Search results for: biosynthesis pathways

Authors: Wafaa M. Abd El-Rahim, Magda A. El-Meleigy, Eman Refaat

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This study dealing with optimization the conditions affecting the formation of extracellular lignin- degrading enzymes to achieve maximal decolorization activity of Direct Violet dye by one fungal strain. In this study Aspergillus fumigates fungal strain used for production extracellular ligninolytic enzymes for removing Direct Violet dye under different conditions: culture medium, incubation period, pH and temperatures. The results indicted that the removal efficiency of A. fumigatus was enhanced by addition glucose and peptone to the culture medium. The addition of peptone and glucose was found to increase the decolorization activity of the fungal isolate from 51.38% to 93.74% after 4 days of incubation. The highest production of extracellular lignin degrading enzymes also recorded in Direct Violet dye medium supplemented with peptone and glucose. It was also found the decolorization activity of A. fumigatus was decreased gradually by increasing the incubation period up to 4 days. Also it was found that the fungal strain can grow and produce extracellular ligninolytic enzymes which accompanied by efficient removal of Direct Violet dye in a wide pH range of 4-8. The results also found that the maximal biosynthesis of ligninolytic enzymes which accompanied with maximal removal of Direct Violet dye was obtained at a temperature of 28C. This indicates that the different conditions of culture medium, incubation period, pH and temperatures are effective on dye decolorization on the fungal biomass and played a role in Direct Violet dye removal along with enzymatic activity of A. fumigatus.

Keywords: A. fumigates, extracellular lignin- degrading enzymes, textile dye, dye removing

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Authors: Vadim Makarov, Stewart T.Cole

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PBTZ169 is novel drug candidate with high efficacy in animals models, and its combination treatment of PBTZ169 with BDQ and pyrazinamide was shown to be more efficacious than the standard treatment for tuberculosis in a mouse model. The target of PBTZ169 is famous DprE1, an essential enzyme in cell wall biosynthesis. The crystal structure of the DprE1-PBTZ169 complex reveals formation of a semimercaptal adduct with Cys387 in the active site and explains the irreversible inactivation of the enzyme. Furthermore, this drug candidate demonstrated during preclinical research ‘drug like’ properties what made it an attractive drug candidate to treat tuberculosis in humans. During first clinical trials several cohorts of the healthy volunteers were treated by the single doses of PBTZ169 as well as two weeks repeated treatment was chosen for two maximal doses. As expected PBTZ169 was well tolerated, and no significant toxicity effects were observed during the trials. The study of the metabolism shown that human metabolism of PBTZ169 is very different from microbial or animals compound transformation. So main pathway of microbial, mice and less rats metabolism connected with reduction processes, but human metabolism mainly connected with oxidation processes. Due to this difference we observed several metabolites of PBTZ169 in humans with antitubercular activity, and now we can conclude that animal antituberculosis activity of PBTZ169 is a result not only activity of the drug itself, but it is a result of the sum activity of the drug and its metabolites. Direct antimicrobial plasma activity was studied, and such activity was observed for 24 hours after human treatment for some doses. This data gets high chance for good efficacy of PBTZ169 in human for treatment TB infection. Second phase of clinical trials was started summer of 2017 and continues to the present day. Available data will be presented.

Keywords: clinical trials, DprE1, PBTZ169, metabolism

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Authors: Jiangbo Pu, Hanhui Xu, Yazhou Wang, Hongyan Cui, Yong Hu

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Spinal cord injury (SCI) brings great negative influence to the patients and society. Neurological loss in human after SCI is a major challenge in clinical. Instead, neural regeneration could have been seen in animals after SCI, and such regeneration could be retarded by blocking neural plasticity pathways, showing the importance of neural plasticity in functional recovery. Here we used sample entropy as an indicator of nonlinear dynamical in the brain to quantify plasticity changes in spontaneous EEG recordings of rats before and after SCI. The results showed that the entropy values were increased after the injury during the recovery in one week. The increasing tendency of sample entropy values is consistent with that of behavioral evaluation scores. It is indicated the potential application of sample entropy analysis for the evaluation of neural plasticity in spinal cord injury rat model.

Keywords: spinal cord injury (SCI), sample entropy, nonlinear, complex system, firing pattern, EEG, spontaneous activity, Basso Beattie Bresnahan (BBB) score

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Authors: Pradeep Lamichhane

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Plasma-assisted nitrogen fixation is a process by which atomic nitrogen generated by plasma is converted into ammonia (NH₃) or related nitrogenous compounds. Nitrogen fixation is essential to plant because fixed inorganic nitrogen compounds are required to them for the biosynthesis of all nitrogen-containing organic compounds, such as amino acids and proteins, nucleoside triphosphates and nucleic acid. Most of our atmosphere is composed of nitrogen; however, the plant cannot absorb it directly from the air ambient. As a portion of the nitrogen cycle, nitrogen fixation fundamental for agriculture and the manufacture of fertilizer. In this study, plasma-assisted nitrogen fixation was performed by exposing a non-thermal atmospheric pressure nitrogen plasma generated a sinusoidal power supply (with an applied voltage of 10 kV and frequency of 33 kHz) on a water surface. Besides this, UV excitation of water molecules at the water interface was also done in order to disassociate water. Hydrogen and hydroxyl radical obtained from this UV photolysis electrochemically combine with nitrogen atom obtained from plasma. As a result of this, nitrogen fixation on plasma-activated water (PAW) significantly enhanced. The amount of nitrogen-based products like NOₓ and ammonia (NH₃) synthesized by this combined process of UV and plasma are 1.4 and 2.8 times higher than those obtained by plasma alone. In every 48 hours, 20 ml of plasma-activated water (pH≈3.15) for 10 minutes with moderate concentrations of NOₓ, NH₃ and hydrogen peroxide (H₂O₂) was irrigated on each corn plant (Zea Mays). It was found that the PAW has shown a significant impact on seeds germination rate and improved seedling growth. The result obtained from this experiment suggested that crop yield could increase in a short duration. In the future, this experiment could open boundless opportunities in plasma agriculture to mobilize nitrogen because nitrite, nitrate, and ammonia are more suitable for plant uptake.

Keywords: plasma-assisted nitrogen fixation, nitrogen plasma, UV excitation of water, ammonia synthesis

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Authors: Alvyra Galkienė, Ona Monkevičienė

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The full participation of all pupils in the overall educational process is defined by the concept of inclusive education, which is gradually evolving in education policy and practice. It includes the full participation of all pupils in a shared learning experience and educational practices that address barriers to learning. Inclusive education applying the principles of Universal Design for Learning (UDL), which includes promoting students' involvement in learning processes, guaranteeing a deep understanding of the analysed phenomena, initiating self-directed learning, and using e-tools to create a barrier-free environment, is a prerequisite for the personal success of each pupil. However, the sustainability of quality education is affected by the transformation of education systems. This was particularly evident during the period of the forced transition from contact to distance education in the COVID-19 pandemic. Research Problem: The transformation of the educational environment from real to virtual one and the loss of traditional forms of educational support highlighted the need for new research, revealing the individual profiles of teachers using UDL-based learning and the pathways of sustainable transfer of successful practices to non-conventional learning environments. Research Methods: In order to identify individual latent teacher profiles that encompass the essential components of UDL-based inclusive teaching and direct leadership of students' learning, the quantitative analysis software Mplius was used for latent profile analysis (LPA). In order to reveal proven, i.e., sustainable, pathways for the transit of the components of UDL-based inclusive learning to distance learning, latent profile transit analysis (LPTA) via Mplius was used. An online self-reported questionnaire was used for data collection. It consisted of blocks of questions designed to reveal the experiences of subject teachers in contact and distance learning settings. 1432 Lithuanian, Latvian, and Estonian subject teachers took part in the survey. Research Results: The LPA analysis revealed eight latent teacher profiles with different characteristics of UDL-based inclusive education or traditional teaching in contact teaching conditions. Only 4.1% of the subject teachers had a profile characterised by a sustained UDL approach to teaching: promoting pupils' self-directed learning; empowering pupils' engagement, understanding, independent action, and expression; promoting pupils' e-inclusion; and reducing the teacher's direct supervision of the students. Other teacher profiles were characterised by limited UDL-based inclusive education either due to the lack of one or more of its components or to the predominance of direct teacher guidance. The LPTA analysis allowed us to highlight the following transit paths of teacher profiles in the extreme conditions of the transition from contact to distance education: teachers staying in the same profile of UDL-based inclusive education (sustainable transit) or jumping to other profiles (unsustainable transit in case of barriers), and teachers from other profiles moving to this profile (ongoing transit taking advantage of the changed new possibilities in the teaching process).

Keywords: distance education, latent teacher profiles, sustainable transit, UDL

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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: Jane E. Hill

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Sexual, physical, or emotional abuses are behaviors used by one person in a relationship or within a family unit to control the other person. Physical abuse can consist of, but not limited to hitting, pushing, and shoving. Sexual abuse is unwanted or forced sexual activity on a person without their consent. Abusive behaviors include intimidation, manipulation, humiliation, isolation, frightening, terrorizing, coercing, threatening, blaming, hurting, injuring, or wounding another individual. Although emotional, psychological and financial abuses are not criminal behaviors, they are forms of abuse and can leave emotional scars on their victim. The purpose of this literature review research was to examine characteristics of female offenders, past abuse, and pathways to offending. The question that guided this research: does past abuse influence recidivism? The theoretical foundation used was relational theory by Jean Baker Miller. One common feature of female offenders is abuse (sexual, physical, or verbal). Abuse can cause mental illnesses and substance abuse. The abuse does not directly affect the women's recidivism. However, results indicated the psychological and maladaptive behaviors as a result of the abuse did contribute to indirect pathways to continue offending. The female offenders’ symptoms of ongoing depression, anxiety, and engaging in substance abuse (self medicating) did lead to the women's incarceration. Using the childhood victimization model as the treatment approach for women's mental illness and substance abuse disorders that were a result from history of child abuse have shown success. With that in mind, if issues surrounding early victimization are not addressed, then the women offenders may not recover from their mental illness or addiction and are at a higher risk of reoffending. However, if the women are not emotionally ready to engage in the treatment process, then it should not be forced onto them because it may cause harm (targeting prior traumatic experiences). Social capital is family support and sources that assist in helping the individual with education, employment opportunities that can lead to success. Human capital refers to internal knowledge, skills, and capacities that help the individual act in new and appropriate ways. The lack of human and social capital is common among female offenders, which leads to extreme poverty and economic marginalization, more often in frequent numbers than men. In addition, the changes in welfare reform have exacerbated women’s difficulties in gaining adequate-paying jobs to support themselves and their children that have contributed to female offenders reoffending. With that in mind, one way to lower the risk factor of female offenders from reoffending is to provide them with educational and vocational training, enhance their self-efficacy, and teach them appropriate coping skills and life skills. Furthermore, it is important to strengthen family bonds and support. Having a supportive family relationship was a statistically significant protective factor for women offenders.

Keywords: characteristics, childhood victimization model, female offenders, treatment

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Authors: Priyanka Sharma, Rajeshwar Nath Srivastava

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Hydrogen has a high level of efficacy in suppressing tumour growth. The role of hydrogen in cancer treatment is unclear. This groundbreaking research will focus on the most effective therapeutic approach for osteosarcoma. Recent data reveals that hydrogen, a naturally occurring gaseous chemical, can protect cells from death. However, little is known about the signalling pathways that regulate cardiac cell death and individual apoptosis signalling by H2 and its downstream targets. According to certain research, the anti-tumor effect of H2 released by magnesium-based biomaterials is mediated by the P53-mediated lysosome-mitochondria apoptosis signalling pathway, bolstering the biomaterial's therapeutic potential as a localised anti-tumor treatment. The role of the H2 molecule in the signalling of apoptotic, autophagic, necroptotic, and pyroptotic cell death in Osteosarcoma is discussed in this paper. Potential Hydrogen-based therapy techniques will broaden the treatment horizon for Osteosarcoma.

Keywords: osteosarcoma, metastasis, hhydrogen, therapeutic

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Authors: Vagolu S. Krishna, Shan Zheng, Estharla M. Rekha, Luke W. Guddat, Dharmarajan Sriram

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Tuberculosis (TB) remains a major threat to human health. This due to the fact that current drug treatments are less than optimal as well as the rising occurrence of multi drug-resistant and extensively drug-resistant strains of the etiological agent, Mycobacterium tuberculosis (Mt). Given the wide-spread significance of this disease, we have undertaken a design and evaluation program to discover new anti-TB drug leads. Here, our attention is focused on ketol-acid reductoisomerase (KARI), the second enzyme in the branched-chain amino acid biosynthesis pathway. Importantly, this enzyme is present in bacteria but not in humans, making it an attractive proposition for drug discovery. In the present work, we used high-throughput virtual screening to identify seventeen potential inhibitors of KARI using the Birla Institute of Technology and Science in-house database. Compounds were selected based on high docking scores, which were assigned as the result of favourable interactions between the compound and the active site of KARI. The Ki values for two leads, compounds 14 and 16 are 3.71 and 3.06 µM, respectively for Mt KARI. To assess the mode of binding, 100 ns molecular dynamics simulations for these two compounds in association with Mt KARI were performed and showed that the complex was stable with an average RMSD of less than 2.5 Å for all atoms. Compound 16 showed an MIC of 2.06 ± 0.91 µM and a 1.9 fold logarithmic reduction in the growth of Mt in an infected macrophage model. The two compounds exhibited low toxicity against murine macrophage RAW 264.7 cell lines. Thus, both compounds are promising candidates for development as an anti-TB drug leads.

Keywords: ketol-acid reductoisomerase, macrophage, molecular docking and dynamics, tuberculosis

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Authors: Nasim Rasuli, Akram Ahmadi, Hossein Riahi, Zeinab Shariatmadari, Majid Ghorbani Nohooji, Pooyan Mehraban Joubani

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Cyanobacteria are one of the most promising sources of new biostimulants and have received much attention due to their diverse applications in biotechnology. These microorganisms enhance the growth and productivity of plants by producing plant growth stimulants and fixing atmospheric nitrogen. Thymus vulgaris L., a valuable medicinal plant from the Lamiaceae family, is widely distributed across the globe. essential oil of T. vulgaris is best characterized by the prominence of phenols, making them the key compounds in its composition. Lignin biosynthesis as a natural plant polyphenol plays a crucial role in promoting plant growth, strengthening cell walls, and increasing resistance to pathogens. In this study, the bioelicitor activity of five cyanobacterial suspensions including Anabaena torulosa ISB213, Nostoc calcicola ISB215, Nostoc ellipsosporum ISB217, Trichormus doliolum ISB214, and Oscillatoria sp. ISB2116 on the lignin content of the T. vulgaris L. was investigated. Pot experiments were performed by inoculation of a %2 algal extract to the soil of treated plants one week before planting and then every 20 days. After four months, the lignin content in the leaves of both treated and control plants was evaluated. The results demonstrated that the application of cyanobacteria significantly increased the lignin content in the leaves of treated plants compared to the control. The treatment with Oscillatoria sp. ISB216 and N. ellipsosporum ISB217 resulted in the highest lignin content, with an increase of 93.33% and 86.67%, respectively. These findings highlight the potential of cyanobacteria as bioelicitors, offering a viable alternative for enhancing the production of secondary metabolites in T. vulgaris. Consequently, this could contribute to the economic value of this medicinal plant.

Keywords: cyanobacteria, bioelicitor, thymus vulgaris, lignin

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Authors: Hanan M. Hassan, Laila Abouzeid, Lamya H. Al-Wahaibi, George S. G. Shehatou, Ali A. El-Emam

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Cancer is a major public health problem and the second leading cause of death worldwide. In 2020, cancer diagnosis and treatment have been negatively affected by the coronavirus 2019 (COVID-19) pandemic. During the quarantine, because of the limited access to healthcare and avoiding exposure to COVID-19 as a contagious disease; patients of cancer suffered deferments in follow-up and treatment regimens leading to substantial worsening of disease, death, and increased healthcare costs. Thus, this study is designed to investigate the molecular mechanisms by which adamantne derivatives attenuate hepatocllular carcinoma experimentally and theoretically. There is a close association between increased resistance to anticancer drugs and defective apoptosis that considered a causative factor for oncogenesis. Cancer cells use different molecular pathways to inhibit apoptosis, BAX and Bcl-2 proteins have essential roles in the progression or inhibition of intrinsic apoptotic pathways triggered by mitochondrial dysfunction. Therefore, their balance ratio can promote the cellular apoptotic fate. In this study, the in vitro cytotoxic effects of seven synthetic adamantyl isothiorea derivatives were evaluated against five human tumor cell lines by MTT assay. Compounds 5 and 6 showed the best results, mostly against hepatocellular carcinoma (HCC). Hence, in vivo studies were performed in male Sprague-Dawley (SD) rats in which experimental hepatocellular carcinoma was induced with thioacetamide (TAA) (200 mg/kg, i.p., twice weekly) for 16 weeks. The most promising compounds, 5 and 6, were administered to treat liver cancer rats at a dose of 10 mg/kg/day for an additional two weeks, and the effects were compared with doxorubicin (DR), the anticancer drug. Hepatocellular carcinoma was evidenced by a dramatic increase in liver indices, oxidative stress markers, and immunohistochemical studies that were accompanied by a plethora of inflammatory mediators and alterations in the apoptotic cascade. Our results showed that treatment with adamantane derivatives 5 and 6 significantly suppressed fibrosis, inflammation, and other histopathological insults resulting in the diminished formation of hepatocyte tumorigenesis. Moreover, administration of the tested compounds resulted in amelioration of EGFR protein expression, upregulation of BAX, and lessening down of Bcl-2 levels that prove their role as apoptosis inducers. Also, the docking simulations performed for adamantane showed good fit and binding to the EGFR protein through hydrogen bond formation with conservative amino acids, which gives a shred of strong evidence for its hepatoprotective effect. In most analyses, the effects of compound 6 were more comparable to DR than compound 5. Our findings suggest that adamantane derivatives 5 and 6 are shown to have cytotoxic activity against HCC in vitro and in vivo, by more than one mechanism, possibly by inhibiting the TLR4-MyD88-NF-κB pathway and targeting EGFR signaling.

Keywords: adamantane, EGFR, HCC, apoptosis

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Authors: Marcel Verwey, Anna M. Joubert, Elsie M. Nolte, Wolfgang Dohle, Barry V. L. Potter, Anne E. Theron

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A tetrahydroisoquinolinone (THIQ) core can be used to mimic the A,B-ring of colchicine site-binding microtubule disruptors such as 2-methoxyestradiol in the design of anti-cancer agents. Steroidomimeric microtubule disruptors were synthesized by introducing C'2 and C'3 of the steroidal A-ring to C'6 and C'7 of the THIQ core and by introducing a decorated hydrogen bond acceptor motif projecting from the steroidal D-ring to N'2. For this in vitro study, four non-steroidal THIQ-based analogues were investigated and comparative studies were done between the non-sulphamoylated compound STX 3450 and the sulphamoylated compounds STX 2895, STX 3329 and STX 3451. The objective of this study was to investigate the modes of cell death induced by these four THIQ-based analogues in A549 lung carcinoma epithelial cells and metastatic breast adenocarcinoma MDA-MB-231 cells. Cytotoxicity studies to determine the half maximal growth inhibitory concentrations were done using spectrophotometric quantification via crystal violet staining and lactate dehydrogenase (LDH) assays. Microtubule integrity and morphologic changes of exposed cells were investigated using polarization-optical transmitted light differential interference contrast microscopy, transmission electron microscopy and confocal microscopy. Flow cytometric quantification was used to determine apoptosis induction and the effect that THIQ-based analogues have on cell cycle progression. Signal transduction pathways were elucidated by quantification of the mitochondrial membrane integrity, cytochrome c release and caspase 3, -6 and -8 activation. Induction of autophagic cell death by the THIQ-based analogues was investigated by morphological assessment of fluorescent monodansylcadaverine (MDC) staining of acidic vacuoles and by quantifying aggresome formation via flow cytometry. Results revealed that these non-steroidal microtubule disrupting analogues inhibited 50% of cell growth at nanomolar concentrations. Immunofluorescence microscopy indicated microtubule depolarization and the resultant mitotic arrest was further confirmed through cell cycle analysis. Apoptosis induction via the intrinsic pathway was observed due to depolarization of the mitochondrial membrane, induction of cytochrome c release as well as, caspase 3 activation. Potential involvement of programmed cell death type II was observed due to the presence of acidic vacuoles and aggresome formation. Necrotic cell death did not contribute significantly, indicated by stable LDH levels. This in vitro study revealed the induction of the intrinsic apoptotic pathway as well as possible involvement of autophagy after exposure to these THIQ-based analogues in both MDA-MB-231- and A549 cells. Further investigation of this series of anticancer drugs still needs to be conducted to elucidate the temporal, mechanistic and functional crosstalk mechanisms between the two observed programmed cell deaths pathways.

Keywords: apoptosis, autophagy, cancer, microtubule disruptor

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Authors: Naomi Seidu, Edward Poluyi, Chibuikem Ikwuegbuenyi, Eghosa Morgan

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The current poor prognosis of glioblastoma has called for the need for an improvement in treatment methods in order to improve its survival rate. Despite the different interventions currently available for this tumor, the average survival is still only a few months. (12-15). The aim is to create a more favorable prognosis and have a reduction in the resistance to treatment currently being experienced, even with surgical interventions and chemotherapy. From the available literature, there is a relationship between the presence of HOX genes (Homeobox genes) and glioblastoma, which could be attributable to the increasing treatment resistance. Hence silencing these genes can be a key to improving survival rates of glioblastoma. A series of studies have highlighted the role that HOX genes play in glioblastoma prognosis. Promotion of human glioblastoma initiation, aggressiveness, and resistance to Temozolomide has been associated with HOXA9. The role of HOX gene expression in cancer stem cells should be studied as it could provide a means of designing CSC-targeted therapies, as CSCs play a part in the initiation and progression of solid tumors.

Keywords: GBM- glioblastoma, HOXA gene- homeobox genes cluster, signaling pathways, temozolomide

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Authors: Margarita Ivanova, Julia Dao, Andrew Friedman, Neil Kasaci, Rekha Gopal, Ozlem Goker-Alpan

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In Fabry disease (FD), α-galactosidase A (α-Gal A) deficiency leads to the accumulation of globotriaosylceramide (Lyso-Gb3 and Gb3), triggering a pathologic cascade that causes the severity of organs damage. The heart is one of the several organs with high sensitivity to the α-Gal A deficiency. A subgroup of patients with significant residual of α-Gal A activity with primary cardiac involvement is occasionally referred to as “cardiac variant.” The cardiovascular complications are most frequently encountered, contributing substantially to morbidity, and are the leading cause of premature death in male and female patients with FD. The deposition of Lyso-Gb-3 and Gb-3 within the myocardium affects cardiac function with resultant progressive cardiovascular pathology. Gb-3 and Lyso-Gb-3 accumulation at the cellular level trigger a cascade of events leading to end-stage fibrosis. In the cardiac tissue, Lyso-Gb-3 deposition is associated with the increased release of inflammatory factors and transforming growth factors. Infiltration of lymphocytes and macrophages into endomyocardial tissue indicates that inflammation plays a significant role in cardiac damage. Moreover, accumulated data suggest that chronic inflammation leads to multisystemic FD pathology even under enzyme replacement therapy (ERT). NF-κB activation plays a subsequent role in the inflammatory response to cardiac dysfunction and advanced heart failure in the general population. TNFalpha/NF-κB signaling protects the myocardial evoking by ischemic preconditioning; however, this protective effect depends on the concentration of TNF-α. Thus, we hypothesize that TNF-α is a critical factor in determining the grade of cardio-pathology. Cardiac hypertrophy corresponds to the expansion of the coronary vasculature to maintain a sufficient supply of nutrients and oxygen. Coronary activation of angiogenesis and fibrosis plays a vital role in cardiac vascularization, hypertrophy, and tissue remodeling. We suggest that the interaction between the inflammatory pathways and cardiac vascularization is a bi-directional process controlled by secreted cytokines and growth factors. The co-coordination of these two processes has never been explored in FD. In a cohort of 40 patients with FD, biomarkers associated with inflammation and cardio hypertrophic remodeling were studied. FD patients were categorized into three groups based on LVmass/DSA, LVEF, and ECG abnormalities: FD with no cardio complication, FD with moderate cardio complication, and severe cardio complication. Serum levels of NF-kB, TNFalpha, Il-6, Il-2, MCP1, ING-gamma, VEGF, IGF-1, TGFβ, and FGF2 were quantified by enzyme-linked immunosorbent assays (ELISA). Among the biomarkers, MCP-1, INF-gamma, VEGF, TNF-alpha, and TGF-beta were elevated in FD patients. Some of these biomarkers also have the potential to correlate with cardio pathology in FD. Conclusion: The study provides information about the role of inflammatory pathways and biomarkers of cardio hypertrophic remodeling in FD patients. This study will also reveal the mechanisms that link intracellular accumulation of Lyso-GB-3 and Gb3 to the development of cardiomyopathy with myocardial thickening and resultant fibrosis.

Keywords: biomarkers, Fabry disease, inflammation, growth factors

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Authors: Rhoda Afriyie Mensah, Lin Jiang, Solomon Asante-Okyere, Xu Qiang, Cong Jin

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Flammability analysis of extruded polystyrene (XPS) has become crucial due to its utilization as insulation material for energy efficient buildings. Using the Kissinger-Akahira-Sunose and Flynn-Wall-Ozawa methods, the degradation kinetics of two pure XPS from the local market, red and grey ones, were obtained from the results of thermogravity analysis (TG) and microscale combustion calorimetry (MCC) experiments performed under the same heating rates. From the experiments, it was discovered that red XPS released more heat than grey XPS and both materials showed two mass loss stages. Consequently, the kinetic parameters for red XPS were higher than grey XPS. A comparative evaluation of activation energies from MCC and TG showed an insignificant degree of deviation signifying an equivalent apparent activation energy from both methods. However, different activation energy profiles as a result of the different chemical pathways were presented when the dependencies of the activation energies on extent of conversion for TG and MCC were compared.

Keywords: flammability, microscale combustion calorimetry, thermogravity analysis, thermal degradation, kinetic analysis

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Authors: Victor Prevost, Solene Landerneau, Michel Duhamel, Joel Sternheimer, Olivier Gallet, Pedro Ferrandiz, Marwa Mokni

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The search for homologous proteins is one of the ongoing challenges in biology and bioinformatics. Traditionally, a pair of proteins is thought to be homologous when they originate from the same ancestral protein. In such a case, their sequences share similarities, and advanced scientific research effort is spent to investigate this question. On this basis, we propose the Protein-Wave Alignment Tool (”P-WAT”) developed within the framework of the France Relance 2030 plan. Our work takes into consideration the mass-related wave aspect of protein biosynthesis, by associating specific frequencies to each amino acid according to its mass. Amino acids are then regrouped within their mass category. This way, our algorithm produces specific alignments in addition to those obtained with a common amino acid coding system. For this purpose, we develop the ”P-WAT” original algorithm, able to address large protein databases, with different attributes such as species, protein names, etc. that allow us to align user’s requests with a set of specific protein sequences. The primary intent of this algorithm is to achieve efficient alignments, in this specific conceptual frame, by minimizing execution costs and information loss. Our algorithm identifies sequence similarities by searching for matches of sub-sequences of different sizes, referred to as primers. Our algorithm relies on Boolean operations upon a dot plot matrix to identify primer amino acids common to both proteins which are likely to be part of a significant alignment of peptides. From those primers, dynamic programming-like traceback operations generate alignments and alignment scores based on an adjusted PAM250 matrix.

Keywords: protein, alignment, homologous, Genodic

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Authors: Rafayel Azizyan, Valeri Arakelyan, Aram Gevorgyan, Varduhi Balayan, Emil Gevorgyan

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Currently, mathematical and computer modeling are widely used in different biological studies to predict or assess behavior of such complex systems as biological ones. This study deals with mathematical and computer modeling of bi-substrate enzymatic reactions, which play an important role in different biochemical pathways. The main objective of this study is to represent the results from in silico investigation of bi-substrate enzymatic reactions in the presence of uncompetitive inhibitors, as well as to describe in details the inhibition effects. Four models of uncompetitive inhibition were designed using different software packages. Particularly, uncompetitive inhibitor to the first [ES1] and the second ([ES1S2]; [FS2]) enzyme-substrate complexes have been studied. The simulation, using the same kinetic parameters for all models allowed investigating the behavior of reactions as well as determined some interesting aspects concerning influence of different cases of uncompetitive inhibition. Besides that shown, that uncompetitive inhibitors exhibit specific selectivity depending on mechanism of bi-substrate enzymatic reaction.

Keywords: mathematical modeling, bi-substrate enzymatic reactions, reversible inhibition

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Authors: Cheng-Cao Sun, Shu-Jun Li, De-Jia Li

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Determinants of growth and metastasis in cancer remain of great interest to define. MicroRNAs (miRNAs) have frequently emerged as tumor metastatic regulator by acting on multiple signaling pathways. Here, we report the definition of miR-346 as an oncogenic microRNA that facilitates non-small cell lung cancer (NSCLC) cell growth and metastasis. XPC, an important DNA damage recognition factor in nucleotide excision repair was defined as a target for down-regulation by miR-346, functioning through direct interaction with the 3'-UTR of XPC mRNA. Blocking miR-346 by an antagomiR was sufficient to inhibit NSCLC cell growth and metastasis, an effect that could be phenol-copied by RNAi-mediated silencing of XPC. In vivo studies established that miR-346 overexpression was sufficient to promote tumor growth by A549 cells in xenografts mice, relative to control cells. Overall, our results defined miR-346 as an oncogenic miRNA in NSCLC, the levels of which contributed to tumor growth and invasive aggressiveness.

Keywords: microRNA-346, miR-346, XPC, non-small cell lung cancer, oncogenesis

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Authors: Simona Moravcova, Jiri Novotny, Zdenka Bendova

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The pineal gland of the vertebrate brain is a circumventricular organ which serves as a major neuroendocrine gland with the primary function of rhythmic secretion of neurohormone melatonin under the control of the hypothalamic suprachiasmatic nucleus (SCN). Soon after the onset of the darkness, the activity of the key rate-limiting enzyme for melatonin synthesis, arylalkylamine N-acetyltransferase (AANAT), raises due to the increased release of norepinephrine from sympathetic neurons terminating on the parenchymal cells where it binds to β-adrenergic receptors. Melatonin codes the length of the night, and it is well recognized for its anti-inflammatory effects. However, to our knowledge, less is known about the effect of the immune system on the melatonin biosynthesis and the precise role of the STAT3 in the signaling pathway leading to the expression of AANAT. Lipopolysaccharide (LPS) is the essential component in the outer surface membrane of gram-negative bacteria and acts as a strong stimulator of natural and innate immunity. STAT3 acts as an important factor in immune response. Here we investigated the effect of LPS on the components of the melatonergic synthetic pathway in the pineal gland. The experiments were performed both in vivo and in vitro. The changes in AANAT activity were determined by radioenzymatic assay. PCR analyses were carried out to detect aa-nat, icer, spi-3 and stat3 gene expression. From our results, it is apparent that the high basal level of phosphorylated forms of STAT3 can be elevated after systemic as well as in vitro administration of LPS. Our experiments have shown that LPS reduces melatonin synthesis, nevertheless, the activity of AANAT was increased. Moreover, the basal level of phosphorylated STAT3 counteracts β-adrenergic receptor-mediated aa-nat gene expression and sustains its own and spi-3 gene expression. In conclusion, LPS can affect immunomodulators such as melatonin in the pineal gland.

Keywords: AANAT, lipopolysaccharide, pineal gland, rat, STAT3

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Authors: Amir Ali, Laura Yael Mendoza

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The application of nanomaterials is becoming the most effective strategy of elicitation to produce a desirable level of plant biomass with complex medicinal compounds. This study was designed to check the influence of phytosynthesized iron nanoparticles (FeNPs) on physical growth characteristics, antioxidant status, and production of steviol glycosides of in vitro grown Stevia rebaudiana. Effect of different concentrations of iron nanoparticles replacement of iron sulfate in MS medium (stock solution) on invitro stevia plant growth following positive control (MS basal medium), negative control (iron sulfate devoid medium), iron sulfate devoid MS medium and supplemented with FeNPs at different concentrations (5.6 mg/L, 11.2 mg/L, 16.8 mg/L, 22.4 mg/L) was evaluated. The iron deficiency leads to a drastic reduction in plant growth. In contrast, applying FeNPs leads to improvement in plant height, leave diameter, improved leave morphology, etc., in a concentration-dependent manner. Furthermore, the stress caused by FeNPs at 16.8 mg/L in cultures produced higher levels of total phenolic content (3.7 ± 0.042 mg/g dry weight: DW) and total flavonoid content (1.9 ± 0.022 mg/g DW and antioxidant activity (78 ± 4.6%). In addition, plants grown in the presence of FeNPs at 22.4 mg/L resulted in higher enzymatic antioxidant activities (SOD = 3.5 ± 0.042 U/mg; POD = 2.6 ± 0.026 U/mg; CAT = 2.8 ± 0.034 U/mg and APx = 3.6 ± 0.043 U/ mg), respectively. Furthermore, exposure to a higher dose of FeNPs (22.4 mg/L) exhibited the maximum amount of stevioside (stevioside: 4.6 ± 0.058 mg/g (DW) and rebaudioside A: 4.9 ± 0.068 mg/g DW) as compared to other doses. The current investigation confirms the effectiveness of FeNPs in growth media. It offers a suitable prospect for commercially desirable production of S. rebaudiana biomass with higher sweet glycosides profiles in vitro.

Keywords: cell culture, stevia, iron nanoparticles, antioxidants

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Authors: Sharmin Ferdewsi Rakhi, AHM Mohsinul Reza, Brynley Davies, Jianzhong Wang, Youhong Tang, Jian Qin

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Mass production of microalgae has become a focus of research owing to their promising aspects for sustainable food, biofunctional compounds, and biofuel feedstock. However, low lipid content with optimum algal biomass is still a challenge that must be resolved for commercial use. This research aims to determine the effects of light spectral shift and reactive oxygen species (ROS) on growth and lipid biosynthesis in a green microalga, Chlamydomonas reinhardtii. Aggregation Induced Emission (AIE)-based photosensitisers, CN-TPAQ-PF6 ([C₃₂H₂₃N₄]+) with high ROS productivity, was introduced into the algal culture media separately for effective conversion of the green-yellow-light to the red spectra. The intense photon energy and high-photon flux density in the photosystems and ROS supplementation induced photosynthesis and lipid biogenesis. In comparison to the control, maximum algal growth (0.15 g/l) was achieved at 2 µM CN-TPAQ-PF6 exposure. A significant increase in total lipid accumulation (146.87 mg/g dry biomass) with high proportion of 10-Heptadecanoic acid (C17:1) linolenic acid (C18:2), α-linolenic acid (C18:3) was observed. The elevated level of cellular NADP/NADPH triggered the Acetyl-Co-A production in lipid biogenesis cascade. Furthermore, MTT analysis suggested that this nanomaterial is highly biocompatible on HaCat cell lines with 100% cell viability. This study reveals that the AIE-based approach can strongly impact algal biofactory development for sustainable food, healthy lipids and eco-friendly biofuel.

Keywords: microalgae, photosensitiser, lipid, biomass, aggregation-induced-emission, reactive oxygen species

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Authors: Rubaiyea Uddin, Rebecca Taylor, Emily Levesque

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The hippocampus, located in the limbic system, is most commonly known for its role in memory and spatial navigation (as cited in Brain Reward and Pathways). It maintains an especially important role in specifically episodic and declarative memory. The hippocampus has also recently been linked to dopamine, the reward pathway’s primary neurotransmitter. Since research has found that dopamine also contributes to memory consolidation and hippocampal plasticity, this neurotransmitter is potentially responsible for contributing to the hippocampus’s role in memory formation. In this experiment we tested to see the effect of tactile cues on spatial navigation for eight different mice. We used a radial arm that had one designated “reward” arm containing sucrose. The presence or absence of bedding was our tactile cue. We attempted to see if the memory of that cue would enhance the mice’s memory of having received the reward in that arm. The results from our study showed there was no significant response from the use of tactile cues on spatial navigation on our 129 mice. Tactile cues therefore do not influence spatial navigation.

Keywords: mice, radial arm maze, memory, spatial navigation, tactile cues, hippocampus, reward, sensory skills, Alzheimer's, neuro-degenerative diseases

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Authors: Patricia M. B. Saint-Vincent, Anna Furches, Stephanie Galanie, Erica Teixeira Prates, Piet Jones, Nancy Engle, David Kainer, Wellington Muchero, Daniel Jacobson, Timothy J. Tschaplinski

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Uridine diphosphate-glycosyltransferases (UGTs) are enzymes that catalyze sugar transfer to a variety of plant metabolites. UGT substrates, which include plant secondary metabolites involved in lignification, demonstrate new activities and incorporation when glycosylated. Knowledge of UGT function, substrate specificity, and enzyme products is important for plant engineering efforts, especially related to increasing plant biomass through lignification. UGTs in Populus trichocarpa, a biofuel feedstock, and model woody plant, were selected from a pool of gene candidates using rapid prioritization strategies. A functional genomics workflow, consisting of a metabolite genome-wide association study (mGWAS), expression of synthetic codon-optimized genes, and high-throughput biochemical assays with mass spectrometry-based analysis, was developed for determining the substrates and products of previously-uncharacterized enzymes. A total of 40 UGTs from P. trichocarpa were profiled, and the biochemical assay results were compared to predicted mGWAS connections. Assay results confirmed seven of 11 leaf mGWAS associations and demonstrated varying levels of substrate specificity among candidate UGTs. P. trichocarpa UGT substrate processing confirms the role of these newly-characterized enzymes in lignan, flavonoid, and phytohormone metabolism, with potential implications for cell wall biosynthesis, nitrogen uptake, and biotic and abiotic stress responses.

Keywords: Populus, metabolite-gene associations, GWAS, bio feedstocks, glycosyltransferase

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Authors: Wanvipa Thongborisute, Punyaphat Sirithanabadeekul, Pichit Suvanprakorn, Anan Jiraviroon

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Background: Acne vulgaris is one of the most common dermatologic problems, and can have a significant psychological and physical effect on patients. Propionibacterium acnes' roles in acne vulgaris involve the activation of toll-like receptor 4 (TLR4), and toll-like receptor 2 (TLR2) pathways. By activating these pathways, inflammatory events of acne lesions, comedogenesis and sebaceous lipogenesis can occur. Currently, there are several topical agents commonly use in treating acne vulgaris that are known to have an effect on TLRs, such as retinoic acid and adapalene, but these drugs still have some irritating effects. At present, there is an alarming increase in rate of bacterial resistance due to irrational used of antibiotics both orally and topically. For this reason, acne treatments should contain bioactive molecules targeting at the site of action for the most effective therapeutic effect with the least side effects. Sparganium stoloniferumis a Chinese aquatic herb containing a compound called Sparstolonin B (SsnB), which has been reported to selectively blocks Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4)-mediated inflammatory signals. Therefore, this topical TLR2 and TLR4 antagonist, in a form of Sparganium stoloniferum-derived compound containing SsnB, should give a benefit in reducing inflammation of acne vulgaris lesions and providing an alternative treatments for patients with this condition. Materials and Methods: The objectives of this randomized double blinded split faced placebo controlled trial is to study the safety and efficacy of the Sparganium stoloniferum-derived compound. 32 volunteered patients with mild to moderate degree of acne vulgaris according to global acne grading system were included in the study. After being informed and consented the subjects were given 2 topical treatments for acne vulgaris, one being topical 2.40% Sparganium stoloniferum extraction (containing Sparstolonin B) and the other, placebo. The subjects were asked to apply each treatment to either half of the face daily morning and night by randomization for 8 weeks, and come in for a weekly follow up. For each visit, the patients went through a procedure of lesion counting, including comedones, papules, nodules, pustules, and cystic lesions. Results: During 8 weeks of experimentation, the result shows a reduction in total lesions number between the placebo and the treatment side show statistical significance starting at week 4, where the 95% confidence interval begin to no longer overlap, and shows a trend of continuing to be further apart. The decrease in the amount of total lesions between week 0 and week 8 of the placebo side shows no statistical significant at P value >0.05. While the decrease in the amount of total lesions of acne vulgaris of the treatment side comparing between week 0 and week 8 shows statistical significant at P value <0.001. Conclusion: The data demonstrates that 2.40% Sparganium stoloniferum extraction (containing Sparstolonin B) is more effective in treating acne vulgaris comparing to topical placebo in treating acne vulgaris, by showing significant reduction in the total numbers of acne lesions. Therefore, this topical Sparganium stoloniferum extraction could become a potential alternative treatment for acne vulgaris.

Keywords: acne vulgaris, sparganium stoloniferum, sparstolonin B, toll-like receptor 2, toll-like receptor 4

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Authors: Patricia Jayshree Jacob, Mas Jaffri Masarudinb, Mohd Zobir Hussein, Raha Abdul Rahim

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Iron based ferromagnetic nanoparticles (IONP) and silver nanostructures (AgNP) have found a wide range of application in antimicrobial therapy, cell targeting, and environmental applications. As such, the design of well-defined monodisperse IONPs and AgNPs have become an essential tool in nanotechnology. Fabrication of these nanostructures using conventional methods is not environmentally conducive and weigh heavily on energy and outlays. Selected microorganisms possess the innate ability to reduce metallic ions in colloidal aqueous solution to generate nanoparticles. Hence, harnessing this potential is a way forward in constructing microbial nano-factories, capable of churning out high yields of well-defined IONP’s and AgNP's with physicochemical characteristics on par with the best synthetically produced nanostructures. In this paper, we report the isolation and characterization of bacterial strains isolated from the tropical marine and freshwater ecosystems of Malaysia that demonstrated facile and rapid generation of ferromagnetic nanoparticles and silver nanostructures when precursors such as FeCl₃.6H₂O and AgNO₃ were added to the cell-free bacterial lysate in colloidal solution. Characterization of these nanoparticles was carried out using FESEM, UV Spectrophotometer, XRD, DLS and FTIR. This aerobic bioprocess was carried out at ambient temperature and humidity and has the potential to be developed for environmental friendly, cost effective large scale production of IONP’s. A preliminary bioprocess study on the harvesting time, incubation temperature and pH was also carried out to determine pertinent abiotic parameters contributing to the optimal production of these nanostructures.

Keywords: iron oxide nanoparticles, silver nanoparticles, biosynthesis, aquatic bacteria

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Authors: C. Fortin, D. Tokmeninova, O. Ushakova

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Among 500 Russian universities Skolkovo Institute of Science and Technology (Skoltech) is one of the youngest (established in 2011), quite small and vastly international, comprising 20 percent of international students and 70 percent of faculty with significant academic experience at top-100 universities (QS, THE). The institute has emerged from close collaboration with MIT and leading Russian universities. Skoltech is an entirely English speaking environment. Skoltech curriculum plans of ten Master programs are based on the CDIO learning outcomes model. However, despite the Institute’s unique focus on industrial innovations and startups, one of the main challenges has become an evident large proportion of nearly half of MSc graduates entering PhD programs at Skoltech or other universities rather than industry or entrepreneurship. In order to increase the share of students joining the industrial sector after graduation, Skoltech started implementing a number of unique practices with a focus on employers’ expectations incorporated into the curriculum redesign. In this sense, extended knowledge exchange with industrial partners via collaboration in learning activities, industrial projects and assessments became essential for students’ headway into industrial and entrepreneurship pathways. Current academic curriculum includes the following types of components based on extended knowledge exchange with industrial partners: innovation workshop, industrial immersion, special industrial tracks, MSc defenses. Innovation workshop is a 4 week full time diving into the Skoltech vibrant ecosystem designed to foster innovators, focuses on teamwork, group projects, and sparks entrepreneurial instincts from the very first days of study. From 2019 the number of mentors from industry and startups significantly increased to guide students across these sectors’ demands. Industrial immersion is an exclusive part of Skoltech curriculum where students after the first year of study spend 8 weeks in an industrial company carrying out an individual or team project and are guided jointly by both Skoltech and company supervisors. The aim of the industrial immersion is to familiarize students with relevant needs of Russian industry and to prepare graduates for job placement. During the immersion a company plays the role of a challenge provider for students. Skoltech has started a special industrial track comprising deep collaboration with IPG Photonics – a leading R&D company and manufacturer of high-performance fiber lasers and amplifiers for diverse applications. The track is aimed to train a new cohort of engineers and includes a variety of activities for students within the “Photonics” MSc program. It is expected to be a successful story and used as an example for similar initiatives with other Russian high-tech companies. One of the pathways of extended knowledge exchange with industrial partners is an active involvement of potential employers in MSc Defense Committees to review and assess MSc thesis projects and to participate in defense procedures. The paper will evaluate the effect and results of the above undertaken measures.

Keywords: Curriculum redesign, knowledge exchange model, learning outcomes framework, stakeholder engagement

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Authors: Sahar Nasr, Lin Li, Edwin Wang

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Bladder cancer (BLCA) is known as the 13th cause of death among cancer patients worldwide, and ~575,000 new BLCA cases are diagnosed each year. Urothelial carcinoma (UC) is the most prevalent subtype among BLCA patients, which can be categorized into muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Currently, various therapeutic options are available for UC patients, including (1) transurethral resection followed by intravesical instillation of chemotherapeutics or Bacillus Calmette-Guérin for NMIBC patients, (2) neoadjuvant platinum-based chemotherapy (NAC) plus radical cystectomy is the standard of care for localized MIBC patients, and (3) systematic chemotherapy for metastatic UC. However, conventional treatments may lead to several challenges for treating patients. As an illustration, some patients may suffer from recurrence of the disease after the first line of treatment. Recently, immune checkpoint therapy (ICT) has been introduced as an alternative treatment strategy for the first or second line of treatment in advanced or metastatic BLCA patients. Although ICT showed lucrative results for a fraction of BLCA patients, ~80% of patients were not responsive to it. Therefore, novel treatment methods are required to augment the ICI response rate within BLCA patients. It has been shown that the infiltration of T-cells into the tumor microenvironment (TME) is positively correlated with the response to ICT within cancerous patients. Therefore, the goal of this study is to enhance the infiltration of cytotoxic T-cells into TME through the identification of target genes within the tumor that are responsible for the non-T-cell inflamed TME and their inhibition. BLCA bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) and immune score for TCGA samples were used to determine the Pearson correlation score between the expression of different genes and immune score for each sample. The genes with strong negative correlations were selected (r < -0.2). Thereafter, the correlation between the expression of each gene and survival in BLCA patients was calculated using the TCGA data and Cox regression method. The genes that are common in both selected gene lists were chosen for further analysis. Afterward, BLCA bulk and single-cell RNA-sequencing data were ranked based on the expression of each selected gene and the top and bottom 25% samples were used for pathway enrichment analysis. If the pathways related to the T-cell infiltration (e.g., antigen presentation, interferon, or chemokine pathways) were enriched within the low-expression group, the gene was included for downstream analysis. Finally, the selected genes will be used to calculate the correlation between their expression and the infiltration rate of the activated CD+8 T-cells, natural killer cells and the activated dendric cells. A list of potential target genes has been identified and ranked based on the above-mentioned analysis and criteria. SUN-1 got the highest score within the gene list and other identified genes in the literature as benchmarks. In conclusion, inhibition of SUN1 may increase the tumor-infiltrating lymphocytes and the efficacy of ICI in BLCA patients. BLCA tumor cells with and without SUN-1 CRISPR/Cas9 knockout will be injected into the syngeneic mouse model to validate the predicted SUN-1 effect on increasing tumor-infiltrating lymphocytes.

Keywords: data analysis, gene expression analysis, gene identification, immunoinformatic, functional genomics, transcriptomics

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Authors: Kaixuan Feng, Ruixiang Lin, Yuyan Hu, Yuheng Feng, Dezhen Chen, Tongcheng Cao

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In this study, we propose a reaction system for the low-temperature reduction of NO by H₂ on carbon-based materials decorated with 5%wt. Ni. This cost-effective catalyst system efficiently utilizes pyrolysis carbon-based materials and waste hydrogen. Additionally, it yields environmentally friendly products without requiring extra heat sources in practical SCR devices. Density functional theory elucidates the mechanism of NO heterogeneous reduction by H₂ on Ni-decorated char surfaces. Two distinct reaction paths were identified, one involving the intermediate product N₂O and the other not. These pathways exhibit different rate-determination steps and activation energies. Kinetic analysis indicates that the N₂O byproduct pathway has a lower activation energy. Experimental results corroborate the theoretical findings. Thus, this research enhances our mechanistic understanding of the NO-H₂ reaction over char and offers insights for optimizing catalyst design in low-temperature NO reduction.

Keywords: char-based catalysis, NO reduction, DFT study, heterogeneous reaction, low-temperature H₂-reduction

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Authors: Antonela Matana, Dubravka Brdar, Vesela Torlak, Marijana Popovic, Ivana Gunjaca, Ozren Polasek, Vesna Boraska Perica, Maja Barbalic, Ante Punda, Caroline Hayward, Tatijana Zemunik

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Parathyroid hormone (PTH) plays a critical role in the regulation of bone mineral metabolism and calcium homeostasis. Higher PTH levels are associated with heart failure, hypertension, coronary artery disease, cardiovascular mortality and poorer bone health. A twin study estimated that 60% of the variation in PTH concentrations is genetically determined. Only one GWAS of PTH concentration has been reported to date. Identified loci explained 4.5% of the variance in circulating PTH, suggesting that additional genetic variants remain undiscovered. Therefore, the aim of this study was to identify novel genetic variants associated with PTH levels in a general population. We have performed a GWAS meta-analysis on 2596 individuals originating from three Croatian cohorts: City of Split and the Islands of Korčula and Vis, within a large-scale project of “10,001 Dalmatians”. A total of 7 411 206 variants, imputed using the 1000 Genomes reference panel, with minor allele frequency ≥ 1% and Rsq ≥ 0.5 were analyzed for the association. GWAS within each data set was performed under an additive model, controlling for age, gender and relatedness. Meta-analysis was conducted using the inverse-variance fixed-effects method. Furthermore, to identify sex-specific effects, we have conducted GWAS meta-analyses analyzing males and females separately. In addition, we have performed biological pathway analysis. Four SNPs, representing one locus, reached genome-wide significance. The most significant SNP was rs11099476 on chromosome 4 (P=1.15x10-8), which explained 1.14 % of the variance in PTH. The SNP is located near the protein-coding gene RASGEF1B. Additionally, we detected suggestive association with SNPs, rs77178854 located on chromosome 2 in the DPP10 gene (P=2.46x10-7) and rs481121 located on chromosome 1 (P=3.58x10-7) near the GRIK1 gene. One of the top hits detected in the main meta-analysis, intron variant rs77178854 located within DPP10 gene, reached genome-wide significance in females (P=2.21x10-9). No single locus was identified in the meta-analysis in males. Fifteen biological pathways were functionally enriched at a P<0.01, including muscle contraction, ion homeostasis and cardiac conduction as the most significant pathways. RASGEF1B is the guanine nucleotide exchange factor, known to be associated with height, bone density, and hip. DPP10 encodes a membrane protein that is a member of the serine proteases family, which binds specific voltage-gated potassium channels and alters their expression and biophysical properties. In conclusion, we identified 2 novel loci associated with PTH levels in a general population, providing us with further insights into the genetics of this complex trait.

Keywords: general population, genome-wide association analysis, parathyroid hormone, single nucleotide polymorphisms.

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Authors: Ayyoub Jamali, Alena Kozlova

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The Russian invasion of Ukraine has tested the mettle of the international community, prompting not only States but also non-state actors to take deterrent action in response. Indeed, international sports organisations, namely FIFA and UEFA, have been rather successful in shifting the power dynamics by introducing a complete ban on the Russian national and club teams. This article aims to inquire into the human rights implications of such actions taken by international sports organisations. First, the article departs from an assessment of the legal status of FIFA and UEFA under international law and reflects on how a legal link could be established vis-à-vis their human rights obligations. Second, it examines the human rights aspects of the impugned measures by FIFA and UEFA on the part of the Russian athletes, further scrutinising them against the international human rights law principle of non-discrimination through a proportionality test. Last, it draws basic pathways for how possible human rights violations committed in the context of measures adopted by such organisations could be remedied, outlining the challenges of arbitration and litigation in Switzerland.

Keywords: FIFA, UEFA, FUR, ban, human rights, Russia, Ukraine, non-state actors

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