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The article discusses recent publications in the journal Grass & Forage Science, which include review papers and articles based on presentations at conferences and symposia. The current issue features a book review and two papers from the European Grassland Federation symposium, as well as two papers from the International Grassland Congress. The journal also covers topics such as green biorefinery, drought impacts on grasslands, plant diversity in grasslands, forage quality, agrivoltaic production systems, tropical grasslands, and plant-soil relationships. The article concludes by acknowledging the organizers of the symposiums and the efforts of the associate editors and referees. [Extracted from the article]

This article discusses a special issue of Grass and Forage Science focused on grassland, forage, and turfgrass science in China. The issue highlights the developments in these areas in China and includes papers on topics such as genetics and grass breeding, forage production and utilization, grassland degradation, and turfgrasses. The article emphasizes the breadth of Chinese grassland science and notes an increase in the number of papers published from China in recent years. The authors express their gratitude to those who contributed to the special issue and anticipate continued growth in research from China in the future. [Extracted from the article]

The conversion of tallgrass prairie to agriculture has negatively affected provisioning of ecosystem services. Successful restoration of ecosystem services could depend on management decisions applied during revegetation projects. We examined the effects of three management decisions (seed mix design, planting time, and first‐year mowing) on targeted ecosystem services (erosion control, weed resistance, and pollinator resources). We tested three seed mixes of varying diversity and grass‐to‐forb seeding ratios: Economy mix (21 species, 3:1 grass:forb), Pollinator mix (38 species, 1:3), and Diversity mix (71 species, 1:1). We established plots at two planting times (dormant‐season and spring) with or without first‐year mowing. To assess ecosystem services, we measured stem density, canopy cover, and floral density and richness of sown species in the second year after planting. The Economy mix had the highest stem density and cover but lowest floral density and richness. The Pollinator mix had the lowest stem density and cover but highest floral density. The Diversity mix had comparable stem density and cover to the Economy mix and comparable floral density and richness to the Pollinator mix. Mowing accelerated native plant establishment in all seed mixes. Dormant‐season planting improved establishment of spring and fall forbs and favored cool‐season graminoids over warm‐season grasses. All three management decisions influenced ecosystem outcomes, and comparison to a previous study revealed these effects to be robust to variation in site and climatic conditions. We recommend a diverse, balanced seed mix design, first‐year mowing, and dormant‐season planting to improve multifunctionality of conservation projects. [ABSTRACT FROM AUTHOR]

Background: Neurofibromatosis type 1 (NF1) is a neurodevelopmental genetic disorder associated with visual–spatial and visuomotor deficits, which have not been studied well in adults with NF1. Methods: In 22 adults with NF1 and 31 controls, visuomotor functioning was assessed by measuring eye latency, hand latency and hand accuracy during visuomotor tasks. Visual–spatial functioning was assessed by measuring eye movement responses during the Visual Threshold Task. Results: The NF1 group had a significantly shorter eye latency than the control group and was less accurate in their hand movements during specific visuomotor tasks. The groups showed no differences in eye movement responses during the Visual Threshold Task and in hand latency during the visuomotor tasks. Conclusions: In contrast to studies in children with NF1, we found no alterations in visual–spatial information processing in adults. Impairments in eye latency and hand accuracy during specific visuomotor tasks may indicate deficits in visuomotor functioning in adults with NF1. [ABSTRACT FROM AUTHOR]

For nearly 40 years, the Conservation Reserve Program (CRP) has implemented practices to reduce soil erosion, improve water quality, and provide habitat for wildlife and pollinators on highly erodible cropland in the United States. However, an approximately 40,470 ha (10 million acres) decline in enrolled CRP land over the last decade has greatly reduced the program's environmental benefits. We sought to assess the program's enduring benefits in the central and western United States by (1) determining the proportion of fields that persist in CRP cover after contracts expired, (2) identifying the type of agricultural production that CRP fields shift to after contract expiration, (3) comparing the vegetation characteristics of expired CRP fields that are persisting in CRP‐type cover with enrolled CRP fields, and (4) identifying differences in management activities (e.g., haying, grazing) between expired and enrolled CRP fields. We conducted edge‐of‐field vegetation cover surveys in 1092 CRP fields with contracts that expired ≥3 years prior and 1786 currently enrolled CRP fields in 14 states. We found that 41% of expired CRP fields retained at least half of their area in CRP‐type cover, with significant variation in persistence among regions ranging from 19% to 84%. When expired fields retained CRP vegetation, bare ground was low in all regions and grass cover was somewhat greater than in fields with current CRP contracts, but at the expense of forb cover in some regions. Evidence of more frequent management in expired CRP fields may explain differences between active and expired CRP fields. Overall, there is clear evidence that CRP‐type cover frequently persists and provides benefits for more than three years after contract expiration. Retaining CRP‐type cover, post‐contract, is an under‐recognized program benefit that persists across the central and western United States long after the initial retirement from cropland. [ABSTRACT FROM AUTHOR]

In the Midwestern United States where the landscape has been largely converted from tallgrass prairie to row crops, thousands of private land parcels have been enrolled in federal pollinator habitat reconstruction programmes.To examine the outcome of pollinator habitat reconstruction, we randomly selected 19 sites that were in the third growing season post restoration and surveyed plant, floral and wild bee richness and abundance. Floral sources were divided into three categories: species from the seed mix (sown), species from the soil seed bank or surrounding landscape (unsown), and species that were likely unintentionally sown (contamination).Seventy‐two percent of captured bees were collected from sown flowers. The majority of oligolectic bees were Asteraceae specialists. Using linear regressions with bee abundance and richness as response variables and floral density and diversity as predictor variables, we showed that sown floral density was positively correlated with the total abundance and richness of bees collected from sown flowers, indicating that the selected pollinator friendly flowers provide support for wild bee communities. Conversely, total plant stem density or richness or the total floral density or richness was not significantly correlated with bee abundance or richness.The plant–pollinator network nestedness and modularity were positively correlated with the ratio of the unsown floral richness at each site, which suggests that the association between unsown flowers and wild bees can increase the long‐term stability of the plant‐pollinator network, even though the unsown species do not directly increase the bee abundance or richness. [ABSTRACT FROM AUTHOR]

Wetlands impact global warming by regulating the atmospheric exchange of greenhouse gases (GHGs), including carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O). We investigated GHG emissions in the Great Lakes coastal wetlands across various hydrologic, temperature, and nitrogen (N) inflow regimes using a process‐based simulation model. We found the emission of CH4, N2O, and sequestration of C (i.e., negative net ecosystem exchange, NEE) in our simulations were all positively related to water residence time and N inflow, primarily due to greater plant productivity and N uptake, which facilitated greater C and N cycling rates in the model. Water level scenarios also had an effect on GHG exchanges by moderating the transitions between aerobic and anaerobic conditions. Temperature effects on GHGs were minimal compared with other factors. The net sustained‐flux global warming potential (SGWP; i.e., sum SGWP of CH4, N2O, and NEE) of wetlands on 20‐year and 100‐year time horizons were both primarily driven by CH4 emissions and strongly controlled by the tradeoffs between CH4 emission and CO2 sequestration, with a negligible amount of simulated N2O emissions. Future research could include model enhancements to provide increased process‐level details on the aerobic‐anaerobic transitions or the direct effects of plants on mediating GHG exchanges. Field studies addressing the interaction of N inflows and water residence time at appropriately large scales are needed to test the complex interactions revealed by our modeling study. Our results highlight the previously under‐appreciated role of nitrogen and water residence time in modulating SGWP in coastal wetlands. Plain Language Summary: Wetlands impact global warming by emitting carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) to the atmosphere, but can absorb these greenhouse gases (GHGs). In our study, we investigated GHG emission in the Great Lakes coastal wetlands under different hydrologic, temperature, and nitrogen (N) inflow regimes using a simulation ecosystem model. We found the emission of CH4 and N2O increased with longer water residence time and higher N inflow in our modeling results, but at the same time, more carbon was absorbed by wetlands because wetland plants produced more biomass with more nutrients. The summed sustained‐flux global warming potential of wetlands on 20‐year and 100‐year time horizons both depend on if global warming potential caused by CH4 could be offset by the negative global warming potential of CO2. Key Points: Wetland methane emissions had a far greater effect on net sustained‐flux global warming potential than carbon dioxide or nitrous oxideThe positive net sustained‐flux global warming potential was dominated by methane emission in our simulationsOur study illustrated the strength of using a process‐based model to reveal the interactions between drivers of greenhouse gas emissions [ABSTRACT FROM AUTHOR]

Half a century ago, Harry Angelman reported three patients with overlapping clinical features, now well known as Angelman syndrome. Angelman syndrome is caused by mutations affecting the maternally inherited UBE3A gene, which encodes an E3-ubiquitin ligase that is critical for typical postnatal brain development. Emerging evidence indicates that UBE3A plays a particularly important role in the nucleus. However, the critical substrates that are controlled by UBE3A remain elusive, which hinders the search for effective treatments. Moreover, given the multitude of signalling mechanisms that are derailed, it is unlikely that targeting a single pathway is going to be very effective. Therefore, expectations are very high for approaches that aim to restore UBE3A protein levels. A particular promising strategy is an antisense oligonucleotide approach, which activates the silenced paternal UBE3A gene. When successful, such treatments potentially offer a disease-modifying therapy for Angelman syndrome and several other neurodevelopmental disorders. What this paper adds Loss of UBE3A affects multiple signalling pathways in the brain. Emerging evidence suggests that UBE3A plays a critical role in the cell nucleus. Trials using antisense oligonucleotides to restore UBE3A levels are continuing. [ABSTRACT FROM AUTHOR]

Coastal wetlands intercept significant amounts of nitrogen (N) from watersheds, especially when surrounding land cover is dominated by agriculture and urban development. Through plant uptake, soil immobilization, and denitrification, wetlands can remove excess N from flow‐through water sources and mitigate eutrophication of connected aquatic ecosystems. Excess N can also change plant community composition in wetlands, including communities threatened by invasive species. Understanding how variable hydrology and N loading impact wetland N removal and community composition can help attain desired management outcomes, including optimizing N removal and/or preventing invasion by nonnatives. By using a dynamic, process‐based ecosystem simulation model, we are able to simulate various levels of hydrology and N loading that would otherwise be difficult to manipulate. We investigate in silico the effects of hydroperiod, hydrologic residence time, N loading, and the NH4+:NO3‐ ratio on both N removal and the invasion success of two nonnative species (Typha × glauca or Phragmites australis) in temperate freshwater coastal wetlands. We found that, when residence time increased, annual N removal increased up to 10‐fold while longer hydroperiods also increased N removal, but only when residence time was >10 d and N loading was >30 g N·m−2·yr−1. N removal efficiency also increased with increasing residence time and hydroperiod, but was less affected by N loading. However, longer hydrologic residence time increased vulnerability of wetlands to invasion by both invasive plants at low to medium N loading rates where native communities are typically more resistant to invasion. This suggests a potential trade‐off between ecosystem services related to nitrogen removal and wetland invasibility. These results help elucidate complex interactions of community composition, N loading and hydrology on N removal, helping managers to prioritize N removal when N loading is high or controlling plant invasion in more vulnerable wetlands. [ABSTRACT FROM AUTHOR]

Dietary restriction (DR) and rapamycin extend healthspan and life span across multiple species. We have recently shown that DR in progeroid DNA repair‐deficient mice dramatically extended healthspan and trippled life span. Here, we show that rapamycin, while significantly lowering mTOR signaling, failed to improve life span nor healthspan of DNA repair‐deficient Ercc1∆/− mice, contrary to DR tested in parallel. Rapamycin interventions focusing on dosage, gender, and timing all were unable to alter life span. Even genetically modifying mTOR signaling failed to increase life span of DNA repair‐deficient mice. The absence of effects by rapamycin on P53 in brain and transcription stress in liver is in sharp contrast with results obtained by DR, and appoints reducing DNA damage and transcription stress as an important mode of action of DR, lacking by rapamycin. Together, this indicates that mTOR inhibition does not mediate the beneficial effects of DR in progeroid mice, revealing that DR and rapamycin strongly differ in their modes of action. [ABSTRACT FROM AUTHOR]

Descriptions of the clinical features of Angelman syndrome (AS) have mainly been focused on children. Here, we describe the evolution of the clinical phenotypes of AS in adulthood, using clinical data from 95 individuals (mean age 31.6 years, median 29.0 years, range 18–83 years), with genetically confirmed AS. Data was collected through physical examination and inspection of medical records, combined with questionnaires and interviews. Adults with AS experience substantial debilitating health problems. Constipation, reflux, visual problems, scoliosis, behavioral and sleeping problems occurred frequently and require appropriate attention. Epilepsy was reported in 57% of adults, negatively affecting the level of functioning. Non‐convulsive status epilepticus was not observed in the adults, however some individuals developed prolonged episodes of rhythmic shaking while awake. A decline in mobility was noted in the majority of adults. A minority of adults with AS showed microcephaly. Taken together, this first phenotypic study of adults with AS to include in person interviews with care‐givers and physical examination of patients, including the eldest adult reported to date, provides important insight in the development of the syndrome into adulthood. This knowledge is required to improve care for adult individuals with AS and to evaluate future therapies for this group. [ABSTRACT FROM AUTHOR]

The year 2020 marks the 75th edition of Grass and Forage Science. From its beginnings as the Journal of the British Grassland Society, the journal has grown to be the major international journal with a primary emphasis on grasslands society. In this paper, to mark this anniversary we note the contributions of the editorial team, past and present, and the legacy of the journal by noting some of the highly cited papers published over the years and discuss the changing trends in science published in recent years. This includes an emphasis on the changing role of grasslands across the globe and the challenges that changing climate and altered production systems place on grazing agriculture. It is through the adoption of science that is being published now that the industries that we serve will be able to respond to these challenges. [ABSTRACT FROM AUTHOR]

Background: Loss of functional UBE3A, an E3 protein ubiquitin ligase, causes Angelman syndrome (AS), a neurodevelopmental disorder characterized by severe developmental delay, speech impairment, epilepsy, movement or balance disorder, and a characteristic behavioral pattern. We identified a novel UBE3A sequence variant in a large family with eight affected individuals, who did not meet the clinical AS criteria. Methods: Detailed clinical examination and genetic analysis was performed to establish the phenotypic diversity and the genetic cause. The function of the mutant UBE3A protein was assessed with respect to its subcellular localization, stability, and E3 ubiquitin ligase activity. Results: All eight affected individuals showed the presence of a novel maternally inherited UBE3A sequence variant (NM_130838.4(UBE3A):c.1018‐1020del, p.(Asn340del), which is in line with a genetic AS diagnosis. Although they presented with moderate to severe intellectual disability, the phenotype did not match the clinical criteria for AS. In line with this, functional analysis of the UBE3A p.Asn340del mutant protein revealed no major deficits in UBE3A protein localization, stability, or E3 ubiquitin ligase activity. Conclusion: The p.(Asn340del) mutant protein behaves distinctly different from previously described AS‐linked missense mutations in UBE3A, and causes a phenotype that is markedly different from AS. This study further extends the range of phenotypes that are associated with UBE3A loss, duplication, or mutation. [ABSTRACT FROM AUTHOR]

The treatment of burn wounds by enzymatic debridement using bromelain has shown promising results in our burn center. However, inadequate debridement occurred in a few cases in which the etiology of the burn was attributed to relatively low temperature burns. We hypothesized that bromelain is ineffective in burns in which collagen denaturation, which occurs approximately at 65°C, has not taken place. Our objective was to assess whether there is a relationship between the denaturation of collagen and the ability of bromelain to debride acute scald burn wounds of different temperatures. Ex vivo human skin from four different donors was cut into 1x1 cm samples, and scald burns were produced by immersion in water at temperatures of 40°C, 50°C, 60°C, 70°C, and 100°C for 20 minutes. Denaturation of collagen was assessed with histology, using hematoxylin and eosin (H&E) staining and a fluorescently labeled collagen hybridizing peptide (CHP), and with second harmonic generation (SHG) microscopy. Burned samples and one control sample (room temperature) were weighed before and after application of enzymatic debridement to assess the efficacy of enzymatic debridement. After enzymatic debridement, a weight reduction of 80% was seen in the samples heated to 70°C and 100°C, whereas the other samples showed a reduction of 20%. Unfolding of collagen, loss of basket‐weave arrangement, and necrosis was seen in samples heated to 60°C or higher. Evident CHP fluorescence, indicative of collagen denaturation, was seen in samples of 60°C, 70°C and 100°C. SHG intensity, signifying intact collagen, was significantly lower in the 70°C and 100°C group (P <.05) compared to the lower temperatures. In conclusion, denaturation of collagen in skin samples occurred between 60°C and 70°C and strongly correlated with the efficacy of enzymatic debridement. Therefore, enzymatic debridement with the use of bromelain is ineffective in scald burns lower than 60°C. [ABSTRACT FROM AUTHOR]

Agricultural intensification continues to diminish many ecosystem services in the North American Corn Belt. Conservation programs may be able to combat these losses more efficiently by developing initiatives that attempt to balance multiple ecological benefits. In this study, we examine how seed mix design and first year management influence three ecosystem services commonly provided by tallgrass prairie reconstructions (erosion control, weed resistance, and pollinator resources). We established research plots with three seed mixes, with and without first year mowing. The grass‐dominated "Economy" mix had 21 species and a 3:1 grass‐to‐forb seeding ratio. The forb‐dominated "Pollinator" mix had 38 species and a 1:3 grass‐to‐forb seeding ratio. The grass:forb balanced "Diversity" mix, which was designed to resemble regional prairie remnants, had 71 species and a 1:1 grass‐to‐forb ratio. To assess ecosystem services, we measured native stem density, cover, inflorescence production, and floral richness from 2015 to 2018. The Economy mix had high native cover and stem density, but produced few inflorescences and had low floral richness. The Pollinator mix had high inflorescence production and floral richness, but also had high bare ground and weed cover. The Diversity mix had high inflorescence production and floral richness (comparable to the Pollinator mix) and high native cover and stem density (comparable to the Economy mix). First year mowing accelerated native plant establishment and inflorescence production, enhancing the provisioning of ecosystem services during the early stages of a reconstruction. Our results indicate that prairie reconstructions with thoughtfully designed seed mixes can effectively address multiple conservation challenges. [ABSTRACT FROM AUTHOR]

This study presents a broad overview of health issues and psychomotor development of 100 children with Angelman syndrome (AS), seen at the ENCORE Expertise Center for AS in Rotterdam, the Netherlands. We aimed to further delineate the phenotype of AS, to evaluate the association of the phenotype with genotype and other determinants such as epilepsy and to get insight in possible targets for intervention. We confirmed the presence of a more severe phenotype in the 15q11.2‐q13 deletion subtype. Novel findings were an association of (early onset of) epilepsy with a negative effect on development, a high occurrence of nonconvulsive status epilepticus, a high rate of crouch gait in the older children with risk of deterioration of mobility, a relatively low occurrence of microcephaly, a higher mean weight for height in all genetic subtypes with a significant higher mean in the nondeletion children, and a high occurrence of hyperphagia across all genetic subtypes. Natural history data are needed to design future trials. With this large clinical cohort with structured prospective and multidisciplinary follow‐up, we provide unbiased data on AS to support further intervention studies to optimize outcome and quality of life of children with AS and their family. [ABSTRACT FROM AUTHOR]

Objective: An epilepsy mouse model for Tuberous Sclerosis Complex (TSC) was developed and validated to investigate the mechanisms underlying epileptogenesis. Furthermore, the possible antiepileptogenic properties of commonly used antiepileptic drugs (AEDs) and new compounds were assessed. Methods: Tsc1 deletion was induced in CAMK2A‐expressing neurons of adult mice. The antiepileptogenic properties of commonly used AEDs and inhibitors of the mTOR pathways were assessed by EEG recordings and by molecular read outs. Results: Mice developed epilepsy in a narrow time window (10 ± 2 days) upon Tsc1 gene deletion. Seizure frequency but not duration increased over time. Seizures were lethal within 18 days, were unpredictable, and did not correlate to seizure onset, length or frequency, reminiscent of sudden unexpected death in epilepsy (SUDEP). Tsc1 gene deletion resulted in a strong activation of the mTORC1 pathway, and both epileptogenesis and lethality could be entirely prevented by RHEB1 gene deletion or rapamycin treatment. However, other inhibitors of the mTOR pathway such as AZD8055 and PF4708671 were ineffective. Except for ketogenic diet, none of commonly used AEDs showed an effect on mTORC1 activity. Vigabatrin and ketogenic diet treatment were able to significantly delay seizure onset. In contrast, survival was shortened by lamotrigine. Interpretation: This novel Tsc1 mouse model is highly suitable to assess the efficacy of antiepileptic and ‐epileptogenic drugs to treat mTORC1‐dependent epilepsy. Additionally, it allows us to study the mechanisms underlying mTORC1‐mediated epileptogenesis and SUDEP. We found that early treatment with vigabatrin was not able to prevent epilepsy, but significantly delayed seizure onset. [ABSTRACT FROM AUTHOR]

The neurofibromatoses, which include neurofibromatosis type I (NF1), neurofibromatosis type II (NF2), and schwannomatosis, are a group of syndromes characterized by tumor growth in the nervous system. The RASopathies are a group of syndromes caused by germline mutations in genes that encode components of the RAS/mitogen‐activated protein kinase (MAPK) pathway. The RASopathies include NF1, Noonan syndrome, Noonan syndrome with multiple lentigines, Costello syndrome, cardio‐facio‐cutaneous syndrome, Legius syndrome, capillary malformation arterio‐venous malformation syndrome, and SYNGAP1 autism. Due to their common underlying pathogenetic etiology, all these syndromes have significant phenotypic overlap of which one common feature include a predisposition to tumors, which may be benign or malignant. Together as a group, they represent one of the most common multiple congenital anomaly syndromes estimating to affect approximately one in 1000 individuals worldwide. The subcontinent of India represents one of the largest populations in the world, yet remains underserved from an aspect of clinical genetics services. In an effort to bridge this gap, the First International Conference on RASopathies and Neurofibromatoses in Asia: Identification and Advances of New Therapeutics was held in Kochi, Kerala, India. These proceedings chronicle this timely and topical international symposium directed at discussing the best practices and therapies for individuals with neurofibromatoses and RASopathies. [ABSTRACT FROM AUTHOR]

The neurofibromatoses are inherited, tumor suppressor disorders that are characterized by multiple, benign peripheral nerve sheath tumors and other nervous system tumors. Each disease is associated with a distinct genetic mutation and with a different pathogenesis and clinical course. Neurofibromatosis 1 (NF1) is common and epitomized by multiple neurofibromas with widespread complications. NF2 and schwannomatosis are rare diseases that are typified by multiple schwannomas that are particularly painful in people with schwannomatosis. Since 1985, the Children's Tumor Foundation (formerly the National Neurofibromatosis Foundation) has hosted an international Neurofibromatosis Conference, bringing together international participants who are focused on NF research and clinical care. The 2017 Conference, held in Washington, DC, was among the largest gatherings of NF researchers to date and included presentations from clinicians and basic scientists, highlighting new data regarding the molecular and cellular mechanisms underlying each of these diseases as well as results from clinical studies and clinical trials. This article summarizes the findings presented at the meeting and represents the current state‐of‐the art for NF research. [ABSTRACT FROM AUTHOR]

Abstract: There is a lack of information on the effects of companion species in grass–legume mixtures on herbage yield and quality changes during prolonged growth. Such information is relevant for harvest planning and estimation of consequences for feeding value of conserved feed when harvesting is delayed. Perennial ryegrass was sown with each of four legumes: red clover, white clover, lucerne and birdsfoot trefoil, and white clover was sown with hybrid ryegrass, meadow fescue and timothy. Effects of species composition on herbage yield, contents of N, neutral detergent fibre (NDF), acid detergent fibre (ADF) and lignin, ash and in vitro organic matter digestibility (IVOMD) were studied in entire herbage and in component species during 2 years in a small‐plot cutting trial in Denmark. In May and August, the dynamic development of components of feed value and their interrelationships were investigated by sampling at optimum harvest date (i.e., normal practice) ± 1 week (t = −1 to t = +1). Herbage digestibility and contents of N and ash decreased while those of fibre compounds increased during the 2 weeks from t = −1 to t = 1 in all species. In May, contents of ADF and lignin increased at a faster rate in legumes than in grasses; in August, NDF and ADF increased most quickly in legumes. Generally, N contents and IVOMD declined at similar rates in grasses and legumes, but, within each group, differences in yield and quality development occurred among species. The relationship between weekly growth rate and change in quality parameters differed among species and functional groups, i.e., grasses and legumes. Results are discussed in the context of quantifying the impact of delaying the harvest date of grass–legume mixtures and relationships between productivity and components of feed quality. [ABSTRACT FROM AUTHOR]

Abstract: Grassland diversity can support sustainable intensification of grassland production through increased yields, reduced inputs and limited weed invasion. We report the effects of diversity on weed suppression from 3 years of a 31‐site continental‐scale field experiment. At each site, 15 grassland communities comprising four monocultures and 11 four‐species mixtures based on a wide range of species' proportions were sown at two densities and managed by cutting. Forage species were selected according to two crossed functional traits, “method of nitrogen acquisition” and “pattern of temporal development”. Across sites, years and sown densities, annual weed biomass in mixtures and monocultures was 0.5 and 2.0 t  DM ha−1 (7% and 33% of total biomass respectively). Over 95% of mixtures had weed biomass lower than the average of monocultures, and in two‐thirds of cases, lower than in the most suppressive monoculture (transgressive suppression). Suppression was significantly transgressive for 58% of site‐years. Transgressive suppression by mixtures was maintained across years, independent of site productivity. Based on models, average weed biomass in mixture over the whole experiment was 52% less (95% confidence interval: 30%–75%) than in the most suppressive monoculture. Transgressive suppression of weed biomass was significant at each year across all mixtures and for each mixture. Weed biomass was consistently low across all mixtures and years and was in some cases significantly but not largely different from that in the equiproportional mixture. The average variability (standard deviation) of annual weed biomass within a site was much lower for mixtures (0.42) than for monocultures (1.77). Synthesis and applications. Weed invasion can be diminished through a combination of forage species selected for complementarity and persistence traits in systems designed to reduce reliance on fertiliser nitrogen. In this study, effects of diversity on weed suppression were consistently strong across mixtures varying widely in species' proportions and over time. The level of weed biomass did not vary greatly across mixtures varying widely in proportions of sown species. These diversity benefits in intensively managed grasslands are relevant for the sustainable intensification of agriculture and, importantly, are achievable through practical farm‐scale actions. [ABSTRACT FROM AUTHOR]

The effect of lowering sympathetic nerve activity by renal denervation (RDN) is highly variable. With the exception of office systolic blood pressure (BP), predictors of the BP-lowering effect have not been identified. Because dietary sodium intake influences sympathetic drive, and, conversely, sympathetic activity influences salt sensitivity in hypertension, we investigated 24-hour urinary sodium excretion in participants of the SYMPATHY trial. SYMPATHY investigated RDN in patients with resistant hypertension. Both 24-hour ambulatory and office BP measurements were end points. No relationship was found for baseline sodium excretion and change in BP 6 months after RDN in multivariable-adjusted regression analysis. Change in the salt intake-measured BP relationships at 6 months vs baseline was used as a measure for salt sensitivity. BP was 8 mm Hg lower with similar salt intake after RDN, suggesting a decrease in salt sensitivity. However, the change was similar in the control group, and thus not attributable to RDN. [ABSTRACT FROM AUTHOR]

Increased species diversity promotes ecosystem function; however, the dynamics of multi-species grassland systems over time and their role in sustaining higher yields generated by increased diversity are still poorly understood. We investigated the development of species' relative abundances in grassland mixtures over 3 years to identify drivers of diversity change and their links to yield diversity effects., A continental-scale field experiment was conducted at 31 sites using 11 different four-species mixtures each sown at two seed abundances. The four species consisted of two grasses and two legumes, of which one was fast establishing and the other temporally persistent. We modelled the dynamics of the four-species mixtures, and tested associations with diversity effects on yield., We found that species' dynamics were primarily driven by differences in the relative growth rates ( RGRs) of competing species, and secondarily by density dependence and climate. The temporally persistent grass species typically had the highest RGRs and hence became dominant over time. Density dependence sometimes induced stabilising processes on the dominant species and inhibited shifts to monoculture. Legumes persisted at most sites at low or medium abundances and persistence was improved at sites with higher annual minimum temperature., Significant diversity effects were present at the majority of sites in all years and the strength of diversity effects was improved with higher legume abundance in the previous year. Observed diversity effects, when legumes had declined, may be due to (i) important effects of legumes even at low abundance, (ii) interaction between the two grass species or (iii) a store of N because of previous presence of legumes., Synthesis. Alongside major compositional changes driven by RGR differences, diversity effects were observed at most sites, albeit at reduced strength as legumes declined. This evidence strongly supports the sowing of multi-species mixtures that include legumes over the long-standing practice of sowing grass monocultures. Careful and strategic selection of the identity of the species used in mixtures is suggested to facilitate the maintenance of species diversity and especially persistence of legumes over time, and to preserve the strength of yield increases associated with diversity. [ABSTRACT FROM AUTHOR]

Gaining a better understanding of carbon (C) dynamics across the terrestrial and aquatic landscapes has become a major research initiative in ecosystem ecology. Wetlands store a large portion of the global soil C, but are also highly dynamic ecosystems in terms of hydrology and N cycling, and are one of the most invaded habitats worldwide. The interactions between these factors are likely to determine wetland C cycling, and specifically C accretion rates. We investigated these interactions using MONDRIAN, an individual-based model simulating plant growth and competition and linking these processes to N and C cycling. We simulated the effects of different levels of (1) N loading, (2) hydroperiod, and (3) plant community (natives only vs. invasion scenarios) and their interactions on C accretion outcomes in freshwater coastal wetlands of the Great Lakes region of North America. Results showed that N loading contributed to substantial rates of C accretion by increasing NPP (net primary productivity). By mediating anaerobic conditions and slowing decomposition, hydroperiod also exerted considerable control on C accretion. Invasion success occurred with higher N loading and contributed to higher NPP, while also interacting with hydroperiod via ecosystem-internal N cycling. Invasion success by both Typha × glauca and Phragmites australis showed a strong nonlinear relationship with N loading in which an invasion threshold occurred at moderate N inputs. This threshold was in turn influenced by duration of flooding, which reduced invasion success for P. australis but not for T. × glauca. The greatest simulated C accretion rates occurred in wetlands invaded by P. australis at the highest N loading in constant anaerobic conditions. These model results suggest that while plant invasion may increase C storage in freshwater coastal wetlands, increased plant productivity (both native and invasive) due to increased N loading is the main driver of increased C accretion. [ABSTRACT FROM AUTHOR]

The RASopathies are a group of disorders due to variations of genes associated with the Ras/MAPK pathway. Some of the RASopathies include neurofibromatosis type 1 (NF1), Noonan syndrome, Noonan syndrome with multiple lentigines, cardiofaciocutaneous (CFC) syndrome, Costello syndrome, Legius syndrome, and capillary malformation-arteriovenous malformation (CM-AVM) syndrome. In combination, the RASopathies are a frequent group of genetic disorders. This report summarizes the proceedings of the 4th International Symposium on Genetic Disorders of the Ras/MAPK pathway and highlights gaps in the field. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Grazing animals walk outdoors and harvest fresh herbage from a three-dimensional canopy. Botanical composition and grassland management in various farming systems affect herbage intake and milk fatty acid (FA) composition. Grazing animals encounter a vertical gradient while grazing down a sward; responses in milk FA composition are discussed. Grazing animals have diets rich in poly-unsaturated fatty acids (PUFA), particularly α-linolenic acid (C18:3n-3). Concentrates and starch-rich fodders affect rumen retention time of the feed, increase linoleic acid (C18:2n-6) intake, and alter biohydrogenation pathways toward less n-3 PUFA and less rumenic acid (conjugated linoleic acid (CLA) isomer C18:2 c9 t11), leading to lower contents of these compounds in the milk. Milk from grazing-based production systems including organic systems, therefore, has less saturated and more n-3PUFA and CLA c9 t11 which is considered beneficial for health. The occurrence of natural trans FA ( t11) in milk predominates with grazing whereas intensive feeding practices enhance t10-FA, with possible negative health effects. FA intake - output relations can differ among plant species due to rapid rumen passage rate or compounds protecting PUFA, resulting in more PUFA in milk. Methodological constraints for FA measurement in herbages are discussed. Trends in grazing and dairy farming systems and implications for milk FA composition are addressed. Practical applications: Grazing is important for fresh forage intake, animal health and natural behaviour, landscape values and grassland biodiversity. Grazing is a political, societal and marketing issue in The Netherlands where retailers since 2011 sell dairy products labelled as 'pasture-milk' and dairies pay a premium to farmers whose cows get access to pasture. Grazing affects green leaf intake because animals can select. Pasture allowance enhances α-linolenic acid and CLA c9 t11 (rumenic acid) concentrations in milk fat. FA need to be designated by unique names; CLA is a generic term and isomers give rise to different biological responses. As some forbs reduce biohydrogenation, grassland species diversity may improve PUFA transfer efficiency from feed to milk. Trends in animal genetics and increased herd size, TMR feeding and automated milking systems cause reduction of grazing in Europe, which can increase saturated and trans-10 milk FA concentrations and reduce naturally occurring fat-soluble vitamins and antioxidants in dairy products. Grazing (pasture-feeding versus indoor with conserved forage and concentrates) increases n-3 PUFA and trans-11 over trans-10 FA in cow milk when cows can select, as leaves have high n-3 PUFA concentrations; biodiverse grasslands enhance this effect as some forbs show less PUFA rumen biohydrogenation than grasses, thus increasing efficiency of PUFA transfer from forage to milk. [ABSTRACT FROM AUTHOR]

'The Third International Meeting on Genetic Disorders in the RAS/MAPK Pathway: Towards a Therapeutic Approach' was held at the Renaissance Orlando at SeaWorld Hotel (August 2-4, 2013). Seventy-one physicians and scientists attended the meeting, and parallel meetings were held by patient advocacy groups (CFC International, Costello Syndrome Family Network, NF Network and Noonan Syndrome Foundation). Parent and patient advocates opened the meeting with a panel discussion to set the stage regarding their hopes and expectations for therapeutic advances. In keeping with the theme on therapeutic development, the sessions followed a progression from description of the phenotype and definition of therapeutic endpoints, to definition of genomic changes, to identification of therapeutic targets in the RAS/MAPK pathway, to preclinical drug development and testing, to clinical trials. These proceedings will review the major points of discussion. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Agronomic data on most broad-leaved species of grasslands are scarce. The aim of this study was to obtain novel information on herbage DM yield and forage quality for several forb species, and on species differences and seasonal patterns across harvests and in successive years. Four non-leguminous forbs [salad burnet ( Sanguisorba minor), caraway ( Carum carvi), chicory ( Cichorium intybus) and ribwort plantain ( Plantago lanceolata)] and three leguminous forbs [yellow sweet clover ( Melilotus officinalis), lucerne ( Medicago sativa) and birdsfoot trefoil ( Lotus corniculatus)] and a perennial ryegrass-white clover mixture were investigated in a small-plot cutting trial in Denmark during 2009 and 2010. Plots were harvested four times per year. On average, annual herbage yield was highest for lucerne (15·4 t DM) and grass-white clover (12·5 t DM ha−1), and lowest for salad burnet (4·6 t DM ha−1) and yellow sweet clover (3·9 t DM ha−1). Ribwort plantain and lucerne had the highest concentrations of acid detergent fibre (339 and 321 g kg−1 DM respectively) and lignin (78 and 67 g kg−1 DM respectively); contents in other species were similar to grass-white clover (275 and 49 g kg−1 DM respectively). No common feature was found within the functional groups of non-leguminous forbs and leguminous forbs, other than higher crude protein contents (198-206 g kg−1 DM) in the legumes. DM yield and fibre content were lowest in October. Digestibility declined with higher temperature and increasing fibre content. Results are discussed in terms of the potential of forbs to contribute to forage resources in farming practice. [ABSTRACT FROM AUTHOR]

Persistence of white clover (Trifolium repens) in mixtures was studied in a long-term experiment. Mixtures of two cultivars of perennial ryegrass (Lolium perenne) with contrasting growth habits and three white clover cultivars differing in leaf size were sown in 1991 and evaluated at two cutting frequencies. During 1995 and 1996 mixtures with large-leaved white clover cv. Alice had the highest dry-matter (DM) content, clover and N yield, and the highest white clover content, and mixtures with medium-leaved Retor the lowest, whereas mixtures with small-leaved Gwenda yielded most grass DM. In 1995 averaged over cutting treatments and mixtures, the mixtures yielded 11·8 t DM ha-1 with a white clover content of 0·6; the apparent N fixation was 393 kg N ha-1. In 1996 these values declined to 8·5 t DM ha-1, 0·48 white clover and 236 kg N ha-1. There was no significant effect of cutting frequency on DM yield or white clover content, whereas the effects of grass cultivar were not consistent. In spring there was a peak in the DM production of the mixtures, coinciding with a peak in production of the grass component. However, in summer and autumn the seasonal pattern of DM production of the mixtures was similar to that of the white clover component. Both cultivars of perennial ryegrass showed the same seasonal response, but the seasonal growth pattern of white clover differed slightly between clover cultivars and cutting treatments. In later years only one cutting frequency was imposed, and no yield measurements were taken. White clover was judged to have performed well during 1997; the clover content in September was very high (0·76), whereas in October 1998 it was 0·45. Mixtures with Alice contained most white clover. Despite fluctuations in white clover content during 1991–98, all clover cultivars had persisted 7 years after sowing, irrespective of companion grass cultivar, at both cutting... [ABSTRACT FROM AUTHOR]

The effect of defoliation interval on growth patterns of contrasting perennial ryegrass (Lolium perenne)–white clover (Trifolium repens) mixtures was studied. The dynamics of increase in leaf area, light interception and dry-matter (DM) production were measured within successive regrowth periods. No N fertilizer was applied. During 1995 six mixtures were cut eight (F1) or six times (F2) at a stubble height of 5 cm. The stubble composition was stable throughout the growing season: after harvest about 50 g DM m-2 (with a white clover proportion of 0·52) was present with a leaf area index (LAI) of 0·5 (0·38 white clover). The percentage of intercepted radiation after cutting was 20–30% and increased during 3 weeks to about 95%. The relative growth rate of leaf area and DM was higher for white clover than for perennial ryegrass, with the proportion of clover in the LAI and DM increasing during each regrowth period. Mixtures with large-leaved white clover cv. Alice had a lower initial clover content after harvest, but a more rapid increase in clover LAI and DM than mixtures with the smaller leaved cvs Gwenda or Retor. Alice had the highest total and clover LAI and DM at harvest. Cutting frequency affected the change in white clover–perennial ryegrass ratio during regrowth. This was significantly higher in mixtures with Alice than in mixtures with Gwenda, but only under less frequent cutting (F2). In spring there was a mean white clover proportion of about 0·55 in the LAI and 0·45 in the total harvested DM. In summer the white clover proportion in the LAI and DM increased to 0·70–0·75. There was a decline during autumn, especially in F2 and in the mixtures with the small-leaved white clover cv. Gwenda and the medium-leaved cv. Retor. In contrast, grass DM and LAI declined from spring to summer. The decline in clover LAI in autumn was similar in Alice and Gwenda at frequent cutting (F1), but... [ABSTRACT FROM AUTHOR]

Editorial: Sustainability of grasslands and grass-based ruminant production - Topics from the 28th General Meeting of the European Grassland Federation I Grass and Forage Science i (GFS) has a history of incidentally publishing articles based on presentations at conferences and symposia of the European Grassland Federation (EGF) (Table 1). This points out the important link between grasslands and ruminant production, although the importance of ecosystem services that grasslands provide has also recently been recognized (D'Ottavio et al., 2018) as well as novel uses of grass biomass such as green biorefineries (Franco et al., 2019). [Extracted from the article]

I Grass and Forage Science i has a strong history of publishing science related to the role of legumes in grassland farming systems. Pasture legumes are uniquely placed to provide high-quality forage and biologically fixed nitrogen despite the challenges associated with the incorporation of legumes into grazing systems. A special theme issue on forage legumes in grassland systems appeared in June 2014 with an emphasis on European farming systems, e.g., Lüscher et al. (2014), although papers on evaluation and management of annual legumes were included (Ates et al., 2014). [Extracted from the article]

Objective Seizure development in tuberous sclerosis complex (TSC) correlates with the presence of specific lesions called cortical tubers. Moreover, heterozygous TSC animal models do not show gross brain pathology and are seizure-free, suggesting that such pathology is a prerequisite for the development of epilepsy. However, cells within TSC lesions show increased activity of the target of rapamycin complex 1 (TORC1) pathway, and recent studies have implicated this pathway in non-TSC-related animal models of epilepsy and neuronal excitability. These findings imply a direct role for TORC1 in epilepsy. Here, we investigate the effect of increased TORC1 signaling induced by acute biallelic deletion of Tsc1 in healthy adult mice. Methods Biallelic Tsc1 gene deletion was induced in adult Tsc1 heterozygous and wild-type mice. Seizures were monitored by electroencephalographic and video recordings. Molecular and cellular changes were investigated by Western blot analysis, immunohistochemistry, and electrophysiology. Results Mice developed epilepsy a few days after biallelic Tsc1 deletion. Acute gene deletion was not accompanied by any obvious histological changes, but resulted in activation of the TORC1 pathway, enhanced neuronal excitability, and a decreased threshold for protein-synthesis-dependent long-term potentiation preceding the onset of seizures. Rapamycin treatment after seizure onset reduced TORC1 activity and fully abolished the seizures. Interpretation Our data indicate a direct role for TORC1 signaling in epilepsy development, even in the absence of major brain pathology. This suggests that TORC1 is a promising target for treating seizures not only in TSC but also in other forms of epilepsy that result from increased TORC1 activation. Ann Neurol 2013;74:569-579 [ABSTRACT FROM AUTHOR]

In reproductive swards, stems can act as a barrier that affects the grazing behaviour of ruminant livestock. The barrier effect of stems is closely associated with both the force required to fracture the stems and the density of these stems (in combination, these make up grazing resistance), and these factors need to be considered when making predictions about the forage intake of ruminants grazing reproductive pastures. Differences in grazing resistance between sward canopy layers of different grass species are thought to affect bite dimensions, but data are scarce. In this study, we assessed the grazing resistance for three canopy layers of seven tropical grass species. Species differed significantly in grazing resistance for every canopy layer, with a general ranking order for grazing resistance, in ascending order: Cenchrus ciliaris (' American' buffel), Digitaria milanjiana (' Jarra' finger grass), Setaria surgens (annual pigeon grass), Setaria sphacelata (' Narok' setaria), Dichanthium sericeum ( Queensland bluegrass), Chloris gayana (' Callide' Rhodes grass). In the top canopy layer, grazing resistance did not appear to create a barrier for any of the species, but in the bottom canopy layer, it did for all species. Species also differed in the relative contribution of fracture force and density to grazing resistance. The results highlight the importance of managing the grazing systems to minimize the barrier effect of the stems, which can be done by controlling the phenological stage of the pasture and the grass species and animal size used in the system. [ABSTRACT FROM AUTHOR]

A coordinated continental-scale field experiment across 31 sites was used to compare the biomass yield of monocultures and four species mixtures associated with intensively managed agricultural grassland systems. To increase complementarity in resource use, each of the four species in the experimental design represented a distinct functional type derived from two levels of each of two functional traits, nitrogen acquisition ( N2-fixing legume or nonfixing grass) crossed with temporal development (fast-establishing or temporally persistent). Relative abundances of the four functional types in mixtures were systematically varied at sowing to vary the evenness of the same four species in mixture communities at each site and sown at two levels of seed density., Across multiple years, the total yield (including weed biomass) of the mixtures exceeded that of the average monoculture in >97% of comparisons. It also exceeded that of the best monoculture (transgressive overyielding) in about 60% of sites, with a mean yield ratio of mixture to best-performing monoculture of 1·07 across all sites. Analyses based on yield of sown species only (excluding weed biomass) demonstrated considerably greater transgressive overyielding (significant at about 70% of sites, ratio of mixture to best-performing monoculture = 1·18)., Mixtures maintained a resistance to weed invasion over at least 3 years. In mixtures, median values indicate <4% of weed biomass in total yield, whereas the median percentage of weeds in monocultures increased from 15% in year 1 to 32% in year 3., Within each year, there was a highly significant relationship ( P < 0·0001) between sward evenness and the diversity effect (excess of mixture performance over that predicted from the monoculture performances of component species). At lower evenness values, increases in community evenness resulted in an increased diversity effect, but the diversity effect was not significantly different from the maximum diversity effect across a wide range of higher evenness values. The latter indicates the robustness of the diversity effect to changes in species' relative abundances., Across sites with three complete years of data (24 of the 31 sites), the effect of interactions between the fast-establishing and temporal persistent trait levels of temporal development was highly significant and comparable in magnitude to effects of interactions between N2-fixing and nonfixing trait levels of nitrogen acquisition., Synthesis and applications. The design of grassland mixtures is relevant to farm-level strategies to achieve sustainable intensification. Experimental evidence indicated significant yield benefits of four species agronomic mixtures which yielded more than the highest-yielding monoculture at most sites. The results are relevant for agricultural practice and show how grassland mixtures can be designed to improve resource complementarity, increase yields and reduce weed invasion. The yield benefits were robust to considerable changes in the relative proportions of the four species, which is extremely useful for practical management of grassland swards. [ABSTRACT FROM AUTHOR]

Learning disabilities and other cognitive disorders represent one of the most important unmet medical needs and a significant source of lifelong disability. To accelerate progress in this area, an international consortium of researchers and clinicians, the Learning Disabilities Network (LeaDNet), was established in 2006. Initially, LeaDNet focused on neurofibromatosis type 1 (NF1), a common single gene disorder with a frequency of 1:3,000. Although NF1 is best recognized as an inherited tumor predisposition syndrome, learning, cognitive, and neurobehavioral deficits account for significant morbidity in this condition and can have a profound impact on the quality of life of affected individuals. Recently, there have been groundbreaking advances in our understanding of the molecular, cellular, and neural systems underpinnings of NF1-associated learning deficits in animal models, which precipitated clinical trials using a molecularly targeted treatment for these deficits. However, much remains to be learned about the spectrum of cognitive, neurological, and psychiatric phenotypes associated with the NF1 clinical syndrome. In addition, there is a pressing need to accelerate the identification of specific clinical targets and treatments for these phenotypes. The successes with NF1 have allowed LeaDNet investigators to broaden their initial focus to other genetic disorders characterized by learning disabilities and cognitive deficits including other RASopathies (caused by changes in the Ras signaling pathway). The ultimate mission of LeaDNet is to leverage an international translational consortium of clinicians and neuroscientists to integrate bench-to-bedside knowledge across a broad range of cognitive genetic disorders, with the goal of accelerating the development of rational and biologically based treatments. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The intake of forage grasses by grazing ruminants is closely related to the mechanical fracture properties of grasses. The relationship between the tensile fracture properties of grasses and foraging behaviour is of particular importance in tropical reproductive swards composed of both stems and leaves. This study (i) quantified and compared the tensile fracture properties of stems and leaves of seven tropical grass species and (ii) provided insight into the underlying plant traits that explain differences in fracture properties between species. Fracture force, tensile strength, fracture energy and toughness of stems (in various phenological stages) and leaves were measured and compared among five introduced tropical grasses ( Cenchrus ciliaris, Chloris gayana, Digitaria milanjiana, Megathyrsus maximus (syn. Panicum maximum), Setaria sphacelata) and two native tropical grasses ( Setaria surgens and Dichanthium sericeum). Species differed significantly in fracture force and fracture energy, with stems and leaves of C. ciliaris and S. surgens requiring less force and energy to fracture and stems and leaves of M. maximus and S. sphacelata requiring more force and energy to fracture in comparison with the other species. Differences in tensile strength and toughness were less pronounced. The differences among species in fracture force and energy mainly resulted from differences in cross-sectional area of plant parts rather than from differences in tensile strength and toughness. [ABSTRACT FROM AUTHOR]

Summary Reasons for performing study: Head and neck positions (HNP) in sport horses are under debate in the equine community, as they could interfere with equine welfare. HNPs have not been quantified objectively and no information is available on their head and neck loading. Objectives: To quantify in vivo HNPs in sport horses and develop o a model to estimate loading on the cervical vertebrae in these positions. Methods: Videos were taken of 7 Warmbloods at walk on a straight line in 5 positions, representing all HNPs during Warmblood training and competition. Markers were glued at 5 anatomical landmarks. Two-dimensional angles and distances were determined from video frames for the 5 HNPs and statistically compared (P<0.05). A new simulation model was developed to estimate nuchal ligament cervical loading at these HNPs. Results: The mean angles were significantly different between the 5 HNPs for the line between C1 and T6 with the horizontal and for the line connecting the facial crest (CF) and C1 with the vertical, while the vertical distance from CF to the lateral styloid process of the radius (PS) was significantly different between all 5 positions (P<0.05). The estimated nuchal ligament loading appeared to be largest at the origin of C2 for all HNPs, except for the 'hyperextended' HNP5; the 'hyperflexed' HNP4 showed the largest loading values on the nuchal ligament origins at all locations. Conclusions: HNPs can be accurately quantified in the sagittal plane from angles and distances based on standard anatomical landmarks and home-video captured images. Nuchal ligament loading showed the largest estimated values at its origin on C2 in hyperflexion (HNP4). Potential relevance: Modelling opens further perspectives to eventually estimate loading for individual horses and thus ergonomically optimise their HNP, which may improve the welfare of the sport horse during training and competition. [ABSTRACT FROM AUTHOR]

Objective Primary postpartum haemorrhage (PPH) is a major cause of maternal morbidity and mortality around the world. Most patients can be managed conservatively, but patients with intractable bleeding require more aggressive treatment. In these cases uterine artery embolisation (UAE) has proven to be a useful tool to control PPH. The reported success rate of UAE is over 90% with only minor complications. In this case series we studied the effectiveness and complications of UAE. Design Retrospective analysis of a case series. Setting Case series in a large peripheral hospital in the Netherlands. Sample Eleven patients who were treated with UAE for intractable PPH from November 2004 to February 2008. Methods In this paper we review the results of all patients treated with UAE for intractable PPH in our hospital and focus on the two cases with adverse outcomes. Main outcome measures Effectiveness, causes of failure of UAE, complications. Results Nine out of eleven patients were treated successfully with UAE. One patient needed an emergency hysterectomy for intractable bleeding. In the aftermath she developed a vesicovaginal fistula (VVF). Another patient suffered a major thrombo-embolic event of the right leg, for which she underwent embolectomies and despite fasciotomy a necrotectomy. Conclusions UAE is a valuable tool in managing major PPH and in most cases it can replace surgery and thus prevent sacrification of the uterus. However, due to blood supply of the uterus by one of the ovarian or aberrant arteries, UAE might fail to control the bleeding. In addition, serious complications such as a thrombo-embolic event or VVF may occur. We hereby present a case of migration of an embolus from the site of re-embolisation into the femoral artery requiring immediate intervention to prevent the loss of the lower leg. This complication demonstrates that gelatine sponge particles could migrate from the internal iliac artery into the external iliac artery. [ABSTRACT FROM AUTHOR]

Corticosterone (100 nm) rapidly increases the frequency of miniature excitatory postsynaptic currents in mouse CA1 pyramidal neurons via membrane-located mineralocorticoid receptors (MRs). We now show that a presynaptic ERK1/2 signalling pathway mediates the nongenomic effect, as it was blocked by the MEK inhibitors U0126 (10 µm) and PD098059 (40 µm) and occluded in H-Ras G12V-mutant mice with constitutive activation of the ERK1/2 presynaptic pathway. Notably, the increase in mEPSC frequency was not mediated by retrograde signalling through endocannabinoids or nitric oxide, supporting presynaptic localization of the signalling pathway. Unexpectedly, corticosterone was also found to have a direct postsynaptic effect, rapidly decreasing the peak amplitude of IA currents. This effect takes place via postsynaptic membrane MRs coupled to a G protein-mediated pathway, as the effect of corticosterone on IA was effectively blocked by 0.5 mm GDP-β-S administered via the recording pipette into the postsynaptic cell. Taken together, these results indicate that membrane MRs mediate rapid, nongenomic effects via pre- as well as postsynaptic pathways. Through these dual pathways, high corticosterone concentrations such as occur after stress could contribute to enhanced CA1 pyramidal excitability. [ABSTRACT FROM AUTHOR]

Objective Tuberous sclerosis complex (TSC) is characterized by brain lesions, epilepsy, increased incidence of mental retardation and autism. The causal link between lesion load and epilepsy on cognitive disabilities has been debated, and these factors explain only part of the intelligence quotient variability. A Tsc2 rat model of the disease provided evidence that the TSC genes are directly involved in neuronal function. However, these lesion- and epilepsy-free animals did not show learning deficits, leaving open the possibility that the presence of brain lesions or epilepsy is a prerequisite for the cognitive deficits to fully develop. Here, we reinvestigated the relation among cerebral lesions, epilepsy, and cognitive function using Tsc1 +/−mice. Methods We used immunocytochemistry and high-resolution magnetic resonance imaging to study the presence of neuronal pathology in Tsc1 +/−mice. We used the Morris water maze, fear conditioning, social interaction, and nest building test to study the presence of cognitive and social deficits. Results We observed no spontaneous seizures or cerebral lesions in the brains of Tsc1 +/−mice. In addition, giant dysmorphic cells were absent, and spine number and dendritic branching appeared to be normal. Nevertheless, Tsc1 +/−mice showed impaired learning in the hippocampus-sensitive versions of the learning tasks and impaired social behavior. Interpretation Tsc1 +/−mice show social and cognitive deficits in the absence of apparent cerebral pathology and spontaneous seizures. These findings support a model in which haploinsufficiency for the TSC genes leads to aberrations in neuronal functioning resulting in impaired learning and social behavior. Ann Neurol 2007 [ABSTRACT FROM AUTHOR]