Saccharomyces cerevisiae glutaredoxin 5-deficient cells subjected to constitutive oxidizing conditions are affected in the expression of specific sets of genes

The Saccharomyces cerevisiae GRX5 gene codes for a mitochondrial glutaredoxin involved in the synthesis ofiron/sulfur clusters. Its absence prevents respiratory growth and causes the accumulation of iron inside cellsand constitutive oxidation of proteins. Null Δgrx5 mutants were used as an example of continuously oxidizedcells, as opposed to situations in which oxidative stress is instantaneously caused by addition of external oxidants.Whole transcriptome analysis was carried out in the mutant cells. The set of genes whose expression wasaffected by the absence of Grx5 does not significantly overlap with the set of genes affected in respiratorypetite mutants. Many Aft1-dependent genes involved in iron utilization that are up-regulated in a frataxin mutantwere also up-regulated in the absence of Grx5. BIO5 is another Aft1-dependent gene induced both upon irondeprivation and in Δgrx5 cells; this links iron and biotin metabolism. Other genes are specifically affected underthe oxidative conditions generated by the grx5 mutation. One of these is MLP1, which codes for a homologueof the Slt2 kinase. Cells lacking MLP1 and GRX5 are hypersensitive to oxidative stress caused by externalagents and exhibit increased protein oxidation in relation to single mutants. This in turn points to a role forMlp1 in protection against oxidative stress. The genes of the Hap4 regulon, which are involved in respiratorymetabolism, are down-regulated in Δgrx5 cells. This effect is suppressed by HAP4 overexpression. Inhibition ofrespiratory metabolism during continuous moderately oxidative conditions could be a protective response bythe cell

Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry.

We used on-line electron capture dissociation (ECD) for the large scale identification and localization of sites of phosphorylation. Each FT-ICR ECD event was paired with a linear ion trap collision-induced dissociation (CID) event, allowing a direct comparison of the relative merits of ECD and CID for phosphopeptide identification and site localization. Linear ion trap CID was shown to be most efficient for phosphopeptide identification, whereas FT-ICR ECD was superior for localization of sites of phosphorylation. The combination of confident CID and ECD identification and confident CID and ECD localization is particularly valuable in cases where a phosphopeptide is identified just once within a phosphoproteomics experiment

Problematising high-stakes assessment in statistics.

Statistics emerged as a discipline to address pressing practical problems. In the UK, this has not been reflected in school statistics curricula, where students often work with small-scale invented data to develop mastery of statistical technique. Recent curriculum reforms set out to improve this situation; students are expected to work in class with a large authentic data set, and to demonstrate appropriate skills on high-stakes assessment. Here, we analyse all the first set of examination papers containing statistics for the new GCE qualification, and also questions using statistical graphs from the GCSE qualifications in summer 2017. We show that there is very little emphasis on statistical skills such as interpreting data and drawing conclusions, and a great deal of emphasis on technical skills. Contexts are (for the most part) banal. Several questions ask students to use inappropriate procedures. We believe systemic flaws have resulted in assessment which is not fit for purpose. We call for curriculum reform, and offer examples of how things might be done better both in curriculum and in assessment

Growth hormone and insulin-like growth factor-I alter hippocampal excitatory synaptic transmission in young and old rats

In rats, as in humans, normal aging is characterized by a decline in hippocampal-dependent learning and memory, as well as in glutamatergic function. Both growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels have been reported to decrease with age, and treatment with either GH or IGF-I can ameliorate age-related cognitive decline. Interestingly, acute GH and IGF-I treatments enhance glutamatergic synaptic transmission in the rat hippocampus of juvenile animals. However, whether this enhancement also occurs in old rats, when cognitive impairment is ameliorated by GH and IGF-I (des-IGF-I), remains to be determined. To address this issue, we used an in vitro CA1 hippocampal slice preparation and extracellular recording techniques to study the effects of acute application of GH and IGF-I on compound field excitatory postsynaptic potentials (fEPSPs), as well as AMPA- and NMDA-dependent fEPSPs, in young adult (10 months) and old (28 months) rats. The results indicated that both GH and IGF-I increased compound-, AMPA-and NMDA-dependent fEPSPs to a similar extent in slices from both age groups and that this augmentation was likely mediated via a postsynaptic mechanism. Initial characterization of the signaling cascades underlying these effects revealed that the GH-induced enhancement was not mediated by the JAK2 signaling element in either young adult or old rats but that the IGF-Iinduced enhancement involved a PI3K-mediated mechanism in old, but not young adults. The present findings are consistent with a role for a GH-or IGF-I-induced enhancement of glutamatergic transmission in mitigating age-related cognitive impairment in old rats. © 2012 American Aging Association

The lusitano native thoroughbred: a genetic study of the important reproductive parameters in plans for conservation and improvement

A idade do primeiro filho, nos garanhões, marca o inicio da sua vida reprodutiva, assim como a idade ao último filho marca o final da mesma. A vida média reprodutiva é calculada fazendo a diferença entre estas duas idades, correspondendo o seu valor ao período de actividade reprodutiva da vida do animal. O número de descendentes por garanhão ao longo da sua vida reprodutiva é variável em função da duração da sua vida média reprodutiva e da sua taxa média de fertilidade. Em geral o comportamento reprodutivo do cavalo não corresponde ao verdadeiro potencial das raças equinas, sendo isto em grande medida devido aos costumes e às actividades desportivas a que são submetidos os seus reprodutores. Em geral, os garanhões só são postos a cobrir depois de demonstrarem o seu valor como desportistas, por essa razão iniciam em geral a sua actividade reprodutiva mais tarde do que as fêmeas. Através da informação fornecida pelo Livro Genealógico do Puro Sangue Lusitano, formouse uma base de dados com informação sobre 704 machos reprodutores. Foram calculados os parâmetros reprodutivos médios da idade ao primeiro filho, idade ao último filho, vida média reprodutiva e número de filhos, cujos valores foram respectivamente, 82,74 meses, 125,68 meses, 50,60 meses e 12,28 descendentes. Foi encontrada como significativa apenas uma correlação com a consanguinidade, que foi para o parâmetro número de descendentes (r= 0,112). A consanguinidade média da amostra foi de 2,67 p.100.The age of the first suckling bounds the beginning of its reproductive life, as well as the age at the last suckling bounds its end. The reproductive average life is stricken by establishing the difference between these two ages, corresponding its value to the lifetime of reproductive activity of the animal. The number of descendants per stallion during its reproductive life is variable according to the lastingness of its reproductive average life and to its average rate of fertility. For the most part of the reproductive behaviour of the horse doesn’t correspond to the true potential of the equine race. One can say this is largely due to the customs and sports to which the stallions are subjected. Usually, stallions are only given the opportunity to copulate after showing their value as athletes and, for that reason, they usually begin their reproductive activity later that the females. With the information given by the Stud-Book of the Lusitanian Thoroughbred, it was installed a data basis with information about 704 stallions. The rated values of the average reproductive parameters of the age of the first suckling, the age at the last suckling, the reproductive average life and number of descendents were, respectively, 82.7 months, 125.7 months, 50.6 months and 12.3 descendents. The average inbreed of the sample was 2,67 p.100. The only significant correlation with inbreed that was found, was to the parameter number of descendents (r= 0.112)

IFNL4 ss469415590 polymorphism is associated with unfavourable clinical and immunological status in HIV-infected individuals

AbstractThe IFNL4 ss469415590 polymorphism, in high linkage disequilibrium with the IL28B rs12979860 variant, has been associated with hepatitis C virus clearance. We evaluated whether ss469415590 is associated with clinical and immunovirological parameters in human immunodeficiency virus-infected subjects. We found an independent association of the IFNL4 ss469415590 polymorphism with higher prevalence of AIDS-defining illnesses and lower CD4 T cell numbers. These results suggest the existence of common host defence mechanisms against different viral infections

Growth hormone modulates hippocampal excitatory synaptic transmission and plasticity in old rats

Alterations in the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPA-R) and N-methyl-D-aspartate receptor (NMDA-R) have been documented in aged animals and may contribute to changes in hippocampal-dependent memory. Growth hormone (GH) regulates AMPA-R and NMDA-R-dependent excitatory transmission and decreases with age. Chronic GH treatment mitigates age-related cognitive decline. An in vitro CA1 hippocampal slice preparation was used to compare hippocampal excitatory transmission and plasticity in old animals treated for 6-8 months with either saline or GH. Our findings indicate that GH treatment restores NMDA-R-dependent basal synaptic transmission in old rats to young adult levels and enhances both AMPA-R-dependent basal synaptic transmission and long-term potentiation. These alterations in synaptic function occurred in the absence of changes in presynaptic function, as measured by paired-pulse ratios, the total protein levels of AMPA-R and NMDA-R subunits or in plasma or hippocampal levels of insulin-like growth factor-I. These data suggest a direct role for GH in altering age-related changes in excitatory transmission and provide a possible cellular mechanism through which GH changes the course of cognitive decline. © 2012 Elsevier Inc

Instabilities and Bifurcations of Nonlinear Impurity Modes

We study the structure and stability of nonlinear impurity modes in the discrete nonlinear Schr{\"o}dinger equation with a single on-site nonlinear impurity emphasizing the effects of interplay between discreteness, nonlinearity and disorder. We show how the interaction of a nonlinear localized mode (a discrete soliton or discrete breather) with a repulsive impurity generates a family of stationary states near the impurity site, as well as examine both theoretical and numerical criteria for the transition between different localized states via a cascade of bifurcations.Comment: 8 pages, 8 figures, Phys. Rev. E in pres

Superficial radiotherapy as haemostatic treatment in breast cancer

Poster Session [EP-1661] Purpose or Objective Breast cancer is a common pathology in which o = 25% in tumor size and absence of bleeding was observed. Conclusion Surface radiotherapy is a treatment modality that should be taken into account in patients with breast cancer who present bleeding as a consequence of local tumor growth, given that this is a treatment comfortable for the patient, non invasive and increases the quality of patient’s life