On the Kernel of Z2s\mathbb{Z}_{2^s}-Linear Hadamard Codes

The $\mathbb{Z}_{2^s}$-additive codes are subgroups of $\mathbb{Z}^n_{2^s}$, and can be seen as a generalization of linear codes over $\mathbb{Z}_2$ and $\mathbb{Z}_4$. A $\mathbb{Z}_{2^s}$-linear Hadamard code is a binary Hadamard code which is the Gray map image of a $\mathbb{Z}_{2^s}$-additive code. It is known that the dimension of the kernel can be used to give a complete classification of the $\mathbb{Z}_4$-linear Hadamard codes. In this paper, the kernel of $\mathbb{Z}_{2^s}$-linear Hadamard codes and its dimension are established for $s > 2$. Moreover, we prove that this invariant only provides a complete classification for some values of $t$ and $s$. The exact amount of nonequivalent such codes are given up to $t=11$ for any $s\geq 2$, by using also the rank and, in some cases, further computations

Autophagy and Apoptosis Have a Role in the Survival or Death of Stallion Spermatozoa during Conservation in Refrigeration

Apoptosis has been recognized as a cause of sperm death during cryopreservation and a cause of infertility in humans, however there is no data on its role in sperm death during conservation in refrigeration; autophagy has not been described to date in mature sperm. We investigated the role of apoptosis and autophagy during cooled storage of stallion spermatozoa. Samples from seven stallions were split; half of the ejaculate was processed by single layer centrifugation, while the other half was extended unprocessed, and stored at 5°C for five days. During the time of storage, sperm motility (CASA, daily) and membrane integrity (flow cytometry, daily) were evaluated. Apoptosis was evaluated on days 1, 3 and 5 (active caspase 3, increase in membrane permeability, phosphatidylserine translocation and mitochondrial membrane potential) using flow cytometry. Furthermore, LC3B processing was investigated by western blotting at the beginning and at the end of the period of storage. The decrease in sperm quality over the period of storage was to a large extent due to apoptosis; single layer centrifugation selected non-apoptotic spermatozoa, but there were no differences in sperm motility between selected and unselected sperm. A high percentage of spermatozoa showed active caspase 3 upon ejaculation, and during the period of storage there was an increase of apoptotic spermatozoa but no changes in the percentage of live sperm, revealed by the SYBR-14/PI assay, were observed. LC3B was differentially processed in sperm after single layer centrifugation compared with native sperm. In processed sperm more LC3B-II was present than in non-processed samples; furthermore, in non-processed sperm there was an increase in LC3B-II after five days of cooled storage. These results indicate that apoptosis plays a major role in the sperm death during storage in refrigeration and that autophagy plays a role in the survival of spermatozoa representing a new pro-survival mechanism in spermatozoa not previously described

Protección de la Heparina a las células B- pancreáticas frente a radicales libres de Oxígeno.

La diabetes autoinmune tipo 1 se caracteriza por la invasión de células mononucleares en los islotes pancreáticos, destruyendo así las células beta productoras de insulina. Se ha visto que in vivo la destrucción autoinmune de los islotes se asocia con la producción de heparanasa, la cual degrada heparán sulfato (molécula imprescindible para la supervivencia de los islotes) y se permite la entrada de las células inmunitarias que atacarán los islotes beta pancreáticos. Se han obtenido resultados mediante la adición de concentraciones conocidas de heparina, la cual confiere una protección extra frente a radicales libres de oxígeno y como consecuencia hay una disminución de la mortalidad celular.A través de tres líneas celulares distintas se ha llevado a cabo el experimento. Primeramente con Rinm5F productora de insulina y somatostatina, con células Ins capaces de responder al estímulo de glucosa produciendo y secretando insulina y finalmente con fibroblastos. El experimento se basa en dejar crecer las cepas celulares en un número determinado de flacs según el tratamiento. Se añade heparina a una concentración conocida y establecida anteriormente y al día siguiente con una concentración exacta de agua oxigenada (aporta los radicales libres de oxígeno) se la añadimos al cultivo. Recogemos las células y gracias al ioduro de propidio con concentración 1 mg/ml marcamos las células muertas para así poder comprobar el porcentaje de supervivencia celular que le ha conferido la heparina a cada línea celular. Procedemos a realizar el contaje con el citómetro que indica el % de muerte celular, ya que el ioduro de propidio es un agente intercalante que se une a los ácidos nucleicos. Esta molécula fluorescente se utiliza para evaluar la viabilidad celular o el contenido de ADN en las células. Se puede utilizar para diferenciar células necróticas, apoptóticas o vivas.Los resultados obtenidos con las líneas celulares Rinm5F y las Ins nos muestran que a bajas concentraciones de agua oxigenada y con heparina, efectivamente hay protección ya que la muerte celular se reduce de un 10 a un 15%. En cambio con los fibroblastos no vemos protección a ninguna de las concentraciones establecidas, resultado que ya esperábamos en nuestra hipótesis inicial. Estos resultados sólo son el inicio de un largo estudio, ya que  primero se ajustan las concentraciones a trabajar con radicales libres de oxígeno, pero en un  futuro el estudio se realizará también con radicales de nitrógeno

Relación entre muerte celular y mantenimiento de la pluripotencialidad de células mES en protocolos de diferenciación con óxido nítrico

En este proyecto se pretende estudiar la relación entre la muerte celular y la diferenciación durante el desarrollo usando como modelo experimental células madre embrionarias de ratón (mESC). Se ha descrito que las altas concentraciones de DETA-NO (500uM) provocan la diferenciación de estas mESC hacia endodermo (Mora-Castilla et al., 2010), pero en estos protocolos no todas consiguen sobrevivir y un alto porcentaje de células muere. Es por ello que se quiere analizar la relación entre ambos eventos. Se estudiará, por un lado, si el bloqueo de la apoptosis con inhibidores de caspasas tiene efectos sobre la diferenciación; y por otro lado si es probable que exista una liberación de moléculas al medio por parte de las células apoptóticas que contribuya a la pérdida de la pluripotencialidad de sus vecinas. Para ello se ha analizado el mantenimiento del estado pluripotente en dos tipos de ensayos. Por un lado se ha estudiado el efecto de inhibidores de caspasas en tratamientos con DETA-NO en dos líneas de mESC (D3 y R1/E), y por otro lado se ha evaluado el efecto del reciclaje de medios de cultivo en la línea celular D3. Para medir el mantenimiento de la pluripotencialidad se han empleado distintas técnicas de biología molecular (extracción de RNA, PCR, qPCR, Western Blotting…) y técnicas de microscopía. Con ello se han buscado diferencias de expresión de los marcadores de pluripotencia (Nanog y Oct4) y marcadores de endodermo (Pdx1, Cxcr4), mesodermo (Brachyury) y ectodermo (Zic1). Se ha demostrado que el uso de inhibidores de caspasas en tratamientos con DETA-NO bloquea la regulación a la baja de Nanog, tanto en niveles de RNAm como de proteína, y disminuye la expresión de los marcadores de diferenciación. Por otro lado, el uso de medios de cultivo reciclados procedentes de tratamientos anteriores con y sin DETA-NO, suplementados y con el factor inhibidor de la diferenciación LIF (Leukemia Inhibitory Factor) estimula la diferenciación de las células. Los resultados obtenidos apuntan a que podría existir una relación entre la muerte celular y la diferenciación, ya que al inhibir la muerte por apoptosis se favorece el mantenimiento del estado pluripotente . Además, el uso de medios reciclados ayuda a la diferenciación de las células incluso en presencia de LIF. Por ello se cree que células apoptóticas podrían estar secretando sustancias al medio que las células vecinas estarían utilizando como señales para diferenciarse

Nuclear envelope protein Lem2 is required for mouse development and regulates MAP and AKT kinases

The nuclear lamina, along with associated nuclear membrane proteins, is a nexus for regulating signaling in the nucleus. Numerous human diseases arise from mutations in lamina proteins, and experimental models for these disorders have revealed aberrant regulation of various signaling pathways. Previously, we reported that the inner nuclear membrane protein Lem2, which is expressed at high levels in muscle, promotes the differentiation of cultured myoblasts by attenuating ERK signaling. Here, we have analyzed mice harboring a disrupted allele for the Lem2 gene (Lemd2). No gross phenotypic defects were seen in heterozygotes, although muscle regeneration induced by cardiotoxin was delayed. By contrast, homozygous Lemd2 knockout mice died by E11.5. Although many normal morphogenetic hallmarks were observed in E10.5 knockout embryos, most tissues were substantially reduced in size. This was accompanied by activation of multiple MAP kinases (ERK1/2, JNK, p38) and AKT. Knockdown of Lem2 expression in C2C12 myoblasts also led to activation of MAP kinases and AKT. These findings indicate that Lemd2 plays an essential role in mouse embryonic development and that it is involved in regulating several signaling pathways. Since increased MAP kinase and AKT/mTORC signaling is found in other animal models for diseases linked to nuclear lamina proteins, LEMD2 should be considered to be another candidate gene for human disease

Probiotic supplementation influences the diversity of the intestinal microbiota during early stages of farmed Senegalese sole (Solea senegalensis, Kaup, 1858)

Ingestion of bacteria at early stages results in establishment of a primary intestinal microbiota which likely undergoes several stages along fish life. The role of this intestinal microbiota regulating body functions is crucial for larval development. Probiotics have been proved to modulate this microbiota and exert antagonistic effects against fish pathogens. In the present study, we aimed to determine bacterial diversity along different developmental stages of farmed Senegalese sole (Solea senegalensis) after feeding probiotic (Shewanella putrefaciens Pdp11) supplemented diet for a short period (10–30 days after hatching, DAH). Intestinal lumen contents of sole larvae fed control and probiotic diets were collected at 23, 56, 87, and 119 DAH and DNA was amplified using 16S rDNA bacterial domain-specific primers. Amplicons obtained were separated by denaturing gradient gel electrophoresis (DGGE), cloned, and resulting sequences compared to sequences in GenBank. Results suggest that Shewanella putrefaciens Pdp11 induces a modulation of the dominant bacterial taxa of the intestinal microbiota from 23 DAH. DGGE patterns of larvae fed the probiotic diet showed a core of bands related to Lactobacillus helveticus, Pseudomonas acephalitica, Vibrio parahaemolyticus,and Shewanella genus, together with increased Vibri o genus presence. In addition, decreased number of clones related to Photobacterium damselae subsp piscicida at 23 and 56 DAH was observed in probiotic-fed larvae. A band corresponding to Shewanella putrefaciens Pdp11 was sequenced as predominant from 23 to 119 DAH samples, confirming the colonization by the probiotics. Microbiota modulation obtained via probiotics addition emerges as an effective tool to improve Solea senegalensis larviculture.En prens

Constant light enhances synchrony among circadian clock cells and promotes behavioral rhythms in VPAC(2)-signaling deficient mice

Individual neurons in the suprachiasmatic nuclei (SCN) contain an intracellular molecular clock and use intercellular signaling to synchronize their timekeeping activities so that the SCN can coordinate brain physiology and behavior. The neuropeptide vasoactive intestinal polypeptide (VIP) and its VPAC2 receptor form a key component of intercellular signaling systems in the SCN and critically control cellular coupling. Targeted mutations in either the intracellular clock or intercellular neuropeptide signaling mechanisms, such as VIP-VPAC2 signaling, can lead to desynchronization of SCN neuronal clocks and loss of behavioral rhythms. An important goal in chronobiology is to develop interventions to correct deficiencies in circadian timekeeping. Here we show that extended exposure to constant light promotes synchrony among SCN clock cells and the expression of ~24 h rhythms in behavior in mice in which intercellular signaling is disrupted through loss of VIP-VPAC2 signaling. This study highlights the importance of SCN synchrony for the expression of rhythms in behavior and reveals how non-invasive manipulations in the external environment can be used to overcome neurochemical communication deficits in this important brain system

Interaction among apoptosis-associated sequence variants and joint effects on aggressive prostate cancer

<p>Abstract</p> <p>Background</p> <p>Molecular and epidemiological evidence demonstrate that altered gene expression and single nucleotide polymorphisms in the apoptotic pathway are linked to many cancers. Yet, few studies emphasize the interaction of variant apoptotic genes and their joint modifying effects on prostate cancer (PCA) outcomes. An exhaustive assessment of all the possible two-, three- and four-way gene-gene interactions is computationally burdensome. This statistical conundrum stems from the prohibitive amount of data needed to account for multiple hypothesis testing.</p> <p>Methods</p> <p>To address this issue, we systematically prioritized and evaluated individual effects and complex interactions among 172 apoptotic SNPs in relation to PCA risk and aggressive disease (i.e., Gleason score ≥ 7 and tumor stages III/IV). Single and joint modifying effects on PCA outcomes among European-American men were analyzed using statistical epistasis networks coupled with multi-factor dimensionality reduction (SEN-guided MDR). The case-control study design included 1,175 incident PCA cases and 1,111 controls from the prostate, lung, colo-rectal, and ovarian (PLCO) cancer screening trial. Moreover, a subset analysis of PCA cases consisted of 688 aggressive and 488 non-aggressive PCA cases. SNP profiles were obtained using the NCI Cancer Genetic Markers of Susceptibility (CGEMS) data portal. Main effects were assessed using logistic regression (LR) models. Prior to modeling interactions, SEN was used to pre-process our genetic data. SEN used network science to reduce our analysis from > 36 million to < 13,000 SNP interactions. Interactions were visualized, evaluated, and validated using entropy-based MDR. All parametric and non-parametric models were adjusted for age, family history of PCA, and multiple hypothesis testing.</p> <p>Results</p> <p>Following LR modeling, eleven and thirteen sequence variants were associated with PCA risk and aggressive disease, respectively. However, none of these markers remained significant after we adjusted for multiple comparisons. Nevertheless, we detected a modest synergistic interaction between <it>AKT3 rs2125230-PRKCQ rs571715 </it>and disease aggressiveness using SEN-guided MDR (p = 0.011).</p> <p>Conclusions</p> <p>In summary, entropy-based SEN-guided MDR facilitated the logical prioritization and evaluation of apoptotic SNPs in relation to aggressive PCA. The suggestive interaction between <it>AKT3-PRKCQ </it>and aggressive PCA requires further validation using independent observational studies.</p

Distinct Salmonella Enteritidis lineages associated with enterocolitis in high-income settings and invasive disease in low-income settings.

An epidemiological paradox surrounds Salmonella enterica serovar Enteritidis. In high-income settings, it has been responsible for an epidemic of poultry-associated, self-limiting enterocolitis, whereas in sub-Saharan Africa it is a major cause of invasive nontyphoidal Salmonella disease, associated with high case fatality. By whole-genome sequence analysis of 675 isolates of S. Enteritidis from 45 countries, we show the existence of a global epidemic clade and two new clades of S. Enteritidis that are geographically restricted to distinct regions of Africa. The African isolates display genomic degradation, a novel prophage repertoire, and an expanded multidrug resistance plasmid. S. Enteritidis is a further example of a Salmonella serotype that displays niche plasticity, with distinct clades that enable it to become a prominent cause of gastroenteritis in association with the industrial production of eggs and of multidrug-resistant, bloodstream-invasive infection in Africa.This work was supported by the Wellcome Trust. We would like to thank the members of the Pathogen Informatics Team and the core sequencing teams at the Wellcome Trust Sanger Institute (Cambridge, UK). We are grateful to D. Harris for work in managing the sequence data