Polo-like kinase 4 controls centriole duplication but does not directly regulate cytokinesis.

Centrioles organize the centrosome, and accurate control of their number is critical for the maintenance of genomic integrity. Centrioles duplicate once per cell cycle, and duplication is coordinated by Polo-like kinase 4 (Plk4). We previously demonstrated that Plk4 accumulation is autoregulated by its own kinase activity. However, loss of heterozygosity of Plk4 in mouse embryonic fibroblasts has been proposed to cause cytokinesis failure as a primary event, leading to centrosome amplification and gross chromosomal abnormalities. Using targeted gene disruption, we show that human epithelial cells with one inactivated Plk4 allele undergo neither cytokinesis failure nor increase in centrosome amplification. Plk4 is shown to localize exclusively at the centrosome, with none in the spindle midbody. Substantial depletion of Plk4 by small interfering RNA leads to loss of centrioles and subsequent spindle defects that lead to a modest increase in the rate of cytokinesis failure. Therefore, Plk4 is a centriole-localized kinase that does not directly regulate cytokinesis

Misfolded Mutant SOD1 Directly Inhibits VDAC1 Conductance in a Mouse Model of Inherited ALS

SummaryMutations in superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by loss of motor neurons. With conformation-specific antibodies, we now demonstrate that misfolded mutant SOD1 binds directly to the voltage-dependent anion channel (VDAC1), an integral membrane protein imbedded in the outer mitochondrial membrane. This interaction is found on isolated spinal cord mitochondria and can be reconstituted with purified components in vitro. ADP passage through the outer membrane is diminished in spinal mitochondria from mutant SOD1-expressing ALS rats. Direct binding of mutant SOD1 to VDAC1 inhibits conductance of individual channels when reconstituted in a lipid bilayer. Reduction of VDAC1 activity with targeted gene disruption is shown to diminish survival by accelerating onset of fatal paralysis in mice expressing the ALS-causing mutation SOD1G37R. Taken together, our results establish a direct link between misfolded mutant SOD1 and mitochondrial dysfunction in this form of inherited ALS

Premature polyadenylation-mediated loss of stathmin-2 is a hallmark of TDP-43-dependent neurodegeneration.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are associated with loss of nuclear transactive response DNA-binding protein 43 (TDP-43). Here we identify that TDP-43 regulates expression of the neuronal growth-associated factor stathmin-2. Lowered TDP-43 levels, which reduce its binding to sites within the first intron of stathmin-2 pre-messenger RNA, uncover a cryptic polyadenylation site whose utilization produces a truncated, non-functional mRNA. Reduced stathmin-2 expression is found in neurons trans-differentiated from patient fibroblasts expressing an ALS-causing TDP-43 mutation, in motor cortex and spinal motor neurons from patients with sporadic ALS and familial ALS with GGGGCC repeat expansion in the C9orf72 gene, and in induced pluripotent stem cell (iPSC)-derived motor neurons depleted of TDP-43. Remarkably, while reduction in TDP-43 is shown to inhibit axonal regeneration of iPSC-derived motor neurons, rescue of stathmin-2 expression restores axonal regenerative capacity. Thus, premature polyadenylation-mediated reduction in stathmin-2 is a hallmark of ALS-FTD that functionally links reduced nuclear TDP-43 function to enhanced neuronal vulnerability

Different Seed Selection and Conservation Practices for Fresh Market and Dried Chile Farmers in Aguascalientes, Mexico

Different Seed Selection and Conservation Practices for Fresh Market and Dried Chile Farmers in Aguascalientes, Mexico. The process of selecting and saving seed is the most basic and oldest of agricultural practices. In today’s modern and highly capital-intensive agriculture, seeds are often treated like another chemical input. This study sought to examine seed selection and saving practices among chile farmers in Aguascalientes, Mexico, where both industrial and traditional agriculture are practiced. We observed a clear division among farmers who plant chile peppers commercially. Sixty-eight chile pepper farmers were surveyed in order to document seed selection and saving practices. Fifteen respondents (22%) planted chile peppers destined for the fresh market and all utilized purchased commercial seed of F1 hybrid varieties. Fifty-three farmers (78%) planted chiles to be dried and either saved their own or purchased seeds that others had saved and selected. Farmers who saved their own seed sought to maintain an ideotype, rather than directionally select for certain traits, much like Cleveland et al. (2000) chronicled in central Mexican maize farmers. Farmers would benefit from a participatory plant-breeding program in order to maintain productive seed stock for the continued cultivation of dried chile pepper in the state

Effects of Igneous Intrusion on the Organic Content of Irati Formation, Paraná Basin, in Sapopema (PR)

The thermal effects of an igneous intrusion on organic-rich sedimentary rocks can be considering an important source of maturation of organic matter. The Permian Irati Formation of Paraná Basin (Brazil) is a carbonatic and organic-rich shale sequence intruded by Jurassic-Cretaceous basic rocks. This study reports possible effects of igneous intrusion on the organic matter content of Irati Formation, in Sapopema region (Paraná State). Total organic carbon (TOC), total sulfur (S) and insoluble residue (IR) data were combined with scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). The relatively low TOC values recorded in well where Irati Formation is in contact with 60 m of diabase sill (SP-58-PR) are residuals, associated with the depletion of organic carbon, caused by the thermal effect from the overlying intrusive rock. It was responsible to promote the cracking of the organic matter and reduced those values in relation to the original ones, observed in SP-32-PR (without thermal influence). When comparing the TOC peaks of the Assisting Member in both wells, it was observed that there was a decrease between 80.7 and 84% in the SP-58-PR. SEM images reveal that organic matter in Taquaral Member is sub-rounded and regular shape, while the organic matter in Assistência Member presents a characteristic pattern of thermally evolved organic matter

Elevated PGC-1α Activity Sustains Mitochondrial Biogenesis and Muscle Function without Extending Survival in a Mouse Model of Inherited ALS

SummaryThe transcriptional coactivator PGC-1α induces multiple effects on muscle, including increased mitochondrial mass and activity. Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, adult-onset neurodegenerative disorder characterized by selective loss of motor neurons and skeletal muscle degeneration. An early event is thought to be denervation-induced muscle atrophy accompanied by alterations in mitochondrial activity and morphology within muscle. We now report that elevation of PGC-1α levels in muscles of mice that develop fatal paralysis from an ALS-causing SOD1 mutant elevates PGC-1α-dependent pathways throughout disease course. Mitochondrial biogenesis and activity are maintained through end-stage disease, accompanied by retention of muscle function, delayed muscle atrophy, and significantly improved muscle endurance even at late disease stages. However, survival was not extended. Therefore, muscle is not a primary target of mutant SOD1-mediated toxicity, but drugs increasing PGC-1α activity in muscle represent an attractive therapy for maintaining muscle function during progression of ALS