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Type two diabetes is associated with adiponectin, which possesses characteristics that makes it sensitive to insulin. The study’s aim was to identify the association of Rs266729 polymorphism in patients attending Murtala Muhammad Specialist Hospital Kano State. Blood sample was obtained from twenty seven (27) participants. DNA was extracted, followed by Polymerase Chain Reaction (PCR) of AdipQ gene promoter region. The PCR product was sequenced to identify mutation. Result from this study identify that, the the distribution of the minor allele G (OR = 6.88, P = 0.012698) of rs266729 polymorphism was found to be associated with an increased risk of T2D compared to control group. The genetic model form of association showed that, the homozygous genotype (GG) and heterozygous genotype (CG) of rs266729 polymorphism were significantly associated with BMI, waist circumference and waist hip ratio under the codominant and dominant genetic models. Present study discovered that the minor allele G of rs266729 constitute a risk factor for the development of type two diabetes mellitus in patients attending Murtala Muhammad Specialist Hospital Kano State. Received: 19 February 2024 Accepted: 15 April 2024 Published: 23 May 2024

Cisplatin is a chemotherapeutic drug which frequently induces hepato- and renal toxicities. Cisplatin-induced hepatic damage is an area less investigated compared to renal damage. In the present study we investigated the hepatic damage caused by cisplatin and its possible protection by the hormone melatonin. Adult male golden hamster Mesocricetus auratus (? 2 months of age, and ± 100 g bw) were randomly divided into four groups (n=5)- Group I- control (injected with normal saline), group II- cisplatin (single dose of 15 mg/kg bw, ip), group III- melatonin (100 ug/100 g bw ip for 4 days) and group IV- Mel pretreatment followed by cisplatin at the above-said doses. The animals were euthanized 48 hr after the last dose. Liver was dissected out for analysis (histology, antioxidant profile, NF-?B, IL-1?, Cox-2, Hemeoxygenase-I and Nrf2). Cisplatin treatment induced steatohepatitis-like changes in the liver, elevated TBARS and suppressed antioxidant profiles. Further, the expression of NF-?B, IL-1?, Cox-2, and Hemeoxygenase-I were increased and the expression of Nrf2 was decreased suggesting inflammatory damage to liver. Pre-treatment of melatonin reduced the cisplatin-mediated hepatic pro-oxidant/antioxidant balance and inflammatory responses. Therefore, melatonin pretreatment might be a supportive approach in cancer therapy as it negates some of the damaging effects of cisplatin on liver to an extent without interfering with its chemotherapeutic attributes.

The mechanisms of larval fish transport have been rigorously studied in the past several decades, building foundational knowledge of key biological and environmental factors with which to inform decisions about species management. This study has been built upon information gained from previous studies to further elucidate the processes involved at the recruitment stage of larval fishes. Vertical swimming behaviors of larval fishes enable deliberate orientation within the water column to allow organisms of limited mobility greater control over their horizontal movements. Vertical accumulation patterns of larvae are found to be tightly dependent on the strength of stratification within the water column at nursery entrances, such as estuaries. Onshore currents, such as upwelling and surface intrusions, are found to be conduits for entry into these systems. This study observed and analyzed the influence of intrusions by the Gulf Stream into the Fort Pierce Inlet and the vertical accumulation patterns of late-stage larvae associated with those events. This study incorporated a well-established zooplanktonic abundance sampling technique to achieve two primary goals: (1) to analyze the vertical abundances of larval fishes in stratified flow during Gulf Stream intrusions and (2) to assess the correlation between larval influx and intrusion events. The results of this study show a significant and positive correlation between propagule pressure of larval fishes and incidence of Gulf Stream intrusion events. Whereas previous studies have primarily described the spatiotemporal aspects of larval transport in a broader sense, our findings revealed a greater layer of complexity in the mechanisms of transport by incorporating localized hydrographic features. The information gleaned from these results can inform the ecological considerations of future fisheries management and study efforts via additional understanding about the role of physical oceanographic events in a critical lif, 2023, Includes bibliography., Degree granted: Thesis (MS)--Florida Atlantic University, 2023., Collection: FAU Electronic Theses and Dissertations Collection

This work encompasses the synthesis, analysis, and optimization of [3.2.1] all-carbon bridged bicyclic compounds, known as resveramorphs (RVM), Studies were conducted using a Caenorhabditis elegans model, where RVMs were tested for antiseizure capabilities. In both applications, RVMs proved potent with activities in the sub-nanomolar level in one case. A structure-activity relationship (SAR) was hypothesized for the identification of the pharmacophore. The six to seven step synthesis route towards the RVM analogues is discussed in further detail. The bicyclization of the RVMs is achieved through a reductive aldol reaction. The reaction suffers from selectivity issues leading to multiple bicyclic products. By following a one-factor-at-a-time (OFAT) methodology, attempts at optimization for this reaction were made, however, despite important gains, the overall yields of the bicyclic product remain low. Other products from this reaction have been used to understand the reaction mechanism, which will be the basis for future efforts to further optimize this key step., 2023, Includes bibliography., Degree granted: Thesis (MS)--Florida Atlantic University, 2023., Collection: FAU Electronic Theses and Dissertations Collection

Tau, a microtubule-associated protein, is involved in more than 20 different tauopathic disorders characterized by aberrant intracellular aggregation of tau in the brain. However, it is still unclear how this highly soluble tau protein aggregates inside the brain. Thus, understanding the mechanistic details of tau aggregation is critical for unraveling the underlying pathology of tauopathies and developing effective strategies to inhibit tau aggregation. Herein, we investigated the aggregation of a novel 20-residue model peptide, tau₂₉₈₋₃₁₇, derived from the key microtubule-binding domain of the full sequence tau. Our study demonstrates that tau₂₉₈₋₃₁₇ highly mimics full-length tau's physical and aggregation properties. The fibrillation of the peptide is strongly dependent on external factors. The presence of polyanionic heparin (Hep) significantly promotes the aggregation of this peptide to form amyloid fibrils. The Hep-induced aggregation is sensitive to the ionic strength of the solution, suggesting an important role of electrostatic interactions in the mechanism of Hep-mediated aggregation. In addition, two positively charged polysaccharides, chitosan (CHT) and its quaternary derivative N-trimethyl chitosan (TMC), effectively inhibit Hep-induced aggregation of tau₂₉₈₋₃₁₇ in a concentration-dependent manner. Attractive electrostatic interactions between the positively charged moieties in CHT/TMC and the negatively charged residues of Hep play a critical role in inhibiting Hep–peptide interactions and suppressing peptide aggregation., 2023, Includes bibliography., Degree granted: Dissertation (PhD)--Florida Atlantic University, 2023., Collection: FAU Electronic Theses and Dissertations Collection

Misfolding and aggregation of Cellular Prion Protein (PrPc) is a major molecular process involved in the pathogenesis of Prion diseases. An N-terminal portion of the Prion protein, PrP106-128, is a 23-residue peptide fragment characterized by an amphipathic structure with two domains: a hydrophilic N-terminal domain and a hydrophobic C-terminal domain. Here, we studied the aggregation properties of the prion fragment peptide PrP106-128. The results show that the peptide aggregates in a concentration-dependent manner in an aqueous solution and that the aggregation is sensitive to pH and the preformed amyloid seeds.Furthermore, we show that the zwitterionic POPC liposomes moderately inhibit the aggregation of PrP(106–128), whereas POPC/cholesterol (8:2) vesicles facilitate peptide aggregation likely due to the increase of the lipid packing order and membrane rigidity in the presence of cholesterol. In addition, anionic lipid vesicles of POPG and POPG/cholesterol above a certain concentration accelerate the aggregation of the peptide remarkably. The strong electrostatic interactions between the N-terminal region of the peptide and POPG may constrain the conformational plasticity of the peptide, preventing insertion of the peptide into the inner side of the membrane and thus promoting fibrillation on the membrane surface. The results suggest that the charge properties of the membrane, the composition of the liposomes, and the rigidity of lipid packing are critical in determining peptide adsorption on the membrane surface and the efficiency of the membrane in catalyzing peptide oligomeric nucleation and amyloid formation., 2023, Includes bibliography., Degree granted: Dissertation (PhD)--Florida Atlantic University, 2023., Collection: FAU Electronic Theses and Dissertations Collection

Alzheimer’s disease (AD) belongs to the class of neurodegenerative disorder and is biochemically characterized by amyloid-β (Aβ) plaques deposition, accumulation of neurofibrillary tangles (NFTs) accumulation and ultimately neuronal loss. Even though, the progress made in developing efficient AD therapy, there is no effective drug capable to stop and/or slow down AD progression. In the current article, we investigated the neuroprotective effect of Khaya grandifololia crude extract and fraction 2 against Aβ42-induced cytotoxicity and hyperphosphorylation of tau protein in differentiated neuronal cells (IMR32).Reactive oxygen species production, apoptosis and mitochondrial dynamics and function, synaptic protein, and tau phosphorylation were evaluated using fluorescence microscopy and immunoblotting. Cell viability was assessed using the MTT assay.Findings revealed that exposure of differentiated IMR32 cells to Aβ42 alone induced the impairment of mitochondrial dynamics, decrease synaptic protein expression and increase hyperphosphorylation of tau protein (phospho tau181). In contrast, the presence of crude extract and KGf2 significantly inhibited the cleavage of Caspase-3 activation. In addition, the levels of synaptic proteins (Symptosomal associated protein 25 and Synaptosin) and superoxide dismutase were restored upon treatment with crude extract and fraction 2. Hyperphosphorylation of tau protein (Thr181) and ERK (Thr202/Tyr205) activities were also significantly reduced after treatment with crude extract and fraction 2.Our findings suggest that KG extract is a potential source for candidate drug against AD and may contribute to the development of efficient therapeutic strategy against AD.

Breast, ovarian, endometrial, prostate and cervical cancers are considered as the major endocrine-dependent malignancies associated with human reproductive system. Current tools used for diagnosis and therapeutics of these malignancies mainly exploit the hormone-sensitivity associated with them. Nonetheless, they often fail to give appreciable outcomes in terms of prognosis and survival rates. miRNAs have emerged as one of the key players dictating the pathophysiology of endocrine-dependent malignancies and present themselves as apt candidates to be developed as potential biomarkers or therapeutic targets for the early prognosis as well as treatment of these diseases. In this review, we have high-lighted the regulatory networks controlled by the promising candidate miRNAs in the pathophysiology of the major endocrinedependent reproductive system-associated malignancies.

Poly-Cystic Ovary Syndrome (PCOS) is the most prevalent endocrine disorder, characterized by hyperandrogenism and hyperinsulinemia, both at systemic and ovarian levels. This study investigated the synergistic effect of hyperinsulinemia and hyperandrogenism on the regulatory mechanism of ovarian steroidogenesis using Luteinized Granulosa Cells (LGCs). LGCs were isolated from 40 weaning female Charles Foster rats by superovulation by PMSG and characterized for purity and stability in modified DMEM: F12 media. The isolated cells were divided into following groups- control, hyperinsulinic group (0.1-2 mIU/ mL of insulin), excess androgen (10-100 ng/mL of DHT) and combination of both. One-way ANOVA was performed with a Bonferroni post-hoc test. Results demonstrate that the LGCs exhibit reduced expression of FSHR and CYP19A and increased expression of LHR, StAR and CYP17A1 at 72 hours. There was reduction in cell viability of LGCs when induced with hyperinsulin and hyperandrogen doses individually or in combination.0.1 mIU/mL of insulin and 50 ng/mL of DHT in combination were the minimum effective dose in inducing PCO like ovarian microenvironment in the primary culture of LGCs. There was exaggerated androgen biosynthesis, reduced progesterone secretion and non-significant change is estradiol levels in the LGCs. The abnormal steroidogenesis can be attributed to upregulation of key genes such as StAR, CYP17A1, AMH and SREBP1-c and down-regulation of genes like CYP19A1, HSD3B2, IGFBP1 and SHBG. This model can be used to study downstream signaling pathways involved with dysregulated ovarian microenvironment as observed in PCOS at cellular level and for screening of drug targets for such pathological conditions.

Occupation is one of the most important extrinsic factors which have the major impact on health. Pedalling the tricycle rickshaw is a most stressful job. Rickshaw Pullers are extensively exposed to the air pollutants in conjunction with strenuous exercise. In the present study demographic details along with nutritional status, hygiene status and morbid conditions were obtained from fifty Rickshaw Pullers (RPs) in Allahabad.

type:Journal Article, Cellular memory is a ubiquitous function of biological systems. By generating a sustained response to a transient inductive stimulus, often due to bistability, memory is central to the robust control of many important biological processes. However, our understanding of the origins of cellular memory remains incomplete. Stochastic fluctuations that are inherent to most biological systems have been shown to hamper memory function. Yet, how stochasticity changes the behavior of genetic circuits is generally not clear from a deterministic analysis of the network alone. Here, we apply deterministic rate equations, stochastic simulations, and theoretical analyses of Fokker-Planck equations to investigate how intrinsic noise affects the memory function in a mutual repression network., source:https://doi.org/10.1186/s12859-019-3315-2

In the present dissertation, we discuss the development of a stereoselective method for the production of phosphorus compounds that utilizes a phospha-Michael addition reaction. Separately, the design and synthesis of compounds that contain an all-carbon bridged bicyclic scaffold is reported; these compounds were used in initial SAR studies in different in vivo models. In Chapter one is presented a mechanistic framework to develop a highly diastereoselective method catalyzed by phase transfer chemistry leading to phosphinate compounds. In this method, phosphinate nucleophiles were added to various alkenyl ketones as Michael acceptors using crown ethers as phase transfer agents to obtain highly diastereoselective products with the generation of a carbon-based quaternary centers. A closed transition state mechanism is proposed to describe the diastereoselectivity observed in the reactions that is consistent with product outcome as established by X-ray crystallography. Analysis using the 31P NMR technique is also reported to ascertain the diastereomeric ratios in product formation. Using products obtained with the newly developed method, we disclose for the first time a novel phospha-heterocycle with high control of stereochemistry. Relative stereochemistry of the phosphorus containing heterocycle was reported using 2D NMR analysis. In Chapter two focus is placed on the use of acrylates as Michael acceptors in both the diastereoselective and enantioselective studies of phospha-Michael addition. In the asymmetric method development, screening of various chiral catalysts and development of HPLC method to quantify the enantiopurity of products obtained under reaction conditions are reported. The role of crown ether catalysts towards diastereoselectivity is reported., 2022, Includes bibliography., Degree granted: Dissertation (Ph.D.)--Florida Atlantic University, 2022., Collection: FAU Electronic Theses and Dissertations Collection

Glycosylation is a frequent and heterogeneous post-translational protein modification occurring in all domains of life. Aberrant cell-surface glycosylation is shown to mediate several processes involved in tumor cell proliferation, adhesion, and metastasis. Recent findings linked altered protein glycosylation to Alzheimer’s disease (AD) pathogenesis. One key obstacle in studying functional consequences of glycosylation has been the lack of structurally defined glycopeptide or protein model compounds for biochemical studies at the molecular level. For tumor progression, studies are crucial towards understanding the glycan-lectin recognition process tied to deciphering the information contained in glycan structures and for AD, foundational studies are necessary for understanding the role of O-glycosylation in protein processing and its fate toward the amyloid pathway. In chapter 1, a highly O-glycosylated transmembrane and cancer-associated mucin protein, MUC1, is used as a model for designing synthetic tools for exploring its role in metastasis via association with lectins and specificity of anti-MUC1 antibodies. This dissertation for the first time presents a MUC1-based positional scanning synthetic glycopeptide combinatorial library that varies in the number and location of tumor-associated Tn antigen. The importance of defined structural complexity for evaluating glycan density and glycosylation patterns for binding to Tn-specific plant lectins and anti-MUC1 (mouse) monoclonal antibodies was revealed using an enzyme-linked lectin assay (ELLA). Chapter 2 addressed the growing significance of peptide lectinomimics for recognizing tumor-specific glycans. Fluorescently labelled alanine scan analogues of odorranalectin (OL), a cyclic peptide that exhibits lectin like properties, were screened for binding BSA-conjugated monosaccharides using ELLA. Results revealed that Lys5, Phe7, Tyr9, Gly12, Leu14, and Thr17 were crucial for binding BSA-L-fucose, BSA-Dgalactose and BS, 2022, Includes bibliography., Degree granted: Dissertation (Ph.D.)--Florida Atlantic University, 2022., Collection: FAU Electronic Theses and Dissertations Collection

Compared to the established monolayer approach of two-dimensional cell cultures, three-dimensional (3D) cultures more closely resemble in vivo models; that is, the cells interact and form clusters mimicking their organization in native tissue. Therefore, the cellular microenvironment of these 3D cultures proves to be more clinically relevant. In this study, we present a novel easy-to-fabricate microfluidic shallow trench induced 3D cell culturing and imaging (STICI3D) platform, suitable for rapid fabrication as well as mass manufacturing. Our design consists of a shallow trench, within which various hydrogels can be formed in situ via capillary action, between and fully in contact with two side channels that allow cell seeding and media replenishment, as well as forming concentration gradients of various molecules. Compared to a micropillar-based burst valve design, which requires sophisticated microfabrication facilities, our capillary-based STICI3D can be fabricated using molds prepared with simple adhesive tapes and razors alone. The simple design supports the easy applicability of mass-production methods such as hot embossing and injection molding as well. To optimize the STICI3D design, we investigated the effect of individual design parameters such as corner radii, trench height, and surface wettability under various inlet pressures on the confinement of a hydrogel solution within the shallow trench using Computational Fluid Dynamics simulations supported with experimental validation. We identified ideal design values that improved the robustness of hydrogel confinement and reduced the effect of end-user dependent factors such as hydrogel solution loading pressure. Finally, we demonstrated cultures of human mesenchymal stem cells and human umbilical cord endothelial cells in the STICI3D to show that it supports 3D cell cultures and enables precise control of cellular microenvironment and real-time microscopic imaging. The easy-to-fabricate and highly adaptable, Scientific and Technological Research Council of Turkey (TÜBİTAK); National Center for High Performance Computing of Turkey

Мета. Хвороба Хашимото (ХХ) є автоімунним захворюванням, у патогенезі якого відіграють роль як генетичні, так і зовнішні чинники. До останніх належить надходження йоду з їжею. Виведення йоду з сечею при збалансованому харчуванні рівною мірою відповідає його надходженню ззовні. Існує думка, згідно з якою висока концентрація йоду в сечі може бути пов’язана з автоімунним захворюванням щитоподібної залози. Мета нашої роботи — вивчити, чи підвищений рівень йоду в сечі у пацієнтів з ХХ порівняно з загальною популяцією. Матеріали та методи. Дослідження включало 64 пацієнтів з ХХ і 39 здорових добровольців. У всіх пацієнтів вивчали такі показники: вік, стать, рівень у сироватці крові вільного трийодтироніну (сТ3), вільного тироксину (сТ4), тиреотропного гормона (ТТГ), антитіл до тиреоїдної пероксидази (АТ-ТПО), антитіл до тиреоглобуліну (АТГ), а також концентрацію йоду в сечі. Було проведено ультрасонографію щитоподібної залози. Концентрацію йоду в сечі визначали з використанням реакції Санделла — ­Колтхофа. Результати. У нашому дослідженні не було виявлено вірогідного зв’язку між загальним обсягом щитоподібної залози і концентрацією йоду в сечі (p > 0,05). Також не було виявлено вірогідної різниці між рівнями сТ3, сТ4, АТ-ТПО, АТГ і об’ємом щитоподібної залози в осіб із концентрацією йоду в сечі вище і нижче від 100 мкг/л. Різниця сягала вірогідного рівня тільки при порівнянні показників ТТГ (р = 0,04). Не було виявлено різниці між загальним обсягом щитоподібної залози. У нашому дослідженні не було виявлено зв’язку між ХХ і рівнем йоду в сечі. З огляду на те, що поширеність ХХ у нашій країні відповідає даним, зазначеним у літературі, постає питання про роль йоду, що надходить з їжею, в патогенезі захворювання. Висновки. У йододефіцитних регіонах, до яких належить зокрема й наша країна, необхідно вивчати зв’язок між рівнем йоду в сечі та ХХ., Background. Hashimoto’s thyroiditis (HT) is an autoimmune disease which genetic and environmental factors play a role. One of the environmental risk factors is dietary iodine intake. Urinary iodine excretion in balanced diet is equally acceptable with received iodine. It’s thought that high urinary iodine excretion was associated with autoimmune thyroid diseases. We purposed to investigate whether urinary iodine level is higher in patients with HT than population. Materials and methods. 64 new patients with HT and 39 healthy volunteers were included. Age, gender, serum free-triiodothyronine (fT3), free-thyroxine (fT4), thyroid-stimulating hormone (TSH), anti thyroid peroxidase antibody (anti-TPO), anti thyroglobulin antibody (anti-TG) and urinary iodine concentration (UIC) were evaluated. Thyroid ultrasonography was performed. UIC were measured by Sandell-Kolthoff method. Results. There was no significant relationship was found between total thyroid volume and UIC in our study (p > 0.05). There was no significant difference between the fT3, fT4, anti-TPO, anti-TG and thyroid volume values of the individuals with urinary iodine levels below and above 100 μg/L. The difference between two subgroups was found to be significant only when TSH values were compared (p = 0.04). There was no significant difference between total thyroid volumes. No relation was found between HT and urine iodine levels in our study. The fact that the prevalence of HT in our country is similar to the literature makes us question the role of dietary iodine in the etiology. Conclusions. At the iodine-deficient regions such as our country relationship between urinary iodine excretion and HT needs to be investigated., Цель. Болезнь Хашимото (БХ) является аутоиммунным заболеванием, в патогенезе которого играют роль как генетические, так и внешние факторы. К последним относится поступление йода с пищей. Выведение йода с мочой при сбалансированном питании в равной мере соответствует его поступлению извне. Существует мнение, согласно которому высокая концентрация йода в моче может быть связана с аутоиммунным заболева­нием щитовидной железы. Цель нашей работы — изучить, повышен ли уровень йода в моче у пациентов с БХ по сравнению с общей популяцией. Материалы и методы. Исследование включало 64 пациентов с БХ и 39 здоровых добровольцев. У всех пациентов изучали следующие показатели: возраст, пол, уровень в сыворотке крови свободного трийодтиронина (сТ3), свободного тироксина (сТ4), тиреотропного гормона (ТТГ), антител к тиреоидной пероксидазе (АТ-ТПО), антител к тиреоглобулину (АТГ), а также концентрацию йода в моче. Была проведена ультрасонография щитовидной железы. Концентрацию йода в моче определяли с использованием реакции Санделла — ­Колтхофа. Результаты. В нашем исследовании не было выявлено достоверной связи между общим объемом щитовидной железы и концентрацией йода в моче (p > 0,05). Также не было обнаружено достоверной разницы между уровнями сТ3, сТ4, АТ-ТПО, АТГ и объемом щитовидной железы у лиц с концентрацией йода в моче выше и ниже 100 мкг/л. Разница достигала достоверного уровня только при сравнении показателей ТТГ (р = 0,04). Не было выявлено разницы между общим объемом щитовидной железы. В нашем исследовании не было обнаружено связи между БХ и уровнем йода в моче. Ввиду того, что распространенность БХ в нашей стране соответствует данным, указанным в литературе, встает вопрос о роли йода, поступающего с пищей, в патогенезе заболевания. Выводы. В йододефицитных регионах, к которым относится в том числе и наша страна, необходимо изучать связь между уровнем йода в моче и БХ.

The present study was aimed to isolate a new bacterial strain for the degradation/decolorization of azo dye Acid Blue 113 (AB 113). The physico-chemical method is inadequate for degradation of azo dyes; therefore, an environmental friendly and competent method such as use of the biological organism was studied for decolorization of AB 113. Bushnell and Hass (BHM) medium containing AB 113 dye were used to perform the decolorization study. 16S rRNA gene sequencing approach was used for identification of bacterial isolate as a Klebsiella variicola. The optimum process parameters for the decolorization of AB 113 were found at pH 8, 35°C temperature and 100 mg/L dye concentration during 72 h incubation. Glucose and ammonium sulphate was the carbon and nitrogen source suited well for the decolorization of dye. The results proved that the Klebsiella variicola, offer huge ability in treating textile wastewater containing the color AB 113.

Objective To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV). Methods Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay. Results PR3-ANCA+ AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 × 10−61, odds ratio (OR) 0.10; rs9277341, P = 1.5 × 10−44, OR 0.22] and with rs28929474 in the SERPINA1 gene (P = 2.7 × 10−10, OR 2.9). MPO-ANCA+ AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P = 5.4 × 10−25, OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P = 7.9 × 10−7, OR 3.0), the latter a novel susceptibility locus for MPO-ANCA+ granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele. Conclusion We identified a novel susceptibility locus for MPO-ANCA+ AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types.

Background: Porang glucomanan has been shown to have a potential properties for the prevention of Metabolic Syndrome (MetS). This study aimed to confirm that porang glucomannan supplementation can improve lipid profile in metabolic syndrome induced rats.Methods: Thirty male Sprague-Dawley rats were randomly divided into 5 groups consisting a contol group standard diet (Normal); Metabolic Syndrome group (SM), metabolic syndrome group + 25mg/200gBW Porang Glucomannan (GMP25), metabolic syndrome group + 50mg/200gBW Porang Glucomannan (GMP50), and metabolic syndrome group + 100mg/200gBW Porang Glucomannan (GMP100). The lipid profile before and after induction with high-fat and high-carbohydrate diet, and after 28 days of porang treatment were evaluated. Data were analyzed using One Way Anova followed by LSD post hoc test. Results: GMP100 rats showed the highest reversal of diet-induced changes, with decreased total cholesterol (TC), triglycerides (TG), and LDL, and also increased HDL level. The mean levels of TC, TG, and LDL in GMP100, GMP50 and GMP25 was significantly lower than those of in MS (p = 0.000), and was significantly higher than those of normal (p = 0.000). While the levels of HDL in GMP 100, GMP50, and GMP25 was significantly higher than those of MS (p = 0.000), but significantly lower than those of normal (p = 0.000). Conclusion: Porang glucomannan supplementation improve lipid profile in metabolic syndrome diet rats, with best dose at 100 mg/200 gBW.

Paullinia pinnata is a plant introduced to tropical Africa and has been reported to be useful in folkloric medicine. Different medicinal potentials of the leaves have been investigated some of which have corroborated reports in traditional medicine. Compounds have been isolated from extracts of the leaves which have been shown to have medicinal value. These compounds are from different classes of secondary metabolites including tannins, flavonoids and alkaloids. Fatty acids have also been shown to be present. This report is set to enumerate the traditional use of the leaves of P.pinnata and research findings already documented.

Ayurveda and Siddha systems are the two ancient medical systems originated in India more than 4000 years ago had given many formulary and treatment methods against influenza like infections. Kabasura churan from Siddha system and Maha sudharshan churan from the Ayurvedic system are the two major formulations along with many other individual herbs mentioned in the texts to treat Influenza like infections. Kabasura churan and Maha Sudarshan churan both have antipyretic, analgesic and anti-inflammatory effects. Both formulations were prepared according to Siddha and Ayurvedic texts. Herbs mentioned in both formulations like Turmeric, Tulsi (Basil), Kalmegh (Andrographis), Black Pepper, Liquorice (Mulethi), and Dronapushpi (Leucas) etc., had direct antiviral effect. Herbs like Aswagandha, Ginger, Guduchi (Tinospora), Kulanjan (Galangal) etc., had immunomodulatory and anti-inflammatory effect. Active compounds from different herbs were selected to study their antiviral activity through molecular docking algorithm. Application of modern of tools like Bioinformatics and Highthroughput screening methods can predict the efficacy of the ancient documented formulations and can be compared as per their literature. Compounds like curcumin, Glycyrrhizin, Ursolic acid, Quercetin, Andrographolide, Coumarins etc. were showed polyspecific activity like inhibition of Spike protein, Furin, Main Protease (Mpro) and Papain like Proteases (PLpro). Thus we propose use of Kabasura churan and Maha Sudharshan churan as alternative complementary medicine as a palliative treatment against COVID-19 caused by SARS-CoV-2 by conducting proper Randomized Clinical Trials

The use of pesticides like Chlorpyrifos in agricultural soil is the primary reason for the pollution of aquatic and terrestrial environments. Today the most effective method used for bioremediation are by using microbes. Different pesticide degrading bacteria were isolated and identified by the mean of cultural, biochemical tests and which is further identified and confirmed by 16S RNA sequencing method. The most potent strain S-1 growth in mineral salt medium supplemented with Chlorpyrifos as sole source of carbon (50 to 1000 ug/ml) its optical density was measured at 600 nm. The bacterial growth is optimised on the parameter of different physiochemical condition were. The result showed that S. aureus shows maximum growth on 12th day. The HPLC analysis was also done for calculating the residual percentage of Chlorpyrifos after 12 days incubation which showed that S. aureus was able to degrade 99% of the pesticide of the 1000 ug/ml CP concentration in the MSM. The results of this research shows that the isolated bacteria have the potential to be used in bioremediation of Chlorpyrifos contaminated soil and water ecosystems.

Matrix Metalloproteinase-28 (MMP-28) is the newest and least characterized member of MMP family. To date several potential substrate candidates for MMP-28 have been proposed but no in vivo substrates for this enzyme were confirmed. In the central nervous system (CNS) MMP-28 is believed to be important factor during myelination of the developing nervous system as well as during remyelination that follows neuronal injury. On the other hand, MMP-28 has been found in actively demyelinating lesions in both experimental autoimmune encephalopathy (EAE) and multiple sclerosis patients suggesting its possible role in pathological events associated with autoimmune neurodegenerative processes. In addition, MMP-28 has been linked to modulation of immune response and activation of macrophages which presents another role of this enzyme in autoimmune pathologies. In the study described herein, MMP-28 has been shown to affect myelin composition and appearance, mitochondrial protein content, and vesicular transport proteins. Moreover, the decrease in myelin basic protein quantity observed in healthy MMP-28KO animals affected the myelin staining intensity in various brain regions including corpus callous. Cellular energetic studies did not reveal differences in mitochondrial function in MMP-28KO animals and no difference in reactive oxygen species was observed. In the EAE model, MMP-28 deletion increased the occurrence of atypical form of EAE characterized by increased inflammation of arbor vitae of the brain. In addition, MMP-28 deletion decreased the inflammatory infiltrates present in brains obtained from EAE animals. Lastly, MMP-28 has been shown to affect cellular energetics and activation of bone marrow derived macrophages during the initial stages and after 24 h activation. In addition, MMP-28 deletion increased proinflammatory cytokines and receptors CD86 and iNOS found in M1 polarized macrophages., 2020, Includes bibliography., Degree granted: Dissertation (Ph.D.)--Florida Atlantic University, 2020., Collection: FAU Electronic Theses and Dissertations Collection

Eutrophication is an increase in primary plant nutrients (Nitrogen [N] and Phosphorus [P]) in oceans, estuaries and lakes. The consequences of eutrophication are harmful algal blooms (HABs), resulting in algal toxin production and the depletion of oxygen as the extensive biomass decays. P is often the limiting nutrient and is viewed as a significant environmental problem. Most of the excess P that enters aquatic ecosystems originates from anthropogenic sources such as fertilizers, sewage, animal wastes, compost, crop residues, and wastewater. Over time, one of the main reservoirs of P becomes organic P (Po). We investigated the chemical nature and dynamics of P in cyanobacteria, horse manure, stormwater treatment areas, and rice fields. To better understand the chemical nature of P, the identification of specific P compounds was required, which was achieved through 31P nuclear magnetic resonance (NMR) spectroscopy. We investigated how paramagnetic metals and quadrupolar nuclei cause severe line broadening, peak shifts, and decreased the signal to noise ratio. Results revealed that certain Po forms are readily bioavailable to Microcystis aeruginosa. Additionally, the potential heterotrophic use of the organic portion (e.g., glucose, glycerol) of these P compounds are indicated for the growth and persistence of Microcystis aeruginosa. We showed that the cultivation of rice (Oryza sativa L.) had been found to effectively reduce P from agrarian soil and water through plant uptake and, therefore, minimizing downstream eutrophication. Soil, water, sugarcane, and rice plants at two different stages were analyzed for twelve different elements. Finally, we examined how a “relic” agrarian ditch in Stormwater Treatment Area 1 East (STA-1E) can be used for the retention and sequestration of P and other nutrients. The STAs were established to capture P from agricultural and other sources before reaching the Everglades. Retained P is primarily stored in the wetland soils and sedi, 2020, Includes bibliography., Degree granted: Dissertation (Ph.D.)--Florida Atlantic University, 2020., Collection: FAU Electronic Theses and Dissertations Collection

Matrix Metalloproteinase-13 (MMP-13) belongs to a large family of proteolytic enzymes which are characterized by their ability to degrade the extracellular matrix components. MMP-13 appears to have a critical role in tumor invasion and metastasis. In this study, several fluorogenic probes specific for MMP-13 were designed and characterized. These synthesized probes could be modified with chelators to be applied for imaging MMP-13 in breast cancer and/or multiple myeloma models. The activity and selectivity of MMP-13 and other MMPs against these probes were studied through two approaches. It was found that these probes were cleaved by all MMPs, but MMP-13 showed the highest activity and selectivity towards these peptides., 2020, Includes bibliography., Degree granted: Thesis (M.S.)--Florida Atlantic University, 2020., Collection: FAU Electronic Theses and Dissertations Collection

The misfolding of native, cellular prion protein (PrPc) to a conformationally altered pathogenic isoform, designated scrapie PrPsc, is the main molecular process involved in the pathogenesis of prion diseases. Prion diseases are marked by the accumulation of conformationally modified forms of cellular prion protein. An N-terminal portion of the prion protein, PrP (106-128), is a 23-residue peptide fragment and is characterized by an amphipathic structure with two domains: a hydrophilic N-terminal domain and a hydrophobic C-terminal domain. In this study, the aggregation characteristics of the PrP (106-128) peptide were investigated using a combination of biophysical approaches. We investigated the effect of different factors including concentrations, pH, and metal ions, on the aggregation of the peptide. Our results demonstrated that the peptide steadily aggregates at concentrations higher than 25 M. The aggregation propensity and fibril formation is higher at pH 7.4 and pH 8.1, and the aggregation is inhibited at pH lower than 6. Furthermore, our results indicate that the Cu2+ has much less effect on the peptide amyloidogenesis, while Zn2+ has a significant influence on the PrP (106-128) amyloidogenesis. We further presented a systematic analysis of the impact of phospholipid liposomes of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1’-racglycerol) (POPG) in the absence or presence of cholesterol, on the amyloidogenesis of PrP (106-128). The results showed that POPC vesicles does not significantly influence the aggregation kinetics of the peptide. However, the anionic lipid POPG delays the aggregation in a concentration-dependent manner, whereas the addition of POPG with the cholesterol shows fast kinetics of fibrillization, thus reducing the lag time of the aggregation kinetics. We also monitored the effect of cholesterol and its derivatives including cholesterol-SO4 and DC-cholesterol on PrP (106-128) amy, 2020, Includes bibliography., Degree granted: Thesis (M.S.)--Florida Atlantic University, 2020., Collection: FAU Electronic Theses and Dissertations Collection

The Metzincins are a superfamily of zinc-dependent endopeptidases associated with the regulation of the extracellular matrix (ECM). Their members include A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTSs), A Disintegrin and Metalloproteinases (ADAMs), and the matrix metalloproteinases (MMPs). Metzincins exhibit diverse functions associated with both physiological and pathological states that include the proteolytic degradation of the ECM, regulation of various growth factors, cell surface receptors, and chemokines, and mediation of biological functions such as extravasation, survival, and proliferation. In pathological conditions such as cancer associated with chronic inflammation and multiple sclerosis associated with neurodegeneration, dysregulation of Metzincin activities are a hallmark of disease progression and severity. Hence, Metzincins are therapeutic targets for various disease states and research into optimal Metzincin inhibitor design is an ongoing exploit., 2020, Includes bibliography., Degree granted: Dissertation (Ph.D.)--Florida Atlantic University, 2020., Collection: FAU Electronic Theses and Dissertations Collection