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Abstract Assessing fertilized human embryos is crucial for in vitro fertilization, a task being revolutionized by artificial intelligence. Existing models used for embryo quality assessment and ploidy detection could be significantly improved by effectively utilizing time-lapse imaging to identify critical developmental time points for maximizing prediction accuracy. Addressing this, we develop and compare various embryo ploidy status prediction models across distinct embryo development stages. We present BELA, a state-of-the-art ploidy prediction model that surpasses previous image- and video-based models without necessitating input from embryologists. BELA uses multitask learning to predict quality scores that are thereafter used to predict ploidy status. By achieving an area under the receiver operating characteristic curve of 0.76 for discriminating between euploidy and aneuploidy embryos on the Weill Cornell dataset, BELA matches the performance of models trained on embryologists’ manual scores. While not a replacement for preimplantation genetic testing for aneuploidy, BELA exemplifies how such models can streamline the embryo evaluation process.

Abstract Background Rapamycin is an inhibitor of the mechanistic target of rapamycin (mTOR) protein kinase, and preclinical data demonstrate that it is a promising candidate for a general gero- and neuroprotective treatment in humans. Results from mouse models of Alzheimer’s disease have shown beneficial effects of rapamycin, including preventing or reversing cognitive deficits, reducing amyloid oligomers and tauopathies and normalizing synaptic plasticity and cerebral glucose uptake. The “Evaluating Rapamycin Treatment in Alzheimer’s Disease using Positron Emission Tomography” (ERAP) trial aims to test if these results translate to humans through evaluating the change in cerebral glucose uptake following six months of rapamycin treatment in participants with early-stage Alzheimer’s disease. Methods ERAP is a six-month-long, single-arm, open-label, phase IIa biomarker-driven study evaluating if the drug rapamycin can be repurposed to treat Alzheimer’s disease. Fifteen patients will be included and treated with a weekly dose of 7 mg rapamycin for six months. The primary endpoint will be change in cerebral glucose uptake, measured using [18F]FDG positron emission tomography. Secondary endpoints include changes in cognitive measures, markers in cerebrospinal fluid as well as cerebral blood flow measured using magnetic resonance imaging. As exploratory outcomes, the study will assess change in multiple age-related pathological processes, such as periodontal inflammation, retinal degeneration, bone mineral density loss, atherosclerosis and decreased cardiac function. Discussion The ERAP study is a clinical trial using in vivo imaging biomarkers to assess the repurposing of rapamycin for the treatment of Alzheimer’s disease. If successful, the study would provide a strong rationale for large-scale evaluation of mTOR-inhibitors as a potential disease-modifying treatment in Alzheimer’s disease. Trial registration ClinicalTrials.gov ID NCT06022068, date of registration 2023–08-30.

Pseudoscorpiones are compose an ancient order of arachnids, occur in a wide variety of terrestrial habitats worldwide, with representatives of various genera occurring exclusively in insular habitats. The primary objective of this study was to determine the composition and distribution of Pseudoscorpiones within the Brazilian equatorial oceanic islands. To determine Pseudoscorpiones communities and distribution in coastal environmental habitats of the Brazilian equatorial oceanic islands (Fernando de Noronha archipelago, Rocas Atoll and St. Peter and St. Paul rocks), was defined three zones along the insular environmental gradient in the Brazilian equatorial oceanic islands. These zones include the Sand Beach (SB) closest to the intertidal zone, the Slope Forest (SF) with a sloping terrain and the Top Forest (TF) farthest from the beach. Collecting points were distributed in each zones (SB, SF, and TF) at distances greater than 1 km, with four samples collected at each point approximately 12.5 m apart from each other. The TF zone is observed only in Fernando de Noronha. In our study we found pseudoscorpions exclusively on the islands of the Fernando de Noronha archipelago. We collected 5 species from the Hesperolpiidae and Syarinidae families. The SF habitats exhibited greater species richness, while the Upper Forest habitats showed greater population abundance. Notably, we recorded pseudoscorpions (Ideoblothrus amazonicus) in bird nests (Sula dactylatra) on Rata Island, suggesting the use of nests as habitat, reproduction, and, possibly, occasional transport to and from other habitats. No pseudoscorpions were found in SB environments. Landscape changes and tourism can threaten this incredible newly discovered community, vital for monitoring environmental changes in this delicate ecosystem.

Abstract Following the reaction of biological membranes to external stimuli reveals fundamental insights into cellular function. Here, self-assembled lipid monolayers act as model membranes containing photoswitchable azobenzene glycolipids for investigating structural response during isomerization by combining Langmuir isotherms with X-ray scattering. Controlled in-situ trans/cis photoswitching of the azobenzene N = N double bond alters the DPPC monolayer structure, causing reproducible changes in surface pressure and layer thickness, indicating monolayer reorientation. Interestingly, for monolayers containing azobenzene glycolipids, along with the expected DPPC phase transitions an additional discontinuity is observed. The associated reorintation represents a crossover point, with the surface pressure and layer thickness changing in opposite directions above and below. This is evidence that the azobenzene glycolipids themselves change orientation within the monolayer. Such behaviour suggests that azobenzene glycolipids can act as a bidirectional switch in DPPC monolayers providing a tool to investigate membrane structure–function relationships in depth.

Abstract. Two new species of terrestrial isopods are described from iron ore caves in Brazil, within the Amazon biome, Circoniscus mendesi López-Orozco, Campos-Filho & Bichuette sp. nov. and C. xikrin López-Orozco, Campos-Filho & Carpio-Díaz sp. nov. (Scleropactidae). In addition, the knowledge of the distribution of Ctenorillo ferrarai Campos-Filho, Araujo & Taiti, 2014 (Armadillidae) is extended to Parauapebas, and Benthanoides tarzan Cardoso & Ferreira, 2023 to south area of the Campos Ferruginosos National Park, both in the State of Pará. Moreover, a distribution map and photographs of the species are given.

The genus Spaeleoleptes was proposed by H. Soares in 1966 to accommodate the first Brazilian troglobitic species of harvestmen, Spaeleoleptes spaeleus H. Soares, 1966. In this work, we redescribe this species, including digital images of the type material and drawings of the male genitalia. Since its description, Spaeleoleptes has remained monotypic, and after 56 years, herein is described the second species of the genus, the troglobitic Spaeleoleptes gimli sp. nov. Both species share sexually dimorphic legs I and II with modified regions and swelling on the tibiae and patellae I and II; a penis with robust conductors covering all or part of the capsula interna and a capsula interna with two lateral projections. They are clearly separated by the shape of the modified region of the tibia; by the presence of an apical projection on the apical lamina of the pars distalis in S. spaeleus; and the lateral projections of the capsula interna, which is flattened in S. gimli. Spaeleoleptes gimli greatly increases the distributional range of the genus, as it is now recorded from caves located in two Brazilian phytophysiognomies from the Cerrado of Minas Gerais to the Caatinga of Bahia.

Abstract Carbon has been deposited on HCFeMn slag from methane-containing gas with and without CO2, creating C-MnO composites and giving a hydrogen-rich off-gas as a by-product. The maximum deposited amount corresponds to 38 ± 6% of the carbon required for reduction of all manganese in the slag to metallic Mn. This was achieved at 1100 °C with a H2-concentration in the off gas of 76%. Temperature was an important parameter. At 790 °C, no deposited carbon was detected, at temperatures ≥ 1000 °C, deposition increased with temperature. A lower gas-flow leads to more methane decomposition. Experiments with CO2 in the process gas gave less deposited carbon than other experiments. This could be caused by dilution of methane or chemical reactions involving CO2, or a combination. Investigations of fines formation indicate that the deposited carbon sticks well to the HCFeMn-slag, and would not fall off easily during transport and handling. This demonstrates that biogas can potentially be a non-fossil source of carbon in manganese production.

In Denmark, appropriate architecture for aging is an engaging topic, often explored through the use of architectural competitions. Since 2013, national guidelines for homelike architecture for eldercare have been in place, open for use in contemporaneous competitions. This study is focused on architectural competitions prior to 2013 and the development of modern architecture for aging. Based on reports on competitions in professional publications for architects, this study covers the period of 1899–2012. Inspired by the French philosopher Paul Ricoeur’s view of architecture as a spatial practice that ‘does not invoke what no longer is there but what has become through what is no longer present’, the present study revisits competitions on architecture for aging in search of inspirational input and links to the national socio-political discussion. This study uses case study methodology with a mixed method approach. A total of 76 competitions are identified, mainly organized by Danish municipalities, and are linked to four paradigms in social legislations. It is concluded that early competitions defined spatial prototypes, both for the homelike setting and the institutional environment, which have been continuously revisited. Since 2008, homelikeness has become the main design criterion for architecture for the frail aging population with an increasing dependency on caregiving.

Growth at liquid-liquid interfaces differ inherently from that on solids, making it attractive for nanomaterial formation. Here, the authors use X-ray scattering to derive a detailed microscopic picture of lead-halide growth on liquid mercury that reveals the key importance of anion adsorption.

Two new species of Pectenoniscus from two caves in karst areas of the Brazilian semiarid region are described. Pectenoniscus pankaru Campos-Filho, Torres & Bichuette, sp. nov. from Gruna do Govi cave, Serra do Ramalho karst area, state of Bahia, and Pectenoniscus fervens Campos-Filho, Taiti & Bichuette, sp. nov. from Toca Coroa do Frade cave, Barra Bonita karst area, state of Piauí. In addition, specimens of Cylindroniscus flaviae from Gruta da Tapagem (= Caverna do Diabo), Açungui karst area were also recorded. An updated diagnosis of Pectenoniscus and a distribution map of the species examined herein are given.

Two new troglobitic species of Xangoniscus are described from two caves of Serra do Ramalho karst area, Bambuí geomorphological group, state of Bahia. Xangoniscus lapaensis sp. nov. is described from Gruna Boca da Lapa cave, and X. loboi sp. nov. from Gruna da Pingueira II cave. Both species are blind and depigmented and show amphibious habits, as observed for all species of Xangoniscus described until now. Xangoniscus lapaensis sp. nov. occurs in travertine pools fed by water of the upper aquifer, and X. loboi sp. nov. occurs in a small stream, an upper vadose tributary. Both species occur in fragile microhabitats. Ecological and behavioral data, conservation remarks, and IUCN conservation assessments are included to provide background data for conservation efforts in this unique karst area.

Background Serotonergic brain signaling is considered critical for an appropriate and dynamic adaptation to stress, seemingly through modulating limbic system functions, such as the hypothalamic-pituitary-adrenal (HPA)-axis. This interplay is of great interest since it holds promise as a target for preventing stress-related brain disorders, e.g., major depression. Our group has previously observed that prefrontal serotonin transporter (5-HTT) binding, imaged with positron emission tomography (PET), is positively associated with the cortisol awakening response (CAR), an index of HPA axis stress hormone dynamics. The aim of this cross-sectional study was to replicate the previous finding in a larger independent group of healthy individuals. Methods Molecular imaging and cortisol data were available for 90 healthy individuals. Prefrontal 5-HTT binding was imaged with [11C]DASB brain PET. Non-displaceable 5-HTT binding potential (BPND) was quantified using the Multilinear Reference Tissue Model 2 (MRTM2) with cerebellum as the reference region. CAR was based on five serial salivary cortisol samples within the first hour upon awakening. The association between CAR and prefrontal 5-HTT BPND was evaluated using a multiple linear regression model adjusted for age and sex. Further, we tested for sex differences in the association. Finally, an exploratory analysis of the association, was performed in 8 additional brain regions. Results We observed no statistically significant association between 5-HTT binding and CAR corrected for age and sex in the prefrontal cortex (β = -0.28, p = 0.26). We saw no interaction with sex on the association (p = 0.99). Conclusion We could not confirm a positive association between CAR and prefrontal 5-HTT BPND in this independent dataset. Also, sex differences in the association were not apparent. Our data do not exclude that the serotonin transporter system is involved in the regulation of stress responses in at-risk or manifest depressed states.

We present a molecular phylogenetic analysis including a survey for overlooked phenotypic characters. Based on both analysis and characters a new cave-dwelling species is described: Tityus (Tityus) spelaeus sp. nov. from the Russão II cave, Posse, state of Goiás, Central Brazil. Characters such as the glandular regions of the female pectinal basal piece and basal middle lamellae of pectines, and the distribution of the ventral setae of telotarsi I–IV proved to be useful to constructing the taxonomy of species and species groups of Tityus. The new species is a member of the Tityus trivittatus species-group of Tityus (Tityus) and can be readily recognized by the immaculate coloration pattern and the more developed glandular region on the female pectinal basal piece. In addition, we provide a discussion of the phylogenetic relationships observed within Tityus, on the relevance of the new phenotypic characters to the modern taxonomy of the genus Tityus, and to the records of Brazilian cave scorpions.

Purpose: To collect information on sociodemographic factors, health indicators, and lifestyle factors in women who attended the nationwide breast cancer-screening program, BreastScreen Norway, with the aim of investigating how these factors influence the risk of breast cancer, other cancer types, and cancer-related outcomes. Participants: The cohort data includes self-reported responses to questionnaires from 554,149 women aged 50-69 years, who attended BreastScreen Norway during the data collection period, 2006-2016. Findings to date: Information about sociodemographic factors, health indicators, and lifestyle factors was collected for the current time and retrospectively back to birth. For the cohort, we have complete mammographic screening data, including information about 24,000 breast cancer cases and other cancer types from the Cancer Registry of Norway. These outcomes are aggregating continuously. Data from the cohort have been utilized in studies related to breast cancer and menopausal status. Future projects: Data will be utilized in studies related to tumour growth and risk of breast cancer as well as other cancer types, in addition to overall and cancer-specific death. Registration: The cohort profile is not registered in Clinical Trials.

Abstract Molecular imaging studies have shown low cerebral concentration of serotonin transporter in patients suffering from depression, compared to healthy control subjects. Whether or not this difference also is present before disease onset and after remission (i.e. a trait), or only at the time of the depressive episode (i.e. a state) remains to be explored. We examined 17 patients with major depressive disorder with positron emission tomography using [11C]MADAM, a radioligand that binds to the serotonin transporter, before and after treatment with internet-based cognitive behavioral therapy. In all, 17 matched healthy control subjects were examined once. Cerebellum was used as reference to calculate the binding potential. Differences before and after treatment, as well as between patients and controls, were assessed in a composite cerebral region and in the median raphe nuclei. All image analyses and confirmatory statistical tests were preregistered. Depression severity decreased following treatment (p

Four new species of recluse spiders from Brazilian caves are described with both males and females. Loxosceles ericsoni Bertani, von Schimonsky & Gallão, sp. n. and L. karstica Bertani, von Schimonsky & Gallão, sp. n. both occur in caves in the Peruaçu region, located in the northern area of the state of Minas Gerais; L. karstica sp. n. is additionally found in the Serra do Ramalho karst area, located in the southwestern region of the state of Bahia. These two species belong to the gaucho group. Loxosceles carinhanha Bertani, von Schimonsky & Gallão, sp. n. and L. cardosoi Bertani, von Schimonsky & Gallão, sp. n. occur exclusively in caves of the Serra do Ramalho karst area and belong to the rufescens/amazonica species group. The discovery of two additional and highly distinct species in the rufescens/amazonica group (L. carinhanha sp. n. and L. cardosoi sp. n.) increases the debate on the origin, evolution, and geographical distribution of this widely distributed group of recluse spiders in the New and Old World. The presence of three species (L. ericsoni sp. n., L. carinhanha sp. n., and L. cardosoi sp. n.) with marked differences in morphological characters in a relatively small area indicates that the region seems to be an important center for Loxosceles diversity, which remains poorly studied.

Dopamine D2 receptors (D2-R) in extrastriatal brain regions are of high interest for research in a wide range of psychiatric and neurologic disorders. Pharmacological competition studies and test–retest experiments have shown high validity and reliability of the positron emission tomography (PET) radioligand [11C]FLB 457 for D2-R quantification in extrastriatal brain regions. However, this radioligand is not available at most research centers. Instead, the medium affinity radioligand [11C]raclopride, which has been extensively validated for quantification of D2-R in the high-density region striatum, has been applied also in studies on extrastriatal D2-R. Recently, the validity of this approach has been questioned by observations of low occupancy of [11C]raclopride in extrastriatal regions in a pharmacological competition study with quetiapine. Here, we utilise a data set of 16 healthy control subjects examined with both [11C]raclopride and [11C]FLB 457 to assess the correlation in binding potential (BPND) in extrastriatal brain regions. BPND was quantified using the simplified reference tissue model with cerebellum as reference region. The rank order of mean regional BPND values were similar for both radioligands, and corresponded to previously reported data, both post-mortem and using PET. Nevertheless, weak to moderate within-subject correlations were observed between [11C]raclopride and [11C]FLB 457 BPND extrastriatally (Pearson's R: 0.30–0.56), in contrast to very strong correlations between repeated [11C]FLB 457 measurements (Pearson's R: 0.82–0.98). In comparison, correlations between repeated [11C]raclopride measurements were low to moderate (Pearson's R: 0.28–0.75). These results are likely related to low signal to noise ratio of [11C]raclopride in extrastriatal brain regions, and further strengthen the recommendation that extrastriatal D2-R measures obtained with [11C]raclopride should be interpreted with caution.

Abstract Background Secondary peritonitis is a condition associated with high morbidity and mortality. Continuous postoperative monitoring of patients to ensure timely intervention to treat complications without delay is important for survival and outcome. We aimed to (1) investigate potential differences in postoperative intraperitoneal biomarker levels between patients with upper and lower gastrointestinal tract lesion, and (2) compare postoperative biomarker levels between complicated and uncomplicated patients. Methods We included a total of 15 consecutive patients operated for upper (n = 7) and lower (n = 8) gastrointestinal tract perforation. We registered postoperative complications during a 30 days follow up-period. Complications were defined as intraabdominal complications, septic shock, and mortality. 5 patients were complicated. A microdialysis catheter was placed intraperitoneally in each patient. Samples were collected every 4th hour for up to 7 postoperative days. Samples were analysed for concentrations of glucose, lactate, pyruvate and glycerol. Results Microdialysis results showed that patients with upper gastrointestinal tract lesions had significantly higher levels of postoperative intraperitoneal glucose and glycerol concentrations, as well as lower lactate/pyruvate ratios and lactate/glucose ratios. In the group with perforation of the lower gastrointestinal tract, those patients with a complicated course showed lower levels of postoperative intraperitoneal glucose concentration and glycerol concentration and higher lactate/pyruvate ratios and lactate/glucose ratios than those patients with an uncomplicated course. Conclusion Patients with upper and lower gastrointestinal tract lesions showed differences in postoperative biomarker levels. A difference was also seen between patients with complicated and uncomplicated postoperative courses.

Pneumonia remains the single leading cause of childhood death worldwide. Despite the commercial availability of multiple pneumococcal conjugate vaccines (PCVs), high dosage cost and supply shortages prevent PCV delivery to much of the developing world. The current work presents high-yield pneumococcal conjugates that are immunogenic in animals and suitable for use in human vaccine development. The 13-valent pneumococcal conjugate vaccine (PCV-13) investigated in this research incorporated serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F. Pneumococcal polysaccharides (PnPSs) and CRM197 carrier protein were produced and purified in-house, and used to prepare PnPS-CRM conjugates using unique, cyanide-free, in vacuo glycation conjugation methods. In vitro characterization confirmed the generation of higher molecular weight PnPS-CRM conjugates low in free protein. In vivo animal studies were performed to compare PnuVax's PCV-13 to the commercially available PCV-13, Prevnar®13 (Pfizer, USA). A boost dose was provided to all groups post-dose 1 at t = 14 days. Post-dose 2 results at t = 28 days showed that all 13 serotypes in PnuVax's PCV-13 were boostable. Per serotype IgG GMCs demonstrated that PnuVax's PCV-13 is immunogenic for all 13 serotypes, with 10 of the 13 serotypes statistically the same or higher than Prevnar®13 post-dose 2. As a result, the novel polysaccharide-protein conjugates developed in this work are highly promising for use in human PCV development. The in vacuo conjugation technique applied in this work could also be readily adapted to develop many other conjugate vaccines.

In this paper, we aim to provide optimal parameters for micro-computed tomography scans of fish otoliths. We tested fifteen different combinations to sagittae. The images were scaled to Hounsfield units, and segmented in two distinct volumes-of-interest (external and internal). The strategy we applied, for identifying optimum scan settings for otoliths, included analyses of the sinogram, the distribution of the Hounsfield units and the signal-to-noise ratio. Based on these tests, the optimum sets of parameters for the acquisition of tomographic images of sagittal otoilths were 80 kV, 220 μA, and 0.5 mm aluminum filter. The method allowed 3D shape analysis, internal and external density distribution, layer-by-layer density segmentation, and a potential objective method to count growth rings in otoliths. It was possible to compare mean densities between species, and we observed a significant difference among them. In addition, there are ontogenic changes, which could be increasing or decreasing the density. In this study, we applied tomography for several otolith analysis, that could be of great interest for future studies in diverse areas that use otoliths as the basic structure of analysis, or represents a new research line called eco-densitometry of otoliths, where tomography could be applied to explore the density within an ecological perspective.

In this paper, beam diagnostic and monitoring tools developed by the MAX IV Operations Group are discussed. In particular, beam position monitoring and accelerator tunes visualization software tools, as well as tools that directly influence the beam quality and stability, are introduced. An availability and downtime monitoring application is also presented.

Crop species separation is essential for a wide range of agricultural applications—in particular, when seasonal information is needed. In general, remote sensing can provide such information with high accuracy, but in small structured agricultural areas, very high spatial resolution data (VHR) are required. We present a study involving spectral and textural features derived from near-infrared (NIR) Red Green Blue (NIR-RGB) band datasets, acquired using an unmanned aerial vehicle (UAV), and an imaging spectroscopy (IS) dataset acquired by the Airborne Prism EXperiment (APEX). Both the single usage and combination of these datasets were analyzed using a random forest-based method for crop separability. In addition, different band reduction methods based on feature factor loading were analyzed. The most accurate crop separation results were achieved using both the IS dataset and the two combined datasets with an average accuracy (AA) of >92%. In addition, we conclude that, in the case of a reduced number of IS features (i.e., wavelengths), the accuracy can be compensated by using additional NIR-RGB texture features (AA > 90%).

Subterranean environments, even though they do not possess a primary production (photosynthesis), may present high biodiversity, faunistic originality, endemism, phylogenetic isolations and unique ecological and/or evolution events, in addition to rare taxa. Studies investigating the biological diversity in Neotropical caves are relatively rare and recent, and most of them have been conducted in Brazil. We sampled caves from the state of Bahia, northeastern Brazil, and through sampling sufficiency tests and richness estimators, we demonstrate that the normatization for the Brazilian cave laws is not adequate for its conservation and that only α diversity index is not enough to verify faunistic patterns. We suggest that a phylogenetic diversity index be more robust and accurate for conservation purposes, particularly the Taxonomic Distinctness index. Moreover, we propose that the sandstone complex caves from Chapada Diamantina National Park need to be classified as being of high subterranean biodiversity in a global scope.

We propose an approach for Bayesian inference in time-varying structural vector autoregressions (SVARs) identified with sign restrictions. The linchpin of our approach is a class of rotation-invariant time-varying SVARs in which the prior and posterior densities of any sequence of structural parameters belonging to the class are invariant to orthogonal transformations of the sequence. Our methodology is new to the literature. In contrast to existing algorithms for inference based on sign restrictions, our algorithm is the first to draw from a uniform distribution over the sequences of orthogonal matrices given the reduced-form parameters. We illustrate our procedure for inference by analyzing the role played by monetary policy during the latest inflation surge. JEL classification: C11, C51, E52, E58 Key words: time-varying parameters, structural vector autoregressions, identification, 1 Introduction Structural vector autoregressions (SVARs) featuring time-varying parameters are commonly used in empirical macroeconomics to study a wide range of classical questions such as the economic consequences of policy [...]

The separation of crop types is essential for many agricultural applications, particularly when within-season information is required. Generally, remote sensing may provide timely information with varying accuracy over the growing season, but in small structured agricultural areas, a very high spatial resolution may be needed that exceeds current satellite capabilities. This paper presents an experiment using spectral and textural features of NIR-red-green-blue (NIR-RGB) bands data sets acquired with an unmanned aerial vehicle (UAV). The study area is located in the Swiss Plateau, which has highly fragmented and small structured agricultural fields. The observations took place between May 5 and September 29, 2015 over 11 days. The analyses are based on a random forest (RF) approach, predicting crop separation metrics of all analyzed crops. Three temporal windows of observations based on accumulated growing degree days (AGDD) were identified: an early temporal window (515−1232 AGDD, 5 May−17 June 2015) with an average accuracy (AA) of 70−75%; a mid-season window (1362−2016 AGDD, 25 June−22 July 2015) with an AA of around 80%; and a late window (2626−3238 AGDD, 21 August−29 September 2015) with an AA of

APETx2 is a peptide isolated from the sea anemone Anthopleura elegantissima. It is the most potent and selective inhibitor of acid-sensing ion channel 3 (ASIC3) and it is currently in preclinical studies as a novel analgesic for the treatment of chronic inflammatory pain. As a peptide it faces many challenges in the drug development process, including the potential lack of stability often associated with therapeutic peptides. In this study we determined the susceptibility of wild-type APETx2 to trypsin and pepsin and tested the applicability of backbone cyclisation as a strategy to improve its resistance to enzymatic degradation. Cyclisation with either a six-, seven- or eight-residue linker vastly improved the protease resistance of APETx2 but substantially decreased its potency against ASIC3. This suggests that either the N- or C-terminus of APETx2 is involved in its interaction with the channel, which we confirmed by making N- and C-terminal truncations. Truncation of either terminus, but especially the N-terminus, has detrimental effects on the ability of APETx2 to inhibit ASIC3. The current work indicates that cyclisation is unlikely to be a suitable strategy for stabilising APETx2, unless linkers can be engineered that do not interfere with binding to ASIC3.

Spiders are the most successful venomous animals and the most abundant terrestrial predators. Their remarkable success is due in large part to their ingenious exploitation of silk and the evolution of pharmacologically complex venoms that ensure rapid subjugation of prey. Most spider venoms are dominated by disulfide-rich peptides that typically have high affinity and specificity for particular subtypes of ion channels and receptors. Spider venoms are conservatively predicted to contain more than 10 million bioactive peptides, making them a valuable resource for drug discovery. Here we review the structure and pharmacology of spider-venom peptides that are being used as leads for the development of therapeutics against a wide range of pathophysiological conditions including cardiovascular disorders, chronic pain, inflammation, and erectile dysfunction.

Land cover maps are indispensable for decision making, monitoring, and management in agricultural areas, but they are often only available after harvesting. To obtain a timely crop map of a small-scale arable landscape in the Swiss Plateau, we acquired uncalibrated, very high-resolution data, with a spatial resolution of 0.05 m and four spectral bands, using a consumer-grade camera on an unmanned aerial vehicle (UAV) in June 2015. We resampled the data to different spatial and spectral resolutions, and evaluated the method using textural features (first order statistics and mathematical morphology), a random forest classifier for best performance, as well as number and size of the structuring elements. Our main findings suggest the overall best performing data consisting of a spatial resolution of 0.5 m, three spectral bands (RGB—red, green, and blue), and five different sizes of the structuring elements. The overall accuracy (OA) for the full set of crop classes based on a pixel-based classification is 66.7%. In case of a merged set of crops, the OA increases by ~7% (74.0%). For an object-based classification based on individual field parcels, the OA increases by ~20% (OA of 86.3% for the full set of crop classes, and 94.6% for the merged set, respectively). We conclude the use of UAV to be most relevant at 0.5 m spatial resolution in heterogeneous arable landscapes when used for crop classification.