The bearing capacity of asteroid (65803) Didymos estimated from boulder tracks.

The bearing capacity - the ability of a surface to support applied loads - is an important parameter for understanding and predicting the response of a surface. Previous work has inferred the bearing capacity and trafficability of specific regions of the Moon using orbital imagery and measurements of the boulder tracks visible on its surface. Here, we estimate the bearing capacity of the surface of an asteroid for the first time using DART/DRACO images of suspected boulder tracks on the surface of asteroid (65803) Didymos. Given the extremely low surface gravity environment, special attention is paid to the underlying assumptions of the geotechnical approach. The detailed analysis of the boulder tracks indicates that the boulders move from high to low gravitational potential, and provides constraints on whether the boulders may have ended their surface motion by entering a ballistic phase. From the 9 tracks identified with sufficient resolution to estimate their dimensions, we find an average boulder track width and length of 8.9 ± 1.5 m and 51.6 ± 13.3 m, respectively. From the track widths, the mean bearing capacity of Didymos is estimated to be 70 N/m2, implying that every 1 m2 of Didymos' surface at the track location can support only ~70 N of force before experiencing general shear failure. This value is at least 3 orders of magnitude less than the bearing capacity of dry sand on Earth, or lunar regolith.

Evidence for multi-fragmentation and mass shedding of boulders on rubble-pile binary asteroid system (65803) Didymos.

Asteroids smaller than 10 km are thought to be rubble piles formed from the reaccumulation of fragments produced in the catastrophic disruption of parent bodies. Ground-based observations reveal that some of these asteroids are today binary systems, in which a smaller secondary orbits a larger primary asteroid. However, how these asteroids became binary systems remains unclear. Here, we report the analysis of boulders on the surface of the stony asteroid (65803) Didymos and its moonlet, Dimorphos, from data collected by the NASA DART mission. The size-frequency distribution of boulders larger than 5 m on Dimorphos and larger than 22.8 m on Didymos confirms that both asteroids are piles of fragments produced in the catastrophic disruption of their progenitors. Dimorphos boulders smaller than 5 m have size best-fit by a Weibull distribution, which we attribute to a multi-phase fragmentation process either occurring during coalescence or during surface evolution. The density per km2 of Dimorphos boulders ≥1 m is 2.3x with respect to the one obtained for (101955) Bennu, while it is 3.0x with respect to (162173) Ryugu. Such values increase once Dimorphos boulders ≥5 m are compared with Bennu (3.5x), Ryugu (3.9x) and (25143) Itokawa (5.1x). This is of interest in the context of asteroid studies because it means that contrarily to the single bodies visited so far, binary systems might be affected by subsequential fragmentation processes that largely increase their block density per km2. Direct comparison between the surface distribution and shapes of the boulders on Didymos and Dimorphos suggest that the latter inherited its material from the former. This finding supports the hypothesis that some asteroid binary systems form through the spin up and mass shedding of a fraction of the primary asteroid.

Fast boulder fracturing by thermal fatigue detected on stony asteroids.

Spacecraft observations revealed that rocks on carbonaceous asteroids, which constitute the most numerous class by composition, can develop millimeter-to-meter-scale fractures due to thermal stresses. However, signatures of this process on the second-most populous group of asteroids, the S-complex, have been poorly constrained. Here, we report observations of boulders' fractures on Dimorphos, which is the moonlet of the S-complex asteroid (65803) Didymos, the target of NASA's Double Asteroid Redirection Test (DART) planetary defense mission. We show that the size-frequency distribution and orientation of the mapped fractures are consistent with formation through thermal fatigue. The fractures' preferential orientation supports that these have originated in situ on Dimorphos boulders and not on Didymos boulders later transferred to Dimorphos. Based on our model of the fracture propagation, we propose that thermal fatigue on rocks exposed on the surface of S-type asteroids can form shallow, horizontally propagating fractures in much shorter timescales (100 kyr) than in the direction normal to the boulder surface (order of Myrs). The presence of boulder fields affected by thermal fracturing on near-Earth asteroid surfaces may contribute to an enhancement in the ejected mass and momentum from kinetic impactors when deflecting asteroids.

Value of D-Dimer in Risk Stratification for Thromboembolism in Patients With Atrial Fibrillation and Low CHA2DS2-VASc Score.

Atrial fibrillation (AF) can cause thrombi formation and subsequent emboli deposition in systemic arteries, leading to various organ ischemia and infarction. Anticoagulation therapy can reduce the risk of thrombus formation and embolization, and is initiated based on a patient's risk score, which is frequently estimated with the CHA2DS2-VASc score. We present a case of thromboembolism (TE) where a low CHA2DS2-VASc score suggested a low-moderate risk of systemic embolization, but an elevated plasma D-dimer value prompted further investigation which revealed an intracardiac thrombus with renal embolism. The patient is a 63-year-old male with past medical history of hypertension and AF treated with ablation 2 years prior presenting with sharp right flank pain of 5-hour duration. Primary workup and imaging were unrevealing at the time, and a low CHA2DS2-VASc score was suggestive of aspirin therapy. However, an elevated D-dimer of 289 ng/mL and a transient increase in creatinine pointed to possible etiology of embolic origin. The diagnosis was confirmed with computed tomography (CT) with contrast and transesophageal echocardiogram, revealing renal infarcts and the source of the emboli, respectively. The patient was treated with heparin and transitioned to apixaban prior to discharge with full resolution of symptoms. Through this case, we wish to show D-dimer's predictive value of TE, as well as its potential benefit in risk assessment in patients with AF.

Useful indices of thrombogenesis in the exclusion of intra-cardiac thrombus.

BACKGROUND: Cardioversion in patients with atrial fibrillation (AF) can cause cardioembolic stroke, and effective clinical management is necessary to reduce morbidity and mortality. Currently, transesophageal echocardiography (TEE) is the accepted standard to diagnose cardiogenic thromboemboli; however, a negative TEE does not eliminate the possibility of left atrial thrombus. The objective of this study was to evaluate the diagnostic value of supplementing the TEE with additional noninvasive markers to ensure thrombus absence. METHODS: A prospective study was conducted on 59 patients who underwent TEE for suspected intra-cardiac thrombi. The TEE indications included acute ischemic stroke (45.7%) and AF or flutter (59.3%). D-dimer level and white blood cell counts were assessed. RESULTS: A negative D-dimer level (<200 ng/mL) excluded the presence of intra-cardiac thrombi. Groups with either negative (n = 14) or positive (n = 45) D-dimer levels had comparable clinical characteristics. Comparing positive D-dimer-level patients with thrombus (n = 7) and without thrombus (n = 33), patients with thrombus had reduced left atrial appendage (LAA) velocity (P = .0024), reduced left ventricular ejection fraction (LVEF) (P = .0263), increased neutrophil percent (P = .0261), decreased lymphocyte percent (P = .0216), and increased monocyte counts (P = .0220). The area under the receiver operating characteristic (ROC) curve for thrombus diagnostics was larger for combinations of clinical and biochemical data than for each parameter individually. CONCLUSIONS: Supplementing the gold standard TEE with the analysis of LAA velocity, noninvasive LVEF, D-dimer, and hemostatic markers provided additional useful diagnostic information. Larger studies are needed to further validate the efficacy of supplementing the TEE to better assess patients for intra-cardiac thrombi.

Images from the surface of asteroid Ryugu show rocks similar to carbonaceous chondrite meteorites.

The near-Earth asteroid (162173) Ryugu is a 900-m-diameter dark object expected to contain primordial material from the solar nebula. The Mobile Asteroid Surface Scout (MASCOT) landed on Ryugu's surface on 3 October 2018. We present images from the MASCOT camera (MASCam) taken during the descent and while on the surface. The surface is covered by decimeter- to meter-sized rocks, with no deposits of fine-grained material. Rocks appear either bright, with smooth faces and sharp edges, or dark, with a cauliflower-like, crumbly surface. Close-up images of a rock of the latter type reveal a dark matrix with small, bright, spectrally different inclusions, implying that it did not experience extensive aqueous alteration. The inclusions appear similar to those in carbonaceous chondrite meteorites.

Mapping autosomal recessive intellectual disability: combined microarray and exome sequencing identifies 26 novel candidate genes in 192 consanguineous families.

Approximately 1% of the global population is affected by intellectual disability (ID), and the majority receive no molecular diagnosis. Previous studies have indicated high levels of genetic heterogeneity, with estimates of more than 2500 autosomal ID genes, the majority of which are autosomal recessive (AR). Here, we combined microarray genotyping, homozygosity-by-descent (HBD) mapping, copy number variation (CNV) analysis, and whole exome sequencing (WES) to identify disease genes/mutations in 192 multiplex Pakistani and Iranian consanguineous families with non-syndromic ID. We identified definite or candidate mutations (or CNVs) in 51% of families in 72 different genes, including 26 not previously reported for ARID. The new ARID genes include nine with loss-of-function mutations (ABI2, MAPK8, MPDZ, PIDD1, SLAIN1, TBC1D23, TRAPPC6B, UBA7 and USP44), and missense mutations include the first reports of variants in BDNF or TET1 associated with ID. The genes identified also showed overlap with de novo gene sets for other neuropsychiatric disorders. Transcriptional studies showed prominent expression in the prenatal brain. The high yield of AR mutations for ID indicated that this approach has excellent clinical potential and should inform clinical diagnostics, including clinical whole exome and genome sequencing, for populations in which consanguinity is common. As with other AR disorders, the relevance will also apply to outbred populations.

Ptchd1 deficiency induces excitatory synaptic and cognitive dysfunctions in mouse.

Synapse development and neuronal activity represent fundamental processes for the establishment of cognitive function. Structural organization as well as signalling pathways from receptor stimulation to gene expression regulation are mediated by synaptic activity and misregulated in neurodevelopmental disorders such as autism spectrum disorder (ASD) and intellectual disability (ID). Deleterious mutations in the PTCHD1 (Patched domain containing 1) gene have been described in male patients with X-linked ID and/or ASD. The structure of PTCHD1 protein is similar to the Patched (PTCH1) receptor; however, the cellular mechanisms and pathways associated with PTCHD1 in the developing brain are poorly determined. Here we show that PTCHD1 displays a C-terminal PDZ-binding motif that binds to the postsynaptic proteins PSD95 and SAP102. We also report that PTCHD1 is unable to rescue the canonical sonic hedgehog (SHH) pathway in cells depleted of PTCH1, suggesting that both proteins are involved in distinct cellular signalling pathways. We find that Ptchd1 deficiency in male mice (Ptchd1-/y) induces global changes in synaptic gene expression, affects the expression of the immediate-early expression genes Egr1 and Npas4 and finally impairs excitatory synaptic structure and neuronal excitatory activity in the hippocampus, leading to cognitive dysfunction, motor disabilities and hyperactivity. Thus our results support that PTCHD1 deficiency induces a neurodevelopmental disorder causing excitatory synaptic dysfunction.

Surface changes on comet 67P/Churyumov-Gerasimenko suggest a more active past.

The Rosetta spacecraft spent ~2 years orbiting comet 67P/Churyumov-Gerasimenko, most of it at distances that allowed surface characterization and monitoring at submeter scales. From December 2014 to June 2016, numerous localized changes were observed, which we attribute to cometary-specific weathering, erosion, and transient events driven by exposure to sunlight and other processes. While the localized changes suggest compositional or physical heterogeneity, their scale has not resulted in substantial alterations to the comet's landscape. This suggests that most of the major landforms were created early in the comet's current orbital configuration. They may even date from earlier if the comet had a larger volatile inventory, particularly of CO or CO2 ices, or contained amorphous ice, which could have triggered activity at greater distances from the Sun.

Biallelic truncating SCN9A mutation identified in four families with congenital insensitivity to pain from Pakistan.

(a) Homozygosity-mapping-by-descent of four Bhakkar congenital indifference/insensitivity to pain (CIP) families. (b) Identification of mutation Met1190* in SCN9A. (c) SCN9A/NaV1.7 2D structure (as predicted by CCTOP and SMART) and approximate position of known nonsense (*) and missense (M) mutations ( www.hgmd.cf.ac.uk), as well as the Bhakkar mutation (this study) in red.

Host associations and beta diversity of fungal endophyte communities in New Guinea rainforest trees.

Processes shaping the distribution of foliar fungal endophyte species remain poorly understood. Despite increasing evidence that these cryptic fungal symbionts of plants mediate interactions with pathogens and herbivores, there remain basic questions regarding the extent to which dispersal limitation and host specificity might shape fungal endophyte community composition in rainforests. To assess the relative importance of spatial pattern and host specificity, we isolated fungi from a sample of mapped trees in lowland Papua New Guinea. Sequences of the internal transcribed spacer (ITS) region were obtained for 2079 fungal endophytes from three sites and clustered into molecular operational taxonomic units (MOTUs) at 95% similarity. Multivariate analyses suggest that host affinity plays a significant role in structuring endophyte community composition whereas there was no evidence of endophyte spatial pattern at the scale of tens to hundreds of metres. Differences in endophyte communities between sampled trees were weakly correlated with variation in foliar traits but not with tree species relatedness. The dominance of relatively few generalist endophytes and the presence of a large number of rare MOTUs was a consistent observation at three sites separated by hundreds of kilometres and regional turnover was low. Host specificity appears to play a relatively weak but more important role than dispersal limitation in shaping the distribution of fungal endophyte communities in New Guinea forests. Our results suggest that in the absence of strong ecological gradients and host turnover, beta diversity of endophyte communities could be low in large areas of contiguous forest.

Sublimation in bright spots on (1) Ceres.

The dwarf planet (1) Ceres, the largest object in the main asteroid belt with a mean diameter of about 950 kilometres, is located at a mean distance from the Sun of about 2.8 astronomical units (one astronomical unit is the Earth-Sun distance). Thermal evolution models suggest that it is a differentiated body with potential geological activity. Unlike on the icy satellites of Jupiter and Saturn, where tidal forces are responsible for spewing briny water into space, no tidal forces are acting on Ceres. In the absence of such forces, most objects in the main asteroid belt are expected to be geologically inert. The recent discovery of water vapour absorption near Ceres and previous detection of bound water and OH near and on Ceres (refs 5-7) have raised interest in the possible presence of surface ice. Here we report the presence of localized bright areas on Ceres from an orbiting imager. These unusual areas are consistent with hydrated magnesium sulfates mixed with dark background material, although other compositions are possible. Of particular interest is a bright pit on the floor of crater Occator that exhibits probable sublimation of water ice, producing haze clouds inside the crater that appear and disappear with a diurnal rhythm. Slow-moving condensed-ice or dust particles may explain this haze. We conclude that Ceres must have accreted material from beyond the 'snow line', which is the distance from the Sun at which water molecules condense.

Phenotypic spectrum associated with PTCHD1 deletions and truncating mutations includes intellectual disability and autism spectrum disorder.

Studies of genomic copy number variants (CNVs) have identified genes associated with autism spectrum disorder (ASD) and intellectual disability (ID) such as NRXN1, SHANK2, SHANK3 and PTCHD1. Deletions have been reported in PTCHD1 however there has been little information available regarding the clinical presentation of these individuals. Herein we present 23 individuals with PTCHD1 deletions or truncating mutations with detailed phenotypic descriptions. The results suggest that individuals with disruption of the PTCHD1 coding region may have subtle dysmorphic features including a long face, prominent forehead, puffy eyelids and a thin upper lip. They do not have a consistent pattern of associated congenital anomalies or growth abnormalities. They have mild to moderate global developmental delay, variable degrees of ID, and many have prominent behavioral issues. Over 40% of subjects have ASD or ASD-like behaviors. The only consistent neurological findings in our cohort are orofacial hypotonia and mild motor incoordination. Our findings suggest that hemizygous PTCHD1 loss of function causes an X-linked neurodevelopmental disorder with a strong propensity to autistic behaviors. Detailed neuropsychological studies are required to better define the cognitive and behavioral phenotype.

Can α-lipoic acid mitigate progression of aging-related decline caused by oxidative stress?

Aging is progressively deteriorating physiological function that leads to increasing risks of illness and death. Increases in life expectancy and the aging of a large segment of the population have made age-related disability and morbidity increasingly important issues. Supplements such as α-lipoic acid may have antiaging effects by positively affecting oxidative stress, cognitive function, and cardiovascular function.

Brain natriuretic hormone predicts stress-induced alterations in diastolic function.

BACKGROUND: Mental stress (MS) reduces diastolic function (DF) and may lead to congestive heart failure with preserved systolic function. Whether brain natriuretic hormone (brain natriuretic peptide [BNP]) mediates the relationship of MS with DF is unknown. METHODS: One hundred sixty individuals aged 30 to 50 years underwent 2-hour protocol of 40-minute rest, videogame stressor and recovery. Hemodynamics, pro-BNP samples and DF indices were obtained throughout the protocol. Separate regression analyses were conducted using rest and stress E/A, E' and E/E' as dependent variables. Predictor variables were entered into the stepwise regression models in a hierarchical fashion. At the first level, age, sex, race, height, body mass index, pro-BNP and left ventricular mass (LVM) were permitted to enter the models. The second level consisted of systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR). The final level contained cross-product terms of race by SBP, DBP and HR. RESULTS: E/A ratio was lower during stress compared to rest and recovery (P < 0.01). Resting E/A ratio was predicted by a regression model of age (-0.31), pro-BNP (0.16), HR (-0.40) and DBP (-0.23) with an R² = 0.33. Stress E/A ratio was predicted by age (-0.24), pro-BNP (0.08), HR (-0.38) and SBP (-0.21) with total R² = 0.22. Resting E' model consisted of age (-0.22), pro-BNP (0.26), DBP (-0.27) and LVM (-0.15) with an R² = 0.29. Stress E' was predicted by age (-0.18), pro-BNP (0.35) and LVM (-0.18) with an R² = 0.18. Resting E/E' was predicted by race (0.17, B > W) and DBP (0.24) with an R² = 0.10. Stress E/E' consisted of pro-BNP (-0.36), height (-0.26) and HR (-0.21) with an R² = 0.15. CONCLUSIONS: pro-BNP predicts both resting and stress DF, suggesting that lower BNP during MS may be a marker of diastolic dysfunction in apparently healthy individuals.

Embolic Stroke Diagnosed by Elevated D-Dimer in a Patient With Negative TEE for Cardioembolic Source.

We report a case of cerebrovascular accident with thromboembolic stroke etiology in a patient who had atrial flutter and negative transesophageal echocardiography (TEE) results. The increased D-dimer levels (1877 ng/mL) initiated referral for magnetic resonance imaging and magnetic resonance angiography of the brain that showed classic recanalization of an embolic thrombus in the angular branch of the left middle cerebral distribution. The D-dimer level of this patient was normalized after 3 months of anticoagulation therapy. Although TEE is considered the gold standard for evaluation of cardiac source of embolism, exclusion of intracardiac thrombus with TEE alone does not eliminate the risk of thromboembolic events. This case highlights the utility of D-dimer as a potential adjunct in the decision-making process to guide investigation of thromboembolism, determine subsequent therapy, and hence reduce the risk of embolic stroke recurrence.

16 kDa heat shock protein from heat-inactivated Mycobacterium tuberculosis is a homodimer - suitability for diagnostic applications with specific llama VHH monoclonals.

BACKGROUND: The 16 kDa heat shock protein (HSP) is an immuno-dominant antigen, used in diagnosis of infectious Mycobacterium tuberculosis (M.tb.) causing tuberculosis (TB). Its use in serum-based diagnostics is limited, but for the direct identification of M.tb. bacteria in sputum or cultures it may represent a useful tool. Recently, a broad set of twelve 16 kDa specific heavy chain llama antibodies (VHH) has been isolated, and their utility for diagnostic applications was explored. METHODOLOGY/PRINCIPAL FINDINGS: To identify the epitopes recognized by the nine (randomly selected from a set of twelve 16 kDa specific VHH antibodies) distinct VHH antibodies, 14 overlapping linear epitopes (each 20 amino acid long) were characterized using direct and sandwich ELISA techniques. Seven out of 14 epitopes were recognized by 8 out of 9 VHH antibodies. The two highest affinity binders B-F10 and A-23 were found to bind distinct epitopes. Sandwich ELISA and SPR experiments showed that only B-F10 was suitable as secondary antibody with both B-F10 and A-23 as anchoring antibodies. To explain this behavior, the epitopes were matched to the putative 3D structure model. Electrospray ionization time-of-flight mass spectrometry and size exclusion chromatography were used to determine the higher order conformation. A homodimer model best explained the differential immunological reactivity of A-23 and B-F10 against heat-treated M.tb. lysates. CONCLUSIONS/SIGNIFICANCE: The concentrations of secreted antigens of M.tb. in sputum are too low for immunological detection and existing kits are only used for identifying M.tb. in cultures. Here we describe how specific combinations of VHH domains could be used to detect the intracellular HSP antigen. Linked to methods of pre-concentrating M.tb. cells prior to lysis, HSP detection may enable the development of protein-based diagnostics of sputum samples and earlier diagnosis of diseases.