Biology subjects

Babu, S.

Publications and source records attributed to Babu, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Keratin 17 Defines an Epithelial-Mesenchymal Transition-Associated Migratory Cell State in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is characterized by early invasion, metastasis, and therapeutic resistance that contribute substantially to its poor clinical outcome. Keratin 17 (K17) is a recognized marker of the aggressive basal-like subtype of PDAC and an independent predictor of adverse prognosis; however, the biological basis for this association remains incompletely understood. To define K17-associated cellular programs, we integrated single-cell RNA sequencing (scRNA-seq) data from 42 patients, Clinical Proteomic Tumor Analysis Consortium (CPTAC) proteomic data from 140 tumors, MACSima multiplex spatial imaging of 63 patients, dual-plex immunohistochemistry of 60 cases, and three-dimensional spheroid migration assays. Single-cell transcriptomic analysis demonstrated significant enrichment of epithelial-mesenchymal transition (EMT)-associated gene programs among K17-positive malignant epithelial cells. Consistent with this finding, K17-positive tumors in the CPTAC cohort exhibited enrichment of the Hallmark EMT pathway at the protein level. Among six candidate markers identified through transcriptomic analyses, laminin subunit gamma-2 (LAMC2) was the only candidate associated with K17 at every validation step. Tumors positive for both K17 and LAMC2 had significantly worse overall survival than double-negative tumors (adjusted hazard ratio = 2.53). Multiplex spatial imaging localized K17-positive cells predominantly to poorly differentiated tumor regions and demonstrated frequent single-cell co-expression with LAMC2. Whole-slide dual-plex immunohistochemistry further confirmed the association between K17 and LAMC2 and showed progressive enrichment of K17/LAMC2-positive tumor cells with increasing intratumoral histologic grade. Functionally, gain- and loss-of-function studies in three-dimensional PDAC spheroids demonstrated that K17 promotes migratory outgrowth, and differences in proliferation did not account for this effect. Collectively, these findings identify K17 as a marker of a poorly differentiated, EMT-associated migratory cell state in PDAC and provide functional evidence that K17 contributes to tumor-cell migration.

cancer biology↗

bioRxiv2026

Characterizing the Assembly and Functional Properties of Gene-Length Mixed DNA Monolayers on Electrodes for Cell-Free Expression

Gold electrodes are attractive substrates for bioelectronic and cell-free synthetic biology platforms because they are conductive, chemically stable, biocompatible, and readily functionalized through thiol-gold chemistry. Here, gene-length DNA monolayers assembled on planar gold electrodes as reusable templates for cell-free protein expression are investigated. Using thiol-modified sfGFP genes, DNA surface density is shown to be tunable by changing the DNA concentration during incubation, with the immobilized genes able to support cell-free sfGFP expression directly from the electrode surface. Further, the effects of applied voltage, storage, repeated reactions, reducing agents, and protein fouling on monolayer stability and expression output are examined. While some conditions lead to loss of reusable expression activity, dense chemisorbed monolayers can retain partial function under neutral, non-reducing conditions and are relatively robust to protein exposure. In contrast, low-density physisorbed monolayers show a stronger relationship between DNA loss and expression output. Finally, when using gold-mediated fluorescence quenching to monitor changes in DNA conformation, surface-bound DNA demonstrates electrophoretic addressability. Together, these results establish DNA- functionalized planar electrodes as a promising foundation for modular, addressable cell-free expression platforms.

bioengineering↗

bioRxiv2026

Virtual Cells Need Context, Not Just Scale

The intersection of AI and biology has entered a phase of explosive growth, driven by the ambition to build "Virtual Cells" or computational models capable of predicting cellular responses to any perturbation. Following the success of structural biology (e.g., AlphaFold) and large language models, the field has converged on training massive, high-capacity models on large-scale single-cell data. This position paper argues that scaling model capacity is insufficient to solve the Virtual Cell problem because the primary failure mode is a lack of adequate coverage over diverse biological contexts, not insufficient model expressivity. We support this claim by reviewing recent studies showing that simple baselines perform on par with sophisticated architectures within a given biological context, and current models fail to consistently generalize across contexts. We connect this finding to the causal inference literature on transportability and contrast it with domains where scaling has succeeded. We substantiate our argument through analysis of a state-of-the-art model on a 22-million-cell immunology dataset. We conclude that the community faces a causal transport problem that cannot be solved by accumulating more data from the same distributions. Instead, we argue that contextual diversity and causal representation learning deserve increased emphasis, complementing ongoing scaling of model capacity and data volume.

genomics↗

bioRxiv2025

Fus depleted oligodendrocytes reduce neuronal damage and attenuate AD progression in the AppNL-G-F mouse

AbstractOligodendrocytes (OL) and myelin abnormalities have emerged as important contributors to the pathogenesis of Alzheimers Disease (AD). OL maintain neuronal health through myelin axon interactions and by supplying neurotrophic and metabolic support. To gain insight on how OL and myelin may improve neuronal deficits associated with AD, we have generated a novel mouse model (AD/cKO) by crossing the AppNL-G-F mouse which carries three human AD mutations in the mouse App gene with the FusOLcKO, which has thicker myelin associated with greater cholesterol biosynthesis. The spatial working memory deficits manifested by the aged AD mouse were fully rescued by the FusOLcKO. This outcome was associated with reduced neuronal oxidative damage, preserved presynaptic structures at the plaque niches and a shift in microglia state at the niches in both hippocampus and cortex. In contrast, plaque burden and microglia density were decreased in the hippocampus but not in cortex, uncoupling the neuronal and microglia effects from the amyloid burden. Single cell transcriptomics of AD/cKO hippocampal OL revealed upregulation of energy metabolism and antioxidant genes, suggesting a role of OL enhanced energy metabolism in protecting neurons and affecting microglia state in AD pathology.

neuroscience↗

bioRxiv2025

A molecular and spinal circuit basis for the functional segregation of itch and pain

Recent advances reveal an extensive cellular diversity within the dorsal horn. How this complexity processes distinct sensations, like itch and pain, remains a fundamental question. We discovered hidden within a population of neurons expressing the gastrin-releasing peptide receptor (Grpr+), thought to be itch-specific, are highly homologous yet functionally distinct subtypes distinguished by expression of Tachykinin-1 (Tac1). While the Tac1- subtype mediates itch, the Tac1+ subtype mediates mechanical allodynia across diverse pain states. Inhibitory populations and differential sensitivities to GRP serve as key modulators of the Grpr+ neuron subtypes, shaping modality specific output. Leveraging computationally designed genomic enhancers to silence the Tac1- population reverses itch while silencing the Tac1+ subtype reverses mechanical allodynia broadly. The work demonstrates the nuance of differential sensory modality coding within the dorsal horn and the power of genomic enhancer-based strategies for modality-specific targeting.

neuroscience↗

bioRxiv2025

Excitatory signal processing in early visual areas based on task-relevance and perceptual salience modulates visual perceptual learning

Adaptive visual perceptual learning (VPL) should occur primarily for visual signals relevant to an observers task but not for task-irrelevant signals. However, it is unclear which neural mechanisms reduce VPL for task-irrelevant signals. Here, we repeatedly exposed participants to a task-irrelevant visual signal (coherent motion in one direction) that was perceptually salient (suprathreshold for coherent motion detection) or weak (near threshold for coherent motion detection). The processing of the task-irrelevant signal in early visual areas during the first and final exposure sessions was measured using functional magnetic resonance spectroscopy (fMRS). The behavioral results showed that discrimination sensitivity for the exposed coherent motion direction increased to a greater extent after near threshold than after suprathreshold exposure. The fMRS results showed that excitatory processing in early visual areas, as reflected in the concentration of glutamate, was lower during suprathreshold than near threshold exposure. The lower the level of excitatory processing in the first exposure session, the more deteriorated the discrimination sensitivity for the coherent motion direction after suprathreshold exposure. When the coherent motion direction was rendered task-relevant, levels of glutamate in early visual areas reversed such that excitatory processing was greater when the coherent motion direction was presented suprathreshold than near threshold. This suggests that the level of excitatory processing in early visual areas changes with the task relevance and perceptual salience of a visual signal, which may modulate the extent of VPL for this signal when it is repeatedly exposed. Significance StatementVisual perceptual learning (VPL) enhances the efficiency in processing visual signals and is fundamental to the brains ability to adapt to changing environmental conditions. However, little is known about neural mechanisms that reduce VPL, although such mechanisms are crucial for adaptive VPL, which occurs primarily for visual signals relevant to an observers task but not for task-irrelevant signals. Here we find that early visual areas decrease excitatory processing for a salient task-irrelevant visual signal, which is associated with reduced VPL for this signal. This suggests, first, that a decrease of excitatory activity may be a mechanism that reduces VPL for salient task-irrelevant signals and, second, that this mechanism exerts its effect already at an early stage of cortical visual processing.

neuroscience↗

bioRxiv2025

Combining Machine Learning and Multiplexed, In Situ Profiling to Engineer Cell Type and Behavioral Specificity

A promising strategy for the precise control of neural circuits is to use cis-regulatory enhancers to drive transgene expression in specific cells. However, enhancer discovery faces key challenges: low in vivo success rates, species-specific differences in activity, challenges with multiplexing adeno-associated viruses (AAVs), and the lack of spatial detail from single-cell sequencing. In order to accelerate enhancer discovery for the dorsal spinal cord--a region critical for pain and itch processing--we developed an end-to-end platform, ESCargoT (Engineered Specificity of Cargo Transcription), combining machine learning (ML)-guided enhancer prioritization, modular AAV assembly, and multiplexed, in situ screening. Using cross-species chromatin accessibility data, we trained ML models to predict enhancer activity in oligodendrocytes and in 15 dorsal horn neuronal subtypes. We first demonstrated that an initial enhancer, Excit-1, targeted excitatory dorsal horn neurons and drove reversal of mechanical allodynia in an inflammatory pain model. To enable parallel profiling of a 27-enhancer-AAV library delivered intraspinally in mice, we developed a Spatial Parallel Reporter Assay (SPRA) by integrating a novel Golden-Gate assembly pipeline with multiplexed, in situ screening. Regression adjustment for spatial confounding enabled specificity comparisons between enhancers, demonstrating the ability to screen enhancers targeting diverse cell types (oligodendrocytes, motoneurons, dorsal neuron subtypes) in one experiment. We then validated two candidates, targeting Exc-LMO3 and Exc-SKOR2 neurons, respectively. In a companion paper by Noh et al, our colleagues show that the functional specificity of the Exc-SKOR2-targeting enhancer, unlike Excit-1, is capable of blocking the sensation of chemical itch in mice. These enhancers were derived from the macaque genome but displayed functional sensitivity in mice. This platform enables spatially resolved, multiplexed in vivo enhancer profiling to accelerate discovery of cell-targeting tools and gene therapy development.

neuroscience↗

bioRxiv2025

Recurrent oncogenic ZC3H18 mutations stabilize endogenous retroviral RNA

Endogenous retroviral (ERV) RNA is highly expressed in cancer, although the molecular causes and consequences remain unknown. We found that ZC3H18 (Z18), a component of multiple nuclear RNA surveillance complexes, has recurrent truncating mutations in cancer. We show that Z18trunc mutations are oncogenic and that Z18 plays an evolutionarily conserved role in nuclear RNA surveillance of ERV RNA. In zebrafish, Z18trunc expedited melanoma onset and promoted a specific accumulation of ERV RNA. Z18 mutant human cell lines from the Cancer Cell Line Encyclopedia also expressed higher levels of ERV RNA. In engineered human melanoma cells, Z18trunc enhanced ERV RNA accumulation more than loss of one Z18 copy, indicating dominant negative activity. Z18trunc directly bound and stabilized ERV RNA. Notably, expression of ERV RNA was sufficient to expedite oncogenesis in a zebrafish model, which is the first evidence of which we are aware that ERV transcripts can play a functional role in cancer. Our work illuminates a mechanism for elevated ERV transcripts in cancer and supports that aberrant RNA accumulation is broadly oncogenic.

cancer biology↗

bioRxiv2024

Specific oncogene activation of the cell of origin in mucosal melanoma

Mucosal melanoma (MM) is a deadly cancer derived from mucosal melanocytes. To test the consequences of MM genetics, we developed a zebrafish model in which all melanocytes experienced CCND1 expression and loss of PTEN and TP53. Surprisingly, melanoma only developed from melanocytes lining internal organs, analogous to the location of patient MM. We found that zebrafish MMs had a unique chromatin landscape from cutaneous melanoma. Internal melanocytes could be labeled using a MM-specific transcriptional enhancer. Normal zebrafish internal melanocytes shared a gene expression signature with MMs. Patient and zebrafish MMs have increased migratory neural crest gene and decreased antigen presentation gene expression, consistent with the increased metastatic behavior and decreased immunotherapy sensitivity of MM. Our work suggests the cell state of the originating melanocyte influences the behavior of derived melanomas. Our animal model phenotypically and transcriptionally mimics patient tumors, allowing this model to be used for MM therapeutic discovery.

cancer biology↗

bioRxiv2023

Systems analysis of multiple diabetes-helminth cohorts reveals markers of disease-disease interaction

Understanding how the molecules in our body respond to the co-occurrence of two diseases in an individual (comorbidity) could lead to mechanistic insights into novel treatments for comorbid conditions. Studies have shown for instance that responses of our immune system to comorbid conditions could be more complex than the union of immune responses to each disease occurring separately, but a data-driven quantification of this complexity is lacking. In this study, we present a systematic methodology to quantify the interaction effect of two diseases on marker variables of interest (using a chronic inflammatory disease diabetes and parasitic infection helminth as illustrative disease pairs to identify cytokines or other immune markers that respond distinctively under a comorbid condition). To perform this systematic comorbidity analysis, we (i) collected and preprocessed data measurements from multiple single- and double-disease cohorts, (ii) extended differential expression analysis of such data to identify disease-disease interaction (DDI) markers (such as cytokines that respond antagonistically or synergistically to the double-disease condition relative to single-disease states), and (iii) interpreted the resulting DDI markers in the context of prior cytokine/immune-cell knowledgebases. We applied this three-step DDI methodology to multiple cohorts of helminth and diabetes (specifically, helminth-infected and helminth-treated individuals in diabetic and non-diabetic conditions, and non-disease control individuals), and identified cytokines such as IFN-{gamma}, TNF-, and IL-2 to be DDI markers acting at the interface of both diseases in data collected prior to helminth treatment. Validating our expectations, for these cytokines and other T helper Th-2 cytokines like IL-13 and IL-4, their DDI statuses were lost after treatment for helminth infection. For instance, the relative contribution of the DDI term in explaining the individual-to-individual variation of IFN-{gamma} and TNF- cytokines were 67.68% and 48.88% respectively before anthelmintics treatment and dropped to 6.09% and 14.56% respectively after treatment. Furthermore, signaling pathways like IL-10 and IL-4/IL-13 were found to be significantly enriched for genes targeted by certain DDI markers, thereby suggesting mechanistic hypotheses on how these DDI markers influence both diseases. Our results quantified the extent of helminth-diabetes DDI exhibited by various tested cytokine markers, and thereby delineated their role in the pathogenesis of both diseases. These results are promising and encourage the application of our DDI methodology (https://github.com/BIRDSgroup/DDI) to dissect the interaction between any two diseases, provided multi-cohort measurements of markers are available.

systems biology↗

bioRxiv2023

Neutrophil-derived IL-17 limits protective host responses and promotes tuberculosis pathogenesis

The protective correlates of Mycobacterium tuberculosis (Mtb) infection-elicited host immune responses are incompletely understood. Here, we report pro-pathogenic crosstalk involving Ly6G+granulocytes (Ly6G+Gra), IL-17 and COX2. We show that in the lungs of Mtb-infected wildtype mice, either BCG-vaccinated or not, most intracellular bacilli are Ly6G+Gra-resident four weeks post-infection onwards. In the genetically susceptible IFN{psi} -/- mice, excessive Ly6G+Gra infiltration correlates with severe bacteraemia. Neutralizing IL-17 (anti-IL17mAb) and COX2 inhibition by celecoxib reverse Ly6G+Gra infiltration, associated pathology and death in IFN{psi} -/- mice. Surprisingly, Ly6G+Gra also serves as the major source of IL-17 in the lungs of Mtb-infected WT or IFN{psi} -/- mice. The IL-17-COX2-Ly6G+Gra interplay also operates in WT mice. Inhibiting ROR{psi}t, the key transcription factor for IL-17 production or COX2, reduces the bacterial burden in Ly6G+Gra, leading to reduced bacterial burden and pathology in the lungs of WT mice. In the Mtb-infected WT mice, COX2 inhibition abrogates IL-17 levels in the lung homogenates and significantly enhances BCGs protective efficacy, mainly by targeting the Ly6G+Gra-resident Mtb pool, a phenotype also observed when IL-17 is blocked by ROR{psi}t inhibitor. Furthermore, in pulmonary TB patients, high neutrophil count and IL-17 correlated with adverse treatment outcomes. Together, our results suggest that IL-17 and PGE2 are the negative correlates of protection, and we propose targeting the pro-pathogenic IL-17-COX2-Ly6G+Gra axis for TB prevention and therapy.

immunology↗

bioRxiv2023

Rice WRKY13 TF protein binds to motifs in the promoter region to regulate downstream disease resistance-related genes

In plants, pathogen resistance is brought about due to the binding of certain transcription factors (TF) proteins to the cis-elements of certain target genes. These cis-elements are present up-stream in the motif of the promoters of each gene. This ensures the binding of a specific transcription factor to a specific promoter, therefore regulating the expression of that gene. Therefore, the study of each promoter sequence of all the rice genes would help identify the target genes of a specific transcription factor. Rice 1kb upstream promoter sequences of 55,986 annotated genes were analyzed using the Perl program algorithm to detect WRKY13 binding motifs (bm). The resulting genes were grouped using gene ontology and gene set enrichment analysis. Gene with more than 4 TFbm in their promoter was selected. Nine genes reported to have a role in rice disease resistance were selected for further analysis. Cis-acting regulatory element analysis was carried out to find the cis-elements and to confirm the presence of the corresponding motifs in the promoter sequences of these genes. The 3D structure of WRKY13 TF and the corresponding nine genes were built and the interacting residues were determined. The binding capacity of WRKY13 to the promoter of these selected genes was analyzed using docking studies. WRKY13 was also considered for docking analysis based on the prior reports of autoregulation. Molecular dynamic simulations provided more details regarding the interactions. Expression data revealed the expression of the genes that helped to provide the mechanism of interaction. Further co-expression network helped to characterize the interaction of these selected diseases resistance-related genes with WRKY13 TF protein. This study suggests the target downstream genes that are regulated by WRKY13 TF. The molecular mechanism involving the gene network regulated by WRKY13 TF in disease resistance against rice fungal pathogens is explored.

plant biology↗

bioRxiv2021

Quantifying the Invasive Secondary Metabolome

Invasive plants drive ecosystem degradation through developing aggressive phenotypes that can outcompete native flora. Several hypotheses explain this, like the Evolution of Increased Competitive Ability hypothesis and the Novel Weapons Hypothesis, but none have been proven conclusively. Changes in plant metabolites are critical to these hypotheses, but complete invasive secondary metabolomes have not been quantified. Here, statistical and unsupervised machine-learning approaches were used to analyse chemotype-to-phenotype relationships in invasive and non-invasive populations in species Ageratum conyzoides, Lantana camara, Melaleuca quinquenervia and Psidium cattleainum and on a family level analysing Asteraceae, Myrtaceae and Verbenaceae. Invasive metabolomes evolved according to the EICA and NWH, involving optimisation of aggressive strategies present in native populations and local adaptation. O_FIG O_LINKSMALLFIG WIDTH=135 HEIGHT=200 SRC="FIGDIR/small/471125v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@1bd2d02org.highwire.dtl.DTLVardef@d5e660org.highwire.dtl.DTLVardef@107d008org.highwire.dtl.DTLVardef@1eaf62a_HPS_FORMAT_FIGEXP M_FIG C_FIG

plant biology↗

bioRxiv2021

Banp regulates DNA damage response and chromosome segregation during the cell cycle in zebrafish retina

Btg3-associated nuclear protein (Banp) was originally identified as a nuclear matrix-associated region (MAR)-binding protein and it functions as a tumor suppressor. At the molecular level, Banp regulates transcription of metabolic genes via a CGCG-containing motif called the Banp motif. However, its physiological roles in embryonic development are unknown. Here we report that Banp is indispensable for the DNA damage response and chromosome segregation during mitosis. Zebrafish banp mutants show mitotic cell accumulation and apoptosis in developing retina. We found that DNA replication stress and tp53-dependent DNA damage responses were activated to induce apoptosis in banp mutants, suggesting that Banp is required for regulation of DNA replication and DNA damage repair. Furthermore, consistent with mitotic cell accumulation, chromosome segregation was not smoothly processed from prometaphase to anaphase in banp morphants, leading to a prolonged M-phase. Our RNA- and ATAC-sequencing identified 31 candidates for direct Banp target genes that carry the Banp motif. Interestingly, a DNA replication fork regulator, wrnip1, and two chromosome segregation regulators, cenpt and ncapg, are included in this list. Thus, Banp directly regulates transcription of wrnip1 for recovery from DNA replication stress, and cenpt and ncapg for chromosome segregation during mitosis. Our findings provide the first in vivo evidence that Banp is required for cell-cycle progression and cell survival by regulating DNA damage responses and chromosome segregation during mitosis.

cell biology↗

bioRxiv2021

Dry heat sterilization as a method to recycle N95 respirator masks: the importance of fit

In times of crisis, including the current COVID-19 pandemic, the supply chain of filtering facepiece respirators, such as N95 respirators, are disrupted. To combat shortages of N95 respirators, many institutions were forced to decontaminate and reuse respirators. While several reports have evaluated the impact on filtration as a measurement of preservation of respirator function after decontamination, the equally important fact of maintaining proper fit to the users face has been understudied. In the current study, we demonstrate the complete inactivation of SARS-CoV-2 and preservation of fit test performance of N95 respirators following treatment with dry heat. We apply scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM/EDS), X-ray diffraction (XRD) measurements, Raman spectroscopy, and contact angle measurements to analyze filter material changes as a consequence of different decontamination treatments. We further compared the integrity of the respirator after autoclaving versus dry heat treatment via quantitative fit testing and found that autoclaving, but not dry heat, causes the fit of the respirator onto the users face to fail, thereby rendering the decontaminated respirator unusable. Our findings highlight the importance to account for both efficacy of disinfection and mask fit when reprocessing respirators to for clinical redeployment.

scientific communication and education↗

bioRxiv2020

Inhibition of phosphodiesterase - 10A by Papaverine protects human cortical neurons from quinolinic acid-induced oxidative stress and synaptic proteins alterations

Phosphodi esterase-10A (PDE10A) hydrolyse the secondary messengers cGMP and cAMP which play critical role in neurodevelopment and brain functions. PDE10A is linked to progression of neurodegenerative diseases like Alzheimers, Parkinsons, Huntingtons diseases etc and a critical role in cognitive functions. The present study was undertaken to determine the possible neuroprotective effects and the associated mechanism of papaverine (PAP) against quinolinic acid (QUIN) induced excitotoxicity using human primary cortical neurons. Cytotoxicity potential of PAP was analysed using MTS assay. Reactive oxygen species (ROS) and mitochondrial membrane potential were measured by DCF-DA and JC10 staining, respectively. Caspase 3/7 and cAMP levels using ELISA kits. Effect of PAP on the CREB, BNDF and synaptic proteins such as SAP-97, synaptophysin, synapsin-I, PSD-95 expression was analysed by Western blotting technique. Pre-treatment with PAP increased intracellular cAMP and nicotinamide adenine dinucleotide (NAD+) levels, restored mitochondrial membrane potential ({Delta}{Psi}m), and decreased ROS and caspase3/7 content in QUIN exposed neurons. PAP up-regulated CREB and BDNF, and synaptic proteins expression. In summary, these data indicate that PDE10A involves in QUIN mediated neurotoxicity and its inhibition can elicit neuroprotection by reducing the oxidative stress and protecting synaptic proteins via upregulation of cAMP signalling cascade.

neuroscience↗

bioRxiv2020

Ultra-high field (7T) functional magnetic resonance imaging in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the central nervous system that results in a progressive loss of motor function and ultimately death. It is critical, yet also challenging, to develop non-invasive biomarkers to identify, localize, measure and/or track biological mechanisms implicated in ALS. Such biomarkers may also provide clues to identify potential molecular targets for future therapeutic trials. Herein we report on a pilot study involving twelve participants with ALS and nine age-matched healthy controls who underwent high-resolution resting state functional magnetic resonance imaging at an ultra-high field of 7 Tesla. A group-level whole-brain analysis revealed a disruption in long-range functional connectivity between the superior sensorimotor cortex (in the precentral gyrus) and bilateral cerebellar lobule VI. Post hoc analyses using atlas-derived left and right cerebellar lobule VI revealed decreased functional connectivity in ALS participants that predominantly mapped to bilateral postcentral and precentral gyri. Cerebellar lobule VI is a transition zone between anterior motor networks and posterior non-motor networks in the cerebellum, and is associated with a wide range of key functions including complex motor and cognitive processing tasks. Our observation of the involvement of cerebellar lobule VI adds to the growing number of studies implicating the cerebellum in ALS. Future avenues of scientific investigation should consider how high-resolution imaging at 7T may be leveraged to visualize differences in functional connectivity disturbances in various genotypes and phenotypes of ALS along the ALS-frontotemporal dementia spectrum.

neuroscience↗

bioRxiv2020

Decision Support Systems based on Scientific Evidence: Bibliometric Networks of Invasive Lantana camara.

Extraction and analysis of useful knowledge from the vast amount of relevant published literature can add valuable insights to any research theme or area of interest. We introduce a simplified bibliometric data analysis protocol for gaining substantial insights into research thematics, which can also serve as a handy practical skill for researchers, while working from home. In this paper, we provide ways of developing a holistic research strategy using bibliometric-data driven approaches that integrate network analysis and information management, without the need of full paper access. This protocol is a comprehensive multi-modular pathway for analysis of metadata obtained from major scientific publishing houses by use of a Decision Support System (DSS). A simple case study on the invasive species Lantana camara has been presented as a proof-of-concept to show how one can implement this DSS based protocol. Some perspectives are also provided on how the outcomes can be used directly or scaled up for long term research interventions. We hope that this work will simplify exploratory literature review, and enable rational design of research objectives for scholars, as well as development of comprehensive grant proposals that address gaps in research.

scientific communication and education↗