Sparse estimation for structural variability

Background  

Proteins are dynamic molecules that exhibit a wide range of motions; often these conformational changes are important for protein function. Determining biologically relevant conformational changes, or true variability, efficiently is challenging due to the noise present in structure data.     

Adiponectin changes in relation to the macronutrient composition of a weight-loss diet

Adiponectin is an adipose-derived protein with beneficial metabolic effects. Low adiponectin is associated with obesity and related diseases. Significant weight loss increases adiponectin, reducing disease risk. This study compared the effects of two weight-loss diets with different macronutrient compositions on adiponectin. Eighty-one obese women in two cohorts were randomized to a low-fat (LF) or a low-carbohydrate (LC) diet. All subjects underwent equivalent weight-loss intervention, with weight and other measures assessed at baseline and after 6 (cohort I) or 4 (cohort II) months. Body fat was measured by dual energy X-ray absorptiometry. Adiponectin was measured by radioimmunoassay. Diet intake was assessed using 24-h recalls and 3-day diet records. Data were analyzed via t-tests and repeated-measures factorial ANOVA using time, diet, and replicate (cohort I vs. cohort II) as factors. Age, weight, body fat, BMI, adiponectin, and diet were similar at baseline. Following intervention, macronutrient composition of the diet was vastly different between the groups, reflecting the assigned diet. Both groups lost weight and body fat (P < 0.001), with effect in LC dieters greater than LF dieters (-9.1 kg vs. -4.97 kg weight, P < 0.05 and -5.45 kg vs. -2.62 kg fat, P < 0.001). Adiponectin increased in the LC (+1.92 mcg/ml, P < 0.01), but not the LF (+0.86 mcg/ml, P = 0.81), group. There was no correlation between weight loss and increase in adiponectin. These results confirm that diet-induced loss of weight and body fat is associated with increased adiponectin concentrations. This effect is evident with weight loss of 10% or more, and may be greater with LC diets.     

Bright Start: Description and Main Outcomes From a Group‐Randomized Obesity Prevention Trial in American Indian Children

The aim of the Bright Start study was to develop and test the effectiveness of a school environment intervention, supplemented with family involvement, to reduce excessive weight gain by increasing physical activity and healthy eating practices among kindergarten and first‐grade American Indian children. Bright Start was a group‐randomized, school‐based trial involving 454 children attending 14 schools on the Pine Ridge Reservation in South Dakota. Children were followed from the beginning of their kindergarten year through the end of first grade. Main outcome variables were mean BMI, mean percent body fat, and prevalence of overweight/obese children. The goals of the intervention were to: increase physical activity at school to at least 60 min/day; modify school meals and snacks; and involve families in making behavioral and environmental changes at home. At baseline, 32% of boys and 25% of girls were overweight/obese. Although the intervention was not associated with statistically significant change in mean levels of BMI, BMI‐Z, skinfolds or percentage body fat, the intervention was associated with a statistically significant net decrease of 10% in the prevalence of overweight. Intervention children experienced a 13.4% incidence of overweight, whereas the control children experienced a corresponding incidence of 24.8%; a difference of ?11.4% (P = 0.033). The intervention significantly reduced parent‐reported mean child intakes of sugar‐sweetened beverages, whole milk, and chocolate milk. Changes in duration of school physical activity were not significant. Because obesity is the most daunting health challenge facing American Indian children today, more intervention research is needed to identify effective approaches.     

Imaging Glioma Initiation In Vivo Through a Polished and Reinforced Thin-skull Cranial Window

Glioma is the one of the most lethal forms of human cancer. The most effective glioma therapy to date-surgery followed by radiation treatment-offers patients only modest benefits, as most patients do not survive more than five years following diagnosis due to glioma relapse ^1,2. The discovery of cancer stem cells in human brain tumors holds promise for having an enormous impact on the development of novel therapeutic strategies for glioma ³. Cancer stem cells are defined by their ability both to self-renew and to differentiate, and are thought to be the only cells in a tumor that have the capacity to initiate new tumors ⁴. Glioma relapse following radiation therapy is thought to arise from resistance of glioma stem cells (GSCs) to therapy ^5-10. In vivo, GSCs are shown to reside in a perivascular niche that is important for maintaining their stem cell-like characteristics ^11-14. Central to the organization of the GSC niche are vascular endothelial cells ¹². Existing evidence suggests that GSCs and their interaction with the vascular endothelial cells are important for tumor development, and identify GSCs and their interaction with endothelial cells as important therapeutic targets for glioma. The presence of GSCs is determined experimentally by their capability to initiate new tumors upon orthotopic transplantation ¹⁵. This is typically achieved by injecting a specific number of GBM cells isolated from human tumors into the brains of severely immuno-deficient mice, or of mouse GBM cells into the brains of congenic host mice. Assays for tumor growth are then performed following sufficient time to allow GSCs among the injected GBM cells to give rise to new tumors-typically several weeks or months. Hence, existing assays do not allow examination of the important pathological process of tumor initiation from single GSCs in vivo. Consequently, essential insights into the specific roles of GSCs and their interaction with the vascular endothelial cells in the early stages of tumor initiation are lacking. Such insights are critical for developing novel therapeutic strategies for glioma, and will have great implications for preventing glioma relapse in patients. Here we have adapted the PoRTS cranial window procedure ¹⁶and in vivo two-photon microscopy to allow visualization of tumor initiation from injected GBM cells in the brain of a live mouse. Our technique will pave the way for future efforts to elucidate the key signaling mechanisms between GSCs and vascular endothelial cells during glioma initiation.     

Functional effects of nanoparticle exposure on Calu-3 airway epithelial cells

High concentrations of manufactured carbon nanoparticles (CNP) are known to cause oxidative stress, inflammatory responses and granuloma formation in respiratory epithelia. To examine the effects of lower, more physiologically relevant concentrations, the human airway epithelial cell line, Calu-3, was used to evaluate potential alterations in transepithelial permeability and cellular function of airway epithelia after exposure to environmentally realistic concentrations of carbon nanoparticles. Three common carbon nanoparticles, fullerenes, single- and multi-wall carbon nanotubes (SWCNT, MWCNT) were used in these experiments. Electrophysiological measurements were performed to assay transepithelial electrical resistance (TEER) and epinephrine-stimulated chloride (Cl(-)) ion secretion of epithelial cell monolayers that had been exposed to nanoparticles for three different times (1 h, 24 h and 48 h) and over a 7 log unit range of concentrations. Fullerenes did not have any effect on the TEER or stimulated ion transport. However, the carbon nanotubes (CNT) significantly decreased TEER and inhibited epinephrine-stimulated Cl(-) secretion. The changes were time dependent and at more chronic exposures caused functional effects which were evident at concentrations substantially lower than have been previously examined. The functional changes manifested in response to physiologically relevant exposures would inhibit mucociliary clearance mechanisms and compromise the barrier function of airway epithelia.     

A feedback inclusive neuromuscular training program alters frontal plane kinematics

Anterior cruciate ligament (ACL) neuromuscular training programs have demonstrated beneficial effects in reducing ACL injuries, yet further evaluation of their effects on biomechanical measures across a sports team season is required to elucidate the specific factors that are modifiable. The purpose of this study was to evaluate the effects of a 10-week off-season neuromuscular training program on lower extremity kinematics. Twelve Division I female soccer players (age: 19.2 ± 0.8 years, height: 1.67 ± 0.1 m, weight: 60.2 ± 6.5 kg) performed unanticipated dynamic trials of a running stop-jump task pretraining and posttraining. Data collection was performed using an 8-camera Vicon system (Los Angeles, CA, USA) and 2 Bertec (Columbus, OH, USA) force plates. The 10-week training program consisted of resistance training 2 times per week and field training, consisting of plyometric, agility, and speed drills, 2 times per week. Repeated measures analyses of variance (ANOVAs) were used to assess the differences between pretraining and posttraining kinetics and kinematics of the hip, knee, and ankle at initial contact (IC), peak knee flexion (PKF), and peak stance. Repeated measures ANOVAs were also used to assess isometric strength differences pretraining and posttraining. The alpha level was set at 0.05 a priori. The training program demonstrated significant increases in left hip extension, left and right hip flexion, and right hip adduction isometric strength. At IC, knee abduction angle moved from an abducted to an adducted position (-1.48 ± 3.65° to 1.46 ± 3.86°, p = 0.007), and hip abduction angle increased (-6.05 ± 4.63° to -10.34 ± 6.83°, p = 0.007). Hip abduction angle at PKF increased (-2.23 ± 3.40° to 6.01 ± 3.82°, p = 0.002). The maximum knee extension moment achieved at peak stance increased from pretraining to posttraining (2.02 ± 0.32 to 2.38 ± 0.75 N·m·kg?1, p = 0.027). The neuromuscular training program demonstrated a potential positive effect in altering mechanics that influence the risk of incurring an ACL injury.