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INTRODUCTION: We examined midlife (1990–1992, mean age 57) and late‐life (2011–2013, mean age 75) nonalcoholic fatty liver disease (NAFLD) and aminotransferase with incident dementia risk through 2019 in the Atherosclerosis Risk in Communities (ARIC) Study. METHODS: We characterized NAFLD using the fatty liver index and fibrosis‐4, and we categorized aminotransferase using the optimal equal‐hazard ratio (HR) approach. We estimated HRs for incident dementia ascertained from multiple data sources. RESULTS: Adjusted for demographics, alcohol consumption, and kidney function, individuals with low, intermediate, and high liver fibrosis in midlife (HRs: 1.45, 1.40, and 2.25, respectively), but not at older age, had higher dementia risks than individuals without fatty liver. A U‐shaped association was observed for alanine aminotransferase with dementia risk, which was more pronounced in late‐life assessment. DISCUSSION: Our findings highlight dementia burden in high‐prevalent NAFLD and the important feature of late‐life aminotransaminase as a surrogate biomarker linking liver hypometabolism to dementia. Highlights: Although evidence of liver involvement in dementia development has been documented in animal studies, the evidence in humans is limited.Midlife NAFLD raised dementia risk proportionate to severity.Late‐life NAFLD was not associated with a high risk of dementia.Low alanine aminotransferase was associated with an elevated dementia risk, especially when measured in late life. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Non‐Hispanic Black, compared to non‐Hispanic White, older adults are at increased risk for dementia. This may be due partly to greater exposure to psychosocial stressors, such as discrimination; however, few studies have examined this association. METHODS: We examined the association of perceived discrimination (e.g., everyday, lifetime, and discrimination burden) with dementia risk in 1583 Black adults co‐enrolled in the Atherosclerosis Risk in Communities (ARIC) Study and the Jackson Heart Study (JHS). Perceived discrimination (defined continuously and using tertiles) was assessed at JHS Exam 1 (2000–2004; mean age ± SD:66.2 ± 5.5) and related to dementia risk through ARIC visit 6 (2017) using covariate‐adjusted Cox proportional hazards models. RESULTS: Associations of perceived everyday, lifetime, and burden of discrimination with dementia risk were not supported in age‐adjusted models or demographic‐ and cardiovascular health‐adjusted models. Results were similar across sex, income, and education. DISCUSSION: In this sample, associations between perceived discrimination and dementia risk were not supported. Highlights: In Black older adults perceived discrimination not associated with dementia risk.Younger age and greater education linked to greater perceived discrimination.Older age and less education among factors associated with dementia risk.Factors increasing exposure to discrimination (education) are also neuroprotective. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We examined whether sex modifies the association between APOE ε2 and cognitive decline in two independent samples. METHODS: We used observational data from cognitively unimpaired non‐Hispanic White (NHW) and non‐Hispanic Black (NHB) adults. Linear mixed models examined interactive associations of APOE genotype (ε2 or ε4 carrier vs. ε3/ε3) and sex on cognitive decline in NHW and NHB participants separately. RESULTS: In both Sample 1 (N = 9766) and Sample 2 (N = 915), sex modified the association between APOE ε2 and cognitive decline in NHW participants. Specifically, relative to APOE ε3/ε3, APOE ε2 protected against cognitive decline in men but not women. Among APOE ε2 carriers, men had slower decline than women. Among APOE ε3/ε3 carriers, cognitive trajectories did not differ between sexes. There were no sex‐specific associations of APOE ε2 with cognition in NHB participants (N = 2010). DISCUSSION: In NHW adults, APOE ε2 may protect men but not women against cognitive decline. Highlights: We studied sex‐specific apolipoprotein E (APOE) ε2 effects on cognitive decline.In non‐Hispanic White (NHW) adults, APOE ε2 selectively protects men against decline.Among men, APOE ε2 was more protective than APOE ε3/ε3.In women, APOE ε2 was no more protective than APOE ε3/ε3.Among APOE ε2 carriers, men had slower decline than women.There were no sex‐specific APOE ε2 effects in non‐Hispanic Black (NHB) adults. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The fraction of dementia attributable to hypertension might vary depending on the age of the population considered and the age through which dementia occurs. METHODS: In the Atherosclerosis Risk in Communities study, we quantified population attributable fractions (PAF) of dementia by age 80 and 90 from hypertension assessed at ages of 45–54 (n = 7572), 55–64 (n = 12,033), 65–74 (n = 6561), and 75–84 (n = 2086). RESULTS: The PAF for dementia by age 80 from all non‐normal blood pressure at ages 45–54 was 15.3% (95% confidence interval [CI] = 6.9%–22.3%), 19.1% (95% CI = 9.9%–26.9%) at ages 55–64, and 19.9% (95% CI = −4.4%–38.5%) at ages 65–74. The strongest PAFs were from stage 2 hypertension (11.9%–21.3%). For dementia by age 90, PAFs from non‐normal blood pressure up through age 75 were smaller (10.9%–13.8%), and non‐significant by age 75–84. DISCUSSION: Interventions targeting hypertension even in early late life might reduce a sizeable proportion of dementia. Highlights: We estimated prospective population attributable risks of dementia for hypertension.15%–20% of dementia cases by age 80 are from non‐normal blood pressure (BP).Associations between hypertension and dementia persisted through age 75.Midlife to early late‐life BP control might reduce a large proportion of dementia. [ABSTRACT FROM AUTHOR]

Introduction: Physical activity (PA) is prospectively inversely associated with dementia risk, but few studies examined accelerometer measures of PA and sitting with rigorously‐adjudicated mild cognitive impairment (MCI) and dementia risk. Methods: We examined the associations of accelerometer measures (PA and sitting) with incident MCI/probable dementia in the Women's Health Initiative (n = 1277; mean age = 82 ± 6 years) Results: Over a median follow‐up of 4.2 years, 267 MCI/probable dementia cases were identified. Adjusted Cox regression HRs (95% CI) across moderate‐to‐vigorous PA (MVPA) min/d quartiles were 1.00 (reference), 1.28 (0.90 to 1.81), 0.79 (0.53 to 1.17), and 0.69 (0.45 to 1.06); P‐trend = 0.01. Adjusted HRs (95% CI) across steps/d quartiles were 1.00 (reference), 0.73 (0.51 to 1.03), 0.64 (0.43 to 0.94), and 0.38 (0.23 to 0.61); P‐trend < 0.001. The HR (95% CI) for each 1‐SD increment in MVPA (31 min/d) and steps/d (1865) were 0.79 (0.67 to 0.94) and 0.67 (0.54 to 0.82), respectively. Sitting was not associated with MCI/probable dementia. Discussion: Findings suggest ≥ moderate intensity PA, particularly stepping, associates with lower MCI and dementia risk. Highlights: Few studies have examined accelerometer‐measured physical activity, including steps, and sitting with incident ADRD.Moderate‐to‐vigorous physical activity and steps, but not light physical activity or sitting, were inversely associated with lower ADRD risk.Among older women, at least moderate intensity physical activity may be needed to reduce ADRD risk. [ABSTRACT FROM AUTHOR]

Introduction: The apolipoprotein E (APOE) genotype is a driver of cognitive decline and dementia. We used causal mediation methods to characterize pathways linking the APOE genotype to late‐life cognition through Alzheimer's disease (AD) and non‐AD neuropathologies. Methods: We analyzed autopsy data from 1671 individuals from the Religious Orders Study, Memory and Aging Project, and Minority Aging Research Study (ROS/MAP/MARS) studies with cognitive assessment within 5 years of death and autopsy measures of AD (amyloid beta (Aβ), neurofibrillary tangles), vascular (athero/arteriolo‐sclerosis, micro‐infarcts/macro‐infarcts), and non‐AD neurodegenerative neuropathologies (TAR DNA protein 43 [TDP‐43], Lewy bodies, amyloid angiopathy, hippocampal sclerosis). Results: The detrimental effect of APOE ε4 on cognition was mediated by summary measures of AD and non‐AD neurodegenerative neuropathologies but not vascular neuropathologies; effects were strongest in individuals with dementia. The protective effect of APOE ε2 was partly mediated by AD neuropathology and stronger in women than in men. Discussion: The APOE genotype influences cognition and dementia through multiple neuropathological pathways, with implications for different therapeutic strategies targeting people at increased risk for dementia. Highlights: Both apolipoprotein E (APOE) ε2 and APOE ε4 effects on late‐life cognition are mediated by AD neuropathology.The estimated mediated effects of most measures of AD neuropathology were similar.Non–Alzheimer's disease (AD) neurodegenerative pathologies mediate the effect of ε4 independently from AD.Non‐AD vascular pathologies did not mediate the effect of the APOE genotype on cognition.The protective effect of APOE ε2 on cognition was stronger in women. [ABSTRACT FROM AUTHOR]

Background: Strong psychosocial health has been linked to preserved cognition and functional independence in older adults. Associations between late‐life psychosocial health and dementia risk have been established in older adults, but it remains less clear how one's social interactions in mid‐life may relate to dementia risk in late life. We hypothesized that social engagement in mid‐life will be negatively associated with the risk of dementia in late‐life. Method: We included data from 13,216 dementia‐free participants at midlife (mean age: 57.0 years, SD: 5.7 years, 54.9% female, 23.8% Black) from the Atherosclerosis Risk in Communities (ARIC) cohort study. Social support and isolation were assessed via interviewer‐administered questionnaires (visit 2: 1990‐1992). Based upon categorization of both factors, participants were classified as having high, intermediate, or low mid‐life social engagement. Incident dementia cases were identified from visit 2 through December 31, 2019 with ongoing surveillance (e.g., in‐person neurocognitive testing, informant interviews, and hospitalization codes). Primary analyses used Cox proportional hazards regression models and were adjusted for demographics, APOE ε4, occupational/marital status, depressive symptoms, and vascular risk factors measured at visit 2. Secondary analyses examined whether sex and/or race modified the association between mid‐life social engagement and dementia risk with formal tests for interaction. Result: Among 13,261 participants, 2,555 developed dementia (median follow‐up: 23.7 years). Participants with high (hazard ratio (HR): 0.77, 95% CI: 0.68 ‐ 0.86) or intermediate social engagement (HR: 0.84, 95% CI: 0.74 – 0.95) in mid‐life had a lower risk for developing dementia, compared to participants with low social engagement in mid‐life (Figure 1, Table 1). Sex modified this effect (p‐value for interaction = 0.042) whereas race did not. In males, only those with high social engagement in mid‐life had a lower risk of dementia; the association between males with intermediate social engagement in mid‐life and dementia risk was not significant (Table 2). Conclusion: Greater social engagement in mid‐life is associated with a lower risk of dementia. This finding provides further evidence that mid‐life may be a critical time window for dementia prevention. Longitudinal studies evaluating the mechanisms by which psychosocial factors modify the likelihood of incident dementia are needed. [ABSTRACT FROM AUTHOR]

Background: Although amyloid deposition in the brain is often associated with subsequent dementia risk, not everyone with brain amyloid will develop dementia. This discrepancy illustrates the potential importance that risk factors and lived experiences may have in modifying this association. Compared to participants with low social engagement (SE) in mid‐life, we hypothesized that participants with high mid‐life SE will show a weaker association between amyloid burden and incident dementia. Method: We included data from 310 non‐demented participants of the Atherosclerosis Risk in Communities (ARIC)‐PET study. Social support and isolation were assessed via interviewer‐administered questionnaires (Visit 2; 1990 – 1992). Based upon categorization of both factors, participants were classified as having high, intermediate, or low mid‐life SE (Table 1). Brain amyloid was evaluated with florbetapir PET (Visit 5; 2011‐2014). Elevated amyloid burden was defined as standardized uptake value ratio (SUVR) >1.2 in the global cortex. Incident dementia cases were identified from visit 5 through 2019 through ongoing surveillance utilizing in‐person neurocognitive testing, informant interviews, and hospitalization codes. Relative contributions of mid‐life SE and elevated florbetapir SUVR to incident dementia, independently and with multiplicative interaction terms, were evaluated with Cox regression models, adjusted for demographics, APOEε4 and vascular risk factors Result: Among 310 participants, 48 developed dementia (median follow‐up: 4.7 years). Mid‐life SE and elevated SUVR each independently predicted dementia risk but did not interact on a multiplicative scale. Participants with high or intermediate mid‐life SE, relative to low mid‐life SE, were less likely to develop dementia (Table 2). Although the interaction between mid‐life SE and elevated SUVR was not significant, stratified models suggested a stronger association between amyloid burden and dementia in participants with high mid‐life SE (Table 3). Conclusion: Greater mid‐life SE was associated with lower odds of developing dementia, independent of elevated SUVR. Although protective, there was no strong evidence for effect modification of mid‐life SE on the association between amyloid and dementia risk. Future longitudinal studies evaluating the potential influence of social factors measured throughout the life course are needed to inform our understanding as to what factors may preserve cognition in the presence of elevated brain pathology. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes (T2D) and parental history of Alzheimer's disease (AD) are independent risk factors for late‐life cognitive impairment. The presence of T2D may strengthen the association of parental AD risk on cognition through pathways of vascular function, insulin signaling, and amyloid β/tau metabolism. Examining the independent and interactive association of parental AD risk and T2D on cognitive function, specifically in non‐Hispanic Black adults may advance our understanding of their contribution to the disproportionate rates of AD in this group. We hypothesize that parental AD risk and T2D would be independently associated with worse cognition and that the association between parental AD risk and cognition would be stronger in participants with T2D. Method: Participants comprised non‐Hispanic Black adults (N = 331; 25.8% with T2D; Table 1) in the Offspring Study who are the adult children of participants in the Washington Heights Inwood Columbia Aging Project (WHICAP). AD risk was operationalized as parental memory performance residualized for age and education and assessed at their last WHICAP visit. Participant T2D was based on self‐reported physician diagnosis and cognition was assessed with measures of attention, language, and memory. Cognitive test scores were residualized for age and education (Table 1). Linear regression models quantified the independent associations and interaction of AD risk and T2D on offspring cognition. Result: T2D was associated with lower language (B = ‐0.13, 95% CI: [‐0.55, ‐0.08]) and memory (B = ‐0.45, 95% CI: [‐0.72, ‐0.17]) scores, but AD risk was not associated with cognition in any domain. However, AD risk was associated with lower language scores among participants without T2D, but not in participants with T2D (B = ‐0.36, 95% CI [‐0.71, ‐0.02]; Figure 1). No interaction was observed for AD risk and T2D with memory and attention (Figure 2). Conclusion: Our results suggest that among middle‐aged non‐Hispanic Black adults, AD risk is associated with lower language performance in individuals without T2D. The association between AD risk and cognition may be masked by exposure to risk factors, such as T2D. [ABSTRACT FROM AUTHOR]

Background: Prior work has shown that cerebrovascular disease contributes to Alzheimer's disease (AD) pathophysiology and progression toward AD dementia. Cerebral amyloid angiopathy (CAA) is a form of cerebrovascular pathology that results from the buildup of β‐amyloid (Aβ) in the vessel walls. CAA commonly co‐occurs with AD pathology and increases the risk of AD dementia. Here, we examined whether CAA influences tau deposition and cognitive decline, independently or synergistically with parenchymal Aβ burden. Secondarily, we examined whether tau burden mediates the association between CAA and cognitive decline. Method: We included data from autopsied subjects recruited from one of three longitudinal clinical‐pathological cohort studies at Rush University. Participants completed annual cognitive evaluations and underwent brain autopsy. CAA pathology was rated as none, mild, moderate, or severe. We used linear regression and linear mixed models to test independent versus interactive effects of CAA and neuritic plaques on tau burden and cognitive decline. We used causal mediation models to examine whether tau mediates the association between CAA and cognitive decline at low and high neuritic plaque burden. Result: We included 1722 autopsied subjects (mean age at baseline = 80.2+7.1; mean age at death = 8.9+6.7; 68% women). CAA interacted with neuritic plaques to promote tau burden and cognitive decline, such that those with more severe CAA and higher neuritic plaque burden exhibited greater tau and faster cognitive decline (Figures 1 and 2). Tau mediated the effect of CAA on cognitive decline among participants with high neuritic plaque burden. Specifically, increased tau pathology due to the presence of severe CAA led to a 5‐year decline in cognition that was 0.10 (95% CI: 0.03 ‐ 0.19) SD units greater than those with no CAA. A direct effect of CAA on cognitive decline (i.e., an effect not mediated by tau) was not significant in the low or high neuritic plaque groups (Figure 3). Conclusion: These results highlight the dynamic interplay between cerebrovascular and AD pathways in the progression of AD. The present findings have implications for AD clinical trials and therapeutic development, and further support the idea that improving and/or preserving the brain's vasculature might be an effective target for AD prevention [ABSTRACT FROM AUTHOR]

Introduction: Motoric cognitive risk (MCR), a clinical syndrome characterized by slow gait speed and subjective cognitive complaints, has been associated with dementia risk. The neuropathological features underlying MCR remain poorly understood. Methods: The Atherosclerosis Risk in Communities (ARIC) community‐based cohort study classified participants using standardized criteria as MCR+/– and mild cognitive impairment (MCI)+/– at study baseline (2011–2013). We examined the 5‐year dementia risk and baseline brain structural/molecular abnormalities associated with MCR+ and MCI+ status. Results: Of 5023 nondemented participants included, 204 were MCR+ and 1030 were MCI+. Both MCR+ and MCI+ participants demonstrated increased dementia risk. The pattern of structural brain abnormalities associated with MCR+ differed from that of MCI+. Whereas MCI+ was associated with comparatively smaller volumes in brain regions vulnerable to Alzheimer's disease pathology, MCR+ status was associated with smaller volumes in frontoparietal regions and greater white matter abnormalities. Discussion: MCR may represent a predementia syndrome characterized by prominent white matter abnormalities and frontoparietal atrophy. [ABSTRACT FROM AUTHOR]

Background: Poor sleep quality, a modifiable risk factor for dementia, that is prevalent in non‐Hispanic Black and Hispanic adults, is associated with greater memory complaints and smaller hippocampal volumes in predominantly non‐Hispanic White samples. These associations among sleep quality, memory complaints, and hippocampal volumes are understudied in non‐Hispanic Black and Hispanic adults—populations disproportionately affected by poor sleep quality and cognitive performance. The objective of the current study was to examine associations among sleep quality, memory complaints, and hippocampal volumes in a racially and ethnically diverse, community‐based sample. Given sociocultural and environmental differences that affect sleep, brain measures, and cognitive performance, we hypothesize that poorer sleep quality is associated with more memory complaints and smaller hippocampal volumes, especially in Black and Hispanic adults. Method: Participants included Black, Hispanic, and White adults from the Northern Manhattan community (n = 1175; 56±11 years; 67% women; 14±3 years of education; 17% Non‐Hispanic White; 20% Non‐Hispanic Black; 63% Hispanic). Participants self‐reported their sleep quality with the 9‐item Pittsburgh Sleep Quality Index, which measures average sleep disturbance over the past month. Participants self‐reported experiences with forgetting (e.g., names, faces, directions) with an abbreviated version of the Memory Functioning Questionnaire. In a subsample of participants, hippocampal volumes were measured on T1‐weighted MRI scans with FreeSurfer software. Sleep quality, hippocampal volume, and memory complaints were treated as continuous variables. We ran multivariable regression analyses adjusted for age, education, gender identity, depression severity, and intracranial volume for analyses with hippocampal volume. Result: Across racial and ethnic groups, poorer sleep quality was associated with more memory complaints (n = 1175, B = ‐0.31, CI: [‐41,‐.22]). These associations were similar when analyses were stratified by racial and ethnic group. Among Hispanic adults, there was a trending association between poorer sleep quality and smaller left hippocampal volumes (n = 246, B = ‐8.94, CI: [‐18.75,0.88]). Conclusion: Poorer sleep quality was associated with more memory complaints across racial and ethnic groups and showed a trending association with smaller hippocampal volumes in Hispanic adults. Future studies with larger samples should replicate these findings with longitudinal data to quantify the temporal relationship of sleep quality with memory complaints and structural brain changes. [ABSTRACT FROM AUTHOR]

Background: While studies have shown that Non‐Latinx Black and Latinx adults sleep less and more poorly than Non‐Latinx White adults, the cognitive consequences of poor sleep in Non‐Latinx Black and Latinx adults are understudied. Moreover, it is unclear if negative factors that disproportionately affect racial/ethnic minorities, including discrimination, may result in racial/ethnic differences in the relationship between sleep and cognition. We hypothesized that poorer quality sleep and inadequate sleep duration (e.g., short or long sleep) is associated with poorer memory performance, and the strength of these associations would differ by racial/ethnic group. Method: Our analysis included non‐Latinx Black, non‐Latinx White, and Latinx participants across the adult lifespan recruited from the community of Northern Manhattan as a part of the Offspring study. Participants self‐reported their sleep duration and quality over the past month using the Pittsburgh Sleep Quality Index, which we used to calculate global sleep quality. We evaluated memory with the Buschke Selective Reminding Task. We used general linear models to estimate mean differences in sleep duration and quality for racial/ethnic groups. We used multivariable regression to estimate relationships of sleep duration and quality with delayed recall in the total sample and stratified by racial/ethnic group. Models were adjusted for age, sex, and years of education. Result: Black and Latinx adults reported lower sleep duration and poorer quality sleep than Non‐Latinx White adults. In the overall sample, higher quality sleep was associated with better delayed recall performance. We also found linear and quadratic relationships between sleep duration and delayed recall. Taken together, high quality sleep and adequate sleep duration was linked with better delayed recall. Stratified analyses revealed that these effects were strongest in the Latinx group and were not present among non‐Latinx Black and non‐Latinx White participants. Conclusion: Non‐Latinx Black and Latinx adults report lower sleep duration and poorer sleep quality compared to Non‐Latinx White adults. We observed stronger associations between poor sleep quality and sleep duration and memory performance in Latinx adults. Future work will determine which psychosocial factors (e.g., social support, discrimination) underlie racial/ethnic sleep disparities and mediate racial/ethnic differences in the cognitive consequences of poor sleep. [ABSTRACT FROM AUTHOR]

Background: Machine learning and artificial intelligence methods have been applied to brain images to estimate measures of brain aging. However, only rarely have these measures been examined in the context of biologic age. Here, we investigated associations of an MRI‐based measure of dementia risk the Alzheimer's disease pattern similarity (AD‐PS) scores with measures of longevity and biological age. Method: Participants were those from visit 5 of the Atherosclerosis Risk in Community Study with cognitive status adjudication and MRI available. The AD‐PS score was estimated based on previously reported machine learning methods. We evaluated associations of the AD‐PS score with all‐cause mortality. Participants were stratified by AD‐PS tertiles and the analyses were adjusted for age, race, sex, hypertension and smoking. AD‐PS score was examined in association with 32 proteins reported to be associated with age. In these analyses, we used Bonferroni correction (α = 0.05,p<0.0016). Finally, associations with a deficit accumulation index(DAI) based on 38 health items was investigated. In both cases, linear regression models were adjusted for age, race and sex. Sensitivity analyses using only cognitively normal (CN) individuals were performed. Result: Mortality – A total of 356 participants died within 8 years of follow‐up. The AD‐PS score was significantly associated(p<0.001) with time to all‐cause mortality. Participants in the lowest tertile had lower all‐cause mortality rate compared to those in the highest tertile (HR: 0.43;95% CI:0.31,0.60). The association remained significant when restricting the sample to only CN subjects (HR for lowest tertile:0.53; 95% CI:0.35,0.81, p = 0.0028). Age related proteins ‐ The AD‐PS scores were significantly associated (p<0.05, uncorrected) with 10 of the 32 proteins. Growth/differentiation factor 15(GDF‐15) and pleiotrophin remained significant after correction for multiple‐testing. Analysis of CN participants showed a subset of the same proteins to be significant (p<0.05,uncorrected) but only the GDF‐15 remained significant after correction for multiple‐testing. DAI ‐ A linear regression model showed a significant association between DAI and AD‐PS scores overall (coeff = 0.52; 95% CI:0.37‐0.67) and in the CN subset (coeff = 0.3,95% CI:0.13‐0.48). Conclusion: While the AD‐PS scores were created as a measure of dementia risk, our analyses suggest that they could also be capturing brain aging. [ABSTRACT FROM AUTHOR]

Competition among plants for limited soil resources is influenced, in part, by seeding rate. This study aimed to investigate how cultivars that differ in root traits affect water acquisition and the optimal seeding rate. Three cultivars of winter wheat (Triticum aestivum L.) with contrasting root systems (CW134, more roots in topsoil and less roots in subsoil; CH58, small root biomass; CH1, less roots in topsoil and more roots in subsoil) were sown at 180, 225, and 280 seeds m-2 in 2014-2015 and 2015-2016 in a semiarid farmland on the Loess Plateau of China. As the seeding rate increased, grain yield declined in CW134, with topsoil roots increasing and subsoil roots decreasing in both seasons. In contrast, both grain yield and subsoil roots increased in CH1, and the highest grain yield was produced by CH1 at 280 seeds m-2 in both seasons. Subsoil root traits had a positive effect on soil water consumption after anthesis, which was strongly affected by yield components in the dryer season (2015-016). However, the reverse was true for topsoil root traits. In 2014-2015, the topsoil roots had a positive effect on soil water consumption before anthesis, and aboveground traits at anthesis had a greater positive effect on yield components. To maintain higher yields in semiarid environments, genotypes with more topsoil roots should have lower seeding rates to alleviate the negative effect of excessive topsoil roots on postanthesis water absorption, while the reverse may be true for genotypes with more roots in subsoil layers. [ABSTRACT FROM AUTHOR]

Introduction: We tested the hypotheses that higher levels of and persistence of midlife leisure‐time physical activity (LTPA) are associated long‐term with lower cognitive decline and less incident dementia. Methods: A total of 10,705 participants (mean age: 60 years) had LTPA (no, low, middle, or high) measured in 1987‐1989 and 1993‐1995. LTPA was assessed in relation to incident dementia and 14‐year change in general cognitive performance. Results: Over a median follow‐up of 17.4 years, 1063 dementia cases were observed. Compared with no LTPA, high LTPA in midlife was associated with lower incidence of dementia (hazard ratio [95% confidence interval], 0.71 [0.61, 0.86]) and lower declines in general cognitive performance (−0.07 standard deviation difference [−0.12 to −0.04]). These associations were stronger when measured against persistence of midlife LTPA over 6 years. Discussion: LTPA is a readily modifiable factor associated inversely with long‐term dementia incidence and cognitive decline. [ABSTRACT FROM AUTHOR]

Introduction: We tested the hypothesis that poor sense of smell is associated with lower cognitive function and higher mild cognitive impairment (MCI) prevalence. Methods: Olfaction, measured by the Sniffin' Sticks test, was categorized as olfactory impairment (OI) (score ≤6) or no OI (score >6). MCI was adjudicated based on review of a neuropsychological examination. Linear regression estimated the mean difference in cognitive factor scores, and log‐binomial regression quantified MCI prevalence among participants with versus without OI. Results: Participants with OI had lower mean factor scores (memory: −0.27 standard deviation [SD], 95% confidence interval [CI]: −0.35 to −0.19; language: −0.24 SD, 95% CI: −0.30 to −0.17; executive function/processing speed: −0.09 SD, 95% CI: −0.12 to −0.06; and general cognitive performance: −0.25 SD, 95% CI: −0.30 to −0.20). OI was also associated with MCI (n = 204; prevalence ratio = 1.56, 95% CI: 1.37, 1.78). Discussion: An impaired sense of smell may serve as a readily accessible early marker of neurodegeneration and improve upon the prevailing delayed diagnoses and underascertainment of MCI/dementia. [ABSTRACT FROM AUTHOR]

Contents: Incomplete or aberrant reprogramming of nuclear genome is one of the major problems in somatic cell nuclear transfer. In this study, we studied the effect of histone deacetylase inhibitor m‐carboxycinnamic acid bishydroxamide (CBHA) on in vitro development of buffalo embryos produced by Hand‐made cloning. Cloned embryos were treated with CBHA (0, 5, 10, 20 or 50 μM) for 10 hr from the start of reconstruction till activation. At 10 μM, but not at other concentrations examined, CBHA increased (p < .05) the blastocyst rate (63.77 ± 3.97% vs 48.63 ± 3.55%) and reduced (p < .05) the apoptotic index of the cloned blastocysts (8.91 ± 1.94 vs 4.36 ± 1.08) compared to untreated controls, to levels similar to those in IVF blastocysts (4.78 ± 0.74). CBHA treatment, at all the concentrations examined, increased (p < .05) the global level of H3K9ac in cloned blastocysts than in untreated controls to that observed in IVF blastocysts. Treatment with CBHA (10 μM) decreased (p < .05) the global level of H3K27me3 in cloned blastocysts than in untreated controls but it was still higher (p < .05) than in IVF blastocysts. CBHA (10 μM) treatment increased (p < .05) the relative expression level of pluripotency‐related genes OCT‐4 and NANOG, and anti‐apoptotic gene BCL‐XL, and decreased (p < .05) that of pro‐apoptotic gene BAX than in untreated controls but did not affect the relative expression level of apoptosis‐related genes p53 and CASPASE3 and epigenetics‐related genes DNMT1, DNMT3a and HDAC1. These results suggest that treatment of cloned embryos with 10 μM CBHA improves the blastocyst rate, reduces the level of apoptosis and alters the epigenetic status and gene expression pattern. [ABSTRACT FROM AUTHOR]

Background: Agitation, a common symptom in Alzheimer's disease (AD), may be related to impaired emotion regulation capacity with involvement of autonomic networks. Heart rate variability (HRV), an index of integrity of neural networks involved in autonomic function and emotion regulation, could be a potential marker of agitation propensity. We investigated the cross‐sectional and longitudinal association between HRV and agitation prevalence in AD using the Atherosclerosis Risk in Communities (ARIC) Study cohort that followed up participants from 1987–2013. Method: Participants at ARIC visit 5 who were clinically diagnosed with dementia (or MCI that subsequently progressed to dementia) primarily or wholly attributed to AD were included. Agitation at visit 5 was defined based on the Neuropsychiatric Inventory agitation/aggression subscale alone, or a composite score comprising agitation/aggression, irritability, disinhibition, and aberrant motor behavior subscales. HRV measures at visits 1–5 were the root mean square of successive differences in R‐R intervals (RMSSD) and standard deviation of normal‐to‐normal R‐R intervals (SDNN) obtained from resting, supine, standard twelve‐lead electrocardiograms. The associations between agitation and visit 5 HRV or visit 1–5 change in HRV (defined as individual slope coefficients from mixed effects models) were assessed using simple regression models. Results: Among 456 participants who had dementia during the study, N = 302 received a primary diagnosis of AD, of whom N = 120 were classified with pure AD (see Flowchart). In the pure AD subgroup, a 0.1 log‐unit higher RMSSD (odds ratio = 1.14 [1.03‐1.29]) and positive RMSSD change over the preceding two decades (odds ratio = 2.23 [1.24‐4.38]) were associated with agitation point prevalence after accounting for heart rate (change), age, sex, cognitive status, study site and race. A 0.1 log‐unit change in HRV approximated the observed difference in HRV with each decade of age. The associations persisted after accounting for use of medications with autonomic effects. Conclusion: The finding that higher HRV was associated with agitation point prevalence in N = 120 participants clinically diagnosed with dementia solely due to AD supports the potential use of HRV as a biomarker of agitation propensity, and autonomic dysfunction as a target of treatment. Future studies are needed to explore this relationship alongside measures of emotion regulation and locus coeruleus‐noradrenergic system integrity. [ABSTRACT FROM AUTHOR]

Background: Women show disproportionate burden of Alzheimer's disease (AD) pathology and higher AD dementia prevalence compared to men, yet the mechanism(s) driving these vulnerabilities are unknown. There is sexual dimorphism in immunologic functioning and neuroimmune processes are implicated in AD genesis. Using neuropathology indicators from human brain tissue, we examined the mediational role of microglial activation on the relationship between amyloid and tau and how it differs by sex. Method: 187 decedents (64% female; 89 years‐old at death; 62% non‐demented) from the Rush Memory and Aging Project completed neuropathological evaluations with brain tissue quantified for microglial activation, amyloid‐β, and tau. Proportion of morphologically activated microglia was determined via immunohistochemistry (HLA‐DP‐DQ‐DR) and morphological staging (stage I, II, or III). Amyloid and tau burden were quantified via immunohistochemistry (M00872 or AT8, respectively). Using causal counterfactual modeling, we estimated the mediational effect of microglial activation on the amyloid to tau relationship in the whole sample and stratified by sex (amyloid→ microglial activation→ tau). Alternative models tested the role of microglia activation as the precipitating event (microglial activation→ amyloid→ tau). Result: Microglial activation significantly mediated 67% (95%CI 32‐90) of the relationship between amyloid and tau in the whole sample; however, stratified analyses suggested this effect was stronger and only statistically significant in women. 57% (95%CI 20‐100) of the effect of amyloid‐β on tau was mediated through microglial activation in women, compared to 19% (95%CI 0‐62) in men. Secondary models suggested that mediational effects were driven by cortical versus subcortical microglial activation. Alternative models suggested that in women, microglial activation was a significant exposure both preceding the amyloid‐β to tau relationship (50%, 95%CI 22‐89) and directly related to tau burden (50%, 95%CI 11‐78). In contrast, in men, only the direct effect of microglial activation to tau reached significance (74%, 95%CI 34‐99) (mediational effect: 25%, 95%CI 1‐66). Conclusion: Our models suggest a reciprocal, bidirectional relationship between amyloid‐β and microglial activation that accounts for tau burden in women. In men, direct independent (non‐mediational) relationships between microglial activation or amyloid‐β with tau were observed. Microglial activation may be disproportionately important for AD pathogenesis in women. [ABSTRACT FROM AUTHOR]

'Accidental' urban wetlands are formed not through deliberate restoration or management activity, but as a product of land use and water infrastructure decisions by municipalities. Often formed in abandoned industrial, residential, or low-lying commercial areas, where overland flows from storms and municipal water use accumulate, these ecosystems support wetland soils and plant communities. Research that we have conducted in the northeastern and southwestern US suggests that accidental wetlands are capable of counteracting anthropogenic eutrophication, providing habitats for important ecological communities, fostering biodiversity, and mitigating heat. Because the factors contributing to their formation are ubiquitous, accidental wetland systems are likely pervasive in urban landscapes, accounting for a substantial portion of aquatic habitat extent and influencing nutrient and water cycles within cities. They also provide ecosystem services at a fraction of the cost associated with more traditional environmental management efforts. [ABSTRACT FROM AUTHOR]

Contents This study was conducted to identify and analyse the expression of gametogenesis-associated genes and proteins in foetal and adult buffalo gonads of both the sexes. Relative quantification of the genes was determined by qPCR and Western blotting. Immunohistochemistry was also performed for various gametogenesis-associated proteins in foetal and adult gonads of both the sexes. We observed significantly (p < 0.05) increased expression of primordial germ cell-specific, meiotic as well as genes associated with oocyte maturation and development in foetal ovaries as compared to the adult ones. However, significantly (p < 0.05) increased expression of proteins associated with oocyte maturation like GDF9 and ZP4 was found in adult ovaries, indicating temporal regulation of mRNA translation during oogenesis. Meiotic genes showed significantly (p < 0.05) increased expression in adult testes as compared to foetal testes and ovaries, indicating onset of meiosis at a later stage in spermatogenesis. In general, the expression of primordial germ cell-associated as well as meiotic genes was higher in adult testes, indicating the increased biological activity in the organ. Immunohistochemistry revealed localized expression of gametogenesis-associated proteins in ovarian follicles and seminiferous tubules of testes, while the surrounding somatic tissues were devoid of these proteins. The study gives an understanding of the sequential and temporal events of gene expression as well as mRNA translation during male and female gametogenesis. It could also be concluded that follicles and seminiferous tubules are the functional units of the female and male gonads, respectively, and their function could be enhanced by appropriate chemical and genetic intervention of the somatic tissue immediately surrounding them. This assumes importance in the context that buffalo attains sexual maturity at an older age of 2-3 years and have smaller ovaries with lesser number of primordial follicles in comparison with cattle, which is suggested to be the main reason of their poor breeding performance. [ABSTRACT FROM AUTHOR]

Contents Following IVF, embryos which cleave early have been shown to have higher developmental competence and quality than those that cleave relatively later across many species. We investigated the effect of time of cleavage on the developmental competence, quality, epigenetic status and gene expression in buffalo embryos produced by handmade cloning ( HMC). Following classification of embryos as early cleaving ( EC) or late cleaving ( LC) based on whether they had cleaved or not at 24 h post in vitro culture, 54% (164/303) were found to be EC and the rest to be LC. The blastocyst rate (58.1 ± 3.4 vs 36.9 ± 1.6%, p < 0.01) and the total cell number (285.5 ± 41.9 vs 141.4 ± 36.1, p < 0.05) were higher, whereas the apoptotic index (3.6 ± 0.6 vs 12.2 ± 1.7, p < 0.01) and the global level of H3K9ac and H3K27me3 were lower (p < 0.05) in the blastocysts produced from EC than in those produced from LC embryos. The relative transcript level of CASPASE3, CASPASE7, DNMT1, DNMT3a and CDX2 was higher (p < 0.05) and that of SOX2 was lower (p < 0.05) in blastocysts produced from LC than in those produced from EC embryos, whereas the expression level of CASPASE6, P53, P21, HDAC1, OCT4 and NANOG was not significantly different between the two groups. These results show that (i) following HMC, blastocysts produced from embryos that cleave early differ from those produced from late cleaving embryos in terms of epigenetic status and expression level of many important apoptosis-, pluripotency-, trophectoderm- and epigenetics-related genes, and (ii) EC embryos are superior to LC embryos in view of their higher developmental competence and quality. [ABSTRACT FROM AUTHOR]

Contents The objective of this study was to explore the possibility of producing wild buffalo embryos by interspecies somatic cell nuclear transfer ( iSCNT) through handmade cloning using wild buffalo somatic cells and domestic buffalo ( Bubalus bubalis) oocytes. Somatic cells derived from the ear skin of wild buffalo were found to express vimentin but not keratin and cytokeratin-18, indicating that they were of fibroblast origin. The population doubling time of skin fibroblasts from wild buffalo was significantly (p < 0.05) higher, and the cell proliferation rate was significantly (p < 0.05) lower compared with that of skin fibroblasts from domestic buffalo. Neither the cleavage (92.6 ± 2.0% vs 92.8 ± 2.0%) nor the blastocyst rate (42.4 ± 2.4% vs 38.7 ± 2.8%) was significantly different between the intraspecies cloned embryos produced using skin fibroblasts from domestic buffalo and interspecies cloned embryos produced using skin fibroblasts from wild buffalo. However, the total cell number ( TCN) was significantly (p < 0.05) lower (192.0 ± 25.6 vs 345.7 ± 42.2), and the apoptotic index was significantly (p < 0.05) higher (15.1 ± 3.1 vs 8.0 ± 1.4) for interspecies than that for intraspecies cloned embryos. Following vitrification in open-pulled straws ( OPS) and warming, although the cryosurvival rate of both types of cloned embryos, as indicated by their re-expansion rate, was not significantly different (34.8 ± 1.5% vs 47.8 ± 7.8), the apoptotic index was significantly (p < 0.05) higher for vitrified-warmed interspecies than that for corresponding intraspecies cloned embryos (48.9 ± 7.2 vs 23.9 ± 2.8). The global level of H3 K18ac was significantly (p < 0.05) lower in interspecies cloned embryos than that in intraspecies cloned embryos. The expression level of HDAC1, DNMT3a and CASPASE3 was significantly (p < 0.05) higher, that of P53 was significantly (p < 0.05) lower in interspecies than in intraspecies embryos, whereas that of DNMT1 was similar between the two types of embryos. In conclusion, these results demonstrate that wild buffalo embryos can be produced by iSCNT. [ABSTRACT FROM AUTHOR]

Contents For investigating the effects of physiologically relevant heat shock, buffalo oocytes/embryos were cultured at 38.5°C (control) or were exposed to 39.5°C (Group II) or 40.5°C (Group III) for 2 h once every day throughout in vitro maturation ( IVM), fertilization ( IVF) and culture ( IVC). Percentage of oocytes that developed to 8-cell, 16-cell or blastocyst stage was lower (p < 0.05) and the number of apoptotic nuclei was higher (p < 0.05) for Group III > Group II > controls. At both 8-16-cell and blastocyst stages, relative mRNA abundance of stress-related genes HSP 70.1 and HSP 70.2 and pro-apoptotic genes CASPASE-3, BID and BAX was higher (p < 0.05) in Groups III and II than that in controls with the exception of stress-related gene HSF1. Expression level of anti-apoptotic genes BCL-XL and MCL-1 was also higher (p < 0.05) in Groups III and II than that in controls at both 8-16-cell and blastocyst stages. Among the genes related to embryonic development, at 8-16-cell stage, the expression level of GDF9 was higher (p < 0.05) in Group III than that in controls, whereas that of GLUT1, ZAR1 and BMP15 was not significantly different among the three groups. At the blastocyst stage, relative mRNA abundance of GLUT1 and GDF9 was higher (p < 0.05) in Group II than that in controls, whereas that of ZAR -1 and BMP15 was not affected. The results of this study demonstrate that exposure of buffalo oocytes and embryos to elevated temperatures for duration of time that is physiologically relevant severely compromises their developmental competence, increases apoptosis and affects stress-, apoptosis- and development-related genes. [ABSTRACT FROM AUTHOR]

Brownfields, previously developed sites that are derelict, vacant, or underused, are ubiquitous in urban areas. Wetlands on brownfields often retain rain and stormwater longer than the surrounding landscape because they are low-lying; this increases the possibility for these areas to process waterborne contaminants from the urban environment. In the northeastern United States, atmospheric deposition of nitrate (NO3-) is high. Denitrification, a microbial process common in wetlands, is a means of removing excess NO3- . Nitrogen gas is the desired end product of denitrification, but incomplete denitrification results in the production of N2O, a greenhouse gas. The goal of this study was to investigate the potential of brownfield wetlands to serve as sinks for inorganic nitrogen and sources of greenhouse gases. We examined limitations to denitrification and N2O production in brownfield wetland soils in New Jersey. Soil C:N ratios were high (18-40) and intact core denitrification (-0.78 to 11.6 mg N2O-N kg dry soil-1 d-1) and N mineralization (0.11-2.97 mg N kg dry soil-1 d-1) were low for all sites. However, soil NO3- increased during dry periods. Nitrate additions to soil slurries increased denitrification rates, whereas labile C additions did not, indicating that soil denitrifiers were nitrogen limited. Incubations indicated that the end product of denitrification was primarily N2O and not N2. These results indicate that brownfield wetlands can develop significant denitrification capacity, potentially causing NO3- limitation. They might be significant sinks for atmospheric NO3- but may also become a significant source of N2O if NO3- deposition were to increase. [ABSTRACT FROM AUTHOR]

Contents This study was carried out to compare the post-thaw cryosurvival rate and the level of apoptosis in vitro produced zona-free cloned buffalo blastocysts subjected to slow freezing or vitrification in open-pulled straws ( OPS). Zona-free cloned embryos produced by handmade cloning were divided into two groups and were cryopreserved either by slow freezing or by vitrification in OPS. Cryosurvival of blastocysts was determined by their re-expansion rate following post-thaw culture for 22-24 h. The post-thaw re-expansion rate was significantly (p < 0.05) higher following vitrification in OPS (71.2 ± 2.3%) compared with that after slow freezing (41.6 ± 4.8%). For examining embryo quality, the level of apoptosis in day 8 frozen-thawed blastocysts was determined by TUNEL staining. The total cell number was not significantly different among the control non-cryopreserved cloned embryos (422.6 ± 67.8) and those cryopreserved by slow freezing (376.4 ± 29.3) or vitrification in OPS (422.8 ± 36.2). However, the apoptotic index, which was similar for embryos subjected to slow freezing (14.8 ± 2.0) or OPS vitrification (13.3 ± 1.8), was significantly (p < 0.05) higher than that for the control non-cryopreserved cloned embryos (3.4 ± 0.6). In conclusion, the results of this study demonstrate that vitrification in OPS is better than slow freezing for the cryopreservation of zona-free cloned buffalo blastocysts because it offers a much higher cryosurvival rate. [ABSTRACT FROM AUTHOR]

Contents This study examined the effects of supplementation of ES-like cell culture medium with bone morphogenetic protein ( BMP)-4 (0, 10, 20 or 100 ng/ml) or Noggin (250, 500 or 750 ng/ml) or TGF-β1 (0, 0.1, 1 or 10 ng/ml) or SB431542 (0, 10, 25 or 50 μ m), an inhibitor of TGF-β1 signalling, on survival, colony area and expression level of pluripotency genes in buffalo ES-like cells at passage 40-80, under different culture conditions. BMP-4 supplementation significantly reduced (p < 0.05) colony survival rate, percentage increase in colony area and relative mRNA abundance of OCT4, whereas that of NANOG and SOX-2 was increased significantly (p < 0.05). Noggin supplementation did not affect the colony survival rate and percentage increase in colony area in the presence of FGF-2 and LIF. In the presence of FGF-2 alone, it significantly reduced (p < 0.05) the relative mRNA abundance of OCT4 and SOX-2 and increased (p < 0.05) that of NANOG. Supplementation with TGF-β1 at 1.0 ng/ml but not at other concentrations increased colony survival rate but had no effect on percentage increase in colony area at any concentration. Supplementation with SB-431542 decreased (p < 0.05) colony survival rate at 50 μ m but not at other concentrations. The percentage increase in colony area was lower (p < 0.05) with 10 μ m SB-431542 than that in the controls, whereas at higher concentrations of 25 or 50 μ m, SB-431542 decreased (p < 0.05) the colony size instead of increasing it. In conclusion, these results suggest that BMP-4 induces differentiation in buffalo ES-like cells, whereas TGF-β/activin/nodal pathway may not be playing a crucial role in maintaining pluripotency in these cells. [ABSTRACT FROM AUTHOR]

Contents When buffalo embryonic stem (ES) cell-like cells that expressed surface markers SSEA-4, TRA-1-60, TRA-1-81, CD9 and CD90 and intracellular markers OCT4, SOX2 and FOXD3, as shown by immunofluorescence, and that expressed REX-1 and NUCLEOSTEMIN as confirmed by RT-PCR, were subjected to suspension culture in hanging drops in absence of LIF and buffalo foetal fibroblast feeder layer support, they differentiated to form three-dimensional embryoid bodies (EBs). Of 231 EBs examined on Day 3 of suspension culture, 141 (61.3 ± 3.09%) were of compact type, whereas 90 (38.4 ± 3.12%) were of cystic type. The cells obtained from EBs were found to express NF-68 and NESTIN (ectodermal lineage), BMP-4 and α-skeletal actin (mesodermal lineage), and α-fetoprotein, GATA-4 and HNF-4 (endodermal lineage). When these EBs were cultured on gelatin-coated dishes, they spontaneously differentiated to several cell types such as epithelial- and neuron-like cells. When EBs were cultured in the presence of 1 or 2% DMSO or 10−8 m or 10−7 m retinoic acid for 25 days, ES cells could be directed to form muscle cell-like cells, the identity of which was confirmed by expression of α-actinin by immunofluorescence and of MYF-5, MYOD and MYOGENIN genes by RT-PCR. MYOD was first detected on Day 10 in both treatment groups and on Day 15 in controls, whereas MYOGENIN was first detected on Day 10, Day 15 and Day 25 in the presence of retinoic acid, in the presence of DMSO and in controls, respectively. The present study demonstrates the ability of buffalo ES cell-like cells to undergo directed differentiation to cells of skeletal myogenic lineage. [ABSTRACT FROM AUTHOR]

Contents This study examined the effects of O2 concentration (5% vs 20%) during in vitro maturation (IVM), fertilization (IVF) and culture (IVC) or supplementation of IVM and IVC media with cysteamine (50 and 100 μ m, respectively; IVM, IVF and IVC carried out in 20% O2), on blastocyst rate and relative mRNA abundance of some apoptosis-related genes measured by real-time qPCR in immature and in vitro-matured buffalo oocytes and in embryos at 2-, 4-, 8- to 16-cell, morula and blastocyst stages. The blastocyst rate was significantly higher (p < 0.05) while the percentage of TUNEL-positive cells was significantly lower (p < 0.05) under 5% O2 than that under 20% O2. The mRNA expression of anti-apoptotic genes BCL-2 and MCL-1 was significantly higher (p < 0.05) and that of pro-apoptotic genes BAX and BID was lower (p < 0.05) under 5% O2 than that under 20% O2 concentration at many embryonic stages. Following cysteamine supplementation, the blastocyst rate and the relative mRNA abundance of BCL-XL and MCL-1 was significantly higher (p < 0.05) and that of BAX but not BID was lower (p < 0.05) at many stages of embryonic development, although it did not affect the percentage of TUNEL positive cells in the blastocysts significantly. The mRNA expression pattern of these genes during embryonic development was different in 5% vs 20% O2 groups and in cysteamine supplemented vs controls. At the 8- to 16-cell stage, where developmental block occurs in buffalo, the relative mRNA abundance of BCL-2 and MCL-1 was highest under 5% O2 concentration and that of BAX and BID was highest (p < 0.05) under 20% O2 concentration. These results suggest that one of the mechanisms through which beneficial effects of low O2 concentration and cysteamine supplementation are mediated during in vitro embryo production is through an increase in the expression of anti-apoptotic and a decrease in the expression of pro-apoptotic genes. [ABSTRACT FROM AUTHOR]

Contents Somatic cells in milk are a potential source of nuclei for nuclear transfer to produce genetically identical animals; this is especially important in animals that are susceptible to risks of bacterial infection on biopsy collection. In this study, a minimum of 10 milk samples were collected from each of the three buffaloes representing Murrah breed. All the samples were processed immediately and cell colonies were obtained. Cell colonies from one buffalo (MU-442) survived beyond 10 passages and were evaluated by fluorescence microscopy and used in nuclear transfer experiments. In culture, these cells expressed vimentin, indicating they were of fibroblast origin similar to ear cells. We compared the effectiveness of cloning using those milk-derived fibroblast (MDF) cells and fibroblast cells derived from the ear derived fibroblast (EDF). Fusion and cleavage rates of MDF-NT and EDF-NT embryos were found to be similar (92.43 ± 1.28% vs 94.98 ± 1.24%, and 80.27 ± 1.75% vs 84.56 ± 3.73%, respectively; p > 0.01); however, development to blastocyst stage and total cell number was higher for EDF-NT embryos (50.24 ± 2.54%, 227.14 ± 13.04, respectively, p < 0.01), than for MDF-NT embryos (16.44 ± 0.75%, 170.57 ± 4.50 respectively). We conclude that somatic cells from milk can be cultured effectively and used as nucleus donor to produce cloned blastocyst-stage embryos. [ABSTRACT FROM AUTHOR]

Contents This study examined the presence of immunoreactivity and mRNA for different nitric oxide synthase (NOS) isoforms in immature and in vitro matured oocytes and in embryos at two-, four- and eight-cell, and morula and blastocyst stages in buffalo. Oocytes obtained from slaughterhouse buffalo ovaries were subjected to in vitro maturation in TCM-199 + 10% FBS + 5 μg/ml pFSH + 1 μg/ml estradiol-17β + 0.81 m m sodium pyruvate + 10% buffalo follicular fluid + 50 μg/ml gentamycin sulphate for 24 h in a CO2 incubator (5% CO2 in air) at 38.5°C. Following in vitro fertilization carried out by incubating them with 2-4 million spermatozoa/ml for 18 h, the presumed zygotes were cultured in mCR2aa medium containing 0.6% BSA and 10% FBS for up to 8 days post insemination. Immunofluorescence staining of NOS using antibodies that cross-reacted either with all the NOS isoforms i.e., universal (uNOS) or specifically with inducible (iNOS) or endothelial (eNOS) isoforms revealed that NOS was present in oocytes and embryos at all the stages examined. Examination of the semi-quantitative expression of NOS genes by RT-PCR revealed that the iNOS, eNOS and nNOS mRNA was present in the immature and mature oocytes and in all the embryonic stages examined. In conclusion, it was demonstrated in the present study that immunoreactivity and mRNA for different NOS isoforms was present in buffalo oocytes and pre-implantation stage embryos. [ABSTRACT FROM AUTHOR]

Parthenogenetic activation using zona-free oocytes offers an alternative model that could be applied to develop protocols for the activation of reconstructed embryos for cloning. The aim of this study was to compare the efficacy of different methods for the activation of zona-free buffalo oocytes in terms of their effects on the developmental competence of parthenogenetic embryos. The effects of zona removal on parthenogenetic activation and in vitro developmental competence of metaphase II oocytes were also examined. All activation methods were followed by incubation of 2 m 6-dimethylaminopurine (6-DMAP) for 4 h. Out of three different pulse strengths (1.2, 2.1 or 3.3 kV/cm) used, 2.1 kV/cm resulted in the highest blastocyst rate (25.3%). On comparing different chemical agents and electric pulse, highest blastocyst rate was observed for calcium ionophore (CaI) (28.6%) followed by ethanol (25.0%), electric pulse (22.5%) and combined CaI and ethanol treatment (16.7%) although differences among them were not significant. Furthermore, a significantly reduced developmental potential was observed in zona-free oocytes when compared to zona-intact ones up to the blastocyst stage (44.3% vs 27.1%). In conclusion, zona-free buffalo oocytes can be successfully activated for parthenogenetic development using chemical or electrical stimulation. Out of different agents examined, CaI followed by 6-DMAP resulted in the highest blastocyst rate. [ABSTRACT FROM AUTHOR]

In this study, inner cell mass (ICM) cells were isolated from in vitro produced buffalo blastocysts and were cultured on mitomycin-C treated buffalo foetal fibroblast feeder layer for producing embryonic stem (ES) cells. Among different sources (hatched vs expanded blastocysts) or methods (enzymatic vs mechanical), mechanical isolation of ICM from hatched blastocysts resulted in the highest primary colony formation rate and the maximum passage number up to which ES cells survived. Putative ES cells expressed alkaline phosphatase and exhibited a normal karyotype up to passage 7. Putative ES cells and embryos at 2- to 4-cell, 8- to 16-cell, morula and blastocyst stages strongly expressed stage-specific embryonic antigen (SSEA)-4 but lacked expressions of SSEA-1 and SSEA-3. Putative ES cells also expressed tumour rejection antigen (TRA)-1-60, TRA-1-81 and Oct4. Whereas in all early embryonic stages, TRA-1-60 was observed only in the periplasmic space, and TRA-1-81 expression was observed as small spots at a few places inside the embryos, both these markers were expressed by ICM. Oct4 expression, which was observed at all the embryonic stages and also in the trophectoderm, was the strongest in the ICM. Buffalo putative ES cells possess a unique pluripotency-related surface antigen phenotype, which resembles that of the ICM. [ABSTRACT FROM AUTHOR]

Comet assay was used in the present study to examine DNA damage to buffalo oocytes and embryos during in vitro culture. Embryos were produced in vitro from oocytes obtained from slaughterhouse ovaries in presence of cysteamine (IVM and IVC media supplemented with 50 and 100 μ, respectively) or in its absence (controls). Compared to controls, cysteamine supplementation increased (p < 0.01) cleavage rate and proportion of oocytes that developed to 8- to 16-cell stage. The incidence of DNA damage was lower (p < 0.01) in cysteamine group than that in controls at 8- to 16- (19.3 ± 4.24 vs 72.0 ± 5.22%) but not in 2-cell stage embryos (11.7 ± 5.63 vs 20.8 ± 5.49%) or in mature oocytes (5.3 ± 3.43 vs 10.3 ± 4.73%). The tail length, which indicates magnitude of DNA damage, was shorter (p < 0.01) in cysteamine group than in controls in mature oocytes (25.5 ± 0.5 vs 36.0 ± 0.71 pixels) and 8- to 16-cell stage (49.2 ± 1.64 vs 152.7 ± 1.28 pixels) but not in 2-cell stage embryos (36.3 ± 1.54 vs 36.4 ± 0.75 pixels). Also, exposure of oocytes/embryos to UV radiation or HO caused extensive DNA damage. In conclusion, these results suggest that oocytes/embryos suffer from DNA damage during progress of in vitro culture, which can be partly ameliorated by cysteamine supplementation of culture media. [ABSTRACT FROM AUTHOR]

Contents [ABSTRACT FROM AUTHOR]

The article determines the effects of insulin on cell proliferation and progesterone production by buffalo ovarian granulosa cells cultured in vitro. The growth of ovarian follicles is a highly complex physiological process that is under the endocrine control of pituitary gonadotropins and is also regulated through paracrine and autocrine mechanisms by various hormones, growth factors and steroids.

Reports on the production of progesterone induced by follicle-stimulating hormone by buffalo granulosa cells based from a study in Great Britain. Optimization of fertility in farm animals through the control and management of ovarian follicles; Estimation of progesterone levels by a direct radio-immunoassay; Aim of the study to develop a culture system for buffalo granulosa cells which is capable of supporting hormone production.

Aging adults experience increased health vulnerability and compromised abilities to cope with stressors, which are the clinical manifestations of frailty. Frailty is complex, and efforts to identify biomarkers to detect frailty and pre-frailty in the clinical setting are rarely reproduced across cohorts. We developed a predictive model incorporating biological and clinical frailty measures to identify robust biomarkers across data sets. Data were from two large cohorts of older adults: "Invecchiare in Chianti (Aging in Chianti, InCHIANTI Study") (n = 1453) from two small towns in Tuscany, Italy, and replicated in the Atherosclerosis Risk in Communities Study (ARIC) (n = 6508) from four U.S. communities. A complex systems approach to biomarker selection with a tree-boosting machine learning (ML) technique for supervised learning analysis was used to examine biomarker population differences across both datasets. Our approach compared predictors with robust, pre-frail, and frail participants and examined the ability to detect frailty status by race. Unique biomarker features identified in the InCHIANTI study allowed us to predict frailty with a model accuracy of 0.72 (95% confidence interval (CI) 0.66-0.80). Replication models in ARIC maintained a model accuracy of 0.64 (95% CI 0.66-0.72). Frail and pre-frail Black participant models maintained a lower model accuracy. The predictive panel of biomarkers identified in this study may improve the ability to detect frailty as a complex aging syndrome in the clinical setting. We propose several concrete next steps to keep research moving toward detecting frailty with biomarker-based detection methods., (© 2023 The Authors. Aging Cell published by John Wiley & Sons Ltd and Anatomical Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Rest-activity rhythms (RARs), a measure of circadian rhythmicity in the free-living setting, are related to mortality risk, but evidence is limited on associations with cardiovascular disease (CVD) and its risk factors., Methods and Results: Participants included 4521 adults from the 2013 to 2014 National Health and Nutrition Examination Survey physical activity monitoring examination. Wrist-worn ActiGraph GT3X+ data were used to estimate RARs. Multivariable logistic models evaluated associations of RARs with prevalent CVD, hypertension, obesity, and central adiposity. Participants (mean age, 49 years) in the highest versus lowest tertile of relative amplitude (greater circadian rhythmicity) had 39% to 62% lower odds of prevalent CVD, hypertension, obesity, and central adiposity. A more active wake period was associated with 19% to 72% lower CVD, hypertension, obesity, and central adiposity odds. Higher interdaily stability (regular sleep-wake and rest-activity patterns) was related to 52% and 23% lower CVD and obesity odds, respectively. In contrast, participants in the highest versus lowest tertile of intradaily variability (fragmented RAR and inefficient sleep) had >3-fold and 24% higher CVD and obesity odds, respectively. A later and less restful sleep period was associated with 36% to 2-fold higher CVD, hypertension, obesity, and central adiposity odds. A statistically significant linear trend was observed for all associations ( P -trend<0.05)., Conclusions: A robust, stable, and less fragmented RAR, an active wake period, and an earlier and more restful sleep period are associated with lower prevalent CVD, hypertension, obesity, and central adiposity, with evidence of a dose-response relationship. The magnitude, timing, and regularity of sleep-wake and rest-activity patterns may be important targets for reducing cardiovascular risk.

Background Frailty and heart failure frequently coexist in late life. Limited data exist regarding the longitudinal associations of frailty and subclinical cardiac dysfunction. We aim to quantify the association of frailty with longitudinal changes in cardiac function and of cardiac function with progression in frailty status in older adults. Methods and Results Participants in the Atherosclerosis Risk in Communities cohort underwent frailty assessments at Visit 5 (V5; 2011-2013), V6 (2016-2017), and V7 (2018-2019), and echocardiographic assessments at V5 and V7. We assessed the association between frailty status at V5 and changes in frailty status from V5 to V7 and changes in cardiac function over 6 years. We then evaluated the association of cardiac function measured at Visit 5 with progression in frailty status over 4 years. Multivariable regression models adjusted for demographics and comorbidities. Among 2574 participants free of heart failure at V5 and V7 (age 74±4 years at V5 and 81±4 years at V7), 3% (n=83) were frail. Frailty at V5 was associated with greater left atrial volume index and E/e' ratio at V5 and 7. Participants who transitioned from robust at V5 to frail at V7 demonstrated greater increases in left ventricular mass index, left atrial volume index, and E/e' over the same period. Among 1648 robust participants at Visit 5, greater left ventricular mass index and mean wall thickness, lower tissue Doppler imaging e', and higher E/e' ratio at Visit 5 were associated with progression in frailty status. Conclusions Among robust, older adults free of heart failure, progression in frailty and subclinical left ventricular remodeling and diastolic dysfunction are interrelated.