Laboratory observations of slow earthquakes and the spectrum of tectonic fault slip modes

Slow earthquakes represent an important conundrum in earthquake physics. While regular earthquakes are catastrophic events with rupture velocities governed by elastic wave speed, the processes that underlie slow fault slip phenomena, including recent discoveries of tremor, slow-slip and low-frequency earthquakes, are less understood. Theoretical models and sparse laboratory observations have provided insights, but the physics of slow fault rupture remain enigmatic. Here we report on laboratory observations that illuminate the mechanics of slow-slip phenomena. We show that a spectrum of slow-slip behaviours arises near the threshold between stable and unstable failure, and is governed by frictional dynamics via the interplay of fault frictional properties, effective normal stress and the elastic stiffness of the surrounding material. This generalizable frictional mechanism may act in concert with other hypothesized processes that damp dynamic ruptures, and is consistent with the broad range of geologic environments where slow earthquakes are observed

The common C-terminal sequences of substance P and neurokinin A contact the same region of the NK-1 receptor

AbstractAlthough neurokinin A (NKA), a tachykinin peptide with sequence homology to substance P (SP), is a weak competitor of radiolabeled SP binding to the NK-1 receptor (NK-1R), more recent direct binding studies using radiolabeled NKA have demonstrated an unexpected high-affinity interaction with this receptor. To document the site of interaction between NKA and the NK-1R, we have used a photoreactive analogue of NKA containing p-benzoyl-L-phenylalanine (Bpa) substituted in position 7 of the peptide. Peptide mapping studies of the receptor photolabeled by 125I-iodohistidyl1-Bpa7NKA have established that the site of photoinsertion is located within a segment of the receptor extending from residues 178 to 190 (VVCMIEWPEHPNR). We have previously shown that 125I-BH-Bpa8SP, a photoreactive analogue of SP, covalently attaches to M181 within this same receptor sequence. Importantly, both of these peptides (125I-iodohistidyl1-Bpa7NKA and 125I-BH-Bpa8SP) have the photoreactive amino acid in an equivalent position within the conserved tachykinin carboxyl-terminal tail. In this report, we also show that site-directed mutagenesis of M181 to A181 in the NK-1R results in a complete loss of photolabeling of both peptides to this receptor site, indicating that the equivalent position of SP and NKA, when bound to the NK-1R, contact the same residue

A Feasibility Study of Supply and Demand for Diabetes Prevention Programs in North Carolina

Diabetes Prevention Programs (DPPs) have shown that healthy eating and moderate physical activity are effective ways of delaying and preventing type 2 diabetes in people with impaired glucose tolerance. We assessed willingness to pay for DPPs from the perspective of potential recipients and the cost of providing these programs from the perspective of community health centers and local health departments in North Carolina

Origin of Hawaiian Tholeiites: Trace Element Constraints

We report here geochemical studies of Hawaiian tholeiites and ultramafic xenoliths from Salt Lake Crater, Oahu. We focus attention on tholeiitic basalts that comprise the bulk of Hawaiian volcanoes. When the samples are screened to include only those lying neat the log-MgO (about 7 percent) end of olivine-control lines (Wright, 1971), tholeiites from individual volcanoes are remarkably uniform. On this basis, we show that, for tholeiites from six volcanoes, systematic geochemical differences exist that cannot be attributed to differentiation of these magmas from a common parental magma. Apparently there have been important differences in the processes of magma generation, source composition, or source mineral constitution. Partial melting calculations based on REE contents emphasize these distinctions, but unique melting models are not presented. In these models, relative REE abundances in the source material is a major uncertainty. Nd isotopic studies of Hawaiian basalts require systematic differences in Sm/Nd for the source material of each volcano. Furthermore, the time-integrated Sm/Nd of the sources must be less than that in chondrites. REE analyses of Hawaiian garnet lherzolite xenoliths show that they have chondritic to light REE-enriched relative abundances with absolute contents (for light REE) about 3 to 8 times chondrites. These data obviously conflict with interpretations of the Nd isotopic data. Several possibilities follow: (1) the available xenoliths are not parental to tholeiite, (2) our simple interpretation of the Nd isotopic data is wrong, and (3) the source regions may have been invaded at geologically recent times by a light REE-enriched phase, in which case the xenoliths may represent the course material. If the xenoliths are characteristic of the source, partial melting calculations indicate that the tholeiites may be generated by 15 to 20 percent melting of garnet lherzolite and at the sane tune conform to constraints imposed by the REE and Ni contents and the partitioning of Fe and Mg between melts and residues. We propose that the primary tholeiitic magmas contain no more than about 12 percent MgO, and that erupted magmas probably fractionated less than 10 to 15 percent of olivine during ascent and storage in high-level chambers

A Hybrid Implementation-Effectiveness Study of a Community Health Worker-Delivered Intervention to Reduce Cardiovascular Disease Risk in a Rural, Underserved Non-Hispanic Black Population: The CHANGE Study

Purpose To evaluate the implementation and effectiveness of the Carolina Heart Alliance Networking for Greater Equity (CHANGE) Program, an adapted evidence-based cardiovascular disease risk reduction intervention delivered by Community Health Workers (CHW) to rural adults. Design Hybrid implementation-effectiveness study with a pre–post design. Setting North Carolina Federally Qualified Health Center and local health department in a rural, medically underserved area. Sample Participants (n = 255) included 87% Non-Hispanic Black with a mean age of 57 years; 84% had diagnosed hypertension, 55% had diabetes, and 65% had hypercholesterolemia. Intervention A CHW-delivered, low-intensity, 4-month behavioral lifestyle intervention promoting a southern-style Mediterranean dietary pattern and physical activity. Measures We measured number and representativeness of participants reached and retained, intervention delivery fidelity, weight, blood pressure, and self-reported dietary and physical activity behaviors. Analysis Pre–post changes at 4 months were analyzed using paired t-tests. Results Study participants completed 90% of planned intervention contacts; 87% were retained. Intervention delivery fidelity measures showed participants receiving a mean of 3.5 counseling visits, 2.7 booster calls, and on average completing 1.7 modules, setting 1.8 goals, and receiving 1.3 referrals per visit. There were significant mean reductions in systolic (−2.5 mmHg, P < .05) and diastolic blood pressure (−2.1 mmHg, P < .01); the proportion of participants with systolic blood pressure <130 increased by 7 % points (P = .05), and diastolic pressure <80 by 9 percentage points (P < .01). Dietary behaviors improved significantly with average weekly servings of nuts increased by .5 serving (P < .0001), and fruits and vegetables by .8 daily serving (P < .0001). Physical activity also increased on average by 45 min./week (P < .001). Weight did not change significantly. Conclusions The CHANGE program showed both implementation and program effectiveness and adds to the evidence supporting CHW-delivered lifestyle interventions to reduce CVD risk among rural, Non-Hispanic Black, and medically underserved populations

Challenges of Integrating an Evidence-based Intervention in Health Departments to Prevent Excessive Gestational Weight Gain among Low-income Women

To examine health departments’ (HD) capacity to adapt and implement an intervention to prevent excessive gestational weight gain

Bone Marrow-Derived Multipotent Stromal Cells Attenuate Inflammation in Obliterative Airway Disease in Mouse Tracheal Allografts

Obliterative bronchiolitis (OB) remains the most significant cause of death in long-term survival of lung transplantation. Using an established murine heterotopic tracheal allograft model, the effects of different routes of administration of bone marrow-derived multipotent stromal cells (MSCs) on the development of OB were evaluated. Tracheas from BALB/c mice were implanted into the subcutaneous tissue of major histocompatibility complex- (MHC-) disparate C57BL/6 mice. At the time of transplant, bone marrow-derived MSCs were administered either systemically or locally or via a combination of the two routes. The allografts were explanted at various time points after transplantation and were evaluated for epithelial integrity, inflammatory cell infiltration, fibrosis, and luminal obliteration. We found that the most effective route of bone marrow-derived MSC administration is the combination of systemic and local delivery. Treatment of recipient mice with MSCs suppressed neutrophil, macrophage, and T-cell infiltration and reduced fibrosis. These beneficial effects were observed despite lack of significant MSC epithelial engraftment or new epithelial cell generation. Our study suggests that optimal combination of systemic and local delivery of MSCs may ameliorate the development of obliterative airway disease through modulation of immune response

Tachykinin receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Tachykinin receptors (provisional nomenclature as recommended by NC-IUPHAR [90]) are activated by the endogenous peptides substance P (SP), neurokinin A (NKA; previously known as substance K, neurokinin &#945;, neuromedin L), neurokinin B (NKB; previously known as neurokinin &#946;, neuromedin K), neuropeptide K and neuropeptide &#947; (N-terminally extended forms of neurokinin A). The neurokinins (A and B) are mammalian members of the tachykinin family, which includes peptides of mammalian and nonmammalian origin containing the consensus sequence: Phe-x-Gly-Leu-Met. Marked species differences in in vitro pharmacology exist for all three receptors, in the context of nonpeptide ligands. Antagonists such as aprepitant and fosaprepitant were approved by FDA and EMA, in combination with other antiemetic agents, for the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy

Epigenetic regulation of 5α reductase-1 underlies adaptive plasticity of reproductive function and pubertal timing

Women facing increased energetic demands in childhood commonly have altered adult ovarian activity and shorter reproductive lifespan, possibly comprising a strategy to optimize reproductive success. Here we sought to understand the mechanisms of early-life programming of reproductive function, by integrating analysis of reproductive tissues in an appropriate mouse model with methylation analysis of proxy tissue DNA in a well-characterized population of Bangladeshi migrants in the UK. Bangladeshi women whose childhood was in Bangladesh were found to have later pubertal onset and lower age-matched ovarian reserve than Bangladeshi women who grew-up in England. Subsequently we aimed to explore the potential relevance to the altered reproductive phenotype of one of the genes that emerged from the screens. Results: Of the genes associated with differential methylation in the Bangladeshi women whose childhood was in Bangladesh as compared to Bangladeshi women who grew up in the UK, 13 correlated with altered expression of the orthologous gene in the mouse model ovaries. These mice had delayed pubertal onset and a smaller ovarian reserve compared to controls. The most relevant of these genes for reproductive function appeared to be SRD5A1, which encodes the steroidogenic enzyme 5α reductase-1. SRD5A1 was more methylated at the same transcriptional enhancer in mice ovaries as in the women’s buccal DNA, and its expression was lower in the hypothalamus of the mice as well, suggesting a possible role in the central control of reproduction. The expression of Kiss1 and Gnrh was also lower in these mice compared to controls, and inhibition of 5α reductase-1 reduced Kiss1 and Gnrh mRNA levels and blocked GnRH release in GnRH neuronal cell cultures. Crucially, we show that inhibition of this enzyme in female mice in vivo delayed pubertal onset. Conclusions: SRD5A1/5α reductase-1 responds epigenetically to the environment and its down-regulation appears to alter the reproductive phenotype. These findings help to explain diversity in reproductive characteristics and how they are shaped by early-life environment, and reveal novel pathways that might be targeted to mitigate health issues caused by life-history trade-offs

Tachykinin receptors in GtoPdb v.2023.1

Tachykinin receptors (provisional nomenclature as recommended by NC-IUPHAR [91]) are activated by the endogenous peptides substance P (SP), neurokinin A (NKA; previously known as substance K, neurokinin &#945;, neuromedin L), neurokinin B (NKB; previously known as neurokinin &#946;, neuromedin K), neuropeptide K and neuropeptide &#947; (N-terminally extended forms of neurokinin A). The neurokinins (A and B) are mammalian members of the tachykinin family, which includes peptides of mammalian and nonmammalian origin containing the consensus sequence: Phe-x-Gly-Leu-Met. Marked species differences in in vitro pharmacology exist for all three receptors, in the context of nonpeptide ligands. Antagonists such as aprepitant and fosaprepitant were approved by FDA and EMA, in combination with other antiemetic agents, for the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy