Biology subjects

Ghosal, A.

Publications and source records attributed to Ghosal, A..

8 recordsLinked to original sources

bioRxiv2026

Uptake and Implementation of Multiverse-style Analyses Across 613 Studies

Empirical conclusions can depend on the many individual choices researchers make when analyzing data. Multiverse-style analyses address this by computing results across a set of specifications rather than a single one, but it is unclear how widely they are being used and how they are being implemented. We searched the Web of Science Core Collection (May 2026) for articles citing six foundational papers on different variants of multiverse-style methods and classified each of the citing articles as implementing such methods or only discussing them. For implementations, we recorded the framework used, the number of specifications, which of four decision nodes (measurement, data processing, modeling, and estimation) were varied, and other aspects such as how results were visualized and interpreted. Of the 1545 classifiable articles, 613 (39.7%) implemented a multiverse-style analysis (primarily multiverse n = 336, specification curve n = 175, vibration of effects n = 20, multimodel n = 59, and multi-analyst/many-analyst n = 23). Uptake spanned many disciplines, most often psychology (39.8%), the social sciences (20.7%), and medicine (19.2%). The number of specifications ranged from fewer than ten to more than ten thousand (median = 144, IQR 24-1248). Modeling (75%) and data-processing (62%) choices were included most often. Interpretation was predominantly descriptive, whereas formal inference (10.5%), preregistration (8.6%), and explicit attention to the defensibility of specifications (3.9%) were uncommon. Multiverse-style analyses are increasingly becoming established across the quantitative sciences, but some implementation practices can be strengthened so that these analyses become more fully transparent and more genuinely informative about the robustness of research findings.

scientific communication and education↗

bioRxiv2025

Differential kinematic control and co-ordination among redundant joints during whole arm reaching movements

Normative upper limb movements are produced by multiple redundant joints. While the reaching task is specified at the endpoint, such task objectives become implicit at the level of joints. A fundamental question is whether planning and control of joints is solely in the service of the endpoint or whether they also include joint trajectories. Using Spearmans correlation and zero crossings, we found differential kinematic signatures of control between shoulder and elbow joints in contrast to the wrist joint. However, the extent of control among joints was substantially diminished compared to the endpoint. Further, when such control measures were compared to the subspaces of inter-trial joint exploration, we found that online control at proximal joints, such as the shoulder and elbow, were significantly associated in regulating the task space, while control at the wrist (distal) joint was associated in regulating joint redundancy in null space. These results suggest that null space is not entirely uncontrolled as per the uncontrolled manifold hypothesis but selectively controlled by some distal joints. Additionally, across different directions, either the shoulder or the elbow contributed dominantly towards the movement of the endpoint while the other joint was lagging and that this strategy reflected in our kinematic measures of online and trajectory control. Taken together, this study shows how the selective implementation of a leading joint in task space and a lagging joint in null space can enable the control of multi-jointed movements and attenuate the problem of joint redundancy. Significance StatementIn this study, we addressed a fundamental question of how our central nervous system resolves the problem of joint redundancy, as to whether planning and control of joints are solely in the service of endpoint or whether they also include joint trajectories. We found significant kinematic control signatures among joints towards their respective average joint trajectories, especially during the early and middle phases of movement. Furthermore, each joint had a distinct task objective, the proximal shoulder or elbow joints controlled the task space and were responsible for driving the whole-arm movements, while the distal wrist joint regulated joint redundancy.

neuroscience↗

bioRxiv2025

N-Alkyl Sulfamates as a New Class of nsP2 Cysteine Protease Inhibitors with Broad Spectrum Antialphaviral Activity

The emergence of mosquito-borne alphaviruses that cause chronic arthritis or encephalitis underscores the urgent need for broad-spectrum antiviral therapeutics. The viral nsP2 cysteine protease, which is essential for alphavirus replication, is a promising antiviral target. Vinyl sulfone-based inhibitors, such as RA-2034, potently inhibit nsP2 protease but suffer from glutathione reactivity and species-dependent systemic clearance catalyzed by glutathione S-transferase. To address these liabilities, we explored alternative electrophilic warheads and identified reverse amide inhibitors bearing N-alkyl sulfamate warheads with improved biochemical and antiviral profiles. N-methyl sulfamate acetamide 5 emerged as a lead compound with potency against both New and Old World alphaviruses, low GSH reactivity, and high proteome-wide selectivity. Despite its promising antialphaviral activity, 5 exhibited rapid clearance due to hepatic glucuronidation. Structure-activity studies revealed modifications that improve metabolic stability while retaining antiviral activity. These findings introduce sulfamate acetamides as a new class of covalent nsP2 protease inhibitors and advance the discovery of direct acting pan-alphavirus drugs.

pharmacology and toxicology↗

bioRxiv2025

Practical considerations for accurate estimation of diffusion parameters from single-particle tracking in living cells

Advances in fluorescence microscopy have enabled high-resolution tracking of individual biomolecules in living cells. However, accurate estimation of diffusion parameters from single-particle trajectories remains challenging due to static and dynamic localization errors inherent in these measurements. While previous studies have characterized how such errors affect mean-squared displacement (MSD) analysis, practical guidelines for minimizing them during data acquisition and correcting them during analysis are still lacking. Here, we combine theoretical modeling and simulations to evaluate how exposure time and sampling rate influence the accuracy of MSD-based inference under fractional Brownian motion (FBM), a canonical model of anomalous diffusion. We demonstrate that decoupling exposure and sampling times enables escape from the error-prone regime, thus improving inference accuracy, and that incorporating an offset in nonlinear MSD fitting substantially improves the estimation of the anomalous diffusion exponent. We validate this framework using trajectories of cytoplasmic particles in Escherichia coli, recovering consistent diffusion parameters across multiple data sets. Our findings offer practical strategies to improve both experimental design and data analysis in single-particle tracking of live or synthetic systems.

biophysics↗

bioRxiv2023

Internal feedback enables rapid trajectory control during goal-directed finger and whole-arm reaching movements

Goal-directed eye, hand, and finger movements follow invariant kinematics consisting of approximate straight-line trajectories and bell-shaped velocity profiles. A fundamental unresolved issue is whether these trajectories are planned or whether they are a consequence of trajectory-free online control. We address this question using Spearmans rank correlation, zero-crossing rate, and z-scores, and analyze within-trial variability to investigate differences in the time evolution of trajectories during the presence or absence of a goal in finger and whole-arm reaching movements, along with analyzing rapid goal-directed saccadic eye movements. We found that the central nervous system (CNS) implements control to follow an average trajectory, where goal-directed movements show an enhanced degree of trajectory control. Further, we found behavioral signatures of rapid control that might operate on these planned trajectories as early as [~]60 ms in finger movements and [~]70 ms in whole-arm reaching movements. Such early signatures of control suggest that the system could exploit internal feedback along with fast feedback processes to implement meaningful corrections during simple voluntary unperturbed movements. The analysis also revealed that the controller gains varied along the movement and peaked distinctly at early (20 %) and late (90 %) phases of finger and arm movements, implying that trajectory control may be accomplished through implicit way-point objectives during the execution of the movement. These later corrections were missing during the late phase of eye movements, pointing to a predominant role of delayed sensory feedback mediating corrections in the context of finger and arm movements during this period.

neuroscience↗

bioRxiv2020

The effect of functionally-guided-connectivity-based rTMS on amygdala activation.

Repetitive transcranial magnetic stimulation (rTMS) has fundamentally transformed how we treat psychiatric disorders, but is still in need of innovation to optimally correct dysregulation that occurs throughout the fronto-limbic network. rTMS is often applied over the prefrontal cortex, a central node in this network, but less attention is given to subcortical areas because they lie at depths beyond the electric field penetration of rTMS. Recent studies have demonstrated that the effectiveness of rTMS is dependent on the functional connectivity between deep subcortical areas and superficial targets, indicating that leveraging such connectivity may improve dosing approaches for rTMS interventions. The current preliminary study, therefore, sought to test whether task-related, fMRI-connectivity-based rTMS could be used to modulate amygdala activation through its connectivity with the medial prefrontal cortex (mPFC). For this purpose, fMRI was collected on participants to identify a node in the mPFC that showed the strongest negative connectivity with right amygdala, as defined by psychophysiological interaction analysis. To promote long-lasting Hebbian-like effects, and potentially stronger modulation, 5Hz rTMS was then applied to this target as participants viewed frightening video-clips that engaged the fronto-limbic network. Post-rTMS fMRI results revealed promising increases in both the left mPFC and right amygdala, for active rTMS compared to sham. While these modulatory findings are promising, they differ from the a priori expectation that excitatory 5Hz rTMS over a negatively connected node would reduce amygdala activity. As such, further research is needed to better understand how connectivity influences TMS effects on distal structures, and to leverage this information to improve therapeutic applications.

neuroscience↗

bioRxiv2019

Basal ganglia contributions during the learning of a visuomotor rotation: effect of dopamine, deep brain stimulation and reinforcement

It is commonly thought that visuomotor adaptation is mediated by the cerebellum while reinforcement learning is mediated by the basal ganglia. In contrast to this strict dichotomy, we demonstrate a role for the basal ganglia in visuomotor adaptation (error-based motor learning) in patients with Parkinsons disease (PD) by comparing the degree of motor learning in the presence and absence of dopamine medication. We further show similar modulation of learning rates in the presence and absence of subthalamic deep brain stimulation. We also report that reinforcement is an essential component of visuomotor adaptation by demonstrating the lack of motor learning in patients with PD during the ON-dopamine state relative to the OFF-dopamine state in the absence of a reinforcement signal. Taken together, these results suggest that the basal ganglia modulate the gain of visuomotor adaptation based on the reinforcement received at the end of the trial.

neuroscience↗

bioRxiv2017

Isolation of nucleic acids from low biomass samples: detection and removal of sRNA contaminants

Sequencing-based analyses of low-biomass samples are known to be prone to misinterpretation due to the potential presence of contaminating molecules derived from laboratory reagents and environments. Due to its inherent instability, contamination with RNA is usually considered to be unlikely. Here we report the presence of small RNA (sRNA) contaminants in widely used microRNA extraction kits and means for their depletion. Sequencing of sRNAs extracted from human plasma samples was performed and significant levels of non-human (exogenous) sequences were detected. The source of the most abundant of these sequences could be traced to the microRNA extraction columns by qPCR-based analysis of laboratory reagents. The presence of artefactual sequences originating from the confirmed contaminants were furthermore replicated in a range of published datasets. To avoid artefacts in future experiments, several protocols for the removal of the contaminants were elaborated, minimal amounts of starting material for artefact-free analyses were defined, and the reduction of contaminant levels for identification of bona fide sequences using ultra-clean extraction kits was confirmed. In conclusion, this is the first report of the presence of RNA molecules as contaminants in laboratory reagents. The described protocols should be applied in the future to avoid confounding sRNA studies.

molecular biology↗