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Low-temperature pyrolysis of biomass produces a product known as biochar. The incorporation of this material into the soil has been advocated as a C sequestration method. Biochar also has the potential to influence the soil N cycle by altering nitrification rates and by adsorbing NH₄⁺ or NH₃. Biochar can be incorporated into the soil during renovation of intensively managed pasture soils. These managed pastures are a significant source of N₂O, a greenhouse gas, produced in ruminant urine patches. We hypothesized that biochar effects on the N cycle could reduce the soil inorganic-N pool available for N₂O-producing mechanisms. A laboratory study was performed to examine the effect of biochar incorporation into soil (20 Mg ha⁻¹) on N₂O-N and NH₃–N fluxes, and inorganic-N transformations, following the application of bovine urine (760 kg N ha⁻¹). Treatments included controls (soil only and soil plus biochar), and two urine treatments (soil plus urine and soil plus biochar plus urine). Fluxes of N₂O from the biochar plus urine treatment were generally higher than from urine alone during the first 30 d, but after 50 d there was no significant difference (P = 0.11) in terms of cumulative N₂O-N emitted as a percentage of the urine N applied during the 53-d period; however, NH₃–N fluxes were enhanced by approximately 3% of the N applied in the biochar plus urine treatment compared with the urine-only treatment after 17 d. Soil inorganic-N pools differed between treatments, with higher NH₄⁺ concentrations in the presence of biochar, indicative of lower rates of nitrification. The inorganic-N pool available for N₂O-producing mechanisms was not reduced, however, by adding biochar.

We analyzed gait and function of the supporting limb in participants of a marathon race at three stages: prerace, midrace (18 km), and near the end of the race (36 km). We confirmed that the most successful runners were able to maintain running speed for the duration of the race with little change in speed or gait. Speed slowed progressively during the race for those with slower race times, but stride frequency-stride length relationships remained normal for the speed they ran. These findings differ from most lab-based studies of fatigue, in which runners are forced to match a constant preset treadmill speed. Small changes in maximum ground force were seen in both slow- and fast-running participants as race end approached.

In the present study, the authors explored the effect of manipulating the distance between footfalls (pace length) in level walking in 3 men. The translational kinetic energy to gravitational potential energy (E k -E p ) exchange was found to be maintained until pace length reached approximately 110% of single limb length. Beyond that pace length, the compliance of the support limb increased, apparently to allow the muscular absorption of excess kinetic energy. E p oscillations decreased with increasing limb compliance, and the participants could control that relationship with pace length alone. The authors compared the present results with previous descriptions of the relationship between limb compliance and pace length in running. An analog of the running relationship holds for walking as well. The trigger for those gait modifications has not yet been identified, however. The present results have implications for the exploration of the integrated control of mechanical consequences in human locomotion and for understanding the walk-run transition in bipeds other than humans, such as ground-dwelling birds.

Verneri Anttila and colleagues report meta-analysis of 29 genome-wide association studies for migraine. They identify five loci newly associated with migraine, three of which are associated with specific subtypes of migraine with or without aura. Migraine is the most common brain disorder, affecting approximately 14% of the adult population, but its molecular mechanisms are poorly understood. We report the results of a meta-analysis across 29 genome-wide association studies, including a total of 23,285 individuals with migraine (cases) and 95,425 population-matched controls. We identified 12 loci associated with migraine susceptibility ( P < 5 × 10 −8 ). Five loci are new: near AJAP1 at 1p36, near TSPAN2 at 1p13, within FHL5 at 6q16, within C7orf10 at 7p14 and near MMP16 at 8q21. Three of these loci were identified in disease subgroup analyses. Brain tissue expression quantitative trait locus analysis suggests potential functional candidate genes at four loci: APOA1BP , TBC1D7 , FUT9 , STAT6 and ATP5B .

Our published model of a lymphatic vessel consisting of multiple actively contracting segments between non-return valves has been further developed by the incorporation of properties derived from observations and measurements of rat mesenteric vessels. These included (1) a refractory period between contractions, (2) a highly nonlinear form for the passive part of the pressure–diameter relationship, (3) hysteretic and transmural-pressure-dependent valve opening and closing pressure thresholds and (4) dependence of active tension on muscle length as reflected in local diameter. Experimentally, lymphatic valves are known to be biased to stay open. In consequence, in the improved model, vessel pumping of fluid suffers losses by regurgitation, and valve closure is dependent on backflow first causing an adverse valve pressure drop sufficient to reach the closure threshold. The assumed resistance of an open valve therefore becomes a critical parameter, and experiments to measure this quantity are reported here. However, incorporating this parameter value, along with other parameter values based on existing measurements, led to ineffective pumping. It is argued that the published measurements of valve-closing pressure threshold overestimate this quantity owing to neglect of micro-pipette resistance. An estimate is made of the extent of the possible resulting error. Correcting by this amount, the pumping performance is improved, but still very inefficient unless the open-valve resistance is also increased beyond the measured level. Arguments are given as to why this is justified, and other areas where experimental data are lacking are identified. The model is capable of future adaptation as new experimental data appear.

Exogenous BMP-4 amplifies asymmetric ureteric branching in the developing mouse kidney in vitro. Exogenous bone morphogenetic protein 4 (BMP-4) has been reported to inhibit ureteric branching morphogenesis and regulate the anterior-posterior axis of the developing kidney in vitro. We examined the role of BMP-4 on ureteric branching in vitro using three-dimensional image analysis software and statistical models. Additionally, in vivo ureteric branching was analyzed and the effect of reduced levels of BMP-4 in vivo on nephron number was examined. Embryonic day 12.5 (E12.5) Balb/c mouse metanephroi cultured for 48 hours with or without 260 ng/mL recombinant human BMP-4 (rhBMP-4) were immunostained to identify the ureteric epithelium which was quantified in three dimensions. In vivo ureteric branching morphogenesis in Hoxb7/GFP mice was also analyzed. The effect of reduced in vivo levels of BMP-4 on nephron number was examined in BMP-4+/− and wild-type mice using an unbiased stereologic method. Qualitative and quantitative studies identified a decrease in total ureteric length and branch number in wild-type mouse metanephroi cultured in the presence of BMP-4. A marked anterior-posterior asymmetry in both ureteric length and branch number was observed in BMP-4-treated metanephroi. A similar asymmetry was revealed in control metanephroi, both in vitro and in vivo. This asymmetry is the result of reduced ureteric branching morphogenesis in the posterior region of the kidney and appears to be due to slower growth rather than the adoption of an alternate branching pattern. Reduction of endogenous BMP-4 in BMP-4+/− mice resulted in no change in total nephron number in macroscopically normal kidneys. These results suggest that BMP-4 plays an important role in the regulation of ureteric branching morphogenesis, and that excess BMP-4 in vitro can amplify the existing asymmetry of the normal mouse kidney.

Smooth muscle cells (SMC) play a central role in maintaining the structural and functional integrity of muscle tissue. Little is known about the early in vitro events that guide the assembly of ‘bioartificial tissue’ (constructs) and recapitulate the key aspects of smooth muscle differentiation and development before surgical implantation. Biomimetic approaches have been proposed that enable the identification of in vitro processes which allow standardized manufacturing, thus improving both product quality and the consistency of patient outcomes. One essential element of this approach is the description of the SMC secretome, that is, the soluble and deposited factors produced within the three-dimensional (3D) extracellular matrix (ECM) microenvironment. In this study, we utilized autologous SMC from multiple tissue types that were expanded ex vivo and generated with a rigorous focus on operational phenotype and genetic stability. The objective of this study was to characterize the spatiotemporal dynamics of the first week of organoid maturation using a well-defined in vitro -like, 3D-engineered scale model of our validated manufacturing process. Functional proteomics was used to identify the topological properties of the networks of interacting proteins that were derived from the SMC secretome, revealing overlapping central nodes related to SMC differentiation and proliferation, actin cytoskeleton regulation, and balanced ECM accumulation. The critical functions defined by the Ingenuity Pathway Analysis included cell signaling, cellular movement and proliferation, and cellular and organismal development. The results confirm the phenotypic and functional similarity of the SMC generated by our platform technology at the molecular level. Furthermore, these data validate the biomimetic approaches that have been established to maintain manufacturing consistency.

Heart failure (HF) with reduced left ventricular ejection fraction (LVEF) after acute myocardial infarction (AMI) is associated with increased readmission rates. This study evaluated the effects of eplerenone, a selective aldosterone blocking agent, on the duration of subsequent hospitalizations for HF in the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). The EPHESUS study included 6,632 patients post-AMI with LVEF ≤40% and clinical HF or diabetes, receiving standard therapy, randomized to either eplerenone 25 mg, titrated to 50 mg daily, or placebo, with a mean follow-up of 16 months. Analyses of the length of stay and total number of days of HF hospitalizations per patient were conducted on a subgroup of 828 patients with subsequent HF hospitalizations, overall and across 5 distinct geographic regions. Eplerenone was associated with a 1.6-day reduction in the mean length of HF hospitalization (9.2 vs 10.8 days with placebo; P = .019) and 3.6-day reduction in the total days spent in the hospital for HF (13.3 vs 16.9 days with placebo; P = .0006). These benefits were observed in all geographic regions. In patients post-AMI with reduced LVEF and HF or diabetes, eplerenone added to standard therapy reduced the mean length and total days of HF hospitalizations compared to placebo in all regions. Given the high cost of hospital care for HF, these findings may translate into an economic benefit to health care worldwide.

Slipping or recurrent dislocation of the patella is a condition “seen almost entirely in girls or women, and is due, in large part, to the fact that the line of pull of the quadriceps extensor muscle is not straight.” Eleven patients with this condition are the basis for this paper. “... it seems to be true that, if the patella has slipped out several times without special violence, it is an evidence of joint instability... and, while the slipping may be controlled by simple measures, the weakness usually remains, and the joint is unable to stand the strain of normal use. For this reason, although bandaging, braces for the knees, the correction of flat or pronated feet, should always be tried in the early stages of the trouble before the slipping has become frequent, comparatively little is to be expected in the way of permanency of relief from such measures... The treatment which has been most satisfactory in meeting this condition is an operation in which the outer half of the patella tendon is reattached to the tibia well to the inside of the tubercle. In this way the angle in the muscle pull is lessened or entirely removed... Of the eight operations which have been performed in which this has been the chief feature, in seven no after-trouble has resulted, and the stability of the joints has made them equal to normal use.”

A total of 1,243 Ezza people living in 10 communities of Ebonyi State, eastern Nigeria were examined between July 2002-January 2003 for lymphatic filariasis. This is the first time a filariasis survey due to Wuchereria bancrofti has been carried out in this state. Of the 1,243 persons examined, 210 (16.9 %) had W. bancrofti microfilariae. Infection varied significantly among communities and ages (p < 0.05) but not sex-related (p > 0.05). The Ezza people are predominantly farmers and professional hired labourers. There was a close association between microfilaria rate and microfilaria -density in various age groups (r = 0.812; p < 0.01). Microfilaria density is an important measure in the epidemiology, treatment and control of human filarisis in this endemic foci. Clinical signs and symptoms of the disease include elephantiasis, hydrocoele, dermatitis and periodic fever. Clinical symptoms without microfilaraemia and microfilaraemia without clinical symptoms were also observed. Of 1,603 mosquitoes dissected, Anopheles gambiae, An. funestus and Culex quinquefasciatus showed infectivity rates of 6.3 %, 5.1 % and 6.0 % respectively. The affected persons and other key informants are unaware of the cause of the disease and attributed it to witchcraft, violation of taboo, bad water and food. Intervention strategies to be integrated into the on-going Community-Directed Treatment with Ivermectin (CDTI) project are discussed.