Lichanura, L. trivirgata

Number of Pages: 2Integrative BiologyGeological Science

The Ohio Supreme Court Sets the Statute of Limitations and Adopts the Discovery Rule for Childhood Sexual Abuse Actions: Now It Is Time for Legislative Action

This Note discusses the issue of childhood sexual abuse and challenges the appropriateness of Ohio\u27s current statute of limitations for prosecuting a civil claim of childhood sexual abuse. Part II of this Note describes the problem of child sexual abuse in our society. Part III examines the short-and long-term effects of childhood sexual abuse, particularly memory repression. Part IV reviews the theory of recovered memories and the associated problems with reliability. Part V addresses Ohio\u27s governing statute of limitations for civil claims of childhood sexual abuse. Part VI reviews the history of the discovery rule in Ohio and its application to claims of childhood sexual abuse. Part VII examines the function of statute of limitations and proposes a new eight-year statute of limitations for childhood sexual abuse actions in Ohio. Finally, Part VIII concludes that a longer statute of limitations is now more appropriate than the discovery rule because of the reliability problems associated with recovered memories

Tibia functionality and Division II female and male collegiate athletes from multiple sports

Background Bone strength is developed through a combination of the size and shape (architecture) of a bone as well as the bone’s material properties; and therefore, no one outcome variable can measure a positive or negative adaptation in bone. Skeletal robusticity (total area/ bone length) a measure of bones external size varies within the population and is independent of body size, but robusticity has been associated with bone strength. Athletes may have similar variability in robusticity values as the general population and thus have a wide range of bone strengths based on the robustness of their bones. Therefore, the purpose of this study was to determine if an athlete’s bone strength and cortical area relative to body size was dependent on robusticity. The second aim was to determine if anthropometry or muscle function measurements were associated with bone robusticity. Methods Bone variables contributing to bone strength were measured in collegiate athletes and a reference group using peripheral quantitative computed tomography (pQCT) at the 50% tibial site. Bone functionality was assessed by plotting bone strength and cortical area vs body size (body weight x tibial length) and robustness (total area/length) vs body size. Bone strength was measured using the polar strength-strain index (SSIp). Based on the residuals from the regression, an athlete’s individual functionality was determined, and two groups were formed “weaker for size” (WS) and “stronger for size” (SS). Grip strength, leg extensor strength and lower body power were also measured. Results Division II athletes exhibited a natural variation in (SSIp) relative to robusticity consistent with previous studies. Bone strength (SSIp) was dependent on the robusticity of the tibia. The bone traits that comprise bone strength (SSIp) were significantly different between the SS and WS groups, yet there were minimal differences in the anthropometric data and muscle function measures between groups. A lower percentage of athletes from ball sports were “weaker for size” (WS group) and a higher percentage of swimmers were in the WS group. Discussion A range of strength values based on robusticity occurs in athletes similar to general populations. Bones with lower robusticity (slender) were constructed with less bone tissue and had less strength. The athletes with slender bones were from all sports including track and field and ball sports but the majority were swimmers. Conclusions Athletes, even after optimal training for their sport, may have weaker bones based on robusticity. Slender bones may therefore be at a higher risk for fracture under extreme loading events but also yield benefits to some athletes (swimmers) due to their lower bone mass

Cellulose synthase ‘class specific regions’ are intrinsically disordered and functionally undifferentiated

Cellulose synthases (CESAs) are glycosyltransferases that catalyze formation of cellulose microfibrils in plant cell walls. Seed plant CESA isoforms cluster in six phylogenetic clades, whose non‐interchangeable members play distinct roles within cellulose synthesis complexes (CSCs). A ‘class specific region’ (CSR), with higher sequence similarity within versus between functional CESA classes, has been suggested to contribute to specific activities or interactions of different isoforms. We investigated CESA isoform specificity in the moss, Physcomitrella patens (Hedw.) B. S. G. to gain evolutionary insights into CESA structure/function relationships. Like seed plants, P. patens has oligomeric rosette‐type CSCs, but the PpCESAs diverged independently and form a separate CESA clade. We showed that P. patens has two functionally distinct CESAs classes, based on the ability to complement the gametophore‐negative phenotype of a ppcesa5 knockout line. Thus, non‐interchangeable CESA classes evolved separately in mosses and seed plants. However, testing of chimeric moss CESA genes for complementation demonstrated that functional class‐specificity is not determined by the CSR. Sequence analysis and computational modeling showed that the CSR is intrinsically disordered and contains predicted molecular recognition features, consistent with a possible role in CESA oligomerization and explaining the evolution of class‐specific sequences without selection for class‐specific function

Bluefin Tuna Larvae in Oligotrophic Ocean Foodwebs, Investigations of Nutrients to Zooplankton: Overview of the BLOOFINZ-Gulf of Mexico program

Western Atlantic bluefin tuna (ABT) undertake long-distance migrations from rich feeding grounds in the North Atlantic to spawn in oligotrophic waters of the Gulf of Mexico (GoM). Stock recruitment is strongly affected by interannual variability in the physical features associated with ABT larvae, but the nutrient sources and food-web structure of preferred habitat, the edges of anticyclonic loop eddies, are unknown. Here, we describe the goals, physical context, design and major findings of an end-to-end process study conducted during peak ABT spawning in May 2017 and 2018. Mesoscale features in the oceanic GoM were surveyed for larvae, and five multi-day Lagrangian experiments measured hydrography and nutrients; plankton biomass and composition from bacteria to zooplankton and fish larvae; phytoplankton nutrient uptake, productivity and taxon-specific growth rates; micro- and mesozooplankton grazing; particle export; and ABT larval feeding and growth rates. We provide a general introduction to the BLOOFINZ-GoM project (Bluefin tuna Larvae in Oligotrophic Ocean Foodwebs, Investigation of Nitrogen to Zooplankton) and highlight the finding, based on backtracking of experimental waters to their positions weeks earlier, that lateral transport from the continental slope region may be more of a key determinant of available habitat utilized by larvae than eddy edges per se.Postprint1,74

Targeting the Transforming Growth Factor-β pathway inhibits human basal-like breast cancer metastasis

<p>Abstract</p> <p>Background</p> <p>Transforming Growth Factor β (TGF-β) plays an important role in tumor invasion and metastasis. We set out to investigate the possible clinical utility of TGF-β antagonists in a human metastatic basal-like breast cancer model. We examined the effects of two types of the TGF-β pathway antagonists (1D11, a mouse monoclonal pan-TGF-β neutralizing antibody and LY2109761, a chemical inhibitor of TGF-β type I and II receptor kinases) on sublines of basal cell-like MDA-MB-231 human breast carcinoma cells that preferentially metastasize to lungs (4175TR, 4173) or bones (SCP2TR, SCP25TR, 2860TR, 3847TR).</p> <p>Results</p> <p>Both 1D11 and LY2109761 effectively blocked TGF-β-induced phosphorylation of receptor-associated Smads in all MDA-MB-231 subclones <it>in vitro</it>. Moreover, both antagonists inhibited TGF-β stimulated <it>in vitro </it>migration and invasiveness of MDA-MB-231 subclones, indicating that these processes are partly driven by TGF-β. In addition, both antagonists significantly reduced the metastatic burden to either lungs or bones <it>in vivo</it>, seemingly independently of intrinsic differences between the individual tumor cell clones. Besides inhibiting metastasis in a tumor cell autonomous manner, the TGF-β antagonists inhibited angiogenesis associated with lung metastases and osteoclast number and activity associated with lytic bone metastases. In aggregate, these studies support the notion that TGF-β plays an important role in both bone-and lung metastases of basal-like breast cancer, and that inhibiting TGF-β signaling results in a therapeutic effect independently of the tissue-tropism of the metastatic cells. Targeting the TGF-β pathway holds promise as a novel therapeutic approach for metastatic basal-like breast cancer.</p> <p>Conclusions</p> <p>In aggregate, these studies support the notion that TGF-β plays an important role in both bone-and lung metastases of basal-like breast cancer, and that inhibiting TGF-β signaling results in a therapeutic effect independently of the tissue-tropism of the metastatic cells. Targeting the TGF-β pathway holds promise as a novel therapeutic approach for metastatic basal-like breast cancer.</p

CD69 is a TGF-β/1α,25-dihydroxyvitamin D3 target gene in monocytes

CD69 is a transmembrane lectin that can be expressed on most hematopoietic cells. In monocytes, it has been functionally linked to the 5-lipoxygenase pathway in which the leukotrienes, a class of highly potent inflammatory mediators, are produced. However, regarding CD69 gene expression and its regulatory mechanisms in monocytes, only scarce data are available. Here, we report that CD69 mRNA expression, analogous to that of 5-lipoxygenase, is induced by the physiologic stimuli transforming growth factor-β (TGF-β) and 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) in monocytic cells. Comparison with T- and B-cell lines showed that the effect was specific for monocytes. CD69 expression levels were increased in a concentration-dependent manner, and kinetic analysis revealed a rapid onset of mRNA expression, indicating that CD69 is a primary TGF-β/1α,25(OH)2D3 target gene. PCR analysis of different regions of the CD69 mRNA revealed that de novo transcription was initiated and proximal and distal parts were induced concomitantly. In common with 5-lipoxygenase, no activation of 0.7 kb or ~2.3 kb promoter fragments by TGF-β and 1α,25(OH)2D3 could be observed in transient reporter assays for CD69. Analysis of mRNA stability using a transcription inhibitor and a 3′UTR reporter construct showed that TGF-β and 1α,25(OH)2D3 do not influence CD69 mRNA stability. Functional knockdown of Smad3 clearly demonstrated that upregulation of CD69 mRNA, in contrast to 5-LO, depends on Smad3. Comparative studies with different inhibitors for mitogen activated protein kinases (MAPKs) revealed that MAPK signalling is involved in CD69 gene regulation, whereas 5-lipoxygenase gene expression was only partly affected. Mechanistically, we found evidence that CD69 gene upregulation depends on TAK1-mediated p38 activation. In summary, our data indicate that CD69 gene expression, conforming with 5-lipoxygenase, is regulated monocyte-specifically by the physiologic stimuli TGF-β and 1α,25(OH)2D3 on mRNA level, although different mechanisms account for the upregulation of each gene

The STOP COVID 2 study: Fluvoxamine vs placebo for outpatients with symptomatic COVID-19, a fully remote randomized controlled trial

BACKGROUND: Prior randomized clinical trials have reported benefit of fluvoxamine ≥200 mg/d vs placebo for patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This randomized, double-blind, placebo-controlled, fully remote multisite clinical trial evaluated whether fluvoxamine prevents clinical deterioration in higher-risk outpatients with acute coronavirus disease 2019 (COVID-19). Between December 2020 and May 2021, nonhospitalized US and Canadian participants with confirmed symptomatic infection received fluvoxamine (50 mg on day 1, 100 mg twice daily thereafter) or placebo for 15 days. The primary modified intent-to-treat (mITT) population included participants who started the intervention within 7 days of symptom onset with a baseline oxygen saturation ≥92%. The primary outcome was clinical deterioration within 15 days of randomization, defined as having both (1) shortness of breath (severity ≥4 on a 0-10 scale or requiring hospitalization) RESULTS: A total of 547 participants were randomized and met mITT criteria (n = 272 fluvoxamine, n = 275 placebo). The Data Safety Monitoring Board recommended stopping early for futility related to lower-than-predicted event rates and declining accrual concurrent with vaccine availability in the United States and Canada. Clinical deterioration occurred in 13 (4.8%) participants in the fluvoxamine group and 15 (5.5%) participants in the placebo group (absolute difference at day 15, 0.68%; 95% CI, -3.0% to 4.4%; log-rank CONCLUSIONS: This trial did not find fluvoxamine efficacious in preventing clinical deterioration in unvaccinated outpatients with symptomatic COVID-19. It was stopped early and underpowered due to low primary outcome rates. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov Identifier: NCT04668950