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Results for “Physiology”

Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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At least 73 records · Page 4Linked to original sources

bioRxiv2017

Bacterial physiological adaptations to contrasting edaphic conditions identified using landscape scale metagenomics

Environmental factors relating to soil pH are widely known to be important in structuring soil bacterial communities, yet the relationship between taxonomic community composition and functional diversity remains to be determined. Here, we analyze geographically distributed soils spanning a wide pH gradient and assess the functional gene capacity within those communities using whole genome metagenomics. Low pH soils consistently had fewer taxa (lower alpha and gamma diversity), but only marginal reductions in functional alpha diversity and equivalent functional gamma diversity. However, coherent changes in the relative abundances of annotated genes between pH classes were identified; with functional profiles clustering according to pH independent of geography. Differences in gene abundances were found to reflect survival and nutrient acquisition strategies, with organic-rich acidic soils harboring a greater abundance of cation efflux pumps, C and N direct fixation systems and fermentation pathways indicative of anaerobiosis. Conversely, high pH soils possessed more direct transporter-mediated mechanisms for organic C and N substrate acquisition. These findings show that bacterial functional versatility may not be constrained by taxonomy, and we further identify the range of physiological adaptations required to exist in soils of varying nutrient availability and edaphic conditions.

microbiology↗

bioRxiv2017

Physiological Preparation Of Hair Cells From The Sacculus Of The American Bullfrog (Rana catesbeiana)

SHORT ABSTRACTThe American bullfrogs sacculus permits direct examination of hair-cell physiology. Here we describe the dissection and preparation of the bullfrogs sacculus for biophysical studies. We show representative experiments from these hair cells, including the calculation of a bundles force-displacement relation and measurement of its spontaneous motion.\n\nLONG ABSTRACTThe study of hearing and balance rests upon insights drawn from biophysical studies of model systems. One such model, the sacculus of the American bullfrog, has become a mainstay of auditory and vestibular research. Studies of this organ have revealed how sensory cells--hair cells--can actively detect signals from the environment. Because of these studies, we now better understand the mechanical gating and localization of a hair cells transduction channels, calciums role in mechanical adaptation, and the identity of hair-cell currents. This highly accessible organ continues to provide insight into the workings of hair cells.\n\nHere we describe the preparation of the bullfrogs sacculus for biophysical studies on its hair cells. We include the complete dissection procedure and provide specific protocols for the preparation of the sacculus in specific contexts. We additionally include representative results using this preparation, including the calculation of a hair bundles force-displacement relation and measurement of a bundles spontaneous motion.

biophysics↗

bioRxiv2017

Mitochondria Are Physiologically Maintained At Close To 50 C

In endothermic species, heat released as a product of metabolism ensures stable internal temperature throughout the organism, despite varying environmental conditions. Mitochondria are major actors in this thermogenic process. Part of the energy released by the oxidation of respiratory substrates drives ATP synthesis and metabolite transport, while a noticeable proportion is released as heat. Using a temperature-sensitive fluorescent probe targeted to mitochondria, we measured mitochondrial temperature in situ under different physiological conditions. At a constant external temperature of 38 {degrees}C, mitochondria were more than 10 {degrees}C warmer when the respiratory chain was fully functional, both in HEK293cells and primary skin fibroblasts. This differential was abolished in cells lacking mitochondrial DNA or by respiratory inhibitors, but preserved or enhanced by expressing thermogenic enzymes such as the alternative oxidase or the uncoupling protein 1. The activity of various RC enzymes was maximal at, or slightly above, 50 {degrees}C. Our study prompts a re-examination of the literature on mitochondria, taking account of the inferred high temperature.

cell biology↗

bioRxiv2017

Physiological Assembly Of Functionally Active 30S Ribosomal Subunits From In Vitro Synthesized Parts

Synthetic ribosomes in vitro can facilitate engineering translation of novel polymers, identifying ribosome biogenesis central components, and paving the road to constructing replicating systems from defined biochemical components. Here, we report functional synthetic Escherichia coli 30S ribosomal subunits constructed using a defined, purified cell free system under physiological conditions. We test hypotheses about key components of natural ribosome biogenesis pathway as required for efficient function - including integration of 16S rRNA modification, cofactors facilitated ribosome assembly and protein synthesis in the same compartment in vitro. We observe ~17% efficiency for fully synthetic 30S and ~70% efficiency from in vitro transcribed 16S rRNA assembled with natural proteins. We observe up to 5 fold improvement over previous crude extracts. We suggest extending the minimal list of components required for central-dogma replication from the 151 gene products previously reported to at least 180 to allow the speed and accuracy of macromolecular synthesis to approach native E. coli values.

biochemistry↗

bioRxiv2017

Aminoglycoside Antibiotics Perturb Physiologically Important MicroRNA Contributing To Drug Toxicity

miRNAs are key non-protein coding regulators of gene expression in various pathophysiological conditions. Targeting miRNA with small molecules offer an unconventional approach, where clinically active compounds with RNA binding activity can be tested for their ability to modulate miRNA levels and thus for drug repositioning. Aminoglycoside antibiotics are highly effective microbicidal RNA binding molecules that bind to prokaryotic rRNA secondary structures. Here, we report that specific subsets of miRNA can be modulated by aminoglycosides. However, ototoxicity (cochlear and vestibular) and nephrotoxicity of multiple origins resulting from prolonged use are a well-known disadvantage of aminoglycosides. Mature non-coding RNAs and their precursors can present off-target sites, by forming secondary structures that resemble ribosomal RNA, thus providing an additional molecular basis for the toxicity of aminoglycosides. Using in vitro, in cellulae and physiological responses, we provide evidence for the direct functional perturbation of the miR- 96 cluster leading to selective cell death in neuromasts- the zebrafish equivalent of cochlear hair cells, by Streptomycin, a prototype aminoglycoside antibiotic, thus contributing to the observed ototoxicity. Our observations, collectively underscore the importance of re- evaluating RNA binding drugs for their off-targeting effects in the context of miRNA and other functional non-coding RNA.

cell biology↗

bioRxiv2017

Physiological tolerance of the early life history stages of fresh water prawn (Macrobrachium rosenbergii De Man, 1879) to environmental stress

Global climate change is transforming life on earth, causing widespread effects on all ecosystems. Among marine ecosystems, estuaries are considered as nursery grounds for marine and fresh water species. M. rosenbergii, a euryhaline species, migrate to the estuaries for breeding and spawning. The subsequent larval rearing takes place by experiencing variations in temperature and salinity conditions. The present study examines the effect of different temperature and salinity on the larval development and survival by observations on stored yolk utilization, cardiac performance, as well as changes in the rate of growth in body appendages and larval activity. The larvae showed 100% mortality at higher temperature (33.5 {+/-} 0.5 {degrees}C) in all the salinity conditions (12 PPT, 15 PPT, and 20 PPT). The survival rate varied between 76-96 % on exposure to lesser temperature conditions. Likewise, the post-embryonic yolk lasted for 4 days at ambient temperature (29 {degrees}C); whereas, at 33.5 {+/-} 0.5 {degrees}C, it lasted only for 2-3 days. There was an increase in total length of larvae, when exposed to higher temperature and salinity, independently or in combination, but at 33.5 {+/-} 0.5 {degrees}C under all salinity conditions the larvae died on the 5th day. For the cardiac performance, larval heart beat (fH) significantly increased for higher temperature and salinity conditions (20 PPT; 33.5 {degrees}C) and lowered at ambient condition 12 PPT; 29{degrees}C. Larval stroke volume Vs, and Cardiac output Q{square} were higher in ambient conditions and lowest in higher temperature and salinity conditions. However, temperature and salinity together did not show any significant effect on cardiac performance. On the other hand, the larval activity decreased significantly at higher temperature and salinity conditions, compared to ambient conditions but the interactive effect did not show any change. Thus, the physiological responses to temperature and salinity by the early life stages of M. rosenbergii could restrain the tolerance capability of the organism, thereby interfering in the successful completion of the larval development under the altered climatic conditions.

developmental biology↗

bioRxiv2017

Characterization of a set of abdominal neuroendocrine cells that regulate stress physiology using colocalized diuretic peptides in Drosophila

Multiple neuropeptides are known to regulate water and ion balance in Drosophila melanogaster. Several of these peptides also have other functions in physiology and behavior. Examples are corticotropin-releasing factor-like diuretic hormone (diuretic hormone 44; DH44) and leucokinin (LK), both of which induce fluid secretion by Malpighian tubules (MTs), but also regulate stress responses, feeding, circadian activity and other behaviors. Here, we investigated the functional relations between the LK and DH44 signaling systems. DH44 and LK peptides are only colocalized in a set of abdominal neurosecretory cells (ABLKs). Targeted knockdown of each of these peptides in ABLKs leads to increased resistance to desiccation, starvation and ionic stress. Food ingestion is diminished by knockdown of DH44, but not LK, and water retention is increased by LK knockdown only. Thus, the two colocalized peptides display similar systemic actions, but differ with respect to regulation of feeding and body water retention. We also demonstrated that DH44 and LK have additive effects on fluid secretion by MTs. It is likely that the colocalized peptides are coreleased from ABLKs into the circulation and act on the tubules where they target different cell types and signaling systems to regulate diuresis and stress tolerance. Additional targets seem to be specific for each of the two peptides and subserve regulation of feeding and water retention. Our data suggest that the ABLKs and hormonal actions are sufficient for many of the known DH44 and LK functions, and that the remaining neurons in the CNS play other functional roles.

neuroscience↗

bioRxiv2017

Genome downsizing, physiological novelty, and the global dominance of flowering plants

During the Cretaceous (145-66 Ma), early angiosperms rapidly diversified, eventually outcompeting the ferns and gymnosperms previously dominating most ecosystems. Heightened competitive abilities of angiosperms are often attributed to higher rates of transpiration facilitating faster growth. This hypothesis does not explain how angiosperms were able to develop leaves with smaller, but densely packed stomata and highly branched venation networks needed to support increased gas exchange rates. Although genome duplication and reorganization have likely facilitated angiosperm diversification, here we show that genome downsizing facilitated reductions in cell size necessary to construct leaves with a high density stomata and veins. Rapid genome downsizing during the early Cretaceous allowed angiosperms to push the frontiers of anatomical trait space. In contrast, during the same time period ferns and gymnosperms exhibited no such changes in genome size, stomatal size, or vein density. Further reinforcing the effect of genome downsizing on increased gas exchange rates, we found that species employing water-loss limiting crassulacean acid metabolism (CAM) photosynthesis, have significantly larger genomes than C3 and C4 species. By directly affecting cell size and gas exchange capacity, genome downsizing brought actual primary productivity closer to its maximum potential. These results suggest species with small genomes, exhibiting a larger range of final cell size, can more finely tune their leaf physiology to environmental conditions and inhabit a broader range of habitats.

ecology↗

bioRxiv2017

Correlation of gene expressions between nucleus and cytoplasm reflects single-cell physiology

BackgroundEukaryotes transcribe RNAs in nuclei and transport them to the cytoplasm through multiple steps of post-transcriptional regulation. Existing single-cell sequencing technologies, however, are unable to analyse nuclear (nuc) and cytoplasmic (cyt) RNAs separately and simultaneously. Hence, there remain challenges to discern correlation, localisation, and translocation between them.\n\nResultsHere we report a microfluidic system that physically separates nucRNA and cytRNA from a single cell and enables single-cell integrated nucRNA and cytRNA-sequencing (SINC-seq). SINC-seq constructs two individual RNA-seq libraries, nucRNA and cytRNA per cell, quantifies gene expression in the subcellular compartments and combines them to create a novel single-cell RNA-seq data enabled by our system, which we here term in-silico single cell.\n\nConclusionsLeveraging SINC-seq, we discovered three distinct natures of correlation among cytRNA and nucRNA that reflected the physiological state of single cells: The cell-cycle-related genes displayed highly correlated expression pattern with minor differences; RNA splicing genes showed lower nucRNA-to-cytRNA correlation, suggesting a retained intron may be implicated in inhibited mRNA transport; A chemical perturbation, sodium butyrate treatment, transiently distorted the correlation along differentiating human leukemic cells to erythroid cells. These data uniquely provide insights into the regulatory network of mRNA from nucleus toward cytoplasm at the single cell level.

genomics↗

bioRxiv2017

White matter haemodynamics: basic physiology and disruption in neuroinflammatory disease

The white matter is highly vascularised by the cerebral venous system. The neuroinflammatory disease multiple sclerosis is associated with infiltration of peripheral immune cells into the brain via these vessels. Understanding venous pathophysiology in multiple sclerosis is thus critical for understanding early disease aetiology. In this paper, we describe a unique blood oxygen-level dependent (BOLD) signal within the white matter using functional MRI and spatial independent components analysis, a blind signal source separation method. The signal was characterised by a narrow peak frequency band between 0.05 and 0.1 Hz. Hypercapnia (transient breath holds), known to alter venous calibre in cortex, induced transient increases in white matter BOLD that disrupted the oscillation indicative of a vasodilatory/contractile mechanism. Comparison of the white matter BOLD oscillations between age and sex matched groups of 18 multiple sclerosis and 14 healthy participants revealed a loss of power in the white matter BOLD signal in the peak frequency band (patients = 6.70{+/-}0.94 dB/Hz vs controls = 7.64{+/-}0.71 dB/Hz; p=0.006). In multiple sclerosis patients, lower power was associated with greater levels of neuroinflammatory activity (R=-0.64, p=0.006) but not neurodegenerative disease markers. Using a signal modelling technique, we assessed the anatomical distribution of white matter BOLD signal abnormalities and detected reduced power in the periventricular white matter, a region of known venous damage in multiple sclerosis patients. These results demonstrate a novel link between neuroinflammation and vascular physiological dysfunction in the cerebral white matter, and could indicate enduring loss of vascular compliance associated with imperfect repair of blood-brain barrier damage after resolution of acute neuroinflammation.

neuroscience↗

bioRxiv2017

The physiological regulation of macropinocytosis during Dictyostelium growth and development

Macropinocytosis is a conserved endocytic process used by Dictyostelium amoebae for feeding on liquid medium. To further Dictyostelium as a model for macropinocytosis, we developed a high-throughput flow cytometry assay for macropinocytosis, and used it to identify inhibitors and investigate the physiological regulation of macropinocytosis. Dictyostelium has two feeding states: phagocytic and macropinocytic. When cells are switched from phagocytic growth on bacteria to liquid media, the rate of macropinocytosis slowly increases, due to increased size and frequency of macropinosomes. Upregulation is triggered by a minimal medium of 3 amino acids plus glucose and likely depends on macropinocytosis itself. Bacteria suppress macropinocytosis while their product, folate, partially suppresses upregulation of macropinocytosis. Starvation, which initiates development, does not of itself suppress macropinocytosis: this can continue in isolated cells, but is shut down by a conditioned-medium factor or activation of PKA signalling. Thus macropinocytosis is a facultative ability of Dictyostelium cells, regulated by environmental conditions that are identified here.\n\nSummaryA high-throughput flow cytometry assay shows that macropinocytosis in D. discoideum is upregulated in the presence of nutrients and absence of bacteria. Development and bacteria induce cells to downregulate macropinocytosis.

microbiology↗

bioRxiv2017

Variation in physiological function across source populations of a New Zealand freshwater snail

Mitochondrial function is critical for energy homeostasis and should shape how genetic variation in metabolism is transmitted through levels of biological organization to generate stability in organismal performance. Mitochondrial function is encoded by genes in two distinct and separately inherited genomes - the mitochondrial genome and the nuclear genome - and selection is expected to maintain functional mito-nuclear interactions. Nevertheless, high levels of polymorphism in genes involved in these mito-nuclear interactions and variation for mitochondrial function are nevertheless frequently observed, demanding an explanation for how and why variability in such a fundamental trait is maintained. Potamopyrgus antipodarum is a New Zealand freshwater snail with coexisting sexual and asexual individuals and, accordingly, contrasting systems of separate vs. co-inheritance of nuclear and mitochondrial genomes. As such, this snail provides a powerful means to dissect the evolutionary and functional consequences of mito-nuclear variation. The lakes inhabited by P. antipodarum span wide environmental gradients, with substantial across-lake genetic structure and mito-nuclear discordance. This situation allows us to use comparisons across reproductive modes and lakes to partition variation in cellular respiration across genetic and environmental axes. Here, we integrated cellular, physiological, and behavioral approaches to quantify variation in mitochondrial function across a diverse set of wild P. antipodarum lineages. We found extensive across-lake variation in organismal oxygen consumption, mitochondrial membrane potential, and behavioral response to heat stress, but few global effects of reproductive mode or sex. Taken together, our data set the stage for applying this important model system for sexual reproduction and polyploidy to dissecting the complex relationships between mito-nuclear variation, performance, plasticity, and fitness in natural populations.

evolutionary biology↗

bioRxiv2018

Physiological and transcriptional response of the diatom Corethron hystrix under robust UVR irradiation

The effect of ultraviolet radiation (UVR) on photosynthetic efficiency and the resulting mechanisms against UV exposure employed by phytoplankton are not completely understood. To address this knowledge gap, we developed a novel close-coupled, wavelength-configurable platform designed to produce precise and repeatable in vitro irradiation of Corethron hystrix, a member of a genera found abundantly in the Southern Ocean where UV exposure is high. We aimed to determine its metabolic, protective, mutative, and repair mechanisms as a function of varying levels of specific electromagnetic energy. Our results show that the physiological responses to each energy level of UV have a negative linear decrease in the photosynthetic efficiency of photosystem II proportional to UV intensity, corresponding to a large increase in the turnover time of quinone re-oxidation. Gene expression changes of photosystem II related reaction center proteins D1, CP43 and CP47 showed coordinated downregulation whereas the central metabolic pathway demonstrated mixed expression of up and downregulated transcripts after UVR exposure. These results suggest that while UVR may damage photosynthetic machinery, oxidative damage may limit production of new photosynthetic and electron transport complexes as a result of UVR exposure.

microbiology↗

bioRxiv2018

Infection By A Giant Virus Induces Widespread Physiological Reprogramming In Aureococcus anophagefferens - A Harmful Bloom Algae

While viruses with distinct phylogenetic origins and different nucleic acid types can infect and lyse eukaryotic phytoplankton, \"giant\" dsDNA viruses have been found to be associated with important ecological processes, including the collapse of algal blooms. However, the molecular aspects of giant virus - host interactions remain largely unknown. AaV, a giant virus in the Mimiviridae clade, is known to play a critical role in regulating the fate of brown tide blooms caused by the pelagophyte Aureococcus anophagefferens. To understand the physiological response of A. anophagefferens CCMP1984 upon AaV infection, we studied the transcriptomic landscape of this host-virus pair over an entire infection cycle using a RNA-sequencing approach. A massive transcriptional reprogramming of the host was evident as early as 5 min post-infection, with modulation of specific processes likely related to both host defense mechanism(s) and viral takeover of the cell. Infected Aureococcus showed a relative suppression of host-cell transcripts associated with photosynthesis, cytoskeleton formation, fatty acid and carbohydrate biosynthesis. In contrast, host cell processes related to protein synthesis, polyamine biosynthesis, cellular respiration, transcription and RNA processing were overrepresented compared to the healthy cultures at different stages of the infection cycle. A large number of redox active host-selenoproteins were overexpressed, which suggested that viral replication and assembly progresses in a highly oxidative environment. The majority (99.2%) of annotated AaV genes were expressed at some point during the infection cycle and demonstrated a clear temporal-expression pattern and an increasing relative expression for the majority of the genes through the time course. We detected a putative early promoter motif for AaV, which was highly similar to the early promoter elements of two other Mimiviridae members, indicating some degree of evolutionary conservation of gene regulation within this clade. This large-scale transcriptome study provides the insight into the Aureococcus virocell, and establishes a foundation to test hypotheses regarding metabolic and regulatory processes critical for AaV and other Mimiviridae members.

microbiology↗

bioRxiv2018

Anatomical, Physiological, and Functional Heterogeneity of the Dorsal Raphe Serotonin System

The dorsal raphe (DR) constitutes a major serotonergic input to the forebrain, and modulates diverse functions and brain states including mood, anxiety, and sensory and motor functions. Most functional studies to date have treated DR serotonin neurons as a single, homogeneous population. Using viral-genetic methods, we found that subcortical-vs. cortical-projecting serotonin neurons have distinct cell body distributions within the DR and different degrees of coexpressing a vesicular glutamate transporter. Further, the amygdala-and frontal cortex-projecting DR serotonin neurons have largely complementary whole-brain collateralization patterns, receive biased inputs from presynaptic partners, and exhibit opposite responses to aversive stimuli. Gain-and loss-of-function experiments suggest that amygdala-projecting DR serotonin neurons promote anxiety-like behavior, whereas frontal cortex-projecting neurons promote active coping in face of challenge. These results provide compelling evidence that the DR serotonin system contains parallel sub-systems that differ in input and output connectivity, physiological response properties, and behavioral functions.

neuroscience↗

bioRxiv2018

Gut microbiota density influences host physiology and is shaped by host and microbial factors

To identify factors that regulate gut microbiota density and the impact of varied microbiota density on health, we assayed this fundamental ecosystem property in fecal samples across mammals, human disease, and therapeutic interventions. Physiologic features of the host (carrying capacity) and the fitness of the gut microbiota shape microbiota density. Therapeutic manipulation of microbiota density in mice altered host metabolic and immune homeostasis. In humans, gut microbiota density was reduced in Crohns disease, ulcerative colitis, and ileal pouch-anal anastomosis. The gut microbiota in recurrent Clostridium difficile infection had lower density and reduced fitness that were restored by fecal microbiota transplantation. Understanding the interplay between microbiota and disease in terms of microbiota density, host carrying capacity, and microbiota fitness provide new insights into microbiome structure and microbiome targeted therapeutics.

microbiology↗

bioRxiv2018

Disabling Gβγ SNARE interaction in transgenic mice disrupts GPCR-mediated presynaptic inhibition leading to physiological and behavioral phenotypes.

Gi/o-coupled G-protein coupled receptors modulate neurotransmission presynaptically through inhibition of exocytosis. Release of G{beta}{gamma} subunits decreases the activity of voltage-gated calcium channels (VGCC), decreasing excitability. A less understood G{beta}{gamma}-mediated mechanism downstream of calcium entry is the binding of G{beta}{gamma} to SNARE complexes. Here, we create a mouse partially deficient in this interaction. SNAP25{Delta}3 homozygote animals are developmentally normalbut impaired gait and supraspinal nociception. They also have elevated stress-induced hyperthermia and impaired inhibitory postsynaptic responses to 2A-AR, but normal inhibitory postsynaptic responses to Gi/o-coupled GABAB receptor activation. SNAP25{Delta}3 homozygotes have deficits in inhibition of hippocampal postsynaptic responses to 5 HT1b agonists that affect hippocampal learning. These data suggest that Gi/o-coupled GPCR inhibition of exocytosis through the G{beta}{gamma}-SNARE interaction is a crucial component of numerous physiological and behavioral processes.

neuroscience↗

bioRxiv2018

Physiological Significance of R-fMRI Indices in Detecting Structural Brain Lesions

Resting-state functional MRI (R-fMRI) research has recently entered the era of \"big data\", however, few studies have provided a rigorous validation of the physiological underpinnings of R-fMRI indices. Although studies have reported that various neuropsychiatric disorders exhibit abnormalities in R-fMRI measures, these \"biomarkers\" have not been validated in differentiating structural lesions (brain tumors) as a concept proof. We enrolled 60 patients with intracranial tumors located in the unilateral cranial cavity and 60 matched normal controls to test whether R-fMRI indices can differentiate tumors, which represents a prerequisite for adapting such indices as biomarkers for neuropsychiatric disorders. Common R-fMRI indices of tumors and their counterpart control regions, which were defined as the contralateral normal areas (for amplitude of low frequency fluctuations (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo) and degree centrality (DC)) and ipsilateral regions surrounding the tumors (for voxel-mirrored homotopic connectivity (VMHC)), were comprehensively assessed. According to paired t-tests with a Bonferroni correction, only ALFF (both with and without Z-standardization) and VMHC (Fishers r-to-z transformed) could successfully differentiate substantial tumors from their counterpart normal regions in patients. And DC was not able to differentiate tumor from normal unless employed Z-standardization. To validate the lower power in the between-subject design than in the within-subject design, each metric was calculated in a matched control group, and two-sample t-tests were used to compare the patient tumors and the normal controls at the same area. Only ALFF (and that with Z-standardization) along with VMHC succeeded in differentiating significant differences between tumors and the sham tumors areas of normal controls. This study tested the premise of R-fMRI biomarkers for differentiating lesions, and brings a new understanding to physical significance of the Z-standardization.

neuroscience↗