Biology subjects

Mukherjee, A.

Publications and source records attributed to Mukherjee, A..

6 recordsLinked to original sources

bioRxiv2026

Feasibility of adopting water displacement and 3D scanning methods to quantify lung volume reduction in ex vivo models

Lung volume reduction is a treatment for chronic obstructive pulmonary disease (COPD) patients with severe emphysema. Currently, in vivo animal models are used as a first step to quantify the efficiency of novel lung volume reduction treatments. By quantifying lung volume reduction in ex vivo samples, animal testing may be reduced. This study proposes two new methods for quantifying lung volume reduction in ex vivo tissue: water displacement and three-dimensional (3D) scanning. Porcine lung lobes were inflated and treated with cyanoacrylate glue to simulate lung volume reduction. Volume changes were measured using a custom water displacement setup and in a ventilated setting using a handheld Artec Space Spider 3D surface scanner. Both techniques detected post-treatment volume reductions. Water displacement offers a simple, cost-effective approach for isolated lung lobes, while 3D scanning enables volumetric analysis of intact lungs under ventilated conditions. These methods provide a reliable intermediate step between in vitro and in vivo testing, reducing animal use and improving preclinical assessment of novel lung volume altering interventions.

bioengineering↗

bioRxiv2018

Cell-intrinsic genetic regulation of peripheral memory-phenotype T cell frequencies

Memory T and B lymphocyte numbers are thought to be regulated by recent and cumulative microbial exposures. We report here that memory-phenotype lymphocyte frequencies in B, CD4 and CD8 T-cells in 3-monthly serial bleeds from healthy young adult humans were relatively stable over a 1-year period, while recently activated -B and -CD4 T cell frequencies were not, suggesting that recent environmental exposures affected steady state levels of recently activated but not of memory lymphocyte subsets. Frequencies of memory B and CD4 T cells were not correlated, suggesting that variation in them was unlikely to be determined by cumulative antigenic exposures. Immunophenotyping of adult siblings showed high concordance in memory, but not of recently activated lymphocyte subsets, suggesting genetic regulation of memory lymphocyte frequencies. To explore this possibility further, we screened effector memory (EM)-phenotype T cell frequencies in common independent inbred mice strains. Using two pairs from these strains that differed predominantly in either CD4EM and/or CD8EM frequencies, we constructed bi-parental bone marrow chimeras in F1 recipient mice, and found that memory T cell frequencies in recipient mice were determined by donor genotypes. Together, these data suggest cell-autonomous determination of memory T niche size, and suggest mechanisms maintaining immune variability.

immunology↗

bioRxiv2018

Hmgcr promotes a long-range signal to attract germ cells which is aided by Wunens but independent of hh

Summary StatementMigrating Drosophila germ cells are attracted by a long range Hmgcr mediated signal which is aided and acts simultaneously with Wunens suggesting that these pathways converge on a single chemoattractant.\n\nAbstractIn a developing embryo, many cell types migrate from their point of specification to their final position. This usually involves highly stereotyped routes which are determined through deployment of cell surface or secreted guidance molecules. Whilst genetic techniques have been successful in identifying these molecules, the distances over which such signals operate in their native context can be difficult to determine. Here we have quantified the range of an attractive signal for the migration of Drosophila germ cells. Their migration is guided by an attractive signal generated by the expression of genes in the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (Hmgcr) pathway, and by a repulsive signal generated by the expression of Wunens. We demonstrate that the attractive signal downstream of Hmgcr operates over a long range and is sufficient to reach germ cells for the entirety of their migration. Furthermore, Hmgcr-mediated attraction and Wunen-mediated repulsion can operate simultaneously ruling out a model in which these pathways operate consecutively. Indeed, we show that Hmgcr-mediated attraction is boosted by Wunens suggesting the action of these two pathways is linked. Lastly, several papers have pointed to the secreted molecule Hedgehog (Hh) as being the germ cell attractant, whose secretion is increased by hmgcr. In this paper, we provide evidence that Hh is not downstream of hmgcr in germ cell migration.

developmental biology↗

bioRxiv2017

Neurexin and Neuroligin-based adhesion complexes drive axonal arborisation growth independent of synaptic activity

Building arborisations of the right size and shape is fundamental for neural network function. Live imaging studies in vertebrate brains strongly suggest that nascent synapses are critical for branch growth during the development of axonal and dendritic arborisations. The molecular mechanisms underlying such synaptotropic events are largely unknown.\n\nHere we present a novel system in Drosophila for studying the development of complex axonal arborisations live, in vivo during metamorphosis. In these growing axonal arborisations we see a relationship between the punctate localisations of presynaptic components and branch dynamics that is very similar to synaptotropic growth described in fish and frogs. These presynaptic components however do not appear to represent functional presynaptic release sites and are not paired with clusters of neurotransmitter receptors. Pharmacological and genetic knockdowns of evoked and spontaneous neurotransmission do not impact the outgrowth of these neurons. Instead, we find that axonal branch growth is regulated by the dynamic focal localisations of synaptic adhesion proteins Neurexin and Neuroligin. These adhesion complexes provide selective stability for filopodia by a stick and grow-based mechanism wholly independent of synaptic activity.

neuroscience↗

bioRxiv2016

Metagenomic Characteristics of Bacterial Response to Petroleum Hydrocarbon Contamination in Diverse Environments as Revealed by Functional Taxonomic Strategies

Microbial remediation of oil polluted habitats remains one of the foremost methods for restoration of petroleum hydrocarbon contaminated environments. The development of effective bioremediation strategies however, require an extensive understanding of the resident microbiome of these habitats. Recent developments such as high-throughput sequencing has greatly facilitated the advancement of microbial ecological studies in oil polluted habitats. However, effective interpretation of biological characteristics from these large datasets remains a considerable challenge. In this study, we have implemented recently developed bioinformatic tools for analyzing 65 publicly available 16S rRNA datasets from 12 diverse hydrocarbon polluted habitats to decipher metagenomic characteristics of bacterial communities of the same. We have comprehensively described phylogenetic and functional compositions of these habitats and additionally inferred a multitude of metagenomic features including 255 taxa and 414 functional modules which can be used as biomarkers for effective distinction between the 12 oil polluted sites. We have identified essential metabolic signatures and also showed that significantly over-represented taxa often contribute to either or both, hydrocarbon degradation and additional important functions. Our findings reveal significant differences between hydrocarbon contaminated sites and establishes the importance of endemic factors in addition to petroleum hydrocarbons as driving factors for sculpting hydrocarbon contaminated bacteriomes.

microbiology↗

bioRxiv2016

Reactive Oxygen Species Regulate Activity-Dependent Neuronal Structural Plasticity

Neurons are inherently plastic, adjusting their structure, connectivity and excitability in response to changes in activity. How neurons sense changes in their activity level and then transduce these to structural changes remains to be fully elucidated. Working with the Drosophila larval locomotor network, we show that neurons use reactive oxygen species (ROS), metabolic byproducts, to monitor their activity. ROS signals are both necessary and sufficient for activity-dependent structural adjustments of both pre- and postsynaptic terminals and for network output, as measured by larval crawling behavior. We find the highly conserved Parkinsons disease-linked protein DJ-1{beta} acts as a redox sensor in neurons where it regulates pre- and postsynaptic structural plasticity, in part via modulation of the PTEN-PI3Kinase pathway. Neuronal ROS thus play an important physiological role as second messengers required for neuronal and network tuning, whose dysregulation in the ageing brain and under neurodegenerative conditions may contribute to synaptic dysfunction.

neuroscience↗