Possible implication of undescribed SMN1-SMN2 genotype in chronic EMG-pattern of SMA with transitory acute denervation

Spinal muscular atrophy (SMA) refers to a group of genetic neuromuscular disorders affecting lower motor neurons causative of numerous phenotypes. To date, according to the age of onset, maximum muscular activity achieved, and life expectation four types of SMA are recognized, all caused by mutations in the SMN1 gene with SMN2 copy number influencing disease severity. Herein, we describe the case of a 31-year-old young male with normal psychomotor development who has experienced fatigue, cramps, and muscle fasciculations in the lower limbs for a period of 2 months. Based on electrophysiological and clinical findings we performed SMA genetic, clinical exome and RNA expression of candidate genes which led us to suggest SMN1-SMN2 genes [(2+0) and (0+0)] combination as possibly being implicated in the phenotype.     

Stabilization strategies for unstable dynamics

The stabilization of the human standing posture was originally attributed to the stiffness of the ankle muscles but direct measurements of the ankle stiffness ruled out this hypothesis, leaving open the possibility for a feedback stabilization strategy driven by proprioceptive signals. This solution, however, could be implemented with two different kinds of control mechanisms, namely continuous or intermittent feedback. The debate is now settled and the latter solution seems to be the most plausible one. Moreover, stabilization of unstable dynamics is not limited to bipedal standing. Indeed many manipulation tasks can be described in the same framework and thus a very general protocol for addressing this kind of problems is the use of haptic virtual reality where instability is generated by some kind of divergent or saddle-like force field. Several studies demonstrated that human subjects can choose to adopt a stiffness or feedback strategy as a combination of biomechanical and task constraints and can learn to switch from one strategy to the other if it is feasible or to use one or the other is infeasible. Understanding such mechanisms is relevant, for example, for the design of novel ergonomic man-machine interfaces in difficult, unstable tasks.     

Axial systems and their actuation: new twists on the ancient body of craniates

Craniate animals – vertebrates and their jawless sister taxa – have evolved a body axis with powerful muscles, a distributed nervous system to control those muscles, and an endoskeleton that starts at the head and ends at the caudal fin. The body axis undulates, bends, twists, or holds firm, depending on the behavior. In this introduction to the special issue on axial systems and their actuation, we provide an overview of the latest research on how the body axis functions, develops, and evolves. Based on this research, we hypothesize that the body axis of craniates has three primary, post-cranial modules: precaudal, caudal, and tail. The term “module” means a portion of the body axis that functions, develops, and evolves in relative independence from other modules; “relative independence” means that structures and processes within a module are more tightly correlated in function, development, and behavior than the same processes are among modules.     

Blood,War, and Ritual: Religious Ecology, ‘Strong’ Culture,and Human Sacrifice in the Premodern World

What social factors predict human sacrifice in premodern societies? After summarising key insights from competing theoretical perspectives that seek to explain the presence of human sacrifice in premodern societies, we empirically assess the explanatory utility of each theory. We draw from Stark's ‘moral communities’ argument and Alexander and Smith's insights regarding cultural autonomy to highlight how the macro-level organisation of premodern societies impacted the practice of human sacrifice. Using data from Murdock and White's Standard Cross-Cultural Sample, logistic regression models suggest that premodern societies that expressed community ties through religious ceremonies were more likely to engage in human sacrifice, while beliefs in spirit aggression are correlated with lower likelihood of human sacrifice. In terms of non-religious factors, societies that experienced frequent famine were slightly less likely to activity in the ancient world are partly a function of societal complexity. We conclude by specifying the theoretical implications of these findings.     

A Toxoplasma gondii Class XIV Myosin,Expressed in Sf9 Cells with a Parasite Co-chaperone,Requires Two Light Chains for Fast Motility

Many diverse myosin classes can be expressed using the baculovirus/Sf9 insect cell expression system, whereas others have been recalcitrant. We hypothesized that most myosins utilize Sf9 cell chaperones, but others require an organism-specific co-chaperone. TgMyoA, a class XIVa myosin from the parasite Toxoplasma gondii, is required for the parasite to efficiently move and invade host cells. The T. gondii genome contains one UCS family myosin co-chaperone (TgUNC). TgMyoA expressed in Sf9 cells was soluble and functional only if the heavy and light chain(s) were co-expressed with TgUNC. The tetratricopeptide repeat domain of TgUNC was not essential to obtain functional myosin, implying that there are other mechanisms to recruit Hsp90. Purified TgMyoA heavy chain complexed with its regulatory light chain (TgMLC1) moved actin in a motility assay at a speed of ∼1.5 μm/s. When a putative essential light chain (TgELC1) was also bound, TgMyoA moved actin at more than twice that speed (∼3.4 μm/s). This result implies that two light chains bind to and stabilize the lever arm, the domain that amplifies small motions at the active site into the larger motions that propel actin at fast speeds. Our results show that the TgMyoA domain structure is more similar to other myosins than previously appreciated and provide a molecular explanation for how it moves actin at fast speeds. The ability to express milligram quantities of a class XIV myosin in a heterologous system paves the way for detailed structure-function analysis of TgMyoA and identification of small molecule inhibitors.     

Colocalization studies of Arp1 and p150Glued to spindle microtubules during mitosis: the effect of cytochalasin on the organization of microtubules and motor proteins in PtK1 cells

Motor proteins play a fundamental role in the congression and segregation of chromosomes in mitosis as well as the formation of the mitotic spindle. In particular, the dynein/dynactin complex is involved in the maintenance of the spindle, formation of astral microtubules, chromosome motion, and chromosome segregation. Dynactin is a multisubunit, high molecular weight protein that is responsible for the attachment of cargo to dynein. There are a number of major subunits in dynactin that are presumed to be important during mitosis. Arp1 is thought to be the attachment site for cargo to the complex while p150(Glued), a side arm of this complex regulates binding to MTs and the binding of dynactin to dynein. We performed colocalization studies of Arp1 and p150(Glued) to spindle microtubules. Both Arp1 and p150(Glued) colocalize with spindle MTs as well as cytoplasmic components. When treated with cytochalasin J, Arp1 concentrates at the centrosomes and is less co-localized with spindle MTs. Cytochalasin J has less of an effect on the colocalization of p150(Glued) with spindle MTs, suggesting that Arp1 may have a cytochalasin J sensitive site.     

Turnover of proteoglycans in cultures of bovine articular cartilage

Proteoglycans in cultures of adult bovine articular cartilage labeled with [35S]sulfate after 5 days in culture and maintained in medium containing 20% fetal calf X serum had longer half-lives (average 11 days) compared with those of the same tissue maintained in medium alone (average 6 days). The half-lives of proteoglycans in cultures of calf cartilage labeled after 5 days in culture and maintained in medium with serum were considerably longer (average 21 days) compared to adult cartilage. If 0.5 mM cycloheximide was added to the medium of cultures of adult cartilage, or the tissue was maintained at 4 degrees C after labeling, the half-lives of the proteoglycans were greater, 24 and greater than 300 days, respectively. Analyses of the radiolabeled proteoglycans remaining in the matrix of the tissue immediately after labeling the tissue and at various times in culture revealed two main populations of proteoglycans; a large species eluting with Kav of 0.21-0.24 on Sepharose CL-2B, of high bouyant density and able to form aggregates with hyaluronate, and a small species eluting with a Kav of 0.63-0.70 on Sepharose CL-2B, of low buoyant density, containing only chondroitin sulfate chains, and unable to form aggregates with hyaluronate. The larger proteoglycan had shorter half-lives than the smaller proteoglycan; in cartilage maintained with serum, the half-lives were 9.8 and 14.5 days, respectively. Labeling cartilage with both [3H]leucine and [35S]sulfate showed the small proteoglycan to be a separate synthetic product. The size distribution of 35S-labeled proteoglycans lost into the medium was shown to be polydisperse on Sepharose CL-2B, the majority eluting with a Kav of 0.27 to 0.35, of high buoyant density, and unable to aggregate with hyaluronate. The size distribution of glycosaminoglycans from 35S-labeled proteoglycans appearing in the medium did not differ from that associated with labeled proteoglycans remaining in the matrix.     

Effects of plyometric jump training on soccer player’s balance: a systematic review and meta-analysis of randomized-controlled trials

Plyometric jump training (PJT) can be used for improving balance through bilateral and unilateral jump-landing drills. Since the increased number of articles testing the effects of PJT on dynamic and static balance, it is relevant to summarize the evidence and determine the effects across different original articles. This systematic review with meta-analysis was conducted to assess the effects of PJT programs on dynamic and static balance in soccer players. The data sources utilized were Cochrane, Medline (PubMed), SPORTDiscus, and Web of Science. (i) Soccer players of any age or sex without injury, illness, or other clinical conditions; (ii) PJT-based programs restricted to a minimum of three weeks (duration); (iii) passive or active control groups; (iv) pre-post interventions values of dynamic and/or static balance; (v) randomized-controlled trials; and (vi) peerreviewed original full-text studies written in English, Portuguese, and/or Spanish. The database search initially identified 803 titles. From those, eight articles were eligible for the systematic review and meta-analysis. The results showed no significant differences between PJT and active controls in dynamic anterior, postero-medial, or postero-lateral balance for both left and right legs (p > 0.05). Additionally, no significant differences were found between PJT and active controls in terms of static balance (p = 0.495). The current evidence suggests that PJT has no significant advantage over active control groups in terms of dynamic or static balance.     

Long-Term Macroevaluation of Environmental Enrichment in Three Brown Bears (Ursus arctos) at Barcelona Zoo

The evaluation of enrichment programs is important to determine their effect on nonhuman animal welfare. The daily activity pattern and use of space of 3 brown bears (Ursus arctos) were used for long-term macroevaluation of enrichment to compare the baseline and enrichment phases. Focal sampling methods were used for data collection, and instantaneous scans were made at 2-min intervals during 15 sessions of 1 hr for each animal during the 2 study periods. The enrichment devices were categorized as feeding, occupational, and sensorial. The long-term macroevaluation in 3 bears showed statistically significant differences in some types of activity but not in others. There were also statistically significant differences for the use of space in 4 of the 8 zones in which the enclosures were divided. A more homogenous pattern in the use of space was only observed during the enrichment phase in the old female. The 3 brown bears followed different patterns concerning the enrichment program.     

Computational analysis of storage synthesis in developing Brassica napus L. (oilseed rape) embryos: flux variability analysis in relation to ¹³C metabolic flux analysis

Plant oils are an important renewable resource, and seed oil content is a key agronomical trait that is in part controlled by the metabolic processes within developing seeds. A large‐scale model of cellular metabolism in developing embryos of Brassica napus (bna572) was used to predict biomass formation and to analyze metabolic steady states by flux variability analysis under different physiological conditions. Predicted flux patterns are highly correlated with results from prior ¹³C metabolic flux analysis of B. napus developing embryos. Minor differences from the experimental results arose because bna572 always selected only one sugar and one nitrogen source from the available alternatives, and failed to predict the use of the oxidative pentose phosphate pathway. Flux variability, indicative of alternative optimal solutions, revealed alternative pathways that can provide pyruvate and NADPH to plastidic fatty acid synthesis. The nutritional values of different medium substrates were compared based on the overall carbon conversion efficiency (CCE) for the biosynthesis of biomass. Although bna572 has a functional nitrogen assimilation pathway via glutamate synthase, the simulations predict an unexpected role of glycine decarboxylase operating in the direction of NH₄⁺ assimilation. Analysis of the light‐dependent improvement of carbon economy predicted two metabolic phases. At very low light levels small reductions in CO₂ efflux can be attributed to enzymes of the tricarboxylic acid cycle (oxoglutarate dehydrogenase, isocitrate dehydrogenase) and glycine decarboxylase. At higher light levels relevant to the ¹³C flux studies, ribulose‐1,5‐bisphosphate carboxylase activity is predicted to account fully for the light‐dependent changes in carbon balance.