Islet amyloid polypeptide (IAPP), a 37 residue polypeptide, is the main protein component of islet amyloid deposits produced in the pancreas in Type 2 diabetes. Human IAPP contains five serine residues at positions 19, 20, 28, 29, and 34. Models of the IAPP amyloid fibril indicate a structure composed of two closely aligned columns of IAPP monomers with each monomer contributing to two intermolecular β-strands. Ser 19 and Ser 20 are in the partially ordered β-turn region, which links the two strands, whereas Ser 28, Ser 29, and Ser 34 are in the core region of the amyloid fibril. Ser 29 is involved in contacts between the two columns of monomers and is the part of the steric zipper interface. We undertook a study of individual serine substitutions with the hydrophobic isostere 2-aminobutyric acid (2-Abu) to examine the site-specific role of serine side chains in IAPP amyloid formation. All five variants formed amyloid. The Ser 19 to 2-Abu mutant accelerates amyloid formation by a factor of 3 to 4, while the Ser 29 to 2-Abu mutation modestly slows the rate of amyloid formation. 2-Abu replacements at the other sites had even smaller effects. The data demonstrate that the cross-column interactions made by residue 29 are not essential for amyloid formation and also show that cross-strand networks of hydrogen-bonded Ser side chains, so called Ser-ladders, are not required for IAPP amyloid formation. The effect of the Ser 19 to 2-Abu mutant suggests that residues in this region are important for amyloid formation by IAPP.

The luciferase isolated from the firefly Photinus pyralis (Ppy) catalyzes a two-step reaction that results in the oxidation of d-luciferin accompanied by emission of yellow-green light with a peak at 560 nm. Among many applications, Ppy luciferase has been used extensively as a reporter gene in living cells and organisms. However, some biological applications are limited by the low stability of the luciferase and limited intracellular luciferin concentration. To address these challenges, efforts to protein engineer Ppy luciferase have resulted in a number of mutants with improved properties such as thermostability, pH tolerance, and catalytic turn over. In this work, we combined amino acid mutations that were shown to enhance the enzyme's thermostability (Mutant E) with those reported to enhance catalytic activity (LGR). The resulting mutant (YY5) contained eight amino acid changes from the wild-type luciferase and exhibited both improved thermostability and brighter luminescence at low luciferin concentrations. Therefore, YY5 may be useful for reporter gene applications.

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported as a worldwide emergency. Due to the extensiveness of spread and death, it has been declared as a pandemic. This review focused on the current pandemic situation and understanding the prevention and control strategies of COVID-19. Data presented here was by April 3, 2020. A total of 1,016,399 cases of COVID-19 with 53,238 deaths was reported from 204 countries and territories including two international conveyances over the world. After China, most of the new cases were from Europe, particularly Italy acting as the source of importation to many of the other countries around the world. China has obtained success by ascribing control strategies against COVID-19. The implementation of Chinas strategy, as well as the development of a vaccine, may control the pandemic of COVID-19. Further robust studies are required for a clear understanding of transmission parameters, prevention, and control strategies of SARS-CoV-2. This review paper describes the nature of COVID-19 and the possible ways for the effective controlling of the COVID-19 or similar viral diseases that may come in the future.

The development of inhibitors of islet amyloid formation is important as pancreatic amyloid deposition contributes to type-2 diabetes and islet transplant failure. The Alzheimer's Aβ peptide and human amylin (h-amylin), the polypeptide responsible for amyloid formation in type-2 diabetes, share common physio-chemical features and some inhibitors of Aβ also inhibit amyloid formation by h-amylin and vice versa. Thus, a popular and potentially useful strategy to find lead compounds for anti-amylin amyloid agents is to examine compounds that have effects on Aβ amyloid formation. The triphenylmethane dye, brilliant blue G (BBG, Sodium;3-[[4-[(E)-[4-(4-ethoxyanilino)phenyl]-[4-[ethyl-[(3-sulfonatophenyl)methyl]azaniumylidene]-2-methylcyclohexa-2,5-dien-1-ylidene]methyl]-N-ethyl-3-methylanilino]methyl]benzenesulfonate) has been shown to modulate Aβ amyloid formation and inhibit Aβ induced toxicity. However, the effects of BBG on h-amylin have not been examined, although other triphenylmethane derivatives inhibit h-amylin amyloid formation. The compound has only a modest impact on h-amylin amyloid formation unless it is added in significant excess. BBG also remodels preformed h-amylin amyloid fibrils if added in excess, however BBG has no significant effect on h-amylin induced toxicity towards cultured β-cells or cultured CHO-T cells except at high concentrations. BBG is shown to interfere with standard thioflavin-T assays of h-amylin amyloid formation and disaggregation, highlighting the difficulty of interpreting such experiments in the absence of other measurements. BBG also interferes with ANS based assays of h-amylin amyloid formation. The work highlights the differences between inhibition of Aβ and h-amylin amyloid formation, illustrates the limitation of using Aβ inhibitors as leads for h-amylin amyloid inhibitors, and reinforces the difficulties in interpreting dye binding assays of amyloid formation.

Islet amyloid formation contributes to β-cell death and dysfunction in type-2 diabetes and to the failure of islet transplants. Amylin (islet amyloid polypeptide, IAPP), a normally soluble 37 residue polypeptide hormone produced in the pancreatic β-cells, is responsible for amyloid formation in type-2 diabetes and is deficient in type-1 diabetes. Amylin normally plays an adaptive role in metabolism, and the development of nontoxic, non-amyloidogenic, bioactive variants of human amylin are of interest for use as adjuncts to insulin therapy. Naturally occurring non-amyloidogenic variants are of interest for xenobiotic transplantation and because they can provide clues toward understanding the amyloidogenicity of human amylin. The sequence of amylin is well-conserved among species, but sequence differences strongly correlate with in vitro amyloidogenicity and with islet amyloid formation in vivo. Bovine amylin differs from the human peptide at 10 positions and is one of the most divergent among known amylin sequences. We show that bovine amylin oligomerizes but is not toxic to cultured β-cells and that it is considerably less amyloidogenic than the human polypeptide and is only a low-potency agonist at human amylin-responsive receptors. The bovine sequence contains several nonconservative substitutions relative to human amylin, including His to Pro, Ser to Pro, and Asn to Lys replacements. The effect of these substitutions is analyzed in the context of wild-type human amylin; the results provide insight into their role in receptor activation, the mode of assembly of human amylin, and the design of soluble amylin analogues.

A multidisciplinary approach was applied to explore deeper knowledge about the reproductive biology and ecology of the green mussel (Perna viridis) by interlinking among ecological factors, ingested gut plankton, gonad fatty acid profile, and reproductive traits. Mussels were collected throughout the year from the coastal region of the Bay of Bengal of Bangladesh, and the histological analysis of 242 mussels revealed five stages of gametogenesis with an annual spawning season from January to April. The gonadosomatic index showed a strong correlation with the water quality parameters, ingested gut plankton groups, and gonadal fatty acids, and also displayed prominent effects of seasonality. In all datasets, we performed principal component analysis in which the first two principal components showed that seasonality explained >65% of the variability, and the multivariate spaces of seasonality corresponded to the gonad development. High salinity, nutrients, chlorophyll a, and plankton abundance in the water column were positively correlated with gonad development and the spawning of mussels. During the development stage, mussel ingested more plankton, particularly Bacillariophyceae and Pyrrophyceae, which were an important source of increased n-3 polyunsaturated fatty acids content in gonads. Furthermore, gonads accumulated more lipids and saturated fatty acids during the mature and spawning stages, which were probably utilized during embryogenesis and early larval development as energy sources and constituents of the cell membrane. This research provides a model toward a better understanding of reproductive biological traits and how these traits are interrelated with the surrounding environmental variables of the green mussel, which would be helpful in marine aquaculture and the sustainable exploitation of the fishery resources.

OBJECTIVES: Migratory birds play a major role in the transmission of pathogens globally, but still their role in the transmission of fungi in Bangladesh is not known. The present study was carried out for the isolation and molecular detection of fungi including Aspergillus from migratory birds traveling to Bangladesh. MATERIALS AND METHODS: A total of 50 fecal samples were collected from BaojaniBaor, Magura, and areas close to Jahangirnagar University, Savar. The isolation of fungus was based on culture on Potato Dextrose Agar (PDA), followed by staining, morphology, and molecular detection using polymerase chain reaction (PCR). RESULTS: Among 50 samples, 40 showed positive for fungal growth on PDA, of which 30 yield only yeast-like colonies, five only molds, and five yielded both yeast and molds. The isolated molds produced various pigmented colonies, namely, black, whitish, grayish, olive green, and yellow. Among 10 molds, six were confirmed as fungi by PCR using genus-specific primers such as ITS1 and ITS4. Later, of these six fungi, five were confirmed as Aspergillus by PCR with primers such as ASAP1 and ASAP2 specific for Aspergillus genus. Therefore, the overall occurrence of Aspergillus was 10% (5/50). PCR specific for Aspergillus fumigatus and Aspergillus niger failed to produce specific PCR amplicon, suggesting that the isolated Aspergillus belongs to other groups. CONCLUSION: This is the first report describing the isolation and molecular detection of Aspergillus from fecal samples of migratory birds in Bangladesh. The present findings confirm that migratory birds are potential source for Aspergillus and other fungus in Bangladesh.

Background: The Addressing Reproductive Coercion in Health Settings (ARCHES) intervention trains existing providers to address reproductive coercion (RC) and intimate partner violence (IPV) within routine family planning counseling. This study evaluated the effectiveness of a single ARCHES counseling session as adapted for use with abortion clients in Bangladesh. Methods: In this cluster-randomized controlled trial conducted between January 2019 and January 2021, health facilities with an abortion clinic with infrastructure for private counseling and onsite violence support services were eligible. Six facilities in Bangladesh met inclusion criteria, and matched pairs randomization with parallel assignment and a 1:1 allocation ratio was used to randomize three facilities to ARCHES and three facilities to control, which implemented standard counseling. Blinding was not possible as providers in intervention facilities participated in a three-day ARCHES training. Participants were abortion clients aged 18–49 years who could provide safe recontact information and be interviewed privately. The primary outcome was past three-month modern contraceptive use without interruption or interference. The trial was registered on clinicaltrials.gov (NCT03539315) on 29 May 2018. Findings: A total of 1492 intervention participants and 1237 control participants were enrolled. Available data were analyzed at each follow-up period: 1331 intervention and 1069 control participants at the three-month follow-up, and 1269 intervention and 1050 control participants at the twelve-month follow-up. ARCHES was associated with higher likelihood of modern contraceptive use at the three-month follow-up (adjusted RR = 1.08, 95% CI: 1.06–1.10) and the twelve-month follow-up (adjusted RR = 1.06, 95% CI: 1.02–1.10). ARCHES was also associated with decreased incident pregnancy, decreased IPV, and increased knowledge of IPV support services. Interpretation: The ARCHES intervention is effective in increasing post-abortion modern contraceptive use and decreasing incident pregnancy and IPV among abortion clients in Bangladesh. Implementation of ARCHES should be considered in facilities with sufficient privacy for counseling. Funding: Society of Family Planning (#SFPRF11-07) and Ipas.

Antibodies with conformational specificity are important for detecting and interfering with polypeptide aggregation linked to several human disorders. We are developing a motif-grafting approach for designing lead antibody candidates specific for amyloid-forming polypeptides such as the Alzheimer peptide (Aβ). This approach involves grafting amyloidogenic peptide segments into the complementarity-determining regions (CDRs) of single-domain (VH) antibodies. Here we have investigated the impact of polar mutations inserted at the edges of a large hydrophobic Aβ42 peptide segment (Aβ residues 17-42) in CDR3 on the solubility and conformational specificity of the corresponding VH domains. We find that VH expression and solubility are strongly enhanced by introducing multiple negatively charged or asparagine residues at the edges of CDR3, whereas other polar mutations are less effective (glutamine and serine) or ineffective (threonine, lysine, and arginine). Moreover, Aβ VH domains with negatively charged CDR3 mutations show significant preference for recognizing Aβ fibrils relative to Aβ monomers, whereas the same VH domains with other polar CDR3 mutations recognize both Aβ conformers. We observe similar behavior for a VH domain grafted with a large hydrophobic peptide from islet amyloid polypeptide (residues 8-37) that contains negatively charged mutations at the edges of CDR3. These findings highlight the sensitivity of antibody binding and solubility to residues at the edges of CDRs, and provide guidelines for designing other grafted antibody fragments with hydrophobic binding loops.