Biology subjects

Brahma, A.

Publications and source records attributed to Brahma, A..

3 recordsLinked to original sources

bioRxiv2026

A CTCF-LDHB axis converts nuclear lactate availability into an H3K18 acylation switch that directs alternative splicing in hypoxic breast cancer

Lactate accumulating in hypoxic tumours lactylates histones, coupling metabolic state to chromatin. Why it differs between tumours of comparable glycolytic rate has remained unresolved. Here we show that nuclear, rather than total intracellular, lactate availability determines histone H3K18 lactylation in breast cancer, and that CCCTC-binding factor (CTCF) and lactate dehydrogenase B (LDHB) jointly set it. CTCF sustains glycolytic gene expression under hypoxia and drives LDHB in triple-negative breast cancer (TNBC), whereas a CTCF-ER complex represses LDHB in non-TNBC. LDHB consumes lactate favouring H3K18 acetylation; where LDHB is low, CTCF-dependent MCT1 delivers lactate into the nucleus and sustains lactylation. At a CTCF site downstream of TACC3 exon 3, an invariant polymerase II pause couples kinetic and adaptor control of splicing, with the mark deciding the outcome: H3K18la recruits SMARCA4 and hnRNPA1 to skip the exon, generating an isoform that drives EMT, whereas H3K18ac recruits TRIM33 and SRSF10 to include it, generating one that confers stemness. Inhibiting LDHB restores exon skipping and suppresses tumour growth in vivo. Nuclear lactate availability therefore acts as a metabolic switch that converts hypoxic stress into subtype-specific splicing decisions and identifies LDHB as a tractable target in TNBC.

cancer biology↗

bioRxiv2021

Parameter exploration improves the accuracy of long-read genome assembly

Long-molecule sequencing is now routinely applied to generate high-quality reference genome assemblies. However, datasets differ in repeat composition, heterozygosity, read lengths and error profiles. The assembly parameters that provide the best results could thus differ across datasets. By integrating four complementary and biologically meaningful metrics, we show that simple fine-tuning of assembly parameters can substantially improve the quality of long-read genome assemblies. In particular, modifying estimates of sequencing error rates improves some metrics more than two-fold. We provide a flexible software, CompareGenomeQualities, that automates comparisons of assembly qualities for researchers wanting a straightforward mechanism for choosing among multiple assemblies.

bioinformatics↗

bioRxiv2018

Ontogeny of familiarity with foraging landscape and foraging abilities in the tropical social wasp Ropalidia marginata

Possessing spatial familiarity with their foraging landscape may enable animals to reduce foraging effort without compromising on foraging benefits. For animals inhabiting feature-rich landscapes, spatial familiarity can increase with increasing age/experience. To check whether this holds for individually foraging tropical social wasp Ropalidia marginata, we recorded the number and duration of all foraging trips, the identity of the materials brought to the nest (building material, water or food) and the directions of outbound and inbound flights (respective to their nests) of known-age foragers from three natural colonies, each for three consecutive days. The average trip duration and time spent daily in foraging increased rapidly until about first four weeks of their life, during which they rarely brought food to their nest, although many of them brought building material and water. Thereafter, their average as well as per day duration of foraging trip started decreasing gradually. Nevertheless, their foraging efficiency and success for food kept on increasing monotonically with age. These results suggest that older wasps were more efficient in foraging despite spending less time doing so. With increasing age, wasps developed individual preferences for the direction of their outbound flights, increased directionality of their inbound trips as well as the angular difference between their outbound and subsequent inbound flights, indicating development of spatial memory. We conclude that wasps acquire familiarity with their foraging landscape in their initial foraging phase and gradually develop robust memory for rewarding sites and routes to those sites, which enables them to increase their foraging capabilities.\n\nSUMMARY STATEMENTContrary to insects inhabiting less-featured landscapes, tropical social wasps invest weeks to get familiar with foraging landscapes during their early foraging lives. This eventually enables them to increase foraging gain with reduced effort.

animal behavior and cognition↗