Hyperhomocysteinemia and its effect on ageing and language functions - HEAL study.

Hyperhomocysteinemia or high levels (> 15 µmol/L) of homocysteine (Hcy)in the blood has been suggested to affect the brain through vascular and neurodegenerative pathways and potentially impact cognition. The current study aims to explore the association of high homocysteine with cognition and brain volume changes in a cohort of middle and old agedr adults. The study recruited 1296 participants aged ≥ 45 years from Tata Longitudinal Study of Ageing (TLSA), an ongoing cohort study. The participants underwent detailed cognitive assessments using Addenbrooke's Cognitive Examination-III (ACE-III) and Computerized Assessment of Adult Information Processing (COGNITO) neuropsychological battery and MR imaging using a 3T scanner. The participants were classified based on the median homocysteine level (16.89 µmol/L) into low Hcy (≤ median) and high Hcy (> median) groups. When adjusted for age, gender, years of education, vitamin B12, folate and dyslipidaemia, Generalised Linear Model (GLM) found a significant association of high Hcy with vocabulary task [ß (95% CI) - 1.354 (- 2.655, - 0.052); p = 0.041]. Significant associations was also obtained between cerebral white matter volume and high Hcy [ß (95% CI) - 5617.182 (- 11062.762, - 173.602); p = 0.043]. The results suggest that people with high Hcy levels performed poorer in cognitive tasks related to language domain and had lesser cerebral white matter volume. This indicates that homocysteine might have a profound impact on brain structure as well as function.

Effect of early menopause on cognition and brain morphology in an Urban Indian Cohort.

BACKGROUND: Evidence for the effect of early menopause on cognition among older women is not consistent and is scant among the Indian population. METHODS: We aimed to examine the effect of early menopause (≤45 years) on cognitive performance and brain morphology among older dementia-free females of the TLSA cohort using a multiple linear regression analysis. RESULTS: In a sample of 528 women, 144 (27%) had early menopause. The linear regression analysis showed that women with early menopause performed poorly in cognition and had lesser total gray matter volume [ß = -11973.94, p = 0.033], left middle frontal [ß = -353.14, p = 0.033], and left superior frontal [ß = -460.97, p < 0.026] volume. CONCLUSION: Dementia-free women with early menopause had poorer cognition, lower total gray matter, and frontal lobe. More research is needed to explore the link between earlier menopause and cognitive decline and develop ways to address it. HIGHLIGHTS: Evidence on the effect of early menopause on brain morphology is inconsistent and scant in low and middle-income countries, such as India. In a cohort of dementia-free individuals in urban Bangalore, we observed that participants with early menopause had significantly lower cognitive performance and lower total gray matter and frontal lobe volume. We recommend increasing awareness of this fact among the medical community and the general public. There is an urgent need to explore the underlying biological mechanism and to discover effective interventions to mitigate the effect.

Alteration in amygdala subfield volumes and their association with cognition in mild cognitive impairment.

BACKGROUND: The amygdala has an important role in cognitive and affective functions. The involvement of amygdala and related limbic structures is implicated in many aspects of memory and emotion in mild cognitive impairment (MCI). In the present study, we aimed to compare the volumetric measurements of amygdala and its subfields as well as their association with cognitive functions in stable MCI (sMCI). METHODS: We performed Addenbrooke's cognitive examination III (ACE-III) test, as well as high-resolution T1-weighted images from 31 participants with sMCI and 31 age-matched healthy controls. The amygdala subfield volumes were extracted using Freesurfer software, and group differences were assessed using general linear model (GLM) with age, gender, education and estimated intracranial volume (ICV) as covariates. Partial correlation was also calculated between cognitive scores and volumes of amygdala subfields in healthy controls and sMCI participants controlling for estimated ICV. RESULTS: sMCI participants exhibited significantly reduced volumes in most of the right amygdala subfields, including basal nucleus, accessory basal nucleus, central nucleus, medial nucleus, corticoamygdaloid transition area, and whole amygdala, as well as significantly reduced right amygdala/hippocampus ratio compared to healthy controls. In addition, our results revealed statistically significant positive correlations between ACE memory scores and the volumes of right central nucleus, right medial nucleus, right cortical nucleus, and the right whole amygdala, in sMCI. CONCLUSIONS: Our findings revealed volumetric reductions in most of the right amygdala subfields along with its association with the memory functions in sMCI. These findings provide valuable insights into the underlying anatomical factors contributing to neurocognitive symptoms in MCI.

Music and the aging brain - Exploring the role of long-term Carnatic music training on cognition and gray matter volumes.

Objectives: Aging is a natural process and is often associated with an increased incidence of cognitive impairment. Physical exercise, diet, and leisure activities (music, dance, and art) are some of the lifestyle factors that contribute to healthy aging. The present study aims to explore the differences in cognitive functioning between aging individuals involved in musical activity throughout their lifetime and the ones who were not. Materials and Methods: Fifty-one healthy elderly individuals (50-80 years of age) residing in an urban locality were selected for the study from the Tata Longitudinal Study of Aging cohort. Participants were divided into two groups: Active musicians trained in Carnatic music for more than five years (n = 18) and age-matched non-musicians (n = 33). Addenbrooke cognitive examination-III, Hindi mental status examination, and trail-making test-B (TMT-B) were used to assess cognitive functioning. A Generalized Linear Regression Model was performed including covariates such as gender, age, and years of education. We also looked at the available brain magnetic resonance imaging data of a subset of our study population to inspect the volumetric differences between musicians and non-musicians. Results: Our results showed that musicians had significantly better visuospatial abilities as compared to non-musicians (P = 0.043). Musicians (130.89 ± 45.16 s) also took less time to complete the TMT-B task than non-musicians (148.73 ± 39.65 s), although it was not a statistically significant difference (P =0.150). In addition, brain imaging data suggested that musicians had increased gray matter volumes in the right precuneus, right post-central gyrus, right medial and superior frontal gyrus, right orbital gyrus, left middle temporal gyrus, left cuneus, left fusiform gyrus, and bilateral cingulate gyrus. Conclusion: Our findings are indicative of music being an important attribute in improving cognitive reserve and predicting cognitive resilience. These findings pave the way to explore the utility of non-pharmacological interventions, such as Music Therapy (especially Carnatic music in the Indian context), as a potential factor for improving cognitive reserve in elderly individuals.

Cortical Gray Matter Thickness and Volume Changes and Their Association with Memory Functions in Hyperthyroid Patients.

INTRODUCTION: Hyperthyroidism, characterized by excessive thyroid hormone production, is a common endocrine disorder that affects various physiological processes, including brain function. Recent advancements in neuroimaging techniques have enabled researchers to investigate structural alterations in the brain associated with hyperthyroidism. This study aimed to examine regional cortical thickness and cortical volume differences across the brain between hyperthyroid patients and control subjects. METHODS: We examined localized cortical thicknesses and volumes in 34 hyperthyroid patients and 35 control subjects with high-resolution T1-weighted images using FreeSurfer software and assessed group differences with analysis of covariance (covariates: age, sex, education, and total intracranial volume). Spearman and partial correlations were performed between clinical variables and cortical thicknesses/volumes and between neuropsychological scores and cortical thicknesses/volumes, respectively. RESULTS: Hyperthyroid patients exhibited significantly increased cortical thickness in bilateral superior temporal and superior frontal gyri, along with higher cortical volumes in various regions, including the right superior temporal gyrus, right superior parietal gyrus, right rostral and caudal middle frontal gyrus, and left superior frontal gyrus. Notably, thyroid hormones (fT3, fT4) correlated positively with cortical thicknesses and volumes in the superior temporal gyrus and superior frontal gyrus. Additionally, recognition memory scores negatively correlated with the right superior temporal gyrus and right superior frontal gyrus cortical thickness. CONCLUSION: The observed cortical thickening and increased cortical volume in specific brain areas provide new insights into the pathophysiological mechanism associated with brain impairment in hyperthyroidism.

Bernoulli trial under restarts: A comparative study of resetting transitions.

A Bernoulli trial describing the escape behavior of a lamb to a safe haven in pursuit by a lion is studied under restarts. The process ends in two ways: either the lamb makes it to the safe haven (success) or is captured by the lion (failure). We study the first passage properties of this Bernoulli trial and find that only mean first passage time exists. Considering Poisson and sharp resetting, we find that the success probability is a monotonically decreasing function of the restart rate. The mean time, however, exhibits a nonmonotonic dependence on the restart rate taking a minimal value at an optimal restart rate. Furthermore, for sharp restart, the mean time possesses a local and a global minima. As a result, the optimal restart rate exhibits a continuous transition for Poisson resetting while it exhibits a discontinuous transition for sharp resetting as a function of the relative separation of the lion and the lamb. We also find that the distribution of first passage times under sharp resetting exhibits a periodic behavior.

Association between thyroid functions, cognition, and functional connectivity of the brain in early-course schizophrenia: A preliminary study.

Background: The functional outcome of the debilitating mental illness schizophrenia (SZ) has an integral role in cognition. The thyroid hormone has a vital role in the developmental stages and functioning of the human brain. Aim: This study aimed to evaluate the relationship between thyroid functions, cognition, and functional imaging of the brain in persons with SZ. Materials and Methods: Sixty SZ (Diagnostic and Statistical Manual (DSM-5)) persons, aged 18-50 years of both genders, were recruited in this cross-sectional observational study. Positive and Negative Syndrome Scale (PANSS) and Trail Making Tests (TMTs) A and B were administered to all patients. To assess the level of thyroid hormone, a test was conducted. Functional connectivity of the brain was assessed using resting-state functional magnetic resonance imaging (rs-fMRI). Data analysis was performed by descriptive and analytical statistical methods. FSL version 5.9 (FMRIB's) software was used for analyses of fMRI neuroimages. Results: There were no significant differences between the two populations on sociodemographic factors. The average value for thyroid-stimulating hormone (TSH) in the hypothyroid group (n = 12) and the euthyroid group (n = 47) was 8.38 mIU/l and 2.44 mIU/l, respectively. The average time in seconds for TMT-A and TMT-B was 87.27 and 218.27 in the hypothyroid group and 97.07 and 293.27 in the euthyroid group, respectively. Similarly, in the sample matched on age, gender, and age at onset of illness, there were no significant differences in demographic and clinical factors and resting-state network (RSN) between the hypothyroid (N = 10) and euthyroid (N = 10) groups. Conclusion: No differences were found in the functional brain network between the hypothyroid and euthyroid groups as the study sample did not include clinically hypothyroid persons with SZ.

Potential of engineering the myo-inositol oxidation pathway to increase stress resilience in plants.

Myo-inositol is one of the most abundant form of inositol. The myo-inositol (MI) serves as substrate to diverse biosynthesis pathways and hence it is conserved across life forms. The biosynthesis of MI is well studied in animals. Beyond biosynthesis pathway, implications of MI pathway and enzymes hold potential implications in plant physiology and crop improvement. Myo-inositol oxygenase (MIOX) enzyme catabolize MI into D-glucuronic acid (D-GlcUA). The MIOX enzyme family is well studied across few plants. More recently, the MI associated pathway's crosstalk with other important biosynthesis and stress responsive pathways in plants has drawn attention. The overall outcome from different plant species studied so far are very suggestive that MI derivatives and associated pathways could open new directions to explore stress responsive novel metabolic networks. There are evidences for upregulation of MI metabolic pathway genes, specially MIOX under different stress condition. We also found MIOX genes getting differentially expressed according to developmental and stress signals in Arabidopsis and wheat. In this review we try to highlight the missing links and put forward a tailored view over myo-inositol oxidation pathway and MIOX proteins.

Cyclic Palladium Formamidinate: Synthesis, Structure, Reactivity, and Application to Suzuki-Miyaura Cross-Coupling.

The deprotonation of acyclic palladium amidine chloride (1) with potassium tert-butoxide in tetrahydrofuran results in palladium bis(formamidinate) (2). 2 undergoes a nucleophilic addition reaction with acetonitrile in the presence of PdCl2 or Pd(OAc)2 (OAc = acetate) to give dinuclear cyclic six-membered (triazapentadiene)palladium complexes (4a and 4b). These compounds are also prepared from cyclic six-membered (tap)PdCl2 (5; tap = triazapentadiene) or formamidinium salts (6a-6c) with Pd(OAc)2/NaOAc in acetonitrile, whereas the direct reaction of 2 with acetonitrile or acrylonitrile resulted in palladium black or an acyclic C-N-coupled product (3). A comparison of structure 4 from 2 suggests a possible intermediate dinuclear palladium complex whose structure was identified through theoretical calculations. Further, Suzuki-Miyaura cross-coupling reactions were carried out under different solvents notably in an ethanol/water medium at room temperature.

Capture of a diffusing lamb by a diffusing lion when both return home.

A diffusing lion pursues a diffusing lamb when both of them are allowed to get back to their homes intermittently. Identifying the system with a pair of vicious random walkers, we study their dynamics under Poissonian and sharp resetting. In the absence of any resets, the location of intersection of the two walkers follows a Cauchy distribution. In the presence of resetting, the distribution of the location of annihilation is composed of two parts: one in which the trajectories cross without being reset (center) and the other where trajectories are reset at least once before they cross each other (tails). We find that the tail part decays exponentially for both the resetting protocols. The central part of the distribution, on the other hand, depends on the nature of the restart protocol, with Cauchy for Poisson resetting and Gaussian for sharp resetting. We find good agreement of the analytical results with numerical calculations.

Brain functional connectivity in patients with hyperthyroidism after anti-thyroid treatment.

Thyroid disease is known to affect brain metabolism and cognitive function, although the recovery of thyroid-induced brain functional changes after treatment remains unclear. We aimed to investigate the alteration in brain functional connectivity and its correlation with neuropsychological variables in hyperthyroid patients before and after anti-thyroid treatment using a resting-state functional magnetic resonance imaging (rsfMRI) technique. This is a follow-up rsfMRI study of previous work that showed impaired brain functional connectivity in hyperthyroid patients compared to healthy controls. We included rsfMRI and neuropsychological data from 21 hyperthyroid patients out of an original cohort of 28 patients, before and after anti-thyroid treatment for 30 weeks. Functional connectivity analysis and neuropsychological scores were compared using paired t tests in patients at baseline and at follow-up. Patients showed an improvement in some of the memory (p < .05) and executive, visuospatial and motor (p < .001) functions after treatment, and also showed increased functional connectivity in the regions of the right fronto-parietal network, left fronto-parietal network, and default mode network (DMN) (p < .05). At follow-up, the functional connectivity of the right fronto-parietal network showed a significantly positive correlation with the recognition of objects memory score. The overall findings suggest that anti-thyroid treatment with carbimazole improves the functional connectivity within some of the resting state networks in the hyperthyroid patients, whereas the remaining networks still show impairment.

Neurometabolite Changes in Hyperthyroid Patients Before and After Antithyroid Treatment: An in vivo 1H MRS Study.

Purpose: Patients with hyperthyroidism have frequent neuropsychiatric symptoms such as lack of attention, concentration, poor memory, impaired executive functions, depression, and anxiety. These neurocognitive impairments such as memory, attention, and executive functions appear to be associated with dysfunction in brain regions. This study was conducted to investigate the metabolic changes in the brain subcortical regions, i.e., posterior parietal cortex and dorsolateral prefrontal cortex (DLPFC), in patients with hyperthyroidism before and after antithyroid treatment using proton magnetic resonance spectroscopy (1H MRS). Materials and Methods: We collected neuropsychological and 1H MRS data from posterior parietal cortex and DLPFC, in both control (N = 30) and hyperthyroid (N = 30) patients. In addition, follow-up data were available for 19 patients treated with carbimazole for 30 weeks. The relative ratios of the neurometabolites were calculated using the Linear Combination Model (LCModel). Analysis of co-variance using Bonferroni correction was performed between healthy controls and hyperthyroid patients, and a paired t-test was applied in patients at baseline and follow-up. Spearman's rank-order correlation was used to analyze bivariate associations between thyroid hormone levels and metabolite ratios, and the partial correlation analysis was performed between neuropsychological scores and metabolite ratios, with age and sex as covariates, in the patients before and after treatment. Results: Our results revealed a significant decrease in choline/creatine [glycerophosphocholine (GPC) + phosphocholine (PCh)/creatine (tCr)] in both the posterior parietal cortex and DLPFC in hyperthyroid patients, and these changes were reversible after antithyroid treatment. The posterior parietal cortex also showed significantly reduced glutamate/creatine (Glu/tCr), (glutamate + glutamine)/creatine (Glx/tCr), and increased glutathione/creatine (GSH/tCr) ratios in the hyperthyroid patients over control subjects. In DLPFC, only (N-acetyl aspartate + N-acetyl aspartyl-glutamate)/creatine (NAA + NAAG)/tCr was increased in the hyperthyroid patients. After antithyroid treatment, (GPC + PCh)/tCr increased, and Glx/tCr decreased in both brain regions in the patients at follow-up. Gln/tCr in the posterior parietal cortex was decreased in patients at follow-up. Interestingly, (GPC + PCh)/tCr in DLPFC showed a significantly inverse correlation with free tri-iodothyronine (fT3) in hyperthyroid patients at baseline, whereas NAA/tCr showed positive correlations with fT3 and free thyroxine (fT4) in hyperthyroid patients before and after antithyroid treatment, in the posterior parietal cortex. In DLPFC, only (NAA + NAAG)/tCr showed positive correlations with fT3 and fT4 in the patients before treatment. Conclusion: The overall findings suggest that all the brain metabolite changes were not completely reversed in the hyperthyroid patients after antithyroid treatment, even after achieving euthyroidism.

Regulatory non-coding RNAs: a new frontier in regulation of plant biology.

Beyond the most crucial roles of RNA molecules as a messenger, ribosomal, and transfer RNAs, the regulatory role of many non-coding RNAs (ncRNAs) in plant biology has been recognized. ncRNAs act as riboregulators by recognizing specific nucleic acid targets through homologous sequence interactions to regulate plant growth, development, and stress responses. Regulatory ncRNAs, ranging from small to long ncRNAs (lncRNAs), exert their control over a vast array of biological processes. Based on the mode of biogenesis and their function, ncRNAs evolved into different forms that include microRNAs (miRNAs), small interfering RNAs (siRNAs), miRNA variants (isomiRs), lncRNAs, circular RNAs (circRNAs), and derived ncRNAs. This article explains the different classes of ncRNAs and their role in plant development and stress responses. Furthermore, the applications of regulatory ncRNAs in crop improvement, targeting agriculturally important traits, have been discussed.

Comprehensive analysis and identification of drought-responsive candidate NAC genes in three semi-arid tropics (SAT) legume crops.

BACKGROUND: Chickpea, pigeonpea, and groundnut are the primary legume crops of semi-arid tropics (SAT) and their global productivity is severely affected by drought stress. The plant-specific NAC (NAM - no apical meristem, ATAF - Arabidopsis transcription activation factor, and CUC - cup-shaped cotyledon) transcription factor family is known to be involved in majority of abiotic stresses, especially in the drought stress tolerance mechanism. Despite the knowledge available regarding NAC function, not much information is available on NAC genes in SAT legume crops. RESULTS: In this study, genome-wide NAC proteins - 72, 96, and 166 have been identified from the genomes of chickpea, pigeonpea, and groundnut, respectively, and later grouped into 10 clusters in chickpea and pigeonpea, while 12 clusters in groundnut. Phylogeny with well-known stress-responsive NACs in Arabidopsis thaliana, Oryza sativa (rice), Medicago truncatula, and Glycine max (soybean) enabled prediction of putative stress-responsive NACs in chickpea (22), pigeonpea (31), and groundnut (33). Transcriptome data revealed putative stress-responsive NACs at various developmental stages that showed differential expression patterns in the different tissues studied. Quantitative real-time PCR (qRT-PCR) was performed to validate the expression patterns of selected stress-responsive, Ca_NAC (Cicer arietinum - 14), Cc_NAC (Cajanus cajan - 15), and Ah_NAC (Arachis hypogaea - 14) genes using drought-stressed and well-watered root tissues from two contrasting drought-responsive genotypes of each of the three legumes. Based on expression analysis, Ca_06899, Ca_18090, Ca_22941, Ca_04337, Ca_04069, Ca_04233, Ca_12660, Ca_16379, Ca_16946, and Ca_21186; Cc_26125, Cc_43030, Cc_43785, Cc_43786, Cc_22429, and Cc_22430; Ah_ann1.G1V3KR.2, Ah_ann1.MI72XM.2, Ah_ann1.V0X4SV.1, Ah_ann1.FU1JML.2, and Ah_ann1.8AKD3R.1 were identified as potential drought stress-responsive candidate genes. CONCLUSION: As NAC genes are known to play role in several physiological and biological activities, a more comprehensive study on genome-wide identification and expression analyses of the NAC proteins have been carried out in chickpea, pigeonpea and groundnut. We have identified a total of 21 potential drought-responsive NAC genes in these legumes. These genes displayed correlation between gene expression, transcriptional regulation, and better tolerance against drought. The identified candidate genes, after validation, may serve as a useful resource for molecular breeding for drought tolerance in the SAT legume crops.

The biotechnological importance of the plant-specific NAC transcription factor family in crop improvement.

Climate change, malnutrition, and food insecurity are the inevitable challenges being faced by the agriculture sector today. Plants are susceptible to extreme temperatures during the crucial phases of flowering and seed development, and elevated carbon levels also lead to yield losses. Productivity is also affected by floods and droughts. Therefore, increasing plant yield and stress tolerance are the priorities to be met through novel biotechnological interventions. The contributions of NAC genes towards enhancing plant survivability under stress is well known. Here we focus on the potential of NAC genes in the regulation of abiotic stress tolerance, secondary cell wall synthesis, lateral root development, yield potential, seed size and biomass, ROS signaling, leaf senescence, and programmed cell death. Once naturally tolerant candidate NAC genes have been identified, and the nature of their association with growth and fitness against multi-environmental stresses has been determined, they can be exploited for building inherent tolerance in future crops via transgenic technologies. An update on the latest developments is provided in this review, which summarizes the current understanding of the roles of NAC in the establishment of various stress-adaptive mechanisms in model and food crop plants.

Transport and tumbling of polymers in viscoelastic shear flow.

Polymers in shear flow are ubiquitous and we study their motion in a viscoelastic fluid under shear. Employing Hookean dumbbells as representative, we find that the center-of-mass motion follows: 〈x_{c}^{2}(t)〉∼γ[over ̇]^{2}t^{α+2}, generalizing the earlier result: 〈x_{c}^{2}(t)〉∼γ[over ̇]^{2}t^{3}(α=1). Here 0<α<1 is the coefficient defining the power-law decay of noise correlations in the viscoelastic media. Motion of the relative coordinate, on the other hand, is quite intriguing in that 〈x_{r}^{2}(t)〉∼t^{ß} with ß=2(1-α), for small α. This implies nonexistence of the steady state, making it inappropriate for addressing tumbling dynamics. We remedy this pathology by introducing a nonlinear spring with FENE-LJ interaction and study tumbling dynamics of the dumbbell. We find that the tumbling frequency exhibits a nonmonotonic behavior as a function of shear rate for various degrees of subdiffusion. We also find that this result is robust against variations in the extension of the spring. We briefly discuss the case of polymers.