Axonal stress kinase activation and tau misbehavior induced by kinesin-1 transport defects

Many neurodegenerative diseases exhibit axonal pathology, transport defects, and aberrant phosphorylation and aggregation of the microtubule binding protein tau. While mutant tau protein in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP17) causes aberrant microtubule binding and assembly of tau into filaments, the pathways leading to tau-mediated neurotoxicity in Alzheimer's disease and other neurodegenerative disorders in which tau protein is not genetically modified remain unknown. To test the hypothesis that axonal transport defects alone can cause pathological abnormalities in tau protein and neurodegeneration in the absence of mutant tau or amyloid β deposits, we induced transport defects by deletion of the kinesin light chain 1 (KLC1) subunit of the anterograde motor kinesin-1. We found that upon aging, early selective axonal transport defects in mice lacking the KLC1 protein (KLC1-/-) led to axonopathies with cytoskeletal disorganization and abnormal cargo accumulation. In addition, increased c-jun N-terminal stress kinase activation colocalized with aberrant tau in dystrophic axons. Surprisingly, swollen dystrophic axons exhibited abnormal tau hyperphosphorylation and accumulation. Thus, directly interfering with axonal transport is sufficient to activate stress kinase pathways initiating a biochemical cascade that drives normal tau protein into a pathological state found in a variety of neurodegenerative disorders including Alzheimer's disease.Fil: Falzone, Tomas Luis. Howard Hughes Medical Institute; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Stokin, Gorazd B.. University Psychiatric Hospital; EsloveniaFil: Lillo, Concepción. University of California at San Diego; Estados UnidosFil: Rodrigues, Elizabeth M.. Howard Hughes Medical Institute; Estados UnidosFil: Westerman, Eileen L.. Howard Hughes Medical Institute; Estados UnidosFil: Williams, David S.. University of California at San Diego; Estados UnidosFil: Goldstein, Lawrence S. B.. Howard Hughes Medical Institute; Estados Unido

Evaluation of serum amyloid A and haptoglobin as prognostic indicators for horses in a referral population

Acute phase protein (APP) measurement can be used to characterize and rapidly detect inflammation. Serum amyloid A (SAA) and haptoglobin (HP) may be useful for diagnostic and prognostic purposes in horses presenting for colic and other inflammatory diseases. The objective of this thesis was to evaluate the use of SAA and HP in horses presenting for colic and inflammatory diseases for prognostic application of case outcome. We examined case outcomes such as development of complications, survival outcome, duration and cost of hospitalization, and requirement for surgical intervention in horses presenting for colic. Specific laboratory values measured included total white blood cell count, neutrophil count, fibrinogen, SAA, HP, which were compared in control horses and horses admitted for colic and inflammatory diseases. Clinicopathologic values were compared in medical and surgical colic cases to test the ability of APPs to predict indication for surgical intervention. Survival outcome, development of complications, and hospitalization cost and duration were analyzed in both in horses presenting for colic and inflammatory diseases. In horses presenting for colic, SAA was significantly higher in the surgical group compared to both the control and medical colic groups. Haptoglobin concentration was not significantly different between all groups. Horses with elevated SAA were more likely to require surgical intervention than those medically managed. Euthanasia due to poor prognosis or the development of serious complications were more likely to occur in horses presenting for colic with an elevated SAA. In horses presenting for inflammatory diseases, admission SAA and HP concentrations were not significantly associated with survival or the development of complications. Increased HP concentration on admission was associated with longer duration of hospitalization in hoses with inflammatory diseases. Horses with an increasing SAA between 24-72 hours compared to admission SAA were more likely to be euthanized or develop complications. The findings of this study show that SAA and HP measurement could be a potential useful diagnostic and prognostic tool in horses presenting for colic and inflammatory diseases

Intuitive learnability of touch gestures for technology-naïve older adults

Touch-based interactions, if intuitive and natural, should be highly learnable. However, the learnability of touch gestures as a computer interaction modality cannot be taken for granted and should be evaluated empirically. This is especially true when technology-naïve older adults are concerned, given the psychological and physical constraints associated with this age range. To investigate this issue, we conducted a study with 17 technology-naïve older adults, whose experience with technology was mostly limited to making calls with mobile phones. Specifically, the participants were presented with three simple digital games on an interactive tabletop surface and asked to play the games on their own with minimal instruction or help. The first two games required the use of a drag gesture whereas the third game required the use of a rotate gesture. The main research question was whether the older adults could learn the gestures effectively and efficiently. A set of variables such as task duration and gesture accuracy were measured. Results showed that the learnability of a drag gesture was relatively high and that the participants could transfer this skill across the games. In contrast, the learnability of a rotate gesture was low and most of the participants failed to demonstrate any improvement over the tasks of the game. These findings partially corroborate those of earlier work. Implications for future work are drawn, especially exploring the potential of social interactions between older adults for enhancing the learning effects

Deploying Big Data To Crack The Genotype To Phenotype Code

Mechanistically connecting genotypes to phenotypes is a longstanding and central mission of biology. Deciphering these connections will unite questions and datasets across all scales from molecules to ecosystems. Although high-throughput sequencing has provided a rich platform on which to launch this effort, tools for deciphering mechanisms further along the genome to phenome pipeline remain limited. Machine learning approaches and other emerging computational tools hold the promise of augmenting human efforts to overcome these obstacles. This vision paper is the result of a Reintegrating Biology Workshop, bringing together the perspectives of integrative and comparative biologists to survey challenges and opportunities in cracking the genotype to phenotype code and thereby generating predictive frameworks across biological scales. Key recommendations include: promoting the development of minimum “best practices” for the experimental design and collection of data; fostering sustained and long-term data repositories; promoting programs that recruit, train, and retain a diversity of talent and providing funding to effectively support these highly cross-disciplinary efforts. We follow this discussion by highlighting a few specific transformative research opportunities that will be advanced by these efforts

Thickness dependence study of current-driven ferromagnetic resonance in Y3Fe5O12/heavy metal bilayers

We use ferromagnetic resonance to study the current-induced torques in YIG/heavy metal bilayers. YIG samples with thickness varying from 14.8 nm to 80 nm, with the Pt or Ta thin film on top, are measured by applying a microwave current into the heavy metals and measuring the longitudinal DC voltage generated by both spin rectification and spin pumping. From a symmetry analysis of the FMR lineshape and its dependence on YIG thickness, we deduce that the Oersted field dominates over spin-transfer torque in driving magnetization dynamics

Agronomic performace in acid soils of wheat lines selected for hematoxylin staining pattern

Laboratory screening techniques enable detection of varying degrees of A1 tolerance during seedling development, but their application to crop improvement programs must be verified in the field. The objective of this study was to compare agronomic responses of wheat (Triticum aestivum L. emend. Thell.) lines differing in hematoxylin- staining pattern under naturally acidic and limed field conditions. Experiments were conducted on Bethany-Kirkland (fine, mixed, thermic Pachic-Udertic Paleustolls) or Grant-Pond Creek (fine-silty, mixed thermic Udic-Pachic Argiustolls) silt loam soil complexes. Four sets of three experimental lines were classified as very susceptible (VS), moderately susceptible (MS), intermediate (I), or tolerant based on hematoxylin staining pattern, and evaluated in limed and unlimed plots as separate experiments in 1988 and 1989. The VS group produced the fewest spikes per square meter and the lowest above-ground biomass and grain yield in the unlimed treatments; no such reductions occurred in the limed treatments. Differences in agronomic performance were found between groups of VS and MS lines, with relatively little differentiation among MS, I, and T groups. Comparison of two sister lines from the VS and T groups revealed a 12% increase in spike density, 11% increase in biomass, and a 14% increase in grain yield of the tolerant sib under acidic conditions. The two sibs performed similarly under limed conditions, except the VS line was superior in grain yield. The hematoxylin staining procedure shows promise for identifying wheat genotypes with potentially high sensitivity to acidic soils in the southern Great Plains.Peer reviewedAgronom

Chemical Composition of Rainfall in the Southern Plains and It's Impact on Soil and Water Quality

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