Biology subjects

Arshad, A.

Publications and source records attributed to Arshad, A..

5 recordsLinked to original sources

bioRxiv2026

Zebrafish larval nitrogen excretion is flexible and resilient to loss of rhesus glycoproteins

Nitrogenous waste excretion is essential for all developmental stages of fish. Embryonic fish excrete urea, transitioning to cutaneous and later branchial ammonia excretion. In zebrafish, ammonia excretion involves rhesus glycoproteins Rhbg and Rhcgb in keratinocytes and ionocytes, but the developmental moment they appear in the gill remains unclear. Potential redundancy between Rhbg and Rhcgb in ammonia excretion is also not fully investigated, nor is the difference in response to low pH. We hypothesized that rhesus glycoproteins are partially redundant, and that they differ in their response to low pH as ammonia excretion enables ionocytes to exchange Na+ and H+ (Rh-NHE-metabolon). We predicted that a loss of rhbg or rhcgb induces compensatory responses. We characterized the transition from urea to branchial ammonia excretion from 0 to 8 days-post fertilization (dpf) and the response to pH 5.0 on the expression and localization of rhesus glycoproteins in control zebrafish and rhbg or rhcgb-crispants. Effects of high external ammonia (HEA, 500 M NH4Cl) and 10 mM HEPES-buffering were further characterized in rhcgb-crispants. Rhag and Rhbg appeared in the gill at 5 dpf, while Rhcgb appeared at 6 dpf. A loss of rhbg or rhcgb did not impact baseline N-excretion, illustrating that zebrafish can maintain ammonia excretion without the full complement of rhesus glycoproteins. We observed no compensatory increase in rhesus glycoproteins, but expression of the transporter hippocampus-abundant transcript 1b increased. HEA-exposed rhcgb-crispants switched to urea as primary nitrogen waste. Together, these findings underline the plasticity of the larval in dealing with nitrogenous waste.

physiology↗

bioRxiv2024

The cytokine receptor Fn14 is a molecular brake on neuronal activity that mediates circadian function in vivo

To survive, organisms must adapt to a staggering diversity of environmental signals, ranging from sensory information to pathogenic infection, across the lifespan. At the same time, organisms intrinsically generate biological oscillations, such as circadian rhythms, without input from the environment. While the nervous system is well-suited to integrate extrinsic and intrinsic cues, how the brain balances these influences to shape biological function system-wide is not well understood at the molecular level. Here, we demonstrate that the cytokine receptor Fn14, previously identified as a mediator of sensory experience-dependent synaptic refinement during brain development, regulates neuronal activity and function in adult mice in a time-of-day-dependent manner. We show that a subset of excitatory pyramidal (PYR) neurons in the CA1 subregion of the hippocampus increase Fn14 expression when neuronal activity is heightened. Once expressed, Fn14 constrains the activity of these same PYR neurons, suggesting that Fn14 operates as a molecular brake on neuronal activity. Strikingly, differences in PYR neuron activity between mice lacking or expressing Fn14 were most robust at daily transitions between light and dark, and genetic ablation of Fn14 caused aberrations in circadian rhythms, sleep-wake states, and sensory-cued and spatial memory. At the cellular level, microglia contacted fewer, but larger, excitatory synapses in CA1 in the absence of Fn14, suggesting that these brain-resident immune cells may dampen neuronal activity by modifying synaptic inputs onto PYR neurons. Finally, mice lacking Fn14 exhibited heightened susceptibility to chemically induced seizures, implicating Fn14 in disorders characterized by hyperexcitation, such as epilepsy. Altogether, these findings reveal that cytokine receptors that mediates inflammation in the periphery, such as Fn14, can also play major roles in healthy neurological function in the adult brain downstream of both extrinsic and intrinsic cues. HighlightsO_LINeuronal activity induces Fn14 expression in pyramidal neurons of the hippocampus C_LIO_LIFn14 constrains neuronal activity near daily transitions between light and dark C_LIO_LILoss of Fn14 lengthens the endogenous circadian period and disrupts sleep-wake states and memory C_LIO_LIMicroglia contact excitatory synapses in an Fn14-dependent manner C_LI

neuroscience↗

bioRxiv2021

Unraveling nitrogen, sulfur and carbon metabolic pathways and microbial community transcriptional responses to substrate deprivation and toxicity stresses in a bioreactor mimicking anoxic brackish coastal sediment conditions

Microbial communities are key drivers of carbon, sulfur and nitrogen cycling in coastal ecosystems, where they are subjected to dynamic shifts in substrate availability and exposure to toxic compounds. However, how these shifts affect microbial interactions and function is poorly understood. Unraveling such microbial community responses is key to understand their environmental distribution and resilience under current and future disturbances. Here, we used metagenomics and metatranscriptomics to investigate microbial community structure and transcriptional responses to prolonged ammonium deprivation and sulfide and nitric oxide toxicity stresses in a controlled bioreactor system mimicking coastal sediment conditions. Candidatus Nitrobium versatile, identified in this study as a sulfide-oxidizing denitrifier, became a rare community member upon ammonium removal. The methanotroph Ca. Methanoperedens nitroreducens showed remarkable resilience to both experimental conditions, dominating transcriptional activity of dissimilatory nitrate reduction to ammonium (DNRA). After the ammonium removal experiment, a novel methanotroph species that we have named Ca. Methylomirabilis tolerans outcompeted Ca. Methylomirabilis lanthanidiphila and the anaerobic ammonium oxidizer (anammox) Ca. Kuenenia stuttgartiensis outcompeted Ca. Scalindua rubra. At the end of the sulfide and nitric oxide experiment, a gammaproteobacterium affiliated to the family Thiohalobacteraceae was enriched and dominated transcriptional activity of sulfide:quinone oxidoreductase. Our results indicate that some community members could be more resilient to stresses than others in coastal ecosystems, leading to dynamic microbial community shifts and novel functional states. Methane and sulfide oxidation could be ecosystem functions preserved across the investigated disturbances, while differing nitrogen cycling pathways might be favored in response to stresses. ImportanceCoastal ecosystems are primary zones of biogeochemical cycling, processing inputs of nutrients both generated in situ and derived from land runoff. Microbial communities that inhabit costal sediments perform these biogeochemical reactions, but microbial responses to dynamic, periodic substrate deprivation and exposure to toxic compounds remain elusive. In this study, we sought to address this knowledge gap in a controlled bioreactor system, unraveling microbial metabolic pathways and monitoring microbial responses to stresses that might occur in costal sediments. We identified key microbial players and shifts in their abundance and transcriptional activity. Our results indicated that methanotrophs were particularly resilient to stresses, sulfide oxidizers differed in resiliency but the community maintained sulfide oxidation function across stresses, and that anaerobic ammonium oxidizing (anammox) bacteria were sensitive to substrate deprivation but could restore activity once favorable conditions were reestablished. These insights will help to understand and predict coastal ecosystem responses to future disturbances.

microbiology↗

bioRxiv2021

Correlation of Computerized Tomography (CT) Severity Score for COVID-19 pneumonia with Clinical Outcomes

IntroductionVarious CT severity scores have already been described in literature since the start of this pandemic. One pertinent issue with all of the previously described severity scores is their relative challenging calculation and variance in inter-observer agreement. The severity score proposed in our study is relatively simpler, easier to calculate and apart from a trained radiologist, can easily be calculated even by physicians with good inter-observer agreement. Therefore, a rapid CT severity score calculation can give a clue to physician about possible clinical outcome without being dependent on radiologist who may not be readily available especially in third world countries. ObjectiveThe objective of this study is to develop a simple CT severity score (CT-SS) with good inter-observer agreement and access its correlation with clinical outcome. MethodsThis retrospective study was conducted by the Department of Radiology and Internal Medicine, at the Aga Khan University Hospital Karachi, from April 2020 to August 2020. Non-probability consecutive sampling was used to include all patients who were positive for COVID-19 on PCR, and underwent CT chest examination at AKUH. Severity of disease was calculated in each lobe on the basis of following proposed CT severity scoring system (CT-SS). For each lobe the percentage of involvement by disease was scored - 0% involvement was scored 0, <50% involvement was scored 1 and >50% involvement was scored 2. Maximum score for one lobe was 2 and hence total maximum overall score for all lobes was 10. Continuous data was represented using mean and standard deviation, and compared using independent sample t-tests. Categorical data was represented using frequencies and percentages, and compared using Chi-squared tests. Inter-observer reliability between radiologist and COVID intensivist for the 10 point CT-SS rated on 0-10 was assessed using the Kappa statistic. A p-value < 0.05 was considered significant for all analyses. ResultsA total of 73 patients were included, the majority male (58.9%) with mean age 55.8 {+/-} 13.93 years. The CT-SS rated on 0-10 showed substantial inter-observer reliability between radiologist and intensivist with a Kappa statistic of 0.78. Patients with CT-SS 8-10 had a significantly higher ICU admission & intubation rate (53.8% vs. 23.5%) and mortality rate (35.9% vs. 11.8%; p = 0.017), as compared to those with CT-SS 0-7. ConclusionWe conclude that the described CT severity score (CT-SS) is a quick, effective and easily reproducible tool for prediction of adverse clinical outcome in patients with COVID 19 pneumonia. The tool shows good inter-observer agreement when calculated by radiologist and physician independently.

pathology↗

bioRxiv2020

Elevated soluble Galectin-3 as a marker of chemotherapy efficacy in Breast cancer patients: a prospective study

PurposeGalectin-3 (Gal-3) is a glycan-binding lectin with a debated role in cancer progression due to its various functions and patterns of expression. The current study investigates the relationship between breast cancer prognosis and secreted Gal-3. MethodsBreast cancer patients with first time cancer diagnosis and no prior treatment (n=88) were placed in either adjuvant or neoadjuvant setting based on their treatment modality. Stromal and plasma Gal-3 levels were measured in each patient at the time of diagnosis and then throughout treatment using immunohistochemistry (IHC) and ELISA respectively. Healthy women (>18 years of age, n=63) were used to establish baseline levels of plasma Gal-3. Patients were followed for 84 months for disease free survival analysis. ResultsEnhanced levels of plasma (adjuvant) and stromal (neo-adjuvant) Gal-3 were found to be markers of chemotherapy efficacy. The patients with chemotherapy induced increase in extracellular Gal-3 had longer disease-free interval and significantly lower rate of recurrence during 84-month follow-up compared to patients with unchanged or decreased secretion. ConclusionThe findings support the use of plasma Gal-3 as a marker for chemotherapy efficacy when no residual tumor is visible through imaging. Furthermore, stromal levels in any remaining tumors post chemotherapy can also be used to predict long term prognosis in patients. Key pointsIncreased Gal-3 secretion due to chemotherapy leads to better prognosis and longer disease-free survival. The analysis of soluble Gal-3 expression could be useful as a support tool in predicting treatment efficacy in patients with no visible tumor remaining for follow up through imaging.

cancer biology↗