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Rajesh, A.

Publications and source records attributed to Rajesh, A..

22 records · Page 2Linked to original sources

A mind-body interface alternates with effector-specific regions in motor cortex

Primary motor cortex (M1) has been thought to form a continuous somatotopic homunculus extending down precentral gyrus from foot to face representations1,2. The motor homunculus has remained a textbook pillar of functional neuroanatomy, despite evidence for concentric functional zones3 and maps of complex actions4. Using our highest precision functional magnetic resonance imaging (fMRI) data and methods, we discovered that the classic homunculus is interrupted by regions with sharpy distinct connectivity, structure, and function, alternating with effector-specific (foot, hand, mouth) areas. These inter-effector regions exhibit decreased cortical thickness and strong functional connectivity to each other, and to prefrontal, insular, and subcortical regions of the Cingulo-opercular network (CON), critical for executive action5 and physiological control6, arousal7, and processing of errors8 and pain9. This interdigitation of action control-linked and motor effector regions was independently verified in the three largest fMRI datasets. Macaque and pediatric (newborn, infant, child) precision fMRI revealed potential cross-species analogues and developmental precursors of the inter-effector system. An extensive battery of motor and action fMRI tasks documented concentric somatotopies for each effector, separated by the CON-linked inter-effector regions. The inter-effector regions lacked movement specificity and co-activated during action planning (coordination of hands and feet), and axial body movement (e.g., abdomen, eyebrows). These results, together with prior work demonstrating stimulation-evoked complex actions4 and connectivity to internal organs (e.g., adrenal medulla)10, suggest that M1 is punctuated by an integrative system for implementing whole-body action plans. Thus, two parallel systems intertwine in motor cortex to form an integrate-isolate pattern: effector-specific regions (foot, hand, mouth) for isolating fine motor control, and a mind-body interface (MBI) for the integrative whole-organism coordination of goals, physiology, and body movement.

neuroscience↗

The systematic assessment of completeness of public metadata accompanying omics studies

Recent advances in high-throughput sequencing technologies have made it possible to collect and share a massive amount of omics data, along with its associated metadata. Enhancing metadata availability is critical to ensure data reusability and reproducibility and to facilitate novel biomedical discoveries through effective data reuse. Yet, incomplete metadata accompanying public omics data may hinder reproducibility and reusability by reducing sample interpretability and limiting secondary analyses. In this study, we performed a comprehensive assessment of metadata completeness shared in both scientific publications and/or public repositories by analyzing over 253 studies encompassing over 164 thousands samples, including both human and non-human mammalian studies. We observed that studies often omit over a quarter of important phenotypes, with an average of only 74.8% of them shared either in the text of publication or the corresponding repository. Notably, public repositories alone contained 62% of the metadata, surpassing the textual content of publications by 3.5%. Only 11.5% of studies completely shared all phenotypes, while 37.9% shared less than 40% of the phenotypes. Studies involving non-human samples were more likely to share metadata than studies involving human samples. We observed similar results on the extended dataset spanning 2.1 million samples across over 61,000 studies from the Gene Expression Omnibus repository. The limited availability of metadata reported in our study emphasizes the necessity for improved metadata sharing practices and standardized reporting. Finally, we discuss the numerous benefits of improving the availability and quality of metadata to the scientific community and beyond, supporting data-driven decision-making and policy development in the field of biomedical research. This work provides a scalable framework for evaluating metadata availability and may help guide future policy and infrastructure development.

bioinformatics↗

Virtual meetings promise to eliminate the geographical and administrative barriers and increase accessibility, diversity, and inclusivity

The COVID-19 pandemic brought a new set of unprecedented challenges not only for healthcare, education, and everyday jobs but also in terms of academic conferences. In this study, we investigate the effect of the broad adoption of virtual platforms for academic conferences as a response to COVID-19 restrictions. We show that virtual platforms enable higher participation from underrepresented minority groups, increased inclusion, and broader geographic distribution. We also discuss emerging challenges associated with the virtual conference format resulting in a decreased engagement of social activities, limited possibilities of cross-fertilization between participants, and reduced peer-to-peer interactions. Lastly, we conclude that a novel comprehensive approach needs to be adopted by the conference organizers to ensure increased accessibility, diversity, and inclusivity of post-pandemic conferences. Our findings provide evidence favoring a hybrid format for future conferences, marrying the strength of both in-person and virtual platforms.

scientific communication and education↗

Cell cycle-gated feedback control mediates desensitization to interferon stimulation

Cells use sophisticated molecular circuits to interpret and respond to extracellular signal factors, such as hormones and cytokines, which are often released in a temporally varying fashion. In this study, we focus on type I interferon (IFN) signaling in human epithelial cells and combine microfluidics, time-lapse microscopy, and computational modeling to investigate how the IFN-responsive regulatory network operates in single cells to process repetitive IFN stimulation. We found that IFN- pretreatments lead to opposite effects, priming versus desensitization, depending on the input durations. These effects are governed by a regulatory network composed of a fast-acting positive feedback loop and a delayed negative feedback loop, mediated by upregulation of ubiquitin-specific peptidase 18 (USP18). We further revealed that USP18 upregulation can only be initiated at the G1 and early S phases of cell cycle upon the treatment onset, resulting in heterogeneous and delayed induction kinetics in single cells. This cell cycle gating provides a temporal compartmentalization of feedback control processes, enabling duration-dependent desensitization to repetitive stimulations. Moreover, our results, highlighting the importance of IFN dynamics, may suggest time-based strategies for enhancing the effectiveness of IFN pretreatment in clinical applications against viruses, such as SARS-CoV-2.

systems biology↗