Age‐associated cholesterol reduction triggers brain insulin resistance by facilitating ligand‐independent receptor activation and pathway desensitization

In the brain, insulin plays an important role in cognitive processes. During aging, these faculties decline, as does insulin signaling. The mechanism behind this last phenomenon is unclear. In recent studies, we reported that the mild and gradual loss of cholesterol in the synaptic fraction of hippocampal neurons during aging leads to a decrease in synaptic plasticity evoked by glutamate receptor activation and also by receptor tyrosine kinase (RTK) signaling. As insulin and insulin growth factor activity are dependent on tyrosine kinase receptors, we investigated whether the constitutive loss of brain cholesterol is also involved in the decay of insulin function with age. Using long‐term depression (LTD) induced by application of insulin to hippocampal slices as a read‐out, we found that the decline in insulin function during aging could be monitored as a progressive impairment of insulin‐LTD. The application of a cholesterol inclusion complex, which donates cholesterol to the membrane and increases membrane cholesterol levels, rescued the insulin signaling deficit and insulin‐LTD. In contrast, extraction of cholesterol from hippocampal neurons of adult mice produced the opposite effect. Furthermore, in vivo inhibition of Cyp46A1, an enzyme involved in brain cholesterol loss with age, improved insulin signaling. Fluorescence resonance energy transfer (FRET) experiments pointed to a change in receptor conformation by reduced membrane cholesterol, favoring ligand‐independent autophosphorylation. Together, these results indicate that changes in membrane fluidity of brain cells during aging play a key role in the decay of synaptic plasticity and cognition that occurs at this late stage of life.     

Mitochondrial Potentiation Ameliorates Age-Related Heterogeneity in Hematopoietic Stem Cell Function

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Computational Modeling of the Hematopoietic Erythroid-Myeloid Switch Reveals Insights into Cooperativity, Priming, and Irreversibility

Hematopoietic stem cell lineage choices are decided by genetic networks that are turned ON/OFF in a switch-like manner. However, prior to lineage commitment, genes are primed at low expression levels. Understanding the underlying molecular circuitry in terms of how it governs both a primed state and, at the other extreme, a committed state is of relevance not only to hematopoiesis but also to developmental systems in general. We develop a computational model for the hematopoietic erythroid-myeloid lineage decision, which is determined by a genetic switch involving the genes PU.1 and GATA-1. Dynamical models based upon known interactions between these master genes, such as mutual antagonism and autoregulation, fail to make the system bistable, a desired feature for robust lineage determination. We therefore suggest a new mechanism involving a cofactor that is regulated as well as recruited by one of the master genes to bind to the antagonistic partner that is necessary for bistability and hence switch-like behavior. An interesting fallout from this architecture is that suppression of the cofactor through external means can lead to a loss of cooperativity, and hence to a primed state for PU.1 and GATA-1. The PU.1–GATA-1 switch also interacts with another mutually antagonistic pair, C/EBPα–FOG-1. The latter pair inherits the state of its upstream master genes and further reinforces the decision due to several feedback loops, thereby leading to irreversible commitment. The genetic switch, which handles the erythroid-myeloid lineage decision, is an example of a network that implements both a primed and a committed state by regulating cooperativity through recruitment of cofactors. Perturbing the feedback between the master regulators and downstream targets suggests potential reprogramming strategies. The approach points to a framework for lineage commitment studies in general and could aid the search for lineage-determining genes.     

Ecological analysis and environmental niche modelling of Dactylorhiza hatagirea (D. Don) Soo: A conservation approach for critically endangered medicinal orchid

The natural populations of Dactylorhiza hatagirea have been greatly affected due to incessant exploitation. As such, studies on its population attributes together with habitat suitability and environmental factors affecting its distribution are needed to be undertaken for its conservation in nature. Present study aimed at accessing an impact of anthropogenic pressure on population structure and locate suitable habitats for the conservation of this critically endangered orchid. Considerable changes in the phytosociological attributes were observed on account of the changing magnitude and extent of anthropogenic threat in their natural abode. The distribution pattern of species indicated that more than 90% of the populations exhibit substantially aggregated spatial distribution. Maximum Entropy (MaxEnt) distribution modelling algorithm was used to predict suitable habitat and potential area for its cultivation and reintroduction. Twenty-seven occurrence records, nineteen bioclimatic variables, altitude, and slope were used. MaxEnt map output gave the habitat suitability for this species and predicted its distribution in the North-Western Himalayas of India for approximately 616 km². Jackknifing indicated that maximum temperature of warmest month, annual mean temperature, mean temperature of the driest quarter, and mean temperature of the wettest quarter were the governing factors for its distribution and hence, presented a higher gain with respect to other variables. According to permutation importance, precipitation seasonality and mean temperature of wettest quarter shows the prominent impact on the habitat distribution. Results of AUC (area under curve) were statistically significant (0.940) and the line of predicted omission falls very close to an omission on training samples, validating a better run of the model. Response curves revealed a probable increase in the occurrence of D. hatagirea with an increase in mean temperature of the wettest quarter and maximum temperature of the warmest month contributed more than 50% to predicted habitat suitability. Direct field observations concurrent with predicted habitat suitability and google-earth images represent greater model thresholds for successful inception of the species. Together, the study proposes that the species can be conserved in or near its present-day natural habitats and is equally effective in determining the possible habitats for its cultivation and reintroduction.     

Molecular characterization and identification of plant growth promoting endophytic bacteria isolated from the root nodules of pea (Pisum sativum L.)

Root nodule accommodates various non-nodulating bacteria at varying densities. Present study was planned to identify and characterize the non-nodulating bacteria from the pea plant. Ten fast growing bacteria were isolated from the root nodules of cultivated pea plants. These bacterial isolates were unable to nodulate pea plants in nodulation assay, which indicate the non-rhizobial nature of these bacteria. Bacterial isolates were tested in vitro for plant growth promoting properties including indole acetic acid (IAA) production, nitrogen fixation, phosphate solubilization, root colonization and biofilm formation. Six isolates were able to produce IAA at varying level from 0.86 to 16.16 μg ml^?1, with the isolate MSP9 being most efficient. Only two isolates, MSP2 and MSP10, were able to fix nitrogen. All isolates were able to solubilize inorganic phosphorus ranging from 5.57 to 11.73 μg ml^?1, except MSP4. Bacterial isolates showed considerably better potential for colonization on pea roots. Isolates MSP9 and MSP10 were most efficient in biofilm formation on polyvinyl chloride, which indicated their potential to withstand various biotic and abiotic stresses, whereas the remaining isolates showed a very poor biofilm formation ability. The most efficient plant growth promoting agents, MSP9 and MSP10, were phylogenetically identified by 16S rRNA gene sequence analysis as Ochrobactrum and Enterobacter, respectively, with 99 % similarity. It is suggested the potential endophytic bacterial strains, Ochrobactrum sp. MSP9 and Enterobacter sp. MSP10, can be used as biofertilizers for various legume and non-legume crops after studying their interaction with the host crop and field evaluation.     

MYP2 locus genes: Sequence variations,genetic association studies and haplotypic association in patients with High Myopia

High Myopia (HM) is a common complex-trait eye disorder. There is essential evidence that genetic factors play a significant role in the development of nonsyndromic high myopia. Identification of susceptibility genes of high myopia will shed light on the pathophysiological mechanism underlying their genesis. This was a case control study examining the prospect of association of DLGAP1, EMILIN2 & MYOM1 genes on MYP2 locus in purely ethnic (Kashmiri) population representing a homogeneous cohort. Genomic DNA was extracted using phenol chloroform and salting out method. Extracted DNA was genotyped for polymorphic variations in MYOM1, EMILIN2 and DLGAP1 genes involving Sanger di-deoxy method. Allele frequencies were tested for Hardy-Weinberg disequilibrium in 224 cases and compared with 220 emmetropic controls. In DLGAP1, documented single nucleotide polymorphism (SNP); Pro517Pro was observed. A previously reported Asn451Asn SNP was observed in EMILIN2. MYOM1 showed five polymorphic variations; two in coding region (Gly333Gly & Gly341Ala) and three intronic (c.1022+23, G>A; c.3418+44 G>T & c.3418+65; C>G). All of the elucidated SNPs were having statistical significant role in increasing or decreasing the risk of disease. Although not statistically significant, a novel Glu507Lys SNP was observed in DLGAP1 (P>0.05). In silico predictions showed MYOM1 Gly341Ala to be benign & tolerated substitution while as DLGAP1 Glu507Lys to be possibly damaging substitution. The studied SNPs followed Over-Dominant, Recessive and Co-Dominant mode of inheritance with specific haplotypes associated with the disease. Our study reveals the involvement of MYP2 locus candidate gene polymorphism in the pathogenesis of HM.     

Secular trend in height in Al Ain-United Arab Emirates

Correlation between cycles in human stature and those in economic variables is well established. A recent review of international trends in this area provided information from most parts of the world but none on Arabs in the Middle East or more specifically the gulf region.The United Arab Emirates experienced a transformation in economic and social life followed the discovery of oil in the late 1960s and the wealth that it generated. No data is available on human growth at this period of time because its population never had health services prior to the 1970s. A study on conventional cardiovascular risk factors in 2004-2005 included 817 randomly selected national adults (≥18 years) from both genders. The relationship between height and age in this study showed both men and women have increased in height with time demonstrating the secular change in height most likely a result of changing socioeconomic factors.     

Photophysical and biological aspects of α, β-unsaturated ketones: Experimental and in silico approach

In this work, four fluorinated α, β-unsaturated ketones named as 3-(3-bromophenyl)−1-(3-(trifluoromethyl)phenyl)prop-2-en-1-one (1), 3-(4-methoxyphenyl)−1-(3-(trifluoromethyl)phenyl) prop-2-en-1-one (2), 3-(3-bromo-5-chloro-2-hydroxyphenyl)-1-(3-(trifluoromethyl)phenyl) prop-2-en-1-one (3) and 3-(2-hydroxy-5-methylphenyl)-1-(3-(trifluoromethyl)phenyl)prop-2-en-1-one (4) were synthesized by Claisen–Schmidt reaction. The synthesized molecules were then characterized through ultraviolet-visible spectroscopy (UV-Vis), Fourier transform infrared (FTIR), ¹H-NMR, ¹³C-NMR, and mass spectrometry. The antioxidant potential, Urease inhibition, and interaction of compounds 1 – 4 with Salmon sperm DNA were experimentally explored and supported by molecular docking studies. The synthesized compounds strongly interact with SS-DNA through intercalative mode. It was noticed that compound 1 served as potent Urease inhibitor while compound 4 as better antioxidant among synthesized compounds. Moreover, frontier molecular orbitals, nonlinear optical (NLO) properties, natural bond orbitals, molecular electrostatic potential, natural population analysis, and photophysical properties of synthesized compounds were accomplished through density functional theory and time-dependent density functional theory. The band gap of all the compounds have been worked out using Taucs method. In addition to that, a precise comparative account of UV and IR data obtained from theoretical and experimental findings showed good agreement between theoretical and experimental data. The findings of our studies reflected that compounds  1 – 4 possess better NLO properties than Urea standard and the band gap data also reflected their prospective use towards optoelectronic materials. The better NLO behavior of compounds was attributed to the noncentrosymmetric structure of synthesized compounds.     

Prospects of Inducing Resistance in Fodder Species against Toxic Ions and Metals

ABSTRACT

Experiments were carried out with various salts and their combinations to ascertain the impact of these salts on seedling traits of fodder species and to identify tolerant species. Length-based traits showed a repressed effect, whereas weight-based traits were increased under salt stress. Furthermore, accumulation of Na⁺, Ca²⁺, and Cl^? ions and metals (Cu²⁺, Fe²⁺, and Al³⁺) increased in various organs of seedlings due to various salt treatments. Contrastingly, K⁺, K⁺/Na⁺, and Ca²⁺/Cl^? decreased, showing priority for specific salts. Seedling traits, such as shoot length sensitivity and shoot biomass, provide an effective mean of selection for tolerant or susceptible genotypes. Diverse types of tolerance mechanisms were present in cultivars to detoxify the effect of ions and metals. Cultivars that showed low susceptibility index, high shoot biomass, and high metal concentration were salt includers and could be utilized for bioremediation of the affected areas, whereas tolerant cultivars that showed low susceptibility index, metals concentration, and comparable shoot biomass to that of the control were salt excluders and could be utilized for fodder purposes.