Biology subjects

Adhikari, A.

Publications and source records attributed to Adhikari, A..

At least 37 records · Page 2Linked to original sources

bioRxiv2022

Identification of potential human pancreatic α-amylase inhibitors from natural products by molecular docking, MM/GBSA calculations, MD simulations, and ADMET analysis

Human pancreatic -amylase (HPA), which works as a catalyst for carbohydrate hydrolysis, is one of the viable targets to control type 2 diabetes. The inhibition of -amylase lowers blood glucose levels and helps to alleviate hyperglycemia complications. Herein, we systematically screened the potential HPA inhibitors from an in-house library of natural products by molecular modeling. The modeling encompasses molecular docking, MM/GBSA binding energy calculations, MD simulations, and ADMET analysis. This research identified newboulaside B, newboulaside A, quercetin-3-O-{beta}-glucoside, and sasastilboside A as the top four potential HPA inhibitors from the library of natural products, whose Glide docking scores and MM/GBSA binding energies range from -9.191 to -11.366 kcal/mol and -19.38 to -50.29 kcal/mol, respectively. Based on the simulation, among them, newboulaside B was found as the best HPA inhibitor. Throughout the simulation, with the deviation of 3[A] (acarbose = 3[A]), it interacted with ASP356, ASP300, ASP197, THR163, ARG161, ASP147, ALA106, and GLN63 via hydrogen bonding. Additionally, the comprehensive ADMET analysis revealed that it has good pharmacokinetic properties having not acutely toxic, moderately bioavailable, and non-inhibitor nature toward cytochrome P450. All the results suggest that newboulaside B might be a promising candidate for drug discovery against type 2 diabetes. Graphical Abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

bioinformatics↗

bioRxiv2022

Extraction and characterization of cellulose from invasive weeds from central Nepal: A potential prospect of environmental management.

The cellulose is made up of long chains of polysaccharide of glucose molecules. Microfibrils are formed when numerous hydrogen-bonded cellulose chains unite, they are extremely stiff and contribute to physical stability, due to this general ability of forming these microfibrils to form long chains, cellulose is an ideal molecule for the manufacturing of packaging materials and bioplastics. On the other hand, Invasive plant species are one of the major constituents for environmental degradation and its application seems outmost. The main purpose of this study is to extract and identify the composition of cellulose fiber and characterize the fiber of invasive plant species that could be used as a replacement for plastics and textiles in some cases. In this study, Cellulose was isolated from 6 invasive species collected in Nepals Ramechhap district using various techniques, the composition of the fiber was identified using AOAC method 973.18, ASTM method D1106-96 and ASTM method E1755-01 and characterized using FTIR spectroscopy with weight analyses. Acid hydrolysis, chlorination, alkaline extraction, and bleaching were among the chemical methods adopted. In all of the samples, there were two primary absorbance peaks. The first occurred at low wavelengths in the 700-1,800 cm-1 range, while the second occurred at higher wavelengths in the 2,700-3,500 cm-1 range.The percentage of lignin within the final sample was determined in the range of 4.4-3.1% and the percentage yield of cellulose was determined within the range of 78-62%.The study shows that the cellulose can be extracted from the taken invasive plant species and can be used for further applications.

biochemistry↗

bioRxiv2022

A Feed-forward Pathway Drives LRRK2 kinaseMembrane Recruitment and Apparent Activation

Activating mutations in the Leucine Rich Repeat Kinase 2 (LRRK2) cause Parkinsons disease and previously we showed that activated LRRK2 phosphorylates a subset of Rab GTPases (Steger et al., 2017). Moreover, Golgi-associated Rab29 can recruit LRRK2 to the surface of the Golgi and activate it there for both auto- and Rab substrate phosphorylation. Here we define the precise Rab29 binding region of the LRRK2 Armadillo domain between residues 360-450 and show that this domain, termed "Site #1", can also bind additional LRRK2 substrates, Rab8A and Rab10. Moreover, we identify a distinct, N-terminal, higher affinity interaction interface between LRRK2 phosphorylated Rab8 and Rab10 termed "Site #2", that can retain LRRK2 on membranes in cells to catalyze multiple, subsequent phosphorylation events. Kinase inhibitor washout experiments demonstrate that rapid recovery of kinase activity in cells depends on the ability of LRRK2 to associate with phosphorylated Rab proteins, and phosphorylated Rab8A stimulates LRRK2 phosphorylation of Rab10 in vitro. Reconstitution of purified LRRK2 recruitment onto planar lipid bilayers decorated with Rab10 protein demonstrates cooperative association of only active LRRK2 with phospho-Rab10-containing membrane surfaces. These experiments reveal a feed-forward pathway that provides spatial control and membrane activation of LRRK2 kinase activity.

biochemistry↗

bioRxiv2022

A genetically-defined population in the lateral and ventrolateral periaqueductal gray selectively promotes flight to safety

When encountering external threats, survival depends on the engagement of appropriate defensive reactions to minimize harm. There are major clinical implications for identifying the neural circuitry and activation patterns that produce such defensive reactions, as maladaptive overactivation of these circuits underlies pathological human anxiety and fear responses. A compelling body of work has linked activation of large glutamatergic neuronal populations in the midbrain periaqueductal gray (PAG) to defensive reactions such as freezing, flight and threat-induced analgesia. These pioneering data have firmly established that the overarching functional organization axis of the PAG is along anatomically-defined columnar boundaries. Accordingly, broad activation of the dorsolateral column induces flight, while activation of the lateral or ventrolateral (l and vl) columns induces freezing. However, the PAG contains a diverse arrangement of cell types that vary in neurochemical profile and location. How these cell types contribute to defensive responses remains largely unknown, indicating that targeting sparse, genetically-defined populations can lead to a deeper understanding of how the PAG generates a wide array of behaviors. Though several prior works showed that broad excitation of the lPAG or vlPAG causes freezing, we found that activation of lateral and ventrolateral PAG (l/vlPAG) cholecystokinin-expressing (cck) cells selectively causes flight to safer regions within an environment. Furthermore, inhibition of l/vlPAG-cck cells reduces avoidance of a predatory threat without altering other defensive behaviors like freezing. Lastly, l/vlPAG-cck activity increases away from threat and during movements towards safer locations. In contrast, activating l/vlPAG cells pan-neuronally promoted freezing and these cells were activated near threat. These data underscore the importance of investigating genetically-identified PAG cells. Using this approach, we found a sparse population of cck-expressing l/vlPAG cells that have distinct and opposing function and neural activation motifs compared to the broader local ensemble defined solely by columnar anatomical boundaries. Thus, in addition to the anatomical columnar architecture of the APG, the molecular identity of PAG cells may confer an additional axis of functional organization, revealing unexplored functional heterogeneity.

neuroscience↗

bioRxiv2021

Longitudinal characterisation of phagocytic and neutralisation functions of anti-Spike antibodies in plasma of patients after SARS-CoV-2 infection.

Phagocytic responses by effector cells to antibody or complement-opsonised viruses have been recognized to play a key role in anti-viral immunity. These include antibody dependent cellular phagocytosis mediated via Fc-receptors, phagocytosis mediated by classically activated complement-fixing IgM or IgG1 antibodies and antibody independent phagocytosis mediated via direct opsonisation of viruses by complement products activated via the mannose-binding lectin pathway. Limited data suggest these phagocytic responses by effector cells may contribute to the immunological and inflammatory responses in SARS-CoV-2 infection, however, their development and clinical significance remain to be fully elucidated. In this cohort of 62 patients, acutely ill individuals were shown to mount phagocytic responses to autologous plasma-opsonised SARS-CoV-2 Spike protein-coated microbeads as early as 10 days post symptom onset. Heat inactivation of the plasma prior to use as an opsonin caused 77-95% abrogation of the phagocytic response, and pre-blocking of Fc-receptors on the effector cells showed only 18-60% inhibition. These results suggest that SARS-CoV-2 can provoke early phagocytosis, which is primarily driven by heat labile components, likely activated complements, with variable contribution from anti-Spike antibodies. During convalescence, phagocytic responses correlated significantly with anti-Spike IgG titers. Older patients and patients with severe disease had significantly higher phagocytosis and neutralisation functions when compared to younger patients or patients with asymptomatic, mild, or moderate disease. A longitudinal study of a subset of these patients over 12 months showed preservation of phagocytic and neutralisation functions in all patients, despite a drop in the endpoint antibody titers by more than 90%. Interestingly, surface plasmon resonance showed a significant increase in the affinity of the anti-Spike antibodies over time correlating with the maintenance of both the phagocytic and neutralisation functions suggesting that improvement in the antibody quality over the 12 months contributed to the retention of effector functions. Author SummaryLimited data suggest antibody dependent effector functions including phagocytosis may contribute to the immunological and inflammatory responses in SARS CoV-2 infection, however, their development, maintenance, and clinical significance remain unknown. In this study we show: O_LIPatients with acute SARS CoV-2 infection can mount phagocytic responses as early as 10 days post symptom onset and these responses were primarily driven by heat labile components of the autologous plasma. These results indicate that the current approach of studying phagocytosis using purified or monoclonal antibodies does not recapitulate contribution by all components in the plasma. C_LIO_LIIn convalescent patients, high phagocytic responses significantly correlated with increasing age, increasing disease severity, high neutralisation functions and high anti-Spike antibody titers, particularly IgG1. C_LIO_LILongitudinal study of convalescent patients over a 12-month period showed maintenance of phagocytic and neutralisation functions, despite a drop in the anti-Spike endpoint antibody titers by more than 90%. However, we found significant increase in the affinity of the anti-Spike antibodies over the 12-month period and these correlated with the maintenance of functions suggesting that improvement in the antibody quality over time contributed to the retention of effector functions. Clinically, measuring antibody titers in sera but not the quality of antibodies is considered a gold standard indicator of immune protection following SARS-CoV 2 infection or vaccination. Our results challenge this notion and recommends change in the current clinical practice. C_LI

immunology↗

bioRxiv2021

Insulin-like growth factor-2 does not improve behavioral deficits in mouse and rat models of Angelman Syndrome

BackgroundAngelman Syndrome (AS) is a rare neurodevelopmental disorder for which there is currently no cure or effective therapeutic. Since the genetic cause of AS is known to be dysfunctional expression of the maternal allele of ubiquitin protein ligase E3A (UBE3A), several genetic animal models of AS have been developed. Both the Ube3a maternal deletion mouse and rat models of AS reliably demonstrate behavioral phenotypes of relevance to AS and therefore offer suitable in vivo systems in which to test potential therapeutics. One promising candidate treatment is insulin-like growth factor-2 (IGF-2), which has recently been shown to ameliorate behavioral deficits in the mouse model of AS and improve cognitive abilities across model systems. MethodsWe used both the Ube3a maternal deletion mouse and rat models of AS to evaluate the ability of IGF-2 to improve electrophysiological and behavioral outcomes. ResultsAcute systemic administration of IGF-2 had an effect on electrophysiological activity in the brain and on a metric of motor ability, however the effects were not enduring or extensive. Additional metrics of motor behavior, learning, ambulation, and coordination were unaffected and IGF-2 did not improve social communication, seizure threshold, or cognition. LimitationsThe generalizability of these results to humans is difficult to predict and it remains possible that dosing schemes (i.e., chronic or subchronic dosing), routes, and/or post-treatment intervals other than that used herein may show more efficacy. ConclusionsDespite a few observed effects of IGF-2, our results taken together indicate that IGF-2 treatment does not profoundly improve behavioral deficits in mice or rat models of AS. These findings shed cautionary light on the potential utility of acute systemic IGF-2 administration in the treatment of AS.

pharmacology and toxicology↗

bioRxiv2021

Essential Loop Dynamics Modulates Catalytic Activity in α-Chymotrypsin

Conformational dynamics of macromolecules including enzymes are essential for their function. The present work reports the role of essential dynamics in alpha-chymotrypsin (CHT) which correlates with its catalytic activity. Detailed optical spectroscopy and classical molecular dynamics (MD) simulation were used to study thermal stability, catalytic activity and dynamical flexibility of the enzyme. The study of the enzyme kinetics reveals an optimum catalytic efficiency at 308K. Polarization gated fluorescence anisotropy with 8-anilino-1-napthelene sulfonate (ANS) have indicated increasing flexibility of the enzyme with an increase in temperature. Examination of the structure of CHT reveal the presence of five loop regions (LRs) around the catalytic S1 pocket. MD simulations have indicated that flexibility increases concurrently with temperature which decreases beyond optimum temperature. Principal component analysis (PCA) of the eigenvectors manifests essential dynamics and gatekeeping role of the five LRs surrounding the catalytic pocket which controls the enzyme activity.

biophysics↗

bioRxiv2021

A Combined Spectroscopic and Molecular Modeling Study on Structure-Function-Dynamics under Chemical Modification: Alpha-Chymotrypsin with Formalin Preservative

Enzyme conformations can be altered via modification of its amino acid residues, side chains and large-scale domain modifications, which are closely linked to its function. Herein, we have addressed the role of residue modification in catalytic activity and molecular recognition of an enzyme alpha-chymotrypsin (CHT) in presence of covalent cross-linker formalin. Optical spectroscopy studies exhibit reduced catalytic activity of the enzyme with increased formalin concentration. Polarization gated anisotropy studies of a fluorophore 8-anilino-1- napthelenesulfonic acid (ANS) in CHT show a dip rise pattern in presence of formalin which is consistent with the generation of multiple ANS binding sites in the enzyme owing to modifications of its local amino acid residues. Molecular docking study on minimal local residue modifications in CHT reveals formation of a stable enzyme-substrate complex even with the serine-histidine cross-linked enzyme which prohibits product formation giving rise to reduced catalytic activity.

biophysics↗

bioRxiv2021

Dorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threats

Escape from threats has paramount importance for survival. However, it is unknown if a single circuit controls escape from innate and conditioned threats. The hypothalamic dorsal premammillary nucleus (PMd) may control escape, as it is activated by escape-inducing threats and projects to the region most implicated in flight, the dorsolateral periaqueductal gray (dlPAG). We show that in mice cholecystokinin (cck)-expressing PMd cells are activated during escape, but not other defensive behaviors. PMd-cck ensemble activity can also predict future escape. Furthermore, PMd inhibition decreases escape speed from both innate and conditioned threats. Inhibition of the PMd-cck projection to the dlPAG also decreased escape speed. Lastly, human fMRI data show that a posterior hypothalamic-to-dlPAG pathway increased activity during exposure to aversive images, indicating that a similar pathway may possibly have a related role in humans. Our data identify the PMd as a central node of the escape network.

neuroscience↗

bioRxiv2021

Invasive grass litter suppresses native species and promotes disease

Plant litter can alter ecosystems and promote plant invasions by changing resource acquisition, depositing toxins, and transmitting microorganisms to living plants. Transmission of microorganisms from invasive litter to live plants may gain importance as invasive plants accumulate pathogens over time since introduction. It is unclear, however, if invasive plant litter affects native plant communities by promoting disease. Microstegium vimineum is an invasive grass that suppresses native populations, in part through litter production, and has accumulated leaf spot diseases since its introduction to the U.S. In a greenhouse experiment, we evaluated how M. vimineum litter and accumulated pathogens mediated resource competition with the native grass Elymus virginicus. Resource competition reduced biomass of both species and live M. vimineum increased disease incidence on the native species. Microstegium vimineum litter also promoted disease on the native species, suppressed establishment of both species, and reduced biomass of M. vimineum. Nonetheless, interference competition from litter had a stronger negative effect on the native species, increasing the relative abundance of M. vimineum. Altogether, invasive grass litter suppressed both species, ultimately favoring the invasive species in competition, and increased disease incidence on the native species.

ecology↗

bioRxiv2021

Ageing impairs the airway epithelium defence response to SARS-CoV-2

Age-dependent differences in the clinical response to SARS-CoV-2 infection is well-documented1-3 however the underlying molecular mechanisms involved are poorly understood. We infected fully differentiated human nasal epithelium cultures derived from healthy children (1-12 years old), young adults (26-34 years old) and older adults (56-62 years old) with SARS-COV-2 to identify age-related cell-intrinsic differences that may influence viral entry, replication and host defence response. We integrated imaging, transcriptomics, proteomics and biochemical assays revealing age-related changes in transcriptional regulation that impact viral replication, effectiveness of host responses and therapeutic drug targets. Viral load was lowest in infected older adult cultures despite the highest expression of SARS-CoV-2 entry and detection factors. We showed this was likely due to lower expression of hijacked host machinery essential for viral replication. Unlike the nasal epithelium of young adults and children, global host response and induction of the interferon signalling was profoundly impaired in older adults, which preferentially expressed proinflammatory cytokines mirroring the "cytokine storm" seen in severe COVID-194,5. In silico screening of our virus-host-drug network identified drug classes with higher efficacy in older adults. Collectively, our data suggests that cellular alterations that occur during ageing impact the ability for the host nasal epithelium to respond to SARS-CoV-2 infection which could guide future therapeutic strategies.

immunology↗

bioRxiv2021

Redox Buffering Capacity of Nanomaterials as an Index of ROS-based Therapeutics and Toxicity: A Preclinical Animal Study

Precise control of intracellular redox status, i.e., maintenance of physiological level of reactive oxygen species (ROS) for mediating normal cellular functions (oxidative eustress) while evading the excess ROS stress (distress) is central to the concept of redox medicine. In this regard, engineered nanoparticles with unique ROS generation, transition, or depletion functions have the potential to be the choice of redox therapeutics. However, it is always challenging to estimate whether ROS-induced intracellular events are beneficial or deleterious to the cell. Here, we propose the concept of redox buffering capacity as a therapeutic index of engineered nanomaterials. As a steady redox state is maintained for normal functioning cells, we hypothesize that the ability of a nanomaterial to preserve this homeostatic condition will dictate its therapeutic efficacy. Additionally, the redox buffering capacity is expected to provide information about the nanoparticle toxicity. Here, using citrate functionalized trimanganese tetroxide nanoparticles (C-Mn3O4 NPs) as a model nanosystem we explored its redox buffering capacity in erythrocytes. Furthermore, we went on to study the chronic toxic effect (if any) of this nanomaterial in animal model in order to co-relate with the experimentally estimated redox buffering capacity. This study could function as a framework for assessing the capability of a nanomaterial as redox medicine (whether maintains eustress or damages by creating distress), thus orienting its application and safety for clinical use.

pharmacology and toxicology↗

bioRxiv2021

Redox Nanomedicine Cures Chronic Kidney Disease (CKD) by Mitochondrial Reconditioning

Targeting reactive oxygen species (ROS) while maintaining cellular redox signaling is crucial in the development of redox medicine for the therapeutic benefit as the origin of several prevailing diseases including chronic kidney disease (CKD) is linked to ROS imbalance and associated mitochondrial dysfunction. Here, we have shown that an indigenously developed nanomedicine comprising of Mn3O4 nanoparticles duly functionalized by biocompatible ligand citrate (C-Mn3O4 NPs) can maintain cellular redox balance in an animal model. We developed a cisplatin-induced CKD model in C57BL/6j mice where severe mitochondrial dysfunction resulting in oxidative distress lead to the pathogenesis. Four weeks of treatment with C-Mn3O4 NPs restored renal function, preserved normal kidney architecture, ameliorated overexpression of pro-inflammatory cytokines, and arrested glomerulosclerosis and interstitial fibrosis in CKD mice. A detailed study involving human embryonic kidney (HEK 293) cells and isolated mitochondria from experimental animals revealed that the molecular mechanism behind the pharmacological action of the nanomedicine involves protection of structural and functional integrity of mitochondria from oxidative damage, the subsequent reduction in intracellular ROS, and maintenance of cellular redox homeostasis. To the best of our knowledge, such studies that efficiently treated a multifaceted disease like CKD using a biocompatible redox nanomedicine are sparse in the literature. Successful clinical translation of this nanomedicine may open a new avenue in redox-mediated therapeutics of several other diseases (e.g., diabetic nephropathy, neurodegeneration, and cardiovascular disease) where oxidative distress plays a central role in pathogenesis.

pharmacology and toxicology↗

bioRxiv2021

Development of Tribo-Electroceutical Fabrics for Potential Application in Self-sanitizing Personal Protective Equipment (PPE)

Attachment of microbial bodies including coronavirus on the surface of personal protective equipment (PPE) is found to be potential threat of spreading infection. Here, we report the development of a novel tribo-electroceutical fabric (TECF) consisting of commonly available materials namely Nylon, and Silicone Rubber (SR) for the fabrication of protective gloves on Nitrile platform, as a model wearable PPE. A small triboelectric device (2 cm x 2 cm) consisting of SR and Nylon on Nitrile can generate more than 20 volt transient or 41 {micro}W output power, which is capable of charging a capacitor up to 65 V in only [~]50 sec. The novelty of the present work relies on the TECF led anti-microbial activity through the generation of an electric current in saline water. The fabrication of TECF based functional prototype gloves can generate hypochlorite ions through the formation of electrolysed water upon rubbing them with saline water. Further a computational modelling has been employed to reveal the optimum structure and mechanistic pathway of anti-microbial hypochlorite generation. Detailed anti-microbial assays have been performed to establish effectiveness of such TECF based gloves to reduce the risk from life threatening pathogen spreading. The present work provides the rationale to consider the studied TECF, or other material with comparable properties, as material of choice for the development of self-sanitizing PPE in the fight against microbial infections including COVID-19.

microbiology↗

bioRxiv2021

Nanoceutical Fabric Prevents COVID-19 Spread through Expelled Respiratory Droplets: A Combined Computational, Spectroscopic and Anti-microbial Study

Centers for Disease Control and Prevention (CDC) warns the use of one-way valves or vents in free masks for potential threat of spreading COVID-19 through expelled respiratory droplets. Here, we have developed a nanoceutical cotton fabric duly sensitized with non-toxic zinc oxide nanomaterial for potential use as membrane filter in the one way valve for the ease of breathing without the threat of COVID-19 spreading. A detailed computational study revealed that zinc oxide nanoflowers (ZnO NF) with almost two-dimensional petals trap SARS-CoV-2 spike proteins, responsible to attach to ACE-2 receptors in human lung epithelial cells. The study also confirm significant denaturation of the spike proteins on the ZnO surface, revealing removal of virus upon efficient trapping. Following the computational study, we have synthesized ZnO NF on cotton matrix using hydrothermal assisted strategy. Electron microscopic, steady-state and picosecond resolved spectroscopic studies confirm attachment of ZnO NF to the cotton (i.e., cellulose) matrix at atomic level to develop the nanoceutical fabric. A detailed antimicrobial assay using Pseudomonas aeruginosa bacteria (model SARS-CoV-2 mimic) reveals excellent anti-microbial efficiency of the developed nanoceutical fabric. To our understanding the novel nanoceutical fabric used in one-way valve of a face mask would be the choice to assure breathing comfort along with source control of COVID-19 infection. The developed nanosensitized cloth can also be used as antibacterial/anti CoV-2 washable dress material in general. GRAPHICAL ABSTRACT O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY A novel nanoceutical cotton fabric duly sensitized with non-toxic zinc oxide nanoflower can potentially be used as membrane filter in the one way valve of face mask to assure breathing comfort along with source control of COVID-19 infection. The nanoceutical fabric denatures the SARS-CoV-2 spike protein and makes the microorganism ineffective.

microbiology↗

bioRxiv2021

A Nanoceutical Agent for Chemoprevention of Bilirubin Encephalopathy

BackgroundTargeted degradation of bilirubin in vivo may enable safer and more effective approach to manage incipient bilirubin encephalopathy consequent to severe neonatal hyperbilirubinemia (SNH). This report builds on the use of a spinel structured mixed-valence transition metal oxide (trimanganese tetroxide) nanoparticle duly functionalized with biocompatible ligand citrate (C-Mn3O4 NP) having the ability to degrade bilirubin without photo-activation. MethodThe efficiency of C-Mn3O4 NP in in vivo degradation of serum bilirubin and amelioration of severe bilirubin encephalopathy and associated neurobehavioral changes was evaluated in C57BL/6j animal model of SNH. ResultsOral single dose (0.25 mg kg-1 body weight) of the NPs efficiently reduced serum bilirubin levels (both conjugated and unconjugated) in study mice. It prevents bilirubin-induced neurotoxicity with reduction of SNH as observed by neurobehavioral and movement studies of SNH-mice. Pharmacokinetic data suggests intestinal reabsorption of the NPs and explain sustainable action. Biodistribution, pharmacokinetics, and biocompatibility of the NPs were tested during sub-chronic exposure. ConclusionThus, we report preliminary studies that explore an affordable chemoprevention mechanism to acutely prevent or minimize bilirubin neurotoxicity in newborn infants. IMPACT STATEMENTO_LIDespite several attempts, no pharmaco-therapeutics are available for the treatment of severe neonatal hyperbilirubinemia (SNH) and associated neurotoxicity. C_LIO_LIOur newly developed nanodrug, citrate functionalized Mn3O4 nanoparticles (C-Mn3O4 NPs), can efficiently ameliorate SNH and associated neurotoxicity as investigated in preclinical rodent model. C_LIO_LIChemoprevention effect of the nanodrug is found to be safe and sustainable. C_LIO_LIIf successfully translated into clinical trials, C-Mn3O4 NPs could become the first drug to treat SNH. C_LI

pharmacology and toxicology↗

bioRxiv2020

Exposure to Traffic-Related Air Pollution is Associated with Greater Bacterial Diversity in the Lower Respiratory Tract of Children

BackgroundExposure to particulate matter has been shown to increase the adhesion of bacteria to human airway epithelial cells. However, the impact of traffic-related air pollution (TRAP) on the respiratory microbiome is unknown. MethodsForty children were recruited through the Cincinnati Childhood Allergy and Air Pollution Study, a longitudinal cohort followed from birth through early adolescence. Saliva and induced sputum were collected at age 14 years. Exposure to TRAP was characterized from birth through the time of sample collection using a previously validated land-use regression model. Sequencing of the bacterial 16S and ITS fungal rRNA genes was performed on sputum and saliva samples. The relative abundance of bacterial taxa and diversity indices were compared in children with exposure to high and low TRAP. We also used multiple linear regression to assess the effect of TRAP exposure, gender, asthma status, and socioeconomic status on the alpha diversity of bacteria in sputum. ResultsWe observed higher bacterial alpha diversity indices in sputum than in saliva. The diversity indices for bacteria were greater in the high TRAP exposure group than the low exposure group. These differences remained after adjusting for asthma status, gender, and mothers education. No differences were observed in the fungal microbiome between TRAP exposure groups. ConclusionOur findings indicate that exposure to TRAP in early childhood and adolescence may be associated with greater bacterial diversity in the lower respiratory tract. Asthma status does not appear to confound the observed differences in diversity. It is still unknown whether the development of asthma changes the lower respiratory tract microbiome or if an altered microbiome mediates a change in disease status. However, these results demonstrate that there may be a TRAP-exposure related change in the lower respiratory microbiota that is independent of asthma status.

microbiology↗

bioRxiv2020

CONCENTRATION OF THIOUREA IS EFFECTIVE IN BREAKING THE DORMANCY OF POTATO VARIETIES.

Potato germination is highly sensitive to ecological conditions. High altitude and low annual average temperature results in tuber dormancy and poor sprouting. Dormancy has become a significant constraint for lowering potato production that hinders the possibility of growing two crops per year. An experiment was conducted from February to April 2020, where two major potato varieties (Desiree and Cardinal) were treated with four concentrations of Thiourea (0, 1, 2, and 3%) in a two factorial completely randomized block design with three replications. Results showed that Thiourea has a significant effect on all observed attributes as per varieties of potato. For Desiree variety, Thiourea (1%) decreased breaking of dormancy by 22 days compared to control (Desiree*Thiourea 0%) and produced the longest average sprout of 7.36cm at 49 days after treatment (DAT). On the other hand, for the Cardinal variety, Thiourea (3%) decreased tuber dormancy by 27 days compared to control (Cardinal*Thiourea 0%) and produced a sprout of 7.75 cm at 49 DAT. In conclusion, for breaking dormancy and enhancing sprouting of potato varieties Desiree and Cardinal, Thiourea concentration of 1% and 3% is recommended, respectively. Author summaryThis work is the combined effort of all the authors; conceptualization and designing the plot experiments, S.R. and M.D.; performing the experiment and data collection, S.R. and A.A.; statistical analysis and preparation of presentation table and figure, S.R. and B.A.; writing the original draft and editing the whole manuscript, S.R., M.D., R.S., S.S., and A.A. All the author have read and agreed to the published version of the manuscript.

plant biology↗