Molecular pathogenesis of Japanese encephalitis and possible therapeutic strategies.

Japanese encephalitis virus (JEV), a single-stranded, enveloped RNA virus, is a health concern across Asian countries, associated with severe neurological disorders, especially in children. Primarily, pigs, bats, and birds are the natural hosts for JEV, but humans are infected incidentally. JEV requires a few host proteins for its entry and replication inside the mammalian host cell. The endoplasmic reticulum (ER) plays a significant role in JEV genome replication and assembly. During this process, the ER undergoes stress due to its remodelling and accumulation of viral particles and unfolded proteins, leading to an unfolded protein response (UPR). Here, we review the overall strategy used by JEV to infect the host cell and various cytopathic effects caused by JEV infection. We also highlight the role of JEV structural proteins (SPs) and non-structural proteins (NSPs) at various stages of the JEV life cycle that are involved in up- and downregulation of different host proteins and are potentially relevant for developing efficient therapeutic drugs.

Discovery of Bispecific Lead Compounds from Azadirachta indica against ZIKA NS2B-NS3 Protease and NS5 RNA Dependent RNA Polymerase Using Molecular Simulations.

Zika virus (ZIKV) has been characterized as one of many potential pathogens and placed under future epidemic outbreaks by the WHO. However, a lack of potential therapeutics can result in an uncontrolled pandemic as with other human pandemic viruses. Therefore, prioritized effective therapeutics development has been recommended against ZIKV. In this context, the present study adopted a strategy to explore the lead compounds from Azadirachta indica against ZIKV via concurrent inhibition of the NS2B-NS3 protease (ZIKVpro) and NS5 RNA dependent RNA polymerase (ZIKVRdRp) proteins using molecular simulations. Initially, structure-based virtual screening of 44 bioflavonoids reported in Azadirachta indica against the crystal structures of targeted ZIKV proteins resulted in the identification of the top four common bioflavonoids, viz. Rutin, Nicotiflorin, Isoquercitrin, and Hyperoside. These compounds showed substantial docking energy (-7.9 to -11.01 kcal/mol) and intermolecular interactions with essential residues of ZIKVpro (B:His51, B:Asp75, and B:Ser135) and ZIKVRdRp (Asp540, Ile799, and Asp665) by comparison to the reference compounds, O7N inhibitor (ZIKVpro) and Sofosbuvir inhibitor (ZIKVRdRp). Besides, long interval molecular dynamics simulation (500 ns) on the selected docked poses reveals stability of the respective docked poses contributed by intermolecular hydrogen bonds and hydrophobic interactions. The predicted complex stability was further supported by calculated end-point binding free energy using molecular mechanics generalized born surface area (MM/GBSA) method. Consequently, the identified common bioflavonoids are recommended as promising therapeutic inhibitors of ZIKVpro and ZIKVRdRp against ZIKV for further experimental assessment.

In vivo removal of profenofos in agricultural soil and plant growth promoting activity on Vigna radiata by efficient bacterial formulation.

This study evaluated the plant growth and profenofos (PF) removal efficiency of Acinetobacter sp.33F and Comamonas sp. 51 F bacteria as individual strains and in combination F1. Plant growth-promoting activities such as indole 3 acetic acid (IAA) production, 1-aminocyclopropane-1-carboxylate (ACC) deaminase, phosphate solubilization, ammonia production, and exopolysaccharide (EPS) production were observed in Acinetobacter sp. 33 F and Comamonas sp. 51 F. However, PGP properties observed were higher in Acinetobacter sp. 33 F as compared to the Comamonas sp. 51 F. In pot sand and pot soil studies, the physiological parameters such as sprout length, shoot length, root length, chlorophyll a, chlorophyll b, and carotenoids were higher for combination F1. PF degradation in pot sand and pot soil resulted in highest degradation by combination F1. In pot soil study, soil enzyme activities such as cellulase, dehydrogenase, urease, protease, and phosphate activities and root cross-section area, total stele area and xylem vessel area were recorded higher for the formulation F1. The study demonstrated that the together Acinetobacter sp. 33 F and Comamonas sp. 51 F as formulation has higher plant growth-promoting activities as compared to the individual bacteria.

Cross-Reactivity of Prokaryotic 16S rDNA-Specific Primers to Eukaryotic DNA: Mistaken Microbial Community Profiling in Environmental Samples.

16S ribosomal RNA gene sequences are characteristically used as gold-standard genetic marker for the determination of bacterial and/or archaeal biodiversity, and community profiling of environmental samples. The 16S rRNA amplicon analysis till-date is taken as a standard method for investigation and identification of uncultivable bacteria in microbial diversity studies. The accuracy of these analyses strongly depends upon the choice of primers. It is presumed that these primers do not participate in non-specific amplifications. In the present study, by in silico, PCR and denaturing gradient gel electrophoresis (DGGE) analysis, we have shown that primers do cross-react with eukaryotic DNAs as well, eventually leading to overestimation of microbial biodiversity. We further demonstrated that the overestimation is not only due to cross-reaction with eukaryotic mitochondrial or plastid DNA, but also with eukaryotic chromosomal DNA, that is ubiquitous in environmental samples. We tried to establish methanogenic diversity in municipal solid waste (MSW) leachates and cow dung samples before and after enrichment of the prokaryotic DNA from eukaryotic ones. Results revealed that bands disappeared/get lightened in bacterial 16S rRNA-based DGGE community profiles, after prokaryotic DNA enrichment, but not in mcrA-based community profiles.

Purification and development of ELISAs for two forms of vitellogenin in Indian walking catfish, Clarias batrachus (L.).

Two forms of vitellogenin (Vg: Vg1 and Vg2) were purified from the plasma of estradiol-17ß (E2)-treated Indian walking catfish, Clarias batrachus, by gel filtration and adsorption chromatography. Native Vg1 and Vg2 had apparent molecular masses of 375 and 450 kDa, respectively, and both Vgs resolved into two similar major bands (95 and 67 kDa) in SDS-PAGE under reducing condition. Polyclonal antisera raised against each form of Vg were absorbed with a combination of hypophysectomized male catfish serum proteins and alternate Vg to ensure specificity. Immunological analyses verified the presence of Vg1 and Vg2 in the plasma of female catfish. Homologous ELISAs were developed for Vg1 and Vg2 using their respective harvested antisera, which exhibited the detection limit of 100 ng ml-1 for Vg1 and 40 ng ml-1 for Vg2, and low level of cross-reactivity (not parallel to the standard) was found with alternate Vg in each assay. Treatment of male catfish with E2 induced both Vgs showing a proportionate ratio of Vg1 to Vg2 at 5.6:1. Plasma concentrations of both Vgs measured by ELISAs at different reproductive phases of field collected female catfish increased in accordance with the ovarian development, keeping the proportionate ratio of Vg1 to Vg2 at about 2:1 in fish undergoing vitellogenesis during prespawning period and 1:20 during spawning period, suggesting that Vg1 may be the major Vg to contribute in yolk formation, whereas Vg2, besides its role in yolk formation, may facilitate other physiological functions. The present study, thus, demonstrates the occurrence of two unequally synthesized Vgs in the catfish.

Molecular Analysis of Methanogen Richness in Landfill and Marshland Targeting 16S rDNA Sequences.

Methanogens, a key contributor in global carbon cycling, methane emission, and alternative energy production, generate methane gas via anaerobic digestion of organic matter. The methane emission potential depends upon methanogenic diversity and activity. Since they are anaerobes and difficult to isolate and culture, their diversity present in the landfill sites of Delhi and marshlands of Southern Assam, India, was analyzed using molecular techniques like 16S rDNA sequencing, DGGE, and qPCR. The sequencing results indicated the presence of methanogens belonging to the seventh order and also the order Methanomicrobiales in the Ghazipur and Bhalsawa landfill sites of Delhi. Sequences, related to the phyla Crenarchaeota (thermophilic) and Thaumarchaeota (mesophilic), were detected from marshland sites of Southern Assam, India. Jaccard analysis of DGGE gel using Gel2K showed three main clusters depending on the number and similarity of band patterns. The copy number analysis of hydrogenotrophic methanogens using qPCR indicates higher abundance in landfill sites of Delhi as compared to the marshlands of Southern Assam. The knowledge about "methanogenic archaea composition" and "abundance" in the contrasting ecosystems like "landfill" and "marshland" may reorient our understanding of the Archaea inhabitants. This study could shed light on the relationship between methane-dynamics and the global warming process.

Potential contribution of monoamine oxidase a gene variants in ADHD and behavioral co-morbidities: scenario in eastern Indian probands.

Attention deficit hyperactivity disorder (ADHD) is the most frequently diagnosed behavioral disorder in children with a high frequency of co-morbid conditions like conduct disorder (CD) and oppositional defiant disorder (ODD). These traits are controlled by neurotransmitters like dopamine, serotonin and norepinephrine. Monoamine oxidase A (MAOA), a mitochondrial enzyme involved in the degradation of amines, has been reported to be associated with aggression, impulsivity, depression, and mood changes. We hypothesized that MAOA can have a potential role in ADHD associated CD/ODD and analyzed 24 markers in a group of Indo-Caucasoid subjects. ADHD probands and controls (N = 150 each) matched for ethnicity and gender were recruited following the Diagnostic and Statistical Manual for Mental Disorders-IV. Appropriate scales were used for measuring CD and ODD traits. Markers were genotyped by PCR-based methods and data obtained analyzed using the Cocaphase program under UNPHASED. Only eight markers were found to be polymorphic. rs6323 "G" allele showed higher frequencies in ADHD (P = 0.0023), ADHD + CD (P = 0.03) and ADHD + ODD (P = 0.01) as compared to controls. Haplotype analysis revealed statistically significant difference for three haplotypes in ADHD cases (P < 0.02). Statistically significant differences were also noticed for haplotypes in ADHD + CD and ADHD + ODD cases (P < 0.01). LD analysis showed significant variation in different groups. Multidimensionality reduction analysis showed independent as well as interactive effects of markers. Genotypes showed correlation with behavioral problems in ADHD and ADHD + CD. We interpret that MAOA gene variants may contribute to the etiology of ADHD as well as associated co-morbid CD and ODD in this ethnic group.

Comparative efficacy and safety of the Ambu(®) AuraOnce(™) laryngeal mask airway during general anaesthesia in adults: a systematic review and meta-analysis.

Previous comparisons between the Ambu(®) AuraOnce(™) and other laryngeal mask airways have revealed different results across various clinical studies. We aimed to perform a systematic review with meta-analysis on the efficacy and safety of the AuraOnce compared with other laryngeal mask airways for airway maintenance in adults undergoing general anaesthesia. Our search of PubMed, PubMed Central, Scopus and the Central Register of Clinical Trials of the Cochrane Collaboration yielded nine randomised controlled trials eligible for inclusion. Comparator laryngeal mask airways were the LMA Unique(™) (four trials), the LMA Classic(®) (five trials) and the Portex(®) Soft Seal(®) (three trials). The AuraOnce provided an oropharyngeal leak pressure higher than the LMA Unique (304 participants, mean (95% CI) difference 3.1 (1.6-4.7) cmH2 O, p < 0.0001) and equivalent to the LMA Classic. The Soft Seal provided a higher leak pressure than the AuraOnce (229 participants, mean (95% CI) difference 3.5 (0.4-6.7) cmH2 O, p = 0.03). Insertion was significantly faster with the AuraOnce than the LMA Unique (304 participants, mean (95% CI) difference 5.4 (2.1-8.71) s, p = 0.001) and Soft Seal (229 participants, mean (95% CI) difference 9.5 (3.0-15.9) s, p = 0.004), but similar to the LMA Classic. The first-insertion success rate of the AuraOnce was equivalent to the LMA Unique, LMA Classic and Soft Seal. We found a higher likelihood of bloodstaining on the cuff with the Soft Seal and a higher incidence of sore throat with the LMA Classic. We conclude that the AuraOnce is an effective alternative to the LMA Classic and LMA Unique, and easier to insert than all three other devices studied.

The effect of noggin interference in a rabbit posterolateral spinal fusion model.

STUDY DESIGN: Noggin protein levels and spinal fusion rates were compared in a rabbit model after application of siRNA against BMP antagonist noggin in paraspinal muscle. OBJECTIVE: To test whether endogenous BMPs are sufficient to form bone in the absence of their antagonists, using noggin siRNA to interrupt the negative feedback loop on endogenous BMP within the paraspinal muscles in rabbits. Unused Posterolateral lumbar fusion is a standard surgical treatment for many spinal disorders, yet even under ideal conditions the rate of non-fusion approaches 25 %. BMPs are effective in promoting bone formation, and are inhibited by antagonists such as noggin. We have previously shown that in this model, endogenous BMPs are present and endogenous BMP antagonist noggin is strongly increased during spinal fusion. Previous studies have found that noggin siRNA enhanced spinal fusion in combination with supra-physiological amounts of exogenous BMP; however, the effect of the siRNA alone remains unknown. METHODS: A posterolateral intertransverse rabbit lumbar fusion was utilized, as established by Boden et al. SiRNA against noggin was electroporated into paraspinal muscle to determine its effect on fusion. Outcome measures included noggin protein expression, and assessment of spinal fusion at 6 weeks. RESULTS: SiRNAs were effective in reducing overexpressed noggin in vitro. Noggin protein was successfully knocked down in vivo for the initial 7 days in our rabbit model and returned to detectable levels by 4 weeks and to normal levels by 6 weeks. The overall fusion rate was not significantly enhanced compared to established controls from our earlier work (Tang et al.). CONCLUSIONS: Early noggin suppression does not appear to enhance the BMP activity sufficiently to significantly affect final fusion rates in our model.

Participation of cAMP-dependent protein kinase and MAP kinase pathways during Anabas testudineus oocyte maturation.

Possible involvement of cyclic nucleotide dependent protein kinase (PKA) and MAP kinase (MAPK) pathways during oocyte maturation in Anabas testudineus was investigated. Pre-incubation with phosphodiesterase (PDE) inhibitor, 3-isobutyl-1-methylxanthine (IBMX), inhibited 17α, 20ß-DHP-induced GVBD dose dependently. PKA inhibitor, H89 could induce resumption of meiosis independent of 17α, 20ß-DHP, in dose and duration dependent manner. The maximum response was obtained with the dose of 10 µM of H89 and 95% of cells underwent GVBD within 18 h. Moreover, stimulation with 17α, 20ß-DHP inhibited endogenous PKA activity significantly within first hour and this effect was attenuated by PDE inhibitor IBMX at all time points. The pattern of PKA inhibition corresponded well with kinetics of histone H1 kinase activation and p34cdc2 phosphorylation. These results suggest physiological relevance of cAMP/PKA signaling in perch oocytes undergoing G2/M transition. MAPK was demonstrated as two distinct isoforms (ERK1 and ERK2) which resolved in the range of 42-44 kDa in immunoblot. Though total protein content did not show significant variation, H89 stimulation was able to stimulate phosphorylation of ERK1/2 from 5h onwards and the strongest response was observed between 10 and 18 h. MEK inhibitor, U0126 completely blocked PKA inhibition induced MAPK activation and GVBD. In addition, inhibition of endogenous PKA by a more selective peptide inhibitor [PKI-(6-22)-amide] was sufficient to resume GVBD and MAPK activation in intact perch oocytes. Also, significant ERK1/2 phosphorylation could be stimulated in cell-free extracts of perch oocytes supplemented with PKI-(6-22)-amide. The results suggest an interaction between cAMP/PKA and MAPK pathways in mediating meiosis resumption in perch oocyte.

A multi-targeted approach to identify potential flavonoids against three targets in the SARS-CoV-2 life cycle.

The advent and persistence of the Severe Acute Respiratory Syndrome Coronavirus - 2 (SARS-CoV-2)-induced Coronavirus Disease (COVID-19) pandemic since December 2019 has created the largest public health emergency in over a century. Despite the administration of multiple vaccines across the globe, there continues to be a lack of approved efficacious non-prophylactic interventions for the disease. Flavonoids are a class of phytochemicals with historically established antiviral, anti-inflammatory and antioxidative properties that are effective against cancers, type 2 diabetes mellitus, and even other human coronaviruses. To identify the most promising bioactive flavonoids against the SARS-CoV-2, this article screened a virtual library of 46 bioactive flavonoids against three promising targets in the SARS-CoV-2 life cycle: human TMPRSS2 protein, 3CLpro, and PLpro. By examining the effects of glycosylation and other structural-activity relationships, the presence of sugar moiety in flavonoids significantly reduces its binding energy. It increases the solubility of flavonoids leading to reduced toxicity and higher bioavailability. Through protein-ligand contact profiling, it was concluded that naringin formed more hydrogen bonds with TMPRSS2 and 3CLpro. In contrast, hesperidin formed a more significant number of hydrogen bonds with PLpro. These observations were complimented by the 100 ns molecular dynamics simulation and binding free energy analysis, which showed a considerable stability of docked bioflavonoids in the active site of SARS-CoV-2 target proteins. Finally, the binding affinity and stability of the selected docked complexes were compared with the reference ligands (camostat for TMPRSS2, GC376 for 3CLpro, and GRL0617 for PLpro) that strongly inhibit their respective SARS-COV-2 targets. Overall analysis revealed that the selected flavonoids could be potential therapeutic agents against SARS-CoV-2. Naringin showed better affinity and stability for TMPRSS2 and 3CLpro, whereas hesperidin showed a better binding relationship and stability for PLpro.

Albendazole induces apoptosis in adults and microfilariae of Setaria cervi.

Setaria cervi, a filarial nematode of cattle, inhabits in the peritoneal cavity and has been used as a suitable model for screening antifilarial agents. Albendazole (ABZ), a tubulin-disrupting benzimidazole (BZ) and a potent microfilaricide binds to ß-tubulin, is causing structural impairment of cytoskeleton and worm death. Our present study has revealed that exposure of microfilaria (Mf) and adult to gradually increasing concentration of ABZ leads to a dose-dependent gradual impairment of their motility followed by early death in vitro. We found extreme cellular disturbances in ABZ-treated worms characterized by nucleosomal DNA laddering and chromatin condensation. However, in the treated Mf no nucleosomal DNA laddering was found although presence of TUNEL reactive DNA was evident, thus indicating an apoptotic pathway independent of DNA fragmentation. We present data from molecular studies to provide evidence for ABZ-induced apoptosis in Mf and adult worms of S. cervi.

Molten Salt Synthesized MgNiO2 Micro/Nano-Particles for High Energy Density Supercapacitor and Electrocatalyst for Hydrogen Evolution Reaction in Alkaline Medium.

In recent years, solid solutions have shown promising results as functional materials for different applications. These materials have tunable physiochemical properties and electronic properties, and are being intensively studied for next generation electrochemical charge storage as well as noble metal free low cost electrocatalyts. In the present work, Magnesium Nickel Oxide (MgNiO2) solid solution is prepared by molten salt synthesis. MgNiO2 particles having octahedron shaped morphology with size of 550 nm with an agglomerative behavior was observed through morphological studies. Raman studies revealed presence of three two-phonon modes as well as two one-phonon modes, which confirm the phase purity of MgNiO2 sample. MgNiO2 particles behaved as a promising supercapacitor candidate by exhibiting a large specific capacitance of 76 F/g. It also revealed electrochemical stability over an expansive potential range under the presence of 0.5 mol L-1Sodium Sulfate (Na2SO4) electrolyte, having a high energy density of nearly 51 Wh/kg with a power density of nearly 825 w/kg. Further, MgNiO2 particle showed improved electrocatalytic potential towards Hydrogen Evolution Reaction (HER) in 1 mol L-1 Potassium Hydroxide (KOH) alkaline medium, by demonstrating an overpotential of 0.636 V with a Tafel slope of 0.22205 v/dec. Based on these observed promising results, it can be conclusively inferred that MgNiO2 solid solution is a potential candidate for environmental friendly high voltage supercapacitor and HER electrocatalyst applications.

Aqueous Mg-Ion Supercapacitor and Bi-Functional Electrocatalyst Based on MgTiO3 Nanoparticles.

Supercapacitor and hydrogen-based fuel cells are cheap and environmental-friendly next-generation energy storage devices that are intended to replace Lithium-ion batteries. Metal oxide nanostructures having perovskite crystal structure have been found to exhibit unique electrochemical properties owing to its unique electronic band structure and multiple redox-active ions. Herein, MgTiO3 nanoparticles (MTO-1) were synthesized by wet-chemical sol-gel technique with an average particle size of 50-55 nm, which exhibited superior supercapacitor performance of capacitance (C) = 25 F/g (at 0.25 A/g), energy density (ED) = 17 Wh/kg, power density (PD) = 275 W/kg and 82.41% capacitance retention (after 1000 cycles). Aqueous 1 M Mg(ClO4)2 solution was used as the electrolyte. MTO-1 revealed an overpotential () = 1.329 V and Tafel slope (b) = 374 mV/dec towards Oxygen Evolution Reaction (OER) electrocatalyst and exhibited = 0.914 V and b = 301.4 mV/dec towards Hydrogen Evolution Reaction (HER) electrocatalyst, both in presence of alkaline 1 M KOH solution, making these MgTiO3 nanoparticles very promising for potential use in various technologically important electrochemical applications.

An STS-based map of the human genome.

A physical map has been constructed of the human genome containing 15,086 sequence-tagged sites (STSs), with an average spacing of 199 kilobases. The project involved assembly of a radiation hybrid map of the human genome containing 6193 loci and incorporated a genetic linkage map of the human genome containing 5264 loci. This information was combined with the results of STS-content screening of 10,850 loci against a yeast artificial chromosome library to produce an integrated map, anchored by the radiation hybrid and genetic maps. The map provides radiation hybrid coverage of 99 percent and physical coverage of 94 percent of the human genome. The map also represents an early step in an international project to generate a transcript map of the human genome, with more than 3235 expressed sequences localized. The STSs in the map provide a scaffold for initiating large-scale sequencing of the human genome.

Improved efficacy of tetracycline by acaciasides on Dirofilaria immitis.

The discovery of Wolbachia, a bacterial endosymbiont that occurs in the filarial parasite and its sensitivity to tetracycline, has fostered a new initiative in the development of suitable antifilarial drugs. The present study is an attempt to investigate whether adding acaciasides (saponins from Acacia auriculiformis) to the standard dose of tetracycline would further improve the efficacy of tetracycline treatment against Dirofilaria immitis microfilariae in vivo. Treatment of microfilaremic adult dogs (body weight range 8-12 kg) with tetracycline at 10 mg/kg/day for 40 days resulted in 72% and 83% reduction in mf count on days 15 and 30, respectively, and the maximum reduction in mf count (91%) was achieved on day 75 post-treatment. However, treatment with tetracycline (10 mg/kg/day for 40 days) followed by acaciasides (10 mg/kg/day for 7 days) resulted in almost 100% clearance of mf at a faster rate on day 45 post-treatment and ensured long-term (until 4 months post-treatment) protection against microfilaremia. Data from polymerase chain reaction analysis reveals that compared to untreated dogs, in treated dogs, there was marked reduction in Wolbachia specific wsp markers in fast depleting mf population. The present data indicate that prior tetracycline treatment enhances microfilaricidal activity of saponins. This effect may be additive or synergistic as the worms are weakened by Wolbachia depletion, and these weakened microfilariae are possibly killed by the saponins.

Accuracy of quick Sequential Organ Failure Assessment (qSOFA) score and systemic inflammatory response syndrome (SIRS) criteria for predicting mortality in hospitalized patients with suspected infection: a meta-analysis of observational studies.

OBJECTIVE: To identify sensitivity, specificity and predictive accuracy of quick sequential organ failure assessment (qSOFA) score and systemic inflammatory response syndrome (SIRS) criteria to predict in-hospital mortality in hospitalized patients with suspected infection. METHODS: This meta-analysis followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) group consensus statement for conducting and reporting the results of systematic review. PubMed and EMBASE were searched for the observational studies which reported predictive utility of qSOFA score for predicting mortality in patients with suspected or proven infection with the following search words: 'qSOFA', 'q-SOFA', 'quick-SOFA', 'Quick Sequential Organ Failure Assessment', 'quick SOFA'. Sensitivity, specificity, area under receiver operating characteristic (ROC) curves with 95% confidence interval (CI) of qSOFA and SIRS criteria for predicting in-hospital mortality was collected for each study and a 2 × 2 table was created for each study. RESULTS: Data of 406 802 patients from 45 observational studies were included in this meta-analysis. Pooled sensitivity (95% CI) and specificity (95% CI) of qSOFA ≥2 for predicting mortality in patients who were not in an intensive care unit (ICU) was 0.48 (0.41-0.55) and 0.83 (0.78-0.87), respectively. Pooled sensitivity (95% CI) of qSOFA ≥2 for predicting mortality in patients (both ICU and non-ICU settings) with suspected infection was 0.56 (0.47-0.65) and pooled specificity (95% CI) was 0.78 (0.71-0.83). CONCLUSION: qSOFA has been found to be a poorly sensitive predictive marker for in-hospital mortality in hospitalized patients with suspected infection. It is reasonable to recommend developing another scoring system with higher sensitivity to identify high-risk patients with infection.

BSAP can repress enhancer activity by targeting PU.1 function.

PU.1 and BSAP are transcription factors crucial for proper B-cell development. Absence of PU.1 results in loss of B, T, and myeloid cells, while absence of BSAP results in an early block in B-cell differentiation. Both of these proteins bind to the immunoglobulin kappa chain 3' enhancer, which is developmentally regulated during B-cell differentiation. We find here that BSAP can repress 3' enhancer activity. This repression can occur in plasmacytoma lines or in a non-B-cell line in which the enhancer is activated by addition of the appropriate enhancer binding transcription factors. We show that the transcription factor PU.1 is a target of the BSAP-mediated repression. Although PU.1 and BSAP can physically interact through their respective DNA binding domains, this interaction does not affect DNA binding. When PU.1 function is assayed in isolation on a multimerized PU.1 binding site, BSAP targets a portion of the PU.1 transactivation domain (residues 7 to 30) for repression. The BSAP inhibitory domain (residues 358 to 385) is needed for this repression. Interestingly, the coactivator protein p300 can eliminate this BSAP-mediated repression. We also show that PU.1 can inhibit BSAP transactivation and that this repression requires PU.1 amino acids 7 to 30. Transfection of p300 resulted in only a partial reversal of PU.1-mediated repression of BSAP. When PU.1 function is assayed in the context of the immunoglobulin kappa chain 3' enhancer and associated binding proteins, BSAP represses PU.1 function by a distinct mechanism. This repression does not require the PU.1 transactivation or PEST domains and cannot be reversed by p300 expression. The possible roles of BSAP and PU.1 antagonistic activities in hematopoietic development are discussed.

Descending thoracic aortic aneurysm presenting as left sided hemorrhagic pleural effusion.

Aneurysm of descending thoracic aorta, in majority of cases is diagnosed either by chance in routine chest imaging for some other reasons or rarely due to it's symptomatic presentation like chest pain and other mediastinal compression symptoms. In this case report we present a case of 69 year old smoker who presented with cough, hemoptysis and left sided massive painless hemorrhagic pleural effusion. Further investigation revealed a large aneurysm of descending thoracic aorta which infiltrated the left lung. We suggest descending thoracic aneurysm be included in the differential diagnosis of this sort of clinical presentation which otherwise imperative with the clinical scenario of bronchogenic carcinoma.

Comparative study on the degradation of dibutyl phthalate by two newly isolated Pseudomonas sp. V21b and Comamonas sp. 51F.

Dibutyl phthalate is (DBP) the top priority toxicant responsible for carcinogenicity, teratogenicity and endocrine disruption. This study demonstrates the DBP degradation capability of the two newly isolated bacteria from municipal solid waste leachate samples. The isolated bacteria were designated as Pseudomonas sp. V21b and Comamonas sp. 51F after scanning electron microscopy, transmission electron microscopy, Gram-staining, antibiotic sensitivity tests, biochemical characterization, 16S-rRNA gene identification and phylogenetic studies. They were able to grow on DBP, benzyl butyl phthalate, monobutyl phthalate, diisodecyl phthalate, dioctyl phthalate, and protocatechuate. It was observed that Pseudomonas sp. V21b was more efficient in DBP degradation when compared with Comamonas sp. 51F. It degraded 57% and 76% of the initial DBP in minimal salt medium and in DBP contaminated samples respectively. Kinetics for the effects of DBP concentration on Pseudomonas sp. V21b and Comamonas sp. 51F growth was also evaluated. Stoichiometry for DBP degradation and biomass formation were compared for both the isolates. Two major metabolites diethyl phthalate and monobutyl phthalates were identified using GC-MS in the extracts. Key genes were amplified from the genomes of Pseudomonas sp. V21b and Comamonas sp. 51F. DBP degradation pathway was also proposed.