hnRNP K: An HDM2 Target and Transcriptional Coactivator of p53 in Response to DNA Damage

SummaryIn response to DNA damage, mammalian cells trigger the p53-dependent transcriptional induction of factors that regulate DNA repair, cell-cycle progression, or cell survival. Through differential proteomics, we identify heterogeneous nuclear ribonucleoprotein K (hnRNP K) as being rapidly induced by DNA damage in a manner that requires the DNA-damage signaling kinases ATM or ATR. Induction of hnRNP K ensues through the inhibition of its ubiquitin-dependent proteasomal degradation mediated by the ubiquitin E3 ligase HDM2/MDM2. Strikingly, hnRNP K depletion abrogates transcriptional induction of p53 target genes and causes defects in DNA-damage-induced cell-cycle-checkpoint arrests. Furthermore, in response to DNA damage, p53 and hnRNP K are recruited to the promoters of p53-responsive genes in a mutually dependent manner. These findings establish hnRNP K as a new HDM2 target and show that, by serving as a cofactor for p53, hnRNP K plays key roles in coordinating transcriptional responses to DNA damage

Modeling the Influence of a Variable Permeability Inclusion on Free-Surface Flow in an Inclined Aquifer

The interaction of sub-surface, gravity-driven flows with inclusions of different permeabilities are investigated theoretically using a model that exploits the relative shallowness of the motion. Numerically computed solutions for steady motion around cylindrical inclusions reveal a range of behaviors dependent on the ratio of the interior to exterior permeability and a dimensionless flow parameter that measures the far-field thickness to the product of the gradient of the slope down which the fluid flows and the width of the inclusion. When the inclusion is relatively narrow, the depth of the flow is little changed from its far-field value and the fluid is focused into inclusions of higher permeability and deflected around those of lower permeability. However, if the inclusion is relatively wide then three qualitatively different regimes emerge, dependent on the ratio of permeabilities. When the interior and exterior permeabilities are similar, then negligible deviation of the flow occurs apart from within thin transition layers at the boundary of the inclusion. When the permeabilities differ significantly, the flow forms deep ponds at either the upstream or downstream boundary of the inclusion for relatively low or high permeability inclusion, respectively, which arise due to deflection or focusing. In each case, asymptotic relationships are derived between the depth of the flow and the parameters. Inclusions of differing cross-section are also analyzed numerically and analytically to draw out the interplay between adjustment, deflection and focusing

Notes: Evaluation Of A Filter Bag System For NDF, ADF, And IVDMD Forage Analysis

A new method of determining in vitro dry matter digestibility (IVDMD) as recently developed in which the digestion is conducted with the forage samples in filter bags. Our objective was to compare the filter bag and conventional IVDMD analysis methods using smooth bromegrass (Bromus inermis Leyss.), switchgrass (Panicum virgatum L.), and forage sorghum [Sorghum bicolor (L.) Moench] samples. In addition, the filter bag analysis systems for determining non-sequential neutral and acid detergent fiber (NDF and ADF), respectively, were compared with the non-sequential conventional analysis systems. In the filter bag systems, the forage samples are sealed in filter bags and the analyses are conducted on a batch basis rather than on an individual basis as in the conventional IVDMD and fiber analysis procedures. The filter bag analysis methods produced results similar to the conventional methods and ranked the forage samples in the same relative order

Notes: Evaluation Of A Filter Bag System For NDF, ADF, And IVDMD Forage Analysis

A new method of determining in vitro dry matter digestibility (IVDMD) as recently developed in which the digestion is conducted with the forage samples in filter bags. Our objective was to compare the filter bag and conventional IVDMD analysis methods using smooth bromegrass (Bromus inermis Leyss.), switchgrass (Panicum virgatum L.), and forage sorghum [Sorghum bicolor (L.) Moench] samples. In addition, the filter bag analysis systems for determining non-sequential neutral and acid detergent fiber (NDF and ADF), respectively, were compared with the non-sequential conventional analysis systems. In the filter bag systems, the forage samples are sealed in filter bags and the analyses are conducted on a batch basis rather than on an individual basis as in the conventional IVDMD and fiber analysis procedures. The filter bag analysis methods produced results similar to the conventional methods and ranked the forage samples in the same relative order

Tide-induced head fluctuations in coastal aquifers of variable thickness

In this work, a new analytical solution to describe tide-induced head fluctuations in aquifers of variable thickness is presented. The proposed model assumes a finite and confined aquifer with a thickness that increases or decreases quadratically with the distance to the coast. A closed-form analytical solution is obtained by solving a boundary-value problem with both a separation of variables method and a change of variables method. This solution is a generalization of the solution obtained by Cuello et al., Hydrogeological Journal, 2017, 25, 1509–1515. The analytical solution is expressed in terms of the wedging parameter, a parameter that depends on the length and thicknesses at the coast and at the inland edge of the aquifer. Positive values of the wedging parameter describe aquifers with increasing thickness towards land and negative values describe aquifers with a decreasing thickness in the inland direction. The comparison of the new solution and the solution for a finite aquifer with constant thickness indicates that the sign of the wedging parameter enhances or decreases the amplitude of the tide-induced signal. However, the differences in time-lag between both solutions are negligible near the coast. The slope factor, which quantifies the inconsistencies between aquifer diffusivities estimated from attenuation and time-lag data, is computed and analysed. Near the coast, slope factor values greater than one are obtained for negative wedging parameters while slope factor values less than one are obtained for positive wedging parameters. The analysis of the new solution also indicates that more reliable estimates of the hydraulic diffusivity can be obtained from time-lag data.Fil: Cuello, Julián Eduardo. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Departamento de Geofísica Aplicada; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Guarracino, Luis. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Departamento de Geofísica Aplicada; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo; Argentin

iSupport for Young Carers: An Adaptation of an e-Health Intervention for Young Dementia Carers

Young dementia carers need to be recognised and supported in their role. They need help to understand the illness, what changes are expected and how it can affect their family member. Many support services, partly due to the COVID pandemic, have moved online and have been shown to be acceptable as they are low cost and reduce access barriers. iSupport is an evidence-informed e-health training programme developed by the World Health Organization (WHO) to support adult dementia carers. This paper reports on the co-design of an adapted version of iSupport for young carers. A theoretically driven co-design approach, drawing on the lived experiences of young dementia carers and experts who work with this target group was followed. As a result of this study iSupport for Young Carers was created. It is the first e-health intervention of its kind and aims to support the mental health, knowledge and skills of young dementia carers. In turn, it could improve the quality of the support that service providers can offer, and this can result in increased levels of identification of these young people. The work presented also provides opportunities for other countries and demographic groups to translate and adapt iSupport for Young Carers to their specific cultural context

Tev Observations of the Variability and Spectrum of Markarian 421

Markarian 421 was the first extragalactic source to be detected with high statistical certainty at TeV energies. The Whipple Observatory gamma-ray telescope has been used to observe the Active Galactic Nucleus, Markarian 421 in 1996 and 1997. The rapid variability observed in TeV gamma rays in previous years is confirmed. Doubling times as short as 15 minutes are reported with flux levels reaching 15 photons per minute. The TeV energy spectrum is derived using two independent methods. The implications for the intergalactic infra-red medium of an observed unbroken power law spectrum up to energies of 5 TeV is discussed.Comment: 4 pages, 4 figures, to appear in proceedings of 25 ICRC (Durban

TeV Observations of the Variability and Spectrum of Markarian 501

Markarian 501 is only the second extragalactic source to be detected with high statistical certainty at TeV energies; it is similar in many ways to Markarian 421. The Whipple Observatory gamma-ray telescope has been used to observe the AGN Markarian 501 in 1996 and 1997, the years subsequent to its initial detection. The apparent variability on the one-day time-scale observed in TeV gamma rays in 1995 is confirmed and compared with the variability in Markarian 421. Observations at X-ray and optical wavelengths from 1997 are also presented.Comment: 4 pages, 2 figures, to appear in proceedings of 25th ICRC (Durban