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The brain is not idle during rest. Functional MRI (fMRI) studies have identified several resting-state networks, including the default mode network (DMN), which contains a set of cortical regions that interact with a hippocampus (HC) subsystem. Age-related alterations in the functional architecture of the DMN and HC may influence memory functions and possibly constitute a sensitive biomarker of forthcoming memory deficits. However, the exact form of DMN–HC alterations in aging and concomitant memory deficits is largely unknown. Here, using both task and resting data from 339 participants (25–80 y old), we have demonstrated age-related decrements in resting-state functional connectivity across most parts of the DMN, except for the HC network for which age-related elevation of connectivity between left and right HC was found along with attenuated HC–cortical connectivity. Elevated HC connectivity at rest, which was partly accounted for by age-related decline in white matter integrity of the fornix, was associated with lower cross-sectional episodic memory performance and declining longitudinal memory performance over 20 y. Additionally, elevated HC connectivity at rest was associated with reduced HC neural recruitment and HC–cortical connectivity during active memory encoding, which suggests that strong HC connectivity restricts the degree to which the HC interacts with other brain regions during active memory processing revealed by task fMRI. Collectively, our findings suggest a model in which age-related disruption in cortico–hippocampal functional connectivity leads to a more functionally isolated HC at rest, which translates into aberrant hippocampal decoupling and deficits during mnemonic processing. Significance Aging is accompanied by disruptive alterations in large-scale brain systems, such as the default mode network (DMN) and the associated hippocampus (HC) subsystem, which support higher cognitive functions. However, the exact form of DMN–HC alterations and concomitant memory deficits is largely unknown. We identified age-related decrements in resting-state functional connectivity of the cortical DMN, whereas elevated connectivity between the bilateral HC was found along with attenuated HC–cortical connectivity. Critically, elevated HC at rest restricts the degree to which HC interacts with other brain regions during memory tasks, and thus results in memory deficits. This study provides empirical evidence of how the relationship between the DMN and HC breaks down in aging and how such alterations underlie deficient mnemonic processing.

Drought is one of the most important environmental factor limiting the growth of woody and non woody plants. In the present paper, we aimed to explore the performance of Maclura pomifera under a prolonged drought period followed by re-watering. M. pomifera plants were exposed to four different watering regimes (100%, 75%, 50% and 30% of the field capacity (FC)) for three weeks and then rewatered. The exposure to drought affected physiological, morphological and biochemical traits of M. pomifera . Leaf area, relative water content and water potential of leaf decreased in parallel with increased water deficit. Malondialdehyde content increased along with the drought stress experiment. Soluble carbohydrates (sucrose, glucose and fructose) accumulated during drought stress, but decreased after 22 days of water deficit in severe stressed plants (30% FC). Proline and mannitol, two compatible osmolytes, were higher in drought stresses plants than in control plants. Additionally the activity of antioxidant enzymes (SOD, APX, DHAR and GR) resulted affected by drought stress. In the recovery period, the physiological parameters as well as the proline content recovered at control levels, whereas soluble sugars, mannitol and total activity of antioxidant enzymes remained slight higher than in control plants, presumably to allow plants a complete recovery after stress. Our results suggest that M. pomifera has a good adaptive response to drought stress, probably corresponded to decreasing oxidative injury by induction of the antioxidant system and accumulation of stable and protective osmolytes such as proline and mannitol at higher rates.

•Hubs had long-distance connections and high metabolic rates.•The topology of structural hubs was relatively age-invariant.•Age effects were larger in hub connections compared to peripheral connections.•Hub connections correlated more with processing speed than peripheral connections.•Hub connections partially accounted for age-related decline in processing speed. The human structural brain network, or connectome, has a rich-club organization with a small number of brain regions showing high network connectivity, called hubs. Hubs are centrally located in the network, energy costly, and critical for human cognition. Aging has been associated with changes in brain structure, function, and cognitive decline, such as processing speed. At a molecular level, the aging process is a progressive accumulation of oxidative damage, which leads to subsequent energy depletion in the neuron and causes cell death. However, it is still unclear how age affects hub connections in the human connectome. The current study aims to address this research gap by constructing structural connectome using fiber bundle capacity (FBC). FBC is derived from Constrained Spherical Deconvolution (CSD) modeling of white-matter fiber bundles, which represents the capacity of a fiber bundle to transfer information. Compared to the raw number of streamlines, FBC is less bias for quantifying connection strength within biological pathways. We found that hubs exhibit longer-distance connections and higher metabolic rates compared to peripheral brain regions, suggesting that hubs are biologically costly. Although the landscape of structural hubs was relatively age-invariant, there were wide-spread age effects on FBC in the connectome. Critically, these age effects were larger in connections within hub compared to peripheral brain connections. These findings were supported by both a cross-sectional sample with wide age-range (N = 137) and a longitudinal sample across 5 years (N = 83). Moreover, our results demonstrated that associations between FBC and processing speed were more concentrated in hub connections than chance level, and FBC in hub connections mediated the age-effects on processing speed. Overall, our findings indicate that structural connections of hubs, which demonstrate greater energy demands, are particular vulnerable to aging. The vulnerability may contribute to age-related impairments in processing speed among older adults.

Healthy aging is accompanied by progressive decline in cognitive performance and concomitant changes in brain structure and functional architecture. Age-accompanied alterations in brain function have been characterized on a network level as weaker functional connections within brain networks along with stronger interactions between networks. This phenomenon has been described as age-related differences in functional network segregation. It has been suggested that functional networks related to associative processes are particularly sensitive to age-related deterioration in segregation, possibly related to cognitive decline in aging. However, there have been only a few longitudinal studies with inconclusive results. Here, we used a large longitudinal sample of 284 participants between 25 to 80 years of age at baseline, with cognitive and neuroimaging data collected at up to three time points over a 10-year period. We investigated age-related changes in functional segregation among two large-scale systems comprising associative and sensorimotor-related resting-state networks. We found that functional segregation of associative systems declines in aging with exacerbated deterioration from the late fifties. Changes in associative segregation were positively associated with changes in global cognitive ability, suggesting that decreased segregation has negative consequences for domain-general cognitive functions. Age-related changes in system segregation were partly accounted for by changes in white matter integrity, but white matter integrity only weakly influenced the association between segregation and cognition. Together, these novel findings suggest a cascade where reduced white-matter integrity leads to less distinctive functional systems which in turn contributes to cognitive decline in aging.

One step toward healthy brain aging may be to entertain a physically active lifestyle. Studies investigating physical activity effects on brain integrity have, however, mainly been based on single brain markers, and few used a multimodal imaging approach. In the present study, we used cohort data from the Betula study to examine the relationships between scores reflecting current and accumulated physical activity and brain health. More specifically, we first examined if physical activity scores modulated negative effects of age on seven resting state networks previously identified by Salami, Pudas, and Nyberg (2014). The results revealed that one of the most age-sensitive RSN was positively altered by physical activity, namely, the posterior default-mode network involving the posterior cingulate cortex (PCC). Second, within this physical activity-sensitive RSN, we further analyzed the association between physical activity and gray matter (GM) volumes, white matter integrity, and cerebral perfusion using linear regression models. Regions within the identified DMN displayed larger GM volumes and stronger perfusion in relation to both current and 10-years accumulated scores of physical activity. No associations of physical activity and white matter integrity were observed. Collectively, our findings demonstrate strengthened PCC–cortical connectivity within the DMN, larger PCC GM volume, and higher PCC perfusion as a function of physical activity. In turn, these findings may provide insights into the mechanisms of how long-term regular exercise can contribute to healthy brain aging. •Higher physical activity score is related to stronger connectivity in the posterior DMN.•Higher physical activity score is related to larger GM volume of the PCC.•Higher physical activity score is related to higher perfusion rate within the PCC.

D1 and D2 dopamine receptors (D1DRs and D2DRs) may contribute differently to various aspects of memory and cognition. The D1DR system has been linked to functions supported by the prefrontal cortex. By contrast, the role of the D2DR system is less clear, although it has been hypothesized that D2DRs make a specific contribution to hippocampus-based cognitive functions. Here we present results from 181 healthy adults between 64 and 68 y of age who underwent comprehensive assessment of episodic memory, working memory, and processing speed, along with MRI and D2DR assessment with [11C]raclopride and PET. Caudate D2DR availability was positively associated with episodic memory but not with working memory or speed. Whole-brain analyses further revealed a relation between hippocampal D2DR availability and episodic memory. Hippocampal and caudate D2DR availability were interrelated, and functional MRI-based resting-state functional connectivity between the ventral caudate and medial temporal cortex increased as a function of caudate D2DR availability. Collectively, these findings indicate that D2DRs make a specific contribution to hippocampus-based cognition by influencing striatal and hippocampal regions, and their interactions.

Intracellular iron is essential for many neurobiological mechanisms. However, at high concentrations, iron may induce oxidative stress and inflammation. Brain iron overload has been shown in various neurodegenerative disorders and in normal aging. Elevated brain iron in old age may trigger brain dysfunction and concomitant cognitive decline. However, the exact mechanism underlying the deleterious impact of iron on brain function in aging is unknown. Here, we investigated the role of iron on brain function across the adult lifespan from 187 healthy participants (20–79 years old, 99 women) who underwent fMRI scanning while performing a working-memory n-back task. Iron content was quantified using R2* relaxometry, whereas neuroinflammation was estimated using myo-inositol measured by magnetic resonance spectroscopy. Striatal iron increased non-linearly with age, with linear increases at both ends of adulthood. Whereas higher frontostriatal activity was related to better memory performance independent of age, the link between brain activity and iron differed across age groups. Higher striatal iron was linked to greater frontostriatal activity in younger, but reduced activity in older adults. Further mediation analysis revealed that, after age 40, iron provided unique and shared contributions with neuroinflammation to brain activations, such that neuroinflammation partly mediated brain-iron associations. These findings promote a novel mechanistic understanding of how iron may exert deleterious effects on brain function and cognition with advancing age.

Cannabis is an annual plant with a long history of use as food, feed, fiber, oil, medicine, and narcotics. Despite realizing its true value, it has not yet found its true place. Cannabis has had a long history with many ups and downs, and now it is our turn to promote it. Cannabis contains approximately 600 identified and many yet unidentified potentially useful compounds. Cannabinoids, phenolic compounds, terpenoids, and alkaloids are some of the secondary metabolites present in cannabis. However, among a plethora of unique chemical compounds found in this plant, the most important ones are phytocannabinoids (PCs). Over hundreds of 21-22-carbon compounds exclusively produce in cannabis glandular hairs through either polyketide and or deoxyxylulose phosphate/methylerythritol phosphate (DOXP/MEP) pathways. Trans-Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) are those that first come to mind while talking about cannabis. Nevertheless, despite the low concentration, cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabinodiol (CBND), and cannabinidiol (CBDL) may have potentially some medical effects. PCs and endocannabinoids (ECs) mediate their effects mainly through CB1 and CB2 receptors. Despite all concerns regarding cannabis, nobody can ignore the use of cannabinoids as promising tonic, analgesic, antipyretic, antiemetic, anti-inflammatory, anti-epileptic, anticancer agents, which are effective for pain relief, depression, anxiety, sleep disorders, nausea and vomiting, multiple sclerosis, cardiovascular disorders, and appetite stimulation. The scientific community and public society have now increasingly accepted cannabis specifically hemp as much more than a recreational drug. There are growing demands for cannabinoids, mainly CBD, with many diverse therapeutic and nutritional properties in veterinary or human medicine. The main objective of this review article is to historically summarize findings concerning cannabinoids, mainly THC and CBD, towards putting these valuable compounds into food, feed and health baskets and current and future trends in the consumption of products derived from cannabis.

Fat-tail content of sheep breeds is varied and the molecular mechanisms regulating fat-tail development have not been well characterized. Aiming at better identifying the important candidate genes and their functional pathways contributing to fat deposition in the tail, a comparative transcriptome analysis was performed between fat- (Lori-Bakhtiari) and thin-tailed (Zel) Iranian sheep breeds using RNA-seq. The experiment was conducted on six male lambs (three lambs per each breed) at seven months of age. Four different combinations of aligners and statistical methods including Hisat2 + edgeR, Hisat2 + DESeq2, STAR + edgeR and STAR + DESeq2 were used to identify the differentially expressed genes (DEGs). The DEGs were selected for functional enrichment analysis and protein-protein interaction (PPI) network construction. Module analysis was also conducted to mine the functional sub-networks from the PPI network. In total, 264 genes including 80 up- and 184 down-regulated genes were identified as DEGs. The RNA-Seq results were validated by Q-RT-PCR. Functional analysis of DEGs and the module analysis of PPI network demonstrated that in addition to pathways affecting lipid metabolism, a series of enriched functional terms related to “response to interleukin”, “MAPK signaling pathways”, “Wnt signaling pathway”, “ECM-receptor interaction”, “regulation of actin cytoskeleton”, and “response to cAMP” might contribute to the deposition of fat in tails of sheep. Overall results using RNA-Seq analysis characterized important candidate genes involved in the fatty acid metabolism and regulation of fat deposition, suggesting novel insights into molecular aspects of fat-tail metabolism in sheep. Selected DEGs should be further investigated as potential markers associated with the fat-tail development in sheep breeds.

The hippocampus is a complex structure critically involved in numerous behavior-regulating systems. In young adults, multiple overlapping spatial modes along its longitudinal and transverse axes describe the organization of its functional integration with neocortex, extending the traditional framework emphasizing functional differences between sharply segregated hippocampal subregions. Yet, it remains unknown whether these modes (i.e. gradients) persist across the adult human lifespan, and relate to memory and molecular markers associated with brain function and cognition. In two independent samples, we demonstrate that the principal anteroposterior and second-order, mid-to-anterior/posterior hippocampal modes of neocortical functional connectivity, representing distinct dimensions of macroscale cortical organization, manifest across the adult lifespan. Specifically, individual differences in topography of the second-order gradient predicted episodic memory and mirrored dopamine D1 receptor distribution, capturing shared functional and molecular organization. Older age was associated with less distinct transitions along gradients (i.e. increased functional homogeneity). Importantly, a youth-like gradient profile predicted preserved episodic memory – emphasizing age-related gradient dedifferentiation as a marker of cognitive decline. Our results underscore a critical role of mapping multidimensional hippocampal organization in understanding the neural circuits that support memory across the adult lifespan.