Biology subjects

Chowdhury, A.

Publications and source records attributed to Chowdhury, A..

At least 19 recordsLinked to original sources

bioRxiv2026

Endothelial protein C receptor is an entry receptor for Langya and related parahenipaviruses

Langya virus is a zoonotic parahenipavirus with pandemic potential that causes acute febrile illness in people. We identified endothelial protein C receptor (EPCR) as an entry receptor for Langya, Wenzhou, and Mojiang parahenipaviruses. A 3.1 [A] cryo-electron microscopy structure reveals that Langya attachment glycoprotein engages EPCR through a site distinct from that of the ephrin binding site of Nipah G. This binding mode resembles those of protein C and a malarial adhesin, demonstrating convergent evolution. Interface substitutions abolish entry, whereas natural variation explains differential human EPCR use and predicts receptor compatibility across 26 animal species. These findings establish EPCR as a receptor for the Langya clade and provide a structural framework for understanding cross-species transmission and human infection potential.

microbiology↗

bioRxiv2026

Photoplethysmography-based glucose estimation with feature selection

Diabetes mellitus is a major global health challenge, and routine blood glucose monitoring still depends on invasive fingerstick sampling. This study examines non-invasive glucose estimation from photoplethysmography (PPG) using a signal quality pipeline and a multi-criteria feature selection framework. PPG recordings from 51 subjects were collected with a custom low-cost system, and 32 passed quality control. Fourteen morphological and autonomic features were extracted and ranked using Pearson and Spearman correlation, partial correlation with confounder adjustment, mutual information and a composite score. The same processing was then applied to a public four-wavelength PPG dataset of 133 subjects with complete metadata, comparing three machine learning input configurations on a held-out test set of 27 subjects. Adding greedy forward-selected PPG features to subject metadata gave a coefficient of determination of 0.410 with Random Forest at 730 nm, compared with 0.355 for metadata alone. Gains at the other wavelengths were at most 0.024, and no significance test was performed. Agreement with the ISO 15197:2013 criterion ranged from 74% to 85%, below the 95% the standard requires. A compact set of amplitude-variability and spectral features may add modest information to demographic predictors, but this needs confirmation in larger cohorts, with longer recordings and independent validation.

bioengineering↗

bioRxiv2026

Parabens Impair Mouse Antral Follicle Growth and Alter Ovarian Hormone and Gene Expression Similar to Phthalates

Benzyl paraben (BzP) and butyl paraben (BuP) are used as preservatives and antimicrobial agents in cosmetics, pharmaceuticals, and foods. BzP and BuP have been detected in urine, placental tissue, and ovarian follicular fluid and are understudied with regards to their endocrine activity, raising concerns on their impact to the reproductive system. We tested the hypothesis that BzP and BuP are toxic to the ovary and behave similarly to other structurally similar endocrine disrupting chemicals, such as phthalates and terephthalates, by altering hormone levels and impacting cell growth and gene expression in vitro. Untreated mouse antral follicles were exposed to vehicle, 0.1, 1, 10, or 100 g/mL BzP, BuP, or the BuP analog monobutyl terephthalate (MBuTP) for 96 hours. The highest dose of BzP and BuP were cytotoxic to follicles, suggesting that medium chain length hydroxybenzoates are more cytotoxic to the ovary than corresponding terephthalic acids. BzP significantly increased levels of estradiol and testosterone compared to control. BuP decreased follicle growth and disrupted expression of cell cycle regulators, similar to phthalates. The peroxisome proliferator-activated receptor gamma (PPARg)-transcriptionally controlled gene Fabp4 was significantly upregulated by both BzP and BuP, whereas MBuTP upregulated all four PPAR target genes and decreased follicle growth. Overall, BzP, BuP, and MBuTP disrupted hormone levels, follicle growth, and cell cycle progression, suggesting similarities in toxicity to phthalates and potential endocrine disruption. Further study should be done on the reproductive toxicity and endocrine disrupting effects of chemicals similar in structure to phthalates to reduce exposure to endocrine disruptors and inform design of safer replacements.

pharmacology and toxicology↗

bioRxiv2026

Action Sequences Structure Human Memory Reactivation

Episodic memory formation is not a passive process but emerges from sequences of actions through which we engage with our environment. Yet, how these action sequences interact with the neural dynamics underlying human memory formation and retrieval remains poorly understood. Here, we investigated whether coordinated gaze shifts, one of the major exploratory actions in humans, structure the reactivation of memories. Participants learned multiple action sequences by pairing images with distinct real-world gaze shifts while we simultaneously recorded EEG and motion tracking data. During subsequent retrieval, the recalled gaze sequences acted as a direct behavioral readout of memory performance. Representational similarity analyses revealed that the reactivation of image memories was precisely timed to recalled gaze shifts within each sequence. Crucially, only correctly executed, but not incorrectly executed gaze shifts elicited significant reactivation of the corresponding image class, directly linking neural reactivation to retrieval success. These findings suggest that exploratory actions are fundamental components of episodic memories, not incidental accompaniments: self-initiated movements can serve as temporal anchors of memory reactivation that predict retrieval success. By investigating memory through natural behavior, our work provides an ecologically grounded perspective on human cognition, revealing that species-typical actions such as gaze shifts are essential to, rather than obstacles for, understanding memorys neural basis.

neuroscience↗

bioRxiv2026

Ferulic acid eicosyl ester enhances cognitive flexibility and modulates arousal-related neural circuits in mice

Cognitive deficits are a major contributor to disability in numerous neuropsychiatric and neurodegenerative disorders, yet effective pharmacological treatments remain limited. Ferulic acid eicosyl ester (FAE-20), a natural constituent of the plant Rhodiola rosea, has previously been identified as an enhancer of simple forms of Pavlovian conditioning in flies, bees, and mice. Here, we investigated whether FAE-20 has further potential to enhance cognitive flexibility, working memory, or spatial learning in mice, and explored potential neurobiological mechanisms underlying such enhancement. Cognitive flexibility was assessed using the attentional set-shifting task (ASST). Subchronic FAE-20 treatment significantly improved ASST performance in both male and female young adult mice, indicating enhanced cognitive flexibility. In contrast, no effects were observed on spatial working memory, assessed by spontaneous alternations in the Y-maze, or on spatial learning in the Barnes maze in either young or aged mice. Notably, FAE-20 enabled spatial learning in the Barnes maze in a subgroup of aged mice that failed to learn the task under vehicle treatment. Histological analyses using c-Fos immunohistochemistry as a marker of neural activity and doublecortin expression and spine density as markers of hippocampal plasticity revealed sex-specific effects on components of the ascending arousal system. FAE-20 increased the activation of orexinergic neurons in the lateral hypothalamus of male mice, whereas it reduced the activity of cholinergic neurons in the laterodorsal tegmental nucleus of females. No effects were detected on hippocampal neurogenesis or dendritic spine density. These findings suggest that the cognitive effects of FAE-20 are selective, depending on the cognitive demands of the task and the baseline cognitive abilities of the animals, and may be mediated, at least in part, by modulation of arousal-related neural circuits. HighlightsO_LIFAE-20 enhanced cognitive flexibility in young adult mice C_LIO_LIEffects of FAE-20 were strongest in demanding cognitive tasks C_LIO_LIAged poor learners benefited from FAE-20 treatment C_LIO_LIFAE-20 activated hypothalamic orexin neurons in male mice C_LIO_LIFAE-20 modulated ascending arousal systems in a sex-specific manner C_LI

neuroscience↗

bioRxiv2026

Seizure-related gene 6 (SEZ6) encodes a Cancer stem cell-specific proangiogenic molecule: A novel glioma therapeutic target

Cancer stem-like cells (CSCs) not only initiate tumors but also orchestrate angiogenesis through multiple mechanisms, thereby sustaining vascularization and promoting tumor growth. In glioblastoma (GBM; WHO grade IV glioma), the most aggressive adult brain tumor, glioma stem-like cells (GSCs; glioma CSCs) are the main drivers of tumor progression, drug resistance, and recurrence. An interrogated multi-omic secretome analysis identified Wnt-{beta}-catenin signaling-regulated, membrane-localized Seizure Related 6 Homolog (SEZ6) as a patient-derived GSC-specific proangiogenic molecule. Silencing of SEZ6 inhibited the ability of the GSC secretome to induce angiogenic network formation by brain- and lung-derived endothelial cells, but not GSC growth as neurospheres in vitro. SEZ6 silencing also suppressed patient-derived GSC-initiated glioma tumors, resulting in reduced tumor vasculature in an orthotopic mouse model. We also found that SEZ6 induces TGF{beta}-dependent IL-8 expression in endothelial cells to promote angiogenesis. Coimmunoprecipitation and molecular dynamics simulation experiments determined that the Sushi 3 domain of SEZ6 mediates the interaction with TGF{beta} RII to activate the TGF{beta} pathway. Pharmacological inhibition of BACE1 with an in-house-developed small molecule, or blockade of the SEZ6-TGF{beta} RII interaction using a rationally designed peptide, markedly attenuated SEZ6-driven TGF{beta} signaling, and suppressed angiogenesis. Thus, our findings identify SEZ6 as a novel CSC-specific therapeutic target for GBM.

cancer biology↗

bioRxiv2026

Glucose-dependent regulation of hepatic adipsin controls glucose uptake and tolerance

Complement factor D, also known as adipsin, is produced by adipose tissue, and the liver that links metabolic regulation with innate immunity. Despite its established systemic functions, the regulation of hepatic adipsin expression and its contribution to metabolic disease remain poorly defined. Here, we show that hepatic adipsin protein abundance is markedly increased in individuals with type 2 diabetes (T2D), and positively correlates with glycated hemoglobin, despite unchanged mRNA expression. Concordantly, hepatic adipsin protein levels were elevated in multiple murine models of hyperglycemia, including type 1 diabetes (T1D), T2D, and following fasting-refeeding transitions. In cultured hepatocytes, glucose exposure induced a rapid, dose-dependent increase in adipsin protein without altering transcript abundance, demonstrating post-transcriptional regulation. Mechanistically, glucose stimulates adipsin translation via dephosphorylation of eukaryotic initiation factor 2 (eIF2), and activation of the mammalian target of rapamycin, mediated by the 5' untranslated region of adipsin mRNA. Functionally, hepatocyte-specific depletion of adipsin impaired postprandial glucose tolerance, with reduced glucose uptake and a marked downregulation of glucose transporter type 2 (GLUT2). Taken together, these findings identify hepatic adipsin as a glucose-responsive translational target that couples nutrient availability to metabolic adaptation, revealing a new layer of regulation with potential relevance to diabetes pathogenesis. HighlightsO_LIHepatic adipsin protein increases in type 2 diabetes and correlates with glycemic status independent of mRNA expression. C_LIO_LIGlucose induces adipsin translation through eIF2 dephosphorylation and mTOR activation. C_LIO_LImTOR controls adipsin synthesis via structured 5'UTR of adipsin mRNA. C_LIO_LILiver-specific adipsin depletion impairs post-prandial glucose tolerance by downregulating GLUT2. C_LIO_LIHepatic adipsin acts as a glucose-responsive effector of glycemic control. C_LI

cell biology↗

bioRxiv2026

PARP16 protects against cardiac hypertrophic response by ADP-ribosylation-dependent inhibition of NFAT transcription factor

Mono-ADP-ribosylation is a post-translational modification that regulates diverse cellular processes. PARP16 is an endoplasmic reticulum-associated mono-ADP-ribosyltransferase implicated in stress-response signalling; however, its role in cardiac remodelling and dysfunction has not been fully defined. Our results suggest that PARP16 expression was reduced in human heart failure samples. Deletion of PARP16 in several mice models promoted ventricular dilatation, fibrosis, fetal gene reactivation, and systolic dysfunction, whereas cardiomyocyte-specific overexpression of PARP16 attenuated isoproterenol-induced remodelling in mice. Transcriptomic profiling and functional studies identified NFAT signalling as a major downstream pathway activated following PARP16 deficiency. Specifically, loss of PARP16 increased nuclear accumulation, promoter occupancy, and transcriptional activity of NFAT1. Mechanistically, PARP16 interacted with NFAT1 and suppressed NFAT-dependent transcription through a catalytic activity-dependent mechanism. Proteomic, structural, and functional analyses identified E398 and T533 residues of NFAT1 associated with PARP16-mediated regulation. Furthermore, pharmacological inhibition of NFAT improved cardiac function and remodelling in PARP16-deficient mice. These findings indicate that PARP16 acts as a negative regulator of NFAT signalling and contributes to protection against adverse cardiac remodelling.

cell biology↗

bioRxiv2026

Rethinking human AMY1 copy number evolution in light of demographic history

Dietary change is often invoked as a major selective force in recent human evolution, with increased copy number of the salivary amylase gene (AMY1) widely cited as an adaptation to starch-rich agricultural diets. However, most evidence for this model comes from limited geographical sampling and analyses that do not fully account for shared ancestry. Here we combine newly generated droplet digital PCR estimates from 390 individuals representing 30 Sub-Saharan African populations with published copy number data from up to 1,307 individuals worldwide and re-evaluate AMY1 evolution using ancestry-aware and phylogenetically informed models. Across Africa, AMY1 copy number shows no consistent association with agriculture once population structure is accounted for. At a global scale, differences between agriculturalists and non-agriculturalists are substantially smaller than previously reported and are largely explained by shared ancestry rather than diet. Phylogenetic analyses further reveal baseline differences in AMY1 copy number between Sub-Saharan and non-Sub-Saharan populations, pointing to deep demographic processes shaping present-day variation. These results challenge the long-standing "agriculture hypothesis" and identify demographic history, rather than subsistence strategy, as the primary driver of AMY1 CN evolution worldwide.

evolutionary biology↗

bioRxiv2026

Enhancer-based AAV approach for selective AADC delivery reduces motor symptoms and dyskinesia in Parkinson's mouse models

Degeneration of midbrain dopamine (DA) neurons and the resulting loss of striatal dopamine signaling are hallmarks of Parkinsons disease (PD). Although the dopamine precursor levodopa (L-DOPA) provides symptomatic relief, prolonged treatment often leads to abnormal involuntary movements (dyskinesia). Previous adeno-associated virus (AAV) approaches delivering aromatic L-amino acid decarboxylase (AADC) to the striatum under a ubiquitous promoter enhanced local dopamine synthesis and improved PD motor deficits, but this broad targeting strategy limited insight into the cellular populations underlying the behavioral improvements. Here, we engineered enhancer-driven AAVs to direct AADC expression to defined striatal and midbrain cell populations and paired these regulatory elements with a blood-brain barrier-penetrant capsid to enable both systemic and direct delivery. Targeted expression restored motor performance at reduced L-DOPA doses and decreased dyskinesia-like behaviors, producing improvements comparable to or greater than those achieved with ubiquitous expression. Distinct neuronal and non-neuronal populations each supported motor rescue but improved different behavioral domains to different extents, indicating complementary cell type-specific roles within PD-relevant circuits. Together, these findings establish enhancer-driven, cell type-specific AADC delivery as a better-tolerated strategy that enables rescue of motor deficits at lower L-DOPA doses in PD models.

neuroscience↗

bioRxiv2025

PARP1 deficiency induces aging-associated cardiac failure via activation of Akt signalling

PARP1, a poly-ADP-ribose transferase, plays a critical role in maintaining genomic stability, transcription, cellular metabolism, and cell death. PARP1 inhibition protects cardiomyocytes against oxidative and genotoxic stress. However, the role of PARP1 in aging-associated heart failure remains poorly explored. In the current study, we report that PARP1 levels are downregulated in aging mouse hearts, and PARP1 deficiency induces aging-related cardiac remodelling and contractile dysfunction in mice. PARP1 deficient mice hearts exhibit spontaneous activation of the Akt signalling pathway, leading to the development of aging-related cardiac hypertrophy and fibrosis. Our findings reveal two distinct mechanisms by which PARP1 regulates Akt signalling, direct interaction of PARP1 with Akt and the transcriptional regulation of phosphatases like PTEN, a negative regulator of Akt signalling. PARP1 binds and inhibits Akt by poly-ADP-ribosylation at E40 and E49 residues, which impairs Akt membrane recruitment and subsequent activation. Inhibition of Akt reversed hypertrophy in PARP1-depleted cardiomyocytes and improved the contractile dysfunction in PARP1-deficient hearts. These findings reveal a previously unrecognized regulatory role for PARP1 in aging-associated cardiac failure.

physiology↗

bioRxiv2025

Calcitonin-Driven Reactivation of the Hippo Tumor-Suppressor Cascade Attenuates YAP/TAZ Oncogenic Signaling in Glioblastoma

Activation of WT calcitonin receptor (WT CTR) by Calcitonin (CT) acts as growth inhibitory axis in GBM, while the patient-derived loss-of-function CTR mutants promote tumor growth and lower patient survival. The precise mechanisms that orchestrate CTR activation, modulate its downstream signaling dynamics, and give rise to structural anomalies in mutant variants remain incompletely defined and warrant comprehensive investigation. Here, we found that salmon CT treatment suppressed the growth of patient-derived glioma stem cells (GSCs) by activating the Hippo pathway through the CTR/cAMP/PKA/LATS1 signaling cascade, while simultaneously inhibiting the oncogenic YAP/TAZ transcription factors. However, GSCs expressing a phosphorylation-resistant YAP mutant were refractory to growth inhibition by CT in vitro. GSCs, unlike differentiated glioma cells (DGCs), expressed high levels of CTR thus making them suitable for CT-based therapy. Furthermore, the intranasal delivery of salmon CT inhibited glioma growth initiated by GSCs in an intracranial orthotopic mouse model, resulting in increased survival in the mice. In addition, unlike the WT, the CTR mutants failed to activate the Hippo pathway. A large-scale, microsecond-long all-atom molecular dynamics simulation study of mutant CTR systems revealed remarkable changes in CTR interactions with the CT and G-GTPase domains. Packing and conformational dynamics data from simulation studies of the WT and mutant CTR systems could explain the perturbed cAMP/PKA signaling that may compromise downstream signaling. Together, we demonstrate that the CT/CTR axis inhibits glioma by activating the Hippo pathway, provide evidence for the structural defects in the loss-of-function CTR mutants, and propose a CT-based therapeutic strategy for GBM. Statement of significanceCT/CTR axis targets YAP/TAZ through Hippo pathway activation. Patient-derived GSCs express higher CTR levels, and intranasally delivered CT suppresses GSC-initiated tumors. All-atom molecular dynamics simulation uncovers structural perturbations in the CTR mutants.

cancer biology↗

bioRxiv2025

The Earlier You Know, the Smoother You Act

Intercepting a moving object with our hands requires that the moving object and the hand come into contact at some point along the objects trajectory. Hand movement must, therefore, be planned in advance so that the hand reaches a chosen spatial location along this trajectory at the correct moment in time. To enable such anticipatory behavior, the objects trajectory must be predicted based on sensory information collected before movement planning is concluded. Early completion of planning would allow for a smooth and economical movement; however, it also requires sufficiently accurate information about the objects movement to be available earlier. We investigate interception in the context of a complex, naturalistic motor task, toss juggling, to understand the extent to which proprioceptive and tactile information influence anticipatory movements of the catching hand. In our study, we compared solo juggling, where the efferent, tactile and proprioceptive information from the throwing hand is available during catch planning, with dyadic juggling, a functionally "deafferented" condition where no such information is available because the ball has been thrown by another person. Our results indicate that when internal and tactile information from the toss is absent, anticipatory behavior is greatly reduced. Experienced jugglers seem to rely more strongly on internal information than vision, allowing earlier planning and lower target uncertainty. In the dyadic condition, when internal information is absent, trajectory planning is delayed, leading to greater target uncertainty.

neuroscience↗

bioRxiv2025

Effects of Cholesterol Modulation on Cisplatin-Induced Hearing Loss

Cisplatin is a widely used and effective anticancer drug. However, it causes permanent sensorineural hearing loss in over 50% of treated patients. There are no FDA-approved therapies to prevent cisplatin-induced hearing loss (CIHL) in adults, highlighting a critical unmet clinical need. Previous studies suggest that statins, commonly prescribed cholesterol-lowering drugs, are associated with reduced incidence and severity of cisplatin-induced hearing loss. Statins are primarily used to lower cholesterol, but they also exert several pleiotropic effects, making the mechanism(s) underlying this protection unclear. Here we examine whether reduced plasma cholesterol confers protection against CIHL independent of statin treatment. We utilized mice lacking serine protease proprotein convertase subtilisin/kexin type 9 (Pcsk9 knockout (KO) mice) as a genetic model of reduced plasma cholesterol. We find that Pcsk9 KO mice are protected against cisplatin-induced hearing loss, as reflected by significantly lower ABR and DPOAE threshold shifts relative to wild type (WT) mice following treatment. Histological analyses confirmed preservation of cochlear outer hair cells (OHCs) in Pcsk9 KO mice treated with cisplatin, whereas WT mice showed significant OHC loss in the high-frequency cochlear regions. Finally, hearing loss positively correlated with baseline plasma cholesterol levels. Together our data demonstrate that systemic cholesterol reduction provides significant protection against CIHL, and they suggest that the protective effect of statins against CIHL is mediated by cholesterol reduction.

neuroscience↗

bioRxiv2025

Structural insights into the mechanism of C3 side chain fragmentation in cephalosporins with SME-1 class A carbapenemase

Cephalosporins remain one of the largest classes of antibiotics used clinically, with a diverse group of dual substituents at C3 and C7 positions. The fragmentation of the C-3 side chain from the C3 position after hydrolysis by Serine or metallo-{beta} lactamase leaving an exo-methylene group has been introduced in the literature recently, but the exact mechnism by which it happens remains unclear until now. Our incrystallo findings suggest that the fragmentation of the C3 side chain will depend on the C3 atom and its hybridization state. A C3 carbon with sp2 hybridization will not allow fragmentation, but a sp3 hybridized carbon will facilitate the detachment of the side chain. Furthermore, heteroatoms like Sulfur, on C3 position, bearing vacant d-orbitals participate in {pi}-cloud delocalization, making the detachment of C3 side chain energetically unfeasible. For the sp3 hybridized carbon at C3, the fragmentation of the bond was independent of the C3 atom. We observed fragmentation of the C3-C3 bond for all three heteroatoms, Nitrogen, Oxygen, and sulfur, at the C3 position. We validated our crystallographic findings with mass spectrometry to confirm the fragmentation of the C3 side chain in sp3 carbon and the unfragmented side chain in sp2 carbon and sulfur at C3 position. QM/MM simulations on three types of enzyme-cephalosporin complexes with different C3 side chains confirm the mechanism of fragmentation. Beyond revealing C3 side chain fragmentation in cephalosporins, useful for inhibitor and diagnostic design, our QM/MM methods are useful on incrystallo complexes to show the enzyme catalysis.

biochemistry↗

bioRxiv2025

Selective decoupling of IgG1 binding to viral Fc receptorsrestores antibody-mediated NK cell activation against HCMV-infected cells

A key mechanism of antiviral antibodies is to bind cell-surface viral antigens and activate cellular immunity to clear infected cells, yet antibodies targeting human cytomegalovirus (HCMV) have exhibited limited efficacy. This appears due to HCMVs multiple immune evasion mechanisms, including viral receptors (vFc{gamma}Rs) which bind human IgG Fc domains to co-operatively inhibit Fc activation of host Fc{gamma} receptors and impair Fc-mediated effector functions. We biochemically characterized and evaluated the functions of two highly conserved vFc{gamma}Rs, gp34 and gp68, and mapped their binding epitopes on the Fc domain. Based on this information, we then engineered Fc variants that retain binding to CD16A, which is essential for NK activation, and to FcRn but have markedly attenuated binding to gp34 and gp68. IgG1 antibodies targeting the gB fusogen with engineered Fc domains were not internalized by infected cells, mediated enhanced CD16A activation and limited viral spread in HCMV-infected fibroblasts more effectively than wild-type Fc. Together, this work demonstrates a strategy to enhance the efficacy of antibody therapies to clear HCMV infections. HighlightsO_LIHost and HCMV FcR compete for IgG1 binding but engage different residues. C_LIO_LIFc-engineering abrogates viral FcR antagonism while retaining CD16A activation. C_LIO_LIAntibodies that resist vFcR capture promote superior ADCC against infected cells. C_LIO_LIDesigner Fc domains complement Fabs to create enhanced disease-specific therapies. C_LI

immunology↗

bioRxiv2025

Revisiting the African mtDNA Landscape: A Continental Update from Complete Mitochondrial Genomes

AbstractAfrica harbors the richest diversity of mitochondrial DNA lineages, reflecting its central role in human evolutionary history. Early studies of mtDNA variation provided the first genetic evidence for the African origin of modern humans. With complete mitochondrial genome sequencing, we can now reconstruct maternal lineages with high resolution, yet large parts of the continent remain underrepresented. Using a newly developed long-range sequencing assay, we generated 1,288 complete mitochondrial genomes from 14 countries across sub-Saharan Africa, focusing on previously understudied regions. We combined these with over 3,600 publicly available African mitogenomes to produce a comprehensive dataset and updated overview of maternal genetic diversity across the continent. We contextualized this diversity with autosomal structure and information on major human expansions, integrating archaeological and linguistic evidence. Our analyses reveal a demographic expansion of Niger-Congo speakers around 17 thousand years ago (kya), followed by a second expansion associated with Bantuspeaking groups around 6 kya. We identify haplogroup L3e as a key marker of this early Bantu expansion, tracking its spread across sub-Saharan Africa. Distinct demographic signatures also emerge for different geographic sub-branches of Bantu speakers. These findings highlight the power of mitochondrial DNA to trace maternal ancestry and demographic history in Africa, while also acknowledging its limitations for phylogeographic reconstruction.

evolutionary biology↗

bioRxiv2025

Thalamic oscillations distinguish natural states of consciousness in humans

Natural states of consciousness are thought to be regulated by deep brain structures such as the thalamus. However, very little is known about the underlying electrophysiology in humans. Here, using a rare opportunity to directly record from the human thalamus, we identify a hitherto-unreported brain-state-specific oscillation of approximately 19-45 Hz. This oscillation is present only during Rapid Eye Movement (REM) sleep and wakefulness, while being absent during Non-REM sleep. The 19-45 oscillation further distinguishes REM sleep microstates, co-occurring with bursts of eye movements, and is specific to the Central Thalamus, a structure implicated in causing global brain state transitions. The discovery of a distinct oscillatory signature in the Central Thalamus that distinguishes conscious states opens up avenues to further investigate thalamic contributions to states of consciousness in humans and potentially to refine interventions to treat disorders of consciousness.

neuroscience↗