Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular and Structural Characterizations of Lipases from Chlorella by Functional Genomics

Microalgae have been poorly investigated for new-lipolytic enzymes of biotechnological interest. In silico study combining analysis of sequences homologies and bioinformatic tools allowed the identification and preliminary characterization of 14 putative lipases expressed by Chlorella vulagaris. These proteins have different molecular weights, subcellular localizations, low instability index range and at least 40% of sequence identity with other microalgal lipases. Sequence comparison indicated that the catalytic triad corresponded to residues Ser, Asp and His, with the nucleophilic residue Ser positioned within the consensus GXSXG pentapeptide. 3D models were generated using different approaches and templates and demonstrated that these putative enzymes share a similar core with common α/β hydrolases fold belonging to family 3 lipases and class GX. Six lipases were predicted to have a transmembrane domain and a lysosomal acid lipase was identified. A similar mammalian enzyme plays an important role in breaking down cholesteryl esters and triglycerides and its deficiency causes serious digestive problems in human. More structural insight would provide important information on the enzyme characteristics.
HIV-1 Entry and Prospects for Protecting against Infection

Human Immunodeficiency Virus type-1 (HIV-1) establishes a latent viral reservoir soon after infection, which poses a major challenge for drug treatment and curative strategies. Many efforts are therefore focused on blocking infection. To this end, both viral and host factors relevant to the onset of infection need to be considered. Given that HIV-1 is most often transmitted mucosally, strategies designed to protect against infection need to be effective at mucosal portals of entry. These strategies need to contend also with cell-free and cell-associated transmitted/founder (T/F) virus forms; both can initiate and establish infection. This review will discuss how insight from the current model of HIV-1 mucosal transmission and cell entry has highlighted challenges in developing effective strategies to prevent infection. First, we examine key viral and host factors that play a role in transmission and infection. We then discuss preventive strategies based on antibody-mediated protection, with emphasis on targeting T/F viruses and mucosal immunity. Lastly, we review treatment strategies targeting viral entry, with focus on the most clinically advanced entry inhibitors.
Systematic Identification of Plasmodium Falciparum Sporozoite Membrane Protein Interactions Reveals an Essential Role for the p24 Complex in Host Infection

Sporozoites are a motile form of malaria-causing Plasmodium falciparum parasites that migrate from the site of transmission in the dermis through the bloodstream to invade hepatocytes. Sporozoites interact with many cells within the host, but the molecular identity of these interactions and their role in the pathology of malaria is poorly understood. Parasite proteins that are secreted and embedded within membranes are known to be important for these interactions, but our understanding of how they interact with each other to form functional complexes is largely unknown. Here, we compile a library of recombinant proteins representing the repertoire of cell surface and secreted proteins from the P. falciparum sporozoite and use an assay designed to detect extracellular interactions to systematically identify complexes. We identify three protein complexes including an interaction between two components of the p24 complex that is involved in the trafficking of glycosylphosphatidylinositol-anchored proteins through the secretory pathway. Plasmodium parasites lacking either gene are strongly inhibited in the establishment of liver-stage infections. These findings reveal an important role for the p24 complex in malaria pathogenesis and show that the library of recombinant proteins represents a valuable resource to investigate P. falciparum sporozoite biology.
Synthesis of backbone thermo and pH dual-responsive hyperbranched poly(amine-ether)s through proton-transfer polymerization

Stimuli-responsive hyperbranched polymers have attracted great attention in recent years because of their wide applications in biomedicine. Through proton-transfer polymerization of triethanolamine and 1,2,7,8-diepoxyoctane with the help of potassium hydride, a series of novel backbone thermo and pH dual-responsive hyperbranched poly(amine-ether)s were prepared successfully in one-pot. The degrees of branching of the resulting polymers were at 0.40–0.49. Turbidity measurements revealed that hyperbranched poly(amine-ether)s exhibited thermo and pH dual-responsive properties in water. Importantly, these responsivities could be readily adjusted by changing the polymer composition as well as the polymer concentration in aqueous solution. Moreover, in vitro evaluation demonstrated that hyperbranched poly(amine-ether)s showed low cytotoxicity and efficient cell internalization against NIH 3T3 cell lines. These results suggest that these backbone thermo and pH dual-responsive hyperbranched poly(amine-ether)s are promising materials for biomedicine. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011
Mechanisms of TTNtv-Related Dilated Cardiomyopathy: Insights from Zebrafish Models

Dilated cardiomyopathy (DCM) is a common heart muscle disorder characterized by ventricular dilation and contractile dysfunction that is associated with significant morbidity and mortality. New insights into disease mechanisms and strategies for treatment and prevention are urgently needed. Truncating variants in the TTN gene, which encodes the giant sarcomeric protein titin (TTNtv), are the most common genetic cause of DCM, but exactly how TTNtv promote cardiomyocyte dysfunction is not known. Although rodent models have been widely used to investigate titin biology, they have had limited utility for TTNtv-related DCM. In recent years, zebrafish (Danio rerio) have emerged as a powerful alternative model system for studying titin function in the healthy and diseased heart. Optically transparent embryonic zebrafish models have demonstrated key roles of titin in sarcomere assembly and cardiac development. The increasing availability of sophisticated imaging tools for assessment of heart function in adult zebrafish has revolutionized the field and opened new opportunities for modelling human genetic disorders. Genetically modified zebrafish that carry a human A-band TTNtv have now been generated and shown to spontaneously develop DCM with age. This zebrafish model will be a valuable resource for elucidating the phenotype modifying effects of genetic and environmental factors, and for exploring new drug therapies.
IN VITRO PRODUCTION OF SOLASODINE ALKALOID IN SOLANUM NIGRUM UNDER SALINITY STRESS

SUMMARY The effect of Salinity stress on solasodine production by Solanum nigrum under tissue culture conditions has been investigated. Solasodine is steroidal alkaloid, alternative to diosgenin, which is used as a precursor for the commercial production of steroidal drugs. Salinity stress has been applied by adding NaCl to the culture medium MS, five concentrations were applied: 0.0 (control), 50, 100, 150, and 200 mM for 8 weeks. The obtained results show the possibility to increase solsasodine level production under salainity stress. However, the highest salinity stress concentration (200 mM of NaCl) has not significant when it is compared to (150 mM of NaCl) concentration. Positive correlations were observed between the NaCl levels and solasodine content accumulation, proline content and solasodine accumulation in Solanum nigrum calli. The solasodine production increased significantly as a result of increasing of NaCl concentrations. However, non-significantly differences were observed between 150 mM and 200 mM of NaCl on solasodine accumulation.
The Identification of Genetic Determinants of Methanol Tolerance in Yeast Suggests Differences in Methanol and Ethanol Toxicity Mechanisms and Candidates for Improved Methanol Tolerance Engineering

Methanol is a promising feedstock for metabolically competent yeast strains-based biorefineries. However, methanol toxicity can limit the productivity of these bioprocesses. Therefore, the identification of genes whose expression is required for maximum methanol tolerance is important for mechanistic insights and rational genomic manipulation to obtain more robust methylotrophic yeast strains. The present chemogenomic analysis was performed with this objective based on the screening of the Euroscarf Saccharomyces cerevisiae haploid deletion mutant collection to search for susceptibility phenotypes in YPD medium supplemented with 8% (v/v) methanol, at 35 °C, compared with an equivalent ethanol concentration (5.5% (v/v)). Around 400 methanol tolerance determinants were identified, 81 showing a marked phenotype. The clustering of the identified tolerance genes indicates an enrichment of functional categories in the methanol dataset not enriched in the ethanol dataset, such as chromatin remodeling, DNA repair and fatty acid biosynthesis. Several genes involved in DNA repair (eight RAD genes), identified as specific for methanol toxicity, were previously reported as tolerance determinants for formaldehyde, a methanol detoxification pathway intermediate. This study provides new valuable information on genes and potential regulatory networks involved in overcoming methanol toxicity. This knowledge is an important starting point for the improvement of methanol tolerance in yeasts capable of catabolizing and copying with methanol concentrations present in promising bioeconomy feedstocks, including industrial residues.
A New Variant among Newcastle Disease Viruses Isolated in the Democratic Republic of the Congo in 2018 and 2019

Newcastle disease (ND) is a highly transmissible and devastating disease that affects poultry and wild birds worldwide. Comprehensive knowledge regarding the characteristics and epidemiological factors of the ND virus (NDV) is critical for the control and prevention of ND. Effective vaccinations can prevent and control the spread of the NDV in poultry populations. For decades, the Democratic Republic of the Congo (DRC) has reported the impacts of ND on commercial and traditional poultry farming systems. The reports were preliminary clinical observations, and few cases were confirmed in the laboratory. However, data on the phylogenetic, genetic, and virological characteristics of NDVs circulating in the DRC are not available. In this study, the whole-genome sequences of three NDV isolates obtained using the next-generation sequencing method revealed two isolates that were a new variant of NDV, and one isolate that was clustered in the subgenotype VII.2. All DRC isolates were velogenic and were antigenically closely related to the vaccine strains. Our findings reveal that despite the circulation of the new variant, ND can be controlled in the DRC using the current vaccine. However, epidemiological studies should be conducted to elucidate the endemicity of the disease so that better control strategies can be implemented.
Comprehensive Echocardiographic Findings in Critically Ill COVID-19 Patients With or Without Prior Cardiac Disease.

Purpose Coronavirus disease 2019 (COVID-19) presents with a spectrum of disease severity, the most serious cases requiring intensive care. Echocardiography is a front-line tool in evaluating cardiovascular complications of COVID-19 in the intensive care unit (ICU); we analyzed transthoracic echocardiograms obtained from this patient population with state-of-the-art ultrasound technology. Methods All patients with COVID-19 requiring ICU admission on whom a transthoracic echocardiogram was obtained were included in the study. Focused transthoracic protocols were performed by experienced sonographers. Echocardiographic variables, including speckle-tracking echocardiography, were collected and analyzed. Clinical information was obtained from the electronic medical record. Patients were followed until discharge. Results Of 52 total patients (mean age: 59.9 ± 11.6 years), 59.6% were male and 15 (29%) had known prior cardiac disease. Cardiac complications identified on echocardiography were prevalent, occurring in 55.7% of patients. Patients with known prior cardiac disease were more likely to have new or worsening left ventricular dysfunction. Right ventricular dysfunction was the most common abnormality (assessed qualitatively in 18 cases and with advanced echocardiographic methods in 34 cases). Known prior cardiac disease, right ventricular enlargement, and pulmonary hypertension were significantly associated with morbidity and mortality. Conclusions Patients requiring intensive care for COVID-19 face significant morbidity and mortality, and cardiac complications occur in the majority of patients admitted to the ICU with COVID-19. Those with known prior cardiac disease fare worse, and other echocardiographic findings (right ventricular enlargement, pulmonary hypertension) are also associated with worse outcomes. State-of-the-art echocardiography performed by experienced sonographers can be critical to identifying cardiac complications and guiding ICU strategy.
Structural similarity-based prediction of host factors associated with SARS-CoV-2 infection and pathogenesis

Abstract The current pandemic resulted from SARS-CoV-2 still remains as the major public health concern globally. The precise mechanism of viral pathogenesis is not fully understood, which remains a major hurdle for medical intervention. Here we generated an interactome profile of protein-protein interactions based on host and viral protein structural similarities information. Further computational biological study combined with Gene enrichment analysis predicted key enriched pathways associated with viral pathogenesis. The results show that axon guidance, membrane trafficking, vesicle-mediated transport, apoptosis, clathrin-mediated endocytosis, Vpu mediated degradation of CD4 T cell, and interferon-gamma signaling are key events associated in SARS-CoV-2 life cycle. Further, degree centrality analysis reveals that IRF1/9/7, TP53, and CASP3, UBA52, and UBC are vital proteins for IFN-γ-mediated signaling, apoptosis, and proteasomal degradation of CD4, respectively. We crafted chronological events of the virus life cycle. The SARS-CoV-2 enters through clathrin-mediated endocytosis, and the genome is trafficked to the early endosomes in a RAB5-dependent manner. It is predicted to replicate in a double-membrane vesicle (DMV) composed of the endoplasmic reticulum, autophagosome, and ERAD machinery. The SARS-CoV-2 down-regulates host translational machinery by interacting with protein kinase R, PKR-like endoplasmic reticulum kinase, and heme-regulated inhibitor and can phosphorylate eIF2a. The virion assembly occurs in the ER-Golgi intermediate compartment (ERGIC) organized by the spike and matrix protein. Collectively, we have established a spatial link between viral entry, RNA synthesis, assembly, pathogenesis, and their associated diverse host factors, those could pave the way for therapeutic intervention. Graphical Abstract Communicated by Ramaswamy H. Sarma
Radiographic Measures Predicting Failure of Arthroscopy in Borderline Hip Dysplasia: Response

center-anterior angle equivalent to anterior coverage of the hip? Clin Orthop Relat Res. 2009;467(11):2865-2871. 6. Siebenrock KA, Kistler L, Schwab JM, Büchler L, Tannast M. The acetabular wall index for assessing anteroposterior femoral head coverage in symptomatic patients. Clin Orthop Relat Res. 2012;470(12):3355-3360. 7. Vaudreuil NJ, McClincy MP. Evaluation and treatment of borderline dysplasia: moving beyond the lateral center edge angle. Curr Rev Musculoskelet Med. 2020;13(1):28-37. 8. Yeung M, Kowalczuk M, Simunovic N, Ayeni OR. Hip arthroscopy in the setting of hip dysplasia: A systematic review. Bone Joint Res. 2016;5(6):225-231.
Effects of quercetin, vitamin E, and estrogen on Metabolic-Related factors in uterus and serum of ovariectomized rat models

Abstract Aims Estrogen (E2) deficiency has been related to uterine metabolic dysfunction, which could be accompanied by infertility in the reproductive ages. Despite having adverse effects, estrogen replacement therapy is considered the fundamental treatment strategy for this problem. The current study sought to determine the palliative effects of quercetin (Q) and vitamin E (Vit.E) on some of the uterine's metabolism-related factors in ovariectomized (OVX) rats and compare them with the effects of estrogen. Materials and methods Sixty-four rats were divided into eight groups. OVX animals were treated with Q (15 mg/kg/day), Vit.E (60 mg/kg/day), E2 (10 µg/kg/day), and Q (7.5 mg/kg/day) + Vit.E (30 mg/kg/day) for 10 weeks. Glucose and adiponectin were measured using glucose oxidase and ELISA, respectively. Furthermore, the present study investigated the alterations in the expression of AdipoR1, nesfatin1, and GluT4 genes. Results Antioxidants suppress the weight gain of OVX animals. Also, Q, Vit.E, and E2 cause a significant decline in glucose and adiponectin levels (p-value < .05). Finally, the expression of AdipoR1, nesfatin1, and GLUT4 genes was significantly increased in treated OVX rats' uterus. Conclusion The present findings suggest that the administration of Q and Vit.E could demonstrate promising characteristics in a similar approach with estradiol and thus be considered as alternatives for estrogen replacement therapy.
The Exposome Approach to Decipher the Role of Multiple Environmental and Lifestyle Determinants in Asthma

Asthma is a widespread respiratory disease caused by complex contribution from genetic, environmental and behavioral factors. For several decades, its sensitivity to environmental factors has been investigated in single exposure (or single family of exposures) studies, which might be a narrow approach to tackle the etiology of such a complex multifactorial disease. The emergence of the exposome concept, introduced by C. Wild (2005), offers an alternative to address exposure–health associations. After presenting an overview of the exposome concept, we discuss different statistical approaches used to study the exposome–health associations and review recent studies linking multiple families of exposures to asthma-related outcomes. The few studies published so far on the association between the exposome and asthma-related outcomes showed differences in terms of study design, population, exposome definition and statistical methods used, making their results difficult to compare. Regarding statistical methods, most studies applied successively univariate (Exposome-Wide Association Study (ExWAS)) and multivariate (adjusted for co-exposures) (e.g., Deletion–Substitution–Addition (DSA) algorithm) regression-based models. This latest approach makes it possible to assess associations between a large set of exposures and asthma outcomes. However, it cannot address complex interactions (i.e., of order ≥3) or mixture effects. Other approaches like cluster-based analyses, that lead to the identification of specific profiles of exposure at risk for the studied health-outcome, or mediation analyses, that allow the integration of information from intermediate biological layers, could offer a new avenue in the understanding of the environment–asthma association. European projects focusing on the exposome research have recently been launched and should provide new results to help fill the gap that currently exists in our understanding of the effect of environment on respiratory health.
Estimation of Total Phenolics and Antioxidant Activity of an Ayurvedic Formulation Containing Aerial Root of F.Bengalensis

A traditional Ayurvedic formulation ‘Vizhal Veradi Kasayam’ containing the aerial root of F. bengalensis as the major constituent was analyzed for reducing power ability , antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and for total Phenolics using the Folin-Ciocalteu method. The total Phenolics determination showed that the formulation has a Phenolics content of 5.786 mg/mL GAE. Linearity range was found to be 20-140 μg/mL with the correlation coefficient of 0.999. The limit of detection and limit of quantification values were found to be1. 55μg/mL and 4.65 μg/mL . The formulation showed significant antiradical activity by bleaching 1,1-diphenyl-2picrylhydrazyl radical (IC50 8.5μg/mL) which is much better than that of Ascorbic acid (IC50 22.0μg/mL). In this simple spectrophotometric method aqueous and alcoholic extracts were used for analysis. The reducing ability, Fe to Fetransformation was found to increase with increasing concentrations of the sample.
Effect of surface charge conditions of carriers on the immobilization of β-d-glucosidase

Abstract In this study, a series of acidic or alkaline polypeptide chains were designed and grafted onto DEG-AM resin using Fmoc solid-phase synthesis to study the relationship between enzyme conformation and carrier surface charge. β-d-glucosidase (βGase) was then immobilized onto these modified carriers by adsorption. Each form of immobilized βGase showed decreasing specific activity compared to that of the free. It could be attributed to both the changes in the enzyme conformation and the decrease in mass transfer efficiency. The optimum temperature of free βGase, DEG@B3-βGase is 55 °C, which of DEG@A3-βGase is 65 °C and they all have the highest activity at pH 5. The Ea values of free βGase, DEG@A3-βGase, and DEG@B3-βGase are 0.546 kJ/mol, 0.224 kJ/mol, and 0.446 kJ/mol, and the Km values were 1.30 mmol/L, 1.44 mmol/L and 2.63 mmol/L, respectively. It shows that free βGase and DEG@A3-βGase are more similar. Meanwhile, the free βGase (1.0 g/L, pH 5.0) stored at 4 °C has a shorter half-life (t1/2), which is only 9 days. However, the half-life of DEG@B3-βGase and DEG@A3-βGase is 20 days and over 60 days, indicating that the negative charged surface was conducive to maintenance of the structure and catalytic property of βGase.
The role of e-commerce platforms in optimizing the HIV care continuum.

In 2014, the Joint United Nations Program on HIV/ AIDS (UNAIDS) set the 90–90–90 targets, aiming to diagnose 90% of all people living with HIV (PLHIV), provide antiretroviral therapy for 90% of those diagnosed with HIV, and achieve viral suppression for 90% of those on treatment [1]. HIV testing is essential to meeting these ambitious goals. However, one in five PLHIV have never been tested and remain unaware of their HIV status [2]. Many high-risk groups, including MSM, sex workers, and people who use drugs, are reluctant to seek venuebased HIV-testing services [3,4]. We need innovative testing strategies that lower barriers to testing while still protecting privacy, controlling costs, and addressing stigma [5]. One such strategy is leveraging e-commerce platforms to expand access to HIV testing.
How Does the Addition of Kollidon®VA64 Inhibit the Recrystallization and Improve Ezetimibe Dissolution from Amorphous Solid Dispersions?

Amorphization serves as a strategy for the improvement of poor dissolution characteristics of many drug compounds. However, in many formulations the content of polymeric stabilizer is high, which is undesirable from the perspective of future applications. Thus, studying the composition-dependent stability of amorphous solid dispersions seems to be demanded. In this paper, we describe the amorphization of ezetimibe, a lipid-lowering drug, in the spray drying process and investigate the effect of polyvinylpyrrolidone-co-poly(vinyl acetate) (PVP/VA) content on the physical stability and dissolution characteristics of the drug. Fully amorphous systems were obtained when the concentration of the polymer in solid dispersion was as low as 20%. The amorphization led to the dissolution enhancement by even 70%, with a noticeable sudden increase at around 40% of PVP/VA content and very small variations for systems having 66–90% PVP/VA. It was also correlated to wettability characteristics of solid dispersions, which may suggest that in the vicinity of 40% of the polymer content, the behavior of the system becomes independent of the PVP/VA content.