Transmission of experimentally-induced rat virus infection

The duration of transmission of rat virus (RV) infection was determined using Sprague-Dawley rats inoculated oronasally as juveniles (4 weeks old) or as infants (2 days old). Contact transmission from rats inoculated as juveniles was detected for 3 weeks, whereas transmission from rats inoculated as infants occurred for 10 weeks. Transmission continued for at least 7 weeks after seroconversion occurred in rats inoculated as infants. Two of three rats that had ceased to transmit infection harbored infectious virus as detected by explantation of kidney. Intrauterine transmission occurred only after pregnant dams were inoculated with large doses of virus and was more efficient when virus was inoculated intravenously than by the oronasal route. Enzyme immunoassay antibody titers to RV in offspring of previously infected dams decreased steadily during the first 13 weeks of life and 27 of 29 offspring tested by immunofluorescence assay at 12 or 13 weeks of age were seronegative. These results indicate that RV was transmitted by rats inoculated as infants for long periods after seroconversion occurred. They also suggest that the offspring of previously-infected dams were not infected. In utero transmission of RV-Y is unlikely to occur after oronasal inoculation unless rats are exposed to large doses of virus.     

Cellular Adaptation Relies on Regulatory Proteins Having Episodic Memory

The ability to memorize changes in the environment is present at all biological levels, from social groups and individuals, down to single cells. Trans-generational memory is embedded subcellularly through genetic and epigenetic mechanisms. Evidence that cells process and remember features of the immediate environment using protein sensors is reviewed. It is argued that this mnemonic ability is encapsulated within the protein conformational space and lasts throughout its lifetime, which can overlap with the lifespan of the organism. Means to determine diachronic changes in protein activity are presented.     

Seasonal trends in morpho-physiological attributes and bioactive content of Valeriana jatamansi Jones under full sunlight and shade conditions

Valeriana jatamansi Jones, an important medicinal herb of the Himalayan region, is an essential source of many therapeutic compounds and is traded/consumed in very high volume. The hypothesis of this study was that different seasons and light conditions may affect the content of medicinally valuable components with changes in the morpho-physiological attributes of the plant. Growing plants under suitable light conditions and harvesting of appropriate plant parts in optimum season is crucial for harnessing the full potential of the crop. Thus, the study was carried out to determine the seasonal response of V. jatamansi plants (genetically identical plants of same age) in terms of growth and phytochemical content under two different light conditions (full sunlight and 50% shade). During all seasons, growth parameters (plant height, leaf number, leaf area, relative water content, plant biomass) and the principle bioactive compounds (valerenic acid) were higher under shade conditions, while total flavonoids, tannins, phenolic compounds and antioxidant activities were higher under full sunlight conditions. HPLC analysis revealed that valerenic acid and most of the phenolic content were higher during summer season, especially in leaf part of the plant. The study suggested harvesting of V. jatamansi plants (especially leaf), during summer season to harness high quality raw material and to prevent loss of belowground parts. This strategy can be adopted by farmers for large scale cultivation of species.Supplementary InformationThe online version of this article contains supplementary material available at 10.1007/s12298-021-00944-0     

Exercise training in childhood-onset systemic lupus erythematosus: a controlled randomized trial

Introduction

Exercise training has emerged as a promising therapeutic strategy to counteract physical dysfunction in adult systemic lupus erythematosus. However, no longitudinal studies have evaluated the effects of an exercise training program in childhood-onset systemic lupus erythematosus (C-SLE) patients. The objective was to evaluate the safety and the efficacy of a supervised aerobic training program in improving the cardiorespiratory capacity in C-SLE patients.

Methods

Nineteen physically inactive C-SLE patients were randomly assigned into two groups: trained (TR, n = 10, supervised moderate-intensity aerobic exercise program) and non-trained (NT, n = 9). Gender-, body mass index (BMI)- and age-matched healthy children were recruited as controls (C, n = 10) for baseline (PRE) measurements only. C-SLE patients were assessed at PRE and after 12 weeks of training (POST). Main measurements included exercise tolerance and cardiorespiratory measurements in response to a maximal exercise (that is, peak VO₂, chronotropic reserve (CR), and the heart rate recovery (ΔHRR) (that is, the difference between HR at peak exercise and at both the first (ΔHRR1) and second (ΔHRR2) minutes of recovery after exercise).

Results

The C-SLE NT patients did not present changes in any of the cardiorespiratory parameters at POST (P > 0.05). In contrast, the exercise training program was effective in promoting significant increases in time-to-exhaustion (P = 0.01; ES = 1.07), peak speed (P = 0.01; ES = 1.08), peak VO₂ (P = 0.04; ES = 0.86), CR (P = 0.06; ES = 0.83), and in ΔHRR1 and ΔHRR2 (P = 0.003; ES = 1.29 and P = 0.0008; ES = 1.36, respectively) in the C-SLE TR when compared with the NT group. Moreover, cardiorespiratory parameters were comparable between C-SLE TR patients and C subjects after the exercise training intervention, as evidenced by the ANOVA analysis (P > 0.05, TR vs. C). SLEDAI-2K scores remained stable throughout the study.

Conclusion

A 3-month aerobic exercise training was safe and capable of ameliorating the cardiorespiratory capacity and the autonomic function in C-SLE patients.

Trial registration

NCT01515163.     

Pharmacological inhibition of the MEK5/ERK5 and PI3K/Akt signaling pathways synergistically reduces viability in triple-negative breast cancer

Triple-negative breast cancers (TNBCs) represent 15% to 20% of all breast cancers and are often associated with poor prognosis. The lack of targeted therapies for TNBCs contributes to higher mortality rates. Aberrations in the phosphoinositide-3-kinase (PI3K) and mitogen-activated protein kinase pathways have been linked to increased breast cancer proliferation and survival. It has been proposed that these survival characteristics are enhanced through compensatory signaling and crosstalk mechanisms. While the crosstalk between PI3K and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways has been characterized in several systems, new evidence suggests that MEK5/ERK5 signaling is a key component in the proliferation and survival of several aggressive cancers. In this study, we examined the effects of dual inhibition of PI3K/protein kinase B (Akt) and MEK5/ERK5 in the MDA-MB-231, BT-549, and MDA-MB-468 TNBC cell lines. We used the Akt inhibitor ipatasertib, ERK5 inhibitors XMD8-92 and AX15836, and the novel MEK5 inhibitor SC-1-181 to investigate the effects of dual inhibition. Our results indicated that dual inhibition of PI3K/Akt and MEK5/ERK5 signaling was more effective at reducing the proliferation and survival of TNBCs than single inhibition of either pathway alone. In particular, a loss of Bad phosphorylation at two distinct sites was observed with dual inhibition. Furthermore, the inhibition of both pathways led to p21 restoration, decreased cell proliferation, and induced apoptosis. In addition, the dual inhibition strategy was determined to be synergistic in MDA-MB-231 and BT-549 cells and was relatively nontoxic in the nonneoplastic MCF-10 cell line. In summary, the results from this study provide a unique prospective into the utility of a novel dual inhibition strategy for targeting TNBCs.     

Screening of antifungal activity of various plant leaves extracts from Indian plants

The present study was designated to evaluate the antifungal activity and to root out the antifungal plant leaf extracts from this Indian folk-flore. The in vitro antifungal assay was performed by agar diffusion test and minimum inhibitory concentration (MIC) for hexane, ethyl acetate, methanol and distilled water plant leaf extracts. Extraction of 17 different plant leaves was carried out in different solvents such as hexane, ethyl acetate, methanol and distilled water. Among them extractive yield of methanol was maximum than the rest of the three solvents. These extracts were screened for their antifungal activity against nine different fungi. Among these ethyl acetate extracts of Adhatoda vasica, Ocimum sanctum and Holoptelea integrifolia exhibited maximum antifungal activity against Alternaria sp., Aspergillus parasi, Aspergillus nidulans, Trichoderma harzianum and Aspergillus flavus with MIC of 80, 40 and 20 ppm against Aspergillus nidulans and Alternaria sp. Ethyl acetate extracts showed promising antifungal activity against Adhatoda vasica, Ocimum sanctum and Holoptelea integrifolia against Aspergillus nidulans, and Alternaria sp. might be applicable as fungicide against fungal plants disease.     

Patterns of morphological and genetic diversity of Valeriana jatamansi Jones in different habitats and altitudinal range of West Himalaya,India

Importance to know and understand diversity of Himalayan plants is increasingly recognized considering the fact that various natural and anthropogenic pressures might bring about serious influences to morphological and genetic diversity of the vegetation in the region. In this context, Valeriana jatamansi was investigated in detail, taking into account its importance in various Ayurvedic and modern medicines. Randomly selected mature plants from twenty five different populations (located between 1215 m to 2775 m asl) of V. jatamansi were analysed for their morphological attributes. Further, ISSR markers were used to detect genetic variation among 151 plants of selected 25 populations. Use of 20 primers yielded 125 reproducible polymorphic loci which were used to estimate different parameters of genetic diversity. These parameters were in turn applied to develop relationships with habitat types and altitude range. Significant variation (p < 0.05) in above ground dry weight (AGDW) and below ground dry weight (BGDW) across the populations was observed. Nei's genetic diversity index (He) ranged from 0.25 to 0.37 across the populations, with a mean of 0.31. Genetic diversity exhibited a decreasing trend with increasing altitude, and maximum diversity (He = 0.325) was observed in the range of 1201–1500 m asl. Among the different habitat conditions, highest genetic diversity (He = 0.334; Pp = 84.38) was observed in grassland habitats while minimum in mixed forest habitats (He = 0.285; Pp = 72.433). The genetic diversity (He) had significant negative relationships with AGDW, BGDW and rhizome diameter (Pearson r = −0.359, −0.424 and −0.317, respectively; p < 0.05). The genetic characterization of V. jatamansi from the western Himalaya by this study suggests influences of habitat types and the altitudinal range upon genetic diversity, and based on these proposals for conservation strategies in favour of the species are made.     

Association of peroxisome proliferator activated receptor-γ gene with non-alcoholic fatty liver disease in Asian Indians residing in north India

Background

Genetics of non-alcoholic fatty liver (NAFLD) in Asian Indians has been inadequately studied. We investigated the association of polymorphisms C161T and Pro12Ala of peroxisome proliferator-activated receptor gamma (PPARγ) with clinical and biochemical parameters in Asian Indians with NAFLD.

Methods

In this case–control study, 162 NAFLD cases and 173 controls were recruited. Abdominal ultrasound, clinical and biochemical profiles, fasting insulin levels and value of homeostasis model assessment of insulin resistance were determined. Polymerase chain reaction–restriction fragment length polymorphisms of two polymorphisms were performed. The association of these polymorphisms with clinical and biochemical parameters was analysed.

Results

Higher frequency of Ala and T alleles of PPARγ was obtained in cases. Ala/Ala genotype of PPARγ (Pro12Ala) was associated with significantly higher serum triglycerides (TG), alkaline phosphatase (ALK) and waist–hip ratio in cases as compared to controls. In C161T polymorphism, TT genotype was significantly increased TG (p = 0.04), total cholesterol (p = 0.01), ALK (p = 0.04) and gamma-glutamyl transpeptidase (p = 0.007) in cases. The linkage disequilibrium for these two single-nucleotide polymorphisms of PPARγ was differed in cases (D1 = 0.1; p = 0.006) and controls (D1 = 0.07; p = 0.1). Using a multivariate analysis after adjusting for age, sex and body mass index, the presence of NAFLD was linked to these two polymorphisms (odds ratio 1.64 (95% CI: 1.09–2.45, p = 0.05)].

Conclusion

Asian Indians in north India carrying the alleles Ala and T of PPARγ (Pro12Ala and C161T) polymorphisms are predisposed to develop NAFLD.     

A prawn transglutaminase: Molecular characterization and biochemical properties

In this study, we report the bioinformatics characterization, gene expression, transglutaminase activity and coagulation assays of transglutaminase (TGase) of freshwater prawn Macrobrachium rosenbergii identified from the constructed cDNA library by GS FLX™ technology. Even though, TGase have sequence similarity, they differ extensively in their substrate specificity and are thought to play an important in variety of functions such as development, tissue differentiation and immune responses etc. Gene expression studies show that MrTGase is widely distributed in the tissues such as heart, muscle, intestine, brain, etc., but higher amounts are found in hemocyte. Results of TGase mRNA relative expression in hemocyte, before and after infected with white spot syndrome baculovirus (WSBV) and Vibrio harveyi show that the gene expression initially increases up to 24 h and then it falls down. Coagulation assay results showed that the endogenous TGase is involved in the rapid assembly of a specific, plasma clotting protein. Structural studies show that MrTGase contains a typical TGc domain between 323 and 424, and two putative integrin-binding motifs at Arg¹⁸⁰–Gly¹⁸¹–Asp¹⁸² and Arg²⁶⁹–Gly²⁷⁰–Asp²⁷¹. The predicted 3D model of MrTGase contains 47.04% coils (366 amino acid residues), 26.74% extended strand (208 residues), 21.72% α-helix (169 residues) and 4.5% beta turns (35 residues). BLASTp analysis of MrTGase exhibited high sequence similarities with other crustacean TGase, with the highest observed in white shrimp (77.1%). Moreover, the phylogenetic analysis also showed that MrTGase clustered with the other members of crustacean TGase. Overall, these results suggested that MrTGase is a major and functional TGase of M. rosenbergii for haemolymph coagulation and also in spread of infection.