hormonally active women. PMS has a negative impact on women’s daily life in terms of work, interpersonal relationships and leisure time activities. The aim of our study was to evaluate the effects of a yoga intervention focusing on the female pelvic area. Materials and methods: 34 women (ages 18-40) with PMS (Premenstrual Syndrome Screening Tool) and no previous experience in yoga were recruited and randomly assigned to either the yoga or the control group. The intervention consisted of 90’ yoga sessions twice a week and a daily 15’ self-practice module with carefully chosen yogic exercises addressing the reproductive organs by toning the pelvic floor and opening the hips as well as relieving stress and improving concentration. Severity of symptoms of PMS was assessed at the beginning and after the 8-week-long intervention. Pre- and post-program data collection included physical and psychological parameters and the evaluation of ACOQ PMS questionnaire and daily symptom diary. Results: Age and educational background were similar in the control and intervention group with an overall mean age of 29.11±4.78 years. PSST scores significantly improved in the yoga group (p=0.002), while difference in the control group’s pre and post-program values were non-significant (p=0.38). Perception and tolerance of anxiety and stress was significantly better after the intervention (p=0.008). As for changes in physical symptoms distinct improvement was registered for breast tenderness (p=0.028) and for meteorism (p=0.015). Discussion: Yoga’s success originates from the synergic positive effects of stress relief and regular physical activity. Benefits (both mental and physical) of strategically planned, focused yoga practice are apparent even after shorter time periods and can help women with PMS manage or eliminate symptoms in order to improve their life-quality.

Keywords: life-quality, physical symptoms, premenstrual syndrome, psychological impact, yoga

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Authors: Fathi Kallel, Abdulelah Alabd Uljabbar, Abdulrahman Aldukhail, Abdulaziz Alomran

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The brain is an important organ in our body since it is responsible about the majority actions such as vision, memory, etc. However, different diseases such as Alzheimer and tumors could affect the brain and conduct to a partial or full disorder. Regular diagnosis are necessary as a preventive measure and could help doctors to early detect a possible trouble and therefore taking the appropriate treatment, especially in the case of brain tumors. Different imaging modalities are proposed for diagnosis of brain tumor. The powerful and most used modality is the Magnetic Resonance Imaging (MRI). MRI images are analyzed by doctor in order to locate eventual tumor in the brain and describe the appropriate and needed treatment. Diverse image processing methods are also proposed for helping doctors in identifying and analyzing the tumor. In fact, a large Computer Aided Diagnostic (CAD) tools including developed image processing algorithms are proposed and exploited by doctors as a second opinion to analyze and identify the brain tumors. In this paper, we proposed a new advanced CAD for brain tumor identification, classification and feature extraction. Our proposed CAD includes three main parts. Firstly, we load the brain MRI. Secondly, a robust technique for brain tumor extraction is proposed. This technique is based on both Discrete Wavelet Transform (DWT) and Principal Component Analysis (PCA). DWT is characterized by its multiresolution analytic property, that’s why it was applied on MRI images with different decomposition levels for feature extraction. Nevertheless, this technique suffers from a main drawback since it necessitates a huge storage and is computationally expensive. To decrease the dimensions of the feature vector and the computing time, PCA technique is considered. In the last stage, according to different extracted features, the brain tumor is classified into either benign or malignant tumor using Support Vector Machine (SVM) algorithm. A CAD tool for brain tumor detection and classification, including all above-mentioned stages, is designed and developed using MATLAB guide user interface.

Keywords: MRI, brain tumor, CAD, feature extraction, DWT, PCA, classification, SVM

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Authors: E. Riani, T. T. Irawadi, S. Nurjanah, K. Syamsu, E. G. Said, Suprihatin, M. R. Cordova

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Especially coastal, Indonesian and Chinese communities have utilized sandfish to improve reproduction quality of men. This study aimed to examine the nutrition on sandfish flesh that has the potency to improve reproduction quality of men. The materials used were sandfish with weight of 200-500 g, and then analysis of proximate, analysis of amino acid, analysis of fatty acid and analysis of mineral contained in the sandfish were performed. The results showed that protein content (39.96%) was the main component of the flesh; the carbohydrate and fat were 25.43% and 4.18%, respectively. Sandfish powder contains several essential amino acids and nonessential amino acids. Nine of ten amino acids needed by human body are contained in sandfish powder, i.e. arginine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, tryptophan, threonine and valine; only tryptophan that are not contained in sandfish powder. Sandfish powder contains saturated fatty acid kaproat, kaprilat, kaprat, laurat, miristat, stearat, arakhidat and behenat; monosaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA). MUFA is composed of fatty acid oleat, while PUFA is composed fatty acid omega 3 (linonenat, eicosapentaenoic acid and docosahexaenoic acid) and omega 6 (linoleat and arakhidonat). The minerals contained in sandfish powder are macrominerals and microminerals. Based on the findings, the nutrition in sandfish powder has a good potency to improve reproduction of men, especially PUFA for the maturation of spermatozoa, zinc for production function and spermatogenesis, motility of spermatozoa, acromoson reaction; Mg for transformation of genetic information and motility of spermatozoa; calcium for spermatogenesis, capacity and fertilization of spermatozoa. Thus, sandfish flesh powder has the potency to improve reproduction quality of men.

Keywords: sandfish flesh powder, nutrition, reproduction quality, men

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Authors: Carmen M. Gonzalez-Henriquez, Mauricio A. Sarabia-Vallejos, Juan Rodriguez-Hernandez

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DMAEMA, as a monomer, has been widely studied and used in several application fields due to their pH-sensitive capacity (tertiary amine protonation), being relevant in the biomedical area as a potential carrier for drugs focused on the treatment of genetic or acquired diseases (efficient gene transfection), among others. Additionally, the inhibition of bacterial growth and, therefore, their antimicrobial activity, can be used as dual-functional antifogging/antimicrobial polymer coatings. According to their interesting physicochemical characteristics and biocompatible properties, DMAEMA was used as a monomer to synthesize a smart pH-sensitive hydrogel, namely poly(HEMA-co-PEGDA575-co-DMAEMA). Thus, different mole ratios (ranging from 5:1:0 to 0:1:5, according to the mole ratio between HEMA, PEGDA, and DEAEMA, respectively) were used in this research. The surface patterns formed via a two-step polymerization (redox- and photo-polymerization) were first chemically studied via 1H-NMR and elemental analysis. Secondly, the samples were morphologically analyzed by using Field-Emission Scanning Electron Microscopy (FE-SEM) and Atomic Force Microscopy (AFM) techniques. Then, a particular relation between HEMA, PEGDA, and DEAEMA (0:1:5) was also characterized at three different pH (5.4, 7.4 and 8.3). The hydrodynamic radius and zeta potential of the micro-hydrogel particles (emulsion) were carried out as a possible control for morphology, exploring the effect that produces hydrogel micelle dimensions in the wavelength, height, and roughness of the wrinkled patterns. Finally, contact angle and cross-hatch adhesion test was carried out for the hydrogels supported on glass using TSM-silanized surfaces in order to measure their mechanical properties.

Keywords: wrinkled patterns, smart pH-sensitive hydrogels, hydrogel micelle diameter, adhesion tests

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Authors: Rahaf Mandura

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Background: Idiopathic intracranial hypertension (IIH) is a disorder with elevated intracranial pressure (ICP) more than 250 mm H₂O, without evidence of meningeal inflammation, space-occupying lesion, or venous thrombosis. The aim of this research is to study the clinical profile, evaluation, management, and visual outcome in a hospital-based population of IIH cases in Jeddah. Methodology: This is a retrospective observational study that included the medical records of all patients referred to neuro-ophthalmology service for evaluation of papilledema. The medical records have been reviewed from October 2018 to February 2020 at Jeddah Eye Hospital (JEH), Saudi Arabia. A total of fifty-one patients presented with papilledema in the studied period. Forty-seven patients met our inclusion criteria and were included in the study. Results: Most of the patients were females (43, 91.5%) with a mean age of presentation of 30.83±11.40 years. The most common presenting symptom was headache (40 patients, 85.1%), followed by transient visual obscuration (20 patients, 42.6%), and reduced visual acuity (15 patients, 31.9%). All 47 patients were started on medical treatment with oral acetazolamide with four patients (8.5%) shifted to topiramate because of the lack of response or intolerance to acetazolamide while four patients (8.5%) underwent lumbar-peritoneal shunt because of inadequate control of the disease despite the treatment with medical therapy. For both eyes, the change in visual acuity across all assessment points was statistically significant. Nevertheless, there were no significant changes in the visual field findings among all of the compared assessment points. Conclusion: The present study has shown that IIH-related papilledema is common in young female patients with headaches, transient visual obscurations and reduced visual acuity. Those are the commonest symptoms in our IIH population. Medical treatment of IIH is significantly efficacious and should be considered in order to enhance the prognosis of IIH-related complications. Therefore, the visual status should be frequently monitored for these patients.

Keywords: idiopathic intracranial hypertension, intracranial hypertension, papilledema, headache

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Authors: Anish Shah, Steve A. Wakelin, Derrick Moot, Aurélie Laugraud, Hayley J. Ridgway

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A mixed pasture system of ryegrass-clover is used in New Zealand, where clovers are generally inoculated with commercially available strains of rhizobia. The community of rhizobia living in the soil and the way in which they interact with the plant are affected by different biotic and abiotic factors. In general, bacterial richness and diversity in soil varies by soil pH. pH also affects cell physiology and acts as a master variable that controls the wider soil physiochemical conditions such as P availability, Al release and micronutrient availability. As such, pH can have both primary and secondary effects on soil biology and processes. The aim of this work was to investigate the effect of soil pH on the genetic diversity and metabolic profile of Rhizobium leguminosarum strains nodulating clover. Soils were collected from 12 farms across New Zealand which had a pH(water) range of between 4.9 and 7.5, with four acidic (pH 4.9 – 5.5), four ‘neutral’ (5.8 – 6.1) and four alkaline (6.5 – 7.5) soils. Bacteria were recovered from nodules of Trifolium repens (white clover) and T. subterraneum (subterranean clover) grown in the soils. The strains were cultured and screened against a range of pH-amended media to demonstrate whether they were adapted to pH levels similar to their native soils. The strains which showed high relative growth at a given pH (~20% of those isolated) were selected for metabolic and taxonomic profiling. The Omnilog (Biolog Inc., Hayward, CA) phenotype array was used to perform assays on carbon (C) utilisation for selected strains. DNA was extracted from the strains which had differing C utilisation profiles and PCR products for both forward and reverse primers were sequenced for the following genes: 16S rRNA, recA, nodC, nodD and nifH (symbiotic).

Keywords: bacterial diversity, clover, metabolic and taxonomic profiling, pH adaptation, rhizobia

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Authors: Tzu-Hao Li, Shie-Liang Hsieh, Han-Chieh Lin, Ying-Ying Yang

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TNF superfamily-stimulated pathogenic cascades and macrophage (M1)/kupffer cells (KC) polarization are important in the pathogenesis of ischemia-reperfusion (IR) liver injury in animals with hepatic steatosis (HS). Decoy receptor 3 (DcR3) is a common upstream inhibitor of the above-mentioned pathogenic cascades. The study evaluated whether modulation of these DcR3-related cascades was able to protect steatotic liver from IR injury. Serum and hepatic DcR3 levels were lower in patients and animals with HS. Accordingly, the effects of pharmacologic and genetic DcR3 replacement on the IR-related pathogenic changes were measured. Significantly, DcR3 replacement protected IR-Zucker(HS) rats and IR-DcR3-Tg(HS) mice from IR liver injury. The beneficial effects of DcR3 replacement were accompanied by decreased serum/hepatic TNF, soluble TNF-like cytokine 1A (TL1A), Fas ligand (Fas-L) and LIGHT, T-helper-cell-1 cytokine (INF) levels, neutrophil infiltration, M1 polarization, neutrophil-macrophage/KC-T-cell interaction, hepatocyte apoptosis and improved hepatic microcirculatory failure among animals with IR-injured steatotic livers. Additionally, TL1A, Fas-L, LIGHT and TLR4/NFB signals were found to mediate the DcR3-related protective effects of steatotic livers from IR injury. Using multimodal in vivo and in vitro approaches, we found that DcR3 was a potential agent to protect steatotic livers from IR injury by simultaneous blocking the multiple IR injury-related pathogenic changes.

Keywords: Decoy 3 receptor, ischemia-reperfusion injury, M1 polarization, TNF superfamily

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Authors: Sonal Sethi, Mukesh Yadav, Abhimanyu Gupta

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The upcoming field of radiogenomics has the potential to upgrade the role of imaging in lung cancer management by noninvasive characterization of tumor histology and genetic microenvironment. Receptor positivity like epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) genotyping are critical in lung adenocarcinoma for treatment. As conventional identification of receptor positivity is an invasive procedure, we analyzed the features on non-invasive computed tomography (CT), which predicts the receptor positivity in lung adenocarcinoma. Retrospectively, we did a comprehensive study from 77 proven lung adenocarcinoma patients with CT images, EGFR and ALK receptor genotyping, and clinical information. Total 22/77 patients were receptor-positive (15 had only EGFR mutation, 6 had ALK mutation, and 1 had both EGFR and ALK mutation). Various morphological characteristics and metastatic distribution on CT were analyzed along with the clinical information. Univariate and multivariable logistic regression analyses were used. On multivariable logistic regression analysis, we found spiculated margin, lymphangitic spread, air bronchogram, pleural effusion, and distant metastasis had a significant predictive value for receptor mutation status. On univariate analysis, air bronchogram and pleural effusion had significant individual predictive value. Conclusions: Receptor positive lung cancer has characteristic imaging features compared with nonreceptor positive lung adenocarcinoma. Since CT is routinely used in lung cancer diagnosis, we can predict the receptor positivity by a noninvasive technique and would follow a more aggressive algorithm for evaluation of distant metastases as well as for the treatment.

Keywords: lung cancer, multidisciplinary cancer care, oncologic imaging, radiobiology

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Authors: Derya Yucel, Nigar Angın, Dürdane Mart, Meltem Turkeri, Volkan Catalkaya, Celal Yucel

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Chickpea (Cicer arietinum L.) is one of the important legumes widely grown for dietery proteins in semi-arid Mediteranean climatic conditions. To evaluate the genetic diversity with improved heat and drought tolerance capacity in chickpea, thirty-four selected chickpea genotypes were tested under different field-growing conditions (rainfed winter sowing, irrigated-late sowing and rainfed-late sowing) in 2015 growing season. A factorial experiment in randomized complete block design with 3 reps was conducted at the Eastern Mediterranean Research Institute Adana, Turkey. Based on grain yields under different growing conditions, several indices were calculated to identify economically higher-yielding chickpea genotypes with greater heat and drought tolerance capacity. Average across chickpea genotypes, the values of tolerance index, mean productivity, yield index, yield stability index, stress tolerance index, stress susceptibility index, and geometric mean productivity were ranged between 1.1 to 218, 38 to 202, 0.3 to 1.7, 0.2 to 1, 0.1 to 1.2, 0.02 to 1.4, and 36 to 170 for drought stress and 3 to 54, 23 to 118, 0.3 to 1.7, 0.4 to 0.9, 0.2 to 2, 0.2to 2.3, and 23 to 118 for heat stress, respectively. There were highly significant differences observed among the tested chickpea genotypes response to drought and heat stresses. Among the chickpea genotypes, the Aksu, Arda, Çakır, F4 09 (X 05 TH 21-16189), FLIP 03-108 were identified with a higher drought and heat tolerance capacity. Based on our field studies, it is suggested that the drought and heat tolerance indicators of plants can be used by breeders to select stress-resistant economically productive chickpea genotypes suitable to grow under Mediteranean climatic conditions.

Keywords: irrigation, rainfed, stress susceptibility, tolerance indice

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Authors: Yuriy A. Knirel

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Enteric bacteria Escherichia coli is the predominant facultative anaerobe of the colonic flora, and some specific serotypes are associated with enteritis, hemorrhagic colitis, and hemolytic uremic syndrome. Shigella spp. are human pathogens that cause diarrhea and bacillary dysentery (shigellosis). They are in effect E. coli with a specific mode of pathogenicity. Strains of Salmonella enterica are responsible for a food-borne infection (salmonellosis), and specific serotypes cause typhoid fever and paratyphoid fever. All these bacteria are closely related in respect to structure and genetics of the lipopolysaccharide, including the O-polysaccharide part (O‑antigen). Being exposed to the bacterial cell surface, the O antigen is subject to intense selection by the host immune system and bacteriophages giving rise to diverse O‑antigen forms and providing the basis for typing of bacteria. The O-antigen forms of many bacteria are unique, but some are structurally and genetically related to others. The sequenced O-antigen gene clusters between conserved galF and gnd genes were analyzed taking into account the O-antigen structures established by us and others for all S. enterica and Shigella and most E. coli O-serogroups. Multiple genetic mechanisms of diversification of the O-antigen forms, such as lateral gene transfer and mutations, were elucidated and are summarized in the present paper. They include acquisition or inactivation of genes for sugar synthesis or transfer or recombination of O-antigen gene clusters or their parts. The data obtained contribute to our understanding of the origins of the O‑antigen diversity, shed light on molecular evolutionary relationships between the O-antigens of enteric bacteria, and open a way for studies of the role of gene polymorphism in pathogenicity.

Keywords: enteric bacteria, O-antigen gene cluster, polysaccharide biosynthesis, polysaccharide structure

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Authors: Olumayowa M. Olowe, Michael D. Asemoloye Odunayo J. Olawuyi, Hilda Vasanthakaalam

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Poor management of maize ear rot caused by fungal infection in Nigeria affected the quantity and quality of maize. This study, therefore, aims at characterizing and controlling Fusarium strains using arbuscular mycorrhizal fungi. Maize ear showing rot symptoms were obtained from some selected farms located at Ilesa East and West using random sampling technique. Isolation of Fusarium pathogen from infected maize grain was done using direct pour plate method on potato dextrose agar (PDA) and was characterized based on morphological and molecular ITS-amplification methods. The reaction of PVASYN8F2, T2LCOMP1STR SYN-W-1, and T2LCOMP4 maize varieties, to the Fusarium ear rot pathogens and biocontrol efficacy of the mycorrhizal fungi were assessed on growth, yield, agronomic parameters and symptoms observed. The strains; olowILH1 and olowILH2 identified as Fusarium napiforme were the most dominant and virulent pathogens associated with the maize. They showed genetic similarity with documented ear rot pathogens on NCBI with accession numbers Fusarium proliferatum KT224027, KT224023, and Fusarium sp AY237110. They both exhibited varying inhibitory effects on the three maize varieties compare to control (uninfected plant) which had better growth characteristics. It was also observed that strain olowILH1 was more virulent than olowILH2. T2LCOMP4 was generally more susceptible to both fungal strains compared to the other two maize (T2LCOMP1STR SYN-W-1 and T2LCOMP4 ). In all, strain olowILH1 was more virulent than olowILH2, and Glomus clarum had higher inhibitory pathogenic effect against Fusarium strains compared to G. deserticola.

Keywords: arbuscular mycorrhizal fungi, disease management, Fusarium strains, identification

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Authors: Leila M. Carvalho, Maria Erica S. Oliveira, Arnoud C. Neto, Elza I. Ida, Massami Shimokomaki, Marta S. Madruga

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The quality of broiler breast meat is changing as a result of the continuing emphasis on genetic selection for a more efficient meat production. Breast meat has been classified as PSE (pale, soft, exudative), DFD (dark, firm, dry) and normal color meat, and recently a third group has emerged: the so-called PFN (pale, firm, non-exudative) meat. This classification was based on pH, color and functional properties. The aim of this work was to confirm the existence of PFN and PSE meat by biochemical characterization and functional properties. Twenty four hours of refrigerated fillet, Pectoralis major, m. samples (n= 838) were taken from Cobb flocks 42-48 days old, obtained in Northeastern Brazil tropical region, the Northeastern, considered to have only dry and wet seasons. Color (L*), pH, water holding capacity (WHC), values were evaluated and compared with PSE group samples. These samples were classified as Normal (465.8), PSE meat (L*≥53; pH<5.8) and PFN (L*≥53; pH>5.8). The occurrence of control meat, PSE and PFN was 69.09%, 11.10% and 19.81%, respectively. Samples from PFN presented 4.0-5.0% higher WHC in relation to PSE meat and similar to control group. These results are explained by the fact that PSE meat syndrome occurs because of higher protein denaturation as the consequence of a simultaneous lower pH values under warm carcass sooner after slaughtering impairing the myofibril proteins functional properties. Conversely, PFN samples follow normal glycolysis rate maintaining the normal proteins activities. In conclusion, the results reported herein confirm the existence of this emerging broiler meat group with similar properties as control group and it should be considered as normal breast meat group.

Keywords: broiler breast meat, funcional properties, PFN, PSE

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Authors: Vidia A. Nuraini, Eugene M. H. Yee, Mohan Bhadbhade, David StC. Black, Naresh Kumar

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Flavonoids are naturally occurring compounds that have been shown to exhibit a wide range of biological properties including anticancer and anti-inflammatory activities. However, flavonoids suffer from low bioavailability, which limits their overall utility for therapeutic applications. One of the methods to overcome this limitation is through structural modification of natural flavonoids. In this study, flavanone, isoflavanone, and isoflavene, were structurally modified through the introduction of additional fused-ring systems via ortho-quinone methide intermediates (o-QMs). These intermediates can readily undergo a [4+2] cycloaddition through an inverse-electron-demand Diels–Alder reaction with electron-rich dienophiles. A regioselective Mannich reaction using bis-(N,N-dimethylamino)methane was employed to generate the o-QM precursors of flavanone, isoflavanone, and isoflavene. The o-QM intermediates were subsequently generated in situ through thermal elimination of the dimethylamine functionality and reacted with a variety of dienophiles to produce novel flavonoids with fused-ring systems. A total of 21 novel flavonoid analogs were successfully synthesized. The X-ray crystal structure of cycloaddition adducts, particularly those derived from 3,4-dihydro-2H-pyran and p-methoxystyrene revealed a special case of enantiomeric disorder, where two enantiomers in equal amounts superpose with one another, with the exception for atoms that have opposite configuration. The anticancer properties of fused-ring systems derived from isoflavene were evaluated against the neuroblastoma SKN-BE(2)C, the triple negative breast cancer MDA-MB-231, and the glioblastoma U87 cancer cell lines. One of these cycloaddition adducts had displayed improved anti-proliferative activity against MDA-MB-231 and U87 cancer cell lines as compared to the parent compound. Further anticancer and anti-inflammatory activities of the flavanone and isoflavanone analogs are currently being investigated.

Keywords: Diels-Alder reaction, flavonoids, Mannich reaction, ortho-quinone methide.

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