Canonical ligand-dependent and non-canonical ligand-independent EphA2 signaling in the eye lens of wild-type, knockout, and aging mice.

Disruption of Eph-ephrin bidirectional signaling leads to human congenital and age-related cataracts, but the mechanisms for these opacities in the eye lens remain unclear. Eph receptors bind to ephrin ligands on neighboring cells to induce canonical ligand-mediated signaling. The EphA2 receptor also signals non-canonically without ligand binding in cancerous cells, leading to epithelial-to-mesenchymal transition (EMT).

Unveiling new genetic insights in rheumatoid arthritis for drug discovery through Taxonomy3 analysis.

Genetic support for a drug target has been shown to increase the probability of success in drug development, with the potential to reduce attrition in the pharmaceutical industry alongside discovering novel therapeutic targets. It is therefore important to maximise the detection of genetic associations that affect disease susceptibility. Conventional statistical methods such as genome-wide association studies (GWAS) only identify some of the genetic contribution to disease, so novel analytical approaches are required to extract additional insights.

Histone demethylase KDM5D upregulation drives sex differences in colon cancer.

Sex exerts a profound impact on cancer incidence, spectrum and outcomes, yet the molecular and genetic bases of such sex differences are ill-defined and presumptively ascribed to X-chromosome genes and sex hormones. Such sex differences are particularly prominent in colorectal cancer (CRC) in which men experience higher metastases and mortality. A murine CRC model, engineered with an inducible transgene encoding oncogenic mutant KRAS and conditional null alleles of Apc and Trp53 tumour suppressors (designated iKAP), revealed higher metastases and worse outcomes specifically in males with oncogenic mutant KRAS (KRAS*) CRC.

Nonpathological inflammation drives the development of an avian flight adaptation.

The development of modern birds provides a window into the biology of their dinosaur ancestors. We investigated avian postnatal development and found that sterile inflammation drives formation of the pygostyle, a compound structure resulting from bone fusion in the tail. Inflammation is generally induced by compromised tissue integrity, but here is involved in normal bone development.

Exotic Carbonate Mineralization Recovered from a Deep Basalt Carbon Storage Demonstration.

Mitigating climate change requires transformational advances for carbon dioxide removal, including geologic carbon sequestration in reactive subsurface environments. The Wallula Basalt Carbon Storage Pilot Project demonstrated that CO injected into >800 m deep Columbia River Basalt Group flow top reservoirs mineralizes on month-year timescales. Herein, we present new optical petrography, micro-computed X-ray tomography, and electron microscopy results obtained from sidewall cores collected two years after CO injection.

Understanding the Electrochemical Performance of FeS Conversion Cathodes.

Conversion cathodes represent a viable route to improve rechargeable Li battery energy densities, but their poor electrochemical stability and power density have impeded their practical implementation. Here, we explore the impact cell fabrication, electrolyte interaction, and current density have on the electrochemical performance of FeS/Li cells by deconvoluting the contributions of the various conversion and intercalation reactions to the overall capacity. By varying the slurry composition and applied pressure, we determine that the capacity loss is primarily due to the large volume changes during (de)lithiation, leading to a degradation of the conductive matrix.

Pyruvate Kinase M1 Suppresses Development and Progression of Prostate Adenocarcinoma.

Differential expression of PKM1 and PKM2 impacts prostate tumorigenesis and suggests a potential therapeutic vulnerability in prostate cancer.

A tunable synthesis of indigoids: targeting indirubin through temperature.

The spontaneous conversion of 3-indoxyl to indigo is a well-established process used to produce indigo dyes. It was recently shown that some indoles, when reacted with molybdenum hexacarbonyl and cumyl peroxide, proceed through an indoxyl intermediate to produce significant amounts of indirubin through a competing mechanism. Modulation of this system to lower temperatures allows for careful tuning, leading to selective production of indirubins in a general process.

Telomerase Reverse Transcriptase Preserves Neuron Survival and Cognition in Alzheimer's Disease Models.

Amyloid-induced neurodegeneration plays a central role in Alzheimer's disease (AD) pathogenesis. Here, we show that haploinsufficiency decreases BDNF and increases amyloid-β (Aβ) precursor in murine brain. Moreover, prior to disease onset, the locus sustains accumulation of repressive epigenetic marks in murine and human AD neurons, implicating repression in amyloid-induced neurodegeneration.

Recent advances in blood rheology: a review.

Due to the potential impact on the diagnosis and treatment of various cardiovascular diseases, work on the rheology of blood has significantly expanded in the last decade, both experimentally and theoretically. Experimentally, blood has been confirmed to demonstrate a variety of non-Newtonian rheological characteristics, including pseudoplasticity, viscoelasticity, and thixotropy. New rheological experiments and the development of more controlled experimental protocols on more extensive, broadly physiologically characterized, human blood samples demonstrate the sensitivity of aspects of hemorheology to several physiological factors.

A comparative study of blood rheology across species.

Recent advances in hemorheology are extended to study blood rheology across species, which has important clinical implications particularly in intravenous drug scaleup as drugs undergoing clinical trials are first tested in animals. Some of the first hemorheological measurements from seven different species under both steady and transient shear conditions are presented and modeled using a rheological model developed and validated on human blood rheology fit to 20 different donors. Despite similar physiological properties across the blood samples from different species, significant differences are observed, particularly at low shear rates.

Clinical and microbiological characterization of sepsis and evaluation of sepsis scores.

Background: Despite the necessity of early recognition for an optimal outcome, sepsis often remains unrecognized. Available tools for early recognition are rarely evaluated in low- and middle-income countries. In this study, we analyzed the spectrum, treatment and outcome of sepsis at an Ethiopian tertiary hospital and evaluated recommended sepsis scores.

A remarkable group of thick-headed Triassic Period archosauromorphs with a wide, possibly Pangean distribution.

The radiation of archosauromorph reptiles in the Triassic Period produced an unprecedented collection of diverse and disparate forms with a mix of varied ecologies and body sizes. Some of these forms were completely unique to the Triassic, whereas others were converged on by later members of Archosauromorpha. One of the most striking examples of this is with Triopticus primus, the early dome-headed form later mimicked by pachycephalosaurid dinosaurs.

Insulin Receptor-Expressing T Cells Appear in Individuals at Risk for Type 1 Diabetes and Can Move into the Pancreas in C57BL/6 Transgenic Mice.

Insulin receptor (IR) expression on the T cell surface can indicate an activated state; however, the IR is also chemotactic, enabling T cells with high IR expression to physically move toward insulin. In humans with type 1 diabetes (T1D) and the NOD mouse model, a T cell-mediated autoimmune destruction of insulin-producing pancreatic β cells occurs. In previous work, when purified IR and IR T cells were sorted from diabetic NOD mice and transferred into irradiated nondiabetic NOD mice, only those that received IR T cells developed insulitis and diabetes.

Software engineering standards for epidemiological models.

There are many tangled normative and technical questions involved in evaluating the quality of software used in epidemiological simulations. In this paper we answer some of these questions and offer practical guidance to practitioners, funders, scientific journals, and consumers of epidemiological research. The heart of our paper is a case study of the Imperial College London (ICL) covid-19 simulator, set in the context of recent work in epistemology of simulation and philosophy of epidemiology.

Right Aortic Arch and Isolated Left Subclavian Artery: Prenatal and Postnatal Echocardiographic and Tomographic Imaging.

• RAA and isolated LSA is a rare congenital cardiac anomaly. • Blood flow to the LSA is supplied by the left vertebral artery. • It can present with limb ischemia, vertebrobasilar insufficiency, or pulmonary steal.

Quantification of CO Mineralization at the Wallula Basalt Pilot Project.

In 2013, the Pacific Northwest National Laboratory led a geologic carbon sequestration field demonstration where ∼1000 tonnes of CO was injected into several deep Columbia River Basalt zones near Wallula, Washington. Rock core samples extracted from the injection zone two years after CO injection revealed nascent carbonate mineralization that was qualitatively consistent with expectations from laboratory experiments and reactive transport modeling. Here, we report on a new detailed analysis of the 2012 pre-injection and 2015 post-injection hydrologic tests that capitalizes on the difference in fluid properties between scCO and water to assess changes in near-field, wellbore, and reservoir conditions that are apparent approximately two years following the end of injection.

An Ion-exchange Bone Demineralization Method for Improved Time, Expense, and Tissue Preservation.

Here, we describe an ethylenediaminetetraacetic acid (EDTA)-based bone demineralization procedure that uses cation-exchange resin and dialysis tubing. This method does not require solution changes or special equipment, is faster than EDTA alone, is cost-effective, and is environmentally friendly. Like other EDTA-based methods, this procedure yields superior tissue preservation than formic acid demineralization.

Molecular engineering of thixotropic, sprayable fluids with yield stress using associating polysaccharides.

Hypothesis: Molecular engineering facilitates the development of a complex fluid with contradictory requirements of yield stress and sprayability, while minimizing the amount of structuring material (<0.05 wt%). This unique system can be achieved by a biopolymer hydrogel with tunable inter- and intra-molecular interactions for microstructural robustness and molecular extensibility by the variation of chemical conformations that microstructure breaks up under shear followed by a low molecularly extensible response.

Publisher Correction: A planet within the debris disk around the pre-main-sequence star AU Microscopii.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Moral Features of the Therapeutic Relationship with Adults: Dignity, Trust, Autonomy, Vulnerability, and Resilience.

Using dignity as a foundational value of morality, this article defines trust, autonomy, vulnerability, and resilience in relational terms. A fictional narrative illustrates these attributes as well as solidarity and care, two core tenets of relational ethics. Medicine and rehabilitation are described as moral enterprises with at the core of our professional obligations to patients-namely, duties of care, trustworthiness, and loyalty.