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Nandi, N.

Publications and source records attributed to Nandi, N..

5 recordsLinked to original sources

Exploring recurrent urinary tract infection: paired microbiota and culture-based profiling reveals stable dysbiosis and multidrug-resistant, virulence-enriched uropathogens

**Objectives:** Recurrent urinary tract infection (rUTI) is increasingly complicated by antimicrobial resistance (AMR), yet urinary microbiome dysbiosis and isolate-level resistance-virulence are rarely examined together across different treatment states. In this study, we characterized both within the same sample in rUTI and in healthy controls. **Methods:** In this cross-sectional cohort, mid-stream urine was collected from women with untreated, treated and prophylaxis rUTI and age-matched healthy controls at four centres in South India. Of 80 samples collected, 75 were analysed (26 controls, 20 untreated, 20 treated, 9 prophylaxis) by 16S rRNA V3-V4 sequencing. In addition, 105 culturable isolates from the same samples were identified and tested for antimicrobial susceptibility (VITEK 2) and phenotypic virulence. **Results:** rUTI groups showed approximately half the alpha diversity of controls (median Shannon 1.07-1.18 vs 2.17; Kruskal-Wallis p = 0.041). Community structure differed from controls in every rUTI subgroup (PERMANOVA R-squared = 0.091, p = 0.004; pairwise FDR = 0.008) but not among subgroups. Mean Lactobacillus relative abundance fell from 29.2% in controls to <=13.2% in rUTI groups, while Escherichia-Shigella rose from 7.2% to 25.0-43.0%. Control-referenced dysbiosis z-scores were elevated in all rUTI groups (community distance: FDR <= 0.003; uropathogen: Lactobacillus index: FDR < 0.001 for treated and prophylaxis groups). Among isolates, Escherichia coli predominated (35/105; 16/35, 45.7% multidrug-resistant), followed by Klebsiella spp. (32% multidrug-resistant); carbapenem susceptibility was largely retained, and multidrug-resistant E. coli co-carried more virulence traits. **Conclusions:** rUTI is associated with a stable dysbiotic state that treatment does not restore, combining Lactobacillus loss and uropathogen dominance with a multidrug-resistant culturable reservoir that co-accumulates virulence traits. Reading the community and its isolates together may support microbiome-sparing, resistance-aware management of rUTI.

microbiology↗

Area- and Layer-Specific Organization of Multimodal Timescales in Macaque Motor Cortex

Hierarchy in the brain emerges across spatial and temporal scales, enabling transformations from rapid sensory encoding to sustained cognitive control, and this organization is well established in sensory systems. In contrast, the hierarchical organization of the primate motor cortex remains debated, partly due to its agranular architecture and the absence of clear layer-constrained input-output projections. In particular, the relative hierarchical position of the dorsal premotor cortex (PMd) and the primary motor cortex (M1) cannot be resolved from anatomy alone. To investigate their relative organization, we adopted a unique multimodal approach using timescales derived from both single-unit spiking activity (SUA) and local field potentials (LFPs) in macaques performing a delayed-match-to-sample reaching task. We found convergent evidence for inter-areal temporal organization, with longer SUA timescales and smaller LFP aperiodic spectral exponents in M1. Across cortical depth, however, temporal dynamics depended on signal modality. LFP autocorrelation timescales were systematically longer in deep layers of M1, and this was accompanied by smaller LFP spectral exponents in deep layers in both areas. In contrast, SUA did not show significant laminar differences in timescales. Functionally, neurons with longer timescales exhibited more stable representations of the movement direction during movement preparation in PMd and broader temporal generalization during execution in both areas. Our results place M1 above PMd in the temporal hierarchy, and provide the first laminar characterization of SUA timescales in any cortical area. The divergence in laminar temporal organization between SUA and LFP possibly reflects their different physiological origins. Extracellular spikes capture neuronal output near the cell body, whereas LFPs primarily reflect synaptic population activity, potentially exhibiting layer differences in integration of apical and basal dendritic inputs. HighlightsSUA and LFP-derived temporal dynamics place M1 above PMd in the cortical hierarchy SUA shows no laminar differences in temporal dynamics LFP exhibits significant layer-dependent temporal differences Longer SUA timescales link to slower movement encoding dynamics

neuroscience↗

Alpha and SSVEP power outperforms Gamma power in capturing Attentional Modulation in Human EEG

The effect of visual attention has been extensively studied using various techniques such as macaque neurophysiology that yields spikes and local field potential (LFP), and human electro/magneto encephalogram (EEG/MEG). Attention typically suppresses power at low frequencies such as alpha band (8-12 Hz) and increases power in gamma band (>30 Hz) in brain signals. In addition, EEG studies often use flickering stimuli that produce a specific measure called steady-state visually evoked potential (SSVEP), whose power also increases with attention. However, effectiveness of these various neural measures in capturing attentional modulation is unknown since the stimuli and task paradigms vary widely across these studies. In a recent macaque neurophysiology study with flickering stimuli, we found that the effect of attention was more salient in the gamma band and beyond of the LFP, compared to alpha or SSVEP. To compare this with human EEG, we designed an orientation change detection task where we presented both static and counterphasing stimuli of matched difficulty levels to male (N=15) and female (N=11) subjects, allowing us to compare attentional modulation of various measures under similar conditions. We report two main results. First, attentional modulation was comparable for SSVEP and alpha. Second, non-foveal stimuli produced weak gamma despite various stimulus optimizations and showed a negligible effect of attention although full-screen gratings showed robust gamma activity. Our results are useful for brain-machine-interfacing studies where suitable features depending on recording modality are used for decoding attention, and also provide clues about the spatial scales of neural mechanisms underlying attention. Significance StatementVarious neural measures such as alpha and gamma band power or SSVEP power capture signatures of visual attention. A systematic comparison of their effectiveness in capturing attentional modulation is important for understanding different neural computations underlying attention and for developing brain-machine-interfaces (BMIs) that can decode the focus of attention. Since stimulus configuration and task paradigms vary widely across visual attention studies, we recorded all the relevant neural signals during an attention task under similar stimulus and behavioral conditions in human EEG. In contrast to invasive recordings in which gamma outperforms other measures, our results show that in human EEG, attentional modulation of alpha and SSVEP are comparable, and non-foveal stimuli produce weak gamma which is not well modulated by attention.

neuroscience↗

A phospho-switch at Acinus-Serine437 controls autophagic responses to cadmium exposure and neurodegenerative stress

Neuronal health depends on quality control functions of autophagy, but mechanisms regulating neuronal autophagy are poorly understood. Previously, we showed that in Drosophila starvation-independent quality control autophagy is regulated by Acinus and the Cdk5-dependent phosphorylation of its serine437 (Nandi et al., 2017). Here, we identify the phosphatase that counterbalances this activity and provides for the dynamic nature of Acinus-S437 phosphorylation. A genetic screen identified six phosphatases that genetically interacted with an Acinus gain-of-function model. Among these, loss of function of only one, the PPM-type phosphatase Nil (CG6036), enhanced pS437-Acinus levels. Cdk5-dependent phosphorylation of Acinus serine437 in nil1 animals elevates neuronal autophagy and reduces the accumulation of polyQ proteins in a Drosophila Huntingtons disease model. Consistent with previous findings that Cd2+ inhibits PPM-type phosphatases, Cd2+-exposure elevated Acinus-serine437 phosphorylation which was necessary for increased neuronal autophagy and protection against Cd2+-induced cytotoxicity. Together, our data establish the Acinus- S437 phospho-switch as critical integrator of multiple stress signals regulating neuronal autophagy.

cell biology↗

Inorganic salts and compatible solutes help mesophilic bacteria inhabit the high temperature waters of a Trans-Himalayan sulfur-borax spring

While geographically-/geologically-distinct hot springs harbor different levels of microbial diversity, some of them encompass several such taxa which have no strain reported for laboratory growth at >45{degrees}C. We, therefore, hypothesized that native geomicrobial factors could be potent determinants of the microbial habitability of hot spring environments. To test this hypothesis, aquatic microbial communities were revealed metataxonomically, and considered in the context of spring-water chemistry, along the 85-14{degrees}C hydrothermal gradient of a sulfur-boron spring named Lotus Pond located at 4,436 m, within the Puga geothermal area of the Indian Trans-Himalayan region of Ladakh. Water samples were studied from four distinct sites along Lotus Ponds spring-water transit from the vent to an adjacent river called Rulang. Insinuations obtained from geomicrobiological data were tested via pure-culture growth experiments in habitat-inspired media. Microbial diversities were found to be high at all the sample-sites; majority of the genera identified at the 70-85{degrees}C sites were found to have no report of laboratory growth at >45{degrees}C; concurrently, these sample-sites had high concentrations of the kosmotropic solutes boron, lithium, sodium, sulfide, thiosulfate and sulfate, which are known to biophysically stabilize macromolecules. Based on the universal thermodynamic status of these solutes, we conjectured that they may be instrumental in helping mesophiles withstand high in situ temperatures. Corroboratively, growth experiments with a mesophilic, 80{degrees}C-isolate, Paracoccus SMMA_5 showed that at 50{degrees}C and 70{degrees}C, depending on the incubation-time, lithium/boron/sulfate/sodium/glycine-betaine either increases the number of colony-forming units present in the culture or arrests decline of the same. Incubations at 70{degrees}C, followed by fluorescein diacetate staining and flow cytometry, showed that these solutes keep more cells under viable condition than in ready-to-divide state. We concluded that kosmotropes and compatible solutes help mesophiles overcome the chaotropic effects of heat by augmenting such indigenous, entropy-minimizing biophysical mechanisms that apparently trade-off cell division for cell viability.

microbiology↗