Mammalian models of extended healthy lifespan

Over the last two centuries, there has been a significant increase in average lifespan expectancy in the developed world. One unambiguous clinical implication of getting older is the risk of experiencing age-related diseases including various cancers, dementia, type-2 diabetes, cataracts and osteoporosis. Historically, the ageing process and its consequences were thought to be intractable. However, over the last two decades or so, a wealth of empirical data has been generated which demonstrates that longevity in model organisms can be extended through the manipulation of individual genes. In particular, many pathological conditions associated with the ageing process in model organisms, and importantly conserved from nematodes to humans, are attenuated in long-lived genetic mutants. For example, several long-lived genetic mouse models show attenuation in age-related cognitive decline, adiposity, cancer and glucose intolerance. Therefore, these long-lived mice enjoy a longer period without suffering the various sequelae of ageing. The greatest challenge in the biology of ageing is to now identify the mechanisms underlying increased healthy lifespan in these model organisms. Given that the elderly are making up an increasingly greater proportion of society, this focused approach in model organisms should help identify tractable interventions that can ultimately be translated to humans

Predictive value of hematological and phenotypical parameters on postchemotherapy leukocyte recovery

Background: Grade IV chemotherapy toxicity is defined as absolute neutrophil count <500/μL. The nadir is considered as the lowest neutrophil number following chemotherapy, and generally is not expected before the 7th day from the start of chemotherapy. The usual prophylactic dose of rHu-G-CSF (Filgrastim) is 300 μg/day, starting 24-48 h after chemotherapy until hematological recovery. However, individual patient response is largely variable, so that rHu-G-CSF doses can be different. The aim of this study was to verify if peripheral blood automated flow cytochemistry and flow cytometry analysis may be helpful in predicting the individual response and saving rHu-G-CSF. Methods: During Grade IV neutropenia, blood counts from 30 cancer patients were analyzed daily by ADVIA 120 automated flow cytochemistry analyzer and by Facscalibur flow cytometer till the nadir. "Large unstained cells" (LUCs), myeloperoxidase index (MPXI), blasts, and various cell subpopulations in the peripheral blood were studied. At nadir rHu-G-CSF was started and 81 chemotherapy cycles were analyzed. Cycles were stratified according to their number and to two dose-levels of rHuG-CSF needed to recovery (300-600 vs. 900-1200 μg) and analyzed in relation to mean values of MPXI and mean absolute number of LUCs in the nadir phase. The linear regressions of LUCs % over time in relation to two dose-levels of rHu-G-CSF and uni-multivariate analysis of lymphocyte subpopulations, CD34+ cells, MPXI, and blasts were also performed. Results: In the nadir phase, the increase of MPXI above the upper limit of normality (>10; median 27.7), characterized a slow hematological recovery. MPXI levels were directly related to the cycle number and inversely related to the absolute number of LUCs and CD34 +/CD45+ cells. A faster hematological recovery was associated with a higher LUC increase per day (0.56% vs. 0.25%), higher blast (median 36.7/μL vs. 19.5/μL) and CD34+/CD45+ cell (median 2.2/μL vs. 0.82/μL) counts. Conclusions: Our study showed that some biological indicators such as MPXI, LUCs, blasts, and CD34 +/CD45+ cells may be of clinical relevance in predicting individual hematological response to rHu-G-CSF. Special attention should be paid when nadir MPXI exceeds the upper limit of normality because the hematological recovery may be delayed. © 2009 Clinical Cytometry Society

Enhancer SINEs Link Pol III to Pol II Transcription in Neurons

Spatiotemporal regulation of gene expression depends on the cooperation of multiple mechanisms, including the functional interaction of promoters with distally located enhancers. Here, we show that, in cortical neurons, a subset of short interspersed nuclear elements (SINEs) located in the proximity of activity-regulated genes bears features of enhancers. Enhancer SINEs (eSINEs) recruit the Pol III cofactor complex TFIIIC in a stimulus-dependent manner and are transcribed by Pol III in response to neuronal depolarization. Characterization of an eSINE located in proximity to the Fos gene (FosRSINE1) indicated that the FosRSINE1-encoded transcript interacts with Pol II at the Fos promoter and mediates Fos relocation to Pol II factories, providing an unprecedented molecular link between Pol III and Pol II transcription. Strikingly, knockdown of the FosRSINE1 transcript induces defects of both cortical radial migration in vivo and activity-dependent dendritogenesis in vitro, demonstrating that FosRSINE1 acts as a strong enhancer of Fos expression in diverse physiological contexts

Giant ambipolar Rashba effect in a semiconductor: BiTeI

We observe a giant spin-orbit splitting in bulk and surface states of the non-centrosymmetric semiconductor BiTeI. We show that the Fermi level can be placed in the valence or in the conduction band by controlling the surface termination. In both cases it intersects spin-polarized bands, in the corresponding surface depletion and accumulation layers. The momentum splitting of these bands is not affected by adsorbate-induced changes in the surface potential. These findings demonstrate that two properties crucial for enabling semiconductor-based spin electronics -- a large, robust spin splitting and ambipolar conduction -- are present in this material.Comment: 4 pages, 3 figure

The momentum and photon energy dependence of the circular dichroic photoemission in the bulk Rashba semiconductors BiTeX (X = I, Br, Cl)

Bulk Rashba systems BiTeX (X = I, Br, Cl) are emerging as important candidates for developing spintronics devices, because of the coexistence of spin-split bulk and surface states, along with the ambipolar character of the surface charge carriers. The need of studying the spin texture of strongly spin-orbit coupled materials has recently promoted circular dichroic Angular Resolved Photoelectron Spectroscopy (cd-ARPES) as an indirect tool to measure the spin and the angular degrees of freedom. Here we report a detailed photon energy dependent study of the cd-ARPES spectra in BiTeX (X = I, Br and Cl). Our work reveals a large variation of the magnitude and sign of the dichroism. Interestingly, we find that the dichroic signal modulates differently for the three compounds and for the different spin-split states. These findings show a momentum and photon energy dependence for the cd-ARPES signals in the bulk Rashba semiconductor BiTeX (X = I, Br, Cl). Finally, the outcome of our experiment indicates the important relation between the modulation of the dichroism and the phase differences between the wave-functions involved in the photoemission process. This phase difference can be due to initial or final state effects. In the former case the phase difference results in possible interference effects among the photo-electrons emitted from different atomic layers and characterized by entangled spin-orbital polarized bands. In the latter case the phase difference results from the relative phases of the expansion of the final state in different outgoing partial waves.Comment: 6 pages, 4 figure

Molecular cloning, promoter analysis and SNP identification of Italian Nicastrese and Saanen lactoferrin gene

Lactoferrin (Lf) is an iron-binding glycoprotein found in exocrine secretions including milk. High levels of lactoferrin may have a role in the prevention of microbial infection of the mammary gland. In this report we sequenced and characterized goat lactoferrin cDNA and its promoter region in two different breeds of goat. The complete cDNA comprised 2356 nucleotides, including 38bp at the 5'-UTR and 194bp at the 3'-UTR. The open reading frame is 2127bp long and it encodes a mature protein of 689 aminoacids. A total of 19 nucleotide differences, 11 of them being responsible for 8 aminoacid changes, were identified through the comparison with French, Korean and Tibetan goat lactoferrin cDNAs. About 1700bp of the lactoferrin gene promoter were sequenced. Sequence analysis revealed a non-canonical TATA box, multiple SP1/GC elements, and other putative binding sites for transcription factors, such as NF-kappaB, STAT3 and AP2. Two SNPs were identified, one of which would seem to create a new putative AP2 consensus sequence. The presence of an additional AP2 binding site could be associated with quantitative differences of such protein fraction, which could enhance all the activities related to such protein, and improve mammary gland defence against bacterial infections

Electronic Instability in a Zero-Gap Semiconductor: The Charge-DensityWave in (TaSe4)(2)I

We report a comprehensive study of the paradigmatic quasi-1D compound (TaSe4)(2)I performed by means of angle-resolved photoemission spectroscopy (ARPES) and first-principles electronic structure calculations. We find it to be a zero-gap semiconductor in the nondistorted structure, with non-negligible interchain coupling. Theory and experiment support a Peierls-like scenario for the charge-density wave formation below T-CDW = 263 K, where the incommensurability is a direct consequence of the finite interchain coupling. The formation of small polarons, strongly suggested by the ARPES data, explains the puzzling semiconductor-to-semiconductor transition observed in transport at T-CDW.open114sciescopu

Electronic Instability in a Zero-Gap Semiconductor: The Charge-DensityWave in (TaSe4)(2)I

International audienceWe report a comprehensive study of the paradigmatic quasi-1D compound (TaSe4)(2)I performed by means of angle-resolved photoemission spectroscopy (ARPES) and first-principles electronic structure calculations. We find it to be a zero-gap semiconductor in the nondistorted structure, with non-negligible interchain coupling. Theory and experiment support a Peierls-like scenario for the charge-density wave formation below T-CDW = 263 K, where the incommensurability is a direct consequence of the finite interchain coupling. The formation of small polarons, strongly suggested by the ARPES data, explains the puzzling semiconductor-to-semiconductor transition observed in transport at T-CDW

TRACEABILITY OF FOUR EUROPEAN PROTECTED GEOGRAPHIC INDICATION (PGI) BEEF PRODUCTS USING SINGLE NUCLEOTIDE POLYMORPHISMS (SNP) AND BAYESIAN STATISTICS

The use of SNPs in combination with Bayesian statistics for the geographic traceability of cattle were evaluated using a dataset comprising 24 breeds from Italy,France,Spain, Denmark, the Netherlands,Switzerland and UK genotyped with 90 polymorphic markers. The percentage of correct assignment of the individuals to their Country of origin was 90%, with an average assignment probability of 93% and an average specificity of 92%. The higher value was observed for UK breeds (97% of correct assignment) while Swiss animals were the most difficult to allocate (77% of correct assignment). Tracing of Protected Geographic Indication (PGI) products, the approach correctly assigned 100% of Guaranteed Pure Highland Beef; 97% of “Vitellone dell’Appennino Centrale” breeds; 84% of Ternera de Navarra, and 80% of Boeuf de Chalosse. Methods to verify Products of Designated Origin (PDO) and Protected Geographic Indication (PGI) products will help to protect regional foods and promote the economic growth of marginal rural areas by encouraging the product on of high quality niche market foods