The CABANA model 2017-2022: research and training synergy to facilitate bioinformatics applications in Latin America.

The CABANA project (Capacity Building for Bioinformatics in Latin America) was funded by the UK's Global Challenges Research Fund in 2017 with the aim to strengthen the bioinformatics capacity and extend its applications in Latin America focused on three challenge areas - communicable diseases, sustainable food production and protection of biodiversity. For 5 years, the project executed activities including data analysis workshops, train-the-trainer workshops, secondments, eLearning development, knowledge exchange meetings, and research projects in 10 countries. The project was successful in accomplishing all its goals with a major impact on the region.

TUDCA modulates drug bioavailability to regulate resistance to acute ER stress in .

Cells counter accumulation of misfolded secretory proteins in the endoplasmic reticulum (ER) through activation of the Unfolded Protein Response (UPR). Small molecules termed chemical chaperones can promote protein folding to alleviate ER stress. The bile acid tauroursodeoxycholic acid (TUDCA), has been described as a chemical chaperone.

Molecular basis of neurodegeneration in a mouse model of -related disease.

Pathogenic variants in subunits of RNA polymerase (Pol) III cause a spectrum of -related neurodegenerative diseases including 4H leukodystrophy. Disease onset occurs from infancy to early adulthood and is associated with a variable range and severity of neurological and non-neurological features. The molecular basis of -related disease pathogenesis is unknown.

Yeast-based assay to identify inhibitors of the malaria parasite sodium phosphate uptake transporter as potential novel antimalarial drugs.

Malaria affects almost 250 million people annually and continues to be a significant threat to global public health. Infection with protozoan parasites from the genus Plasmodium causes malaria. The primary treatment for malaria is artemisinin-based combination therapies (ACTs).

Molecular basis of neurodegeneration in a mouse model of -related disease.

Pathogenic variants in subunits of RNA polymerase (Pol) III cause a spectrum of -related neurodegenerative diseases including 4H leukodystrophy. Disease onset occurs from infancy to early adulthood and is associated with a variable range and severity of neurological and non-neurological features. The molecular basis of -related disease pathogenesis is unknown.

Contrasting effects of whole-body and hepatocyte-specific deletion of the RNA polymerase III repressor in the mouse.

MAF1 is a nutrient-sensitive, TORC1-regulated repressor of RNA polymerase III (Pol III). MAF1 downregulation leads to increased lipogenesis in , , and mice. However, mice are lean as increased lipogenesis is counterbalanced by futile pre-tRNA synthesis and degradation, resulting in increased energy expenditure.

MAF1, a repressor of RNA polymerase III-dependent transcription, regulates bone mass.

MAF1, a key repressor of RNA polymerase (pol) III-mediated transcription, has been shown to promote mesoderm formation in vitro. Here, we show that MAF1 plays a critical role in regulating osteoblast differentiation and bone mass. Global deletion of ( mice) produced a high bone mass phenotype.

Microbiome Profiling of Enterotoxigenic Escherichia coli (ETEC) Carriers Highlights Signature Differences between Symptomatic and Asymptomatic Individuals.

Enterotoxigenic Escherichia coli (ETEC) is an important cause of diarrhea in children in low- and middle-income countries (LMICs). However, large-scale pathogen burden studies in children have identified ETEC in the guts of both symptomatic patients and controls. The factors that influence this balance are poorly understood, but it is postulated that the gut microbiome may play a role in either resistance or progression to disease.

Defective myelination in an RNA polymerase III mutant leukodystrophic mouse.

RNA polymerase (Pol) III synthesizes abundant short noncoding RNAs that have essential functions in protein synthesis, secretion, and other processes. Despite the ubiquitous functions of these RNAs, mutations in Pol III subunits cause Pol III-related leukodystrophy, an early-onset neurodegenerative disease. The basis of this neural sensitivity and the mechanisms of disease pathogenesis are unknown.

Alteration of the Premature tRNA Landscape by Gammaherpesvirus Infection.

Transfer RNAs (tRNAs) are transcribed by RNA polymerase III (RNAPIII) and play a central role in decoding our genome, yet their expression and noncanonical function remain understudied. Many DNA tumor viruses enhance the activity of RNAPIII, yet whether infection alters tRNA expression is largely unknown. Here, we present the first genome-wide analysis of how viral infection alters the tRNAome.

Functional characterization of Polr3a hypomyelinating leukodystrophy mutations in the S. cerevisiae homolog, RPC160.

Mutations in RNA polymerase III (Pol III) cause hypomeylinating leukodystrophy (HLD) and neurodegeneration in humans. POLR3A and POLR3B, the two largest Pol III subunits, together form the catalytic center and carry the majority of disease alleles. Disease-causing mutations include invariant and highly conserved residues that are predicted to negatively affect Pol III activity and decrease transcriptional output.

MAF1 is a chronic repressor of RNA polymerase III transcription in the mouse.

Maf1 mice are lean, obesity-resistant and metabolically inefficient. Their increased energy expenditure is thought to be driven by a futile RNA cycle that reprograms metabolism to meet an increased demand for nucleotides stemming from the deregulation of RNA polymerase (pol) III transcription. Metabolic changes consistent with this model have been reported in both fasted and refed mice, however the impact of the fasting-refeeding-cycle on pol III function has not been examined.

Outcome-based education: evaluation, implementation and faculty development.

This article was migrated. The article was marked as recommended. Developments in Outcome-based education (OBE) and innovative shifts in its pedagogical approaches have reshaped the learning environment of curricula at medical schools.

Conserved Herpesvirus Kinase ORF36 Activates B2 Retrotransposons during Murine Gammaherpesvirus Infection.

Short interspersed nuclear elements (SINEs) are RNA polymerase III (RNAPIII)-transcribed, retrotransposable noncoding RNA (ncRNA) elements ubiquitously spread throughout mammalian genomes. While normally silenced in healthy somatic tissue, SINEs can be induced during infection with DNA viruses, including the model murine gammaherpesvirus 68 (MHV68). Here, we explored the mechanisms underlying MHV68 activation of SINE ncRNAs.

Participatory approaches, local stakeholders and cultural relevance facilitate an impactful community-based project in Uganda.

Sanitation is a major global challenge that is often addressed at national and international levels, while community opinions and beliefs are neglected. To promote water, sanitation and hygiene (WASH) we organized a cross-cultural knowledge exchange workshop to assess participatory methods for engaging local stakeholders. The workshop included 22 participants from all sectors of society.

Structural basis for RNA polymerase III transcription repression by Maf1.

Maf1 is a conserved inhibitor of RNA polymerase III (Pol III) that influences phenotypes ranging from metabolic efficiency to lifespan. Here, we present a 3.3-Å-resolution cryo-EM structure of yeast Maf1 bound to Pol III, establishing that Maf1 sequesters Pol III elements involved in transcription initiation and binds the mobile C34 winged helix 2 domain, sealing off the active site.

The leukodystrophy mutation Polr3b R103H causes homozygote mouse embryonic lethality and impairs RNA polymerase III biogenesis.

Recessive mutations in the ubiquitously expressed POLR3A and POLR3B genes are the most common cause of POLR3-related hypomyelinating leukodystrophy (POLR3-HLD), a rare childhood-onset disorder characterized by deficient cerebral myelin formation and cerebellar atrophy. POLR3A and POLR3B encode the two catalytic subunits of RNA Polymerase III (Pol III), which synthesizes numerous small non-coding RNAs. We recently reported that mice homozygous for the Polr3a mutation c.

Surface Pond Energy Absorption Across Four Himalayan Glaciers Accounts for 1/8 of Total Catchment Ice Loss.

Glaciers in High Mountain Asia, many of which exhibit surface debris, contain the largest volume of ice outside of the polar regions. Many contain supraglacial pond networks that enhance melt rates locally, but no large-scale assessment of their impact on melt rates exists. Here we use surface energy balance modeling forced using locally measured meteorological data and monthly satellite-derived pond distributions to estimate the total melt enhancement for the four main glaciers within the 400-km Langtang catchment, Nepal, for a 6-month period in 2014.

Direct measurements of ice-shelf flexure caused by surface meltwater ponding and drainage.

Global sea-level rise is caused, in part, by more rapid ice discharge from Antarctica, following the removal of the restraining forces of floating ice-shelves after their break-up. A trigger of ice-shelf break-up is thought to be stress variations associated with surface meltwater ponding and drainage, causing flexure and fracture. But until now, there have been no direct measurements of these processes.

Metabolic programming a lean phenotype by deregulation of RNA polymerase III.

As a master negative regulator of RNA polymerase (Pol) III, Maf1 modulates transcription in response to nutrients and stress to balance the production of highly abundant tRNAs, 5S rRNA, and other small noncoding RNAs with cell growth and maintenance. This regulation of Pol III transcription is important for energetic economy as mice lacking are lean and resist weight gain on normal and high fat diets. The lean phenotype of knockout (KO) mice is attributed in part to metabolic inefficiencies which increase the demand for cellular energy and elevate catabolic processes, including autophagy/lipophagy and lipolysis.

Enhanced Isotopic Ratio Outlier Analysis (IROA) Peak Detection and Identification with Ultra-High Resolution GC-Orbitrap/MS: Potential Application for Investigation of Model Organism Metabolomes.

Identifying non-annotated peaks may have a significant impact on the understanding of biological systems. In silico methodologies have focused on ESI LC/MS/MS for identifying non-annotated MS peaks. In this study, we employed in silico methodology to develop an Isotopic Ratio Outlier Analysis (IROA) workflow using enhanced mass spectrometric data acquired with the ultra-high resolution GC-Orbitrap/MS to determine the identity of non-annotated metabolites.

Signaling to and from the RNA Polymerase III Transcription and Processing Machinery.

RNA polymerase (Pol) III has a specialized role in transcribing the most abundant RNAs in eukaryotic cells, transfer RNAs (tRNAs), along with other ubiquitous small noncoding RNAs, many of which have functions related to the ribosome and protein synthesis. The high energetic cost of producing these RNAs and their central role in protein synthesis underlie the robust regulation of Pol III transcription in response to nutrients and stress by growth regulatory pathways. Downstream of Pol III, signaling impacts posttranscriptional processes affecting tRNA function in translation and tRNA cleavage into smaller fragments that are increasingly attributed with novel cellular activities.

Maf1 phenotypes and cell physiology.

As a master regulator of transcription by RNA polymerase (Pol) III, Maf1 represses the synthesis of highly abundant non-coding RNAs as anabolic signals dissipate, as the quality or quantity of nutrients decreases, and under a wide range of cellular and environmental stress conditions. Thus, Maf1 responds to changes in cell physiology to conserve metabolic energy and to help maintain appropriate levels of tRNAs and other essential non-coding RNAs. Studies in different model organisms and cell-based systems show that perturbations of Maf1 can also impact cell physiology and metabolism.

Impact of a Social Media Group Page on Undergraduate Medical Physiology Learning.

Objective: To investigate the impact of associating classroom learning of medical physiology with a Facebook group page in an all-women medical college of a conservative small city in Pakistan.

Study Design: Qualitative interpretivist study using semi-structured interviews.

Place And Duration Of Study: Women Medical College Abbottabad, Pakistan, from March to December 2014.