Activity-related Changes Research Articles

Antagonistic behavior of brain networks mediated by low-frequency oscillations: electrophysiological dynamics during internal–external attention switching

Antagonistic activity of brain networks likely plays a fundamental role in how the brain optimizes its performance by efficient allocation of computational resources. A prominent example involves externally/internally oriented attention tasks, implicating two anticorrelated, intrinsic brain networks: the default mode network (DMN) and the dorsal attention network (DAN). To elucidate electrophysiological underpinnings and causal interplay during attention switching, we recorded intracranial EEG (iEEG) from 25 epilepsy patients with electrode contacts localized in the DMN and DAN. We show antagonistic network dynamics of activation-related changes in high-frequency (> 50 Hz) and low-frequency (< 30 Hz) power. The temporal profile of information flow between the networks estimated by functional connectivity suggests that the activated network inhibits the other one, gating its activity by increasing the amplitude of the low-frequency oscillations. Insights about inter-network communication may have profound implications for various brain disorders in which these dynamics are compromised.

Multimodal imaging analysis of autosomal recessive bestrophinopathy: Case series.

Autosomal recessive bestrophinopathy (ARB) is a subtype of bestrophinopathy caused by biallelic mutations of the BEST1 gene, which affect the retinal pigment epithelium (RPE). Studying RPE abnormalities through imaging is essential for understanding ARB. This case series involved the use of multimodal imaging techniques, namely autofluorescence (AF) imaging at 488 nm [short-wavelength AF] and 785 nm [near-infrared AF (NIR-AF)] and polarization-sensitive optical coherence tomography (PS-OCT), to investigate RPE changes in 2 siblings with ARB. Two Japanese siblings (Case 1: male, followed for 20-23 years; Case 2: female, followed for 13-17 years) carried compound heterozygous mutations of the BEST1 gene. Both siblings were diagnosed with ARB. Multimodal imaging techniques were used to evaluate RPE changes. Both siblings had funduscopic changes similar to those seen in the vitelliruptive stage of Best vitelliform macular dystrophy during the follow-up period. NIR-AF imaging showed hypo-AF of the entire macular lesion in both cases, and this hypo-AF remained stable over time. PS-OCT confirmed reduced RPE melanin content in these hypo-AF areas. Additionally, hyper-NIR-AF dots were observed within hypo-NIR-AF areas. Concomitant identification of focally thickened RPE melanin on PS-OCT imaging and hyper-AF on short-wavelength AF imaging at the sites containing hyper-NIR-AF dots indicated that the hyper-NIR-AF dots had originated from either stacked RPE cells or RPE dysmorphia. We confirmed RPE abnormalities in ARB, including diffuse RPE melanin damage in the macula alongside evidence of RPE activity-related changes. This case series demonstrates that multimodal imaging, particularly NIR-AF and PS-OCT, provides detailed insights into RPE alterations in ARB.

Salinity-induced succession of phototrophic communities in a southwestern Siberian soda lake during the solar activity cycle

A variety of lakes located in the dry steppe area of southwestern Siberia are exposed to rapid climatic changes, including intra-century cycles with alternating dry and wet phases driven by solar activity. As a result, the salt lakes of that region experience significant fluctuations in water level and salinity, which have an essential impact on the indigenous microbial communities. But there are few microbiological studies that have analyzed this impact, despite its importance for understanding the functioning of regional water ecosystems. This work is a retrospective study aimed at analyzing how solar activity-related changes in hydrological regime affect phototrophic microbial communities using the example of the shallow soda lake Tanatar VI, located in the Kulunda steppe (Altai Region, Russia, southwestern Siberia). The main approach used in this study was the comparison of hydrochemical and microscopic data obtained during annual field work with satellite and solar activity data for the 12-year observation period (2011–2022). The occurrence of 33 morphotypes of cyanobacteria, two key morphotypes of chlorophytes, and four morphotypes of anoxygenic phototrophic bacteria was analyzed due to their easily recognizable morphology. During the study period, the lake surface changed threefold and the salinity changed by more than an order of magnitude, which strongly correlated with the phases of the solar activity cycles. The periods of high (2011–2014; 100–250 g/L), medium (2015–2016; 60 g/L), extremely low (2017–2020; 13–16 g/L), and low (2021–2022; 23–34 g/L) salinity with unique biodiversity of phototrophic communities were distinguished. This study shows that solar activity cycles determine the dynamics of the total salinity of a southwestern Siberian soda lake, which in turn determines the communities and microorganisms that will occur in the lake, ultimately leading to cyclical changes in alternative states of the ecosystem (dynamic stability).

A magyarországi 10–11. századi sebészi trepanációk összehasonlító vizsgálata a validált oszteoarcheológiai adatok tükrében

Trepanations are divided into three groups in the Eastern European osteological practice: surgical, cultical and symbolic trepanations. Classical surgical interventions are conducted on living subjects, and all three layers of the cranial vault are removed. My examinations were conducted in skeletal series with skulls bearing surgical trepanations that derive from the Conquest Period and the early Árpádian Age (9–11th c. CE). I examined all cases applying a unified protocol for comparability, and I also made efforts to verify the dating and the trepanation diagnosis of each possible case. This type of work creating a cadastre of 10–11th century trepanations is unprecedented in the Hungarian osteological practice. In 51 cases, the earlier diagnosis of trepanation was verified. I examined all the available remains of each affected individuals, and also investigated 5 more individuals of the same sex and similar age-at-death in each series for comparison. Instead of the usual nosology-based palaeopathological diagnostical process, I observed types of lesion in the endocranial and ectocranial surfaces, and made statistical comparison between the trepanned and non-trepanned samples. The work hypothesis was that trepanations were conducted for real therapeutic reasons. If pathological features are more frequent among individuals with trepanations than their peers, it indirectly implies that trepanation might have been applied as a therapeutic measure in most cases and was not a ritual intervention as often hypothesized elsewhere. Beside the comparative work, we also put forward a change in nomenclature; we wish to introduce the word ‘cranioglyph’ instead of ‘symbolic trepanation’, since the latter tends to be confused with other interventions in the Western practice. In the future, we wish to carry on the comparative approach to postcranial elements and activity-related changes to further elucidate the indication of these ancient surgical techniques.

Studying early structural changes in SOS1 mediated KRAS activation mechanism

KRAS activation is known to be modulated by a guanine nucleotide exchange factor (GEF), namely, Son of Sevenless1 (SOS1). SOS1 facilitates the exchange of GDP to GTP thereby leading to activation of KRAS. The binding of GDP/GTP to KRAS at the REM/allosteric site of SOS1 regulates the activation of KRAS at CDC25/catalytic site by facilitating its exchange. Different aspects of the allosteric activation of KRAS through SOS1 are still being explored. To understand the SOS1 mediated activation of KRAS, molecular dynamics simulations for a total of nine SOS1 complexes (KRAS-SOS1-KRAS) were performed. These nine systems comprised different combinations of KRAS-bound nucleotides (GTP/GDP) at REM and CDC25 sites of SOS1. Various conformational and thermodynamic parameters were analyzed for these simulation systems. MMPBSA free energy analysis revealed that binding at CDC25 site of SOS1 was significantly low for GDP-bound KRAS as compared to that of GTP-bound KRAS. It was observed that presence of either GDP/GTP bound KRAS at the REM site of SOS1 affected the activation related changes in the KRAS present at CDC25 site. The conformational changes at the catalytic site of SOS1 resulting from GDP/GTP-bound KRAS at the allosteric changes may hint at KRAS activation through different pathways (slow/fast/rare). The allosteric effect on activation of KRAS at CDC25 site may be due to conformations adopted by switch-I, switch-II, beta2 regions of KRAS at REM site. The effect of structural rearrangements occurring at allosteric KRAS may have led to increased interactions between SOS1 and KRAS at both the sites. The SOS1 residues involved in these important interactions with KRAS at the REM site were R694, S732 and K735. Whereas the ones interacting with KRAS at CDC25 site were S807, W809 and K814. This may suggest the crucial role of these residues in guiding the allosteric activation of KRAS at CDC25 site. The conformational shifts observed in the switch-I, switch-II and alpha3 regions of KRAS at CDC25 site may be attributed to be a part of allosteric activation. The binding affinities, interacting residues and conformational dynamics may provide an insight into development of inhibitors targeting the SOS1 mediated KRAS activation.

Combination of furosemide, gold, and dopamine as a potential therapy for breast cancer.

Breast cancer is one of the leading causes of death in women worldwide. Initially, it develops in the epithelium of the ducts or lobules of the breast glandular tissues with limited growth and the potential to metastasize. It is a highly heterogeneous malignancy; however, the common molecular mechanisms could help identify new targeted drugs for treating its subtypes. This study uses computational drug repositioning approaches to explore fresh drug candidates for breast cancer treatment. We also implemented reversal gene expression and gene expression-based signatures to explore novel drug candidates computationally. The drug activity profiles and related gene expression changes were acquired from the DrugBank, PubChem, and LINCS databases, and then in silico drug screening, molecular dynamics (MD) simulation, replica exchange MD simulations, and simulated annealing molecular dynamics (SAMD) simulations were conducted to discover and verify the valid drug candidates. We have found that compounds like furosemide, gold, and dopamine showed significant outcomes. Furthermore, the expression of genes related to breast cancer was observed to be reversed by these shortlisted drugs. Therefore, we postulate that combining furosemide, gold, and dopamine would be a potential combination therapy measurement for breast cancer patients.

P-550 Transgenerational epigenetic influences of maternal circadian rhythm changes during pregnancy and lactation periods on cognition and behavior in male offspring

Abstract Study question Do maternal circadian rhythm changes during pregnancy and lactation periods cause transgenerational behavioral and cognitive alterations in male offspring? Summary answer Maternal circadian rhythm changes cause impaired behavioral alterations such as motor activity impairments, increased anxiety and weakening of spatial memory in male offspring. What is known already The circadian system regulates the daily temporal organization in behavior and physiology in most species. Recent publications in model systems have emphasized the negative effects of circadian rhythm disruption on both female and male reproduction and fertility. There is growing concern about the long-term effects of circadian rhythm disruptions during pregnancy and lactation periods on human offspring and their descendants as circadian regulation during these periods can potentially alter epigenetic programing in offspring. However, there is a lack of information about the possible transgenerational effects of circadian rhythm disorders for the health of offspring in the literature. Study design, size, duration Male offspring from pregnant Wistar rats (n = 60) which were exposed to control (12 hours light/12 hours dark), short day (SD) (8 hours light/16 hours dark) or long day (LD) periods (16 hours light/8 hours dark) during only pregnancy, only lactation or both periods (n = 15/group) categorized as control, SD pregnancy (SD-P), SD lactation (SD-L), SD pregnancy and lactation (SD-P+L), LD pregnancy (LD-P), LD lactation (LD-L), LD pregnancy and lactation (LD-P+L) groups. Participants/materials, setting, methods The length of gestation, litter size, sex ratio of pups (fraction male) and birth weights were recorded. The maternal locomotor activity and anxiety were analyzed by open field (OF) and elevated plus maze (EPM) tests, respectively (n = 15 mothers/group). Learning and memory, locomotor activity and anxiety related changes were studied in the male offspring in pre-pubertal, pubertal and adult periods with object localization (OL) and Morris water maze (MWM), OF and EPM tests, respectively. Main results and the role of chance Newborn weights was significantly increased in SD (5.01±0.07) and LD (4.47±0.29) groups compared to control group (3.73±0.03) (p &amp;lt; 0.001). Male sex ratio of pups born to mothers on SD schedule was unusually low (0.21±0.62) compared to mothers on normal light schedule (0.48±0.05) (p &amp;lt; 0.001). The gestation length was not altered. Locomotor activity was increased in mothers exposed to SD schedule (p &amp;lt; 0.01). A significant motor activity impairment in the prepubertal period was remarkable in SD-P+L, LD-P, LD-L and LD-P+L groups (p &amp;lt; 0.001). Compared to control group, EPM test showed that all the offspring in SD groups had significant increase in their anxiety in the prepubertal period. Motor functions that decreased before puberty seems gradually improved at adulthood. Weakened short-term spatial memory was observed at puberty, especially in SD-P (p &amp;lt; 0.001), SD-P+L (p &amp;lt; 0.05), LD-P (p &amp;lt; 0.05) groups. Time to find the platform was significantly higher than those measured for control group for SD-P-L (p &amp;lt; 0.001) in the prepubertal period and LD-P+L group (p &amp;lt; 0.001) in the pubertal period meaning decreased spatial memory and learning. A probe trial given on day 6 with MWM test showed that LD groups had no alterations in spatial memory whereas SD-P (p &amp;lt; 0.05) and SD-G+L (p &amp;lt; 0.001) groups showed impaired changes in long-term spatial memory. Limitations, reasons for caution Due to limitations of working with human subjects exposed to shift work schedules, most chronoregulation research including ours has used rodent models with limitations in translating to human studies. However, to truly know if such concerns apply to humans will require retrospective and prospective human studies. Wider implications of the findings Epigenetic transitions are crucial for transcriptional reprogramming triggered by environmental cues. Our study might provide valuable information regarding transgenerational effects of maternal chronodisruption on health later in life of the offspring, particularly at prepubertal and pubertal periods, create suggestions and guidelines for reproductive biology, shift work and possible infertility problems. Trial registration number This work was supported by research grants from the Scientific and Technological Research Council of Turkey (TUBITAK) (SBAG 219S636) and Akdeniz University, The Scientific Research Projects Coordination Unit (TYL-2018-3580).

Increase in thalamic cerebral blood flow is associated with antidepressant effects of ketamine in major depressive disorder

Ketamine is a promising treatment option for patients with Major Depressive Disorder (MDD) and has become an important research tool to investigate antidepressant mechanisms of action. However, imaging studies attempting to characterise ketamine’s mechanism of action using blood oxygen level-dependent signal (BOLD) imaging have yielded inconsistent results- at least partly due to intrinsic properties of the BOLD contrast, which measures a complex signal related to neural activity. To circumvent the limitations associated with the BOLD signal, we used arterial spin labelling (ASL) as an unambiguous marker of neuronal activity-related changes in cerebral blood flow (CBF). We measured CBF in 21 MDD patients at baseline and 24 h after receiving a single intravenous infusion of subanesthetic ketamine and examined relationships with clinical outcomes. Our findings demonstrate that increase in thalamus perfusion 24 h after ketamine administration is associated with greater improvement of depressive symptoms. Furthermore, lower thalamus perfusion at baseline is associated both with larger increases in perfusion 24 h after ketamine administration and with stronger reduction of depressive symptoms. These findings indicate that ASL is not only a useful tool to broaden our understanding of ketamine’s mechanism of action but might also have the potential to inform treatment decisions based on CBF-defined regional disruptions.

MORPHIOUS: an unsupervised machine learning workflow to detect the activation of microglia and astrocytes

BackgroundIn conditions of brain injury and degeneration, defining microglial and astrocytic activation using cellular markers alone remains a challenging task. We developed the MORPHIOUS software package, an unsupervised machine learning workflow which can learn the morphologies of non-activated astrocytes and microglia, and from this information, infer clusters of microglial and astrocytic activation in brain tissue.MethodsMORPHIOUS combines a one-class support vector machine with the density-based spatial clustering of applications with noise (DBSCAN) algorithm to identify clusters of microglial and astrocytic activation. Here, activation was triggered by permeabilizing the blood–brain barrier (BBB) in the mouse hippocampus using focused ultrasound (FUS). At 7 day post-treatment, MORPHIOUS was applied to evaluate microglial and astrocytic activation in histological tissue. MORPHIOUS was further evaluated on hippocampal sections of TgCRND8 mice, a model of amyloidosis that is prone to microglial and astrocytic activation.ResultsMORPHIOUS defined two classes of microglia, termed focal and proximal, that are spatially adjacent to the activating stimulus. Focal and proximal microglia demonstrated activity-associated features, including increased levels of ionized calcium-binding adapter molecule 1 expression, enlarged soma size, and deramification. MORPHIOUS further identified clusters of astrocytes characterized by activity-related changes in glial fibrillary acidic protein expression and branching. To validate these classifications following FUS, co-localization with activation markers were assessed. Focal and proximal microglia co-localized with the transforming growth factor beta 1, while proximal astrocytes co-localized with Nestin. In TgCRND8 mice, microglial and astrocytic activation clusters were found to correlate with amyloid-β plaque load. Thus, by only referencing control microglial and astrocytic morphologies, MORPHIOUS identified regions of interest corresponding to microglial and astrocytic activation.ConclusionsOverall, our algorithm is a reliable and sensitive method for characterizing microglial and astrocytic activation following FUS-induced BBB permeability and in animal models of neurodegeneration.

In search of the ‘great horse’: A zooarchaeological assessment of horses from England (AD 300–1650)

AbstractPopular culture presents a deep‐rooted perception of medieval warhorses as massive and powerful mounts, but medieval textual and iconographic evidence remains highly debated. Furthermore, identifying warhorses in the zooarchaeological record is challenging due to both a paucity of horse remains relative to other domesticates, and the tendency of researchers to focus on osteological size, which makes it difficult to reconstruct in‐life usage of horses and activity related changes. This paper presents the largest zooarchaeological dataset of English horse bones (n = 1964) from 171 unique archaeological sites dating between AD 300 and 1650. Using this dataset alongside a modern comparative sample of known equids (n = 490), we examine trends in size and shape to explore how the skeletal conformation of horses changed through time and reflected their domestic, elite and military roles. In addition to evidencing the generally small stature of medieval horses relative to both earlier and later periods, we demonstrate the importance of accurately exploring the shape of skeletal elements to describe the morphological characteristics of domestic animals. Furthermore, we highlight the need to examine shape variation in the context of entheseal changes and biomechanics to address questions of functional morphology and detect possible markers of artificial selection on past horses.

The Prospective Prognostic Value of Biopsychosocial Indices of Sensitivity to Physical Activity Among People With Back Pain.

Many people living with musculoskeletal pain conditions experience a range of negative biopsychosocial responses to physical activity, referred to as increased sensitivity to physical activity (SPA), that may undermine successful rehabilitation. This exploratory study aims to provide the first prospective analysis of the potential prognostic value of 3 biopsychosocial indices of SPA in relation to rehabilitation outcomes. This study also aimed to shed light on the cross-sectional interrelationships between these 3 biopsychosocial indices of SPA. Adults with back pain were evaluated upon starting physical therapy and then again 3 months later. The initial testing session consisted of self-reported pain-related questionnaires and assessment of activity-related changes in pressure pain thresholds (SPA-Sensory), pain intensity ratings (SPA-Pain), and situational catastrophizing (SPA-Psych). The 3-month follow-up consisted of self-reported disability and pain questionnaires. Correlational and hierarchical linear regression analyses were conducted. A total of 97 participants completed both the initial visit and 3-month follow-up. The SPA-Pain index and the SPA-Psych index were significantly intercorrelated, but neither were correlated with the SPA-Sensory index. The SPA-Sensory index was not correlated with outcomes. The SPA-Pain index was correlated only with cross-sectional disability and pain outcomes. The SPA-Psych index was the only SPA index significantly correlated with outcomes both cross-sectionally and at 3-month follow-up. After controlling for baseline pain/disability and pain catastrophizing, SPA-Psych was no longer a significant prognostic factor for pain, but remained a significant prognostic factor for disability at 3-month follow-up (β=0.272, t=2.674, P=0.008, R2 Δ=5.60%). This study highlights the importance of conceptualizing and measuring SPA as a biopsychosocial (rather than unidimensional) construct and points toward the added prognostic value of this construct. Implications for future research and practice are discussed.

Unintended consequences: quantifying the benefits, iatrogenic harms and downstream cascade costs of musculoskeletal MRI in UK primary care

ObjectivesThe largest proportion of general practitioner (GP) magnetic resonance imaging (MRI) is musculoskeletal (MSK), with consistent annual growth. With limited supporting evidence and potential harms from early imaging overuse, we...

Left ventricular rotational mechanics in elite athletes with high dynamic component of their training - a three-dimensional speckle-tracking echocardiographic study

Abstract Funding Acknowledgements Type of funding sources: None. Introduction. In normal circumstances left ventricular (LV) apex and base rotate different directions during cardiac cycle, while LV apex rotates counterclocwise, LV base has a clockwise movement at the same time. This sort of towel-wringing-like movement is called LV twist. Three-dimensional speckle-tracking echocardiography (3DSTE) is a new, promising, easy-to-perform and reproducible modality for the evaluation of LV apical and basal rotations. Although cardiac adaptation is a known feature seen in highly trained athletes, there are conflicting results according to sport activity-related changes in LV rotational mechanics. The present study was designed to test whether differences in LV rotational mechanics could be detected in elite athletes with high dynamic, but different grade of static components of their training by 3DSTE. Methods. The subjects group comprised 80 elite sportmen, which group of athletes was further divided according to the task force classification of the American College of Cardiology considering dynamic and static components of their training. The following groups were created regarding to their physical activity: Group C1 (high dynamic/low static)(n = 13, mean age: 24.0 ± 5.1 years, Group C2 (high dynamic/moderate static)(n = 23, mean age: 24.6 ± 7.7 years) and Group C3 (high dynamic/high static)(n = 34, mean age: 22.8 ± 6.0 years). Their results were compared to 67 age- and gender-matched non-athletic healthy controls (mean age: 24.0 ± 5.1 years, 33 men). 3DSTE was used for the evaluation of LV rotational abnormalities. Results. Increased LV end-diastolic and end-systolic volumes could be detected in Groups C2 and C3 subjects as compared to controls. No changes in LV volumes and rotational mechanics could be detected in Group C1 cases. Reduced LV basal rotation was seen in Group C2 and C3 subjects compared to that of controls (-3.17 ± 2.81 degree and -2.88 ± 1.88 degree vs. -4.31 ± 1.82 degree, p &amp;lt; 0.05 and p &amp;lt; 0.05, respectively). It was accompanied with LV twist reduction in Groups C2 and C3 subjects compared to that of controls (11.3 ± 4.3 degree and 11.5 ± 4.1 degree vs. 14.0 ± 3.4 degree, p &amp;lt; 0.05 and p &amp;lt; 0.05, respectively). None of elite athletes showed absence of LV twist called as LV ‘rigid body rotation’ (LV-RBR). Conclusions. Significant LV basal rotation and twist reduction could be detected in elite athletes with high dynamic and moderate/high static components of their training.

Loss of muscular force in isolated rat diaphragms is related to changes in muscle fibre size

Objective. Passivity of the diaphragm during prolonged mechanical ventilation can lead to ventilation-induced diaphragmatic dysfunction reasoned by a reduction of diaphragmatic muscle strength. Electrical stimulation may be utilised to modulate diaphragm muscle strength. Therefore we intended to investigate diaphragmatic muscle strength based on stimulation with electric impulses. Approach. Diaphragms of Wistar rats were excised, embedded in various incubation solutions and placed in a diaphragm force measurement device. Pressure amplitudes generated by the diaphragm in dependency of the embedding solution, stimulation frequency and time (360 min) were determined. Furthermore, the diaphragms were histologically evaluated. Main results. The ex vivo diaphragms evoked no pressure if embedded in incubation solutions with high potassium concentrations and up to >20 cmH2O if embedded in incubation solutions with extracellular potassium concentrations. Although vitality was well maintained after 360 min (78%) cultivation, the diaphragm’s force dropped by 90.8% after 240 min. The decline in the diaphragm’s force progressed faster if stimulation was performed every 20 min compared to every 120 min. The size of Type I muscle fibres was largest in diaphragms stimulated every 120 min. The fibre size of Type 2b/x muscle cells was lower in diaphragms after electrical stimulation compared to non-stimulated diaphragms. Significance. The force that the diaphragm can develop in ex vivo conditions depends on the incubation solution and the conditions of activation. Activity-related changes in the diaphragm’s muscular force are accompanied by specific changes in muscle fibre size.

ACTION for Men: Study Protocol of a Community Capacity Building Intervention to Develop and Implement Gender-Sensitive Physical Activity Programs for Men 50 Plus.

Introduction: Capacity building for health promotion is a relevant precondition for sustainable, health-related changes in community settings. So far, there are few evidence-based recommendations about how to implement and evaluate community capacity building approaches. ACTION for men (A4M) is a project designed to build and evaluate capacities for health promotion in three rural communities in Bavaria, Germany, via a participatory approach including multiple community stakeholders. The project specifically aims at improving physical activity (PA) in men over 50 years of age (50 plus).Methods and Analysis: As a strategy to build the communities' capacities, we set up stakeholder groups in so far two communities. Those stakeholder groups will be facilitated over a period of 1–3 years. In regular meetings, the group members will be motivated to actively participate in planning and implementing PA programs for men 50 plus. The facilitation will systematically address key domains of community capacity (e.g., critical awareness, problem assessment, resource mobilization). The evaluation of the capacity building processes will be carried out using a mixed-methods design. Evaluation instruments consist of structured documentations and face-to-face interviews with stakeholder group participants (and drop-outs) as well as a pre-post-test using a standardized questionnaire in order to detect activity-related changes in men 50 plus from the involved communities. In community three, we will conduct the same procedure with a delay of 6 months.Discussion: Building community capacity for health promotion programs is the primary aim in A4M, and thus differs from previous research in which capacity is mostly a means to an end or an “incidental” result of a health promotion program. Therefore, A4M is expected to deliver important findings about how to implement and evaluate capacity building processes for health promotion, as well as how to address physical activity in community settings.

Effect of melatonin on T/B cell activation and immune regulation in pinealectomy mice

Melatonin is an indole neuroendocrine hormone that is mainly secreted by the pineal gland to regulate circadian rhythm, antioxidation, and immune regulation. Melatonin plays an important role in T cell-mediated immune responses against cancer, infections, and the development of many autoimmune diseases. The aim of this study was to investigate the immunomodulatory effects of melatonin on T/B cell activation in pinealectomy mice. The improved pinealectomy procedure for mice presented in this study is a good animal model to be used in follow-up studies on melatonin. After pinealectomy, the tissue removed was identified as the pineal body using HE staining. The effects of melatonin supplementation on T cell activation and activation-related changes to the MAPK/NF-κ B pathways were analyzed by flow cytometry and real-time PCR. We found that expression levels of Th1, Th2 and Th17-related cytokines in peripheral blood were lower in mice that had undergone pinealectomy, compared with normal mice. After melatonin supplementation, cytokine levels rapidly increased within a short period of time, which resulted in the gradual recovery of cytokine expression levels. Moreover, activation of T/B cells in mice was weakened and decreased after pineal gland removal. Melatonin was found to inhibit the expression of TLR3, p38, JNK, and MAPK/NF-κ B within a short period (2 weeks) of melatonin replenishment. This inhibition gradually weakened with time, since the degree of inhibition is negatively related with the dosage of melatonin. In conclusion, melatonin may regulate the activation of T/B cells, playing a critical role in the regulation of immune balance.

Signatures of Magnetic Activity: On the Relation between Stellar Properties and p-mode Frequency Variations

Abstract In the Sun, the properties of acoustic modes are sensitive to changes in the magnetic activity. In particular, mode frequencies are observed to increase with increasing activity level. Thanks to CoRoT and Kepler, such variations have been found in other solar-type stars and encode information on the activity-related changes in their interiors. Thus, the unprecedented long-term Kepler photometric observations provide a unique opportunity to study stellar activity through asteroseismology. The goal of this work is to investigate the dependencies of the observed mode frequency variations on the stellar parameters and whether those are consistent with an activity-related origin. We select the solar-type oscillators with highest signal-to-noise ratio, in total, 75 targets. Using the temporal frequency variations determined in Santos et al., we study the relation between those variations and the fundamental stellar properties. We also compare the observed frequency shifts with chromospheric and photometric activity indexes, which are only available for a subset of the sample. We find that frequency shifts increase with increasing chromospheric activity, which is consistent with an activity-related origin of the observed frequency shifts. Frequency shifts are also found to increase with effective temperature, which is in agreement with the theoretical predictions for the activity-related frequency shifts by Metcalfe et al. Frequency shifts are largest for fast rotating and young stars, which is consistent with those being more active than slower rotators and older stars. Finally, we find evidence for frequency shifts increasing with stellar metallicity.

Strigolactone-Based Node-to-Bud Signaling May Restrain Shoot Branching in Hybrid Aspen.

The biosynthesis and roles of strigolactones (SLs) have been investigated in herbaceous plants, but so far, their role in trees has received little attention. In this study, we analyzed the presence, spatial/temporal expression and role of SL pathway genes in Populus tremula � Populus tremuloides. In this proleptic species, axillary buds (AXBs) become para-dormant at the bud maturation point, providing an unambiguous starting point to study AXB activation. We identified previously undescribed Populus homologs of DWARF27 (D27), LATERAL BRANCHING OXIDOREDUCTASE (LBO) and DWARF53-like (D53-like) and analyzed the relative expression of all SL pathway genes in root tips and shoot tissues. We found that, although AXBs expressed MORE AXILLARY GROWTH1 (MAX1) and LBO, they did not express MAX3 and MAX4, whereas nodal bark expressed high levels of all SL biosynthesis genes. By contrast, expression of the SL perception and signaling genes MAX2, D14 and D53 was high in AXBs relative to nodal bark and roots. This suggests that AXBs are reliant on the associated nodes for the import of SLs and SL precursors. Activation of AXBs was initiated by decapitation and single-node isolation. This rapidly downregulated SL pathway genes downstream of MAX4, although later these genes were upregulated coincidently with primordia formation. GR24-feeding counteracted all activation-related changes in SL gene expression but did not prevent AXB outgrowth showing that SL is ineffective once AXBs are activated. The results indicate that nodes rather than roots supply SLs and its precursors to AXBs, and that SLs may restrain embryonic shoot elongation during AXB formation and para-dormancy in intact plants.

Solar activity influences on planetary atmosphere evolution: Lessons from observations at Venus, Earth, and Mars

AbstractThe Pioneer Venus and Venus Express missions, and the Mars Express and MAVEN missions, along with numerous Earth orbiters carrying space physics and aeronomy instruments, have utilized the increasing availability of space weather observations to provide better insight into the impacts of present-day solar activity on the atmospheres of terrestrial planets. Of most interest among these are the responses leading to escape of either ion or neutral constituents, potentially altering both the total atmospheric reservoirs and their composition. While debates continue regarding the role(s) of a planetary magnetic field in either decreasing or increasing these escape rates, observations have shown that enhancements can occur in both situations in response to solar activity-related changes. These generally involve increased energy inputs to the upper atmospheres, increases in ion production, and/or increases in escape channels, e.g. via interplanetary field penetration or planetary field ‘opening’. Problems arise when extrapolations of former loss rates are needed. While it is probably safe to suggest lower limits based simply on planet age multiplied by currently measured ion and neutral escape rates, the evolution of the Sun, including its activity, must be folded into these estimations. Poor knowledge of the history of solar activity, especially in terms of coronal mass ejections and solar wind properties, greatly compounds the uncertainties in related planetary atmosphere evolution calculations. Prospects for constraining their influences will depend on our ability to do a better job of solar activity history reconstruction.

Effect of immune-enhancing enteral nutrition formula enriched with plant-derived n-3 fatty acids on natural killer cell activity in rehabilitation patients.

BACKGROUND/OBJECTIVESEnteral nutrition formulas with immune-enhancing nutrients, such as n-3 fatty acids, may manage patients' nutritional status and pathophysiological processes. The aim of our study was to investigate natural killer (NK) cell activity alterations and related cytokine changes resulting from feeding with soybean oil-containing enteral nutrition formula (control group) and plant-derived n-3 fatty acid-enriched enteral nutrition formula.SUBJECTS/METHODSSubjects participated for 14 consecutive days and consumed enteral formula containing canola and flaxseed oil (n3EN, test group) in nonsurgical patients hospitalized for rehabilitation. Blood samples were collected on the first day and 14 days after the consumption of each formula daily, and anthropometric parameters were collected. Hematology and biochemical values were analyzed, and NK cell activities and serum cytokine concentration were measured. A total of sixty subjects were included in the analysis, excluding dropouts.RESULTSNo significant differences were found in biochemical parameters. The n3EN group's NK cell activities at effector:tumor cell ratios of 10:1, 5:1, 2.5:1 and 0.625:1 were significantly higher than those of the control group after two weeks (P < 0.05). However, there were no statistically significant differences in serum cytokine interleukin (IL)-12, interferon-γ, IL-1β, IL-6 and tumor necrosis factor-α values between the two groups.CONCLUSIONSIn conclusion, this study elucidates the beneficial effects of plant-derived n-3 fatty acid supplementation in enteral formula on NK cell activity.