Biology subjects

Shah, A.

Publications and source records attributed to Shah, A..

At least 73 records · Page 4Linked to original sources

bioRxiv2023

Bacterial mixed cultures followed mixed-order kinetics during mono-azo dye decolourization and degradation in batch studies

Over the years little has been focused on kinetic and thermodynamic aspect of bioremediation studies on dyes. In this study, detailed kinetic and thermodynamic analyses of results obtained during a primary study on a mono-azo dye: Reactive violet 5R (RV5), decolourization and degradation by bacterial mixed cultures SB4 were performed. Various kinetic models (zero-, first- and second-order behaviour and Monod model) were applied to understand the decolourization mechanism in batch process. Similarly, steady-state kinetics for determination of Michaelis-constant and maximal dye removal rate was derived. With increasing RV5 concentration, the specific decolourization rate had increased from 0.61mg/L/h to 1.38mg/L/h. The apparent kinetics of RV5 decolourization reaction followed mixed-order behaviour. The process was endothermic. The enthalpy and entropy values calculated to 45.6kJ/mol and 146J/mol/K, respectively, with an activation energy of 87kJ/mol. The Gibbs free energy change suggests that, decolourization reaction under experimental conditions was non-spontaneous below 20{degrees}C but was spontaneous at higher temperatures.

microbiology↗

bioRxiv2023

Cytokine-Mediated Degradation of the Transcription Factor ERG Impacts the Pulmonary Vascular Response to Systemic Inflammatory Challenge

BackgroundDuring infectious diseases, pro-inflammatory cytokines transiently destabilize interactions between adjacent vascular endothelial cells (ECs) to facilitate the passage of immune molecules and cells into tissues. However, in the lung the resulting vascular hyperpermeability can lead to organ dysfunction. Previous work identified the transcription factor ERG as a master regulator of endothelial homeostasis. Here we investigate whether the sensitivity of pulmonary blood vessels to cytokine-induced destabilization is due to organotypic mechanisms affecting the ability of endothelial ERG to protect lung ECs from inflammatory injury. MethodsCytokine-dependent ubiquitination and proteasomal degradation of ERG was analyzed in cultured Human Umbilical Vein ECs (HUVECs). Systemic administration of TNF or the bacterial cell wall component lipopolysaccharide (LPS) was used to cause a widespread inflammatory challenge in mice; ERG protein levels were assessed by immunoprecipitation, immunoblot, and immunofluorescence. Murine Erg deletion was genetically induced in ECs (Ergfl/fl;Cdh5(PAC)CreERT2), and multiple organs were analyzed by histology, immunostaining, and electron microscopy. ResultsIn vitro, TNF promoted the ubiquitination and degradation of ERG in HUVECs, which was blocked by the proteasomal inhibitor MG132. In vivo, systemic administration of TNF or LPS resulted in a rapid and substantial degradation of ERG within lung ECs, but not ECs of the retina, heart, liver, or kidney. Pulmonary ERG was also downregulated in a murine model of influenza infection. Ergfl/fl;Cdh5(PAC)-CreERT2 mice spontaneously recapitulated aspects of inflammatory challenges, including lung-predominant vascular hyperpermeability, immune cell recruitment, and fibrosis. These phenotypes were associated with a lung-specific decrease in the expression of Tek, a gene target of ERG previously implicated in maintaining pulmonary vascular stability during inflammation. ConclusionsCollectively, our data highlight a unique role for ERG in pulmonary vascular function. We propose that cytokine-induced ERG degradation and subsequent transcriptional changes in lung ECs play critical roles in the destabilization of pulmonary blood vessels during infectious diseases.

cell biology↗

bioRxiv2023

Interference with the HNF4-dependent gene regulatory network diminishes ER stress in hepatocytes

In all eukaryotic cell types, the unfolded protein response (UPR) upregulates factors that promote protein folding and misfolded protein clearance to help alleviate endoplasmic reticulum (ER) stress. Yet ER stress in the liver is uniquely accompanied by the suppression of metabolic genes, the coordination and purpose of which is largely unknown. Here, we used unsupervised machine learning to identify a cluster of correlated genes that were profoundly suppressed by persistent ER stress in the liver. These genes, which encode diverse functions including metabolism, coagulation, drug detoxification, and bile synthesis, are likely targets of the master regulator of hepatocyte differentiation HNF4. The response of these genes to ER stress was phenocopied by liver-specific deletion of HNF4. Strikingly, while deletion of HNF4 exacerbated liver injury in response to an ER stress challenge, it also diminished UPR activation and partially preserved ER ultrastructure, suggesting attenuated ER stress. Conversely, pharmacological maintenance of hepatocyte identity in vitro enhanced sensitivity to stress. Several pathways potentially link HNF4 to ER stress sensitivity, including control of expression of the tunicamycin transporter MFSD2A; modulation of IRE1/XBP1 signaling; and regulation of Pyruvate Dehydrogenase. Together, these findings suggest that HNF4 activity is linked to hepatic ER homeostasis through multiple mechanisms.

cell biology↗

bioRxiv2023

Broad-spectrum antiviral inhibitors targeting pandemic potential RNA viruses

RNA viruses continue to remain a clear and present threat for potential pandemics due to their rapid evolution. To mitigate their impact, we urgently require antiviral agents that can inhibit multiple families of disease-causing viruses, such as arthropod-borne and respiratory pathogens. Potentiating host antiviral pathways can prevent or limit viral infections before escalating into a major outbreak. Therefore, it is critical to identify broad-spectrum antiviral agents. We have tested a small library of innate immune agonists targeting pathogen recognition receptors, including TLRs, STING, NOD, Dectin and cytosolic DNA or RNA sensors. We observed that TLR3, STING, TLR8 and Dectin-1 ligands inhibited arboviruses, Chikungunya virus (CHIKV), West Nile virus (WNV) and Zika virus, to varying degrees. Cyclic dinucleotide (CDN) STING agonists, such as cAIMP, diABZI, and 2,3-cGAMP, and Dectin-1 agonist scleroglucan, demonstrated the most potent, broad-spectrum antiviral function. Comparative transcriptome analysis revealed that CHIKV-infected cells had larger number of differentially expressed genes than of WNV and ZIKV. Furthermore, gene expression analysis showed that cAIMP treatment rescued cells from CHIKV-induced dysregulation of cell repair, immune, and metabolic pathways. In addition, cAIMP provided protection against CHIKV in a CHIKV-arthritis mouse model. Cardioprotective effects of synthetic STING ligands against CHIKV, WNV, SARS-CoV-2 and enterovirus D68 (EV-D68) infections were demonstrated using human cardiomyocytes. Interestingly, the direct-acting antiviral drug remdesivir, a nucleoside analogue, was not effective against CHIKV and WNV, but exhibited potent antiviral effects against SARS-CoV-2, RSV (respiratory syncytial virus), and EV-D68. Our study identifies broad-spectrum antivirals effective against multiple families of pandemic potential RNA viruses, which can be rapidly deployed to prevent or mitigate future pandemics.

microbiology↗

bioRxiv2023

Efficient chemical and enzymatic syntheses of FAD nucleobase analogues and their analysis as enzyme cofactors

Flavin adenine dinucleotide (FAD), an essential cofactor in cellular metabolism, catalyses a wide range of redox reactions. The organic synthesis of FAD is typically conducted by coupling flavin mononucleotide (FMN) and adenosine monophosphate. The reported synthesis routes have certain limitations such as multiple reaction steps, low yields, and/or difficult-to-obtain starting materials. In this study, we report the synthesis of FAD nucleobase analogues using chemical and enzymatic methods with readily available starting materials achieved in 1-3 steps with moderate yields (10-51%). Further, we demonstrate that Escherichia coli glutathione reductase can use these analogues to catalyse the reduction of glutathione. Finally, we show that FAD nucleobase analogues can also be synthesized inside a cell from cellular substrates FMN and nucleoside triphosphates. This lays the foundation for their use in studying the molecular role of FAD in cellular metabolism and as biorthogonal reagents in biotechnology and synthetic biology applications.

molecular biology↗

bioRxiv2022

A comprehensive update to the Mycobacterium tuberculosis H37Rv reference genome

H37Rv is the most widely used M. tuberculosis strain. Its genome is globally used as the M. tuberculosis reference sequence. We developed Bact-Builder, a pipeline that leverages consensus building to generate complete and highly accurate gap-closed bacterial genomes and applied it to three independently sequenced cultures of a parental H37Rv laboratory stock. Two of the 4,417,942 base-pair long H37Rv assemblies were 100% identical, with the third differing by a single nucleotide. Compared to the existing H37Rv reference, the new sequence contained approximately 6.4 kb additional base pairs encoding ten new regions. These regions included insertions in PE/PPE genes and new paralogs of esxN and esxJ, which were differentially expressed compared to the reference genes. Additional sequencing and assembly with Bact-Builder confirmed that all 10 regions were also present in widely accepted strains of H37Rv: NR123 and TMC102. Bact-builder shows promise as an improved method to perform extremely accurate and reproducible de novo assemblies of bacterial genomes. Furthermore, our findings provide important updates to the primary tuberculosis reference genome.

microbiology↗

bioRxiv2022

DNA methylation and proteomics integration uncover dose-dependent group and individual responses to exercise in human skeletal muscle

ObjectiveExercise is a major regulator of muscle metabolism, and health benefits acquired by exercise are a result of molecular shifts occurring across multiple OMIC levels (i.e. epigenome, transcriptome, proteome). Identifying robust targets associated with exercise response, at both group and individual levels, is therefore important to develop health guidelines and targeted health interventions. MethodsTwenty, apparently healthy, moderately trained (VO2 max= 51.0{+/-}10.6 mL{middle dot}min-1{middle dot}kg-1) males (age range= 18-45yrs) from the Gene SMART (Skeletal Muscle Adaptive Responses to Training) study completed a 12-week High-Intensity Interval Training (HIIT) intervention. Muscle biopsies were collected at baseline and after 4, 8, and 12 weeks of HIIT. High throughput DNA methylation ([~]850 CpG sites), and proteomic ([~]3000 proteins) analyses were conducted at all-time points. Mixed-models were applied to estimate group and individual changes, and methylome and proteome integration was conducted using a holistic multilevel approach with the mixOmics package. ResultsSignificant shifts in the methylome (residual analysis) and proteome profiles were observed after 12 weeks of HIIT. 461 proteins significantly changed over time (at 4, 8, and 12 weeks), whilst only one differentially methylated position (DMP) was changed (adj.p-value <0.05). K-means analysis revealed clear protein clustering exhibiting similar changes over time. Individual responses to training were observed in 101 proteins. Seven proteins had a large effect-sizes >0.5, among them are two novel exercise-related proteins, LYRM7 and EPN1. Integration analysis uncovered bidirectional relationships between the methylome and proteome. ConclusionsWe showed a significant influence of HIIT on the epigenome and proteome in human muscle, and uncovered groups of proteins clustering according to similar patterns across the exercise intervention. Individual responses to exercise were observed in the proteome with novel mitochondrial and metabolic proteins consistently changed across individuals. Future work is required to elucidate the role of such proteins in response to exercise as well as to investigate the mechanisms associating genes and proteins in response to exercise.

molecular biology↗

bioRxiv2022

Disease-modifying effects of sodium selenate in a model of drug-resistant, temporal lobe epilepsy.

There are no pharmacological disease-modifying treatments that can mitigate the seizures and comorbidities associated with established chronic temporal lobe epilepsy (TLE). This study evaluated the effect of sodium selenate in the post-status epilepticus (SE) rat model of chronic drug resistant TLE. Wistar rats underwent kainic acid-induced SE or sham. Ten-weeks post-SE, rats were randomly assigned to receive either sodium selenate, levetiracetam, or vehicle treatments continuously for 4 weeks. To evaluate the effects of the treatments, 1 week of continuous video-EEG was acquired before, during, and 4, 8 weeks post-treatment, followed by behavioral tests. Targeted and untargeted proteomics and metabolomics were performed on post-mortem brain tissue to identify potential pathways associated with modified disease outcomes. Telomere length was investigated as a novel surrogate marker of disease severity. Sodium selenate treatment was able to mitigate disease severity, reducing the number of spontaneous seizures (p< 0.05), cognitive dysfunction (p< 0.05 in both novel object placement and recognition tasks), and sensorimotor deficits (p< 0.01) 8 weeks post-treatment cessation. Moreover, increased protein phosphatase 2A (PP2A) expression, reduced hyperphosphorylated tau, and reversed telomere length shortening caused by SE (p< 0.05). Network medicine integration of multi-omics/ pre-clinical outcomes identified protein-metabolite modules positively correlated with the TLE phenotype. Our results provide evidence that treatment with sodium selenate results in a sustained disease modifying effect in chronically epileptic rats in the post-KA SE model of TLE, including improved comorbid learning and memory deficits.

neuroscience↗

bioRxiv2022

Symbolic quantitative cognition in wild zebrafish (Danio rerio)

Zebrafish (Danio rerio) constitute an excellent model system to investigate the neural and genetic basis of quantitative cognition We tested the ability of reward quantity discrimination of wild-type zebrafish in an associative learning task. We used an operant conditioning paradigm in which the number of horizontal lines zebrafish approached in a 2-alternative forced choice task predicted the number of food reward pellets they would receive. Zebrafish did not learn a preference for the 2-line stimulus predictive of receiving 2 food pellets. However, a subset of the fish performed significantly above chance in a discrimination task with the same apparatus, in which the 2-line stimulus was associated with the same reward but the choice of the 1-line stimulus was not rewarded. Zebrafish also showed a population level learning in a simpler spatial association task with the same apparatus. We also explored the explanatory value of alternative spatial learning hypotheses such as a Win-Stay, Lose-Shift (WSLS) strategy at the individual level for fish in navigating these spatially randomised tasks.

animal behavior and cognition↗

bioRxiv2022

Evaluation of the antimicrobial, anti-adhesion, anti-biofilm and cell proliferation assay of a de-novo goji berry extract against periodontal pathogens: a comparative in-vitro study

Lycium barbarum, commonly known as goji berry, Chinese berry, or Tibetian berry, is emerging as a popular "superfood" with anti-inflammatory and antioxidant properties. Goji berry is being used for the treatment of various cancers, gastrointestional disorders, stroke, diabetes, Alzheimers disease, and glaucoma. However, its use for management of oral inflammatory diseases has not been explored. Therefore, the present study aims to evaluate the antimicrobial, anti-adhesion, and anti-biofilm, and cytotoxic properties of an ethanolic extract of Lycium barbarum (LBE) against oral and periodontal pathogens. The antimicrobial properties of LBE against five microorganisms were tested and compared against Chlorhexidine and doxycycline along with cytotoxicity and cell viability on the gingival fibroblast and modified keratinocyte cell lines. The anti-adhesion and anti-biofilm properties of LBE against Porphyromonas gingivalis, at its minimal bactericidal value, were evaluated. The antimicrobial, anti-adhesion and antibiofilm properties of LBE were found to be comparable to chlorhexidine but less than that of doxycycline. The LBE extract was also compactible to gingival fibroblast tissues and oral keratinocytes at 1 mg/ml. The results proved that goji berry is as effective as chlorhexidine and can be used as a promising natural herb for the management of inflammatory diseases of oral cavity.

microbiology↗

bioRxiv2022

Lem2 is essential for cardiac development by maintaining nuclear integrity

Nuclear envelope integrity is essential for compartmentalisation of nucleus and cytoplasm. Importantly, mutations in nuclear envelope-encoding genes are the second-highest cause of familial dilated cardiomyopathy. One such nuclear envelope protein that causes cardiomyopathy in humans and affects mouse heart development is Lem2. However, its role in mechanically active tissue such as heart remains poorly understood. We generated mice in which Lem2 was specifically ablated in cardiomyocytes and carried out detailed physiological, tissue and cellular analyses. Importantly, our data showed that Lem2 was essential for cardiac development, and hearts from Lem2 cKO mice were morphologically and transcriptionally underdeveloped. Lem2 cKO hearts displayed high levels of DNA damage, nuclear rupture, and apoptosis. Crucially, we found that these defects were driven by muscle contraction as they were ameliorated by inhibiting myosin contraction and conversely were exacerbated upon myosin activation. Our data suggest that Lem2 is critical for integrity at the nascent nuclear envelope in fetal hearts, and protects the nucleus from the mechanical forces of muscle contraction. Taken together, these data provide novel insight into mechanisms underlying striated muscle diseases caused by altered nuclear envelope integrity.

cell biology↗

bioRxiv2022

Nrf2 attenuates the innate immune response after experimental myocardial infarction

ObjectivesWe aimed to investigate the contribution of the transcription factor nuclear factor erythroid-derived 2-like 2 (Nrf2) to the inflammatory response after experimental myocardial infarction (MI). BackgroundThere is compelling evidence implicating dysregulated inflammation in the mechanism of ventricular remodeling and heart failure (HF) after MI. The transcription factor Nrf2 (encoded by Nfe2l2) is a promising target in this context. It impedes transcriptional upregulation of pro-inflammatory cytokines and is anti-inflammatory in various murine models. MethodsWe subjected Nrf2-/- mice and wild type (WT) controls to permanent left coronary artery (LCA) ligation. The inflammatory response was investigated with fluorescence-activated cell sorting (FACS) analysis of peripheral blood and heart cell suspensions, together with qRT-PCR of infarcted tissue for chemokines and their receptors. To investigate whether Nrf2-mediated transcription is a dedicated function of leukocytes, we interrogated publicly available RNA-sequencing (RNA-seq) data from mouse hearts after permanent LCA ligation for Nrf2-regulated gene (NRG) expression. ResultsFACS analysis demonstrated a profoundly inflamed phenotype in the hearts of global Nrf2-/- mice as compared to WT mice after MI. Moreover, infarcted tissue from Nrf2-/- mice displayed higher expression of inflammatory cytokines, chemokines, and their receptors, including IL6, Ccl2, and Cxcr4. RNA-seq analysis showed upregulated NRG expression in WT mice after MI compared to untreated mice, which was significantly higher in bioinformatically isolated CCR2+ cells. ConclusionsTaken together, the results suggest that Nrf2 signalling in leukocytes, and possibly CCR2+ monocyte-derived cardiac resident macrophages, may be potential targets to prevent post-MI ventricular remodeling.

immunology↗

bioRxiv2021

MK2 Expression Promotes Non-Small Cell Lung Cancer Cell Death and Predicts Survival

Non-small cell lung cancers demonstrate intrinsic resistance to cell death even in response to chemotherapy. Previous work suggested that defective nuclear translocation of active caspase 3 may play a role in resistance to cell death. Separately, our group has identified that mitogen activated protein kinase activated protein kinase 2 (MK2) is required for nuclear translocation of active caspase 3 in the execution of apoptosis. This study demonstrates a relatively low expression of MK2 in non-small cell lung carcinoma cell lines compared to small cell carcinoma cell lines. Further, overexpression of MK2 in non-small cell lung carcinoma cell lines results in increased caspase 3 activity and caspase 3 mediated cell death. Higher MK2 transcript levels were observed in patients with earlier-stage non-small cell lung cancer. Higher expression of MK2 is associated with better survival in patients with early stage non-small cell lung cancer across two independent clinical datasets. Using data sets spanning multiple cancer types, we observed improved survival with higher MK2 expression was unique to lung adenocarcinoma. Mechanistically, MK2 promotes nuclear translocation of caspase 3 leading to PARP1 cleavage and execution of cell death. While MK2 can directly phosphorylate caspase 3, neither phosphorylation status of caspase 3 nor the kinase activity of MK2 impacts caspase 3 activation, nuclear translocation and execution of cell death. Rather, a non-kinase function of MK2, specifically trafficking via its nuclear localization sequence, is required for caspase 3 mediated cell death. In summary this study highlights the importance of a non-enzymatic function of MK2 in the execution of apoptosis, which may be leveraged in the adjunctive treatment of NSCLC or other conditions where regulation of apoptosis is crucial.

cancer biology↗

bioRxiv2021

Distinct mechanoreceptor pezo-1 isoforms modulate food intake in the nematode Caenorhabditis elegans

Two PIEZO mechanosensitive cation channels, PIEZO1 and PIEZO2, have been identified in mammals, where they are involved in numerous sensory processes. While structurally similar, PIEZO channels are expressed in distinct tissues and exhibit unique properties. How different PIEZOs transduce force, how their transduction mechanism varies, and how their unique properties match the functional needs of the tissues they are expressed in remain all-important unanswered questions. The nematode Caenorhabditis elegans has a single PIEZO ortholog (pezo-1) predicted to have twelve isoforms. These isoforms share many transmembrane domains but differ in those that distinguish PIEZO1 and PIEZO2 in mammals. We used transcriptional and translational reporters to show that putative promoter sequences immediately upstream of the start codon of long pezo-1 isoforms predominantly drive GFP expression in mesodermally derived tissues (such as muscle and glands). In contrast, sequences upstream of shorter pezo-1 isoforms resulted in GFP expression primarily in neurons. Putative promoters upstream of different isoforms drove GFP expression in different cells of the same organs of the digestive system. The observed unique pattern of complementary expression suggests that different isoforms could possess distinct functions within these organs. We used mutant analysis to show that pharyngeal muscles and glands require long pezo-1 isoforms to respond appropriately to the presence of food. The number of pezo-1 isoforms in C. elegans, their putative differential pattern of expression, and roles in experimentally tractable processes make this an attractive system to investigate the molecular basis for functional differences between members of the PIEZO family of mechanoreceptors.

genetics↗

bioRxiv2021

Single-cell gene regulatory network inference atscale: The Inferelator 3.0

MotivationGene regulatory networks define regulatory relationships between transcription factors and target genes within a biological system, and reconstructing them is essential for understanding cellular growth and function. Methods for inferring and reconstructing networks from genomics data have evolved rapidly over the last decade in response to advances in sequencing technology and machine learning. The scale of data collection has increased dramatically; the largest genome-wide gene expression datasets have grown from thousands of measurements to millions of single cells, and new technologies are on the horizon to increase to tens of millions of cells and above. ResultsIn this work, we present the Inferelator 3.0, which has been significantly updated to integrate data from distinct cell types to learn context-specific regulatory networks and aggregate them into a shared regulatory network, while retaining the functionality of the previous versions. The Inferelator is able to integrate the largest single-cell datasets and learn cell-type specific gene regulatory networks. Compared to other network inference methods, the Inferelator learns new and informative Saccharomyces cerevisiae networks from single-cell gene expression data, measured by recovery of a known gold standard. We demonstrate its scaling capabilities by learning networks for multiple distinct neuronal and glial cell types in the developing Mus musculus brain at E18 from a large (1.3 million) single-cell gene expression dataset with paired single-cell chromatin accessibility data. AvailabilityThe inferelator software is available on GitHub (https://github.com/flatironinstitute/inferelator) under the MIT license and has been released as python packages with associated documentation (https://inferelator.readthedocs.io/).

systems biology↗

bioRxiv2021

Sesamol and its derivative investigated as antiandrogen - A potential prevention to prostate cancer in rats

Androgen signaling is essential for the development of prostate cancer (PCa) initiated from prostatic basal cells with collocation of androgen receptor gene mutations. Phytoestrogens, the naturally occurring compounds are AR antagonist. These compounds downregulate prostate-specific antigen (PSA) expression and cell proliferation. Thus, this gives a track to research these compounds as a possible treatment for PCa. In this work, STITCH and molecular docking predict the conformation of ligands inside the suitable target binding site. Therefore, a study was planned to know the interactions among SM and its derivatives with AR. It was further, evaluated for in vitro evaluation on LNCaP, PC-3, and DU-145 using MTT studies. The two lead compounds shortlisted from MTT studies were further analyzed for androgen-regulated genes by using RT-PCR, western blot studies and an animal model of prostate cancer. We found that SM and its derivative (3-MA) may prevent the development of PCa by androgen pathway.

cancer biology↗

bioRxiv2021

Ultrastructural insight into SARS-CoV-2 attachment, entry and budding in human airway epithelium

Ultrastructural studies of SARS-CoV-2 infected cells are crucial to better understand the mechanisms of viral entry and budding within host cells. Many studies are limited by the lack of access to appropriate cellular models. As the airway epithelium is the primary site of infection it is essential to study SARS-CoV-2 infection of these cells. Here, we examined human airway epithelium, grown as highly differentiated air-liquid interface cultures and infected with three different isolates of SARS-CoV-2 including the B.1.1.7 variant (Variant of Concern 202012/01) by transmission electron microscopy and tomography. For all isolates, the virus infected ciliated but not goblet epithelial cells. Two key SARS-CoV-2 entry molecules, ACE2 and TMPRSS2, were found to be localised to the plasma membrane including microvilli but excluded from cilia. Consistent with these observations, extracellular virions were frequently seen associated with microvilli and the apical plasma membrane but rarely with ciliary membranes. Profiles indicative of viral fusion at the apical plasma membrane demonstrate that the plasma membrane is one site of entry where direct fusion releasing the nucleoprotein-encapsidated genome occurs. Intact intracellular virions were found within ciliated cells in compartments with a single membrane bearing S glycoprotein. Profiles strongly suggesting viral budding from the membrane was observed in these compartments and this may explain how virions gain their S glycoprotein containing envelope.

microbiology↗

bioRxiv2021

Conserved hormonal and molecular mechanisms underlying behavioural maturation in open- and cavity-nesting honey bees

Division of labour in honey bees is based on a process of behavioural development where the worker bee successively performs different tasks at different ages. Workers start with tasks related to brood care and nest maintenance and move on to become foragers. This process of worker behavioural maturation is well studied in Apis mellifera. Juvenile hormone is one of the major drivers of this behavioural maturation, which is also accompanied by changes in brain physiology and anatomy including changes in neuronal gene expression and connections of neurons. Recent studies have identified whole networks of genes associated with specific tasks like nursing, guarding and foraging. Based on this detailed knowledge in A. mellifera, we ask whether major characteristics of the behavioural maturation process and the underlying hormonal and molecular changes are similar or different in two other honey bee species, the phylogenetically ancestral open-nesting A. florea and the more derived cavity-nesting A. cerana. Our behavioural studies show that workers of A. florea exhibit a slower pace of behavioural maturation and on average start foraging at a later age. However, the basic hormonal and molecular changes associated with onset of foraging are similar between both species. Based on our findings, we propose that evolution of accelerated behavioural maturation in cavity-nesting species is likely attributed to changes in the temporal dynamics of juvenile hormone titres.

molecular biology↗