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OBJECTIVES: Current experimental approaches cannot elucidate the effect of maladaptive changes on the main cartilage constituents during the degeneration process in osteoarthritis (OA). In silico approaches, however, allow creating 'virtual knock-out' cases to elucidate these effects in a constituent-specific manner. We used such an approach to study the main mechanisms of cartilage degeneration in different mechanical loadings associated with the following OA etiologies: (1) physiological loading of degenerated cartilage, (2) injurious loading of healthy intact cartilage and (3) physiological loading of cartilage with a focal defect. METHODS: We used the recently developed Cartilage Adaptive REorientation Degeneration (CARED) framework to simulate cartilage degeneration associated with primary and secondary OA (OA cases (1)-(3)). CARED incorporates numerical description of tissue-level cartilage degeneration mechanisms in OA, namely, collagen degradation, collagen reorientation, fixed charged density loss and tissue hydration increase following mechanical loading. We created 'virtual knock-out' scenarios by deactivating these degenerative processes one at a time in each of the three OA cases. RESULTS: In the injurious loading of intact and physiological loading of degenerated cartilage, collagen degradation drives degenerative changes through fixed charge density loss and tissue hydration rise. In contrast, the two later mechanisms were more prominent in the focal defect cartilage model. CONCLUSION: The virtual knock-out models reveal that injurious loading to intact cartilage and physiological loading to degenerated cartilage induce initial degenerative changes in the collagen network, whereas, in the presence of a focal cartilage defect, mechanical loading initially causes proteoglycans (PG) depletion, before changes in the collagen fibril network occur. ispartof: Osteoarthritis And Cartilage vol:31 issue:6 pages:741-752 ispartof: location:England status: published

The erosive force of rainfall (rainfall erosivity) is a major driver of soil, nutrient losses worldwide and an important input for soil erosion assessments models. Here, we present a comprehensive set of future erosivity projections at a 30 arc-second (∼1 km2) spatial scale using 19 downscaled General Circulation Models (GCMs) simulating three Representative Concentration Pathways (RCPs) for the periods 2041–2060 and 2061–2080. The future rainfall erosivity projections were obtained based on a Gaussian Process Regression (GPR) approach relating rainfall depth to rainfall erosivity through a series of (bio)climatic covariates. Compared to the 2010 Global Rainfall erosivity baseline, we estimate a potential average increase in global rainfall erosivity between 26.2 and 28.8% for 2050 and 27–34.3% for 2070. Therefore, climate change and the consequential increase in rainfall erosivity is the main driver of the projected + 30–66% increase in soil erosion rates by 2070. Our results were successfully compared with 20 regional studies addressing the rainfall erosivity projections. We release the whole dataset of future rainfall erosivity projections composed of 102 simulation scenarios, with the aim to support further research activities on soil erosion, soil conservation and climate change communities. We expect these datasets to address the needs of both the Earth system modeling community and policy makers. In addition, we introduce a modeling approach to estimate future erosivity and make further assessments at global and continental scales.

As wheat (Triticum aestivum) is an important staple food across the world, preservation of stable yields and increased productivity are major objectives in breeding programs. Drought is a global concern because its adverse impact is expected to be amplified in the future due to the current climate change. Here, we analyzed the effects of edaphic, environmental, and host factors on the wheat root microbiomes collected in soils from six regions in Belgium. Amplicon sequencing analysis of unplanted soil and wheat root endosphere samples indicated that the microbial community variations can be significantly explained by soil pH, microbial biomass, wheat genotype, and soil sodium and iron levels. Under drought stress, the biodiversity in the soil decreased significantly, but increased in the root endosphere community, where specific soil parameters seemingly determine the enrichment of bacterial groups. Indeed, we identified a cluster of drought-enriched bacteria that significantly correlated with soil compositions. Interestingly, integration of a functional analysis further revealed a strong correlation between the same cluster of bacteria and β-glucosidase and osmoprotectant proteins, two functions known to be involved in coping with drought stress. By means of this in silico analysis, we identified amplicon sequence variants (ASVs) that could potentially protect the plant from drought stress and validated them in planta. Yet, ASVs based on 16S rRNA sequencing data did not completely distinguish individual isolates because of their intrinsic short sequences. Our findings support the efforts to maintain stable crop yields under drought conditions through implementation of root microbiome analyses. ispartof: COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL vol:19 pages:4235-4247 ispartof: location:Netherlands status: published

Functional magnetic resonance imaging (fMRI) has revolutionized the investigation of brain function. Similar approaches can be translated to probe spinal mechanisms. However, imaging the spinal cord remains challenging, notably due to its size and location. Technological advances are gradually tackling these issues, though there is yet no consensus on optimal acquisition protocols. In this study, we assessed the performance of three sequences during a simple motor task and at rest, in 15 healthy humans. Building upon recent literature, we selected three imaging protocols: a sequence integrating outer volume suppression (OVS) and two sequences implementing inner field-of-view imaging (ZOOMit) with different spatial and temporal resolutions. Images acquired using the OVS sequence appeared more prone to breathing-induced signal fluctuations, though they exhibited a higher temporal signal-to-noise ratio than ZOOMit sequences. Conversely, the spatial signal-to-noise ratio was higher for the two ZOOMit schemes. In spite of these differences in signal properties, all sequences yielded comparable performance in detecting group-level task-related activity, observed in the expected spinal levels. Nevertheless, our results suggest a superior sensitivity and robustness of patterns imaged using the OVS acquisition scheme. To analyze the data acquired at rest, we deployed a dynamic functional connectivity framework, SpiCiCAP, and we evaluated the ability of the three acquisition schemes to disentangle intrinsic spinal signals. We demonstrated that meaningful subdivisions of the spinal cord's functional architecture could be uncovered for all three sequences, with similar spatio-temporal properties across acquisition parameters. Cleaner and more stable components were, however, obtained using ZOOMit sequences. This study emphasizes the potential of fMRI as a robust tool to image spinal activity in vivo and it highlights specificities and similarities of three acquisition methods. This represents a key step towards the establishment of standardized spinal cord fMRI protocols.

Summary The germinal center (GC) response is critical for generating high-affinity humoral immunity and immunological memory, which forms the basis of successful immunization. Control of the GC response is thought to require follicular regulatory T (Tfr) cells, a subset of suppressive Foxp3+ regulatory T cells located within GCs. Relatively little is known about the exact role of Tfr cells within the GC and how they exert their suppressive function. A unique feature of Tfr cells is their reported CXCR5-dependent localization to the GC. Here, we show that the lack of CXCR5 on Foxp3+ regulatory T cells results in a reduced frequency, but not an absence, of GC-localized Tfr cells. This reduction in Tfr cells is not sufficient to alter the magnitude or output of the GC response. This demonstrates that additional, CXCR5-independent mechanisms facilitate Treg cell homing to the GC., Graphical Abstract, Highlights • CXCR5-deficient Tfr cells can migrate into the B cell follicle and the germinal center • Absence of CXCR5 on Treg cells reduces the number of Tfr cells by half • Halving Tfr cell numbers does not affect germinal center B cell or Tfh cell frequency, Vanderleyden et al. show that CXCR5-deficient Treg cells can migrate into the B cell follicle. In the absence of CXCR5, fewer Tfr cells participate in the germinal center reaction, but the reduction in Tfr cell number does not affect the magnitude of the germinal center response.

Objective: To systematically review the literature related to the effectiveness of parents' active involvement during painful interventions for their preterm infants. Data Sources: We performed a systematic search of PubMed, EMBASE/Ovid, CINAHL, Livivio, and PsycInfo using the keywords "preterm infants," "pain," and "parents." Study Selection: Articles were eligible for inclusion if they were published between 2000 and 2021 and reported randomized controlled trials (RCTs) in which preterm infants underwent painful interventions, and parents were pre-sent and actively involved in pain-reducing measures. Data Extraction: We used the Consolidated Standards of Reporting Trials (CONSORT) checklist for RCTs for data extraction. We assessed methodologic quality using critical appraisal for RCTs according to the Joanna Briggs Institute. Data Synthesis: In total, 22 articles met the inclusion criteria. These articles reported 19 studies focused on kangaroo/ skin-to-skin care, one focused on breastfeeding, and two focused on facilitated tucking. The methods used to evaluate pain in the infant varied substantially. Overall, kangaroo/skin-to-skin care and facilitated tucking resulted in clinically and statistically significant decreases in pain. For breastfeeding, effectiveness was linked to a more mature sucking pattern of the preterm infant. Conclusion: The current evidence suggests that involving parents in pain-reducing measures during painful in-terventions for their preterm infants is beneficial. However, more research is needed for the different methods of involving parents in pain-reducing measures. JOGNN, 51, 6-15; 2022. https://doi.org/10.1016/j.jogn.2021.08.100 Accepted September 1, 2021; Published online October 8, 2021

Boreal peatlands, of which Sphagnum bogs are one of the main types, play essential roles in the terrestrial soil carbon pool. Vegetation phenology is a sensitive indicator that reveals the underlying processes as well as responses to climate change, while currently there remain knowledge gaps in exploring and monitoring the longterm bog vegetation phenology due to insufficient remote sensing application experiences. In this study, we investigated three remotely sensed vegetation phenological parameters, the start of growing season (SOS), the end of growing season (EOS), and the length of growing season (LOS) in two bogs located in norther China by using double-logistic reconstructed MOD13Q1-EVI from 2001 to 2018, which were evaluated by the flux phenology. Also combing with meteorological data to detect interactions between vegetation phenology and climate change. The results showed that remotely sensed EOS had 8-day time lags with flux phenological date, while that outperformed SOS. Bog vegetation generally with a life pattern of SOS at the 108th day of year (doy) and EOS at the 328th doy, though the life cycle of individual vegetation groups varies among different vegetation communities. There was no significant delayed (or extended) trend in each phenological features in bogs. Precipitation and minimum temperature (monthly and annual) were the driving forces for bog vegetation growth (R2 0.9, P < 0.01), and other features presented weaker correlations. Overall, this study determined the remote sensing phenology and climate drivers in two Chinese bogs, we suggested that vegetation phenology alternation should be concerned when carry on ecological processes and carbon dynamics researches in peatlands.

Background: Low-carbohydrate diets, including the modified Atkins diet (mAD), are commonly used to promote weight loss, improve exercise performance, and treat refractory epilepsy and inherited metabolism disorders. However, the effects of the high-fat-low-carbohydrate diet on the physiology of healthy subjects still need further study. We evaluated the physiological influence of mAD on cardiopulmonary exercise results in healthy adult subjects. Materials and methods: Ten healthy volunteers followed mAD for four weeks with laboratory follow-up. Cardiopulmonary exercise tests were performed before, and at the end of mAD, and venous lactate, ammonia, and blood gases were collected before, during, and after exercise testing. Results and conclusions: Four-week mAD decreased the subjects' mechanical efficiency in the cardiopulmonary exercise test and caused increased ventilation and decreased fraction of expired CO2 in maximal exercise. This evidence suggests that mAD can cause hyperventilation tendency at least in the short term, a possible adverse effect of the diet.

Background and objectivesIn psychoeducation before exposure treatment patients are sometimes provided with information about the (low) probability that the feared outcome would occur. Since it has been proposed in the literature that this might have adverse effects, the current study investigated the effect of providing participants with this type of safety information on return of fear.MethodIn an ABA-renewal paradigm, participants in the experimental group were instructed between acquisition and extinction that the probability of US-occurrence would be extremely small in the remainder of the experiment. Participants in the control group did not receive this information.ResultsLess return of fear in US-expectancy ratings was observed in participants who received the safety information.LimitationsWe failed to find successful acquisition in the skin-conductance data, which prevented us from interpreting the results of this outcome measure.ConclusionsThese results suggest that providing safety information is not deleterious for the effects of exposure and can even be beneficial for its effects. However, further clinical research is needed.

Summary: We describe therapeutic monoclonal antibodies isolated from human volunteers vaccinated with recombinant adenovirus expressing Ebola virus glycoprotein (EBOV GP) and boosted with modified vaccinia virus Ankara. Among 82 antibodies isolated from peripheral blood B cells, almost half neutralized GP pseudotyped influenza virus. The antibody response was diverse in gene usage and epitope recognition. Although close to germline in sequence, neutralizing antibodies with binding affinities in the nano- to pico-molar range, similar to “affinity matured” antibodies from convalescent donors, were found. They recognized the mucin-like domain, glycan cap, receptor binding region, and the base of the glycoprotein. A cross-reactive cocktail of four antibodies, targeting the latter three non-overlapping epitopes, given on day 3 of EBOV infection, completely protected guinea pigs. This study highlights the value of experimental vaccine trials as a rich source of therapeutic human monoclonal antibodies. : Most antibodies used for Ebola virus treatment originate from convalescent donors or highly immunized animals. Rijal et al. find that monoclonal antibodies isolated early after vaccination from humans can be powerfully therapeutic, despite the relative immaturity of their sequences. Vaccine trials therefore can provide a valuable source of therapeutic antibodies. Keywords: Ebola virus, human monoclonal antibodies, immunotherapy, therapeutic antibodies, guinea pig model, Ebola virus glycoprotein epitopes, E-S-FLU virus, antibody binding kinetics, affinity maturation

Emotion dysregulation and hyperreactivity are considered central features of Borderline Personality Disorder (BPD). We assumed that such emotion dysregulation is also reflected in increased crying behavior of these patients and, consequently, hypothesized that BPD patients (N = 62), compared to Cluster C personality disorder patients (Cluster C-PD; N = 25) and non-patients (N = 54), would show higher scores on crying measures. To evaluate crying behavior, we used a set of specially designed tools. Compared to non-patients, BPD patients showed the anticipated higher crying frequency despite a similar crying proneness and ways of dealing with tears. They also reported less awareness of the influence of crying on others. However, Cluster C-PD patients showed a very similar pattern of findings. Overall, our results suggest that the increased crying of BPD patients likely results from environmental factors or the misperception of situations, rather than from stable traits. Remarkable is that the observed discrepancies in crying behavior compared to non-patients seem to be similar for Cluster-C PDs and BPD.

A striking feature of atherosclerosis is its highly non-uniform distribution within the arterial tree. This has been attributed to variation in the haemodynamic wall shear stress (WSS) experienced by endothelial cells, but the WSS characteristics that are important and the mechanisms by which they lead to disease remain subjects of intensive investigation despite decades of research. In vivo evidence suggests that multidirectional WSS is highly atherogenic. This possibility is increasingly being studied by culturing endothelial cells in wells that are swirled on an orbital shaker. The method is simple and cost effective, has high throughput and permits chronic exposure, but interpretation of the results can be difficult because the fluid mechanics are complex; hitherto, their description has largely been restricted to the engineering literature. Here we review the findings of such studies, which indicate that putatively atherogenic flow characteristics occur at the centre of the well whilst atheroprotective ones occur towards the edge, and we describe simple mathematical methods for choosing experimental variables that avoid resonance, wave breaking and uncovering of the cells. We additionally summarise a large number of studies showing that endothelium cultured at the centre of the well expresses more pro-inflammatory and fewer homeostatic genes, has higher permeability, proliferation, apoptosis and senescence, and shows more endothelial-to-mesenchymal transition than endothelium at the edge. This simple method, when correctly interpreted, has the potential to greatly increase our understanding of the homeostatic and pathogenic mechanobiology of endothelial cells and may help identify new therapeutic targets in vascular disease., Graphical abstract Image 1, Highlights • Endothelial cells experience pro- or anti-atherogenic flow in swirling culture wells. • Flow characteristics in different parts of the well can be estimated or computed. • Inflammatory, homeostatic and other cell properties depend on location in the well.

There has been a growing recognition of the involvement of the immune system in stress-related disorders. Acute stress leads to the activation of neuroendocrine systems, which in turn orchestrate a large-scale redistribution of innate immune cells, such as monocytes. Even though acute stress/monocyte interactions have been well-characterized in mice, this is not the case for humans. As such, this study aimed to investigate whether acute stress modulates blood monocyte levels in a subtype-dependent manner and whether the receptor expression of stress-related receptors is affected in humans. Blood was collected from healthy female volunteers at baseline and 1 h after the socially evaluated cold pressor test, after which blood monocyte levels and receptor expression were assessed by flow cytometry. Our results reveal a stress-induced increase in blood monocyte levels, which was independent of monocyte subtypes. Furthermore, colony stimulating factor 1 receptor (CSF-1R) and CD29 receptor expression was increased, while CD62L showed a trend towards increased expression. These results provide novel insights into how acute stress affects the innate immune system.

Communication constitutes a fundamental component of mammalian social behavior. Rats are highly social animals and emit 50-kHz ultrasonic vocalizations (USV), which function as social contact calls. Playback of 50-kHz USV leads to strong and immediate social approach responses in receiver rats, but this response is weak or even absent during repeated 50-kHz USV playback. Given the important role of 50-kHz USV in initiating social contact and coordinating social interactions, the occurrence of habituation is highly unexpected. It is not clear why a social signal characterized by significant incentive salience loses its power to change the behavior of the receiver so rapidly. Here, we show that the habituation phenomenon displayed by rats in response to repeated playback of 50-kHz USV (1) is characterized by limited generalizability because it is present in Wistar but not Sprague-Dawley rats, (2) can be overcome by amphetamine treatment, and (3) depends on the subject's internal state. ispartof: ISCIENCE vol:24 issue:5 ispartof: location:United States status: published

Submitted by Lilian Teresa Gobbi (lilian.gobbi@unesp.br) on 2021-11-17T19:47:18Z No. of bitstreams: 1 beretta_vs_postprint_rcla_does.pdf: 8207632 bytes, checksum: 0352da417800c416e8a5e93404af214d (MD5) Approved for entry into archive by Marcia Correa Bueno Degasperi null (mcbueno@rc.unesp.br) on 2022-01-05T18:34:18Z (GMT) No. of bitstreams: 2 beretta_vs_postprint_rcla_does.pdf: 8207632 bytes, checksum: 0352da417800c416e8a5e93404af214d (MD5) beretta_vs_ressalva_rcla_does.pdf: 26685 bytes, checksum: e3d6f95e5184ee30b5ee34c40a27dfee (MD5) Made available in DSpace on 2022-01-05T18:34:18Z (GMT). No. of bitstreams: 2 beretta_vs_postprint_rcla_does.pdf: 8207632 bytes, checksum: 0352da417800c416e8a5e93404af214d (MD5) beretta_vs_ressalva_rcla_does.pdf: 26685 bytes, checksum: e3d6f95e5184ee30b5ee34c40a27dfee (MD5) Previous issue date: 2021-04-22 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Background: How people with Parkinson’s disease habituate their postural response to unpredictable translation perturbation is not totally understood. We compared the capacity to change the postural responses after unexpected external perturbation and investigated the habituation plateaus of postural responses to non-sequential perturbation trials in people with Parkinson’s disease and healthy older adults. Methods: In people with Parkinson’s disease (n = 37) and older adults (n = 20), sudden posterior support-surface translational were applied in 7 out of 17 randomized trials to ensure perturbation unpredictability. Electromyography and center of pressure parameters of postural response were analyzed by ANOVAs (Group vs. Trials). Two simple planned contrasts were performed to determine at which trial the responses first significantly habituate, and by which trials the habituation plateaus. Findings: Older adults demonstrated a first response change in trial 5 and habituation plateaus after trial 4, while for people with Parkinson’s disease, the first change occurred in trial 2 and habituation plateau after trial 5 observed by center of pressure range. People with Parkinson’s disease demonstrated a greater center of pressure range in trial 1 compared to older adults. Independent of trial, people with Parkinson’s disease vs. older adults demonstrated a greater ankle muscle co-activation and recovery time. Interpretation: Despite the greater center of pressure range in the first trial, people with Parkinson’s disease can habituate to unpredictable perturbations. This is reflected by little, to no difference in the time-course of adaptation for all but 2 parameters that showed only marginal differences between people with Parkinson’s disease and older adults. Postprint São Paulo State University (UNESP), Institute of Biosciences, Graduate Program in Movement Sciences, Posture and Gait Studies Laboratory (LEPLO), Rio Claro, São Paulo, Brazil School of Kinesiology, The University of British Columbia, Vancouver, British Columbia, Canada São Paulo State University (Unesp), School of Sciences, Graduate Program in Movement Sciences, Human Movement Research Laboratory (MOVI-LAB), Bauru, Brazil Center for Human Movement Sciences, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands FAPESP: 2016/00503-0 Capes: 001 CNPq 142057/2017-7 CNPq 309045/2017-7

International audience; In recent years, specific cortical networks have been proposed to be crucial for sustaining consciousness, including the posterior hot zone and frontoparietal resting state networks (RSN). Here, we computationally evaluate the relative contributions of three RSNs - the default mode network (DMN), the salience network (SAL), and the central executive network (CEN) - to consciousness and its loss during propofol anaesthesia. Specifically, we use dynamic causal modelling (DCM) of 10 min of high-density EEG recordings (N = 10, 4 males) obtained during behavioural responsiveness, unconsciousness and post-anaesthetic recovery to characterise differences in effective connectivity within frontal areas, the posterior 'hot zone', frontoparietal connections, and between-RSN connections. We estimate - for the first time - a large DCM model (LAR) of resting EEG, combining the three RSNs into a rich club of interconnectivity. Consistent with the hot zone theory, our findings demonstrate reductions in inter-RSN connectivity in the parietal cortex. Within the DMN itself, the strongest reductions are in feed-forward frontoparietal and parietal connections at the precuneus node. Within the SAL and CEN, loss of consciousness generates small increases in bidirectional connectivity. Using novel DCM leave-one-out cross-validation, we show that the most consistent out-of-sample predictions of the state of consciousness come from a key set of frontoparietal connections. This finding also generalises to unseen data collected during post-anaesthetic recovery. Our findings provide new, computational evidence for the importance of the posterior hot zone in explaining the loss of consciousness, highlighting also the distinct role of frontoparietal connectivity in underpinning conscious responsiveness, and consequently, suggest a dissociation between the mechanisms most prominently associated with explaining the contrast between conscious awareness and unconsciousness, and those maintaining consciousness.

Highly processed foods tend to form weak structures which breakdown rapidly in the gastrointestinal (GI) tract, often causing negative effects on human metabolism and health. Developing healthier foods has been limited by the lack of understanding of how foods are digested. Through computational modelling we reveal mechanical gastric food breakdown phenomena and relate food mechanical properties with performance during critical initial digestion stages. Our model relies strictly on a viscoplastic-damage constitutive law, calibrated via rheological experiments on an artificial biscuit bolus and validated by simulating cutting tests. Simulations suggest that bolus separation during bolus backward extrusion and/or indentation by peristaltic waves, and, bolus agglomeration due to hydrostatic compression near the pylorus, are two competing phenomena that can influence the bolus free surface to volume ratio. This showcases the importance of including mechanical aspects of breakdown when designing foods for controlled chemo-mechanical breakdown and associated nutrient release rates.

Redox reactions control fundamental processes of human biology. Therefore, it is safe to assume that the responses and adaptations to exercise are, at least in part, mediated by redox reactions. In this review, we are trying to show that redox reactions are the basis of exercise physiology by outlining the redox signaling pathways that regulate four characteristic acute exercise-induced responses (muscle contractile function, glucose uptake, blood flow and bioenergetics) and four chronic exercise-induced adaptations (mitochondrial biogenesis, muscle hypertrophy, angiogenesis and redox homeostasis). Based on our analysis, we argue that redox regulation should be acknowledged as central to exercise physiology., Graphical abstract Image 1, Highlights • Redox reactions are a fundamental part of human biology. • Exercise responses and adaptations are partially controlled by redox reactions. • Redox signaling should be acknowledged as central to exercise physiology.

Acute Hepatopancreatic Necrosis Disease (AHPND), a disease caused by Vibrio parahaemolyticus (VpAHPND), kills Penaeid shrimps worldwide, resulting in severe economic losses during aquaculture. To further understand how Penaeus monodon post-larvae (PL) respond towards infection of this pathogenic bacterium, the expression of several important immune and bacterial toxin genes in three stages of P. monodon PL (PL15, PL30 and PL45) upon VpAHPND challenge, were determined. A 20-hrs challenge test with 2.7 × 107 cfu ml−1 of VpAHPND resulted 81, 65 and 1.7% mortality respectively for PL30, PL15 and PL45, indicating that PL30 was most vulnerable to VpAHPND. The immune response of shrimp PL at this stage was robust, with Toll-like receptor (TLR), prophenoloxidase (proPO), lysozyme (lyso) and penaeidin (PEN) augmented approximately 10.7, 4.7, 6.5 and 3.2-fold, respectively. The expression initiated at one hour post-infection (h.p.i), peaked at 16 h.p.i and 20 h.p.i, and decreased at 18 h.p.i, indicating the crucial involvement of these immune related genes in the defence and recovery of the first-line defence mechanisms during VpAHPND infection. This work also revealed that toxR gene represents a good indicator gene for Vibrio detection whereas PIR A, for VpAHPND pathogenicity determination of P. monodon. Overall, these findings provided novel insights into the immune response and VpAHPND susceptibility of different P. monodon PL stages during infection, with outcomes potentially useful in enhancing the application of health therapy and biosecured aquaculture practices to minimize the damaging risk of AHPND towards sustainable production of P. monodon. Keywords: Penaeus monodon, AHPND, PIR a, Immunity genes, Bacterial toxin gene

Physical activity (PA) in urban environments may lead to increased inhalation of air pollutants. As PA and air pollution (AP) have respectively beneficial and detrimental effects on the cardiorespiratory system, the responses to these exposures can interact. Therefore, we assessed the short-term effects of PA, AP and their interaction on a set of subclinical cardiovascular and respiratory outcomes in a panel of healthy adults: heart rate variability (HRV), retinal vessel diameters, lung function and fractional exhaled nitric oxide (FeNO).One hundred twenty two participants measured their PA level and exposure to black carbon (BC), a marker of AP exposure, with wearable sensors during an unscripted week in three different seasons. The study was part of the PASTA project in three European cities (Antwerp: 41 participants, Barcelona: 41 participants, London: 40 participants). At the end of each measurement week, the health outcomes were evaluated. Responses to PA, BC and their interaction were assessed with mixed effect regression models. Separate models were used to account for a 2-h and 24-h time window.During the 2-h time window, HRV and lung function changed statistically significantly in response to PA (METhours) and logarithmic BC (%change). Changes in HRV marked an increased sympathetic tone with both PA (logarithmic LF/HF: +7%; p

BACKGROUND AND OBJECTIVES: In psychoeducation before exposure treatment patients are sometimes provided with information about the (low) probability that the feared outcome would occur. Since it has been proposed in the literature that this might have adverse effects, the current study investigated the effect of providing participants with this type of safety information on return of fear. METHOD: In an ABA-renewal paradigm, participants in the experimental group were instructed between acquisition and extinction that the probability of US-occurrence would be extremely small in the remainder of the experiment. Participants in the control group did not receive this information. RESULTS: Less return of fear in US-expectancy ratings was observed in participants who received the safety information. LIMITATIONS: We failed to find successful acquisition in the skin-conductance data, which prevented us from interpreting the results of this outcome measure. CONCLUSIONS: These results suggest that providing safety information is not deleterious for the effects of exposure and can even be beneficial for its effects. However, further clinical research is needed. ispartof: Journal of Behavior Therapy and Experimental Psychiatry vol:63 pages:73-78 ispartof: location:Netherlands status: published

Serotonin 5-HT2A receptors (5-HT(2A)Rs) have been implicated in schizophrenia. However, postmortem studies on 5-HT(2A)Rs expression and functionality in schizophrenia are scarce. The 5-HT2AR mRNA and immunoreactive protein expression were evaluated in postmortem tissue from dorsolateral prefrontal cortex (DLPFC) of antipsychotic-free (n = 18) and antipsychotic-treated (n = 9) subjects with schizophrenia, and matched controls (n = 27). Functional coupling of 5-HT2AR to G-proteins was tested by measuring the activation induced by the agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride ((+/-)DOI) in antibody-capture [S-35]GTP gamma S scintillation proximity assays (SPA). In antipsychotic-free schizophrenia subjects, 5-HT2AR mRNA expression and protein immunoreactivity in total homogenates was similar to controls. In contrast, in antipsychotic-treated schizophrenia subjects, lower mRNA expression (60 +/- 9% vs controls) and a trend to reduced protein immunoreactivity (86 +/- 5% vs antipsychotic-free subjects) just in membrane-enriched fractions was observed. [S-35]GTP gamma S SPA revealed a significant (similar to)6% higher stimulation of G(alpha i1)-protein by (+/-)DOI in schizophrenia, whereas activation of the canonical G(alpha q/11)-protein pathway by (+/-)DOI remained unchanged. Expression of G(alpha i1) - and G(alpha q/11)-proteins did not differ between groups. Accordingly, in rats chronically treated with clozapine, but not with haloperidol, a 30-40% reduction was observed in 5-HT2AR mRNA expression, 5-HT2AR protein immunoreactivity and [H-3]ketanserin binding in brain cortical membranes. Overall, the data suggest a supersensitive 5-HT2AR signaling through inhibitory G(alpha i1)-proteins in schizophrenia. Together with previous results, a dysfunctional pro-hallucinogenic agonist-sensitive 5-HT2AR conformation in postmortem DLPFC of subjects with schizophrenia is proposed. Atypical antipsychotic treatment would contribute to counterbalance this 5-HT2AR supersensitivity by reducing receptor expression. (C) 2019 The Author(s). Published by Elsevier B.V. This study was supported by US National Institutes of Health (NIH) (R01 MH084894 and R01MH111940 to JG-M), Spanish Ministry of Science, Innovation and Universities and European ERDF Funds (SAF2009-08460 and 2017-88126-R to JJM), and the Basque Government (IT-616-13 and IT-1211-19 to JJM).

Human mesenchymal stromal/stem cells (hMSCs) are used in experimental cell therapy to treat various immunological disorders, and the extracellular vesicles (hMSC-EVs) they produce have emerged as an option for cell-free therapeutics. The immunomodulatory function of hMSCs resembles the resolution of inflammation, in which proresolving lipid mediators (LMs) play key roles. Multiple mechanisms underlying the hMSC immunosuppressive effect has been elucidated; however, the impact of LMs and EVs in the resolution is poorly understood. In this study, we supplemented hMSCs with polyunsaturated fatty acids (PUFAs); arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid, which serve as precursors for multiple LMs. We then determined the consequent compositional modifications in the fatty acid, phospholipid, and LM profiles. Mass spectrometric analyses revealed that the supplemented PUFAs were incorporated into the main membrane phospholipid classes with different dynamics, with phosphatidylcholine serving as the first acceptor. Most importantly, the PUFA modifications were transferred into hMSC-EVs, which are known to mediate hMSC immunomodulation. Furthermore, the membrane-incorporated PUFAs influenced the LM profile by increasing the production of downstream prostaglandin E-2 and proresolving LMs, including Resolvin E2 and Resolvin D6. The production of LMs was further enhanced by a highly proinflammatory stimulus, which resulted in an increase in a number of mediators, most notably prostaglandins, while other stimulatory conditions had less a pronounced impact after a 48-h incubation. The current findings suggest that PUFA manipulations of hMSCs exert significant immunomodulatory effects via EVs and proresolving LMs, the composition of which can be modified to potentiate the therapeutic impact of hMSCs.

In gait stability research, neither self-selected walking speeds, nor the same prescribed walking speed for all participants, guarantee equivalent gait stability among participants. Furthermore, these options may differentially affect the response to different gait perturbations, which is problematic when comparing groups with different capacities. We present a method for decreasing inter-individual differences in gait stability by adjusting walking speed to equivalent margins of stability (MoS). Eighteen healthy adults walked on a split-belt treadmill for two-minute bouts at 0.4m/s up to 1.8m/s in 0.2m/s intervals. The stability-normalised walking speed (MoS=0.05m) was calculated using the mean MoS at touchdown of the final 10 steps of each speed. Participants then walked for three minutes at this speed and were subsequently exposed to a treadmill belt acceleration perturbation. A further 12 healthy adults were exposed to the same perturbation while walking at 1.3m/s: the average of the previous group. Large ranges in MoS were observed during the prescribed speeds (6-10cm across speeds) and walking speed significantly (P

Both agricultural interventions and social protection interventions are needed for combatting hunger and poverty among poor smallholder farmers. Yet, coordination between these two sectors is generally limited and, until recently, little attention has been paid to the interaction between them and how this potentially improves rural livelihoods. Our review analyses the empirical evidence on how social protection impacts agricultural production and how agricultural interventions reduce risks and vulnerability at the household and local economy levels. Most studies show that social protection can increase agricultural production while agricultural interventions can lower vulnerability. However, the availability of evidence is uneven across outcomes and developing regions. We conclude that existing evidence largely provides an empirical rationale for building synergies between social protection and smallholder agriculture. (C) 2016 Elsevier B.V. All rights reserved.

BACKGROUND: Grass pollen-specific immunotherapy involves immunomodulation of allergen-specific T helper 2 cell (Th2) responses and induction of IL-10+ and/or TGF-β+CD4+CD25+ regulatory T cells (iTregs). IL-35+CD4+CD25+Foxp3- T (iTR35) cells have been reported as a novel subset of iTregs with modulatory characteristics. OBJECTIVE: To investigate the mechanisms underlying the induction and maintenance of immunological tolerance induced by IL-35 and iTR35 cells. METHODS: The biological effects of IL-35 was assessed on Group II innate lymphoid cells (ILC2s), dendritic cells (DCs) primed with TSLP, IL-25 and IL-33, B and Th2 cells by flow cytometry and qRT-PCR. Grass pollen-driven Th2 cell proliferation and cytokine production was measured by [3H]-thymidine and Luminex MagPix, respectively. iTr35 cells were quantified in grass pollen allergics (SAR, n=16), sublingual immunotherapy-treated patients (SLIT, n=16) and non-atopic controls (NAC, n=16). RESULTS: SAR had elevated proportions of ILC2s (P=.002), IL5+ (P=.042), IL13+ (P=.042) and IL5+IL13+ILC2s (P=.003) compared to NAC. IL-35 inhibited IL-5 and IL-13 production by ILC2s in the presence of IL-25 or IL-33 (P=.031) and allergen-driven Th2 cytokines by Teff cells. IL-35 inhibited CD40L, IL-4 and IL-21-mediated IgE production by B cells (P=.015), allergen-driven T cell proliferation (P=.001) and Th2 cytokine production by primed DCs. iTR35 cells suppressed Th2 cell proliferation and cytokine production. In addition, allergen-driven IL-35 levels and iTR35 cells were elevated in SLIT (all, P

Effective ecosystem management requires a robust methodology to analyse, remedy and avoid ecosystem damage. Here we propose that the overall conceptual framework and approaches developed over millennia in medical science and practice to diagnose, cure and prevent disease can provide an excellent template. Key principles to adopt include combining well-established assessment methods with new analytical techniques and restricting both diagnosis and treatment to qualified personnel at various levels of specialization, in addition to striving for a better mechanistic understanding of ecosystem structure and functioning, as well as identifying the proximate and ultimate causes of ecosystem impairment. In addition to applying these principles, ecosystem management would much benefit from systematically embracing how medical doctors approach and interview patients, diagnose health condition, select treatments, take follow-up measures, and prevent illness. Here we translate the overall conceptual framework from medicine into environmental terms and illustrate with examples from rivers how the systematic adoption of the individual steps proven and tested in medical practice can improve ecosystem management. (C) 2017 The Authors. Published by Elsevier B.V. This paper benefited from funding by the EU Commission (projects GLOBAQUA, grant agreement no. 603629-ENV-2013-6.2-1, and MARS, grant agreement no. 603378-ENV-2013.6.2-1) and the New Zealand government (MBIE Rehabilitation of Aquatic Ecosystems programme C01X1002). We are grateful to Emily S. Bernhardt (Nicholas School of the Environment, Duke University, USA), Pedro R. Grandes (Faculty of Medicine, University of the Basque Country, Spain), Linda Reinemer (Department of General Psychiatry, Clinic Konigshof, Germany), Laszlo Matefi (Swiss Accident Insurance, SUVA, Switzerland), Sergi Sabater (Catalan Institute of Water Research, ICRA, Spain) and Klement Tockner (IGB Berlin, Germany) for discussion or comments on a previous draft.

The aim of this trial was to assess the effects of the administration of different combinations of mycotoxins in naturally contaminated maize grains on dairy heifer growth, blood measurements and puberty onset. A total of 35 Friesian female heifers were randomly allotted to three experimental groups from 18-21 to 42-45 weeks of age. During the 24-week experimental period (EP), heifers were fed the same diet, but with maize meal derived from three differently contaminated lots: very low contamination, as control (C); medium-low aflatoxin-contaminated (A); and mixed aflatoxin-fumonisin contaminated (A-F). At the end of the EP, they returned to a common diet without contaminated maize, and they were monitored for an additional period of 12 weeks (post-experimental period, PEP). BW, wither height, hip height, body length and heart girth were measured every 4 weeks from the beginning of EP to the end of PEP. At the same time, body condition score was evaluated and blood samples were taken from the jugular vein to be analysed for haematological, serum protein and metabolic profiles. Age at puberty was assessed by measuring weekly plasma progesterone levels from 40 to 52 weeks of age. Body growth measurements were processed both by ANOVA of average daily gain of EP and PEP separately, and by the analysis of growth curve parameters. Haematological, serum protein and metabolic profile were evaluated using a mixed model, taking into account the repeated measurements in time on each animal. Heifers' growth was delayed both in A and A-F groups during EP, as evidenced by the different linear coefficients of the BW growth curve in the three groups. Differently contaminated diets did not affect the haematological profile, so that it can be concluded that these levels of mycotoxin contamination do not determine any specific effect on haematopoiesis and immunity in growing heifers. The main blood marker of mycotoxin chronic toxicity was the γ-glutamyl transferase activity level in plasma, which appeared to be altered even after the removal of mycotoxins. During EP, plasma glucose was lower in the groups fed contaminated diet compared with C. The joint actions of an altered nutritional status and a long-lasting liver damage were probably the causes of the delay in puberty attainment in A and, particularly, in the A-F group. The results from this trial evidenced that a chronic aflatoxin-fumonisin contamination in diets of dairy heifers can determine an important delay in the reproductive career of these animals.

This article presents an innovative framework for analysing environmental governance challenges by focusing on their Drivers, Responses and Impacts (DRI). It builds on and modifies the widely applied Drivers, Pressures, States, Impacts and Responses (DPSIR) model. It suggests, firstly and most importantly, that the various temporal and spatial scales at which Drivers, Responses and Impacts operate should be included in the DRI conceptual framework. Secondly, the framework focuses on Drivers, Impacts and Responses in order to provide a parsimonious account of a drought system that can be informed by a range of social science, humanities and science data. ‘Pressures’ are therefore considered as a sub-category of ‘Drivers’. ‘States’ are a sub-category of ‘Impacts’. Thirdly, and most fundamentally in order to facilitate cross-disciplinary research of droughts, the DRI framework defines each of its elements, ‘Drivers’, ‘Pressures’, ‘States’, ‘Impacts’ and ‘Responses’ as capable of being shaped by both linked natural and social factors. This is different from existing DPSIR models which often see ‘Responses’ and ‘Impacts’ as located mainly in the social world, while ‘States’ are considered to be states within the natural environment only. The article illustrates this argument through an application of the DRI framework to the 1976 and 2003–6 droughts. The article also starts to address how - in cross-disciplinary research that encompasses physical and social sciences – claims about relationships between Drivers as well as Impacts of and Responses to drought over time can be methodologically justified. While the DRI framework has been inductively developed out of research on droughts we argue that it can be applied to a range of environmental governance challenges.

In this paper we study to what extent electric propulsion is disrupting ‘the order’ in the automotive industry with six extensions to Christensen's notion of disruptive innovation (1997). For decades the automotive sector has relied on the internal combustion engine (ICE) as the established propulsion technology, but due to environmental regulation and geo-political scarcity problems associated with fossil fuel use, electric propulsion is increasingly applied as sole or additional power source.We elaborate the Christensen typology, rooted in industrial analysis, with a regime evolution framework based on changes in technology and the institutional context of production and use, with special attention to consumer perspectives and government regulation. We offer a hypothesis for structural conditions for market disruption and test this hypothesis against the development trajectory of full-electric vehicles (FEV). Drawing on evidence from a range of recent FEV studies, our analysis suggests that the disruptive niche of full-electric mobility is currently insufficient to displace the ICE regime.

This study aimed to investigate whether pre- and early postnatal experiences of rearing hens contribute to the ability to cope with infectious challenges at an older age. In a 2 × 2 factorial arrangement, 352 Lohmann Brown chicks were exposed to either suboptimal or optimized incubation plus hatch conditions, and to cage or enriched rearing from week 0 to 7 of age. After week 7 all rearing conditions were similar until the end of the experiment. The development of adaptive capacity to infectious challenges was investigated by introducing an Eimeria and Infectious Bronchitis (IB) infection on day 53 and day 92, respectively. BW gain and feed intake during the infections, duodenal lesions and amount of positive stained CD4+ T cells, CD8+ T cells and macrophages at day 4 and day 7 after Eimeria infection, as well as the IB antibody titer throughout the experimental period were determined. The results showed a significant interaction between incubation plus hatch and rearing environment. Optimized incubation plus hatch conditions followed by an enriched rearing environment resulted in the least weight loss (P < 0.05) and the highest feed intake (P < 0.01) from day 3 to day 7 after the Eimeria infection (day 56 to 60 of age), compared with all other treatments. In addition, the optimized × enriched chicks had the highest BW gain from day 7 to day 14 after IB infection (day 99 to 106 of age), compared with chicks housed in a cage environment (P < 0.01). Besides the interaction, optimized incubation plus hatch alone resulted in reduced macrophage numbers in the duodenal tissue at day 4 after Eimeria infection, compared with suboptimal incubation plus hatch, whereas the enriched rearing environment stimulated the recovery of intestinal damage caused by Eimeria (P < 0.05) and reduced the production of specific antibodies after IB infection (P < 0.05), compared with the cage environment. In conclusion, this study shows that early life experiences can indeed affect the capacity of rearing hens to cope with an Eimeria and IB infection at an older age, in which performance of chicks is best maintained after optimized incubation plus hatch followed by enriched rearing. This suggests that the development of adaptive capacity to infectious challenges can be influenced with management during a short period in pre- or early postnatal life, but that effects last for a considerable time after cessation of the specific management.