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The Winchcombe meteorite is a CM chondrite breccia composed of eight distinct lithological units plus a cataclastic matrix. The degree of aqueous alteration varies between intensely altered CM2.0 and moderately altered CM2.6. Although no lithology dominates, three heavily altered rock types (CM2.1–2.3) represent >70 area%. Tochilinite–cronstedtite intergrowths (TCIs) are common in several lithologies. Their compositions can vary significantly, even within a single lithology, which can prevent a clear assessment of alteration extent if only TCI composition is considered. We suggest that this is due to early alteration under localized geochemical microenvironments creating a diversity of compositions and because later reprocessing was incomplete, leaving a record of the parent body's fluid history. In Winchcombe, the fragments of primary accretionary rock are held within a cataclastic matrix (~15 area%). This material is impact-derived fallback debris. Its grain size and texture suggest that the disruption of the original parent asteroid responded by intergranular fracture at grain sizes

In the United States, the Boys Town Teaching Family Model, in its earliest iteration as Achievement Place, pioneered the use of applied behavior analysis in a group home setting and designated specially trained married couples (Teaching Parents) as the primary agents of intervention. From its origins in Achievement Place, the Boys Town Teaching Family Model has systematically included ongoing evaluation of all program components in its many replications both on the home campus in Omaha, Nebraska, and in many sites around the United States. Largely as the result of the corpus of this evaluation and related research, the Teaching Family Model at Boys Town, as an accredited and founding member of the Teaching Family Association, has been awarded the scientific rating of 3 (Promising Research Evidence) with “high” relevance for child welfare by the California Evidence-Based Clearinghouse for Child Welfare.

Blood pressure (BP) screening using an office-based measurement is recommended for adults 18 years and older without a history of hypertension. If abnormal, the BP measurement should be repeated twice with the average of those final two readings used to determine the BP category. Home BP monitoring and ambulatory BP monitoring are beneficial in patients for whom there is a concern for masked or white-coat hypertension. Guidelines differ regarding the BP cutoff used for the diagnosis of hypertension. Lifestyle modifications are the foundation of hypertension management with the Dietary Approaches to Stop Hypertension (DASH) diet being the most effective dietary modification. First-line pharmacotherapy should include one or more of the following: an angiotensin-converting enzyme inhibitor, an angiotensin receptor blocker, a dihydropyridine calcium channel blocker, and a thiazide or thiazidelike diuretic. Compared with standard BP control, intensive BP control (ie, systolic BP less than 120 mm Hg) leads to a decrease in atherosclerotic cardiovascular disease and all-cause mortality in patients with elevated risk but increases adverse effects, including hypotension, electrolyte abnormalities, acute kidney injury, and syncope.

Secondary hypertension (HTN) refers to high blood pressure (BP) caused by an identifiable and potentially correctable condition or disease. Common causes of secondary HTN include renovascular disease, renal parenchymal disease, primary hyperaldosteronism, drug and substance use, and obstructive sleep apnea; less common etiologies include pheochromocytoma/paraganglioma, Cushing syndrome, thyroid and parathyroid conditions, congenital adrenal hyperplasia, and aortic coarctation. An identifiable secondary cause of HTN is present in approximately 10% of adult patients with HTN. Early recognition of suggestive clinical findings and laboratory results enables the timely diagnosis of specific secondary causes of HTN. Correct diagnosis of a causative underlying condition can lead to more effective, even curative management and subsequent cardiovascular risk reduction. Management involves treating the underlying condition. Some patients may benefit from referral to a specialist with specific expertise in treating the causative condition.

Hypertension (HTN) in children and adolescents is a spectrum of disease, ranging from elevated blood pressure (BP) to stage 1 and 2 HTN. The prevalence of elevated BP and HTN in this age group has increased significantly over the past 20 years, particularly in girls. Screening for HTN in asymptomatic children and adolescents is controversial. Primary HTN is now the predominant cause of HTN among the pediatric population in the United States, especially among adolescents. Secondary pediatric HTN is high BP due to an underlying medical condition and is more common among children 6 years and younger. Ambulatory BP monitoring should be considered in pediatric patients with repeatedly elevated office BP measurements. All children with BP greater than the 90th percentile should be encouraged to adopt lifestyle changes, but those with persistent or severe elevations in BP may benefit from pharmacotherapy.

Retromer controls cellular homeostasis through regulating integral membrane protein sorting and transport and by controlling late-stage maturation of the endo-lysosomal network. Retromer dysfunction, which is linked to neurodegenerative disorders including Parkinson’s and Alzheimer’s diseases, manifests in complex cellular phenotypes, though the precise nature of this dysfunction, and its relation to neurodegeneration, remain unclear. Here, we perform the first integrated multiomics approach to provide precise insight into the impact of Retromer dysfunction on endo-lysosomal health and homeostasis within a human neuroglioma cell model. We quantify profound changes to the lysosomal proteome, indicative of broad lysosomal dysfunction and inefficient autophagic lysosome reformation, coupled with a reconfigured cell surface proteome and secretome reflective of increased lysosomal exocytosis. Through this global proteomic approach and parallel transcriptomic analysis, we provide an unprecedented integrated view of Retromer function in regulating lysosomal homeostasis and emphasise its role in neuroprotection.

The symbiotic relationships shared between humans and their gastrointestinal parasites present opportunities to discover novel therapies for inflammatory diseases. A prime example of this phenomenon is the interaction of humans and roundworms such as the hookworm, Necator americanus. Epidemiological observations, animal studies and clinical trials using experimental human hookworm infection show that hookworms can suppress inflammation in a safe and well-tolerated way, and that the key to their immunomodulatory properties lies within their secreted proteome. Herein we describe the identification of 2 netrin domain-containing proteins from the N. americanus secretome, and explore their potential in treating intestinal inflammation in mouse models of ulcerative colitis. One of these proteins, subsequently named Na-AIP-1, was effective at suppressing disease when administered prophylactically in the acute TNBS-induced model of colitis. This protective effect was validated in the more robust CD4 T cell transfer model of chronic colitis, where prophylactic Na-AIP-1 reduced T-cell-dependent type-1 cytokine responses in the intestine and the associated intestinal pathology. Mechanistic studies revealed that depletion of CD11c+ cells abrogated the protective anticolitic effect of Na-AIP-1. Next generation sequencing of colon tissue in the T-cell transfer model of colitis revealed that Na-AIP-1 induced a transcriptomic profile associated with the downregulation of metabolic and signaling pathways involved in type-1 inflammation, notably TNF. Finally, co-culture of Na-AIP-1 with a human monocyte-derived M1 macrophage cell line resulted in significantly reduced secretion of TNF. Na-AIP-1 is now a candidate for clinical development as a novel therapeutic for the treatment of human inflammatory bowel diseases.

In the Southern Ocean, several zooplankton taxonomic groups, euphausiids, copepods, salps and pteropods, are notable because of their biomass and abundance and their roles in maintaining food webs and ecosystem structure and function, including the provision of globally important ecosystem services. These groups are consumers of microbes, primary and secondary producers, and are prey for fishes, cephalopods, seabirds, and marine mammals. In providing the link between microbes, primary production, and higher trophic levels these taxa influence energy flows, biological production and biomass, biogeochemical cycles, carbon flux and food web interactions thereby modulating the structure and functioning of ecosystems. Additionally, Antarctic krill (Euphausia superba) and various fish species are harvested by international fisheries. Global and local drivers of change are expected to affect the dynamics of key zooplankton species, which may have potentially profound and wide-ranging implications for Southern Ocean ecosystems and the services they provide. Here we assess the current understanding of the dominant metazoan zooplankton within the Southern Ocean, including Antarctic krill and other key euphausiid, copepod, salp and pteropod species. We provide a systematic overview of observed and potential future responses of these taxa to a changing Southern Ocean and the functional relationships by which drivers may impact them. To support future ecosystem assessments and conservation and management strategies, we also identify priorities for Southern Ocean zooplankton research.

Cytoskeletal assemblies produce functionality through multiscale structural reconfiguration by exploiting a family of protein crosslinkers. Inspired by these principles, we designed an array of complementary peptide-DNA monomers able to form multistranded junctions with different geometries and stabilities and tested their effect on the structural organization of co-polymerized filament-forming peptides. In striking similarity to their biological counterparts, the peptide-DNA crosslinkers organized fibers into bundled architectures with base-pair tunable aspect ratios. Controlling solvent or temperature drove assembly through distinct pathways to form different structural and mechanical states exhibiting multiple levels of hierarchy from the same set of components. The thermal reversibility of DNA crosslinks drove structures to form, disassemble, and rebuild over multiple cycles. Sequential transitioning between bundles and fibers using orthogonal triggers enabled the dosed release of proteins to modulate catalytic reactions. This programmable peptide-DNA nanotechnology framework will pave the way towards the design of hierarchical materials with reconfigurable properties.

Two new galloyl glucosides, galloyl-lawsoniaside A (4) and uromyrtoside (6), were isolated from the polar fraction of Uromyrtus metrosideros leaf extract along with another four previously identified phytochemicals (1, 2, 3, and 5). The structures of these six compounds were characterised using low and high-resolution mass spectrometry (L/HRMS) and 1D and 2D Nuclear Magnetic Resonance (NMR) spectroscopy. These compounds were not toxic to human peripheral blood mononuclear cells (PBMCs) at 10 μg/mL over 24 h, yet showed significant in vitro suppression of proinflammatory cytokines involved in the pathogenesis of inflammatory bowel disease (IBD). Specifically, the release of interferon γ (IFN-γ), interleukin (IL)-17A, and IL-8 from phorbol myristate acetate/ionomycin (P/I) and anti-CD3/anti-CD28-activated cells were significantly suppressed by compounds 4 and 5. Interestingly, no effect on tumour necrosis factor (TNF) release was observed. These results show that the newly characterised compound 4 has promising cytokine suppressive properties, which could be further investigated as a candidate for IBD treatment.

The Martian nakhlite meteorites, which represent multiple events that belong to a single magma source region represent a key opportunity to study the evolution of Martian petrogenesis. Here 16 of the 26 identified nakhlite specimens are studied using coupled electron backscatter diffraction (EBSD) and emplacement end-member calculations. EBSD was used to determine shape preferred orientation (SPO) of contained augite (high Ca-clinopyroxene) phenocrysts by considering their crystallographic preferred orientation (CPO). Parameters derived from EBSD, and energy dispersive X-ray spectroscopy (EDS) data were used in basic emplacement models to assess their dominant mechanism against three end-member scenarios: thermal diffusion, crystal settling, and crystal convection. Results from CPO analyses indicate low intensity weak-moderate CPO. In all samples, a consistent foliation within the axes of augite are observed typically coupled with a weaker lineation CPO in one of the other crystallographic axes. These CPO results agree best with crystal settling being the dominant emplacement mechanism for the nakhlites. Modelled crystal settling results identify two distinguishable groups outside of the model’s resolution indicating the presence of secondary emplacement mechanisms. Comparison of the two identified groups against petrofabric, geochemical, and age parameters indicate random variability between individual meteorites. Therefore, coupled petrofabric and emplacement modelling results identify an overarching characteristic of a dominant crystal settling emplacement mechanism for the nakhlite source volcano despite exhibiting random variation with each discharge through time.

Deformation is a near ubiquitous process that is observed within nearly all naturally forming rocks. Electron backscatter diffraction (EBSD) is a technique that enables slip-systems (a form of plastic deformation) to be inferred from intra-crystalline misorientations at a comparable scale to representative CPO analysis (≥300 crystals for the nakhlites). Extensive laboratory and studies on naturally occurring samples have identified preferential mantle condition extrinsic parameters for specific slip-system signatures within olivine and clinopyroxene. Intra-crystalline misorientation patterns for olivine and augite (high Ca-clinopyroxene) for 16 different Martian nakhlite meteorites (21 sections) were analysed and assessed against these known parameters. Investigation of high and low deformation regions within the nakhlites revealed a shift in intra-crystalline misorientation patterns for 10 of the 21 sections. Interpreted as both shock (high deformations) and emplacement (low deformation) signatures. The observed variations in deformation patterns for the two main regimes of deformation indicate heterogeneous sampling of the nakhlite ejecta crater. Our findings indicate that shock deformation is prevalent throughout the nakhlites, and that great care needs to be taken when interpreting intra-crystalline misorientations of crystals within apparent lower deformation regions.

Background The IgE- and IgG4-binding patterns of the major fish allergen parvalbumins are not clearly understood. IgE antibody-binding to parvalbumin from Asian seabass, Lat c 1.01, is implicated in up to 90 % of allergic reactions, although the region of IgE or IgG4 epitopes are unknown. In the present study, we characterized the specific IgE- and IgG4-binding regions of Lat c 1.01 using serum from pediatric and adult patients with clinically-confirmed fish allergy. Methods A comparative investigation of patient IgE- and IgG4-binding to recombinant Lat c 1.01 was performed by immunoblotting and indirect ELISA using serum from 15 children and eight adults with clinically confirmed IgE-mediated reactions to fish. The IgE- and IgG4-binding regions of Lat c 1.01 were determined by inhibition ELISA using seven overlapping peptides spanning the entire 102 amino acid sequence. Elucidated IgE-binding regions were modelled and compared to known antibody-binding regions of parvalbumins from five other fish species. Results Ninety five percent (22/23) patients demonstrated IgE-binding to rLat c 1.01, while fewer patients (10/15 children and 7/8 adults) demonstrated robust IgG4 binding when determined by immunoblots. IgE-binding for both cohorts was significantly higher compared to IgG4-binding by ELISA. All patients in this study presented individual IgE and IgG4 epitope-recognition profiles. In addition to these patient-specific antibody binding sites, general IgE epitopes were also identified at the C- and N-terminal regions of this major fish allergen. Conclusions and Clinical relevance Our findings demonstrate two specific IgE epitopes on parvalbumin from Asian seabass, while IgG4 binding is much lower and patient specific. This study highlights the importance of advancement in epitope analysis regardless of the age group for diagnostics and immunotherapies for fish allergy.

Racism in America has deep roots that impact maternal health, particularly through pervasive inequities among Black women as compared with White, although other racial and ethnic groups also suffer. Health care providers caring for pregnant women are optimally positioned to maintain vigilance for these disparities in maternal care, and to intervene with their diverse skillsets and knowledge. By increasing awareness of how structural racism drives inequities in health, these providers can encourage hospitals and practices to develop and implement national bundles for patient safety, and use bias training and team-based training practices aimed at improving care for racially diverse mothers.

Marine organisms produce a diverse range of toxins and bioactive peptides to support predation, competition, and defense. The peptide repertoires of stony corals (order Scleractinia) remain relatively understudied despite the presence of tentacles used for predation and defense that are likely to contain a range of bioactive compounds. Here, we show that a tentacle extract from the mushroom coral, Heliofungia actiniformis, contains numerous peptides with a range of molecular weights analogous to venom profiles from species such as cone snails. Using NMR spectroscopy and mass spectrometry we characterized a 12-residue peptide (Hact-1) with a new sequence (GCHYTPFGLICF) and well-defined β-hairpin structure stabilized by a single disulfide bond. The sequence is encoded within the genome of the coral and expressed in the polyp body tissue. The structure present is common among toxins and venom peptides, but Hact-1 does not show activity against select examples of Gram-positive and Gram-negative bacteria or a range of ion channels, common properties of such peptides. Instead, it appears to have a limited effect on human peripheral blood mononuclear cells, but the ecological function of the peptide remains unknown. The discovery of this peptide from H. actiniformis is likely to be the first of many from this and related species.

Immune-modulating therapies have revolutionized the treatment of chronic diseases, particularly cancer. However, their success is restricted and there is a need to identify new therapeutic targets. Here, we show that natural killer cell granule protein 7 (NKG7) is a regulator of lymphocyte granule exocytosis and downstream inflammation in a broad range of diseases. NKG7 expressed by CD4+ and CD8+ T cells played key roles in promoting inflammation during visceral leishmaniasis and malaria-two important parasitic diseases. Additionally, NKG7 expressed by natural killer cells was critical for controlling cancer initiation, growth and metastasis. NKG7 function in natural killer and CD8+ T cells was linked with their ability to regulate the translocation of CD107a to the cell surface and kill cellular targets, while NKG7 also had a major impact on CD4+ T cell activation following infection. Thus, we report a novel therapeutic target expressed on a range of immune cells with functions in different immune responses.

Racism in the United States has deep roots that affect maternal health, particularly through pervasive inequalities among black women compared with white. Anesthesiologists are optimally positioned to maintain vigilance for these disparities in maternal care, and to intervene with their unique acute critical care skills and knowledge. As leaders in patient safety, anesthesiologists should drive hospitals and practices to develop and implement national bundles for patient safety, as well as using team-based training practices designed to improve hospitals that care for racially diverse mothers.

Evidence indicates that Antarctic minke whales (AMWs) in the Ross Sea affect the foraging behaviour, especially diet, of sympatric Adélie penguins (ADPEs) by, we hypothesize, influencing the availability of prey they have in common, mainly crystal krill. To further investigate this interaction, we undertook a study in McMurdo Sound during 2012–2013 and 2014–2015 using telemetry and biologging of whales and penguins, shore-based observations and quantification of the preyscape. The 3D distribution and density of prey were assessed using a remotely operated vehicle deployed along and to the interior of the fast-ice edge where AMWs and ADPEs focused their foraging. Acoustic surveys of prey and foraging behaviour of predators indicate that prey remained abundant under the fast ice, becoming successively available to air-breathing predators only as the fast ice retreated. Over both seasons, the ADPE diet included less krill and more Antarctic silverfish once AMWs became abundant, but the penguins' foraging behaviour (i.e. time spent foraging, dive depth, distance from colony) did not change. In addition, over time, krill abundance decreased in the upper water column near the ice edge, consistent with the hypothesis (and previously gathered information) that AMW and ADPE foraging contributed to an alteration of prey availability.