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Healthy aging is associated with structural and functional alterations in the brain and declines in multiple facets of motor performance such as balance, fine motor skills and motor coordination. Inhibitory processes are essential for optimal brain function and undergo agerelated alterations that may account for these behavioral deficits. Specifically, the inability to successfully modulate corticospinal excitability has been linked to declined motor performance in older adults  . In thisdoi:10.18632/aging.101480 pmid:29905530 pmcid:PMC6046222 fatcat:if3zyib2cvci3lmqdimyotoy7m
more »... ard, a key role is played by gamma-aminobutyric acid (GABA), i.e. the main inhibitory neurotransmitter. To demonstrate the importance of GABA in human movement control, complementary neuroimaging as well as non-invasive brain stimulation techniques can be employed to unravel age-related alterations in inhibitory function. On the one hand, GABA levels can be regionally quantified in vivo using magnetic resonance spectroscopy (MRS). Multiple MRS studies point towards an age-related decline in GABA levels, correlating with degraded motor performance as well as poor cognitive functioning. In terms of measurement of age-related changes in GABA levels using MRS, a major question of interest is whether brain structure alterations need to be considered. More specifically, the identification of age-related decreases in GABA level in the brain seems to be dependent on whether loss of gray matter is considered in the quantification of GABA levels or not  . Besides improvements in measurement techniques, more insight into the reliability of MRS-based measures over time as well as differences in GABA levels across areas covering the cortical-subcortical territory across the lifespan is warranted. Furthermore, GABA modulation is a critical entry point for the emergence of neuroplasticity. More specifically, a reduction in GABA level is associated with training-induced motor plasticity. The question remains whether and how GABA modulation can be facilitated in the brains of older adults to promote lifelong plasticity. Alternatively, noninvasive brain stimulation techniques (such as transcranial magnetic stimulation, TMS) provide tools to study the functional status and task-related modulation of two major receptor subtypes, i.e. GABAA (fast acting ionotropic) and GABAB (slower acting metabotropic), mediating inhibition at shorter and longer time scales, respectively . Motor evoked potentials (MEPs) provide a peripheral window into the Editorial central dynamic balance between inhibition and facilitation. Although most studies demonstrate age-related declines in both GABAA and GABAB-mediated inhibition within the primary motor cortex (M1), a minority report no age-related differences or even increased inhibition in older as compared to younger adults  . Interestingly, the ability to modulate GABAA-ergic inhibition appears related to motor performance in older adults  . Notably, MRS-obtained GABA levels do not seem to correlate with TMSobtained measures of GABAergic inhibition  and this requires further investigation to unravel their unique contribution to brain function and behavior. Alternative brain stimulation techniques allow scientists to reach beyond the motor cortical network to determine inhibitory mechanisms at work across the broader cortical territory. One area that has received prominent attention concerns the use of transcranial direct or alternating current stimulation (tDCS, tACS) to probe dynamic effects on GABA level in particular brain areas and their associated cortical networks . More research is warranted to establish the conditions under which stimulation effects can be obtained in older adults and how individual differences in brain status mediate these effects. Another recent development enabling exploration of the broader cortical territory for the study of inhibitory function is TMS combined with electroencephalography (EEG). With this technique TMS-evoked EEG potentials (TEPs) can be measured, characterized by a wave with peaks at shorter and longer latencies reflecting GABAA-and GABAB-mediated inhibition, respectively. Preliminary work has shown an agerelated deterioration of GABAA-mediated inhibition in the prefrontal cortex, whereas other studies have shown GABAB-mediated inhibition within M1 to increase with advancing age [5, 7] . Future research is warranted to shed light on the relationship between different methodologies as well as the exact relationship between GABA-mediated processses and behavioral performance across the lifespan. In this regard, besides focusing on GABA-mediated inhibitory processes alone, a promising avenue is to also consider measures of glutamate (i.e. the main excitatory neurotransmitter) and other neurochemical compounds to elaborate on the balance between excitatory and inhibitory processes in relation to (degraded) motor
The concept of inhibition is deeply rooted in our society. This is not only evident in our day-to-day activities but also in our scientific endeavors to reveal its underlying mechanisms. Indeed, inhibition is expressed in various functional domains such as cognition, action and emotion. Being able to suppress preferred, addictive or intended behaviors is at the heart of our well-being and how we succeed in society. There is no single construct that fully captures the different expressions ofdoi:10.18632/aging.101696 pmid:30521483 pmcid:PMC6326700 fatcat:ji4mx5y4vfajviyqviwp2q37fm
more »... ibition. Here we focus on motor inhibition, defined as the ability to successfully cancel a planned or already initiated action. This so-called motor inhibition plays a crucial role in everyday life. In life-threatening situations such as holding yourself from crossing the street when noticing a fast approaching car, efficient inhibitory control is even key to survival. Despite the fact that observing or measuring inhibition may be challenging as it implies absence of behavior, clearly, the role of inhibitory motor control should not be underestimated as it is of key importance for adaptability in many real-world situations. Clinical expressions of deficits in inhibitory function illustrate this such as for example Tourette Syndrome where inhibitory failure leads to production of awkward movements or sounds. Attention-Deficit/Hyperactivity Disorder also illustrates how lack of inhibition compromises everyday function and mental development. More recently, inhibition has also become a prominent focus of attention in aging research because there is mounting evidence that inhibitory motor function gradually declines with advancing age . This does not only contribute to impaired motor control in general but also to general alterations in brain functioning, such as expansion of neural activity, reduced neural distinctiveness of neural representations, and increases in connectivity among the brain networks. Interestingly, recent developments in brain-behavioral approaches have provided a new window into the neural mechanisms mediating efficient inhibitory control in the context of healthy aging  . This topic has been investigated from the cellular to the systems level. At the cellular level, γ-aminobutyric acid (GABA) is known to be the most prominent inhibitory neurotransmitter in the mammalian brain. At the systems level, one way to probe the GABA system in the human brain is the use of non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS). Editorial This technique identifies intracortical inhibitory circuits in the primary motor cortex, as driven by GABA A and GABA B receptor activity. However, whereas TMS studies can only provide an indirect measure of inhibitory mechanisms and its implicated neurotransmitter, recent advances in medical imaging techniques allow scientists to accurately quantify the level of neurochemical compounds such as GABA in the brain by means of magnetic resonance spectroscopy (MRS)  . Furthermore, in comparison with TMS, MRS allows for the registration of GABA across the broader cortical/ subcortical territory and thus reaches beyond the primary motor cortex. To date, considerable research efforts have already been devoted to the study of the GABAergic system in the aging brain. In that regard, both animal and human research has shown age-related alterations in the GABA system, either related to (1) the synthesis of GABA at the presynaptic level, (2) altered subunit composition of both GABA A and GABA B receptors at the postsynaptic level, (3) a reduction of GABA level assessed with MRS, and (4) altered intracortical inhibitory circuits as measured with TMS [4, 5] . These findings have sparked interest in using aging as a model for identifying the role of GABA in motor inhibitory control. Recently, we used MRS to register baseline GABA levels within key regions of the motor inhibition network in order to identify its role in age-related deterioration of inhibitory control  . We acquired GABA levels in various cortical as well as subcortical regions constituting the motor inhibition network, i.e. the pre-supplementary motor area, right inferior frontal cortex, left sensorimotor cortex and bilateral striatum  . In line with previous work, our results indicated that older adults showed deficits in inhibitory control as determined with a task requiring suppression of a planned movement following presentation of a visual warning signal shortly before movement initiation. With respect to the neural process of inhibition, our MRS data indicated that older adults exhibited reduced levels of the neurochemical compound GABA within regions of the motor inhibition network as compared to their younger counterparts. More specifically, older adults with lower GABA levels within the pre-supplementary motor area were found to show poorer inhibitory motor control. Thus, the level of GABA in a key node of the Aging, inhibition and GABA
Polyadenylation is thought to be involved in the degradation and quality control of bacterial RNAs but relatively few examples have been investigated. We used a combination of 5 -tagRACE and RNA-seq to analyze the total RNA content from a wild-type strain and from a poly(A)polymerase deleted mutant. A total of 178 transcripts were either up-or down-regulated in the mutant when compared to the wild-type strain. Poly(A)polymerase up-regulates the expression of all genes related to the FliAdoi:10.1093/nar/gkw894 pmid:28426097 pmcid:PMC5389530 fatcat:g3srokvpvrectb7uga355luhc4
more »... and several previously unknown transcripts, including numerous transporters. Notable down-regulation of genes in the expression of antigen 43 and components of the type 1 fimbriae was detected. The major consequence of the absence of poly(A)polymerase was the accumulation of numerous sRNAs, antisense transcripts, REP sequences and RNA fragments resulting from the processing of entire transcripts. A new algorithm to analyze the position and composition of post-transcriptional modifications based on the sequence of unencoded 3 -ends, was developed to identify polyadenylated molecules. Overall our results shed new light on the broad spectrum of action of polyadenylation on gene expression and demonstrate the importance of poly(A) dependent degradation to remove structured RNA fragments.
We investigated the effect of age on the ability to modulate GABAA-ergic and GABAB-ergic inhibitory activity during stopping of action (reactive inhibition) and preparation to stop (proactive inhibition). Twenty-five young and twenty-nine older adults performed an anticipated response version of the stop-signal task with varying levels of stop-signal probability. Paired-pulse transcranial magnetic stimulation was applied to left primary motor cortex to assess the modulation of GABAA-mediateddoi:10.18632/aging.101741 pmid:30670675 pmcid:PMC6366958 fatcat:6tkmmjqbnverfkkt73jkf3kl4y
more »... rt-interval intracortical inhibition (SICI) during stopping and GABAB-mediated long-interval intracortical inhibition (LICI) during the anticipation of a stop-signal. At the behavioral level, reactive inhibition was affected by aging as indicated by longer stop-signal reaction times in older compared to young adults. In contrast, proactive inhibition was preserved at older age as both groups slowed down their go response to a similar degree with increasing stop-signal probability. At the neural level, the amount of SICI was higher in successful stop relative to go trials in young but not in older adults. LICI at the start of the trial was modulated as a function of stop-signal probability in both young and older adults. Our results suggest that specifically the recruitment of GABAA-mediated intracortical inhibition during stopping of action is affected by aging.
Hailey-Hailey disease (HHD) is an uncommon acantholytic disorder of the skin. This is a case of a 64-year-old Filipino female with a chronic history of painful and malodorous intertriginous plaques. Histopathologic evaluation showed overlapping features of pemphigus vulgaris and Hailey-Hailey disease. A negative direct immunofluorescence test clinched the diagnosis of Hailey-Hailey disease. The patient was advised regarding preventive measures and treated with topical antibiotics and corticosteroids with improvement of her lesions.doi:10.47895/amp.v55i5.2872 fatcat:o7jf7gpvovdcblcg7tychfvegi
In line with previous MRS research in aging Cuypers et al., 2020 ; Hermans et al., 2018 ; Maes et al., 2018 ) , water was used as a reference compound. ... Indeed, previous studies reported age-related differences in motor performance across a wide range of bimanual coordination tasks (for a review, see Maes et al., 2017 ) . ...doi:10.1016/j.neuroimage.2021.117871 pmid:33607278 pmcid:PMC8275071 fatcat:xvxtngkdobdn7pvgki2sj7d7oq
Treatment of Chronic Obstructive Pulmonary Disease (COPD) is based on bronchodilation, with inhaled corticosteroids or azithromycin associated when frequent exacerbations occur. Despite the proven benefits of current treatment regimens, the need for new interventions in delineated subgroups remains. There is convincing evidence for oral vitamin D supplementation in reducing exacerbations in COPD patients severely deficient for circulating vitamin D. However, little is known about local vitamindoi:10.1186/s12931-020-01405-0 pmid:32493333 fatcat:ohpju7favfejxazgy76oppjpuu
more »... metabolism in the airways and studies examining expression of the vitamin D receptor (VDR), the activating enzyme (CYP27B1) and inactivating enzyme (CYP24A1) of vitamin D in lung tissue of COPD patients are lacking. Therefore, the expression and localization of key enzymes and the receptor of the vitamin D pathway were examined in tissue of 10 unused donor lungs and 10 COPD explant lungs. No differences in the expression of CYP27B1 and CYP24A1 were found. Although protein expression of VDR was significantly lower in COPD explant tissue, there was no difference in downstream expression of the antimicrobial peptide cathelicidin. Whereas CYP27B1 and CYP24A1 were present in all layers of the bronchial epithelium, VDR was only expressed at the apical layer of a fully differentiated bronchial epithelium with no expression in vascular endothelial cells. By contrast, CYP24A1 expression was highly present in lung endothelial cells suggesting that systemic vitamin D can be inactivated before reaching the epithelial compartment and the tissue immune cells. These data support the idea of exploring the role of vitamin D inhalation in patients with COPD.
Skill acquisition capabilities vary substantially from one individual to another. Volumetric brain studies have demonstrated that global volume of several subcortical structures predicts variations in learning outcome in young adults (YA) and older adults (OA). In this study, for the first time, we utilized shape analysis, which offers a more sensitive detection of subregional brain anatomical deformations, to investigate whether subregional anatomy of subcortical structures is associated withdoi:10.1093/cercor/bhw382 pmid:27909002 fatcat:cfimzcs5ijgwxphxhmrd6axi3u
more »... raininginduced performance improvement on a bimanual task in YA and OA, and whether this association is age-dependent. Compared with YA, OA showed poorer performance, greater performance improvement, and smaller global volume and compressed subregional shape in subcortical structures. In OA, global volume of the right nucleus accumbens and subregional shape of the right thalamus, caudate, putamen and nucleus accumbens were positively correlated with acquisition of difficult (non-preferred) but not easy (preferred) task conditions. In YA, global volume and subregional shape of the right hippocampus were negatively correlated with performance improvement in both the easy and difficult conditions. We argue that pre-existing neuroanatomical measures of subcortical structures involved in motor learning differentially predict skill acquisition potential in YA and OA.
Motor performance deteriorates with age. Hence, studying the effects of different training types on performance improvement is particularly important. Here, we investigated the neural correlates of the contextual interference (CI) effect in 32 young (YA; 16 female) and 28 older (OA; 12 female) human adults. Participants were randomly assigned to either a blocked or a random practice schedule, practiced three variations of a bimanual visuomotor task over 3 d, and were retested 6 d later.doi:10.1523/jneurosci.2640-17.2018 pmid:29483284 pmcid:PMC6596055 fatcat:inb3u4jj4jewjhah4csozrnpry
more »... al magnetic resonance imaging data were acquired during the first and last training days and during retention. Although the overall performance level was lower in OA than YA, the typical CI effects were observed in both age groups, i.e., inferior performance during acquisition but superior performance during retention for random relative to blocked practice. At the neural level, blocked practice showed higher brain activity in motor-related brain regions compared with random practice across both age groups. However, although activity in these regions decreased with blocked practice in both age groups, it was either preserved (YA) or increased (OA) as a function of random practice. In contrast, random compared with blocked practice resulted in greater activations in visual processing regions across age groups. Interestingly, in OA, the more demanding random practice schedule triggered neuroplastic changes in areas of the default mode network, ultimately leading to better long-term retention. Our findings may have substantial implications for the optimization of practice schedules, and rehabilitation settings in particular.SIGNIFICANCE STATEMENT In aging societies, it is critically important to understand how motor skills can be maintained or enhanced in older adults, with the ultimate goal to prolong functional independence. Here, we demonstrated that a more challenging random as opposed to a blocked practice environment temporarily reduced performance during the acquisition phase but resulted in lasting benefits for skill retention. In older adults, learning success was critically dependent on reduction of activation in areas of the default mode network, pointing to plastic functional changes in brain regions that are vulnerable to aging effects. The random practice context led to increased economy of brain activity and better skill retention. This provides new perspectives for reversing the negative consequences of aging.
In bromeliads, nothing is known about the associations fungi form with seeds and seedling roots. We investigated whether fungal associations occur in the seeds and seedling roots of two epiphytic Aechmea species, and we explored whether substrate and fungal associations contribute to seed germination, and seedling survival and performance after the first month of growth. We found a total of 21 genera and 77 species of endophytic fungi in the seeds and seedlings for both Aechmea species bydoi:10.1016/j.funeco.2019.01.004 fatcat:2e7mff3fi5drzpeyw2jkfzvham
more »... na Miseq sequencing. The fungal associations in seeds were found in the majority of corresponding seedlings, suggesting that fungi are transmitted vertically. Substrate quality modulated the germination and growth of seedlings, and beneficial endophytic fungi were not particularly crucial for germination but contributed positively to survival and growth. Overall, this study provides the first evidence of an endophytic fungal community in both the seeds and seedlings of two epiphytic bromeliads species that subsequently benefit plant growth.
This feasibility study aims to establish a University of Bohol Student Center at Tagbilaran City. The main proponent of this research is the University of Bohol, and the participants are the college students of the University of Bohol. The establishment of the student center will be situated particularly in Tabaco Street Tagbilaran City. The goal of the study is to determine the viability of establishing a UB Student Center of the different aspects, namely; management, marketing, technical,doi:10.15631/ub.mrj.v7i0.103 fatcat:dqal2giqpzcivhdxv2imyu5brq
more »... ncial, and socio-economic, respectively. This study used researcher-made questionnaires to gather data from the respondents. The researchers used questionnaires with randomly selected respondents with a total of 360 students from different colleges in the University of Bohol. Based on the conducted research, the researchers found out that UB Student Center is feasible in all aspects covered by this study. The majority of the target respondents are willing to patronize the student center with appropriate facilities and equipment to be offered to their students. With proper management and competent personnel in imposing policies, guidelines, the student center will be efficient and effective in the conduct of business operations. The student center shows profitability is feasible, and the investment is expected to be recouped within twelve years and three months. This feasibility study will contribute a social and economic advantage to the community. The researchers recommend that marketing programs and efforts shall be administered to announce the establishment of the student center publicly.
Platelets have been involved in both immune surveillance and host defense against severe infection. To date, whether platelet phenotype or other hemostasis components could be associated with predisposition to sepsis in critical illness remains unknown. The aim of this work was to identify platelet markers that could predict sepsis occurrence in critically ill injured patients. Methods: This single-center, prospective, observational, 7-month study was based on a cohort of 99 non-infected adultdoi:10.1186/s40635-017-0145-2 pmid:28699088 pmcid:PMC5505890 fatcat:uhwbtdfbq5gpde6qchv3plcyte
more »... atients admitted to ICUs for elective cardiac surgery, trauma, acute brain injury, and post-operative prolonged ventilation and followed up during ICU stay. Clinical characteristics and severity score (SOFA) were recorded on admission. Platelet activation markers, including fibrinogen binding to platelets, platelet membrane P-selectin expression, plasma soluble CD40L, and platelet-leukocytes aggregates were assayed by flow cytometry at admission and 48 h later, and then at the time of sepsis diagnosis (Sepsis-3 criteria) and 7 days later for sepsis patients. Hospitalization data and outcomes were also recorded. Methods: Of the 99 patients, 19 developed sepsis after a median time of 5 days. These patients had a higher SOFA score at admission; levels of fibrinogen binding to platelets (platelet-Fg) and of D-dimers were also significantly increased compared to the other patients. Levels 48 h after ICU admission no longer differed between the two patient groups. Platelet-Fg % was an independent predictor of sepsis (P = 0. 0031). By ROC curve analysis, cutoff point for Platelet-Fg (AUC = 0.75) was 50%. In patients with a SOFA cutoff of 8, the risk of sepsis reached 87% when Platelet-Fg levels were above 50%. Patients with sepsis had longer ICU and hospital stays and higher death rate. Conclusions: Platelet-bound fibrinogen levels assayed by flow cytometry within 24 h of ICU admission help identifying critically ill patients at risk of developing sepsis.
Structural studies of cell wall components of the pathogenic yeast Candida albicans have demonstrated the presence of ␤-1,2-linked oligomannosides in phosphopeptidomannan and phospholipomannan. During C. albicans infection, ␤-1,2-oligomannosides play an important role in host/pathogen interactions by acting as adhesins and by interfering with the host immune response. Despite the importance of ␤-1,2-oligomannosides, the genes responsible for their synthesis have not been identified. The maindoi:10.1074/jbc.m708825200 pmid:18234669 fatcat:sadboedombfxbjpqzdq6dtyrom
more »... son is that the reference species Saccharomyces cerevisiae does not synthesize ␤-linked mannoses. On the other hand, the presence of ␤-1,2-oligomannosides has been reported in the cell wall of the more genetically tractable C. albicans relative, P. pastoris. Here we present the identification, cloning, and characterization of a novel family of fungal genes involved in ␤-mannose transfer. Employing in silico analysis, we identified a family of four related new genes in P. pastoris and subsequently nine homologs in C. albicans. Biochemical, immunological, and structural analyses following deletion of four genes in P. pastoris and deletion of four genes acting specifically on C. albicans mannan demonstrated the involvement of these new genes in ␤-1,2-oligomannoside synthesis. Phenotypic characterization of the strains deleted in ␤-mannosyltransferase genes (BMTs) allowed us to describe the stepwise activity of Bmtps and acceptor specificity. For C. albicans, despite structural similarities between mannan and phospholipomannan, phospholipomannan ␤-mannosylation was not affected by any of the CaBMT1-4 deletions. Surprisingly, depletion in mannan major ␤-1,2-oligomannoside epitopes had little impact on cell wall surface ␤-1,2-oligomannoside antigenic expression.
doi:10.1093/ofid/ofv116 pmid:26389126 pmcid:PMC4564806 fatcat:yw4gmn2p4rdlneofeaezqea2ke
There is massive information and addresses that can be found through the internet. Internet users visit websites like forums and blogs worldwide to seek information, communicate especially to get ideas. Stack Overflow is one of the popular sites ever visited by communities. The main objective of this site is to enable users to ask questions, collaborate and seek help commonly to a certain programming context or errors. Furthermore, programmers find it an effective and interesting collaboratingdoi:10.47772/ijriss.2021.51105 fatcat:7nebqgc25na5bfl2tsyv5xfkre
more »... ite. Considering this site has been for many years on the internet. May it be a beginner trying to figure out programming, average or professionals with different logics and ways of contributions find this site very influential. This alone has shaped individuals' programming skills both negatively and positively. This study aims to produce a statistical record of correlation between developer interactions of Stack Overflow within Jose Maria College IT students and perceived programming skills. Jose Maria College is an institution that runs an IT program which means programming as one of their core subjects, students are no excuse and exposed to encountering programming issues. Often, the students are susceptible to visiting Stack Overflow to find answers for their assignments and projects. Nevertheless, this study will show the impact of the site on the programming skills of the students. Commonly visualization figures and text inputs indicating the instruments and findings.
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