Biology subjects

Hossain, M. I.

Publications and source records attributed to Hossain, M. I..

18 recordsLinked to original sources

bioRxiv2025

Evaluation of Morpho-physiological Traits of F1 Hybrids and Estimation of Standard Heterosis of Sweet Pepper (Capsicum annuum L.) in Sylhet

Sweet pepper (Capsicum annuum L.) is a highly demanded crop valued for its culinary and nutritional benefits. This study aimed to evaluate the morphological, physiological, and yield-contributing traits of developed hybrids and check varieties, as well as estimate standard heterosis. The experiment was conducted at the Horticulture Department, Sylhet Agricultural University, from October 2022 to June 2023, using eight hybrids (P3xP1, P4xP3, P6xP5, P5xP1, P7xP1, P5xP3, P3xP2, and P6xP3) and two check varieties (CV1 and CV2). The field and laboratory experiments followed RCBD and CRD designs, respectively, with three replications. Significant morphological variations were observed in growth habit, leaf shape, flower position, fruit color, size, and nodal anthocyanin. The hybrids P5xP1, P7xP1, P6xP5, P3xP2, and P5xP3 exhibited superior morphological, physiological, and yield traits compared to check varieties. Earliness in flowering (30.33 days) and fruit setting (38.33 days) was recorded in P3xP1. Maximum fruit length (13.57 cm) was observed in P5xP1, while the highest fruit diameter (8.71 cm) and individual fruit weight (214.51 g) were found in P3xP2. The highest fruit yield per plant (1.94 kg) and per hectare (61.98 kg) was recorded in P5xP1. Positive standard heterosis was observed for key traits over check variety and mostly developed hybrids showed better performance in all traits compared to check variety. Pearson correlation and PCA analysis revealed key trait associations and genetic variation among sweet pepper hybrids, aiding breeding strategies. Considering morphological, physiological, yield potential and heterosis, P5xP1, P7xP1, P6xP5, P3xP2, and P5xP3 are recommended for further evaluation and breeding programs.

plant biology↗

bioRxiv2025

Mixed fertilization strategies but not mono fertilization enhances the net primary productivity and quality of chili (Capsicum frutescens)

While the effects of different fertilization strategies on chili (Capsicum frutescens) cultivation have been extensively studied, the comparative assessment of mixed versus mono fertilization approaches remains still under the shadow. To address this gap, we have conducted an experiment using a completely randomized design (CRD) with five fertilization treatments along with four replications of each treatment (e.g., Leucaena leucocephala leaf litter and recommended dose of fertilizers (RFD)) to observed the effect of these treatments on plant productivity traits, NPP (net primary productivity), quality and overall yield of chili. Our results revealed that the mixed fertilization treatment (T: 100 g kg-1 L. leucocephala + [1/2] RFD) produced the highest yield (15.50 t ha-{superscript 1}), a 63.9% increase over the control. We also found that plant height (73.75 cm), number of leaves (1000.25 plant-1), number of fruits (93.00 plant-1) were higher at 60 DAT (days after transplanting) however, number of flowering (44.50 plant-1) at 45 DAT. Similarly, Above- and belowground NPP (26.47 g plant-1), vitamin C (124.65 mg 100 g-{superscript 1} ), capsaicin content (1.22 %) and SPAD chlorophyll index (48.61) were higher in T4 treatment compared to T0 treatment. Furthermore, regression results showed that ANPP and yield significantly increased with increase the number of leaves (ANPP: R{superscript 2} = 0.51, p = 0.02; Yield: R{superscript 2} = 0.34, p = 0.002) and number of flowering (ANPP: R{superscript 2} = 0.41, p = 0.014; Yield: R{superscript 2} = 0.42, p = 0.037) as well. Our results suggest that mixed fertilization enhances both productivity and quality traits in chili. Therefore, promotion of integrated (organic and inorganic together) nutrient management practices is recommended to improve yield and quality of chili.

ecology↗

bioRxiv2025

Environmental and Maternal Imprints on Infant Gut Metabolic Programming

Early life is a critical period for immune and metabolic programming, but developmental patterns remain underexplored in populations from low- and middle-income countries. Here, we profiled the microbiome and metabolome of 55 Bangladeshi mother-infant dyads over the first six months of life. Importantly, we observed an increase in microbially-derived bile amidates and N-acyl lipids with age in conjunction with reads matching the bile salt hydrolase/transferase (bsh) gene. While microbial source tracking confirmed maternal fecal seeding, a substantial environmental contribution was also highlighted. Differences in infant fecal metabolic profiles were associated with delivery mode, maternal milk composition, household assets, and household-level water treatment. C-section delivery and untreated drinking water were linked to transient metabolic differences, including increases in bile amidates, N-acyl lipids, and other host-microbe co-metabolic products, including acylcarnitines. Multi-omics analysis revealed specific microbial-metabolite relationships, highlighting how early environmental and maternal living circumstances shape metabolic gut programming through the microbiome.

microbiology↗

bioRxiv2025

Serosurveillance Studies of Peste des Petits Ruminants (PPR) Virus in Sheep and Goats in South Asia: A Systematic Review and Meta-analysis

BackgroundPeste des Petits Ruminants (PPR), also known as the goat plague, is one of the WOAH-listed A, highly contagious and economically important viral transboundary animal diseases affecting small ruminants, and having a significant impact on the global livestock industry and international animal traffic. ObjectiveThe present study aimed to use a systematic approach to assess the pooled seroprevalence of PPRV in sheep and goats in South Asia, through a systematic review and meta-analysis of published data. MethodsA thorough search on various databases was performed to identify published research articles published between January 2000 and June 2025 reporting the seroprevalence of PPRV in small ruminants in South Asia. The articles were chosen on the basis of specific inclusion and exclusion criteria. Since the heterogeneity among the studies was significant, the pooled seroprevalence was estimated via a random effects meta-analysis model, using Stata (v19) and R software (v4.5.0). ResultsIn sheep and goats, the estimated pooled seroprevalence of PPR was 42.4% (95% CI: 35.0-49.9), whereas it was 41.8% (95% CI: 33.7-50.1) in goats and 44.5% (95% CI: 37.0- 52.0) in sheep. Subgroup analysis revealed that the pooled seroprevalence of PPRV in sheep and goat by country and vaccination status was greater in Nepal (57.0%, 95% CI: 8.4-97.7) and in vaccinated animals (57.5%, 95% CI: 47.9-66.9). ConclusionThis study highlights the need for coordinated actions, including vaccination, surveillance, and strict biosecurity, to control and eradicate the disease effectively. Moreover, authorities should adopt evidence-based strategies to support the global goal of eradicating PPR by 2030, as recommended by the WOAH.

microbiology↗

bioRxiv2025

Sulfotransferase 4A1 (SULT4a1): A Novel Neuroprotective Protein in Stroke

SULT4a1, a member of the cytosolic sulfotransferase family, is predominantly expressed in neurons and plays potentially vital roles in regulating neural survival and function. SULT4a1 protects against mitochondrial dysfunction and oxidative stress. SULT4a1 levels decrease in experimental stroke models and may play a critical neuroprotective role in mitigating neuronal injury caused by oxygen-glucose deprivation (OGD) and ischemic stroke, as shown in a transient middle cerebral artery occlusion (tMCAO) mouse model. In this study, we investigated the neuroprotective role of SULT4a1 in OGD and tMCAO and highlighted its expression pattern and involvement in maintaining mitochondrial function and reducing oxidative stress, two early pathophysiological features in stroke and related neuronal injury. Our data show that decreased SULT4a1 expression in OGD conditions and in the tMCAO mouse brain leads to enhanced neuronal damage, emphasizing the importance of SULT4a1 in preserving neuronal integrity. Loss of SULT4a1 alone was sufficient to decrease mitochondrial function in mouse cortical neurons. Notably, overexpression of SULT4a1 preserved mitochondrial function, reduced the loss of mitochondrial membrane potential, and diminished oxidative stress, as evidenced by lower reactive oxygen species (ROS) production and reduced protein carbonylation. These results indicate that modulating SULT4a1 expression in stroke could offer a promising strategy for preventing neuronal damage. Indeed, overexpression of SULT4a1 via stereotaxic injection of AAV9 into the mouse brain mitigated tMCAO-related brain injury and functional deficits over time. The findings of this study indicate that SULT4a1 may protect neurons in stroke and related brain injury, possibly by maintaining mitochondrial function and redox homeostasis through mechanisms that are still unknown. It is likely that SULT4a1 regulates neuroprotective processes in both the mitochondria and the cytosol. However, further research is needed to clarify the specific molecular pathways involved in its neuroprotective function.

neuroscience↗

bioRxiv2024

Genomic characterization and functional insights of multidrug-resistant Klebsiella pneumoniae strain BCSIR-JUMIID

Klebsiella pneumoniae is a prominent opportunistic pathogen associated with multidrug resistance (MDR) and high morbidity and mortality rates in healthcare settings. The emergence of strains resistant to last-resort antibiotics, such as colistin and carbapenems, poses significant therapeutic challenges. This study presents the complete genome analysis of the MDR strain K. pneumoniae BCSIR-JUMIID to elucidate its genetic architecture, resistance mechanisms, and virulence factors. The genome of K. pneumoniae BCSIR-JUMIID, isolated from a pharmaceutical wastewater in Dhaka, Bangladesh, was sequenced using next-generation sequencing technologies. Bioinformatics tools were employed for genome assembly, annotation, and functional analysis. Phylogenetic relationships were established through whole-genome comparisons. Antibiotic resistance genes, virulence factors, and mobile genetic elements were identified using the Comprehensive Antibiotic Resistance Database (CARD), ResFinder-4.5.0, Virulence Factors Database (VFDB), and various phage identification tools. The genome of K. pneumoniae BCSIR-JUMIID consists of 5,769,218 bp with a G+C content of 56.79%, assembled into 343 contigs. A total of 6,062 coding sequences (CDS), including 1,087 hypothetical proteins, 49 tRNA genes, and 4 rRNA genes, were identified. Key loci involved in capsular polysaccharide and O-antigen biosynthesis (KL150, KL107-D1, O3b) were detected. A diverse array of antibiotic resistance genes was uncovered, including those conferring resistance to beta-lactams, quinolones, and colistin. Phage analysis revealed the presence of multiple dsDNA bacteriophages, and CRISPR-Cas systems indicated robust phage defense mechanisms. The genomic analysis of K. pneumoniae BCSIR-JUMIID provides a detailed understanding of its resistance and virulence mechanisms, highlighting its potential for horizontal gene transfer and rapid adaptation. These findings underscore the necessity for continued surveillance and novel therapeutic strategies to combat MDR K. pneumoniae infections effectively.

microbiology↗

bioRxiv2024

Oxidative Injury to Lung Mitochondrial DNA is a Key Contributorfor the Development of Chemical Lung Injury

The mechanisms and extent to which inhalation of oxidant gases damage the mitochondrial genome contributing to the development of acute and chronic lung injury have not been investigated. C57BL/6 mice exposed to chlorine (Cl2) gas and returned to room air, developed progressive loss of lung DNA glycosylase OGG1, significant oxidative injury to mtDNA, decreased intact lung mitochondrial (mt) DNA, generation of inflammatory pathway by DAMPs causing airway and alveolar injury with significant mortality. Global proteomics identified over 1400 lung proteins with alteration of key mitochondrial proteins at 24 h post Cl2 exposure. Intranasal instillation of a recombinant protein containing mitochondrial targeted OGG1 (mitoOGG1) post exposure, decreased oxidative injury to mtDNA, lung mitochondrial proteome, severity of the acute and chronic lung injury and increased survival. These data show that injury to the mt-genome is a key contributor to the development of acute and chronic lung injury.

physiology↗

bioRxiv2024

Phytochemical and Therapeutic Evaluation of Ficus nervosa Leaves: Impact on Oxidative Stress, Analgesic, Diarrhea, and Blood Clotting in a Mice Model

BackgroundFicus nervosa (FN) leaves have been traditionally used in ethnomedicine for the treatment of various ailments, this study aimed to investigate the cold methanol extract of FN for its antioxidant, analgesic, antidiarrheal, and thrombolytic properties, along with preliminary phytochemical screening to identify key bioactive compounds and acute toxicity test to assess the safety profile of the extract. MethodsIn this study, we conducted an initial investigation to identify the major phytochemical groups present in the leaves of Ficus nervosa. Using conventional phytochemical screening methods on cold methanol extracts, we consistently identified phenols and flavonoids as the predominant bioactive compounds. Following this phytochemical characterization, we assessed the biological activities of the extracts across multiple models. The antioxidant capacity and free radical-scavenging ability of the leaves extracts were evaluated using the DPPH (2,2-Diphenyl-1-picrylhydrazyl) assay. Analgesic efficacy was assessed through acetic acid-induced writhing and electrically induced heat nociception tests. Antidiarrheal effects were examined using castor oil-induced diarrhea and an enteropooling assay in mice. To determine thrombolytic activity, we conducted a human blood clot lysis assay, while preclinical toxicity testing was conducted to evaluate the safety profile of the extracts. Statistical analysis was performed using one-way ANOVA with Duncans Multiple Range Test (DMRT) to validate the significance of the results. ResultsThe study of Antioxidant Potential, the ESFs (ethyl soluble fraction) antioxidant capacity, measured at 409.91 {+/-} 0.59 mg of ascorbic acid equivalent (AAE)/g in the phosphomolybdenum assay, signifies a strong free radical scavenging activity. This level of antioxidant action, alongside a potent free radical neutralizing concentration (IC of 9.99 {+/-} 0.41 g/mL), suggests that the ESF could effectively counteract oxidative stress. Analgesic activity at 500 mg/kg, FN extract produced a 68.05% suppression of writhing in mice, which was statistically significant (p<0.001) compared to standard morphines (74.05%) inhibition. The extract also significantly prolonged reaction latency to thermal-induced pain in hotplate model. The antidiarrheal activity showed 52.09% and 59.0% suppression of defecation, compared to standard loperamides 73.1%, with statistically significant p-values (p<0.04 and p<0.01). These effects, combined with the notable decrease in intestinal fluid accumulation and defecation frequency in enteropooling assays, indicate that FN extract might interact with intestinal motility or fluid secretion pathways, providing antidiarrheal benefits. Additionally, the chloroform-soluble fraction of FN exhibited moderate thrombolytic activity, achieving 39.79% clot lysis compared to streptokinase (69.52%). Although this thrombolytic potential is moderate, it indicates that the fraction contains compounds with some fibrinolytic properties, which could be useful as adjunctive agents in preventing thrombosis. ConclusionOverall, the cold methanol extract of FN leaves demonstrates the therapeutic potential in preclinical settings. Future research is warranted to isolate the specific bioactive compounds and explain their mechanisms of action to further support the development of new treatments and contributing to modern medicinal practices based on this plant leaves.

plant biology↗

bioRxiv2024

Phytochemical screening, analgesic, anti-pyretic and antibacterial potentials of Litsea glutinosa (L) leaves extracts in vivo and in vitro technique

BackgroundLitsea glutinosa leaves (LG) have been used as traditional medicine to treat diseases since ancient times. This study aimed to investigate the cold methanol extract of LG for its analgesic, antipyretic and antibacterial activities, along with preliminary phytochemical screening and acute toxicity test. MethodsIn this study, we first investigated the major phytochemicals group present applying modern chromatographic technique HPLC in addition to conventional methods for Phyto screening in cold methanol extracts LG leaves. Both methods simultaneously demonstrated major bioactive compounds found in the extract were phenol, flavonoid. The purposive efficacy and toxicity were then assessed through preclinical testing ResultsIn hot plate method, the highest pain inhibitory activity was found at a dose of 500 mg/kg of crude extract (3.37{+/-} 0.31sec) which differed significantly (P <0.01 and P <0.001) with that of the standard drug morphine (6.47{+/-} 0.23 sec). The extract significantly prolonged reaction latency to thermal-induced pain in hotplate model. Analgesic activity at 500 mg/kg, LG extract produced a 70% suppression of writhing in mice, which was statistically significant (p<0.001) compared to standard morphines (77.5%) inhibition. In antipyretic activity assay, the crude extract showed notable reduction in body temperature (36.17 {+/-} 0.32{degrees}C) at dose of 300 mg/kg-body weight, when the standard (at dose 100 mg/kg-body weight) exerted (36.32 {+/-} 0.67{degrees}C) after 3 h of administration. In antibacterial studies, results showed that inhibition of bacterial growth at 400 g dose of each extract clearly inhibited growth of bacteria from 11 to 22 mm. The extractives carbon tetrachloride fraction, chloroform soluble fraction, ethyl acetate fraction demonstrated notably greater inhibitory zone widths (p < 0.05) against tested strains. ConclusionOverall, the cold methanol extract of LG leaves demonstrates the therapeutic potential in preclinical settings.

pharmacology and toxicology↗

bioRxiv2023

Bacterial risk evaluation of widely consumed fast foods by the younger population in Bangladesh and its potential health effects

Food-borne illness is a significant public health concern in Bangladesh, especially among the younger generation. They often consume spicy street foods, such as Fusca, Hog plum bedfellow, and Chotpoti. These foods can be contaminated with harmful bacteria, which can cause various diseases, including diarrhea, cholera, and dysentery. This study investigated the microbiological quality of three commonly consumed street foods in Bangladesh. We collected samples of Fusca, Hog plum bedfellow, and Chotpoti from different vendors in Dhaka and analyzed them in a laboratory. We found that all three of the food samples were contaminated with a variety of bacteria, including Bacillus spp., Haemophilus spp., Salmonella spp., Klebsiella spp., Staphylococcus spp., and Streptococcus spp. Some of these bacteria, such as Haemophilus spp., were resistant to the antibiotic ciprofloxacin. Our findings suggest that there is a high risk of food-borne illness associated with the consumption of street foods in Bangladesh. We urge vendors and consumers to take steps to improve food safety, such as proper food handling and cooking and clean water and utensils.

microbiology↗

bioRxiv2023

Poly(ADP-ribose) mediates bioenergetic defects and redox imbalance in neurons following oxygen and glucose deprivation

PARP-1 over-activation results in cell death via excessive PAR generation in different cell types, including neurons following brain ischemia. Glycolysis, mitochondrial function, and redox balance are key cellular processes altered in brain ischemia. Studies show that PAR generated after PARP-1 over-activation can bind hexokinase-1 (HK-1) and result in glycolytic defects and subsequent mitochondrial dysfunction. HK-1 is the neuronal hexokinase and catalyzes the first reaction of glycolysis, converting glucose to glucose-6-phosphate (G6P), a common substrate for glycolysis, and the pentose phosphate pathway (PPP). PPP is critical in maintaining NADPH and GSH levels via G6P dehydrogenase activity. Therefore, defects in HK-1 will not only decrease cellular bioenergetics but will also cause redox imbalance due to the depletion of GSH. In brain ischemia, whether PAR-mediated inhibition of HK-1 results in bioenergetics defects and redox imbalance is not known. We used oxygen-glucose deprivation (OGD) in mouse cortical neurons to mimic brain ischemia in neuronal cultures and observed that PARP-1 activation via PAR formation alters glycolysis, mitochondrial function, and redox homeostasis in neurons. We used pharmacological inhibition of PARP and adenoviral-mediated overexpression of wild-type HK-1 (wtHK-1) and PAR-binding mutant HK-1 (pbmHK-1). Our data show that PAR inhibition or overexpression of HK-1 significantly improves glycolysis, mitochondrial function, redox homeostasis, and cell survival in mouse cortical neurons exposed to OGD. These results suggest that PAR binding and inhibition of HK-1 during OGD drives bioenergetic defects in neurons due to inhibition of glycolysis and impairment of mitochondrial function.

neuroscience↗

bioRxiv2022

N-Terminomic Changes of Neurons During Excitotoxicity Reveals Proteolytic Events Associated with Synaptic Dysfunctions and Potential Targets for Neuroprotection

Excitotoxicity is a neuronal death process initiated by over-stimulation of ionotropic glutamate receptors. Although dysregulation of proteolytic signaling networks is critical for excitotoxicity, the identity of affected proteins and mechanisms by which they induce neuronal cell death remain unclear. To address this, we used quantitative N-terminomics to identify proteins modified by proteolysis in neurons undergoing excitotoxic cell death. We found that most proteolytically processed proteins in excitotoxic neurons are likely substrates of calpains, including key synaptic regulatory proteins such as CRMP2, doublecortin-like kinase I, Src tyrosine kinase and calmodulin-dependent protein kinase II{beta} (CaMKII{beta}). Critically, calpain-catalyzed proteolytic processing of these proteins generates stable truncated fragments with altered activities that potentially contribute to neuronal death by perturbation of synaptic organization and function. Blocking calpain-mediated proteolysis of one of these proteins, Src protected against neuronal loss in a rat model of neurotoxicity. Extrapolation of our N-terminomic results led to the discovery that CaMKII, an isoform of CaMKII{beta} undergoes differential processing in mouse brains under physiological conditions and during ischemic stroke. In summary, our findings inform excitotoxic neuronal death mechanism and suggest potential therapeutic strategies for neuroprotection. In BriefAmeen, et al. used a proteomic method called N-terminomics to identify proteolytic events occurring in neurons during excitotoxicity. They found that most proteolytic processing is mediated by calpains, resulting in the generation of stable truncated fragments with the potential to induce synaptic dysfunction and loss, eventually leading to neuronal death. They further showed that some of these proteolytic processed proteins, such as the protein kinases Src and CaMKII, are potential targets for neuroprotection. HighlightsO_LIIdentification of over 300 neuronal proteins cleaved by calpains to form stable truncated fragments during excitotoxicity. C_LIO_LIThe calpain cleavage sites of these proteins unveil for the first time the preferred cleavage sequences of calpains in neurons. C_LIO_LIThese pathological proteolytic events potentially induce synaptic dysfunction and loss, which likely contribute to excitotoxic neuronal death. C_LIO_LISome of the neuronal proteins proteolyzed by calpains are potential targets of neuroprotection. C_LI Graphical abstract: Pathological proteolytic events in neurons during excitotoxicity unveiled by N-terminomic analyses(A) N-terminomic and global proteomic analyses identified neo-N-terminal sites and neuronal proteins undergoing significant abundance changes during excitotoxicity. (B) Informatic analysis of the proteomic results predicted (i) the preferred sequences of proteolytic processing of neuronal proteins catalyzed by calpains during excitotoxicity and (ii) perturbation of synaptic organization and functions as the major consequence of calpain-mediated proteolytic events. (C) Validation of these predictions and further experimentations unveiled: (i) calpain-mediated cleavage of proteins associated with synaptic damage in excitotoxic neurons, (ii) a new mechanism of dysregulation of CaMKII and CaMKII{beta}, which are key protein kinases governing synaptic dysfunctions and excitotoxic neuronal death and (iii) potential therapeutic targets such as the protein kinases Src and CaMKII for neuroprotection O_FIG O_LINKSMALLFIG WIDTH=194 HEIGHT=200 SRC="FIGDIR/small/484119v2_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@1c69873org.highwire.dtl.DTLVardef@142db3forg.highwire.dtl.DTLVardef@481521org.highwire.dtl.DTLVardef@6359e2_HPS_FORMAT_FIGEXP M_FIG C_FIG One Sentence SummaryProteolytic events in neurons during excitotoxicity inform neuronal death mechanism and potential therapeutic strategies for neuroprotection.

neuroscience↗

bioRxiv2022

Voltage-Sensing Phosphatase (VSP) Regulates Endocytosis-Dependent Nutrient Absorption in Chordate Enterocytes

Voltage-sensing phosphatase (VSP) is a unique membrane protein that translates membrane electrical activities into the changes of phosphoinositide profiles. VSP orthologs from various species have been intensively investigated toward their biophysical properties, primarily using a heterologous expression system. In contrast, the physiological role of VSP in native tissues remains largely unknown. Here we report that zebrafish VSP (Dr-VSP) is functionally expressed on the endomembranes of lysosome-rich enterocytes (LREs) that mediate dietary protein absorption via endocytosis in the zebrafish mid-intestine. Dr-VSP-deficient LREs were remarkably defective in forming endosomal vacuoles after initial uptake of dextran and mCherry. Dr-VSP-deficient zebrafish exhibited growth restriction and higher mortality during the critical period when zebrafish larvae rely primarily on exogenous feeding via intestinal absorption. Furthermore, our comparative study on marine invertebrate Ciona intestinalis VSP (Ci-VSP) revealed co-expression with endocytosis-associated genes in absorptive epithelial cells of the Ciona digestive tract, corresponding to zebrafish LREs. These findings signify a crucial role of VSP in regulating endocytosis-dependent nutrient absorption in specialized enterocytes across animal species. Summary statementVoltage-sensing phosphatase (VSP) is identified in absorptive enterocytes, revealing its crucial role in promoting endocytosis and nutrient absorption during early development.

cell biology↗

bioRxiv2020

An Atlas of Phosphorylation and Proteolytic Processing Events During Excitotoxic Neuronal Death Reveals New Therapeutic Opportunities

Excitotoxicity, a neuronal death process in neurological disorders, is initiated by over-stimulation of neuronal ionotropic glutamate receptors. The over-stimulated receptors dysregulate proteases, protein kinases and phosphatases, which in turn modify target neuronal proteins to induce cell death. To decipher this cell death mechanism, we used quantitative proteomics, phosphoproteomics and N-terminomics to identify modified proteins in excitotoxic neurons. Data, available in ProteomeXchange (identifiers: PXD019527 and PXD019211), enabled us to identify over one thousand such proteins with calpains, cathepsins and over twenty protein kinases as their major modifiers. These protein modification events can potentially perturb signalling pathways governing cell survival, synaptogenesis, axonal guidance and mRNA processing. Importantly, blocking the modification of Src protein kinase, a signalling hub in excitotoxic neurons, protected against neuronal loss in vivo in a rat model of neurotoxicity. Besides offering new insights into excitotoxic neuronal death mechanism, our findings suggest potential neuroprotective therapeutic targets for treating neurological disorders. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=162 SRC="FIGDIR/small/151456v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@1f0191forg.highwire.dtl.DTLVardef@17ba2org.highwire.dtl.DTLVardef@15c0848org.highwire.dtl.DTLVardef@123d28b_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIMulti-dimensional proteomic analysis identified proteins modified by proteolysis and altered phosphorylation in neurons undergoing excitotoxic cell death. C_LIO_LICalpains, cathepsins and over twenty protein kinases are major modifiers of these proteins. C_LIO_LIThese protein modification events are predicted to impact cell survival, axonal guidance, synaptogenesis and mRNA processing. C_LIO_LIBlocking modification of an identified protein Src, which acts as a major signalling hub in neurons, was protective against excitotoxic injury in vivo. C_LI In BriefUsing multidimensional proteomic approaches, Ameen, et al. mapped the changes of proteome, phosphoproteome and N-terminome of cultured primary neurons during excitotoxicity, a crucial neuronal death process in neurological disorders. These proteomic changes document new excitotoxicity-associated molecular events, and offer insights into how these events are organized to induce neuronal death. Potential therapeutic relevance of these molecular events is illustrated by the demonstration that in vivo blockade of one of these events could protect against excitotoxic neuronal loss.

biochemistry↗

bioRxiv2020

Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: a computational biology approach

The newly identified SARS-CoV-2 has now been reported from around 183 countries with more than a million confirmed human cases including more than 68000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins have gotten substantial attention recently. Spike glycoprotein is widely considered as a possible target to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment tools. In this study, 483 unique variations have been identified among the genomes including 25 non-synonymous mutations and one deletion in the spike protein of SARS-CoV-2. Among the 26 variations detected, 12 variations were located at the N-terminal domain and 6 variations at the receptor-binding domain (RBD) which might alter the interaction with receptor molecules. In addition, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on our findings, potential inhibitors can be designed and tested targeting these proposed sites of variation.

bioinformatics↗

bioRxiv2020

Recognition of A Highly Conserved DSRCPTQ Epitope in Envelope Protein of Zika Virus Through in silico Approaches

The recurrent and recent outbreak of Zika Virus (ZIKV) has turned into global concern as yet there is no appropriate preventive measure been found. Situation getting worse as this virus also associates with several birth defects in neonatal such as primary microcephaly as well as many other neurological disorders. ZIKV adopts a wide host range which has hastened its expansion more recklessly. Hence, now there is an acute demand for developing a preventive vaccine against ZIKV. Immunoinformatic techniques have been employed in this study to pick out a highly conserved versatile antigenic B-cell linear epitope for all strains of ZIKV. Capsid protein (C), Membrane Glycoprotein Precursor (PrM), envelope protein (E) and RNA-dependent RNA Polymerase (NS5) have investigated by the implementation of sequence analysis and different epitope prediction methods. Some potential linear peptides have been recognized and tested for hydrophilicity and conservancy. Peptide with best antigenic properties was selected as ultimate final epitope and further structural exploration revealed its compatible position in protein 3D structure. Being fully conserved in all strains of ZIKV and its position in Envelope protein suggested epitope DSRCPTQ can be a quantum leap in the advancement of ZIKV prevention. However, extensive in vitro plus in vivo experimentations are needed to be clarified about the real potency of the selected epitope.

bioinformatics↗

bioRxiv2019

LSO:Ce Inorganic Scintillators are Biocompatible with Neuronal and Circuit Function

Optogenetics is widely used in neuroscience to control neural circuits. However, non-invasive methods for light delivery in brain are needed to avoid physical damage caused by current methods. One potential strategy could employ x-ray activation of radioluminescent particles (RPLs), enabling localized light generation within the brain. RPLs composed of inorganic scintillators can emit light at various wavelengths depending upon composition. Cerium doped lutetium oxyorthosilicate (LSO:Ce), an inorganic scintillator that emits blue light in response to x-ray or UV stimulation, could potentially be used to control neural circuits through activation of channelrhodopsin-2 (ChR2), a light-gated cation channel. Whether inorganic scintillators themselves negatively impact neuronal processes and synaptic function is unknown, and was investigated here using cellular, molecular, and electrophysiological approaches. As proof of principle, we applied UV stimulation to 4 m LSO:Ce particles during whole-cell recording of CA1 pyramidal cells in acutely prepared hippocampal slices from mice that expressed ChR2 in glutamatergic neurons. We observed an increase in frequency and amplitude of spontaneous excitatory postsynaptic currents (EPSCs), indicating UV activation of ChR2 and excitation of neurons. Importantly, we found that LSO:Ce particles have no effect on survival of primary mouse cortical neurons, even after 24 hours of exposure. In extracellular dendritic field potential recordings, we observed no change in strength of basal glutamatergic transmission up to 3 hours of exposure to LSO:Ce microparticles. However, there was a slight decrease in the frequency of spontaneous EPSCs in whole-cell voltage-clamp recordings from CA1 pyramidal cells, with no change in current amplitudes. No changes in the amplitude or frequency of spontaneous inhibitory postsynaptic currents (IPSCs) were observed. Finally, long term potentiation (LTP), a synaptic modification believed to underlie learning and memory and a robust measure of synaptic integrity, was successfully induced, although the magnitude was slightly reduced. Together, these results show LSO:Ce particles are biocompatible even though there are modest effects on baseline synaptic function and long-term synaptic plasticity. Importantly, we show that light emitted from LSO:Ce particles is able to activate ChR2 and modify synaptic function. Therefore, LSO:Ce inorganic scintillators are potentially viable for use as a new light delivery system for optogenetics.

neuroscience↗

bioRxiv2018

Different features of cholera in malnourished and non-malnourised children: analysis of 10-year surveillance data from a large diarrheal disease hospital in urban Bangladesh

Background: Malnourished children are more prone to infectious diseases including severe diarrhea compared to non-malnourished children. Understanding of the differences in the presentation of severe diarrhea such as cholera in children with varying nutritional status may help in the early identification and management these children. However, data are scarce on differences in the presentation in such children. Thus, we aimed to identify the clinical differentials among children with cholera with or without malnutrition.\n\nMethods: Data were extracted from diarrheal disease surveillance system (DDSS) of the Dhaka Hospital of icddr,b for the period, January 2008 to December 2017. Among under-five children, cholera positive (culture confirmed) and malnourished children (weight-for-age, weight-for-length or height-for-age Z score (WAZ, WHZ or HAZ) <-2) were considered as the cases (n=305) and children with cholera but non-malnourished (WAZ, HAZ, and WHZ [≥]-2.00 to [≤]+2.00) were the controls (n=276).\n\nResults: A total of 14,403 under-five children were enrolled in the surveillance system during the study period. After adjusting for potential covariates such as maternal illiteracy and slum dwelling, it was revealed that under-five malnourished children with cholera significantly more often presented to the hospital during evening hours (6 pm to 12 mid-night) (OR=1.64, 95% CI=1.16-2.31, P<0.05), had fathers who were illiterate (OR=1.70, 95% CI=1.11-2.62, P<0.05), presented with history of cough within last 7 days (OR=1.64, 95% CI=1.10-2.43, P<0.05), dehydrating diarrhea (OR=1.70, 95% CI=1.15-2.53, P<0.05), and had longer hospitalization (OR=1.50, 95% CI=1.05-2.14, P<0.05).\n\nConclusions: The study results underscore the importance of understanding of the basic differences in the presentation of severe cholera in malnourished children for prompt identification and the subsequent management of these children. These observations may help policy makers in formulating better case management strategy.\n\nAuthor SummaryMalnourished children are more vulnerable to infectious diseases including cholera in comparison to the non-malnourished children. They often have suboptimal immune function, though there is no precise information on whether there is any difference in associated factor(s) or clinical course of cholera in under-five children with varying nutritional status. Therefore, this study was conducted to elucidate these insights by using the surveillance data of the Dhaka hospital of icddr,b. Among all the under-five children with cholera, 305 malnourished (WAZ or WLZ or HAZ <-2) children constituted as the cases (malnourished), and another 276 non-malnourished (WAZ, HAZ, and WHZ [≥]-2.00GtoG[≤]+2.00) cholera children formed the comparison group.\n\nIn this study we revealed that care seeking at evening time was more common in the malnourished children with cholera compared to those without malnutrition. Dehydrating diarrhea was about two folds higher and prolonged hospitalization was frequent in malnourished children with cholera than their counterparts. These key findings may help policy makers in formulating better case management strategy in the near future.

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