Does Glyphosate Acting as a Glycine Analogue Contribute To ALS?

 Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease involving several protein mutations in glycine-rich regions with limited treatment options. 90 - 95% of all cases are non-familial with epidemiological studies showing a significant increased risk in glyphosate-exposed workers. In this paper, we propose that glyphosate, the active ingredient in Roundup®, plays a role in ALS, mainly through mistakenly substituting for glycine during protein synthesis, disruption of mineral homeostasis as well as setting up a state of dysbiosis. Mouse models of ALS reveal a pre-symptomatic profile of gut dysbiosis. This dysbiotic state initiate a cascade of events initially impairing metabolism in the gut, and, ultimately, through a series of intermediate stages, leading to motor neuron axonal damage seen in ALS. Lipopolysaccharide, a toxic by-product of dysbiosis which contributes to the pathology, is shown to be statistically higher in ALS patients. In this paper we paint a compelling view of how glyphosate exerts its deleterious effects, including mitochondrial stress and oxidative damage through glycine substitution. Furthermore, its mineral chelation properties disrupt manganese, copper and zinc balance, and it induces glutamate toxicity in the synapse, which results in a die-back phenomenon in axons of motor neurons supplying the damaged skeletal muscles

Effective use of a horizontally-transferred pathway for dichloromethane catabolism requires post–transfer refinement

When microbes acquire new abilities through horizontal gene transfer, the genes and pathways must function under conditions with which they did not coevolve. If newly-acquired genes burden the host, their utility will depend on further evolutionary refinement of the recombinant strain. We used laboratory evolution to recapitulate this process of transfer and refinement, demonstrating that effective use of an introduced dichloromethane degradation pathway required one of several mutations to the bacterial host that are predicted to increase chloride efflux. We then used this knowledge to identify parallel, beneficial mutations that independently evolved in two natural dichloromethane-degrading strains. Finally, we constructed a synthetic mobile genetic element carrying both the degradation pathway and a chloride exporter, which preempted the adaptive process and directly enabled effective dichloromethane degradation across diverse Methylobacterium environmental isolates. Our results demonstrate the importance of post–transfer refinement in horizontal gene transfer, with potential applications in bioremediation and synthetic biology. DOI: http://dx.doi.org/10.7554/eLife.04279.00

Sensory imagery in craving: From cognitive psychology to new treatments for addiction

Sensory imagery is a powerful tool for inducing craving because it is a key component of the cognitive system that underpins human motivation. The role of sensory imagery in motivation is explained by Elaborated Intrusion (EI) theory. Imagery plays an important role in motivation because it conveys the emotional qualities of the desired event, mimicking anticipated pleasure or relief, and continual elaboration of the imagery ensures that the target stays in mind. We argue that craving is a conscious state, intervening between unconscious triggers and consumption, and summarise evidence that interfering with sensory imagery can weaken cravings. We argue that treatments for addiction can be enhanced by the application of EI theory to maintain motivation, and assist in the management of craving in high-risk situations

Lumbopelvic Stability During a Single Leg Step Down Predicts Elbow Varus Torque During Baseball Pitching

During a baseball pitch, energy is transferred from the lower extremities through the lumbopelvic junction to produce ball velocity. Reduced lumbopelvic stability has been associated with elbow injury in pitchers, and commonly ulnar collateral ligament (UCL) tears. The primary biomechanical mechanism of UCL tears is high elbow varus torque. Understanding how decreased lumbopelvic stability influences the development of elbow varus torque could identify risk factors of UCL elbow injury. PURPOSE: Characterize the predictive ability of lumbopelvic stability on elbow varus torque during a baseball pitch. METHODS: NCAA Division 1 baseball players (N=44; 19.6+1.3yrs) participated. Pitchers threw ten fastballs from a mound to a catcher over regulation distance. Elbow varus torque was recorded using an inertial measurement unit and ball velocity was recorded with a radar gun. Pitchers also completed a single leg step down (SLSD) task. Triplanar kinematics were recorded for both legs, pelvis and trunk using inertial measurement units. Statistical analysis consisted of a cluster analysis, principal component analysis (PCA), and a multivariate logistic regression model to determine the relationship between lumbopelvic stability and elbow varus torque. RESULTS: Cluster analysis revealed 2 subgroups of pitchers: Low Torque-High Velocity and High Torque-Low Velocity. PCA analysis indicated 4 patterns of SLSD motion variability (principal components): 1-sagittal plane, 2-transverse plane, 3-frontal plane trail limb, and 4-frontal plane lead limb. Increased transverse plane motion of the trunk and pelvis predicted higher odds of belonging to the High Torque-Low Velocity cluster; trunk [Odds Ratio=2.9 (95%CI:1.1,8.0), p=0.036] and pelvis [Odds Ratio=2.6 (95%CI:1.1,6.0), p=0.031]. CONCLUSIONS: Lumbopelvic motion assessed during the SLSD in pitchers can identify deficits that predict high elbow varus torque and low ball velocity during the baseball pitch. Specifically, higher pelvis and trunk transverse plane motion was associated with pitchers in the High Torque-Low Velocity cluster. The SLSD provides an easily accessible method for coaches and clinicians to identify a potential risk factor related to increased elbow varus torque and UCL injury in pitchers

Importance of thermophilous habitats for protection of wild bees (Apiformes)

Research on wild bees (Apiformes) was conducted in the Lower Oder Valley (NW Poland) at Natura 2000 sites near the border between Poland and Germany. The analysis involved 3 landscape types with xerothermic and sandy grasslands, differing in the proportion of woody vegetation. In total, we collected there 4158 specimens of Apiformes, representing 180 species. We have proved that mid-forest grasslands with a high proportion of thermophilous broad-leaved forests and xerothermic shrub communities are equally attractive to wild bees as open habitats (sandy grasslands, xerothermic grasslands/heaths). We observed varied responses of wild bee species with specific functional characteristics to increasing proportion of woody vegetation. The grasslands surrounded by forests were characterized by the highest number of cleptoparasitic species. In contrast, solitary and social bee species preferred forest-steppe habitats. However, in open habitats, solitary bees were the most abundant. Moreover, open habitats were distinguished by the highest number and abundance of rare species. Active protection of thermophilous grasslands is crucial for biodiversity conservation, also with respect to the natural resources of Apiformes. Preservation of biodiversity in threatened xerothermic and sandy grasslands should be one of the key objectives of nature conservation in European countries. Currently, more and more actions are undertaken to improve their condition and to restore those particularly valuable and threatened habitat types

Acute gamma-secretase inhibition of nonhuman primate CNS shifts amyloid precursor protein (APP) metabolism from amyloid-beta production to alternative APP fragments without amyloid-beta rebound

The accumulation of amyloid beta (Aβ) in Alzheimer’s disease is caused by an imbalance of production and clearance, which leads to increased soluble Aβ species and extracellular plaque formation in the brain. Multiple Aβ-lowering therapies are currently in development: an important goal is to characterize the molecular mechanisms of action and effects on physiological processing of Aβ, as well as other amyloid precursor protein (APP) metabolites, in models which approximate human Aβ physiology. To this end, we report the translation of the human in vivo stable-isotope-labeling kinetics (SILK) method to a rhesus monkey cisterna magna ported (CMP) nonhuman primate model, and use the model to test the mechanisms of action of a γ-secretase inhibitor (GSI). A major concern of inhibiting the enzymes which produce Aβ (β- and γ-secretase) is that precursors of Aβ may accumulate and cause a rapid increase in Aβ production when enzyme inhibition discontinues. In this study, the GSI MK-0752 was administered to conscious CMP rhesus monkeys in conjunction with in vivo stable isotope labeling, and dose-dependently reduced newly generated CNS Aβ. In contrast to systemic Aβ metabolism, CNS Aβ production was not increased after the GSI was cleared. These results indicate that most of the CNS APP was metabolized to products other than Aβ, including C-terminal truncated forms of Aβ: 1–14, 1–15 and 1–16; this demonstrates an alternative degradation pathway for CNS amyloid precursor protein during γ-secretase inhibition

Effective use of a horizontally-transferred pathway for dichloromethane catabolism requires post-transfer refinement

When microbes acquire new abilities through horizontal gene transfer, the genes and pathways must function under conditions with which they did not coevolve. If newly-acquired genes burden the host, effective use will depend on further evolutionary refinement of the recombinant strain. We used laboratory evolution to recapitulate this process of transfer and refinement, demonstrating that effective use of an introduced dichloromethane degradation pathway required one of several mutations to the bacterial host that are predicted to increase chloride efflux. We then used this knowledge to identify parallel, beneficial mutations that independently evolved in two natural dichloromethane-degrading strains. Finally, we constructed a synthetic mobile genetic element carrying both the degradation pathway and a chloride exporter, which preempted the adaptive process and directly enabled effective dichloromethane degradation across diverse Methylobacterium environmental isolates. Our results demonstrate the importance of post-transfer refinement in horizontal gene transfer, with potential applications in bioremediation and synthetic biology

Effective use of a horizontally-transferred pathway for dichloromethane catabolism requires post-transfer refinement. eLife 2014

Abstract When microbes acquire new abilities through horizontal gene transfer, the genes and pathways must function under conditions with which they did not coevolve. If newly-acquired genes burden the host, their utility will depend on further evolutionary refinement of the recombinant strain. We used laboratory evolution to recapitulate this process of transfer and refinement, demonstrating that effective use of an introduced dichloromethane degradation pathway required one of several mutations to the bacterial host that are predicted to increase chloride efflux. We then used this knowledge to identify parallel, beneficial mutations that independently evolved in two natural dichloromethane-degrading strains. Finally, we constructed a synthetic mobile genetic element carrying both the degradation pathway and a chloride exporter, which preempted the adaptive process and directly enabled effective dichloromethane degradation across diverse Methylobacterium environmental isolates. Our results demonstrate the importance of post-transfer refinement in horizontal gene transfer, with potential applications in bioremediation and synthetic biology

Population genetic evidence for sex-specific dispersal in an inbred social spider

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Dispersal in most group-living species ensures gene flow among groups, but in cooperative social spiders, juvenile dispersal is suppressed and colonies are highly inbred. It has been suggested that such inbred sociality is advantageous in the short term, but likely to lead to extinction or reduced speciation rates in the long run. In this situation, very low levels of dispersal and gene flow among colonies may have unusually important impacts on fitness and persistence of social spiders. We investigated sex-specific differences in dispersal and gene flow among colonies, as reflected in the genetic structure within colonies and populations of the African social spider Stegodyphus dumicola Pocock, 1898 (Eresidae). We used DNA fingerprinting and mtDNA sequence data along with spatial mapping of colonies to compare male and female patterns of relatedness within and among colonies at three study sites. Samples were collected during and shortly after the mating season to detect sex-specific dispersal. Distribution of mtDNA haplotypes was consistent with proliferation of social nests by budding and medium- to long-distance dispersal by ballooning females. Analysis of molecular variance and spatial autocorrelation analyses of AFLPs showed high levels of genetic similarity within colonies, and STRUCTURE analyses revealed that the number of source populations contributing to colonies ranged from one to three. We also showed significant evidence of male dispersal among colonies at one site. These results support the hypothesis that in social spiders, genetic cohesion among populations is maintained by long-distance dispersal of female colony founders. Genetic diversity within colonies is maintained by colony initiation by multiple dispersing females, and adult male dispersal over short distances. Male dispersal may be particularly important in maintaining gene flow among colonies in local populations