Genetic targeting of NRXN2 in mice unveils role in excitatory cortical synapse function and social behaviors

Human genetics has identified rare copy number variations and deleterious mutations for all neurexin genes (NRXN1-3) in patients with neurodevelopmental diseases, and electrophysiological recordings in animal brains have shown that Nrxns are important for synaptic transmission. While several mouse models for Nrxn1α inactivation have previously been studied for behavioral changes, very little information is available for other variants. Here, we validate that mice lacking Nrxn2α exhibit behavioral abnormalities, characterized by social interaction deficits and increased anxiety-like behavior, which partially overlap, partially differ from Nrxn1α mutant behaviors. Using patch-clamp recordings in Nrxn2α knockout brains, we observe reduced spontaneous transmitter release at excitatory synapses in the neocortex. We also analyse at this cellular level a novel NRXN2 mouse model that carries a combined deletion of Nrxn2α and Nrxn2β. Electrophysiological analysis of this Nrxn2-mutant mouse shows surprisingly similar defects of excitatory release to Nrxn2α, indicating that the β-variant of Nrxn2 has no strong function in basic transmission at these synapses. Inhibitory transmission as well as synapse densities and ultrastructure remain unchanged in the neocortex of both models. Furthermore, at Nrxn2α and Nrxn2-mutant excitatory synapses we find an altered facilitation and N-methyl-D-aspartate receptor (NMDAR) function because NMDAR-dependent decay time and NMDAR-mediated responses are reduced. As Nrxn can indirectly be linked to NMDAR via neuroligin and PSD-95, the trans-synaptic nature of this complex may help to explain occurrence of presynaptic and postsynaptic effects. Since excitatory/inhibitory imbalances and impairment of NMDAR function are alledged to have a role in autism and schizophrenia, our results support the idea of a related pathomechanism in these disorders

Evidenz und Tradition am Beispiel der Phytopharmaka

Summary Herbal medicinal products - Evidence and tradition from a historical perspective Background: Aside from the fully licensed herbal medicines there are products on the European pharmaceutical market which are registered by virtue of their longstanding traditional use. The normal registration procedure does not apply to them because presently they do not meet the legal requirements for a full license as set out in the relevant European Union Directive. One of these requirements, proof of tradition, has so far been dealt with in different ways and fails to meet the criteria of good practice. Method: This analysis is based on a selective literature search in PubMed and in databases of medical and pharmaceutical history, interviews with licensing experts, a consensus meeting attended by researchers with a background in general medicine, phytotherapy, medical and pharmaceutical history, biometry, ethnopharmacology, pharmacognosy and the pharmaceutical industry. Results and discussion: The 2004 EU Directive, which governs the registration of Traditional Herbal Medicinal Products and demands proof of tradition, is a regulatory construct and, above all, the outcome of a political process that has ended in a pragmatic compromise. The concept of tradition applied in the Directive does not sufficiently reflect the semantic breadth of the term. The only condition defined is that a specific commercial preparation needs to have been on the market for 30 years (15 of them inside the EU). Such an approach does not make full scientific use of the evidence available because the information excerpted from historical sources, if adequately processed, may yield valuable insights. This applies to indications, modes of application, efficacy and product safety (innocuousness). Such criteria should enter in full into the benefit-risk-analysis of applied preparations, in the registration process as well as in the therapeutic practice. Conclusion: When registering Traditional Herbal Medicinal Products the criterion of evidence-based medicine will only be met if all the facts available are assessed and evaluated, over and above the formally stipulated regulatory provisions (30 years, product reference). To this end, the scientific methods (from among the natural, life or cultural sciences), which are recognized as authoritative in each case, must be applied

The impact of reach averaging Manning's equation for an in-situ dataset of water surface elevation, width, and slope

The Surface Water and Ocean Topography Mission (SWOT) will generate global, spatially continuous maps of water surface elevation and extent for large inland water bodies when it launches in 2021. We present an analysis of water surface elevation, width, and bathymetry timeseries data from a medium-sized (average annual discharge 14 m3/s) river to explore Manning's equation, an empirical open channel flow equation, in the context of SWOT discharge algorithms. While this equation is in theory inapplicable to natural channels due to the non-uniform and spatially heterogeneous nature of river systems, we explored approaches to adapt it to this context using reach-averaged variables. At twenty sites along a 6.5 km stretch of the Olentangy River in Ohio, USA, we collected automated and manual measurements of water surface elevation and river width, undertook a full bathymetric survey of the study area, and built a hydraulic model. The stretch of river was divided into five reaches, and hydraulic variables were reach-averaged. Using these variables, we used a modified form of Manning's equation to compute a reach-averaged roughness coefficient. Reach-averaged roughness coefficients varied nonlinearly with discharge and were 2–10 times larger at low flow than at high flow in the in-situ data, ranging from 0.06 to 0.61 in one of the study reaches. These results were compared with the output of an unsteady flow simulation using a calibrated 1-D hydraulic model which was run with constant roughness coefficients at each cross section. When reach-averaged data was used, model-derived roughness coefficient also varied by more than an order of magnitude, with a range of 0.02–0.82 for one reach. For both in-situ and model-derived datasets, using a two-parameter roughness coefficient which scaled with a power law on either discharge or stage reduced discharge estimation error, with error for one reach dropping from 81% to 8% relative root-mean square error (rRMSE) in the in-situ data and 58% to 8% nRMSE in the modeled data. These results imply that spatial averaging of hydraulic variables leads to large variations in reach averaged Manning's n, which we term the reach's “effective resistance”, and suggest that this variability can be accounted for with a simple parameterization in estimates of discharge that use spatially averaged data

A High-Resolution Airborne Color-Infrared Camera Water Mask for the NASA ABoVE Campaign

The airborne AirSWOT instrument suite, consisting of an interferometric Ka-band synthetic aperture radar and color-infrared (CIR) camera, was deployed to northern North America in July and August 2017 as part of the NASA Arctic-Boreal Vulnerability Experiment (ABoVE). We present validated, open (i.e., vegetation-free) surface water masks produced from high-resolution (1 m), co-registered AirSWOT CIR imagery using a semi-automated, object-based water classification. The imagery and resulting high-resolution water masks are available as open-access datasets and support interpretation of AirSWOT radar and other coincident ABoVE image products, including LVIS, UAVSAR, AIRMOSS, AVIRIS-NG, and CFIS. These synergies offer promising potential for multi-sensor analysis of Arctic-Boreal surface water bodies. In total, 3167 km2 of open surface water were mapped from 23,380 km2 of flight lines spanning 23 degrees of latitude and broad environmental gradients. Detected water body sizes range from 0.00004 km2 (40 m2) to 15 km2. Power-law extrapolations are commonly used to estimate the abundance of small lakes from coarser resolution imagery, and our mapped water bodies followed power-law distributions, but only for water bodies greater than 0.34 (±0.13) km2 in area. For water bodies exceeding this size threshold, the coefficients of power-law fits vary for different Arctic-Boreal physiographic terrains (wetland, prairie pothole, lowland river valley, thermokarst, and Canadian Shield). Thus, direct mapping using high-resolution imagery remains the most accurate way to estimate the abundance of small surface water bodies. We conclude that empirical scaling relationships, useful for estimating total trace gas exchange and aquatic habitats on Arctic-Boreal landscapes, are uniquely enabled by high-resolution AirSWOT-like mappings and automated detection methods such as those developed here

Bouveret's syndrome complicated by distal gallstone ileus after laser lithotropsy using Holmium: YAG laser

BACKGROUND: Bouveret's syndrome is an unusual presentation of duodenal obstruction caused by the passage of a large gallstone through a cholecystoduodenal fistula. Endoscopic therapy has been used as first-line treatment, especially in patients with high surgical risk. CASE PRESENTATION: We report a 67-year-old woman who underwent an endoscopic attempt to fragment and retrieve a duodenal stone using a Holmium: Yttrium-Aluminum-Garnet Laser (Ho:YAG) which resulted in small bowel obstruction. The patient successfully underwent enterolithotomy without cholecystectomy or closure of the fistula. CONCLUSION: We conclude that, distal gallstone obstruction, due to migration of partially fragmented stones, can occur as a possible complication of laser lithotripsy treatment of Bouveret's syndrome and might require urgent enterolithotomy

A Participatory Science Approach to Expanding Instream Infrastructure Inventories

Over the past decade, remote sensing data have improved in resolution and become more widely available, bringing new opportunities for its use in environmental science and conservation. One potential application is to identify and map instream infrastructure across the world, with important implications for fisheries, hydrology, flooding, and more. To date, databases of instream infrastructure focus on larger dams with reservoirs that are comparatively easy to detect with remotely sensed imagery. Despite their impact on freshwater ecosystems, smaller infrastructure is often overlooked. To overcome these challenges, we require more systematic approaches, such as the Global River Obstruction Database (GROD) presented here, to map instream infrastructure. We present a participatory approach to identify, map, and validate infrastructure and provide an initial data set for the contiguous United States (n = 4,197). We highlight the value of participatory methods that include the public and suggest ways they could be fused with machine learning for future applications