The Adirondack Mountain region is an extensive geographic area (26,305 km2) in upstate New York where acid deposition has negatively affected water resources for decades and caused the extirpation of ...local fish populations. The water quality decline and loss of an established brook trout (Salvelinus fontinalis Mitchill) population in Brooktrout Lake were reconstructed from historical information dating back to the late 1880s. Water quality and biotic recovery were documented in Brooktrout Lake in response to reductions of S deposition during the 1980s, 1990s, and 2000s and provided a unique scientific opportunity to re-introduce fish in 2005 and examine their critical role in the recovery of food webs affected by acid deposition. Using C and N isotope analysis of fish collagen and state hatchery feed as well as Bayesian assignment tests of microsatellite genotypes, we document in situ brook trout reproduction, which is the initial phase in the restoration of a preacidification food web structure in Brooktrout Lake. Combined with sulfur dioxide emissions reductions promulgated by the 1990 Clean Air Act Amendments, our results suggest that other acid-affected Adirondack waters could benefit from careful fish re-introduction protocols to initiate the ecosystem reconstruction of important components of food web dimensionality and functionality.
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IJS, KILJ, NUK, PNG, UL, UM
Endogenous mechanisms in the resolution of acute inflammation are of interest since excessive inflammation underlies many pathologies. We report a new aspirin-triggered DHA metabolome that ...biosynthesizes a potent product in inflammatory exudates and human leukocytes, namely aspirin-triggered Neuroprotectin D1/Protectin D1 AT-(NPD1/PD1). The complete stereochemistry of AT-(NPD1/PD1) proved to be 10
R
,17
R
-dihydroxydocosa- 4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid. The chirality of hydroxyl groups and geometry of the conjugated triene system essential for bioactivity were established by matching biological materials with stereochemically pure isomers prepared by organic synthesis. AT-(NPD1/PD1) reduced neutrophil (PMN) recruitment in murine peritonitis in a dose-dependent fashion where neither a Δ
15
-trans-isomer nor DHA was effective. With human cells, AT-(NPD1/PD1) decreased transendothelial PMN migration as well as enhanced efferocytosis of apoptotic human PMN by macrophages. These results indicate that AT-(NPD1/PD1) is a potent antiinflammatory-pro-resolving molecule.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Asymmetric bioreduction of an (E)‐β‐cyano‐2,4‐dienoic acid derivative by ene‐reductases allowed a shortened access to a precursor of pregabalin (S)‐3‐(aminomethyl)‐5‐methylhexanoic acid possessing ...the desired configuration in up to 94% conversion and >99% ee. Deuterium labelling studies showed that the nitrile moiety was the preferred activating/anchor group in the active site of the enzyme over the carboxylic acid or the corresponding methyl ester.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Asymmetric bioreduction of an (E)-beta-cyano-2,4-dienoic acid derivative by ene-reductases allowed a shortened access to a precursor of pregabalin (S)-3-(aminomethyl)-5-methylhexanoic acid possessing ...the desired configuration in up to 94% conversion and >99% ee. Deuterium labelling studies showed that the nitrile moiety was the preferred activating/anchor group in the active site of the enzyme over the carboxylic acid or the corresponding methyl ester.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In 1990, the US Congress amended the Clean Air Act (CAA) to reduce regional-scale ecosystem degradation from SO
x
and NO
x
emissions which have been responsible for acid deposition in regions such as ...the Adirondack Mountains of New York State. An ecosystem assessment project was conducted from 1994 to 2012 by the Darrin Fresh Water Institute to determine the effect of these emission reduction policies on aquatic systems. The project investigated water chemistry and biota in 30 Adirondack lakes and ponded waters. Although regulatory changes made in response to the 1990 CAA amendments resulted in a reduction of acid deposition within the Adirondacks, the ecosystem response to these reductions is complicated. A statistical analysis of SO
4
, pH, Al, and DOC data collected during this project demonstrates positive change in response to decreased deposition. The changes in water chemistry also have lowered the risk of Al toxicity to brook trout (
Salvelinus fontinalis
Mitchill), which allowed the re-introduction of this species to Brooktrout Lake from which it had been extirpated. However, pH and labile aluminum (Al
im
) fluctuate and are not strongly correlated to changes in acid deposition. As such, toxicity to
S. fontinalis
also is cyclic and provides rationale for the difficulties inherent in re-establishing resident populations in impacted aquatic environments. Overall, aquatic ecosystems of the Adirondacks show a positive response to reduced deposition driven by changes in environmental policy, but the response is more complex and indicates an ecosystem-wide interaction between aquatic and watershed components of the ecosystem.
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background. A mean of 9–10 years of human immunodeficiency virus type 1 (HIV-1) infection elapse before clinical AIDS develops in untreated persons, but this rate of disease progression varies ...substantially among individuals. To investigate host genetic determinants of the rate of progression to clinical AIDS, we performed a multistage genomewide association study. Methods. The discovery stage comprised 156 individuals from the Multicenter AIDS Cohort Study, enriched with rapid and long-term nonprogressors to increase statistical power. This was followed by replication tests of putatively associated genotypes in an independent population of 590 HIV-1-infected seroconverters. Results. Significant associations with delayed AIDS progression were observed in a haplotype located at 1q41, 36 kb upstream of PROX1 on chromosome 1 (relative hazard ratio, 0.69; Fisher's combined P=6.23×10−7). This association was replicated further in an analysis stratified by transmission mode, with the effect consistent in sexual or mucosal and parenteral transmission (relative hazard ratios, 0.72 and 0.63, respectively; combined P=1.23×10−7). Conclusions. This study identified and replicated a locus upstream of PROX1 that is associated with delayed progression to clinical AIDS. PROX1 is a negative regulator of interferon-γ expression in T cells and also mitigates the advancement of vascular neoplasms, such as Kaposi sarcoma, a common AIDS-defining malignancy. This study adds to the cumulative polygenic host component that effectively regulates the progression to clinical AIDS among HIV-1-infected individuals, raising prospects for potential new avenues for therapy and improvements in AIDS prognosis.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Concurrent regional and global environmental changes are affecting freshwater ecosystems. Decadal-scale data on lake ecosystems that can describe processes affected by these changes are important as ...multiple stressors often interact to alter the trajectory of key ecological phenomena in complex ways. Due to the practical challenges associated with long-term data collections, the majority of existing long-term data sets focus on only a small number of lakes or few response variables. Here we present physical, chemical, and biological data from 28 lakes in the Adirondack Mountains of northern New York State. These data span the period from 1994-2012 and harmonize multiple open and as-yet unpublished data sources. The dataset creation is reproducible and transparent; R code and all original files used to create the dataset are provided in an appendix. This dataset will be useful for examining ecological change in lakes undergoing multiple stressors.
Long-lived perennial plants, with distinctive habits of inter-annual growth, defense, and physiology, are of great economic and ecological importance. However, some biological mechanisms resulting ...from genome duplication and functional divergence of genes in these systems remain poorly studied. Here, we discovered an association between a poplar (Populus trichocarpa) 5-enolpyruvylshikimate 3-phosphate synthase gene (PtrEPSP) and lignin biosynthesis. Functional characterization of PtrEPSP revealed that this isoform possesses a helix-turn-helix motif in the N-terminus and can function as a transcriptional repressor that regulates expression of genes in the phenylpropanoid pathway in addition to performing its canonical biosynthesis function in the shikimate pathway. We demonstrated that this isoform can localize in the nucleus and specifically binds to the promoter and represses the expression of a SLEEPER-like transcriptional regulator, which itself specifically binds to the promoter and represses the expression of PtrMYB021 (known as MYB46 in Arabidopsis thaliana), a master regulator of the phenylpropanoid pathway and lignin biosynthesis. Analyses of overexpression and RNAi lines targeting PtrEPSP confirmed the predicted changes in PtrMYB021 expression patterns. These results demonstrate that PtrEPSP in its regulatory form and PtrhAT form a transcriptional hierarchy regulating phenylpropanoid pathway and lignin biosynthesis in Populus.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Sickle cell trait (SCT) has been associated with chronic kidney disease (CKD) in African Americans, although evidence for its impact in Africans and people with HIV is currently lacking. We conducted ...a cross-sectional study investigating the association between SCT and kidney disease in people of African ancestry with HIV in the UK.
The primary outcome was estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2. Secondary outcomes were eGFR <90 ml/min per 1.73 m2, end-stage kidney disease (ESKD; eGFR <15 ml/min per 1.73 m2, chronic dialysis, or having received a kidney transplant), proteinuria (protein-to-creatinine ratio >50 mg/mmol), and albuminuria (albumin-to-creatinine ratio >3 mg/mmol). Multivariable logistic regression was used to estimate the associations between SCT and kidney disease outcomes.
A total of 2895 participants (mean age 48.1 SD 10.3, 57.2% female) were included, of whom 335 (11.6%) had SCT and 352 (12.2%) had eGFR <60 ml/min per 1.73 m2. After adjusting for demographic, HIV, and kidney risk factors including APOL1 high-risk genotype status, individuals with SCT were more likely to have eGFR <60 ml/min per 1.73 m2 (odds ratio 1.62 95% CI 1.14–2.32), eGFR <90 ml/min per 1.73 m2 (1.50 1.14–1.97), and albuminuria (1.50 1.09–2.05). Stratified by APOL1 status, significant associations between SCT and GFR <60 ml/min per 1.73 m2, eGFR <90 ml/min per 1.73 m2, proteinuria, and albuminuria were observed for those with APOL1 low-risk genotypes.
Our results extend previously reported associations between SCT and kidney disease to people with HIV. In people of African ancestry with HIV, these associations were largely restricted to those with APOL1 low-risk genotypes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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