The Prenucleation Equilibrium of the Parathyroid Hormone Determines the Critical Aggregation Concentration and Amyloid Fibril Nucleation.

Nucleation and growth of amyloid fibrils were found to only occur in supersaturated solutions above a critical concentration (c ). The biophysical meaning of c remained mostly obscure, since typical low values of c in the sub-μM range hamper investigations of potential oligomeric states and their structure. Here, we investigate the parathyroid hormone PTH as an example of a functional amyloid fibril forming peptide with a comparably high c of 67±21 μM.

Increased health risk assessment in different vegetables grown under untreated sewerage irrigation regime due to higher heavy metals accumulation.

Heavy metals are environmental pollutants and carcinogenic for human health if ingested. In developing countries, including Pakistan, untreated sewerage water is one of the major sources of irrigation for vegetable production in the vicinities of urban areas which might be toxic to human health due to heavy metals contamination. The present study was conducted to investigate the uptake of heavy metals by sewage water application and its impact on human health.

Comprehensive Mechanistic View of the Hydrolysis of Oxadiazole-Based Inhibitors by Histone Deacetylase 6 (HDAC6).

Histone deacetylase (HDAC) inhibitors used in the clinic typically contain a hydroxamate zinc-binding group (ZBG). However, more recent work has shown that the use of alternative ZBGs, and, in particular, the heterocyclic oxadiazoles, can confer higher isoenzyme selectivity and more favorable ADMET profiles. Herein, we report on the synthesis and biochemical, crystallographic, and computational characterization of a series of oxadiazole-based inhibitors selectively targeting the HDAC6 isoform.

Phylogenetic relationships of a novel bat fly species infesting the geographically widespread Old World fruit bat, Rousettus leschenaultii, in Southern Asia.

The global epidemiological significance of bats and their blood-sucking ectoparasites is increasingly recognized. However, relevant data are scarce from Pakistan where the Palearctic and Oriental zoogeographic regions meet. In this study, 200 bats belonging to five species were examined for the presence of ectoparasites in Pakistan.

Valorization of Using Agro-Wastes for Levan through Submerged Fermentation and Statistical Optimization of the Process Variables Applying Response Surface Methodology (RSM) Design.

Levan is a homopolysaccharide of fructose units that repeat as its structural core. As an exopolysaccharide (EPS), it is produced by a great variety of microorganisms and a small number of plant species. The principal substrate used for levan production in industries, i.

Evidence for direct interaction between the oncogenic proteins E6 and E7 of high-risk human papillomavirus (HPV).

Human papillomaviruses (HPVs) are DNA tumor viruses that infect mucosal and cutaneous epithelial cells of more than 20 vertebrates. High-risk HPV causes about 5% of human cancers worldwide, and the viral proteins E6 and E7 promote carcinogenesis by interacting with tumor suppressors and interfering with many cellular pathways. As a consequence, they immortalize cells more efficiently in concert than individually.

In-silico assessment of high-risk non-synonymous SNPs in ADAMTS3 gene associated with Hennekam syndrome and their impact on protein stability and function.

Hennekam Lymphangiectasia-Lymphedema Syndrome 3 (HKLLS3) is a rare genetical disorder caused by mutations in a few genes including ADAMTS3. It is characterized by lymphatic dysplasia, intestinal lymphangiectasia, severe lymphedema and distinctive facial appearance. Up till now, no extensive studies have been conducted to elucidate the mechanism of the disease caused by various mutations.

Whole Exome Sequencing Reveals Clustering of Variants of Known Vitiligo Genes in Multiplex Consanguineous Pakistani Families.

Vitiligo is an autoimmune complex pigmentation disease characterized by non-pigmented patches on the surface of the skin that affect approximately 0.5-2% population worldwide. The exact etiology is still unknown; however, vitiligo is hypothesized to be a multifactorial and genetically heterogeneous condition.

Structural assessment of the full-length wild-type tumor suppressor protein p53 by mass spectrometry-guided computational modeling.

The tetrameric tumor suppressor p53 represents a great challenge for 3D-structural analysis due to its high degree of intrinsic disorder (ca. 40%). We aim to shed light on the structural and functional roles of p53's C-terminal region in full-length, wild-type human p53 tetramer and their importance for DNA binding.

Structural analysis of an endogenous 4-megadalton succinyl-CoA-generating metabolon.

The oxoglutarate dehydrogenase complex (OGDHc) participates in the tricarboxylic acid cycle and, in a multi-step reaction, decarboxylates α-ketoglutarate, transfers succinyl to CoA, and reduces NAD+. Due to its pivotal role in metabolism, OGDHc enzymatic components have been studied in isolation; however, their interactions within the endogenous OGDHc remain elusive. Here, we discern the organization of a thermophilic, eukaryotic, native OGDHc in its active state.

Insights into nanoparticles-induced neurotoxicity and cope up strategies.

Nanoparticle applications are becoming increasingly popular in fields such as photonics, catalysis, magnetics, biotechnology, manufacturing of cosmetics, pharmaceuticals, and medicines. There is still a huge pile of undermining information about the potential toxicity of these products to humans, which can be encountered by neuroprotective antioxidants and anti-inflammatory compounds. Nanoparticles can be administered using a variety of methods, including oronasal, topical applications, and enteral and parenteral routes of administration.

Dissecting Rubella Placental Infection in an In Vitro Trophoblast Model.

Vertical transmission of rubella virus (RuV) occurs at a high rate during the first trimester of pregnancy. The modes of vertical transmission including the response of trophoblasts to RuV are not well understood. Here, RuV-trophoblast interaction was studied in the BeWo trophoblast cell line.

Molecular characterization of vancomycin-resistant Staphylococcus aureus isolated from bovine milk.

Vancomycin-resistant Staphylococcus aureus (VRSA) is a zoonotic life-threatening pathogen. Vancomycin exhibits anti-bacterial activity by inhibiting peptidoglycan synthesis by binding to the D-ala-D-ala terminus of the peptidoglycan. But in VRSA, D-ala-D-ala is replaced by D-ala-D-lactate due to the presence of vanA, vanB or vanD genes.

Expression of symptoms elicited by a hammerhead viroid through RNA silencing is related to population bottlenecks in the infected host.

Chlorosis is frequently incited by viroids, small nonprotein-coding, circular RNAs replicating in nuclei (family Pospiviroidae) or chloroplasts (family Avsunviroidae). Here, we investigated how chrysanthemum chlorotic mottle viroid (CChMVd, Avsunviroidae) colonizes, evolves and initiates disease. Progeny variants of natural and mutated CChMVd sequence variants inoculated in chrysanthemum plants were characterized, and plant responses were assessed by molecular assays.

Continuous Fluorescent Sirtuin Activity Assay Based on Fatty Acylated Lysines.

Lysine deacetylases, like histone deacetylases (HDACs) and sirtuins (SIRTs), are involved in many regulatory processes such as control of metabolic pathways, DNA repair, and stress responses. Besides robust deacetylase activity, sirtuin isoforms SIRT2 and SIRT3 also show demyristoylase activity. Interestingly, most of the inhibitors described so far for SIRT2 are not active if myristoylated substrates are used.

Antifungal Activity of -Mediated Silver Nanoparticles (AgNPs) against -Induced Toxicity in In Vitro and In Vivo Settings.

Aflatoxins produced by some species of are considered secondary toxic fungal by-products in feeds and food. Over the past few decades, many experts have focused on preventing the production of aflatoxins by and also reducing its toxicity. Applications of various nanomaterials in preventing the production of these toxic aflatoxins have received a lot of attention recently.

Presence of endometrioma decreased blastocyst formation rate but not impair Assisted Reproductive Technology (ART) outcome.

Purpose: This study aims to assess the impact of endometrioma on patients who undergo ART treatment due to endometriosis.

Methods: A retrospective study was conducted on women ≤ 40 years of age who underwent ART treatment at an academic medical center between January 2014 and December 2020. Two-hundred-and-eight women had received IVF/ICSI treatment due to endometriosis and there were 89 patients presence of endometrioma.

Synthesis of Complex Thiazoline-Containing Peptides by Cyclodesulfhydration of N-Thioacyl-2-Mercaptoethylamine Derivatives.

Herein we report a mild, efficient, and epimerization-free method for the synthesis of peptide-derived 2-thiazolines and 5,6-dihydro-4H-1,3-thiazines based on a cyclodesulfhydration of N-thioacyl-2-mercaptoethylamine or N-thioacyl-3-mercaptopropylamine derivatives. The described reaction can be easily carried out in aqueous solutions at room temperature and it is triggered by change of the pH, leading to complex thiazoline or dihydrothiazine derivatives without epimerization in excellent to quantitative yields. The new method was applied in the total synthesis of the marine metabolite mollamide F, resulting in the revision of its stereochemistry.

Enabling cryo-EM density interpretation from yeast native cell extracts by proteomics data and AlphaFold structures.

In the cellular context, proteins participate in communities to perform their function. The detection and identification of these communities as well as in-community interactions has long been the subject of investigation, mainly through proteomics analysis with mass spectrometry. With the advent of cryogenic electron microscopy and the "resolution revolution," their visualization has recently been made possible, even in complex, native samples.

Novel exotic alleles of EARLY FLOWERING 3 determine plant development in barley.

EARLY FLOWERING 3 (ELF3) is an important regulator of various physiological and developmental processes and hence may serve to improve plant adaptation which will be essential for future plant breeding. To expand the limited knowledge on barley ELF3 in determining agronomic traits, we conducted field studies with heterogeneous inbred families (HIFs) derived from selected lines of the wild barley nested association mapping population HEB-25. During two growing seasons, phenotypes of nearly isogenic HIF sister lines, segregating for exotic and cultivated alleles at the ELF3 locus, were compared for 10 developmental and yield-related traits.

Antioxidant and hypoglycemic potential of phytogenic cerium oxide nanoparticles.

Plants provide humans with more than just food and shelter; they are also a major source of medications. The purpose of this research was to investigate the antioxidant and hypoglycemic potential of green synthesized CeONPs using Mentha royleana leaves extract. The morphological and physicochemical features of CeONPs were evaluated by UV-Visible spectrophotometry, Scanning Electron Microscopy, Energy Dispersive X-rays and Fourier-transform infrared spectrometry, Dynamic light scattering, Atomic Force Microscopy, Zeta Potential.

Cracking the code of cellular protein-protein interactions: Alphafold and whole-cell crosslinking to the rescue.

Integration of experimental and computational methods is crucial to better understanding protein-protein interactions (PPIs), ideally in their cellular context. In their recent work, Rappsilber and colleagues (O'Reilly et al, 2023) identified bacterial PPIs using an array of approaches. They combined whole-cell crosslinking, co-fractionation mass spectrometry, and open-source data mining with artificial intelligence (AI)-based structure prediction of PPIs in the well-studied organism Bacillus subtilis.