Sesquiterpene lactone from Salmalia malbarica

A new cadalane type sesquiterpenoid, 1, 6-dihydroxy-3-methyl-5-(1-methylethyl)-7-methoxy-8-carboxylic acid (8 → 1 lactone) has been isolated from a 50% aqueous methanolic extract of 6–9 months old cultivated roots of Salmalia malbarica (Bombax malbaricum).     

Novel secopyrrolizidine alkaloids from Crotalaria verrucosa

Crotaverrine and O-acetylcrotaverrine, isolated from the seeds of C. verrucosa Linn., have been shown by spectroscopy and chemical evidence to be the macrocyclic diesters of otonecine and diastereoisomeric integerrinecic acid. Hitherto, diastereoisomeric integerrinecic acid esters were not known to occur in nature.     

Predictive Factors of Late Venous Aortocoronary Graft Failure: Ultrastructural Studies

Background

Venous aortocoronary graft arterialization may precede a preterm occlusion in some coronary artery bypass grafting (CABG) patients. The aim of the present study was to identify ultrastructural variations in the saphenous vein wall that may have an impact on the development of venous graft disease in CABG patients.

Methods

The study involved 365 consecutive patients with a mean age of 62.9±9.4 years who underwent isolated CABG. The thickness and area of the whole venous wall, the tunica intima, the tunica media and the adventitia and the number and shape (length, thickness and length/thickness ratio) of the nuclei in the medial smooth muscle cells nuclei in the distal saphenous vein segments were evaluated by ultrastructural studies. Patients were followed up for 41 to 50 months (mean 45.1±5.1). Saphenous vein graft patency was assessed by follow-up coronary angiography. Logistic regression models were used to identify independent risk factors for late graft failure.

Results

In 71 patients significant lesions in the saphenous vein grafts were observed. The whole venous wall thickness (437.5 µm vs. 405.5 µm), tunica media thickness (257.2 µm vs. 211.5 µm), whole venous wall area (2.23 mm² vs. 2.02 mm²) and tunica media area (1.09 mm² vs. 0.93 mm²) were significantly larger for this group of patients than for those without graft disease. In the latter group more elongated smooth muscle cell nuclei (higher length/thickness ratio) were found in the tunica media of the saphenous vein segments. Thickening of the saphenous vein tunica media and chunky smooth muscle cell nuclei were identified as independent risk factors for graft disease development.

Conclusions

Saphenous vein tunica media hypertrophy (resulting in wall thickening) and chunky smooth muscle cell nuclei might predict the development of venous graft disease.     

Removal of a C-terminal serine residue proximal to the inter-chain disulfide bond of a human IgG1 lambda light chain mediates enhanced antibody stability and antibody dependent cell-mediated cytotoxicity

Optimization of biophysical properties is a critical success factor for the developability of monoclonal antibodies with potential therapeutic applications. The inter-domain disulfide bond between light chain (Lc) and heavy chain (Hc) in human IgG1 lends structural support for antibody scaffold stability, optimal antigen binding, and normal Fc function. Recently, human IgG1λ has been suggested to exhibit significantly greater susceptibility to reduction of the inter Lc-Hc disulfide bond relative to the same disulfide bond in human IgG1κ. To understand the molecular basis for this observed difference in stability, the sequence and structure of human IgG1λ and human IgG1κ were compared. Based on this Lc comparison, three single mutations were made in the λ Lc proximal to the cysteine residue, which forms a disulfide bond with the Hc. We determined that deletion of S214 (dS) improved resistance of the association between Lc and Hc to thermal stress. In addition, deletion of this terminal serine from the Lc of IgG1λ provided further benefit, including an increase in stability at elevated pH, increased yield from transient transfection, and improved in vitro antibody dependent cell-mediated cytotoxicity (ADCC). These observations support the conclusion that the presence of the terminal serine of the λ Lc creates a weaker inter-chain disulfide bond between the Lc and Hc, leading to slightly reduced stability and a potential compromise in IgG1λ function. Our data from a human IgG1λ provide a basis for further investigation of the effects of deleting terminal serine from λLc on the stability and function of other human IgG1λ antibodies.     

Bio-functionalized graphene-graphene oxide nanocomposite based electrochemical immunosensing

We report a novel in-situ electrochemical synthesis approach for the formation of functionalized graphene-graphene oxide (fG-GO) nanocomposite on screen-printed electrodes (SPE). Electrochemically controlled nanocomposite film formation was studied by transmission electron microscopy (TEM) and Raman spectroscopy. Further insight into the nanocomposite has been accomplished by the Fourier transformed infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA) and X-ray diffraction (XRD) spectroscopy. Configured as a highly responsive screen-printed immunosensor, the fG-GO nanocomposite on SPE exhibits electrical and chemical synergies of the nano-hybrid functional construct by combining good electronic properties of functionalized graphene (fG) and the facile chemical functionality of graphene oxide (GO) for compatible bio-interface development using specific anti-diuron antibody. The enhanced electrical properties of nanocomposite biofilm demonstrated a significant increase in electrochemical signal response in a competitive inhibition immunoassay format for diuron detection, promising its potential applicability for ultra-sensitive detection of range of target analytes.     

Application of higher order statistics for atrial arrhythmia classification

Atrial fibrillation (AF) and atrial flutter (AFL) are the two common atrial arrhythmia encountered in the clinical practice. In order to diagnose these abnormalities the electrocardiogram (ECG) is widely used. The conventional linear time and frequency domain methods cannot decipher the hidden complexity present in these signals. The ECG is inherently a non-linear, non-stationary and non-Gaussian signal. The non-linear models can provide improved results and capture minute variations present in the time series. Higher order spectra (HOS) is a non-linear dynamical method which is highly rugged to noise. In the present study, the performances of two methods are compared: (i) 3rd order HOS cumulants and (ii) HOS bispectrum. The 3rd order cumulant and bispectrum coefficients are subjected to dimensionality reduction using independent component analysis (ICA) and classified using classification and regression tree (CART), random forest (RF), artificial neural network (ANN) and k-nearest neighbor (KNN) classifiers to select the best classifier. The ICA components of cumulant coefficients have provided the average accuracy, sensitivity, specificity and positive predictive value of 99.50%, 100%, 99.22% and 99.72% respectively using KNN classifier. Similarly, the ICA components of HOS bispectrum coefficients have yielded the average accuracy, sensitivity, specificity and PPV of 97.65%, 98.16%, 98.75% and 99.53% respectively using KNN. So, the ICA performed on the 3rd order HOS cumulants coupled with KNN classifier performed better than the HOS bispectrum method. The proposed methodology is robust and can be used in mass screening of cardiac patients.     

Fine‐scale ecological and anthropogenic variables predict the habitat use and detectability of sloth bears in the Churia habitat of east Nepal

Once widespread throughout the tropical forests of the Indian Subcontinent, the sloth bears have suffered a rapid range collapse and local extirpations in the recent decades. A significant portion of their current distribution range is situated outside of the protected areas (PAs). These unprotected sloth bear populations are under tremendous human pressures, but little is known about the patterns and determinants of their occurrence in most of these regions. The situation is more prevalent in Nepal where virtually no systematic information is available for sloth bears living outside of the PAs. We undertook a spatially replicated sign survey‐based single‐season occupancy study intending to overcome this information gap for the sloth bear populations residing in the Trijuga forest of southeast Nepal. Sloth bear sign detection histories and field‐based covariates data were collected between 2 October and 3 December 2020 at the 74 randomly chosen 4‐km² grid cells. From our results, the model‐averaged site use probability (ψ ± SE) was estimated to be 0.432 ± 0.039, which is a 13% increase from the naïve estimate (0.297) not accounting for imperfect detections of sloth bear signs. The presence of termite mound and the distance to the nearest water source were the most important variables affecting the habitat use probability of sloth bears. The average site‐level detectability (p ± SE) of sloth bear signs was estimated to be 0.195 ± 0.003 and was significantly determined by the index of human disturbances. We recommend considering the importance of fine‐scale ecological and anthropogenic factors in predicting the sloth bear‐habitat relationships across their range in the Churia habitat of Nepal, and more specifically in the unprotected areas.     

Establishment of embryonic cultures and somatic embryogenesis in callus culture of guggul-Commiphora wightii (Arnott.) Bhandari

Somatic embryogenesis in callus cultures of Commiphora wightii (Arnott.) Bhandari was achieved. Though the frequency of explants producing embryonic culture was low, immature zygotic embryos were the only suitable explants to produce embryonic callus after reciprocal transfers on media containing 2,4,5-trichlorophenoxy acetic acid (0.1 mgl(-1)) and kinetin (0.1 mgl(-1)) or devoid of growth regulators. All other media failed to produce embryonic callus. Embryonic cells were small, densely filled with cytoplasm and isodiametric as compared to non-embryonic cells, which were large, elongated and vacuolated. Maximum growth of embryonic callus was recorded on modified MS medium (MS-2 medium) supplemented with BA (0.25 mgl(-1)) and IBA (0.1 mgl(-1)). MS-2 salts supported higher growth of callus as compared to tissues grown on B5 medium containing same concentrations of plant growth regulators. Exogenous medium nutrients had no effect on somatic embryo development whereas plant growth regulators had little effect. Asynchronously growing embryos formed plantlets regularly which were successfully transferred to the field conditions.