Permeability of Dermatological Solutes through the Short Periodicity Phase of Human Stratum Corneum Lipid Bilayers.

Determining the permeability of drug-like solutes through the densely packed and heterogeneous stratum corneum lipid layer presents a significant challenge. In this study, we employed umbrella sampling with a periodic weighing function applied to the center of mass of the lipid bilayers. Precise umbrella sampling was conducted with an interframe distance of 0.

Phasevarions in biogroup control expression of multiple proteins.

biogroup is a human-adapted pathogen and the causative agent of Brazilian purpuric fever (BPF), an invasive disease with high mortality, that sporadically manifests in children previously suffering conjunctivitis. Phase variation is a rapid and reversible switching of gene expression found in many bacterial species, and typically associated with outer-membrane proteins. Phase variation of cytoplasmic DNA methyltransferases has been shown to play important roles in bacterial gene regulation and can act as epigenetic switches, regulating the expression of multiple genes as part of systems called phasevarions (phase-variable regulons).

Reassessing the putative molecular Target(s) of potent antitubercular 2-(Alkylsulfonyl)acetamides.

Simple alkyl-sulfonylacetamides have potent antitubercular activity and significantly decrease mycolic acid levels in mycobacteria. Although these compounds were originally designed to inhibit the ketoacyl synthase domain of fatty acid synthase, structure-activity relationships and biochemical evidence do not fully support fatty acid synthase as the target. In 2004, an enzyme family involved in the activation and transfer of fatty acids as acyl-adenylates was identified in mycobacteria, separate from the universal acetyl-CoA carrier mechanism.

Revolutionizing orofacial pain management: the promising potential of stem cell therapy.

Orofacial pain remains a significant health issue in the United States. Pain originating from the orofacial region can be composed of a complex array of unique target tissue that contributes to the varying success of pain management. Long-term use of analgesic drugs includes adverse effects such as physical dependence, gastrointestinal bleeding, and incomplete efficacy.

High-depth RNA-Seq data sets to investigate the differences in gene expression mediated by phasevarions in non-typeable .

Non-typeable (NTHi) is a major bacterial pathogen of the human airway. We report high-depth coverage RNA-Seq data from prototype NTHi strains 723 and R2866, encoding two of the most common phase-variable ModA alleles found in NTHi strains, ModA2 and ModA10, respectively.

A Guideline for Assessment and Characterization of Bacterial Biofilm Formation in the Presence of Inhibitory Compounds.

jejuni, a zoonotic foodborne pathogen, is the worldwide leading cause of acute human bacterial gastroenteritis. Biofilms are a significant reservoir for survival and transmission of this pathogen, contributing to its overall antimicrobial resistance. Natural compounds such as essential oils, phytochemicals, polyphenolic extracts, and D-amino acids have been shown to have the potential to control biofilms formed by bacteria, including spp.

A CAF01-adjuvanted whole asexual blood-stage liposomal malaria vaccine induces a CD4 T-cell-dependent strain-transcending protective immunity in rodent models.

Malaria is a devastating disease that has claimed many lives, especially children <5 years of age in Sub-Saharan Africa, as documented in World Malaria Reports by WHO. Even though vector control and chemoprevention tools have helped with elimination efforts in some, if not all, endemic areas, these efforts have been hampered by serious issues (including drug and insecticide resistance and disruption to social cohesion caused by the COVID-19 pandemic). Development of an effective malaria vaccine is the alternative preventative tool in the fight against malaria.

Multiple sequence alignment-based RNA language model and its application to structural inference.

Compared with proteins, DNA and RNA are more difficult languages to interpret because four-letter coded DNA/RNA sequences have less information content than 20-letter coded protein sequences. While BERT (Bidirectional Encoder Representations from Transformers)-like language models have been developed for RNA, they are ineffective at capturing the evolutionary information from homologous sequences because unlike proteins, RNA sequences are less conserved. Here, we have developed an unsupervised multiple sequence alignment-based RNA language model (RNA-MSM) by utilizing homologous sequences from an automatic pipeline, RNAcmap, as it can provide significantly more homologous sequences than manually annotated Rfam.

HIV-1 diverts cortical actin for particle assembly and release.

Enveloped viruses assemble and bud from the host cell membranes. Any role of cortical actin in these processes have often been a source of debate. Here, we assessed if cortical actin was involved in HIV-1 assembly in infected CD4 T lymphocytes.

Protocol to quantify glycan-mediated binding between viral particles and human peripheral blood mononuclear cells using nanoluciferase.

Prior to receptor engagement, a specific, non-electrostatic glycan-glycan interaction between viral particles and host cells may lengthen the dwell time of the virus at the cellular surface, thereby facilitating subsequent virus entry. Here, we present a protocol for quantifying the level of glycan-mediated binding between virus or virus-like-particles and human peripheral blood mononuclear cells (PBMCs) using a nanoluciferase reporter system. We describe steps for virus production, isolation of PBMCs, and performing a nanoluciferase binding assay.

Protocol to visualize glycan-mediated binding between virus and human blood mononuclear cells using thin-section transmission electron microscopy.

Glycan-glycan interactions between viral particles and host cells may lengthen the dwell time of the virus on the cell surface to facilitate cellular receptor engagement. Here, we present a protocol for visualizing glycan-mediated binding between virus or virus-like-particles (VLPs) and human peripheral blood mononuclear cells using transmission electron microscopy (TEM). We describe steps for virus and VLP production, isolation of human peripheral blood mononuclear cells, and sample preparation.

Development of a model for granule-bound starch synthase I activity using free-energy calculations.

Starch is a branched polymer of glucose with two components, both of which have (1 → 4)-α linear links and (1 → 6)-α branch points: amylopectin, of high molecular weight with many short branches, and amylose, of lower molecular weight and only a few long-chain branches. Granule-bound starch synthase I (GBSSI) is one of the main enzymes controlling amylose synthesis and chain-length distribution. As production of different GBSSI mutants is time-consuming and laborious, molecular dynamics (MD) simulations are used here to predict the binding of different GBSSI mutants to a representative amylose fragment.

Spontaneous metastasis xenograft models link CD44 isoform 4 to angiogenesis, hypoxia, EMT and mitochondria-related pathways in colorectal cancer.

Hematogenous metastasis limits the survival of colorectal cancer (CRC) patients. Here, we illuminated the roles of CD44 isoforms in this process. Isoforms 3 and 4 were predominantly expressed in CRC patients.

Roles of long noncoding RNA in triple-negative breast cancer.

Introduction: Long noncoding RNAs (lncRNAs) play crucial roles in regulating various hallmarks in cancers. Triple-negative (Estrogen receptor, ER; Human epidermal growth factor receptor 2, HER2; Progesterone receptor, PR) breast cancer (TNBC) is the most aggressive form of breast cancers with a poor prognosis and no available molecular targeted therapy.

Methods: We reviewed the current literature on the roles of lncRNAs in the pathogenesis, therapy resistance, and prognosis of patients with TBNC.

Studying the interaction of glycans with intact virions and virus-like particles by ligand-observed NMR spectroscopy.

Virus-glycan interactions play a crucial role in the infection process of many viruses. NMR spectroscopy has emerged as a powerful tool for studying these interactions at the molecular level. In this article, we review several published papers and reports that have highlighted the application of NMR spectroscopy in understanding the complex questions of how viruses engage with and bind to receptor glycans.

Malaria Vaccines: Progress to Date.

Malaria is a mosquito-borne disease caused by protozoan parasites of the genus Plasmodium. Despite significant declines in malaria-attributable morbidity and mortality over the last two decades, it remains a major public health burden in many countries. This underscores the critical need for improved strategies to prevent, treat and control malaria if we are to ultimately progress towards the eradication of this disease.

Hiding in plain sight: an epitope-based strategy for a subunit malaria vaccine.

Recent data suggest that approaches to developing a subunit blood-stage malaria vaccine may be misdirected. While antigenic polymorphism is recognized as a challenge, efforts to counter this have primarily involved enhancing the quantity and quality of antibody with potent adjuvants, identifying conserved target proteins, or combining multiple antigens to broaden the immune response. However, paradoxically, evidence has emerged that narrowing, rather than broadening, the immune response may be required to obtain an immune response protective against multiple Plasmodium strains.

Exploring the landscape of Babesia bovis vaccines: progress, challenges, and opportunities.

Bovine babesiosis, caused by different Babesia spp. such as B. bovis, B.

Probing Disaccharide Binding to Triplatin as Models for Tumor Cell Heparan Sulfate (GAG) Interactions.

In this study, we have used [H, N] NMR spectroscopy to investigate the interactions of the trinuclear platinum anticancer drug triplatin () (1,0,1 or BBR3464) with site-specific sulfated and carboxylated disaccharides. Specifically, the disaccharides GlcNS(6)-GlcA () and GlcNS(6)-IdoA(2S) () are useful models of longer-chain glycosaminoglycans (GAGs) such as heparan sulfate (HS). For both the reactions of N with and , equilibrium conditions were achieved more slowly (65 h) compared to the reaction with the monosaccharide GlcNS(6S) (9 h).

Thymus-derived hormonal and cellular control of cancer.

The thymus gland is a central lymphoid organ in which developing T cell precursors, known as thymocytes, undergo differentiation into distinct type of mature T cells, ultimately migrating to the periphery where they exert specialized effector functions and orchestrate the immune responses against tumor cells, pathogens and self-antigens. The mechanisms supporting intrathymic T cell differentiation are pleiotropically regulated by thymic peptide hormones and cytokines produced by stromal cells in the thymic microenvironment and developing thymocytes. Interestingly, in the same way as T cells, thymic hormones (herein exemplified by thymosin, thymulin and thymopoietin), can circulate to impact immune cells and other cellular components in the periphery.

The potential impact of a vaccine on Neisseria gonorrhoeae prevalence among heterosexuals living in a high prevalence setting.

Background: Treatment of Neisseria gonorrhoeae is under threat with the emergence and spread of antimicrobial resistance. Thus, there is a growing interest in the development of a gonorrhoea vaccine. We used mathematical modelling to assess the impact of a hypothetical vaccine in controlling gonorrhoea among heterosexuals living in a setting of relatively high N.