Resource Development and Conservation History Along the Ohio River

Author Institution: School of Natural Resources, The Ohio State UniversityThe 1578 km-long Ohio River has a rich history of natural resource use and abuse, starting with the development of the river itself for navigational purposes. There is a rich early record of natural history studies by Bartram, Michaux, Lesueur, Rafinesque and others. The navigational use of the river began with snag pulling and has progressed to modern high-lift dams. Flood control, navigation of tributaries, and canal-building have been water resource development projects of the past. Early industries that developed around the availability and abundance of coal, oil, natural gas, salt, iron ore, timber, and clay in the valley ultimately led to the more recent pottery, iron and steel, chemical, and power generation industries along the river and its tributaries. There were also major horticultural developments of apple orchards, wine vineyards, and even silk worm farms along the river and a modest button industry from the mussels in the river itself. The pollution of the Ohio River has been a concern for decades, and the involvement of the federal government and the establishment of interstate compacts have led to the development of significant understanding of the science of water pollution and to the general improvement of the river's water quality

Peripheral Tolerance of CD8 T Lymphocytes

SummaryWhereas high-avidity recognition of peptide-MHC complexes by developing T cells in the thymus results in deletion and promotes self-tolerance, such recognition by mature T cells in the periphery results in activation and clonal expansion. This dichotomy represents the basis of a dilemma that has stumped immunologists for many years, how are self-specific T cells tolerized in the periphery? There appear to be two important criteria used to achieve this goal. The first is that in the absence of inflammatory pathogens, tolerance is promoted when T cells recognize antigen presented by quiescent dendritic cells (DCs) expressing low levels of costimulatory molecules. A second critical factor that defines “self” and drives tolerance through deletion, anergy, or suppression is the persistence of antigen

Prospective Relations between Red Blood Cell ω-6 and ω-3 Fatty Acid Composition and Cognitive Function among Older Puerto Rican Adults

Objectives: To examine the association between red blood cell (RBC) ω-6 and ω-3 fatty acid (FA) composition and cognitive function over 2-y follow-up among older U.S. mainland Puerto Ricans. Methods: Data are from the Boston Puerto Rican Health Study (74% female; 57±8 y). RBC membrane FA status was ascertained at baseline. Individual FA were expressed as a percentage of total FA identified. Cognitive function was measured at baseline and at 2-y using the Mini-Mental State Exam (MMSE), where a higher score ranging from 0-30 indicates better function. Cognitive impairment was defined as MMSE scores ≤21, ≤23, and ≤24 for those with less than a 9th grade education, a 9th to 12th grade education, and some college education or higher, respectively. Relations between FA and MMSE scores were examined in 946 participants and incidence of cognitive impairment among those considered to be cognitively normal at baseline (n=639). Results: In multivariate models additionally adjusted for baseline MMSE, total ω-6 FA (quartiles) were associated with lower MMSE score at 2-y (P-trend=0.003). Total ω-3 FA were positively (P-trend=0.04) and the ω-6:ω-3 ratio inversely (P-trend=0.007) related to 2-y MMSE, but these relationships attenuated with adjustment for baseline score. The incidence of cognitive impairment at follow-up was 22%. In multivariate models, a 1% increase in total ω-6 FA related to a 9% greater incidence of cognitive impairment [RR=1.09 (95% CI: 1.00, 1.18), P=0.04]. Total ω-3 FA were inversely related to incident cognitive impairment [RR=0.92 (0.81 to 1.05), P=0.21], whereas the ω-6:ω-3 ratio was positively associated [RR=1.12 (95% CI: 0.98, 1.26), P=0.08]. Conclusions: An objective biomarker of ω-6 FA consumption was associated with poorer cognitive function and incidence of cognitive impairment over 2-y follow-up, suggesting that greater intakes of food sources of ω-6 FA may play a role in cognitive decline among older U.S. mainland Puerto Ricans

Sotatercept safety and effects on hemoglobin, bone, and vascular calcification

Introduction: Patients with end-stage kidney disease (ESKD) exhibit anemia, chronic kidney disease‒mineral bone disorder (CKD-MBD), and cardiovascular disease. The REN-001 and REN-002 phase II, multicenter, randomized studies examined safety, tolerability, and effects of sotatercept, an ActRIIA-IgG1 fusion protein trap, on hemoglobin concentration; REN-001 also explored effects on bone mineral density (BMD) and abdominal aortic vascular calcification. Methods: Forty-three patients were treated in REN-001 (dose range: sotatercept 0.3‒0.7 mg/kg or placebo subcutaneously [s.c.] for 200 days) and 50 in REN-002 (dose range: 0.1‒0.4 mg/kg i.v. and 0.13‒0.5 mg/kg s.c. for 99 days). Results: In REN-001, frequency of achieving target hemoglobin response (\u3e10 g/dl [6.21 mmol/l]) with sotatercept was dose-related and greater than placebo (0.3 mg/kg: 33.3%; 0.5 mg/kg: 62.5%; 0.7 mg/kg: 77.8%; 0.7 mg/kg [doses 1 and 2]/0.4 mg/kg [doses 3‒15]: 33.3%; placebo: 27.3%). REN-002 hemoglobin findings were similar (i.v.: 16.7%-57.1%; s.c.: 11.1%‒42.9%). Dose-related achievement of ≥2% increase in femoral neck cortical BMD was seen among only REN-001 patients receiving sotatercept (0.3‒0.7 mg/kg: 20.0%‒57.1%; placebo: 0.0%). Abdominal aortic vascular calcification was slowed in a dose-related manner, with a ≤15% increase in Agatston score achieved by more REN-001 sotatercept versus placebo patients (60%‒100% vs. 16.7%). The most common adverse events during treatment were hypertension, muscle spasm, headache, arteriovenous fistula site complication, and influenza observed in both treatment and placebo groups. Conclusion: In patients with ESKD, sotatercept exhibited a favorable safety profile and was associated with trends in dose-related slowing of vascular calcification. Less-consistent trends in improved hemoglobin concentration and BMD were observed

A multicenter study investigating factors that influence initiation of return to sport functional testing following ACL reconstruction

Despite advances in surgical technique and rehabilitation following anterior cruciate ligament (ACL) reconstruction, re-injury rates after return to play (RTP) are high. There remains controversy over the most effective criteria utilized to initiate RTP functional testing following ACL reconstruction. The purpose of this study is to investigate factors that influence provider decision to initiate RTP functional testing

Structure and activity of DmmA, a marine haloalkane dehalogenase

DmmA is a haloalkane dehalogenase (HLD) identified and characterized from the metagenomic DNA of a marine microbial consortium. Dehalogenase activity was detected with 1,3‐dibromopropane as substrate, with steady‐state kinetic parameters typical of HLDs ( K m = 0.24 ± 0.05 mM, k cat = 2.4 ± 0.1 s −1 ). The 2.2‐Å crystal structure of DmmA revealed a fold and active site similar to other HLDs, but with a substantially larger active site binding pocket, suggestive of an ability to act on bulky substrates. This enhanced cavity was shown to accept a range of linear and cyclic substrates, suggesting that DmmA will contribute to the expanding industrial applications of HLDs. PDB Code(s): 3U1TPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90241/1/PRO_2009_sm_suppinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/90241/2/2009_ftp.pd

A comparison of renal phosphorus regulation in thermally-injured and multiple trauma patients receiving specialized nutrition support

To compare phosphorus intake and renal phosphorus regulation between thermally injured patients and multiple trauma patients, 40 consecutive critically ill patients, 20 with thermal injury and 20 with multiple trauma, who required enteral tube feeding were evaluated. Phosphorus intakes were recorded for 14 days from the initiation of tube feeding which was started 1 to 3 days post-injury. Serum for determination of phosphorus concentrations was collected at days 1, 3, 7, and 14 of the study period. A 24-hour urine collection was obtained during the first and second weeks of nutrition support for urinary phosphorus excretion, fractional excretion of phosphorus, renal threshold phosphate concentration, and phosphorus clearance. Average total daily phosphorus intake during the 14-day study for thermally injured patients and multiple trauma patients was 0.99 ± 0.26 mmol/kg/d vs 0.58 ± 0.21 mmol/kg/d, respectively, p \u3c .001. Serum phosphorus concentration on the third day of observation was significantly lower in the thermally injured group than those with multiple trauma (1.9 ± 0.8 mg/dL vs 3.0 ± 0.8 mg/dL, p ≤ .01). A trend toward hypophosphatemia in the thermally injured group persisted by the seventh day of feeding (2.7 ± 1.2 mg/dL vs 3.3 ± 0.6 mg/dL, p ≤ .04). Differences in urinary phosphorus excretion was not statistically significant between the thermally injured and multiple trauma groups (271 ± 213 mg/d vs 171 ± 181 mg/d for week 1, and 320 ± 289 mg/d vs 258 ± 184 mg/d for week 2, respectively). Urinary phosphorus clearance, fractional excretion of phosphorus, or renal threshold phosphate concentrations were also not significantly different between thermally injured and multiple trauma patients. During nutrition support, serum phosphorus concentrations are lower in thermally injured patients compared with multiple trauma patients despite receiving a significantly greater intake of phosphorus. Renal phosphorus regulation does not significantly contribute to the profound hypophosphatemia observed in thermally injured patients when compared with multiple trauma patients during nutrition support

Repurposing the GNAT Fold in the Initiation of Polyketide Biosynthesis.

Natural product biosynthetic pathways are replete with enzymes repurposed for new catalytic functions. In some modular polyketide synthase (PKS) pathways, a GCN5-related N-acetyltransferase (GNAT)-like enzyme with an additional decarboxylation function initiates biosynthesis. Here, we probe two PKS GNAT-like domains for the dual activities of S-acyl transfer from coenzyme A (CoA) to an acyl carrier protein (ACP) and decarboxylation. The GphF and CurA GNAT-like domains selectively decarboxylate substrates that yield the anticipated pathway starter units. The GphF enzyme lacks detectable acyl transfer activity, and a crystal structure with an isobutyryl-CoA product analog reveals a partially occluded acyltransfer acceptor site. Further analysis indicates that the CurA GNAT-like domain also catalyzes only decarboxylation, and the initial acyl transfer is catalyzed by an unidentified enzyme. Thus, PKS GNAT-like domains are re-classified as GNAT-like decarboxylases. Two other decarboxylases, malonyl-CoA decarboxylase and EryM, reside on distant nodes of the superfamily, illustrating the adaptability of the GNAT fold

Characteristics of patients with chronic back pain who benefit from acupuncture

<p>Abstract</p> <p>Background</p> <p>Although many clinicians believe there are clinically important subgroups of persons with "non-specific" low back pain, such subgroups have not yet been clearly identified. As part of a large trial evaluating acupuncture for chronic low back pain, we sought to identify subgroups of participants that were particularly responsive to acupuncture.</p> <p>Methods</p> <p>We performed a secondary analysis of data for the 638 participants in our clinical trial comparing different types of acupuncture to usual care to identify baseline characteristics that predicted responses to individualized, standardized, or simulated acupuncture treatments. After identifying factors that predicted improvements in back-related function or symptoms, we determined if these factors were more likely to predict improvement for those receiving the acupuncture treatments than for those receiving usual care. This was accomplished by testing for an interaction between the prognostic factors and treatment group in four models: functional outcomes (measured by the Roland-Morris Disability Scale) at 8 and 52 weeks post-randomization and symptom outcomes (measured with a numerical rating scale) at 8 and 52 weeks.</p> <p>Results</p> <p>Overall, the strongest predictors of improvement in back function and symptoms were higher baseline levels of these measures, receipt of an acupuncture treatment, and non-use of narcotic analgesics. Benefit from acupuncture compared to usual care was greater with worse pre-treatment levels of back dysfunction (interaction p < 0.004 for the functional outcome, Roland Morris Disability Scale at 8 weeks). No other consistent interactions were observed.</p> <p>Conclusion</p> <p>This secondary analysis found little evidence for the existence of subgroups of patients with chronic back pain that would be especially likely to benefit from acupuncture. However, persons with chronic low back pain who had more severe baseline dysfunction had the most short-term benefit from acupuncture.</p