In-Vivo Nucleus Pulposus-Specific Regulation of Adult Murine Intervertebral Disc Degeneration via Wnt/Beta-Catenin Signaling

B-Catenin, transcription factor of Wnt signaling, is promoted in patients with intervertebral disc (IVD) degeneration, but Wnt signaling decreases with aging. We hypothesize that IVD degeneration is associated with decreased Wnt signaling despite more b-Catenin. Chronic compression of tail IVDs of young-adult and aged Wnt-reporter (TOPGAL) animals initiated an age-related cascade of degenerative-like changes, which included reduced Wnt ligand expression and Wnt signaling in nucleus pulposus cells, despite elevation of b-Catenin protein and gene expression. To determine the effect of upregulated and downregulated Wnt signaling in adult discs, b-Catenin in the nucleus pulposus was stabilized (Shh-CreErT2/b-Cateninfl(Ex3)/fl(Ex3), cACT) or knocked out (Shh-CreErT2/b-Cateninfl/fl, cKO). cACT discs had promoted expression of Wnt-targets and -ligands, brachyury, extracellular matrix production and 34% greater compressive stiffness than WT (b-Cateninfl(Ex3)/fl(Ex3)) discs, but 50% less tensile stiffness. By contrast, knockout reversed the cACT phenotype: less protein expression of b-catenin in the nucleus pulposus, less expression of brachyury, heightened expression of extracellular matrix breakdown and 46% less compressive stiffness than wild-type (b-Cateninfl/fl,WT) discs. These data suggest that intervertebral disc degeneration is associated with loss of Wnt signaling and that the concomitant increase in b-catenin is a regenerative response, potentially offering a therapeutic approach to degeneration

Manejo del material de siembra de yuca (Manihot esculenta Crantz)

Several cassava trials were planted at CIAT to study the effect of the maturity of stem cuttings, depth of planting, cutting length, planting position and the angle of the cut on root yield. Cuttings from the top and middle part of vigorous 1-yr-old plants produced greater than root yields than those proceeding from the lower part of the plant or from older stem parts. Cuttings planted vertically 10, 20 and 30 cm deep do not affect the yield but do affect root distribution, the no. of roots/plant and the difficulty of harvesting; planting at 10 cm in depth was the most adequate. Twenty-cm long, selected and treated cuttings gave slightly higher yields than 40 or 60 cm ones. Cuttings placed vertically assure more rapid emergence, greater than percentage of germination, greater than yields and prevent lodging in comparison to those planted in a horizontal or inclined position. When the stems were cut rectangularly or bevel-edged, different rooting systems were produced; the former produced roots with a more uniform distribution; nevertheless, yield was not affected. Vertical planting, either with a straight or bevel-edged cut, gave greater than yields than horizontal planting. To obtain max yields, planting material should be selected from the middle part of mature, vigorous plants, cut at right angles 20 cm long and planted vertically 10 cm deep. (AS-CIAT)Se sembraron varios ensayos de yuca en el CIAT para estudiar el efecto de la madurez de las estacas, profundidad de siembra, longitud de la estaca, posicion de siembra y angulo de corte de la misma, en el rendimiento de las raices. Las estacas de la parte media y superior de plantas vigorosas de un ano de edad produjeron mayores rendimientos de raices que aquellas provenientes de la parte baja de la planta o de estacas viejas. Las estacas sembradas verticalmente a 10, 20 y 30 cm de profundidad no influyen en el rendimiento, pero afectan la distribucion de raices, el numero de raices/planta y la facilidad de cosecha; la siembra a 10 cm de profundidad fue la mas adecuada. Las mayores estacas de 20 cm de largo seleccionadas y tratadas dieron rendimientos ligeramente mayores que las de 40 o 60 cm. La siembra vertical de las estacas aseguro una emergencia mas rapida, un mayor porcentaje de germinacion, mayores rendimientos y previno el volcamiento de las plantas, en comparacion con la posicion horizontal o inclinada. El corte de la estaca en forma rectangular o en bisel produjo diferentes sistemas de enraizamiento; el primero produce raices mas uniformemente distribuidas; sin embargo, no afecta el rendimiento. La siembra vertical, ya sea con angulo de corte recto o en bisel, da mayores rendimientos que la siembra horizontal. Para obtener los rendimientos maximos, el material de siembra se debe seleccionar de la parte media de plantas vigorosas maduras, cortado en un angulo recto, en trozos de 20 cm de largo y sembrado verticalmente a 10 cm de profundidad. (RA-CIAT

INIA 317: Altiplano, variedad de papa con buena adaptacion en la region altiplanica del Peru.

La papa constituye uno de los cultivos alimenticios más importantes en la agricultura familiar de la región andina del Perú. En las condiciones agroecológicas de esta región, uno de los factores más importantes que limita los niveles de producción y productividad de la papa es el clima adverso. Con el objetivo de lograr genotipos de papa; que además, de tener buena capacidad de rendimiento, respondan mejor a los nuevos estreses abióticos y bióticos provocados por el cambio climático, el Centro Internacional de la Papa realizó cruzamientos entre los cultivares nativos pertenecientes a Solanum tuberosum subsp. andigena. La evaluación de los genotipos se realizó a partir del año 2000 en las diferentes localidades de la región andina. Desde del año 2005, la Estación Experimental Illpa-Puno del Instituto Nacional de Innovación Agraria (INIA) y el Centro Internacional de la Papa (CIP) dentro de las actividades del Proyecto ALTAGRO, evaluaron un grupo de estos clones en diversas comunidades de la Región Altiplánica del Perú, a través de la metodología de selección participativa, con el objetivo de obtener una variedad de papa con alta capacidad productiva, adaptada a las condiciones climáticas de la Región Altiplánica y con aptitud para procesamiento en tunta. Como resultado de este trabajo de investigación se ha logrado seleccionar un genotipo de papa adaptada a la Región Altiplánica del Perú, con alto potencial de rendimiento y alto contenido de materia seca. Este genotipo de papa inicialmente identificado como el clon 399085.30 (B1C5041.30), actualmente es denominado variedad INIA 317 – ALTIPLAN

Post-traumatic osteoarthritis in mice following mechanical injury to the synovial joint

We investigated the spectrum of lesions characteristic of post-traumatic osteoarthritis (PTOA) across the knee joint in response to mechanical injury. We hypothesized that alteration in knee joint stability in mice reproduces molecular and structural features of PTOA that would suggest potential therapeutic targets in humans. The right knees of eight-week old male mice from two recombinant inbred lines (LGXSM-6 and LGXSM-33) were subjected to axial tibial compression. Three separate loading magnitudes were applied: 6N, 9N, and 12N. Left knees served as non-loaded controls. Mice were sacrificed at 5, 9, 14, 28, and 56 days post-loading and whole knee joint changes were assessed by histology, immunostaining, micro-CT, and magnetic resonance imaging. We observed that tibial compression disrupted joint stability by rupturing the anterior cruciate ligament (except for 6N) and instigated a cascade of temporal and topographical features of PTOA. These features included cartilage extracellular matrix loss without proteoglycan replacement, chondrocyte apoptosis at day 5, synovitis present at day 14, osteophytes, ectopic calcification, and meniscus pathology. These findings provide a plausible model and a whole-joint approach for how joint injury in humans leads to PTOA. Chondrocyte apoptosis, synovitis, and ectopic calcification appear to be targets for potential therapeutic intervention

The prostate cancer-associated human retrovirus XMRV lacks direct transforming activity but can induce low rates of transformation in cultured cells.

The human retrovirus XMRV (xenotropic murine leukemia virus-related virus) is associated with prostate cancer, but a causal relationship has not been established. Here, we have used cultured fibroblast and epithelial cell lines to test the hypothesis that XMRV might have direct transforming activity but found only rare transformation events, suggestive of indirect transformation, even when the target cells expressed the human Xpr1 cell entry receptor for XMRV. Characterization of cells from three transformed foci showed that all were infected with and produced XMRV, and one produced a highly active transforming virus, presumably generated by recombination between XMRV and host cell nucleic acids. Given the sequence similarity of XMRV to mink cell focus-forming (MCF) viruses and the enhanced leukemogenic activity of the latter, we tested XMRV for related MCF-like cytopathic activities in cultured mink cells but found none. These results indicate that XMRV has no direct transforming activity but can activate endogenous oncogenes, resulting in cell transformation. As part of these experiments, we show that XMRV can infect and be produced at a high titer from human HT-1080 fibrosarcoma cells that express TRIM5alpha (Ref1), showing that XMRV is resistant to TRIM5alpha restriction. In addition, XMRV poorly infects NIH 3T3 cells expressing human Xpr1 but relatively efficiently infects BALB 3T3 cells expressing human Xpr1, showing that XMRV is a B-tropic virus and that its infectivity is regulated by the Fv1 mouse locus

Living on the Edge: High-Latitude Porites Carbonate Production Under Temperate Eutrophic Conditions

Non-framework building high-latitude coral communities have recently received increased attention as a result of their potential to act as refugia during global change, as proxies for such change and for testing the environmental tolerance limits of various species of coral. In this study, we report on high-resolution in situ measured environmental factors influencing the development of monospecific (Porites panamensis) non-framework building coral communities and the resulting coral-derived carbonate sediment production in the northern Gulf of California, Mexico (Bahía de Los Angeles, 29°N, 113°E). Half-hourly measurements of temperature and chlorophyll a (a nutrient proxy) for a 1-year period indicate temperature extremes ranging from 14°C to 30°C, and average chlorophyll a values of 2.2 mg Chl a/m3(eutrophic). Even though P. panamensis only occur as small massive and encrusting colonies, they nonetheless show a significant carbonate sediment production potential (0.14 kg CaCO3/m2/year). A calculation of carbonate production rates vs amount of coral found in the sediment shows that this high-latitude community must have persisted for an extended period of time

Aging aggravates intervertebral disc degeneration by regulating transcription factors toward chondrogenesis

Osterix is a critical transcription factor of mesenchymal stem cell fate, where its loss or loss of Wnt signaling diverts differentiation to a chondrocytic lineage. Intervertebral disc (IVD) degeneration activates the differentiation of prehypertrophic chondrocyte-like cells and inactivates Wnt signaling, but its interactive role with osterix is unclear. First, compared to young-adult (5 mo), mechanical compression of old (18 mo) IVD induced greater IVD degeneration. Aging (5 vs 12 mo) and/or compression reduced the transcription of osterix and notochordal marker T by 40-75%. Compression elevated the transcription of hypertrophic chondrocyte marker MMP13 and pre-osterix transcription factor RUNX2, but less so in 12 mo IVD. Next, using an Ai9/td reporter and immunohistochemical staining, annulus fibrosus and nucleus pulposus cells of young-adult IVD expressed osterix, but aging and compression reduced its expression. Lastly, in vivo LRP5-deficiency in osterix-expressing cells inactivated Wnt signaling in the nucleus pulposus by 95%, degenerated the IVD to levels similar to aging and compression, reduced the biomechanical properties by 45-70%, and reduced the transcription of osterix, notochordal markers and chondrocytic markers by 60-80%. Overall, these data indicate that age-related inactivation of Wnt signaling in osterix-expressing cells may limit regeneration by depleting the progenitors and attenuating the expansion of chondrocyte-like cells

Strain Gage Load Calibration of the Wing Interface Fittings for the Adaptive Compliant Trailing Edge Flap Flight Test

The safety-of-flight parameters for the Adaptive Compliant Trailing Edge (ACTE) flap experiment require that flap-to-wing interface loads be sensed and monitored in real time to ensure that the structural load limits of the wing are not exceeded. This paper discusses the strain gage load calibration testing and load equation derivation methodology for the ACTE interface fittings. Both the left and right wing flap interfaces were monitored; each contained four uniquely designed and instrumented flap interface fittings. The interface hardware design and instrumentation layout are discussed. Twenty-one applied test load cases were developed using the predicted in-flight loads. Pre-test predictions of strain gage responses were produced using finite element method models of the interface fittings. Predicted and measured test strains are presented. A load testing rig and three hydraulic jacks were used to apply combinations of shear, bending, and axial loads to the interface fittings. Hardware deflections under load were measured using photogrammetry and transducers. Due to deflections in the interface fitting hardware and test rig, finite element model techniques were used to calculate the reaction loads throughout the applied load range, taking into account the elastically-deformed geometry. The primary load equations were selected based on multiple calibration metrics. An independent set of validation cases was used to validate each derived equation. The 2-sigma residual errors for the shear loads were less than eight percent of the full-scale calibration load; the 2-sigma residual errors for the bending moment loads were less than three percent of the full-scale calibration load. The derived load equations for shear, bending, and axial loads are presented, with the calculated errors for both the calibration cases and the independent validation load cases

Differential Response and the Reduction of Child Maltreatment and Foster Care Services Utilization in the U.S. From 2004 to 2017.

By 2014, the majority of U.S. states had implemented differential response (DR), a system policy that seeks to serve families of low-to moderate-risk for child maltreatment through family engagement, diversion from formal child protective services investigations, and service provision. However, the effects of DR programs on child welfare dynamics have yet to be evaluated nationally using causal methods. Using a quasi-experimental study design with data drawn from the National Child Abuse and Neglect Data System from 2004 to 2017, we found states with DR programs had approximately 19% fewer substantiated reports, 25% fewer children substantiated for neglect, and a 17% reduction in foster care services utilization when compared to states without DR programs. We find these estimates to be robust to the opioid epidemic and incarceration rates. Additional research is needed to better characterize DR programs and isolate the effects of DR programs geographically

Selectron Mass Reconstruction and the Resolution of the Linear Collider Detector

We have used ISAJET and the JAS LCD fast simulation to explore the precision of Snowmass Point SPS1a selectron mass reconstruction for the Silicon Detector concept. Simulating collisions at E_cm = 1 TeV, we have found that most of the information constraining the selectron mass is carried in the forward (|cos(theta)| \u3e 0.8) region. We have also found that, for a beam energy spread of 1% (conventional RF design), detector resolution limitations compromise the selectron mass reconstruction only in the forward region. However, for a beam energy spread of less than 0.2% (superconducting RF design), the detector resolution compromises the selectron mass reconstruction over the full angular region