Mass Spectrometry Identification of Biomarkers in Extracellular Vesicles From Plasmodium vivax Liver Hypnozoite Infections.

Latent liver stages termed hypnozoites cause relapsing Plasmodium vivax malaria infection and represent a major obstacle in the goal of malaria elimination. Hypnozoites are clinically undetectable, and presently, there are no biomarkers of this persistent parasite reservoir in the human liver. Here, we have identified parasite and human proteins associated with extracellular vesicles (EVs) secreted from in vivo infections exclusively containing hypnozoites.

Causality in transcription and genome folding: Insights from X inactivation.

The spatial organization of genomes is becoming increasingly understood. In mammals, where it is most investigated, this organization ties in with transcription, so an important research objective is to understand whether gene activity is a cause or a consequence of genome folding in space. In this regard, the phenomena of X-chromosome inactivation and reactivation open a unique window of investigation because of the singularities of the inactive X chromosome.

Pancreas agenesis mutations disrupt a lead enhancer controlling a developmental enhancer cluster.

Sequence variants in cis-acting enhancers are important for polygenic disease, but their role in Mendelian disease is poorly understood. Redundancy between enhancers that regulate the same gene is thought to mitigate the pathogenic impact of enhancer mutations. Recent findings, however, have shown that loss-of-function mutations in a single enhancer near PTF1A cause pancreas agenesis and neonatal diabetes.

Developmental RNA-Seq transcriptomics of haploid germ cells and spermatozoa uncovers novel pathways associated with teleost spermiogenesis.

In non-mammalian vertebrates, the molecular mechanisms involved in the transformation of haploid germ cells (HGCs) into spermatozoa (spermiogenesis) are largely unknown. Here, we investigated this process in the marine teleost gilthead seabream (Sparus aurata) through the examination of the changes in the transcriptome between cell-sorted HGCs and ejaculated sperm (SPZ). Samples were collected under strict quality controls employing immunofluorescence microscopy as well as by determining the sperm motion kinematic parameters by computer-assisted sperm analysis.

Beacon v2 Reference Implementation: a toolkit to enable federated sharing of genomic and phenotypic data.

Summary: Beacon v2 is an API specification established by the Global Alliance for Genomics and Health initiative (GA4GH) that defines a standard for federated discovery of genomic and phenotypic data. Here, we present the Beacon v2 Reference Implementation (B2RI), a set of open-source software tools that allow lighting up a local Beacon instance 'out-of-the-box'. Along with the software, we have created detailed 'Read the Docs' documentation that includes information on deployment and installation.

The trophectoderm acts as a niche for the inner cell mass through C/EBPα-regulated IL-6 signaling.

IL-6 has been shown to be required for somatic cell reprogramming into induced pluripotent stem cells (iPSCs). However, how Il6 expression is regulated and whether it plays a role during embryo development remains unknown. Here, we describe that IL-6 is necessary for C/EBPα-enhanced reprogramming of B cells into iPSCs but not for B cell to macrophage transdifferentiation.

Wiki: Functional annotation of the minimal model organism .

The human pathogen is viable independently from host cells or organisms, despite its strongly reduced genome with only about 700 protein-coding genes. The investigation of can therefore help to obtain general insights concerning the basic requirements for cellular life. Accordingly, has become a model organism for systems biology in the past decade.

CHIKV infection reprograms codon optimality to favor viral RNA translation by altering the tRNA epitranscriptome.

Ample evidence indicates that codon usage bias regulates gene expression. How viruses, such as the emerging mosquito-borne Chikungunya virus (CHIKV), express their genomes at high levels despite an enrichment in rare codons remains a puzzling question. Using ribosome footprinting, we analyze translational changes that occur upon CHIKV infection.

Sorting and Export of Proteins at the Endoplasmic Reticulum.

Secretory proteins are transported from the endoplasmic reticulum (ER) to the Golgi complex in carriers that are formed by the concerted activities of cytoplasmic proteins in the coat protein complex II (COPII). COPII was first described in and its basic functions are largely conserved throughout eukaryotes. The discovery of the TANGO1 (transport and Golgi organization 1) family of proteins is revealing insights into how cells can adapt COPII proteins to reorganize the ER exit site for the export of the most abundant and bulky molecules, collagens.

Differences in clinical presentation, severity, and treatment of COVID-19 among individuals with Down syndrome from India and high-income countries: Data from the Trisomy 21 Research Society survey.

Background: People with Down syndrome (DS) are one of the highest risk groups for mortality associated with COVID-19, but outcomes may differ across countries due to different co-morbidity profiles, exposures, and societal practices, which could have implications for disease management. This study is designed to identify differences in clinical presentation, severity, and treatment of COVID-19 between India and several high-income countries (HICs).

Methods: We used data from an international survey to examine the differences in disease manifestation and management for COVID-19 patients with DS from India vs HIC.

Prepandemic Alzheimer Disease Biomarkers and Anxious-Depressive Symptoms During the COVID-19 Confinement in Cognitively Unimpaired Adults.

Background And Objectives: Increased anxious-depressive symptomatology is observed in the preclinical stage of Alzheimer disease (AD), which may accelerate disease progression. We investigated whether β-amyloid, cortical thickness in medial temporal lobe structures, neuroinflammation, and sociodemographic factors were associated with greater anxious-depressive symptoms during the COVID-19 confinement.

Methods: This retrospective observational study included cognitively unimpaired older adults from the Alzheimer's and Families cohort, the majority with a family history of sporadic AD.

The HDAC7-TET2 epigenetic axis is essential during early B lymphocyte development.

Correct B cell identity at each stage of cellular differentiation during B lymphocyte development is critically dependent on a tightly controlled epigenomic landscape. We previously identified HDAC7 as an essential regulator of early B cell development and its absence leads to a drastic block at the pro-B to pre-B cell transition. More recently, we demonstrated that HDAC7 loss in pro-B-ALL in infants associates with a worse prognosis.

Cohesin couples transcriptional bursting probabilities of inducible enhancers and promoters.

Innate immune responses rely on inducible gene expression programmes which, in contrast to steady-state transcription, are highly dependent on cohesin. Here we address transcriptional parameters underlying this cohesin-dependence by single-molecule RNA-FISH and single-cell RNA-sequencing. We show that inducible innate immune genes are regulated predominantly by an increase in the probability of active transcription, and that probabilities of enhancer and promoter transcription are coordinated.

Into the Dark: Exploring the Deep Ocean with Single-Virus Genomics.

Single-virus genomics (SVGs) has been successfully applied to ocean surface samples allowing the discovery of widespread dominant viruses overlooked for years by metagenomics, such as the uncultured virus vSAG 37-F6 infecting the ubiquitous spp. In SVGs, one uncultured virus at a time is sorted from the environmental sample, whole-genome amplified, and sequenced. Here, we have applied SVGs to deep-ocean samples (200-4000 m depth) from global Malaspina and MEDIMAX expeditions, demonstrating the feasibility of this method in deep-ocean samples.

Impact of COVID-19 Lockdown on the Nasopharyngeal Microbiota of Children and Adults Self-Confined at Home.

The increased incidence of COVID-19 cases and deaths in Spain in March 2020 led to the declaration by the Spanish government of a state of emergency imposing strict confinement measures on the population. The objective of this study was to characterize the nasopharyngeal microbiota of children and adults and its relation to SARS-CoV-2 infection and COVID-19 severity during the pandemic lockdown in Spain. This cross-sectional study included family households located in metropolitan Barcelona, Spain, with one adult with a previous confirmed COVID-19 episode and one or more exposed co-habiting child contacts.

Stochastic particle unbinding modulates growth dynamics and size of transcription factor condensates in living cells.

Liquid-liquid phase separation (LLPS) is emerging as a key physical principle for biological organization inside living cells, forming condensates that play important regulatory roles. Inside living nuclei, transcription factor (TF) condensates regulate transcriptional initiation and amplify the transcriptional output of expressed genes. However, the biophysical parameters controlling TF condensation are still poorly understood.

MED27, SLC6A7, and MPPE1 Variants in a Complex Neurodevelopmental Disorder with Severe Dystonia.

Background: Despite advances in next generation sequencing technologies, the identification of variants of uncertain significance (VUS) can often hinder definitive diagnosis in patients with complex neurodevelopmental disorders.

Objective: The objective of this study was to identify and characterize the underlying cause of disease in a family with two children with severe developmental delay associated with generalized dystonia and episodic status dystonicus, chorea, epilepsy, and cataracts.

Methods: Candidate genes identified by autozygosity mapping and whole-exome sequencing were characterized using cellular and vertebrate model systems.

Oocytes maintain ROS-free mitochondrial metabolism by suppressing complex I.

Oocytes form before birth and remain viable for several decades before fertilization. Although poor oocyte quality accounts for most female fertility problems, little is known about how oocytes maintain cellular fitness, or why their quality eventually declines with age. Reactive oxygen species (ROS) produced as by-products of mitochondrial activity are associated with lower rates of fertilization and embryo survival.

The emerging landscape of spatial profiling technologies.

Improved scale, multiplexing and resolution are establishing spatial nucleic acid and protein profiling methods as a major pillar for cellular atlas building of complex samples, from tissues to full organisms. Emerging methods yield omics measurements at resolutions covering the nano- to microscale, enabling the charting of cellular heterogeneity, complex tissue architectures and dynamic changes during development and disease. We present an overview of the developing landscape of in situ spatial genome, transcriptome and proteome technologies, exemplify their impact on cell biology and translational research, and discuss current challenges for their community-wide adoption.

Melanoma RBPome identification reveals PDIA6 as an unconventional RNA-binding protein involved in metastasis.

RNA-binding proteins (RBPs) have been relatively overlooked in cancer research despite their contribution to virtually every cancer hallmark. Here, we use RNA interactome capture (RIC) to characterize the melanoma RBPome and uncover novel RBPs involved in melanoma progression. Comparison of RIC profiles of a non-tumoral versus a metastatic cell line revealed prevalent changes in RNA-binding capacities that were not associated with changes in RBP levels.

Complement activation contributes to subretinal fibrosis through the induction of epithelial-to-mesenchymal transition (EMT) in retinal pigment epithelial cells.

Background: We previously reported higher plasma levels of complement fragments C3a and C5a in neovascular Age-related Macular Degeneration (nAMD) patients with macular fibrosis. This study aimed to understand whether complement activation contributes to the development of macular fibrosis and the underlying mechanisms involved.

Methods: Complement activation was blocked using a C5 neutralizing antibody (BB5.

Somatic Mutations Detected in Parkinson Disease Could Affect Genes With a Role in Synaptic and Neuronal Processes.

The role of somatic mutations in complex diseases, including neurodevelopmental and neurodegenerative disorders, is becoming increasingly clear. However, to date, no study has shown their relation to Parkinson disease's phenotype. To explore the relevance of embryonic somatic mutations in sporadic Parkinson disease, we performed whole-exome sequencing in blood and four brain regions of ten patients.