The Translation Regulatory Subunit eIF3f Controls the Kinase-Dependent mTOR Signaling Required for Muscle Differentiation and Hypertrophy in Mouse

The mTORC1 pathway is required for both the terminal muscle differentiation and hypertrophy by controlling the mammalian translational machinery via phosphorylation of S6K1 and 4E-BP1. mTOR and S6K1 are connected by interacting with the eIF3 initiation complex. The regulatory subunit eIF3f plays a major role in muscle hypertrophy and is a key target that accounts for MAFbx function during atrophy. Here we present evidence that in MAFbx-induced atrophy the degradation of eIF3f suppresses S6K1 activation by mTOR, whereas an eIF3f mutant insensitive to MAFbx polyubiquitination maintained persistent phosphorylation of S6K1 and rpS6. During terminal muscle differentiation a conserved TOS motif in eIF3f connects mTOR/raptor complex, which phosphorylates S6K1 and regulates downstream effectors of mTOR and Cap-dependent translation initiation. Thus eIF3f plays a major role for proper activity of mTORC1 to regulate skeletal muscle size

Andreev reflections on Y1-xCaxBa2Cu3O7-delta evidence for an unusual proximity effect

We have measured Andreev reflections between an Au tip and Y_{1-x}Ca_{x}Ba_{2}Cu_{3}O_{7 - \delta} thin films in the in-plane orientation. The conductance spectra are best fitted with a pair potential having the "d_{x^{2}-y^{2}+is" symmetry. We find that the amplitude of the "is" component is enhanced as the contact transparency is increased. This is an indication for an unusual proximity effect that modifies the pair potential in the superconductor near the surface with the normal metal.Comment: 4 pages, 4 figure

Human herpesvirus multiplex ddPCR detection in brain tissue from low- and high-grade astrocytoma cases and controls.

BACKGROUND: Glioblastoma (GBM) is a fatal CNS malignancy, representing 50 % of all gliomas with approximately 12-18 months survival time after initial diagnosis. Recently, the human herpesvirus cytomegalovirus (CMV) has been suggested to have an oncogenic role, yet this association remains controversial. In addition, human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) have also been associated with low-grade gliomas, but few studies have examined HHV-6 and EBV in glioblastomas. Droplet digital PCR (ddPCR) is a highly precise diagnostic tool that enables the absolute quantification of target DNA. This study examines the association between multiple human herpesviruses and astrocytomas. METHODS: This study analyzed 112 brain tissue specimens, including 45 glioblastoma, 12 astrocytoma grade III, 2 astrocytoma grade II, 4 astrocytoma grade I, and 49 controls. All brain tissue samples were de-identified and pathologically confirmed. Each tissue block was sectioned for DNA extraction and CMV, EBV, HHV-6A and HHV-6B, and a cellular housekeeping gene were amplified by ddPCR. RESULTS: Neither CMV nor HHV-6A were detected in any of the astrocytoma samples. However, HHV-6B (p = 0.147) and EBV (p = 0.049) had a higher positivity frequency in the GBM compared to the controls. CONCLUSION: The undetectable CMV DNA in the astrocytoma cohort does not support the observation of an increased prevalence of CMV DNA in GBM, as reported in other studies. EBV has a significantly higher positivity in the GBM cohort compared to the controls, while HHV-6B has a higher but not statistically significant positivity in the case cohort. Whether these viruses play an oncogenic role in GBM remains to be further investigated

Plant growth promoting rhizobacteria and kinetin as ways to promote corn growth and yield in a short growing season area

Abstract The base temperature for germination of corn is approximately 10°C, which results in slow germination and emergence of corn crops sown into cool soils. The effects of plant-growth-promoting rhizobacteria (PGPR) and kinetin on grain and sweet corn emergence, plant growth and yield were studied under short season conditions in 1996 and 1997. Two PGPR strains (Serratia proteamaculans 1-102 and Serratia liquefaciens 2-68) were used. The kinetin concentrations were 0, 1 and 5 mM. The experiment was structured as a randomized complete block design with four replicates. The plant growth responses were variable and depended on the PGPR strain, harvest date and growth parameters evaluated. There were interactions among PGPR, kinetin and corn hybrid. PGPR provided a greater stimulation of seedling emergence than kinetin. PGPR strain 1-102 was best at promoting emergence. One month after planting, both PGPR and kinetin increased plant growth, and PGPR strain 2-68 resulted in a greater growth than that of strain 1-102. PGPR strain 2-68 plus 1 mM kinetin was the best treatment for promoting plant growth. The plant height and root dry weight of sweet corn were less affected than those of grain corn. The effects of PGPR on plant growth decreased as the plants developed. Two months after planting, there were no effects of kinetin on plant growth, however, PGPR still had positive effects on the leaf area of grain corn, but they decreased the leaf area of sweet corn. The plant dry weight of grain corn was increased by PGPR strain 2-68. The grain corn yield was increased by PGPR strain 2-68 in both years. In 1997, PGPR strain 2-68 increased the sweet corn yield. Kinetin alone had no effects on yields in either year for the two cultivars studied

Mohs math – where the error hides

BACKGROUND: Mohs surgical technique allows a full view of surgical margins and has a reported cure rate approaching 100%. METHOD: A survey amongst Mohs surgeons was performed to assess operator technique. In addition, an animated clay model was constructed to identify and quantify tissue movement seen during the processing of Mohs surgical specimens. RESULTS: There is variability in technique used in Mohs surgery in regards to the thickness of layers, and the number of blocks layers are cut into. A mathematical model is described which assesses the clinical impact of this variability. CONCLUSION: Our mathematical model identifies key aspects of technique that may contribute to error. To keep the inherent error rate at a minimum, we advocate minimal division and minimal physical thickness of Mohs specimens

Scanning tunneling spectroscopy of a-axis YBa_2Cu_3O_7-\delta films:k-selectivity and the shape of the superconductor

Tunneling spectroscopy of epitaxial (100) oriented \chem{YBa_2Cu_3O_{7-\delta}} films was performed using an STM at 4.2 K. On atomically smooth areas, tunneling spectra revealing clear U-shaped gaps with relatively low zero bias conductance were measured. These spectra can be well fitted to the tunneling theory into a d-wave superconductor only when introducing a strong dependence of the tunneling probability on the wave-vector \emph{\textbf{k}}. Possible origins for this \emph{\textbf{k}}-selectivity in STM measurements will be discussed. On other areas, V-shaped gaps as well as zero bias conductance peaks are observed, indicating relaxation of \emph{\textbf{k}}-selectivity and the effect of nanofaceting, respectively.Comment: 7 epl pages, 4 embeded figure

Inhibition of Atrogin-1/MAFbx Mediated MyoD Proteolysis Prevents Skeletal Muscle Atrophy In Vivo

Ubiquitin ligase Atrogin1/Muscle Atrophy F-box (MAFbx) up-regulation is required for skeletal muscle atrophy but substrates and function during the atrophic process are poorly known. The transcription factor MyoD controls myogenic stem cell function and differentiation, and seems necessary to maintain the differentiated phenotype of adult fast skeletal muscle fibres. We previously showed that MAFbx mediates MyoD proteolysis in vitro. Here we present evidence that MAFbx targets MyoD for degradation in several models of skeletal muscle atrophy. In cultured myotubes undergoing atrophy, MAFbx expression increases, leading to a cytoplasmic-nuclear shuttling of MAFbx and a selective suppression of MyoD. Conversely, transfection of myotubes with sh-RNA-mediated MAFbx gene silencing (shRNAi) inhibited MyoD proteolysis linked to atrophy. Furthermore, overexpression of a mutant MyoDK133R lacking MAFbx-mediated ubiquitination prevents atrophy of mouse primary myotubes and skeletal muscle fibres in vivo. Regarding the complex role of MyoD in adult skeletal muscle plasticity and homeostasis, its rapid suppression by MAFbx seems to be a major event leading to skeletal muscle wasting. Our results point out MyoD as the second MAFbx skeletal muscle target by which powerful therapies could be developed

The prognosis of allocentric and egocentric neglect : evidence from clinical scans

We contrasted the neuroanatomical substrates of sub-acute and chronic visuospatial deficits associated with different aspects of unilateral neglect using computed tomography scans acquired as part of routine clinical diagnosis. Voxel-wise statistical analyses were conducted on a group of 160 stroke patients scanned at a sub-acute stage. Lesion-deficit relationships were assessed across the whole brain, separately for grey and white matter. We assessed lesions that were associated with behavioural performance (i) at a sub-acute stage (within 3 months of the stroke) and (ii) at a chronic stage (after 9 months post stroke). Allocentric and egocentric neglect symptoms at the sub-acute stage were associated with lesions to dissociated regions within the frontal lobe, amongst other regions. However the frontal lesions were not associated with neglect at the chronic stage. On the other hand, lesions in the angular gyrus were associated with persistent allocentric neglect. In contrast, lesions within the superior temporal gyrus extending into the supramarginal gyrus, as well as lesions within the basal ganglia and insula, were associated with persistent egocentric neglect. Damage within the temporo-parietal junction was associated with both types of neglect at the sub-acute stage and 9 months later. Furthermore, white matter disconnections resulting from damage along the superior longitudinal fasciculus were associated with both types of neglect and critically related to both sub-acute and chronic deficits. Finally, there was a significant difference in the lesion volume between patients who recovered from neglect and patients with chronic deficits. The findings presented provide evidence that (i) the lesion location and lesion size can be used to successfully predict the outcome of neglect based on clinical CT scans, (ii) lesion location alone can serve as a critical predictor for persistent neglect symptoms, (iii) wide spread lesions are associated with neglect symptoms at the sub-acute stage but only some of these are critical for predicting whether neglect will become a chronic disorder and (iv) the severity of behavioural symptoms can be a useful predictor of recovery in the absence of neuroimaging findings on clinical scans. We discuss the implications for understanding the symptoms of the neglect syndrome, the recovery of function and the use of clinical scans to predict outcome

Mathematical Manipulative Models: In Defense of Beanbag Biology

Mathematical manipulative models have had a long history of influence in biological research and in secondary school education, but they are frequently neglected in undergraduate biology education. By linking mathematical manipulative models in a four-step process-1) use of physical manipulatives, 2) interactive exploration of computer simulations, 3) derivation of mathematical relationships from core principles, and 4) analysis of real data sets-we demonstrate a process that we have shared in biological faculty development workshops led by staff from the BioQUEST Curriculum Consortium over the past 24 yr. We built this approach based upon a broad survey of literature in mathematical educational research that has convincingly demonstrated the utility of multiple models that involve physical, kinesthetic learning to actual data and interactive simulations. Two projects that use this approach are introduced: The Biological Excel Simulations and Tools in Exploratory, Experiential Mathematics (ESTEEM) Project (http://bioquest.org/esteem) and Numerical Undergraduate Mathematical Biology Education (NUMB3R5 COUNT; http://bioquest.org/numberscount). Examples here emphasize genetics, ecology, population biology, photosynthesis, cancer, and epidemiology. Mathematical manipulative models help learners break through prior fears to develop an appreciation for how mathematical reasoning informs problem solving, inference, and precise communication in biology and enhance the diversity of quantitative biology education