Search results for: recombinant human bone morphogenetic protein

Authors: R. Ranjith Kumar

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Computer modeling and simulation of human movement is playing an important role in sports and rehabilitation. Accurate modeling and analysis of human knee join is more complex because of complicated structure whose geometry is not easily to represent by a solid model. As part of this project, from the number of CT scan images of human knee join surface reconstruction is carried out using 3D slicer software, an open source software. From this surface reconstruction model, using mesh lab (another open source software) triangular meshes are created on reconstructed surface. This final triangular mesh model is imported to Solid Works, 3D mechanical CAD modeling software. Finally this CAD model is imported to ABAQUS, finite element analysis software for analyzing the knee joints. The results obtained are encouraging and provides an accurate way of modeling and analysis of biological parts without human intervention.

Keywords: solid works, CATIA, Pro-e, CAD

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Authors: Hamim Abbas, Jean Luc-Hornick, Isabelle Dufrasne

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Feed costs constitute over 60% of total expenses in organic layer poultry production, with feed protein supply being a significant concern. Alfalfa-based dehydrated silage pellets are mainly diets composed of leaves (ABSP), which are non-conventional protein sources that could enhance profits by reducing feed costs and ensuring consistent availability. This experiment studied the effects on the performances of Novogen Brown light layers of a commercial control diet replaced with 10% ABSP. After a 21-day trial, this diet (ABSP) has improved the laying rate, yolk color of eggs, feed conversion rate, ω−3 (PUFAs) and ω−6/ω−3 ratio (P<0.05) while the body weight and egg weight were degraded with the substitution of the ABSP in the diet(P>0.05). The laying rate showed a tendency to increase (P=0.06). These findings suggest that ABSP can replace at least 10% of the feed in organic layer diets without compromising production parameters negatively.

Keywords: alfalfa, silage, pellet, organic layers

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Authors: Anjelika Kremer, Irina Nachimov, Dan Justo

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Background: C-reactive protein (CRP) serum levels are commonly measured in hospitalized patients. Elevated admission CRP serum levels and in-hospital mortality has been seldom studied in the general population of elderly patients admitted to the acute Geriatrics department. Methods: A retrospective cross-sectional study was conducted at a tertiary medical center. Included were all elderly patients (age 65 years or more) admitted to a single acute Geriatrics department from the emergency room between April 2014 and January 2015. CRP serum levels were measured routinely in all patients upon the first 24 hours of admission. A logistic regression analysis was used to study if admission CRP serum levels were associated with in-hospital mortality independent of age, gender, functional status, and co-morbidities. Results: Overall, 498 elderly patients were included in the analysis: 306 (61.4%) female patients and 192 (38.6%) male patients. The mean age was 84.8±7.0 years (median: 85 years; IQR: 80-90 years). The mean admission CRP serum levels was 43.2±67.1 mg/l (median: 13.1 mg/l; IQR: 2.8-51.7 mg/l). Overall, 33 (6.6%) elderly patients died during the hospitalization. A logistic regression analysis showed that in-hospital mortality was independently associated with history of stroke (p < 0.0001), heart failure (p < 0.0001), and admission CRP serum levels (p < 0.0001) – and to a lesser extent with age (p = 0.042), collagen vascular disease (p=0.011), and recent venous thromboembolism (p=0.037). Receiver operating characteristic (ROC) curve showed that admission CRP serum levels predict in-hospital mortality fairly with an area under the curve (AUC) of 0.694 (p < 0.0001). Cut-off value with maximal sensitivity and specificity was 19.7 mg/L. Conclusions: Admission CRP serum levels may be used to predict in-hospital mortality in the general population of elderly patients admitted to the acute Geriatrics department.

Keywords: c-reactive protein, elderly, mortality, prediction

Procedia PDF Downloads 239

Authors: Ampe Mohottige Sachinthi Sandaruwani Amarasiri, Anoja Priyadarshani Attanayake, Kamani Ayoma Perera Wijewardana Jayatilaka, Lakmini Kumari Boralugoda Mudduwa

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The search for alternative pharmacological therapies based on natural extracts for renal failure has become an urgent need, due to paucity of effective pharmacotherapy. The current study was undertaken to evaluate the acute nephroprotective effect of aqueous leaf extract of Plectranthus amboinicus (Roxb.) (Family: Lamiaceae), a medicinal plant used in traditional Ayurvedic medicine for the management of renal diseases in Sri Lanka. The study was performed in adriamycin (ADR) induced nephrotoxic in Wistar rats. Wistar rats were randomly divided into four groups each with six rats. A single dose of ADR (20 mg/kg body wt., ip) was used for the induction of nephrotoxicity in all groups of rats except group one. The treatments were started 24 hours after induction of nephrotoxicity and continued for three days. Group one and two served as healthy and nephrotoxic control rats and were administered equivalent volumes of normal saline (0.9% NaCl) orally. Group three and four nephrotoxic rats were administered the lyophilized powder of the aqueous extract of P. amboinicus (400 mg/ kg body wt.; equivalent human therapeutic dose) and the standard drug, fosinopril sodium (0.09 mg/ kg body wt.) respectively. Urine and blood samples were collected from rats in each group at the end of the period of intervention for the estimation of selected renal parameters. H and E stained sections of the kidney tissues were examined for histopathological changes. Rats treated with the plant extract showed significant improvement in biochemical parameters and histopathological changes compared to ADR induced nephrotoxic group. The elevation of serum concentrations of creatinine and β2-microglobulin were decreased by 38%, and 66% in plant extract treated nephrotoxic rats respectively (p < 0.05). In addition, serum concentrations of total protein and albumin were significantly increased by 25% and 14% in rats treated with P. amboinicus respectively (p < 0.05). The results of β2 –microglobulin and serum total protein demonstrated a significant reduction in the elevated values in rats administered with the plant extract (400 mg/kg) compared to that of fosinopril (0.09 mg/kg). Urinary protein loss in 24hr urine samples was significantly decreased in rats treated with both fosinopril (86%) and P. ambonicus (56%) at the end of the intervention (p < 0.01). Accordingly, an attenuation of morphological destruction was observed in the H and E stained sections of the kidney with the treatments of plant extract and fosinopril. The results of the present study revealed that the aqueous leaf extract of P. amboinicus possesses significant nephroprotective activity at the equivalent therapeutic dose of 400 mg/ kg against adriamycin induced acute nephrotoxicity.

Keywords: biochemical assessment, histopathological assessment, nephroprotective activity, Plectranthus amboinicus

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Authors: Su Mon Saw, Joe Rothnagel

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Short open reading frames (sORFs) located in 5’UTR of mRNAs are known as uORFs. Characterization of uORF-encoded peptides (uPEPs) i.e., a subset of short open reading frame encoded peptides (sPEPs) and their translation regulation lead to understanding of causes of genetic disease, proteome complexity and development of treatments. Existence of uORFs within cellular proteome could be detected by LC-MS/MS. The ability of uORF to be translated into uPEP and achievement of uPEP identification will allow uPEP’s characterization, structures, functions, subcellular localization, evolutionary maintenance (conservation in human and other species) and abundance in cells. It is hypothesized that a subset of sORFs are translatable and that their encoded sPEPs are functional and are endogenously expressed contributing to the eukaryotic cellular proteome complexity. This project aimed to investigate whether sORFs encode functional peptides. Liquid chromatography-mass spectrometry (LC-MS) and bioinformatics were thus employed. Due to probable low abundance of sPEPs and small in sizes, the need for efficient peptide enrichment strategies for enriching small proteins and depleting the sub-proteome of large and abundant proteins is crucial for identifying sPEPs. Low molecular weight proteins were extracted using SDS-PAGE from Human Embryonic Kidney (HEK293) cells and Strong Cation Exchange Chromatography (SCX) from secreted HEK293 cells. Extracted proteins were digested by trypsin to peptides, which were detected by LC-MS/MS. The MS/MS data obtained was searched against Swiss-Prot using MASCOT version 2.4 to filter out known proteins, and all unmatched spectra were re-searched against human RefSeq database. ProteinPilot v5.0.1 was used to identify sPEPs by searching against human RefSeq, Vanderperre and Human Alternative Open Reading Frame (HaltORF) databases. Potential sPEPs were analyzed by bioinformatics. Since SDS PAGE electrophoresis could not separate proteins <20kDa, this could not identify sPEPs. All MASCOT-identified peptide fragments were parts of main open reading frame (mORF) by ORF Finder search and blastp search. No sPEP was detected and existence of sPEPs could not be identified in this study. 13 translated sORFs in HEK293 cells by mass spectrometry in previous studies were characterized by bioinformatics. Identified sPEPs from previous studies were <100 amino acids and <15 kDa. Bioinformatics results showed that sORFs are translated to sPEPs and contribute to proteome complexity. uPEP translated from uORF of SLC35A4 was strongly conserved in human and mouse while uPEP translated from uORF of MKKS was strongly conserved in human and Rhesus monkey. Cross-species conserved uORFs in association with protein translation strongly suggest evolutionary maintenance of coding sequence and indicate probable functional expression of peptides encoded within these uORFs. Translation of sORFs was confirmed by mass spectrometry and sPEPs were characterized with bioinformatics.

Keywords: bioinformatics, HEK293 cells, liquid chromatography-mass spectrometry, ProteinPilot, Strong Cation Exchange Chromatography, SDS-PAGE, sPEPs

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Authors: V. Diaz, B. Pardo , D. Villegas

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In premature births most babies have complications at birth, these complications can be reduced, if an atmosphere of relaxation is provided and is also similar to intrauterine life, for this, there are programs where their mothers lull and sway them; however, the conditions in which they do so and the way in they do it may not be the indicated. Here we describe an investigation based on the biomimics of the kinematics of human fetal movement, which consists of determining the movements that the fetus experiences and the deformations of the components that surround the fetus during a gentle walk at week 32 of the gestation stage. This research is based on a 3D model that has the anatomical structure of the pelvis, fetus, muscles, uterus and its most important supporting elements (ligaments). Normal load conditions are applied to this model according to the stage of gestation and the kinematics of a gentle walk of a pregnant mother, which focuses on the pelvic bone, this allows to receive a response from the other elements of the model. To accomplish this modeling and subsequent simulation Solidworks software was used. From this analysis, the curves that describe the movement of the fetus at three different points were obtained. Additionally, we could found the deformation of the uterus and the ligaments that support it, showing the characteristics that these tissues can have in the face of the support of the fetus. These data can be used for the construction of artifacts that help the normal development of premature infants.

Keywords: simulation, biomimic, uterine model, fetal movement study

Procedia PDF Downloads 165

Authors: P. Annapurna, Cecil Ross, Sudhir Krishna, Sweta Srivastava

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Irradiation plays a pivotal role in cervical cancer treatment, however some tumors exhibit resistance to therapy while some exhibit relapse, due to better repair and enhanced resistance mechanisms operational in their cells. The present study aims to understand the signaling mechanism operational in resistance phenotype and in the present study we report the role of Rho GTPase associated protein kinase (ROCK) signaling in cervical carcinoma radio-resistance. ROCK signaling has been implicated in several tumor progressions and is important for DNA repair. Irradiation of spheroid cultures of SiHa cervical carcinoma derived cell line at 6Gy resulted in generation of resistant cells in vitro which had better clonogenic abilities and formed larger and more colonies, in soft agar colony formation assay, as compared to the non-irradiated cells. These cells also exhibited an enhanced motility phenotype. Cell cycle profiling showed the cells to be blocked in G2M phase with enhanced pCDC2 levels indicating onset of possible DNA repair mechanism. Notably, 3 days post-irradiation, irradiated cells showed increased ROCK2 translocation to the nucleus with enhanced protein expression as compared to the non-irradiated cells. Radio-sensitization of the resistant cells was enhanced using Y27632, an inhibitor to ROCK signaling. The treatment of resistant cells with Y27632 resulted in increased cell death upon further irradiation. This observation has been confirmed using inhibitory antibodies to ROCK1/2. Result show that both ROCK1/2 have a functional contribution in radiation resistance of cervical cancer cells derived from cell lines. Interestingly enrichment of stem like cells (Hoechst negative cells) was also observed upon irradiation and these cells were markedly sensitive to Y27632 treatment. Our results thus suggest the role of ROCK signaling in radio-resistance in cervical carcinoma. Further studies with human biopsies, mice models and mechanistic of ROCK signaling in the context of radio-resistance will clarify the role of this molecule further and allow for therapeutics development.

Keywords: cervical carcinoma, radio-resistance, ROCK signaling, cancer treatment

Procedia PDF Downloads 332

Authors: Kalinina Anastasiya, Pevnaya Mariya

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The authors present the results of research of educational and cultural habitat of international students at Ural Federal University, revealing problem zones in the organization of adaptation program in 2014-2015 as well as innovations in adaptation program for 2015-2016. The research is based on U-curve theory of culture shock and theory of human capital. The authors provide also the first results for all stakeholders of practically implemented pilot adaptation program for foreign students which was based on the human capital approach.

Keywords: adaptation, human capital, international students, student volunteering, social community, youth politics

Procedia PDF Downloads 350

Authors: Feifei Wu, Pius Babuna, Xiaohua Yang

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The suitability evaluation of human settlements over time and space is essential to track potential challenges towards suitable human settlements and provide references for policy-makers. This study established a theoretical framework of human settlements based on the nature, human, economy, society and residence subsystems. Evaluation indicators were determined with the consideration of the coupling effect among subsystems. Based on the extended Fourier amplitude sensitivity test algorithm, the global sensitivity analysis that considered the coupling effect among indicators was used to determine the weights of indicators. The human settlement suitability was evaluated at both subsystems and comprehensive system levels in 30 provinces of China between 2000 and 2016. The findings were as follows: (1) human settlements suitability index (HSSI) values increased significantly in all 30 provinces from 2000 to 2016. Among the five subsystems, the suitability index of the residence subsystem in China exhibited the fastest growinggrowth, fol-lowed by the society and economy subsystems. (2) HSSI in eastern provinces with a developed economy was higher than that in western provinces with an underdeveloped economy. In con-trast, the growing rate of HSSI in eastern provinces was significantly higher than that in western provinces. (3) The inter-provincial difference of in HSSI decreased from 2000 to 2016. For sub-systems, it decreased for the residence system, whereas it increased for the economy system. (4) The suitability of the natural subsystem has become a limiting factor for the improvement of human settlements suitability, especially in economically developed provinces such as Beijing, Shanghai, and Guangdong. The results can be helpful to support decision-making and policy for improving the quality of human settlements in a broad nature, human, economy, society and residence context.

Keywords: human settlements, suitability evaluation, extended fourier amplitude, human settlement suitability

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Authors: Sajad A. Rather, F. A. Masoodi, Rehana Akhter, S. M. Wani, Adil Gani

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Modern trend towards convenience foods has resulted in increased production and consumption of restructured meat products and are of great importance to the meat industry. In meat products fat plays an important role in cooking properties, texture & sensory scores, however, high fat contents in particular animal fats provide high amounts of saturated fatty acids and cholesterol and are associated with several types of non communicable diseases such as obesity, hypertension and coronary heart diseases. Thus, fat reduction has generally been seen as an important strategy to produce healthier meat products. This study examined the effects of reducing fat level from 20% to 10% and substituting mutton back fat with guar gum (0.5%, 1% & 1.5%) on cooking properties, proximate composition, lipid and protein oxidation, texture, microstructure and sensory characteristics of goshtaba- a traditional meat product of J & K, India were investigated and compared with high fat counterparts. Reduced- fat goshtaba samples containing guar gum had significantly (p ≤ 0.05) higher yield, less shrinkage, more moisture retention and more protein content than the control sample. TBARs and protein oxidation (carbonyl content) values of the control was significantly (p ≤ 0.05) higher than reduced fat goshtaba samples and showed a positive correlation between lipid and protein oxidation. Hardness, gumminess & chewiness of the control (20%) were significantly higher than reduced fat goshtaba samples. Microstructural differences were significant (p ≤ 0.05) between control and treated samples due to an increased moisture content in the reduced fat samples. Sensory evaluation showed significant (p ≤ 0.05) reduction in texture, flavour and overall acceptability scores of treatment products; however the scores for 0.5% and 1% treated samples were in the range of acceptability. Guar gum may also be used as a source of soluble dietary fibre in food products and a number of clinical studies have shown a reduction in postprandial glycemia and insulinemia on consumption of guar gum, with the mechanism being attributed to an increased transit time in the stomach and small intestine, which may have been due to the viscosity of the meal hindering the access of glucose to the epithelium.

Keywords: goshtaba, guar gum, traditional, fat reduction, acceptability

Procedia PDF Downloads 281

Authors: Ellen Kirkpatrick

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Deforestation, toxification, and loss of environmental habitats, accompanied by expanding production and urbanization, are visibly altering planetary life. This is bringing humans and non-human nature into closer contact, resulting in the emergence of infectious diseases such as the Covid-19 virus which, while zoonotic in origin, spread through market relations and networks of local and global production. However, while the pandemic sharply illuminated the role of labour within social transformations, the question remains about the role of labour in transforming ecological relations. Drawing on a historical materialist approach, this paper explores the emergence and transmission of the COVID-19 virus through the Marxist conceptualization of metabolic rift. This allows for a perspective of human and non-human nature, which is in constant motion and dialectical. This negotiates distinctions and binaries between them as humans and non-human nature are taken to mutually constrain, enable and constitute one another. This is particularly significant when considering the ongoing transformations of a climate-changing world and the corresponding effects on social life. To do this, this paper empirically focuses on the Huanan Seafood Wholesale Market in Wuhan, China, where the COVID-19 virus was first detected. It examines how the virus jumped from non-human animals to humans through concrete production operations locally before traveling globally through networks of abstract market relations based on the logic of circulation, trade and exchange. As a mediating relation between human and non-human nature, labour is an analytical tool that can create a dialogue between the concrete and the abstract, as well as the local and global.

Keywords: Marxism, social reproduction, metabolic rift, labour

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Authors: Nusrat Praween, Krishna Thej Pammi Guru, Palash Kumar Basu

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Designing non-invasive biosensors for cancer diagnosis is essential for developing an affordable and specific tool to measure cancer-related exosome biomarkers. Exosomes, released by healthy as well as cancer cells, contain valuable information about the biomarkers of various diseases, including cancer. Despite the availability of various isolation techniques, ultracentrifugation is the standard technique that is being employed. Post isolation, exosomes are traditionally exposed to detergents for extracting their proteins, which can often lead to protein degradation. Further to this, it is very essential to develop a sensing platform for the quantification of clinically relevant proteins in a wider range to ensure practicality. In this study, exosomes were immobilized on the Au Screen Printed Electrode (SPE) using EDC/NHS chemistry to facilitate binding. After immobilizing the exosomes on the screen-printed electrode (SPE), we investigated the impact of the electric field by applying various voltages to induce exosome lysis and release their contents. The lysed solution was used for sensing TSG101, a crucial biomarker associated with various cancers, using both faradaic and non-faradaic electrochemical impedance spectroscopy (EIS) methods. The results of non-faradaic and faradaic EIS were comparable and showed good consistency, indicating that non-faradaic sensing can be a reliable alternative. Hence, the non-faradaic sensing technique was used for label-free quantification of the TSG101 biomarker. The results were validated using ELISA. Our electrochemical immunosensor demonstrated a consistent response of TSG101 from 125 pg/mL to 8000 pg/mL, with a detection limit of 0.125 pg/mL at room temperature. Additionally, since non-faradic sensing is label-free, the ease of usage and cost of the final sensor developed can be reduced. The proposed immunosensor is capable of detecting the TSG101 protein at low levels in healthy serum with good sensitivity and specificity, making it a promising platform for biomarker detection.

Keywords: biosensor, exosomes isolation on SPE, electric field lysis of exosome, EIS sensing of TSG101

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Authors: Ramazan F. Akkoc, Elif Erdem, Nalan Kaya, Gonca Ozan, D. Özlem Dabak, Enver Ozan

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Maternal tobacco smoke exposure is known to cause growth retardation in the neonatal skeletal system. Alpha lipoic acid, a natural antioxidant found in some foods, limits the activities of osteoclasts and supports the osteoblast's bone formation mechanism. In this study, it was aimed to investigate the effects of alpha lipoic acid (ALA) on the height, long bones and tail lengths of pups exposed to maternal tobacco smoke. The rats were divided into four groups: 1) control group, 2) tobacco smoke group, 3) tobacco smoke + ALA group, and 4) ALA group. Rats in the group 2 (tobacco smoke), group 3 (tobacco smoke + ALA) were exposed to tobacco smoke twice a day for one hour starting from eight weeks before mating and during pregnancy. In addition to tobacco smoke, 20 mg/kg of alpha lipoic acid was administered via oral gavage to the rats in the group 3 (tobacco smoke + ALA). Only alpha lipoic acid was administered to the rats in the group 4. On day 21 postpartum, the height and tail lengths of the pups in all groups were measured, and the length of the extremity long bones was measured after decapitation. All morphometric measurements performed in group 2 (tobacco smoke) showed a significant decrease compared to group 1 (control), while all measurements in group 3 (tobacco smoke + ALA) showed a significant increase compared to group 2 (tobacco smoke). It has been shown that ALA has a protective effect against the regression of height, long bones and tail lengths of pups exposed to maternal tobacco smoke.

Keywords: alpha lipoic acid, bone, morphometry, rat, tobacco smoke

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Authors: Rishi Saxena

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Cyanobacteria is a photosynthetic prokaryote, and these obtain their energy through photosynthesis. In this paper, we studied the effect of iron on metabolic changes in the diazotrophic cyanobacterium Anabaena PCC 7120. Nowadays, metal contamination due to natural and anthropogenic sources is a global environment concern. Iron induced changes in growth, N2-fixation, CO2 fixation and photosynthetic activity were studied in a diazotrophic cyanobacterium Anabaena PCC 7120. Iron at 50 uM concentration supported the maximum growth, heterocyst frequency, CO2 fixation, photosystem I (PS I), photosystem II (PS II) and nitrogenase activities in the organism. Higher concentration of iron inhibited these processes. Chl a and PS II activities were more sensitive to iron than the protein and PS I activity. Here, it is also mentioned that heavy metal induced altered macromolecules metabolism and changes in the central dogma of life (DNA→ mRNA → Protein). And also recent advances have been made in understanding heavy metal-cyanobacteria interaction and their application for metal detoxification.

Keywords: cyanobacterium anabaena 7120, nitrogen fixation, photosystem I (PS I), photosystem II (PS II)

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Authors: S. Alireza Mirghasemi, Javad Parvizi, Narges R. Gabaran, Shervin Rashidinia, Mahdi M. Bijanabadi, Dariush G. Savadkoohi

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Background: The anterior cruciate ligament is one of the most frequent ligament to be disrupted. Surgical reconstruction of the anterior cruciate ligament is a common practice to treat the disability or chronic instability of the knee. Several factors associated with success or failure of the ACL reconstruction including preoperative laxity of the knee, selection of the graft material, surgical technique, graft tension, and postoperative rehabilitation. We aimed to examine the biomechanical properties of any graft type and initial graft tensioning during ACL reconstruction using 3-dimensional computational finite element simulation. Methods: In this paper, 3-dimensional model of the knee was constructed to investigate the effect of graft tensioning on the knee joint biomechanics. Four different grafts were compared: 1) Bone-patellar tendon-bone graft (BPTB) 2) Hamstring tendon 3) BPTB and a band of gracilis4) Hamstring and a band of gracilis. The initial graft tension was set as “0, 20, 40, or 60N”. The anterior loading was set to 134 N. Findings: The resulting stress pattern and deflection in any of these models were compared to that of the intact knee. The obtained results showed that the combination of a band of gracilis with the former graft (BPTB or Hamstring) increases the structural stiffness of the knee. Conclusion: Required pretension during surgery decreases significantly by adding a band of gracilis to the proper graft.

Keywords: ACL reconstruction, deflection, finite element simulation, stress pattern

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Authors: M. Dezyani, R. Ezzati, H. Mirzaei

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The objectives of this study were to determine the effect of pH on chemical, structural, and functional properties of Fetta cheese, and to relate changes in structure to changes in cheese unctionality. Fetta cheese was obtained from a cheese-production facility and stored at 4°C. Ten days after manufacture, the cheese was cut into blocks that were vacuum-packaged and stored for 4 d at 4°C. Cheese blocks were then high-pressure injected one, three, or five times with a 20% (wt/wt) glucono-δ-lactone solution. Successive injections were performed 24 h apart. Cheese blocks were then analyzed after 40 d of storage at 4°C. Acidulant injection decreased cheese pH from 5.3 in the uninjected cheese to 4.7 after five injections. Decreased pH increased the content of soluble calcium and slightly decreased the total calcium content of cheese. At the highest level, injection of acidulant promoted syneresis. Thus, after five injections, the moisture content of cheese decreased from 34 to 31%, which esulted in decreased cheese weight. Lowered cheese pH, 4.7 compared with 5.3, also resulted in contraction of the protein matrix. Acidulant injection decreased cheese hardness and cohesiveness, and the cheese became more crumbly.

Keywords: calcium, high-pressure injection, protein matrix, syneresis

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Authors: Mahsa Jalili, Essa Ehsan Khan, Signe Dille Lovmo, Augustine Akruwe, Egil Lien, Rolf Erik Olsen, Trygve Sigholt, Atle Magnus Bones

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Data from the Norwegian Directorate of Fisheries reported that >1.2 million tons of Atlantic salmon were produced in Norway aquaculture industry in 2016. Peroxisome proliferator-activated receptors (PPARs) are one of the key transcription factor families that respond to nutritional ligands. Recent studies have shown the connection between PPARs with lipid and carbohydrate metabolism in aquaculture. To our knowledge, there is no published data about the effects of krill meal, soybean meal, Bactocell ® and butyrate feedings compared to control group on PPARs gene and protein expressions in Atlantic salmon. Fish, 1year +postsmolt, average weight 250 gram were cultured for 12 weeks after acclimatization by control commercial feeding in 2 weeks after hatchery. Water oxygen rate, salinity, and temperature were monitored every second day. At the end of the trial, fish were taken from tanks randomly, and four replicates per group were collected and stored in -80 freezers until analysis. Total RNA extracted from posterior part of dorsal fin muscle tissues and Nanodrop and Bioanalyzer was used to check the quality of RNA. Gene expression of PPAR α, β and γ were determined by RT-PCR. The expression of genes of interest was measured relative to control group after normalization to three reference genes. Total protein concentration was calculated by Bradford method, and protein expression was determined with primary PPARγ antibody by western blot. All data were analyzed by ANOVA followed by Benjamini-Hochberg and Bonferroni tests. Probability values <0.05 considered significant. Bactocell® and butyrate groups showed significantly lower PPARα expression. PPARβ and γ were not significantly different among groups. PPARγ mRNA expression was approximately consistent with protein expression pattern, except than butyrate group showed lower mRNA level. The order of PPARγ expression was Bactocell® > soy meal > butyrate > krill meal > control respectively. PPARβ gene expression decreased more in soy meal > butyrate > krill meal > Bactocell® > control groups respectively. In conclusion, the increased expression of PPARγ and α is proposed to represent a reduction tendency of lipid storage in fish fed by Bactocell®, butyrate, soy and krill meal.

Keywords: aquaculture, blotting western, gene expression, krill protein extract, prebiotics, probiotics, Salmo salar

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Authors: Xiwu Feng

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The paper is to analyze research ethics in social and behavioral sciences from a cross-cultural perspective. A multi-phase study investigated implementations of ethical standards and guidelines in higher institutions in China. Institutional policies and procedures on human subject research and perceptions of human subject protection were assessed in the Chinese research universities from different regions. The findings of the study indicate that the implementations of ethical standards and guidelines vary from institution to institution and from region to region. Education and cultural backgrounds of the participants influence their perceptions of the welfare and privacy of human subjects. The results of the study reveal great differences and complexities in ethical standards for the protection of human subjects of research in contrast to the Western world. The Chinese collectivistic values and the cooperative-harmonious democracy play a significant role in perceiving and implementing ethical guidelines. Chinese researchers find themselves a long way to go before seeing implementations of regulations and guidelines on human subject research in social and behavioral sciences.

Keywords: ethical standards, human subjects, research ethics, social and behavioral research

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Authors: Khelladi Hadj Mostefa, Krouf Djamil, Taleb-Dida Nawel

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Background: Obesity results from a prolonged imbalance between energy intake and energy expenditure, as depending on basal metabolic rate. Oils and proteins from sea have important therapeutic (such as obesity and hypercholesterolemia) and antioxidant effects. Sardine are a widely consumed fish in the Mediterranean region. Its consumption provides humans with various nutrients such as oils (rich in omega 3 plyunsaturated fatty acids)) and proteins. Methods: Sardine oil (SO) and sardine proteins (SP) were extracted and purified. Mixture of vegetable oils (olive-walnut-sunflower) were prepared from oils produced in Algeria. Eighteen wistar rats are fed a high fat diet enriched with 1% cholesterol for 30 days to induce obesity and hypercholesterolemia. The rats are divided into 3 groups. The first group consumes 20% sardine protein combined with 5% sardine oil (38% SFA (saturated fatty acids), 31% MIFA (monounsaturated fatty acids) and 31% PIFA (polyunsaturated fatty acids)) (SPso). The second group consumes 20% sardine protein combined with 5% of a mixture of vegetable oils (VO) containing 13% SFA, 58% MIFA and 29% PIFA (PSvo), and the third group consuming 20% casein combined with 5% of the mixture of vegetable oils and serves as a semi-synthetic reference (CASvo). Body weights and glycaemia are measured weekly After 28 days of experimentation, the rats are sacrificed, the blood and the liver removed. Serum assays of total cholesterol (TC) and triglycerides (TG) were performed by enzymatic colorimetric methods. Evaluation of lipid peroxidation was performed by assaying thiobarbituric acid reactive species (TBARS) and hydroperoxides values. The protein oxidation was performed by assaying carbonyl derivatives values. Finally, evaluation of antioxidant defense is made by measuring the activity of antioxidant enzymes, the superoxide dismutase (SOD) and the catalase (CAT).Results: After 28 days, the body weight (BW) of the rats increased significantly in SPso and SPvo groups compared to CAS group, by +11% and 7%, respectively. Cholesterolemia (TC) increased significantly in the SPso and SPvo groups compared to the CAS group (P<0.01), while triglyceridemia (TG) decreased significantly in the SPso group compared to SPvo and CAS groups (P<0.01). Albumin (marker of inflammation) increased in the PSs group compared to SPvo and CAS groups by +35% and +13%, respectively. The serum TBARS levels are -40% lower in SPso group compared to SPvo group, and they are -80% and -76% lower in SPso compared to SPvo and CAS groups, respectively. The level of carbonyls derivatives in the serum and liver are significantly reduced in the SPso group compared to the SPvo and CAS groups. Superoxide dismutase (SOD) activity decreased in liver of SPso group compared to SPvo group (P<0.01). While that of CAT is increased in liver tissue of SPso group compared to SPvo group (P<0.01). Conclusion: Sardine oil combined with sardine protein has a hypotriglyceridemic effect, reduces body weight, attenuates inflammation and seems to protect against lipid peroxidation and protein oxidation and increases antioxidant defense in hypercholesterolemic and obese rats. This could be in favor of a protective effect against obesity and cardiovascular diseases.

Keywords: rat, obesity, hypercholesterolemia, sardine protein, sardine oil, vegetable oils mixture, lipid peroxidation, protein oxidation, antioxidant defense

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Authors: Elena I. Oprita, Oana Craciunescu, Rodica Tatia, Teodora Ciucan, Reka Barabas, Orsolya Raduly, Anca Oancea

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Healing of osteochondral defects requires repair of the damaged articular cartilage, the underlying subchondral bone and the interface between these tissues (the functional calcified layer). For this purpose, developing a single monophasic scaffold that can regenerate two specific lineages (cartilage and bone) becomes a challenge. The aim of this work was to develop variants of biodegradable cross-linked composite hydrogel based on natural polypeptides (gelatin), polysaccharides components (chondroitin-4-sulphate and hyaluronic acid), in a ratio of 2:0.08:0.02 (w/w/w) and mixed with Si-hydroxyapatite (Si-Hap), in two ratios of 1:1 and 2:1 (w/w). Si-Hap was synthesized and characterized as a better alternative to conventional Hap. Subsequently, both composite hydrogel variants were cross-linked with (N, N-(3-dimethylaminopropyl)-N-ethyl carbodiimide (EDC) and enriched with a small bioactive molecule (icariin). The small molecule icariin (Ica) (C33H40O15) is the main active constituent (flavonoid) of Herba epimedium used in traditional Chinese medicine to cure bone- and cartilage-related disorders. Ica enhances osteogenic and chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), facilitates matrix calcification and increases the specific extracellular matrix (ECM) components synthesis by chondrocytes. Afterward, the composite hydrogels were characterized for their physicochemical properties in terms of the enzymatic biodegradation in the presence of type I collagenase and trypsin, the swelling capacity and the degree of crosslinking (TNBS assay). The cumulative release of Ica and real-time concentration were quantified at predetermined periods of time, according to the standard curve of standard Ica, after hydrogels incubation in saline buffer at physiological parameters. The obtained cross-linked composite hydrogels enriched with small-molecule Ica were also characterized for morphology by scanning electron microscopy (SEM). Their cytocompatibility was evaluated according to EN ISO 10993-5:2009 standard for medical device testing. Thus, analyses regarding cell viability (Live/Dead assay), cell proliferation (Neutral Red assay) and cell adhesion to composite hydrogels (SEM) were performed using NCTC clone L929 cell line. The final results showed that both cross-linked composite hydrogel variants enriched with Ica presented optimal physicochemical, structural and biological properties to be used as a natural scaffold able to repair osteochondral defects. The data did not reveal any toxicity of composite hydrogels in NCTC stabilized cell lines within the tested range of concentrations. Moreover, cells were capable of spreading and proliferating on both composite hydrogel surfaces. In conclusion, the designed biodegradable cross-linked composites enriched with Si and Ica are recommended for further testing as natural temporary scaffolds, which can allow cell migration and synthesis of new extracellular matrix within osteochondral defects.

Keywords: composites, gelatin, osteochondral defect, small molecule

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Authors: Filip Franciszek Karuga, Szymon Turkiewicz, Marta Ditmer, Marcin Sochal, Piotr Białasiewicz, Agata Gabryelska

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Circadian rhythm, an internal coordinator of physiological processes is composed of a set of semi-autonomous clocks. Clocks are regulated through the expression of circadian clock genes which form feedback loops, creating an oscillator. The primary loop consists of activators: CLOCK, BMAL1 and repressors: CRY, PER. CLOCK can be substituted by the Neuronal PAS Domain Protein 2 (NPAS2). Orphan nuclear receptor (REV-ERB-α) is a component of the secondary major loop, modulating the expression of BMAL1. Circadian clocks might be disrupted by the obstructive sleep apnea (OSA), which has also been associated with type II diabetes mellitus (DM2). Interestingly, studies suggest that dysregulation of NPAS2 and REV-ERB-α might contribute to the pathophysiology of DM2 as well. The goal of our study was to examine the role of NPAS2 and REV-ERB-α in DM2 in OSA patients. After examination of the clinical data, all participants underwent polysomnography (PSG) to assess their apnea-hypopnea index (AHI). Based on the acquired data participants were assigned to one of 3 groups: OSA (AHI>30, no DM2; n=17 for NPAS2 and 34 for REV-ERB-α), DM2 (AHI>30 + DM2; n=7 for NPAS2 and 15 for REV-ERB-α) and control group (AHI<5, no DM2; n=16 for NPAS2 and 31 for REV-ERB-α). ELISA immunoassay was performed to assess the serum protein level of REV-ERB-α and NPAS2. The only statistically significant difference between groups was observed in NPAS2 protein level (p=0.037). Post-hoc analysis showed significant differences between the OSA and the control group (p=0.017). AHI and NPAS2 level was significantly correlated (r=-0.478, p=0.002) in all groups. A significant correlation was observed between the REV-ERB-α level and sleep efficiency (r=0.617, p=0.005) as well as sleep maintenance efficiency (r=0.645, p=0.003) in the OSA group. We conclude, that NPAS2 is associated with OSA severity and might contribute to metabolic sequelae of this disease. REV-ERB-α on the other hand can influence sleep continuity and efficiency.

Keywords: OSA, diabetes mellitus, endocrinology, chronobiology

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Authors: Weikang Gong, Chunhua Li

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Dynamics plays an essential role in function exertion of proteins. Elastic network model (ENM), a harmonic potential-based and cost-effective computational method, is a valuable and efficient tool for characterizing the intrinsic dynamical properties encoded in biomacromolecule structures and has been widely used to detect the large-amplitude collective motions of proteins. Gaussian network model (GNM) and anisotropic network model (ANM) are the two often-used ENM models. In recent years, many ENM variants have been proposed. Here, we propose a small but effective modification (denoted as modified mENM) to the multiscale ENM (mENM) where fitting weights of Kirchhoff/Hessian matrixes with the least square method (LSM) is modified since it neglects the details of pairwise interactions. Then we perform its comparisons with the original mENM, traditional ENM, and parameter-free ENM (pfENM) on reproducing dynamical properties for the six representative proteins whose molecular dynamics (MD) trajectories are available in http://mmb.pcb.ub.es/MoDEL/. In the results, for B-factor prediction, mENM achieves the best performance among the four ENM models. Additionally, it is noted that with the weights of the multiscale Kirchhoff/Hessian matrixes modified, interestingly, the modified mGNM/mANM still has a much better performance than the corresponding traditional ENM and pfENM models. As to dynamical cross-correlation map (DCCM) calculation, taking the data obtained from MD trajectories as the standard, mENM performs the worst while the results produced by the modified mENM and pfENM models are close to those from MD trajectories with the latter a little better than the former. Generally, ANMs perform better than the corresponding GNMs except for the mENM. Thus, pfANM and the modified mANM, especially the former, have an excellent performance in dynamical cross-correlation calculation. Compared with GNMs (except for mGNM), the corresponding ANMs can capture quite a number of positive correlations for the residue pairs nearly largest distances apart, which is maybe due to the anisotropy consideration in ANMs. Furtherly, encouragingly the modified mANM displays the best performance in capturing the functional motional modes, followed by pfANM and traditional ANM models, while mANM fails in all the cases. This suggests that the consideration of long-range interactions is critical for ANM models to produce protein functional motions. Based on the analyses, the modified mENM is a promising method in capturing multiple dynamical characteristics encoded in protein structures. This work is helpful for strengthening the understanding of the elastic network model and provides a valuable guide for researchers to utilize the model to explore protein dynamics.

Keywords: elastic network model, ENM, multiscale ENM, molecular dynamics, parameter-free ENM, protein structure

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Authors: Z. Terzopoulou, I. Koliakou, D. Bikiaris

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Tissue engineering offers a new approach to regenerate diseased or damaged tissues such as bone. Great effort is devoted to eliminating the need of removing non-degradable implants at the end of their life span, with biodegradable polymers playing a major part. Poly(ε-caprolactone) (PCL) is one of the best candidates for this purpose due to its high permeability, good biodegradability and exceptional biocompatibility, which has stimulated extensive research into its potential application in the biomedical fields. However, PCL degrades much slower than other known biodegradable polymers and has a total degradation of 2-4 years depending on the initial molecular weight of the device. This is due to its relatively hydrophobic character and high crystallinity. Consequently, much attention has been given to the tunable degradation of PCL to meet the diverse requirements of biomedicine. Poly(ε-caprolactone) (PCL) is a biodegradable polyester that lacks bioactivity, so when used in bone tissue engineering, new bone tissue cannot bond tightly on the polymeric surface. Therefore, it is important to incorporate reinforcing fillers into PCL matrix in order to result in a promising combination of bioactivity, biodegradability, and strength. Natural clay halloysite nanotubes (HNTs) were incorporated into PCL polymeric matrix, via in situ ring-opening polymerization of caprolactone, in concentrations 0.5, 1 and 2.5 wt%. Both unmodified and modified with aminopropyltrimethoxysilane (APTES) HNTs were used in this study. The effect of nanofiller concentration and functionalization with end-amino groups on the physicochemical properties of the prepared nanocomposites was studied. Mechanical properties were found enhanced after the incorporation of nanofillers, while the modification increased further the values of tensile and impact strength. Thermal stability of PCL was not affected by the presence of nanofillers, while the crystallization rate that was studied by Differential Scanning Calorimetry (DSC) and Polarized Light Optical Microscopy (POM) increased. All materials were subjected to enzymatic hydrolysis in phosphate buffer in the presence of lipases. Due to the hydrophilic nature of HNTs, the biodegradation rate of nanocomposites was higher compared to neat PCL. In order to confirm the effect of hydrophilicity, contact angle measurements were also performed. In vitro biomineralization test confirmed that all samples were bioactive as mineral deposits were detected by X-ray diffractometry after incubation in SBF. All scaffolds were tested in relevant cell culture using osteoblast-like cells (MG-63) to demonstrate their biocompatibility

Keywords: biomaterials, nanocomposites, scaffolds, tissue engineering

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Authors: Itumeleng Judith Maome, Robert Walter Dumisani Zondo

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The concept of Corporate Social Responsibility (CSR) has gained popularity as a management philosophy in companies. They integrate social and environmental concerns into their operations and interactions with stakeholders. While CSR has mostly been associated with large organisations, it contributes to societal goals by engaging in activities or supporting volunteering or ethically oriented practices. However, small and medium enterprises (SMEs) have been recognised for their contributions to the social and economic development of any country. Consequently, this study examines the effect of CSR practices on human resource performance in the selected manufacturing SME in South Africa. This study was quantitative in design and examined the production and related experiences of the manufacturing SME organisation that had adopted a CSR strategy for human resource improvement. The study was achieved by collecting pre- and post-quarterly data, overtime, for employee turnover and labour absenteeism for analysis using the regression model. The results indicate that both employee turnover and labour absenteeism have no relationship with human resource performance post-CSR implementation. However, CSR has a relationship with human resource performance. Any increase in CSR activities results in an increase in human resource performance.

Keywords: corporate social responsibility, employee turnover, human resource, labour absenteeism, manufacturing SME

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Authors: Dake Xiong, Ben Hankamer, Ian Ross

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The most urgent challenge of our time is to replace the depleting resources of fossil fuels by sustainable environmentally friendly alternatives. Hydrogen is a promising CO2-neutral fuel for a more sustainable future especially when produced photo-biologically. Hydrogen can be photosynthetically produced in unicellular green alga like Chlamydomonas reinhardtii, catalysed by the inducible highly active and bidirectional [FeFe]-hydrogenase enzymes (HydA). However, evolutionary and physiological constraints severely restrict the hydrogen yield of algae for industrial scale-up, mainly due to its competition among other metabolic pathways on photosynthetic electrons. Among them, a major challenge to be resolved is the inferior competitiveness of hydrogen production (catalysed by HydA) with NADPH production (catalysed by ferredoxin-NADP+-reductase (FNR)), which is essential for cell growth and takes up ~95% of photosynthetic electrons. In this work, the in vivo hydrogen production efficiency of mutants with ferredoxin-hydrogenase (Fd*-HydA1*) fusion protein construct, where the electron donor ferredoxin (Fd*) is fused to HydA1* and expressed in the model organism C. reinhardtii was investigated. Once Fd*-HydA1* fusion gene is expressed in algal cells, the fusion enzyme is able to draw the redistributed photosynthetic electrons and use them for efficient hydrogen production. From preliminary data, mutants with Fd*-HydA1* transgene showed a ~2-fold increase in the photosynthetic hydrogen production rate compared with its parental strain, which only possesses the native HydA in vivo. Therefore, a solid method of having more efficient hydrogen production in microalgae can be achieved through the expression of the synthetic enzymes.

Keywords: Chlamydomonas reinhardtii, ferredoxin, fusion protein, hydrogen production, hydrogenase

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Authors: Goksen Capar, Levent Dogankaya

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According to the circular economy model, resource productivity should be maximized and wastes should be reduced. Since earth’s natural resources are continuously depleted, resource recovery has gained great interest in recent years. As part of our research study on the recovery and reuse of silk wastes, this paper focuses on the utilization of silkworm pupae as fishmeal replacement, which would replace the original fishmeal raw material, namely the fish itself. This, in turn, would contribute to sustainable management of wild fish resources. Silk fibre is secreted by the silkworm Bombyx mori in order to construct a 'room' for itself during its transformation process from pupae to an adult moth. When the cocoons are boiled in hot water, silk fibre becomes loose and the silk yarn is produced by combining thin silk fibres. The remaining wastes are 1) sericin protein, which is dissolved in water, 2) remaining part of cocoon, including the dead body of B. mori pupae. In this study, an eight weeks trial was carried out to determine the growth performance of common carp juveniles fed with waste silkworm pupae meal (SWPM) as a replacement for fishmeal (FM). Four isonitrogenous diets (40% CP) were prepared replacing 0%, 33%, 50%, and 100% of the dietary FM with non-defatted silkworm pupae meal as a dietary protein source for experiments in C. carpio. Triplicate groups comprising of 20 fish (0.92±0.29 g) were fed twice/day with one of the four diets. Over a period of 8 weeks, results showed that the diet containing 50% of its protein from SWPM had significantly higher (p ≤ 0.05) growth rates in all groups. The increasing levels of SWPM were resulted in a decrease in growth performance and significantly lower growth (p ≤ 0.05) was observed with diets having 100% SWPM. The study demonstrates that it is practical to replace 50% of the FM protein with SWPM with a significantly better utilization of the diet but higher SWPM levels are not recommended for juvenile carp. Further experiments are under study to have more detailed results on the possible effects of this alternative diet on the growth performance of juvenile carp.

Keywords: Bombyx mori, Cyprinus carpio, fish meal, silk, waste pupae

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Authors: Xiaolin Li, Terence Turney, John Forsythe, Bryce Feltis, Paul Wright, Vinh Truong, Will Gates

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Clay-hydrogel nanocomposites have attracted great attention recently, mainly because of their enhanced mechanical properties and ease of fabrication. Moreover, the unique platelet structure of clay nanoparticles enables the incorporation of bioactive molecules, such as proteins or drugs, through ion exchange, adsorption or intercalation. This study seeks to improve the mechanical and rheological properties of a novel hydrogel system, copolymerized from a tetrapodal polyethylene glycol (PEG) thiol and a linear, triblock PEG-PPG-PEG (PPG: polypropylene glycol) α,ω-bispropynoate polymer, with the simultaneous incorporation of various amounts of Na-saturated, montmorillonite clay (MMT) platelets (av. lateral dimension = 200 nm), to form a bioactive three-dimensional network. Although the parent hydrogel has controlled swelling ability and its PEG groups have good affinity for the clay platelets, it suffers from poor mechanical stability and is currently unsuitable for potential applications. Nanocomposite hydrogels containing 4wt% MMT showed a twelve-fold enhancement in compressive strength, reaching 0.75MPa, and also a three-fold acceleration in gelation time, when compared with the parent hydrogel. Interestingly, clay nanoplatelet incorporation into the hydrogel slowed down the rate of its dehydration in air. Preliminary results showed that protein binding by the MMT varied with the nature of the protein, as horseradish peroxidase (HRP) was more strongly bound than bovine serum albumin. The HRP was no longer active when bound, presumably as a result of extensive structural refolding. Further work is being undertaken to assess protein binding behaviour within the nanocomposite hydrogel for potential diabetic wound healing applications.

Keywords: hydrogel, nanocomposite, small molecule, wound healing

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Authors: A. Y. Mukhtar, J. B. Munyakazi, R. Ouifki

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Over the past few decades, the unprecedented increase in mobility has raised considerable concern about the relationship between mobility and vector-borne diseases and malaria in particular. Thus, one can claim that human mobility is one of the contributing factors to the resurgence of malaria. To assess human mobility on malaria burden among hosts, we formulate a movement-based model on a network of patches. We then extend human multi-group SEIAR deterministic epidemic models into a system of stochastic differential equations (SDEs). Our quantitative stochastic model which is expressed in terms of average rates of movement between compartments is fitted to time-series data (weekly malaria data of 2011 for each patch) using the maximum likelihood approach. Using the metapopulation (multi-group) model, we compute and analyze the basic reproduction number. The result shows that human movement is sufficient to preserve malaria disease firmness in the patches with the low transmission. With these results, we concluded that the sensitivity of malaria to the human mobility is turning to be greatly important over the implications of future malaria control in South Sudan.

Keywords: basic reproduction number, malaria, maximum likelihood, movement, stochastic model

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Authors: Mei-Ling Chan, Jin-Ming Wu, Konstantin V. Kudryavtsev, Jih-Hwa Guh

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Prostate cancer is one of the most common malignant disease in men. KUD983 is an enantiomerically pure β-dipeptide derivative, which may have anti-cancer effects. In the present study, KUD983 exhibits powerful activity against hormone-refractory prostate cancer (HRPC) PC-3 and DU145 cells. The IC50 values of KUD983 in PC-3 and DU145 cells are 0.56±0.07M and 0.50±0.04 M respectively. KUD983 induced G1 arrest of the cell cycle and subsequent apoptosis associated with the down-regulation of several related proteins including cyclin D1, cyclin E and Cdk4, and the de-phosphorylation of RB. The protein expressions of nuclear and total c-Myc protein, which was able to regulate the expression of both cyclin D1 and cyclin E, were significantly suppressed by KUD983. Phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is an important signaling pathway that influences the energy metabolism, cell cycle, proliferation, survival and apoptosis of cells, and is associated with numerous other signaling pathways. The Western Blot data revealed that KUD983 inhibited PI3K/Akt and mTOR/p70S6K/4E-BP1 pathways. The transient transfection of constitutively active myristylated Akt (myr-Akt) cDNA significantly reversed KUD983-induced caspase activation but did not abolish the suppression of mTOR/p70S6K/4E-BP1 signaling cascade indicating the presence of both Akt-dependent and -independent pathways. Moreover, KUD983-induced effect was collaborated with the down-regulation of anti-apoptotic Bcl-2 members (e.g., Bcl-2, and Mcl-1) and IAP family members (e.g., survivin). Furthermore, KUD983 induced autophagic cell death using confocal microscopic examination, investigating the level of conversion of LC3-I to LC3-II and flow cytometric detection of AVO-positive cells. Taken together, the data suggest that KUD983 is an anticancer β-dipeptide against HRPCs through the inhibition of cell proliferation and induction of apoptotic and autophagic cell death. The suppression of signaling pathways mediated by c-Myc, PI3K/Akt and mTOR/p70S6K/4E-BP1 and the collaboration with down-regulation of Mcl-1 and survivin may indicate the mechanism of KUD983 against HRPC.

Keywords: β-dipeptide, hormone-refractory prostate cancer, mTOR, PI3K/Akt

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Authors: Alireza Jalalvand, Maryam Saleh, Somayeh Behjat Khatouni, Zahra Bahri Najafi, Foroozan Fatahinia, Narges Ismailzadeh, Behrokh Farahmand

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Object: In the last two decades, the recent outbreak of Coronavirus (SARS-CoV-2) imposed a global pandemic in the world. Despite the increasing prevalence of the disease, there are no effective drugs to treat it. A suitable and rapid way to afford an effective drug and treat the global pandemic is a computational drug study. This study used molecular docking methods to examine the potential inhibition of over 50 antiviral drugs against three fundamental proteins of SARS-CoV-2. METHODS: Through a literature review, three important proteins (a key protease, RNA-dependent RNA polymerase (RdRp), and spike) were selected as drug targets. Three-dimensional (3D) structures of protease, spike, and RdRP proteins were obtained from the Protein Data Bank. Protein had minimal energy. Over 50 antiviral drugs were considered candidates for protein inhibition and their 3D structures were obtained from drug banks. The Autodock 4.2 software was used to define the molecular docking settings and run the algorithm. RESULTS: Five drugs, including indinavir, lopinavir, saquinavir, nelfinavir, and remdesivir, exhibited the highest inhibitory potency against all three proteins based on the binding energies and drug binding positions deduced from docking and hydrogen-bonding analysis. Conclusions: According to the results, among the drugs mentioned, saquinavir and lopinavir showed the highest inhibitory potency against all three proteins compared to other drugs. It may enter laboratory phase studies as a dual-drug treatment to inhibit SARS-CoV-2.

Keywords: covid-19, drug repositioning, molecular docking, lopinavir, saquinavir

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