Change in iceberg calving behavior preceded North Sea ice shelf disintegration during the last deglaciation.

Understanding how regime shifts in iceberg calving behavior affect ice shelf stability remains a challenge for numerical models. This is an important question as we consider the fate of the ice shelves that currently buttress the Antarctic Ice Sheet and hold back the bulk of its potential upstream sea-level contribution. Using buried landforms, we demonstrate that ice shelves fringed the former British-Irish Ice Sheet (BIIS) and document their disintegration ~18,000 years ago.

Synchronous retreat of Thwaites and Pine Island glaciers in response to external forcings in the presatellite era.

Today, relatively warm Circumpolar Deep Water is melting Thwaites Glacier at the base of its ice shelf and at the grounding zone, contributing to significant ice retreat. Accelerating ice loss has been observed since the 1970s; however, it is unclear when this phase of significant melting initiated. We analyzed the marine sedimentary record to reconstruct Thwaites Glacier's history from the early Holocene to present.

Group B streptococcus induces cellular senescence in human amnion epithelial cells through a partial interleukin-1-mediated mechanism.

Group B streptococcus (GBS) infection is a significant public health concern associated with adverse pregnancy complications and increased neonatal mortality and morbidity. However, the mechanisms underlying the impact of GBS on the fetal membrane, the first line of defense against pathogens, are not fully understood. Here, we propose that GBS induces senescence and inflammatory factors (IL-6 and IL-8) in the fetal membrane through interleukin-1 (IL-1).

Using mass spectrometry imaging to visualize age-related subcellular disruption.

Metabolic homeostasis balances the production and consumption of energetic molecules to maintain active, healthy cells. Cellular stress, which disrupts metabolism and leads to the loss of cellular homeostasis, is important in age-related diseases. We focus here on the role of organelle dysfunction in age-related diseases, including the roles of energy deficiencies, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, changes in metabolic flux in aging (e.

The CD38 glycohydrolase and the NAD sink: implications for pathological conditions.

Nicotinamide adenine dinucleotide (NAD) acts as a cofactor in several oxidation-reduction (redox) reactions and is a substrate for a number of nonredox enzymes. NAD is fundamental to a variety of cellular processes including energy metabolism, cell signaling, and epigenetics. NAD homeostasis appears to be of paramount importance to health span and longevity, and its dysregulation is associated with multiple diseases.

Implications of the NADase CD38 in COVID pathophysiology.

During the COVID-19 pandemic, efforts have been made worldwide to develop effective therapies to address the devastating immune-mediated effects of SARS-CoV-2. With the exception of monoclonal antibody-mediated therapeutics and preventive approaches such as mass immunization, most experimental or repurposed drugs have failed in large randomized clinical trials (https://www.who.

Inclusion in neuroscience through high impact courses.

Recognizing that STEM disciplines, including neuroscience, have a long way to go to attract and retain diverse talent, educators can take action by being more intentional about their departmental curricula, course design, and pedagogical strategies. A deep body of research suggests that one way we can promote inclusion is through the use of high impact practices (HIPs). These active learning teaching practices promote deep learning and student engagement and have been shown to have a positive differential impact on historically underserved student populations.

CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD and NMN levels.

Decreased NAD levels have been shown to contribute to metabolic dysfunction during aging. NAD decline can be partially prevented by knockout of the enzyme CD38. However, it is not known how CD38 is regulated during aging, and how its ecto-enzymatic activity impacts NAD homeostasis.

The wasting-associated metabolite succinate disrupts myogenesis and impairs skeletal muscle regeneration.

Background: Muscle wasting is a debilitating co-morbidity affecting most advanced cancer patients. Alongside enhanced muscle catabolism, defects in muscle repair/regeneration contribute to cancer-associated wasting. Among the factors implicated in suppression of muscle regeneration are cytokines that interfere with myogenic signal transduction pathways.

Tert-Butyl Hydroperoxide Stimulated Apoptosis Independent of Prostaglandin E and IL-6 in the HTR-8/SVneo Human Placental Cell Line.

Significant gaps exist in our knowledge of how cellular redox status, sometimes referred to as oxidative stress, impacts placental trophoblasts. The present study used tert-butyl hydroperoxide (TBHP) as a known generator of reactive oxygen species (ROS) in the extravillous trophoblast cell line HTR-8/SVneo to examine the role of cellular redox disruption of prostaglandin E (PGE) and the cytokine IL-6 in cell death. Cells were exposed to 0, 12.

The Multi-faceted Ecto-enzyme CD38: Roles in Immunomodulation, Cancer, Aging, and Metabolic Diseases.

CD38 (Cluster of Differentiation 38) is a multifunctional ecto-enzyme that metabolizes NAD+ and mediates nicotinamide dinucleotide (NAD+) and extracellular nucleotide homeostasis as well as intracellular calcium. CD38 is also an emerging therapeutic target under conditions in which metabolism is altered including infection, aging, and tumorigenesis. We describe multiple enzymatic activities of CD38, which may explain the breadth of biological roles observed for this enzyme.

The NADase CD38 is induced by factors secreted from senescent cells providing a potential link between senescence and age-related cellular NAD decline.

Tissue nicotinamide adenine dinucleotide (NAD) decline has been implicated in aging. We have recently identified CD38 as a central regulator involved in tissue NAD decline during the aging process. CD38 is an ecto-enzyme highly expressed in endothelial and inflammatory cells.

Examining Joint Effects of Air Pollution Exposure and Social Determinants of Health in Defining "At-Risk" Populations Under the Clean Air Act: Susceptibility of Pregnant Women to Hypertensive Disorders of Pregnancy.

Pregnant women are uniquely susceptible to adverse effects of air pollution exposure due to vulnerabilities and health consequences during pregnancy (e.g., hypertensive disorders of pregnancy [HDP]) compared to the general population.

The Holocene retreat dynamics and stability of Petermann Glacier in northwest Greenland.

Submarine glacial landforms in fjords are imprints of the dynamic behaviour of marine-terminating glaciers and are informative about their most recent retreat phase. Here we use detailed multibeam bathymetry to map glacial landforms in Petermann Fjord and Nares Strait, northwestern Greenland. A large grounding-zone wedge (GZW) demonstrates that Petermann Glacier stabilised at the fjord mouth for a considerable time, likely buttressed by an ice shelf.

Tumor-derived cytokines impair myogenesis and alter the skeletal muscle immune microenvironment.

Muscle wasting is a decline in skeletal muscle mass and function that is associated with aging, obesity, and a spectrum of pathologies including cancer. Cancer-associated wasting not only reduces quality of life, but also directly impacts cancer mortality, chemotherapeutic efficacy, and surgical outcomes. There is an incomplete understanding of the role of tumor-derived factors in muscle wasting and sparse knowledge of how these factors impact in vivo muscle regeneration.

Role of cytokine signaling in group B Streptococcus-stimulated expression of human beta defensin-2 in human extraplacental membranes.

Problem: Group B Streptococcus (GBS) is a leading cause of neonatal morbidity and mortality. We tested the hypothesis that the choriodecidua plays a role in GBS-stimulated human beta defensin(HBD)-2 increases in amnion cells through a secreted factor of choriodecidual origin.

Method Of Study: Human amnion epithelial cells were treated with choriodecidual GBS-conditioned medium, live GBS, lipoteichoic acid (LTA), or lipopolysaccharide (LPS), with and without IL-1 inhibitors.

Getting under the hood: how and for whom does increasing course structure work?

At the college level, the effectiveness of active-learning interventions is typically measured at the broadest scales: the achievement or retention of all students in a course. Coarse-grained measures like these cannot inform instructors about an intervention's relative effectiveness for the different student populations in their classrooms or about the proximate factors responsible for the observed changes in student achievement. In this study, we disaggregate student data by racial/ethnic groups and first-generation status to identify whether a particular intervention-increased course structure-works better for particular populations of students.

The TGFβ1 pathway is required for NFκB dependent gene expression in mouse keratinocytes.

The transforming growth factor-beta 1 (TGFβ1) and NFκB pathways are important regulators of epidermal homeostasis, inflammatory responses and carcinogenesis. Previous studies have shown extensive crosstalk between these pathways that is cell type and context dependent, but this has not been well-characterized in epidermal keratinocytes. Here we show that in primary mouse keratinocytes, TGFβ1 induces NFκB-luciferase reporter activity that is dependent on both NFκB and Smad3.

Transforming growth factor beta1 enhances tumor promotion in mouse skin carcinogenesis.

Transforming growth factor beta1 (TGFbeta1) expression is elevated by tumor promoters in the mouse skin, but its role in tumor promotion has not been well defined. To investigate this, we have compared TGFbeta1+/+ and +/- mice in a two-stage skin chemical carcinogenesis protocol. Surprisingly, TGFbeta1+/- mice had fewer number and incidence of benign papillomas, reduced epidermal and tumor cell proliferation and reduced epidermal TGFbeta1 and nuclear p-Smad2 localization in response to the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) compared with TGFbeta1+/+ mice.

A sonic hedgehog signaling domain in the arterial adventitia supports resident Sca1+ smooth muscle progenitor cells.

We characterize a sonic hedgehog (Shh) signaling domain restricted to the adventitial layer of artery wall that supports resident Sca1-positive vascular progenitor cells (AdvSca1). Using patched-1 (Ptc1(lacZ)) and patched-2 (Ptc2(lacZ)) reporter mice, adventitial Shh signaling activity was first detected at embryonic day (E) 15.5, reached the highest levels between postnatal day 1 (P1) and P10, was diminished in adult vessels, and colocalized with a circumferential ring of Shh protein deposited between the media and adventitia.

Blood vessel patterning at the embryonic midline.

The reproducible pattern of blood vessels formed in vertebrate embryos has been described extensively, but only recently have we obtained the genetic and molecular tools to address the mechanisms underlying these processes. This review describes our current knowledge regarding vascular patterning around the vertebrate midline and presents data derived from frogs, zebrafish, avians, and mice. The embryonic structures implicated in midline vascular patterning, the hypochord, endoderm, notochord, and neural tube, are discussed.

Stimulation of insulin-like growth factor (IGF) binding protein-3 synthesis by IGF-I and transforming growth factor-alpha is mediated by both phosphatidylinositol-3 kinase and mitogen-activated protein kinase pathways in mammary epithelial cells.

IGF binding protein (IGFBP)-3 is an important regulator of mammary epithelial cell (MEC) growth and can enhance the ability of both IGF-I and epidermal growth factor ligands such as TGFalpha to stimulate MEC proliferation. Here we investigate the role of the phosphatidylinositol-3 kinase (PI3K) and MAPK pathways in the regulation of IGFBP-3 expression by IGF-I and TGFalpha in bovine MECs. Both growth factors stimulated DNA synthesis, although IGF-I was the stronger mitogen.

The neural tube patterns vessels developmentally using the VEGF signaling pathway.

Embryonic blood vessels form in a reproducible pattern that interfaces with other embryonic structures and tissues, but the sources and identities of signals that pattern vessels are not well characterized. We hypothesized that the neural tube provides vascular patterning signal(s) that direct formation of the perineural vascular plexus (PNVP) that encompasses the neural tube at mid-gestation. Both surgically placed ectopic neural tubes and ectopic neural tubes engineered genetically were able to recruit a vascular plexus, showing that the neural tube is the source of a vascular patterning signal.