: a -based indexing algorithm for kilohertz serial crystallography.

Serial crystallography (SX) involves combining observations from a very large number of diffraction patterns coming from crystals in random orientations. To compile a complete data set, these patterns must be indexed ( their orientation determined), integrated and merged. Introduced here is (-powered robust optimization) , a robust and adaptable indexing algorithm developed using the framework.

Signatures of wave erosion in Titan's coasts.

The shorelines of Titan's hydrocarbon seas trace flooded erosional landforms such as river valleys; however, it is unclear whether coastal erosion has subsequently altered these shorelines. Spacecraft observations and theoretical models suggest that wind may cause waves to form on Titan's seas, potentially driving coastal erosion, but the observational evidence of waves is indirect, and the processes affecting shoreline evolution on Titan remain unknown. No widely accepted framework exists for using shoreline morphology to quantitatively discern coastal erosion mechanisms, even on Earth, where the dominant mechanisms are known.

A Novel Peptide Driving Neurodegeneration Appears Exclusively Linked to the α7 Nicotinic Acetylcholine Receptor.

T14, a 14mer peptide, is significantly increased in the pre-symptomatic Alzheimer's disease brain, and growing evidence implies its pivotal role in neurodegeneration. Here, we explore the subsequent intracellular events following binding of T14 to its target α7 nicotinic acetylcholine receptor (nAChR). Specifically, we test how various experimental manipulations of PC12 cells impact T14-induced functional outcomes.

A cyclin D1 intrinsically disordered domain accesses modified histone motifs to govern gene transcription.

The essential G-cyclin, CCND1, is frequently overexpressed in cancer, contributing to tumorigenesis by driving cell-cycle progression. D-type cyclins are rate-limiting regulators of G-S progression in mammalian cells via their ability to bind and activate CDK4 and CDK6. In addition, cyclin D1 conveys kinase-independent transcriptional functions of cyclin D1.

The Role and Therapeutic Targeting of CCR5 in Breast Cancer.

The G-protein-coupled receptor C-C chemokine receptor 5 (CCR5) functions as a co-receptor for the entry of HIV into immune cells. CCR5 binds promiscuously to a diverse array of ligands initiating cell signaling that includes guided migration. Although well known to be expressed on immune cells, recent studies have shown the induction of CCR5 on the surface of breast cancer epithelial cells.

Reconstructing river flows remotely on Earth, Titan, and Mars.

Alluvial rivers are conveyor belts of fluid and sediment that provide a record of upstream climate and erosion on Earth, Titan, and Mars. However, many of Earth's rivers remain unsurveyed, Titan's rivers are not well resolved by current spacecraft data, and Mars' rivers are no longer active, hindering reconstructions of planetary surface conditions. To overcome these problems, we use dimensionless hydraulic geometry relations-scaling laws that relate river channel dimensions to flow and sediment transport rates-to calculate in-channel conditions using only remote sensing measurements of channel width and slope.

The genome displays differential chromatin accessibility.

Whilst the regulation of chromatin accessibility and its effect on gene expression have been well studied in eukaryotic species, the role of chromatin dynamics and 3D organisation in genome reduced bacteria remains poorly understood [1,2]. In this study we profiled the accessibility of the genome, these data were collected fortuitously as part of an experiment where ATAC-Seq was conducted on contaminated mammalian cells. We found a differential and highly reproducible chromatin accessibility landscape, with regions of increased accessibility corresponding to genes important for the bacteria's life cycle and infectivity.

A Novel Bioactive Peptide, T14, Selectively Activates mTORC1 Signalling: Therapeutic Implications for Neurodegeneration and Other Rapamycin-Sensitive Applications.

T14 modulates calcium influx via the α-7 nicotinic acetylcholine receptor to regulate cell growth. Inappropriate triggering of this process has been implicated in Alzheimer's disease (AD) and cancer, whereas T14 blockade has proven therapeutic potential in in vitro, ex vivo and in vivo models of these pathologies. Mammalian target of rapamycin complex 1 (mTORC1) is critical for growth, however its hyperactivation is implicated in AD and cancer.

Preparing to strike: Acute events in signaling by the serpentine receptor for thromboxane A.

Over the last two decades, awareness of the (patho)physiological roles of thromboxane A signaling has been greatly extended. From humble beginnings as a short-lived stimulus that activates platelets and causes vasoconstriction to a dichotomous receptor system involving multiple endogenous ligands capable of modifying tissue homeostasis and disease generation in almost every tissue of the body. Thromboxane A receptor (TP) signal transduction is associated with the pathogenesis of cancer, atherosclerosis, heart disease, asthma, and host response to parasitic infection amongst others.

Transcriptomic Comparison of Human Peripartum and Dilated Cardiomyopathy Identifies Differences in Key Disease Pathways.

Peripartum cardiomyopathy (PPCM) is a rare form of acute onset heart failure that presents in otherwise healthy pregnant women around the time of delivery. While most of these women respond to early intervention, about 20% progress to end-stage heart failure that symptomatically resembles dilated cardiomyopathy (DCM). In this study, we examined two independent RNAseq datasets from the left ventricle of end-stage PPCM patients and compared gene expression profiles to female DCM and non-failing donors.

Expression of the wheat multipathogen resistance hexose transporter Lr67res is associated with anion fluxes.

Many disease resistance genes in wheat (Triticum aestivum L.) confer strong resistance to specific pathogen races or strains, and only a small number of genes confer multipathogen resistance. The Leaf rust resistance 67 (Lr67) gene fits into the latter category as it confers partial resistance to multiple biotrophic fungal pathogens in wheat and encodes a Sugar Transport Protein 13 (STP13) family hexose-proton symporter variant.

DUSP15 expression is reduced in the hippocampus of Myrf knock-out mice but attention and object recognition memory remain intact.

The atypical protein tyrosine phosphatase enzyme, dual-specificity phosphate 15 (DUSP15) is thought to be activated by myelin regulatory factor (MyRF) and to have a role in oligodendrocyte differentiation. Here, we assess whether Dusp15 is reduced in the hippocampus of mice with conditional knock-out of Myrf in oligodendrocyte precursor cells. Using quantitative polymerase chain reaction (qPCR) we found that Dusp15 expression was indeed lower in these mice.

The DACH1 gene is frequently deleted in prostate cancer, restrains prostatic intraepithelial neoplasia, decreases DNA damage repair, and predicts therapy responses.

Prostate cancer (PCa), the second leading cause of death in American men, includes distinct genetic subtypes with distinct therapeutic vulnerabilities. The gene encodes a winged helix/Forkhead DNA-binding protein that competes for binding to FOXM1 sites. Herein, gene deletion within the 13q21.

Retinoic Acid Signalling in the Pineal Gland Is Conserved across Mammalian Species and Its Transcriptional Activity Is Inhibited by Melatonin.

The pineal gland is integral to the circadian timing system due to its role in nightly melatonin production. Retinoic acid (RA) is a potent regulator of gene transcription and has previously been found to exhibit diurnal changes in synthesis and signalling in the rat pineal gland. This study investigated the potential for the interaction of these two systems.

Pilot study to evaluate hypercoagulation and inflammation using rotational thromboelastometry and calprotectin in COVID-19 patients.

Introduction: Abnormal coagulation and inflammation are hallmarks of SARs-COV-19. Stratifying affected patients on admission to hospital may help identify those who at are risk of developing severe disease early on. Rotational Thromboelastometry (ROTEM) is a point of care test that can be used to measure abnormal coagulation and calprotectin is a measure of inflammation.

Sleep and circadian rhythm disruption alters the lung transcriptome to predispose to viral infection.

Sleep and circadian rhythm disruption (SCRD), as encountered during shift work, increases the risk of respiratory viral infection including SARS-CoV-2. However, the mechanism(s) underpinning higher rates of respiratory viral infection following SCRD remain poorly characterized. To address this, we investigated the effects of acute sleep deprivation on the mouse lung transcriptome.

Acetylation of nuclear receptors in health and disease: an update.

Lysine acetylation is a common reversible post-translational modification of proteins that plays a key role in regulating gene expression. Nuclear receptors (NRs) include ligand-inducible transcription factors and orphan receptors for which the ligand is undetermined, which together regulate the expression of genes involved in development, metabolism, homeostasis, reproduction and human diseases including cancer. Since the original finding that the ERα, AR and HNF4 are acetylated, we now understand that the vast majority of NRs are acetylated and that this modification has profound effects on NR function.

The Renaissance of CDK Inhibitors in Breast Cancer Therapy: An Update on Clinical Trials and Therapy Resistance.

Cyclin-dependent kinases (CDKs) govern cell-cycle checkpoint transitions necessary for cancer cell proliferation. Recent developments have illustrated nuanced important differences between mono CDK inhibitor (CDKI) treatment and the combination therapies of breast cancers. The CDKIs that are currently FDA-approved for breast cancer therapy are oral agents that selectively inhibit CDK4 and CDK6, include palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (Verzenio).

The impact of socio-economic deprivation on recovery following robotic assisted radical cystectomy.

Background: Despite enhanced recovery programmes, length of stay is variable following robotic assisted radical cystectomy (RARC). The aim of this study was to assess the impact socioeconomic deprivation on recovery following RARC.

Methods: The prospectively maintained RARC databases at two tertiary referral hospitals were reviewed from 2015 to 2017.