IN VITRO ANTICHOLINERGIC AND ANTIHISTAMINIC ACTIVITIES OF ACORUS CALAMUS LINN. LEAVES EXTRACTS

The present investigation was aimed at determining the effects of hexane, acetone, methanol and aqueous extracts of Acorus calamus leaves (ACHE, ACAE, ACME and ACAQE) on cholinergic and histaminic system using isolated frog rectus abdominis muscle and guinea pig ileum. A dose dependent potentiation of Ach response (anticholinesterase like effect) was found with ACAE and ACME at 0.25, 0.5, 0.75 and 1 mg/ml, but at higher dose of ACAE, ACME, ACAQE and ACHE (5, 20 mg/ml) inhibit the Ach response (antinicotinic effect). These results revealed biphasic effect of Acorus calamus leaves extracts on acetylcholine induced contractile response in isolated frog rectus abdominis muscle preparation (i.e. potentiation effect at lower dose and inhibitory effect at higher dose). Studies on isolated guinea pig ileum demonstrated antihistaminic effect in a dose dependent manner (100-1000 µg/ml) with ACAE, ACME and ACAQE. In addition, the dose dependent inhibition of Ach response (antimuscarinic effect) was observed with ACAE and ACME. In conclusion, Acorus calamus leaves extracts exerts antinicotinic, anticholinesterase like activities in isolated frog rectus abdominis muscle and antihistaminic, antimuscarinic effect in guinea pig ileum. It has been suggested that these observed activities can be further studied for therapeutic potential of Acorus calamus leaves in the treatment of cognitive disorders and asthma

Emerging WuHan (COVID-19) coronavirus:glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26

The recent outbreak of pneumonia-causing COVID-19 in China is an urgent global public health issue with an increase in mortality and morbidity. Here we report our modelled homo-trimer structure of COVID-19 spike glycoprotein in both closed (ligand-free) and open (ligand-bound) conformation, which is involved in host cell adhesion. We also predict the unique N- and O-linked glycosylation sites of spike glycoprotein that distinguish it from the SARS and underlines shielding and camouflage of COVID-19 from the host the defence system. Furthermore, our study also highlights the key finding that the S1 domain of COVID-19 spike glycoprotein potentially interacts with the human CD26, a key immunoregulatory factor for hijacking and virulence. These findings accentuate the unique features of COVID-19 and assist in the development of new therapeutics

Structural Insights into SARS-CoV‑2 Nonstructural Protein 1 Interaction with Human Cyclophilin and FKBP1 to Regulate Interferon Production

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 coronavirus and the perpetual rise of new variants warrant investigation of the molecular and structural details of the infection process and modulation of the host defense by viral proteins. This Letter reports the combined experimental and computational approaches to provide key insights into the structural and functional basis of Nsp1’s association with different cyclophilins and FKBPs in regulating COVID-19 infection. We demonstrated the real-time stability and functional dynamics of the Nsp1-CypA/FKBP1A complex and investigated the repurposing of potential inhibitors that could block these interactions. Overall, we provided insights into the inhibitory role Nsp1 in downstream interferon production, a key aspect for host defense that prevents the SARS-CoV-2 or related family of corona virus infection

SeqMatchNet: Contrastive Learning with Sequence Matching for Place Recognition and Relocalization

Visual Place Recognition (VPR) for mobile robot global relocalization is a well-studied problem, where contrastive learning based representation training methods have led to state-of-the-art performance. However, these methods are mainly designed for single image based VPR, where sequential information, which is ubiquitous in robotics, is only used as a post-processing step for filtering single image match scores, but is never used to guide the representation learning process itself. In this work, for the first time, we bridge the gap between single image representation learning and sequence matching through SeqMatchNet which transforms the single image descriptors such that they become more responsive to the sequence matching metric. We propose a novel triplet loss formulation where the distance metric is based on sequence matching, that is, the aggregation of temporal order-based Euclidean distances computed using single images. We use the same metric for mining negatives online during the training which helps the optimization process by selecting appropriate positives and harder negatives. To overcome the computational overhead of sequence matching for negative mining, we propose a 2D convolution based formulation of sequence matching for efficiently aggregating distances within a distance matrix computed using single images. We show that our proposed method achieves consistent gains in performance as demonstrated on four benchmark datasets. Source code available at https://github.com/oravus/SeqMatchNet.</p

NrdR overexpression influences changes in bacterial morphology.

<p><b>(A)</b> Colony morphology of WT, ΔNrdR and OE-NrdR <i>E</i>. <i>coli</i> strains grown on LB medium. <b>(B)</b> Magnification (×100) of <i>E</i>. <i>coli</i> strains. Overexpression of NrdR resulted in bacterial aggregates (red arrows) and coccobacilli (short rods; green arrows). <b>(C)</b> Transmission electron microscopy of the WT, ΔNrdR and OE-NrdR <i>E</i>. <i>coli</i> strains at high magnification (magnification, ×21,000). Differences in flagella and cell walls among the <i>E</i>. <i>coli</i> strains can be observed.</p

Bacterial NrdR regulates adhesion to mammalian epithelial cells.

<p><b>(A)</b> Human epithelial cells in culture were infected with WT, ΔNrdR and OE-NrdR <i>E</i>. <i>coli</i> strains. Adherent bacteria were counted 3 hours after infection. Results are reported as CFUs/ml. <b>(B)</b> Direct observation of GFP-tagged WT, ΔNrdR and OE-NrdR <i>E</i>. <i>coli</i> adhering to mammalian cells by fluorescent microscopy at ×1000 magnification. The GFP signals were observed under the FITC filter of a UV laser at 475nm.</p

Complementary expression of PolA, ThiL & Eno shows partial rescue of the bacterial fitness defect caused by NrdR overexpression.

<p>The downregulated essential genes of Appa, ThiL, PolA, Eno, FbaA and Pgk were complementarily expressed under the NrdR overexpression background to test fitness rescue. Partial rescue of bacterial fitness was observed for PolA, Thil or Eno complementary expression. Complementary expression of genes Appa, FbaA and Pgk resulted in fitness defects resembling those of NrdR overexpression alone and did not result in fitness rescue. Empty vectors pET-duet (Kan⁺) and pCA24N (Cam⁺) were transformed into WT strains as controls. The <i>E</i>. <i>coli</i> with DnaK overexpression was used as both negative and positive controls by excluding or incorporating NrdR overexpression, respectively. Dilution factors for the <i>E</i>. <i>coli</i> cultures are labeled over the panels.</p