Integrative determination of atomic structure of mutant huntingtin exon 1 fibrils implicated in Huntington disease.

Neurodegeneration in Huntington's disease (HD) is accompanied by the aggregation of fragments of the mutant huntingtin protein, a biomarker of disease progression. A particular pathogenic role has been attributed to the aggregation-prone huntingtin exon 1 (HTTex1), generated by aberrant splicing or proteolysis, and containing the expanded polyglutamine (polyQ) segment. Unlike amyloid fibrils from Parkinson's and Alzheimer's diseases, the atomic-level structure of HTTex1 fibrils has remained unknown, limiting diagnostic and treatment efforts.

Light-dependent modulation of protein localization and function in living bacteria cells.

Most bacteria lack membrane-enclosed organelles and rely on macromolecular scaffolds at different subcellular locations to recruit proteins for specific functions. Here, we demonstrate that the optogenetic CRY2-CIB1 system from Arabidopsis thaliana can be used to rapidly direct proteins to different subcellular locations with varying efficiencies in live Escherichia coli cells, including the nucleoid, the cell pole, the membrane, and the midcell division plane. Such light-induced re-localization can be used to rapidly inhibit cytokinesis in actively dividing E.

Cas12e orthologs evolve variable structural elements to facilitate dsDNA cleavage.

Exceptionally diverse type V CRISPR-Cas systems provide numerous RNA-guided nucleases as powerful tools for DNA manipulation. Two known Cas12e nucleases, DpbCas12e and PlmCas12e, are both effective in genome editing. However, many differences exist in their in vitro dsDNA cleavage activities, reflecting the diversity in Cas12e's enzymatic properties.

Hydronium Ions Are Less Excluded from Hydrophobic Polymer-Water Interfaces than Hydroxide Ions.

The cloud point temperatures of aqueous poly(-isopropylacrylamide) (PNIPAM) and poly(ethylene) oxide (PEO) solutions were measured from pH 1.0 to pH 13.0 at a constant ionic strength of 100 mM.

Investigating the Mechanisms Involved in Scopolamine-induced Memory Degradation.

In the present study, the mechanisms involved in scopolamine-induced memory impairment have been investigated. The molecular events that take place during memory mostly include mechanisms that are seen in the acquisition phase. Results showed that one of the mechanisms of memory destruction caused by scopolamine, in addition to weakening the cholinergic system, is the indirect effect of scopolamine on other neurotransmitter systems, including the glutamatergic system.

The eusocial non-code: Unveiling the impact of noncoding RNAs on Hymenoptera eusocial evolution.

Eusociality, characterized by reproductive division of labor, cooperative brood care, and multi-generational cohabitation, represents a pinnacle of complex social evolution, most notably manifested within the Hymenoptera order including bees, ants, and wasps. The molecular underpinnings underlying these sophisticated social structures remain an enigma, with noncoding RNAs (ncRNAs) emerging as crucial regulatory players. This article delves into the roles of ncRNAs in exerting epigenetic control during the development and maintenance of Hymenopteran eusociality.

Distinct regulation of Tau Monomer and aggregate uptake and intracellular accumulation in human neurons.

Background: The prion-like spreading of Tau pathology is the leading cause of disease progression in various tauopathies. A critical step in propagating pathologic Tau in the brain is the transport from the extracellular environment and accumulation inside naïve neurons. Current research indicates that human neurons internalize both the physiological extracellular Tau (eTau) monomers and the pathological eTau aggregates.

Harnessing 3D models to uncover the mechanisms driving infectious and inflammatory disease in the intestine.

Representative models of intestinal diseases are transforming our knowledge of the molecular mechanisms of disease, facilitating effective drug screening and avenues for personalised medicine. Despite the emergence of 3D in vitro intestinal organoid culture systems that replicate the genetic and functional characteristics of the epithelial tissue of origin, there are still challenges in reproducing the human physiological tissue environment in a format that enables functional readouts. Here, we describe the latest platforms engineered to investigate environmental tissue impacts, host-microbe interactions and enable drug discovery.

Discovery of a Natural Ent-Kaurene Diterpenoid Oridonin as an E3 Ligase Recruiter for PROTACs.

PROTACs have emerged as a therapeutic modality for the targeted degradation of proteins of interest (POIs). Central to PROTAC technology are the E3 ligase recruiters, yet only a few of them have been identified due to the lack of ligandable pockets in ligases, especially among single-subunit ligases. We propose that binders of partner proteins of single-subunit ligases could be repurposed as new ligase recruiters.

A single-plasmid-based, easily curable CRISPR/Cas9 system for rapid, iterative genome editing in Pseudomonas putida KT2440.

Background: Pseudomonas putida KT2440, a non-pathogenic soil bacterium, is a key platform strain in synthetic biology and industrial applications due to its robustness and metabolic versatility. Various systems have been developed for genome editing in P. putida, including transposon modules, integrative plasmids, recombineering systems, and CRISPR/Cas systems.

Shielding siRNA by peptide-based nanofibers: An efficient approach for turning off EGFR gene in breast cancer.

Peptide-based self-assembled nanosystems show great promise as non-viral gene and siRNA delivery vectors. In the current study, we designed and functionalized nanofibers for the delivery of siRNA, targeting and silencing EGFR gene overexpressed in triple-negative breast cancer. The nanofiber-mediated siRNA delivery was characterized in terms of zeta potential, morphology, and structural stability by circular dichroism spectroscopy.

Environmental DNA to track endangered Gobiobotia naktongensis: Assessment of distribution and habitat requirements.

Because of their noninvasive nature and high detection sensitivity, eDNA-based aquatic ecosystem surveys are useful for monitoring rare, elusive indicator species. Advancements in statistical techniques have expanded their use beyond simple population tracking to predict potential habitats based on the environmental conditions of sites detected eDNA. This study used species-specific molecular marker and targeted qPCR techniques to assess the distribution and habitat requirements of the endangered Gobiobotia naktongensis, a flagship fish species in Korean sandy river systems with increased public interest related to habitat restoration evaluations associated with dam construction.

Best Practices and Pitfalls in Developing Nanomaterial Delivery Tools for Plants.

Numerous reports of nanomaterial-assisted delivery of DNA, RNA, and protein to plants for biotechnology applications emerged over the past decade. While the field has experienced rapid growth, best practices for developing and validating nanomaterial delivery tools for plants have not yet been established. Best practices are well-established for clinical/animal cell delivery experiments, yet plants pose a distinct challenge requiring separate considerations due to their unique tissue structures and cellular morphology.

Polyneuropathy in Parkinson's Disease is Highly Prevalent and Not Related to Treatment.

Purpose: An increased prevalence of peripheral polyneuropathy (PN) in Parkinson's disease (PD) associated with greater functional impairment has previously been reported. A possible cause has been suggested as levodopa therapy. The aim of this real-world study was to assess the prevalence and the characteristics of PN in PD and to investigate the putative association between PN and oral levodopa.

Electromagnetic radiation and biophoton emission in neuronal communication and neurodegenerative diseases.

The intersection of electromagnetic radiation and neuronal communication, focusing on the potential role of biophoton emission in brain function and neurodegenerative diseases is an emerging research area. Traditionally, it is believed that neurons encode and communicate information via electrochemical impulses, generating electromagnetic fields detectable by EEG and MEG. Recent discoveries indicate that neurons may also emit biophotons, suggesting an additional communication channel alongside the regular synaptic interactions.

Multi-omics profiling reveals altered mitochondrial metabolism in adipose tissue from patients with metabolic dysfunction-associated steatohepatitis.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and its more severe form steatohepatitis (MASH) contribute to rising morbidity and mortality rates. The storage of fat in humans is closely associated with these diseases' progression. Thus, adipose tissue metabolic homeostasis could be key in both the onset and progression of MASH.

Drug repositioning in castration-resistant prostate cancer using systems biology and computational drug design techniques.

Background And Objective: Castration-resistant prostate cancer (CRPC) is caused by resistance to androgen deprivation treatment and leads to the death of patients and there is almost no chance of survival. Therefore, finding a cure to overcome CRPC is challenging and important, but discovering a new drug is very time-consuming and expensive. To overcome these problems, we used Drug repositioning (drug repurposing) strategy in this study.

LCRAnnotationsDB: a database of low complexity regions functional and structural annotations.

Low Complexity Regions (LCRs) are segments of proteins with a low diversity of amino acid composition. These regions play important roles in proteins. However, annotations describing these functions are dispersed across databases and scientific literature.

Molecular profiles of blood from numerous species that differ in sensitivity to acute inflammation.

Vertebrates differ over 100,000-fold in responses to pro-inflammatory agonists such as bacterial lipopolysaccharide (LPS), complicating use of animal models to study human sepsis or inflammatory disorders. We compared transcriptomes of resting and LPS-exposed blood from six LPS-sensitive species (rabbit, pig, sheep, cow, chimpanzee, human) and four LPS-resilient species (mice, rats, baboon, rhesus), as well as plasma proteomes and lipidomes. Unexpectedly, at baseline, sensitive species already had enhanced expression of LPS-responsive genes relative to resilient species.

Defining the role of Hmu and Hus systems in Porphyromonas gingivalis heme and iron homeostasis and virulence.

Iron and heme are essential nutrients for all branches of life. Pathogenic members of the Bacteroidota phylum, including Porphyromonas gingivalis, do not synthesize heme and rely on host hemoproteins for heme as a source of iron and protoporphyrin IX. P.

Comparative evaluation of feature reduction methods for drug response prediction.

Personalized medicine aims to tailor medical treatments to individual patients, and predicting drug responses from molecular profiles using machine learning is crucial for this goal. However, the high dimensionality of the molecular profiles compared to the limited number of samples presents significant challenges. Knowledge-based feature selection methods are particularly suitable for drug response prediction, as they leverage biological insights to reduce dimensionality and improve model interpretability.

Double step screening using endogenous marker improves relative gene targeting efficiency in Arabidopsis.

Gene targeting (GT) is a powerful tool for manipulating endogenous genomic sequences as intended. However, its efficiency is rather low, especially in seed plants. Numerous attempts have been made to improve the efficiency of GT via the CRISPR/Cas systems in plants, but these have not been sufficiently effective to be used routinely by everyone.

A conserved pilin from uncultured gut bacterial clade TANB77 enhances cancer immunotherapy.

Immune checkpoint blockade (ICB) has become a standard anti-cancer treatment, offering durable clinical benefits. However, the limited response rate of ICB necessitates biomarkers to predict and modulate the efficacy of the therapy. The gut microbiome's influence on ICB efficacy is of particular interest due to its modifiability through various interventions.

Development and implementation of a 3d-HDR brachytherapy program for cervical cancer in a sub-Saharan African centre.

Background: Cervical cancer is the second most common cancer among women in Nigeria where, the gap between need for, and access to, radiation therapy including brachytherapy is significant. This report documents the implementation of the first three-dimensional high-dose-rate (3D-HDR) brachytherapy service for cervical cancer in Nigeria.

Purpose: This report details the steps taken to implement the 3D-HDR brachytherapy program, the challenges faced, and the adaptive strategies employed to overcome them.