Squalicum Creek re-route

Squalicum Creek is one of the largest independent drainages in Whatcom County, draining most of Northern Bellingham. The creek originates in the Cascade foothills and empties into Bellingham Bay. Squalicum Creek has the highest potential for high water quality and productive fish habitat within the Bellingham city limits. The location of the creek is shown in Figure 1 with the reach addressed in this document highlighted as the Project Area. Current conditions within the project area impede fish passage and provide few spawning areas. In addition, Bug Lake and Sunset Pond currently create the highest thermal loading in Squalicum Creek. The creek also fails to meet water quality standards for dissolved oxygen (DO) and fecal coliform. The proposed action will improve water quality and native fish habitat as well as reduce predation by non-native species. This report examines three possible outcomes: the proposed action, an alternative action and a no-action alternative. The proposed action involves creating a new stream channel to route the creek around Sunset Pond. The creek will maintain its route through Bug Lake, however, it will be partially filled to create wetlands and a narrower and more complex stream channel. Increased riparian zones and installations of large woody debris (LWD) in the creek will improve water quality, stream complexity, and provide resting spaces for fish. This plan also includes the modification of existing and construction of new in-stream structures to improve fish passage by enabling salmon to out-migrate as juveniles and move upstream to spawning grounds as adults. The alternative action proposes to fill in large portions of both Bug Lake and Sunset Pond, leaving a narrow channel and transforming the remaining pond areas from manmade aqueducts to riparian areas and emergent wetlands. Riparian planting would also be added around the current stream channel between the lakes and fish passage barriers improved to facilitate fish migration. The no-action alternative would leave the creek in its current condition, leaving habitat issues unresolved. Adverse impacts from the proposed project include increased sediment loading and stormwater pollution from surrounding current and future development as well as disruption of some existing wetland areas. Water quality benefits from the lakes during high flows would also be lost. Temporary impacts as a result of infrastructure and channel improvements would be mitigated by the addition of engineered wetlands as well as continued monitoring, adaptive management strategies and education and outreach efforts to prevent further contamination via stormwater. Short term increased sediment loading during construction cannot be completely mitigated and will have potential significant adverse effects such as increased turbidity, temperature, and lowered dissolved oxygen levels which could be harmful to fish remaining in the stream. Long term goals of the project will improve these temporarily decreased water quality parameters. Impacts of the alternative action would be similar to the proposed action. There are additional potential impacts from non-native soils and even more sediment loading during construction from filling in the ponds. The alternative does not improve floodplain conveyance, though increased wetlands will help manage high-flow conditions. This alternative requires very little new infrastructure. Some supporters of the proposed Bay to Baker Trail disapprove of the current Squalicum Creek re-route because the new channel would follow the old Burlington Northern Railroad grade, which was the original location for the Bay to Baker Trail. If the re-route is completed, then the trail would have to circumvent the bridge by following James Street to the nearest intersection at McLeod Rd. These supporters claim that the Bay to Baker Trail deserves priority since that project\u27s development began years ago. In addition, some members of the community disagree over the future recreation use of Sunset Pond

A cautionary tale of low-pass sequencing and imputation with respect to haplotype accuracy

BACKGROUND: Low-pass whole-genome sequencing and imputation offer significant cost savings, enabling substantial increases in sample size and statistical power. This approach is particularly promising in livestock breeding, providing an affordable means of screening individuals for deleterious alleles or calculating genomic breeding values. Consequently, it may also be of value in companion animal genomics to support pedigree breeding. We sought to evaluate in dogs the impact of low coverage sequencing and reference-guided imputation on genotype concordance and association analyses.RESULTS: DNA isolated from saliva of 30 Labrador retrievers was sequenced at low (0.9X and 3.8X) and high (43.5X) coverage, and down-sampled from 43.5X to 9.6X and 17.4X. Genotype imputation was performed using a diverse reference panel (1021 dogs), and two subsets of the former panel (256 dogs each) where one had an excess of Labrador retrievers relative to other breeds. We observed little difference in imputed genotype concordance between reference panels. Association analyses for a locus acting as a disease proxy were performed using single-marker (GEMMA) and haplotype-based (XP-EHH) tests. GEMMA results were highly correlated (r ≥ 0.97) between 43.5X and ≥ 3.8X depths of coverage, while for 0.9X the correlation was lower (r ≤ 0.8). XP-EHH results were less well correlated, with r ranging from 0.58 (0.9X) to 0.88 (17.4X). Across a random sample of 10,000 genomic regions averaging 17 kb in size, we observed a median of three haplotypes per dog across the sequencing depths, with 5% of the regions returning more than eight haplotypes. Inspection of one such region revealed genotype and phasing inconsistencies across sequencing depths.CONCLUSIONS: We demonstrate that saliva-derived canine DNA is suitable for whole-genome sequencing, highlighting the feasibility of client-based sampling. Low-pass sequencing and imputation require caution as incorrect allele assignments result when the subject possesses alleles that are absent in the reference panel. Larger panels have the capacity for greater allelic diversity, which should reduce the potential for imputation error. Although low-pass sequencing can accurately impute allele dosage, we highlight issues with phasing accuracy that impact haplotype-based analyses. Consequently, if accurately phased genotypes are required for analyses, we advocate sequencing at high depth (&gt; 20X).</p

Method for the Destruction of Endotoxin in Synthetic Spider Silk Proteins

Although synthetic spider silk has impressive potential as a biomaterial, endotoxin contamination of the spider silk proteins is a concern, regardless of the production method. The purpose of this research was to establish a standardized method to either remove or destroy the endotoxins present in synthetic spider silk proteins, such that the endotoxin level was consistently equal to or less than 0.25 EU/mL, the FDA limit for similar implant materials. Although dry heat is generally the preferred method for endotoxin destruction, heating the silk proteins to the necessary temperatures led to compromised mechanical properties in the resultant materials. In light of this, other endotoxin destruction methods were investigated, including caustic rinses and autoclaving. It was found that autoclaving synthetic spider silk protein dopes three times in a row consistently decreased the endotoxin level 10–20 fold, achieving levels at or below the desired level of 0.25 EU/mL. Products made from triple autoclaved silk dopes maintained mechanical properties comparable to products from untreated dopes while still maintaining low endotoxin levels. Triple autoclaving is an effective and scalable method for preparing synthetic spider silk proteins with endotoxin levels sufficiently low for use as biomaterials without compromising the mechanical properties of the materials

Using the Persuasive Design Model to Refine a Novel Stimuli Responsive Polymeric Sensor in Head and Neck Cancer Patients

https://openworks.mdanderson.org/sumexp22/1143/thumbnail.jp

The Making of Modern America: Quantifying Chaos

As we begin to explore the Gilded Age (1870-1900), that era in American History sandwiched between the Civil War/Reconstruction and the Progressive Era to the Great War, we want students to grasp the enormity of the changes impacting the lives of Americans who have largely been engaged in farming in many cases not so different than their ancestors had for several hundreds of years. Technological changes in the first half of the 19th century contributed to some mechanization and manufacturing, but the enormity of the Civil War and the acquisition of the entire continental territory in the 1850s, accelerated changes in the production of goods, in the development of communication and transportation, in the growth of cities, in the opportunities for immigrants, for participation in politics, and in the reach of the government. In this lesson, students will dip into the many changes over the decades from 1860 to 1900 by searching for information on a variety of topics, including: Banking or Finance, Demographics, Government, Industrialization, Immigration, Middle Class Angst, Military, Natural Resources, Politics, Racism, Robber Barons/Captains of Industry, Technological Innovations, Transportation, Urbanization, Voter Turnout, and Xenophobia.https://repository.stcloudstate.edu/gilded_age/1001/thumbnail.jp

Genetic Variants of VEGFA and FLT4 Are Determinants of Survival in Renal Cell Carcinoma Patients Treated with Sorafenib

Molecular markers of sorafenib efficacy in patients with metastatic renal cell carcinoma (mRCC) are not available. The purpose of this study was to discover genetic markers of survival in patients with mRCC treated with sorafenib. Germline variants from 56 genes were genotyped in 295 patients with mRCC. Variant-overall survival (OS) associations were tested in multivariate regression models. Mechanistic studies were conducted to validate clinical associations. VEGFA rs1885657, ITGAV rs3816375, and WWOX rs8047917 (sorafenib arm), and FLT4 rs307826 and VEGFA rs3024987 (sorafenib and placebo arms combined) were associated with shorter OS. FLT4 rs307826 increased VEGFR-3 phosphorylation, membrane trafficking, and receptor activation. VEGFA rs1885657 and rs58159269 increased transcriptional activity of the constructs containing these variants in endothelial and RCC cell lines, and VEGFA rs58159269 increased endothelial cell proliferation and tube formation. FLT4 rs307826 and VEGFA rs58159269 led to reduced sorafenib cytotoxicity. Genetic variation in VEGFA and FLT4 could affect survival in sorafenib-treated patients with mRCC. These markers should be examined in additional malignancies treated with sorafenib and in other angiogenesis inhibitors used in mRCC. Significance: Clinical and mechanistic data identify germline genetic variants in VEGFA and FLT4 as markers of survival in patients with metastatic renal cell carcinoma.Peer reviewe

Transferrable protection by gut microbes against STING-associated lung disease

STING modulates immunity by responding to bacterial and endogenous cyclic dinucleotides (CDNs). Humans and mice with STING gain-of-function mutations develop a syndrome known as STING-associated vasculopathy with onset in infancy (SAVI), which is characterized by inflammatory or fibrosing lung disease. We hypothesized that hyperresponsiveness of gain-of-function STING to bacterial CDNs might explain autoinflammatory lung disease in SAVI mice. We report that depletion of gut microbes with oral antibiotics (vancomycin, neomycin, and ampicillin [VNA]) nearly eliminates lung disease in SAVI mice, implying that gut microbes might promote STING-associated autoinflammation. However, we show that germ-free SAVI mice still develop severe autoinflammatory disease and that transferring gut microbiota from antibiotics-treated mice to germ-free animals eliminates lung inflammation. Depletion of anaerobes with metronidazole abolishes the protective effect of the VNA antibiotics cocktail, and recolonization with the metronidazole-sensitive anaerobe Bacteroides thetaiotaomicron prevents disease, confirming a protective role of a metronidazole-sensitive microbe in a model of SAVI

Intestinal antiviral signaling is controlled by autophagy gene Epg5 independent of the microbiota

Mutations in the macroautophagy/autophagy gen

Automated deep learning segmentation of high-resolution 7 T postmortem MRI for quantitative analysis of structure-pathology correlations in neurodegenerative diseases

Postmortem MRI allows brain anatomy to be examined at high resolution and to link pathology measures with morphometric measurements. However, automated segmentation methods for brain mapping in postmortem MRI are not well developed, primarily due to limited availability of labeled datasets, and heterogeneity in scanner hardware and acquisition protocols. In this work, we present a high resolution of 135 postmortem human brain tissue specimens imaged at 0.3 mm$^{3}$ isotropic using a T2w sequence on a 7T whole-body MRI scanner. We developed a deep learning pipeline to segment the cortical mantle by benchmarking the performance of nine deep neural architectures, followed by post-hoc topological correction. We then segment four subcortical structures (caudate, putamen, globus pallidus, and thalamus), white matter hyperintensities, and the normal appearing white matter. We show generalizing capabilities across whole brain hemispheres in different specimens, and also on unseen images acquired at 0.28 mm^3 and 0.16 mm^3 isotropic T2*w FLASH sequence at 7T. We then compute localized cortical thickness and volumetric measurements across key regions, and link them with semi-quantitative neuropathological ratings. Our code, Jupyter notebooks, and the containerized executables are publicly available at: https://pulkit-khandelwal.github.io/exvivo-brain-upennComment: Preprint submitted to NeuroImage Project website: https://pulkit-khandelwal.github.io/exvivo-brain-upen

HIV-Specific Antibodies Capable of ADCC Are Common in Breastmilk and Are Associated with Reduced Risk of Transmission in Women with High Viral Loads

There are limited data describing the functional characteristics of HIV-1 specific antibodies in breast milk (BM) and their role in breastfeeding transmission. The ability of BM antibodies to bind HIV-1 envelope, neutralize heterologous and autologous viruses and direct antibody-dependent cell cytotoxicity (ADCC) were analyzed in BM and plasma obtained soon after delivery from 10 non-transmitting and 9 transmitting women with high systemic viral loads and plasma neutralizing antibodies (NAbs). Because subtype A is the dominant subtype in this cohort, a subtype A envelope variant that was sensitive to plasma NAbs was used to assess the different antibody activities. We found that NAbs against the subtype A heterologous virus and/or the woman's autologous viruses were rare in IgG and IgA purified from breast milk supernatant (BMS) – only 4 of 19 women had any detectable NAb activity against either virus. Detected NAbs were of low potency (median IC50 value of 10 versus 647 for the corresponding plasma) and were not associated with infant infection (p = 0.58). The low NAb activity in BMS versus plasma was reflected in binding antibody levels: HIV-1 envelope specific IgG titers were 2.2 log10 lower (compared to 0.59 log10 lower for IgA) in BMS versus plasma. In contrast, antibodies capable of ADCC were common and could be detected in the BMS from all 19 women. BMS envelope-specific IgG titers were associated with both detection of IgG NAbs (p = 0.0001)and BMS ADCC activity (p = 0.014). Importantly, BMS ADCC capacity was inversely associated with infant infection risk (p = 0.039). Our findings indicate that BMS has low levels of envelope specific IgG and IgA with limited neutralizing activity. However, this small study of women with high plasma viral loads suggests that breastmilk ADCC activity is a correlate of transmission that may impact infant infection risk