The Annual Surface and Ground Water Nutrient Budget of Spirit Lake, Mount Saint Helens, Wa

https://digitalcommons.tacoma.uw.edu/gis_projects/1018/thumbnail.jp

DO ANKLE STABILIZERS INFLUENCE DYNAMIC STABILITY IN PERSONS WITH FUNCTIONAL ANKLE INSTABILITY?

Ankle sprains are the most common injury in the physically active, and reoccurrence rate is high. Repetitive ankle sprains can cause functional ankle instability (FAI), leading to deficits in balance, strength, and stability. Sports medicine professionals prescribe and administer bracing and taping as extrinsic methods of enhancing ankle stability. What is not clear is how these methods affect neuromuscular control during dynamic movements in persons with FAI. The purpose of this study was to determine the effects of taping and bracing on time to stabilization (TTS), as a measure of dynamic stability, in persons with FAI during two landing tasks

PRE-SEASON DYNAMIC STABILIZATION MEASURES IN FIVE COLLEGIATE TEAMS

The purpose of this study was to measure baseline dynamic stability using time to stabilization (TTS) during two landing tasks at the start of pre-season training in a group of college athletes. Seventy-one male and female athletes representing men’s soccer (n=22), women’s soccer (n=13), women’s volleyball (n=12), men’s basketball (n=12), and women’s basketball (n=11) performed single-leg forward jump and lateral drop landing tasks on each leg onto a force plate. GRF data were used to calculate TTS in the anteroposterior (A/P) and mediolateral (M/L) directions. Data were assessed descriptively using SPSS for differences between sports. Results showed that men’s basketball players had higher TTS values for 6 of 8 measures while women’s volleyball players had lower TTS values for 6 of 8 measures

Chemerin Suppresses Breast Cancer Growth by Recruiting Immune Effector Cells Into the Tumor Microenvironment

Infiltration of immune cells into the tumor microenvironment (TME) can regulate growth and survival of neoplastic cells, impacting tumorigenesis and tumor progression. Correlations between the number of effector immune cells present in a tumor and clinical outcomes in many human tumors, including breast, have been widely described. Current immunotherapies utilizing checkpoint inhibitors or co-stimulatory molecule agonists aim to activate effector immune cells. However, tumors often lack adequate effector cell numbers within the TME, resulting in suboptimal responses to these agents. Chemerin (RARRES2) is a leukocyte chemoattractant widely expressed in many tissues and is known to recruit innate leukocytes. CMKLR1 is a chemotactic cellular receptor for chemerin and is expressed on subsets of dendritic cells, NK cells, and macrophages. We have previously shown that chemerin acts as a tumor suppressive cytokine in mouse melanoma models by recruiting innate immune defenses into the TME. Chemerin/RARRES2 is down-regulated in many tumors, including breast, compared to normal tissue counterparts. Here, using a syngeneic orthotopic EMT6 breast carcinoma model, we show that forced overexpression of chemerin by tumor cells results in significant recruitment of NK cells and T cells within the TME. While chemerin secretion by EMT6 cells did not alter their phenotypic behavior in vitro, it did significantly suppress tumor growth in vivo. To define the cellular effectors required for this anti-tumor phenotype, we depleted NK cells or CD8+ T cells and found that either cell type is required for chemerin-dependent suppression of EMT6 tumor growth. Finally, we show significantly reduced levels of RARRES2 mRNA in human breast cancer samples compared to matched normal tissues. Thus, for the first time we have shown that increasing chemerin expression within the breast carcinoma TME can suppress growth by recruitment of NK and T cells, thereby supporting this approach as a promising immunotherapeutic strategy

Secreted IgM Modulates IL-10 Expression in B Cells

IL-10+ B cells are critical for immune homeostasis and restraining immune responses in infection, cancer, and inflammation; however, the signals that govern IL-10+ B cell differentiation are ill-defined. Here we find that IL-10+ B cells expand in mice lacking secreted IgM ((s)IgM–/–) up to 10-fold relative to wildtype (WT) among all major B cell and regulatory B cell subsets. The IL-10+ B cell increase is polyclonal and presents within 24 hours of birth. In WT mice, sIgM is produced prenatally and limits the expansion of IL-10+ B cells. Lack of the high affinity receptor for sIgM, FcμR, in B cells translates into an intermediate IL-10+ B cell phenotype relative to WT or sIgM–/– mice. Our study thus shows that sIgM regulates IL-10 programming in B cells in part via B cell-expressed FcμR, thereby revealing a function of sIgM in regulating immune homeostasis

Cluster-Cluster Lensing and the Case of Abell 383

Extensive surveys of galaxy clusters motivate us to assess the likelihood of cluster-cluster lensing (CCL), namely, gravitational-lensing of a background cluster by a foreground cluster. We briefly describe the characteristics of CCLs in optical, X-ray and SZ measurements, and calculate their predicted numbers for $\Lambda$CDM parameters and a viable range of cluster mass functions and their uncertainties. The predicted number of CCLs in the strong-lensing regime varies from several ($<10$) to as high as a few dozen, depending mainly on whether lensing triaxiality bias is accounted for, through the c-M relation. A much larger number is predicted when taking into account also CCL in the weak-lensing regime. In addition to few previously suggested CCLs, we report a detection of a possible CCL in A383, where background candidate high-$z$ structures are magnified, as seen in deep Subaru observations.Comment: 9 pages, 5 figures, submitted to MNRA

Infiltration efficiency and subsurface water processes of a sustainable drainage system and consequences to flood management

With increased intensity rainfall events globally and urban expansion decreasing permeable surfaces, there is an increasing problem of urban flooding. This study aims to better understand rainfall infiltration into a Sustainable Drainage System (SuDS) permeable pavement, compared with an adjacent Green Area of made ground, in relationship to groundwater levels below both areas. Both areas were instrumented with soil water content and matric potential sensors and four shallow boreholes were instrumented with groundwater level sensors. Surface infiltration rates were measured using a double‐ring infiltrometer. Results showed that average infiltration rates of the SuDS (1,925 mm/hr) were significantly higher than the Green Area (56 mm/hr). The SuDS was well designed to transfer rainfall rapidly to the aquifer below, where groundwater levels rapidly rose within 1 hr of a 1 in 30 year event (32.8 mm/hr). In comparison, soil compaction of the made ground Green Area decreased infiltration rates, but still enabled the majority of rainfall events to infiltrate. The aquifer below the Green Area responded more slowly, as lower matrix potentials facilitated water retention in the soil profile, slowing water draining to the aquifer. This work reiterates the importance of ensuring a 1 m separation depth between the base of the SuDS infiltration zone and aquifer depth

Vaccination with Plasmodium knowlesi AMA1 Formulated in the Novel Adjuvant Co-Vaccine HT™ Protects against Blood-Stage Challenge in Rhesus Macaques

Plasmodium falciparum apical membrane antigen 1 (PfAMA1) is a leading blood stage vaccine candidate. Plasmodium knowlesi AMA1 (PkAMA1) was produced and purified using similar methodology as for clinical grade PfAMA1 yielding a pure, conformational intact protein. Combined with the adjuvant CoVaccine HT™, PkAMA1 was found to be highly immunogenic in rabbits and the efficacy of the PkAMA1 was subsequently tested in a rhesus macaque blood-stage challenge model. Six rhesus monkeys were vaccinated with PkAMA1 and a control group of 6 were vaccinated with PfAMA1. A total of 50 µg AMA1 was administered intramuscularly three times at 4 week intervals. One of six rhesus monkeys vaccinated with PkAMA1 was able to control parasitaemia, upon blood stage challenge with P. knowlesi H-strain. Four out of the remaining five showed a delay in parasite onset that correlated with functional antibody titres. In the PfAMA1 vaccinated control group, five out of six animals had to be treated with antimalarials 8 days after challenge; one animal did not become patent during the challenge period. Following a rest period, animals were boosted and challenged again. Four of the six rhesus monkeys vaccinated with PkAMA1 were able to control the parasitaemia, one had a delayed onset of parasitaemia and one animal was not protected, while all control animals required treatment. To confirm that the control of parasitaemia was AMA1-related, animals were allowed to recover, boosted and re-challenged with P. knowlesi Nuri strain. All control animals had to be treated with antimalarials by day 8, while five out of six PkAMA1 vaccinated animals were able to control parasitaemia. This study shows that: i) Yeast-expressed PkAMA1 can protect against blood stage challenge; ii) Functional antibody levels as measured by GIA correlated inversely with the day of onset and iii) GIA IC50 values correlated with estimated in vivo growth rates

Outcomes in pediatric studies of medium-chain acyl-coA dehydrogenase (MCAD) deficiency and phenylketonuria (PKU): a review.

BACKGROUND: Inherited metabolic diseases (IMDs) are a group of individually rare single-gene diseases. For many IMDs, there is a paucity of high-quality evidence that evaluates the effectiveness of clinical interventions. Clinical effectiveness trials of IMD interventions could be supported through the development of core outcome sets (COSs), a recommended minimum set of standardized, high-quality outcomes and associated outcome measurement instruments to be incorporated by all trials in an area of study. We began the process of establishing pediatric COSs for two IMDs, medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and phenylketonuria (PKU), by reviewing published literature to describe outcomes reported by authors, identify heterogeneity in outcomes across studies, and assemble a candidate list of outcomes. METHODS: We used a comprehensive search strategy to identify primary studies and guidelines relevant to children with MCAD deficiency and PKU, extracting study characteristics and outcome information from eligible studies including outcome measurement instruments for select outcomes. Informed by an established framework and a previously published pediatric COS, outcomes were grouped into five, mutually-exclusive, a priori core areas: growth and development, life impact, pathophysiological manifestations, resource use, and death. RESULTS: For MCAD deficiency, we identified 83 outcomes from 52 articles. The most frequently represented core area was pathophysiological manifestations, with 33 outcomes reported in 29/52 articles (56%). Death was the most frequently reported outcome. One-third of outcomes were reported by a single study. The most diversely measured outcome was cognition and intelligence/IQ for which eight unique measurement instruments were reported among 14 articles. For PKU, we identified 97 outcomes from 343 articles. The most frequently represented core area was pathophysiological manifestations with 31 outcomes reported in 281/343 articles (82%). Phenylalanine concentration was the most frequently reported outcome. Sixteen percent of outcomes were reported by a single study. Similar to MCAD deficiency, the most diversely measured PKU outcome was cognition and intelligence/IQ with 39 different instruments reported among 82 articles. CONCLUSIONS: Heterogeneity of reported outcomes and outcome measurement instruments across published studies for both MCAD deficiency and PKU highlights the need for COSs for these diseases, to promote the use of meaningful outcomes and facilitate comparisons across studies

The experimental power of FR900359 to study Gq-regulated biological processes.

Despite the discovery of heterotrimeric αβγ G proteins ∼25 years ago, their selective perturbation by cell-permeable inhibitors remains a fundamental challenge. Here we report that the plant-derived depsipeptide FR900359 (FR) is ideally suited to this task. Using a multifaceted approach we systematically characterize FR as a selective inhibitor of Gq/11/14 over all other mammalian Gα isoforms and elaborate its molecular mechanism of action. We also use FR to investigate whether inhibition of Gq proteins is an effective post-receptor strategy to target oncogenic signalling, using melanoma as a model system. FR suppresses many of the hallmark features that are central to the malignancy of melanoma cells, thereby providing new opportunities for therapeutic intervention. Just as pertussis toxin is used extensively to probe and inhibit the signalling of Gi/o proteins, we anticipate that FR will at least be its equivalent for investigating the biological relevance of Gq