dKDM5/LID regulates H3K4me3 dynamics at the transcription-start site (TSS) of actively transcribed developmental genes

H3K4me3 is a histone modification that accumulates at the transcription-start site (TSS) of active genes and is known to be important for transcription activation. The way in which H3K4me3 is regulated at TSS and the actual molecular basis of its contribution to transcription remain largely unanswered. To address these questions, we have analyzed the contribution of dKDM5/LID, the main H3K4me3 demethylase in Drosophila, to the regulation of the pattern of H3K4me3. ChIP-seq results show that, at developmental genes, dKDM5/LID localizes at TSS and regulates H3K4me3. dKDM5/LID target genes are highly transcribed and enriched in active RNApol II and H3K36me3, suggesting a positive contribution to transcription. Expression-profiling show that, though weakly, dKDM5/LID target genes are significantly downregulated upon dKDM5/LID depletion. Furthermore, dKDM5/LID depletion results in decreased RNApol II occupancy, particularly by the promoter-proximal Pol lloser5 form. Our results also show that ASH2, an evolutionarily conserved factor that locates at TSS and is required for H3K4me3, binds and positively regulates dKDM5/LID target genes. However, dKDM5/LID and ASH2 do not bind simultaneously and recognize different chromatin states, enriched in H3K4me3 and not, respectively. These results indicate that, at developmental genes, dKDM5/LID and ASH2 coordinately regulate H3K4me3 at TSS and that this dynamic regulation contributes to transcription.

Nutrient-based dietary patterns and the risk of head and neck cancer: a pooled analysis in the International Head and Neck Cancer Epidemiology consortium.

Background The association between dietary patterns and head and neck cancer has rarely been addressed. Patients and methods We used individual-level pooled data from five case-control studies (2452 cases and 5013 controls) participating in the International Head and Neck Cancer Epidemiology consortium. A posteriori dietary patterns were identified through a principal component factor analysis carried out on 24 nutrients derived from study-specific food-frequency questionnaires. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using unconditional logistic regression models on quintiles of factor scores. Results We identified three major dietary patterns named 'animal products and cereals', 'antioxidant vitamins and fiber', and 'fats'. The 'antioxidant vitamins and fiber' pattern was inversely related to oral and pharyngeal cancer (OR = 0.57, 95% CI 0.43-0.76 for the highest versus the lowest score quintile). The 'animal products and cereals' pattern was positively associated with laryngeal cancer (OR = 1.54, 95% CI 1.12-2.11), whereas the 'fats' pattern was inversely associated with oral and pharyngeal cancer (OR = 0.78, 95% CI 0.63-0.97) and positively associated with laryngeal cancer (OR = 1.69, 95% CI 1.22-2.34). Conclusions These findings suggest that diets rich in animal products, cereals, and fats are positively related to laryngeal cancer, and those rich in fruit and vegetables inversely related to oral and pharyngeal cancer.

Cytoskeletal and DNA structure abnormalities result from bypass of requirement for the cdc10 start gene in the fission yeast Schizosaccharomyces pombe.

The cdc10 gene of the fission yeast S. pombe is required for traverse of the start control in late G1 and commitment to the mitotic cell cycle. To increase our understanding of the events which occur at start, a pseudoreversion analysis was undertaken to identify genes whose products may interact with cdc10 or bypass the requirement for it. A single gene, sct1+ (suppressor of cdc ten), has been identified, mutation of which suppresses all conditional alleles and a null allele of cdc10. Bypass of the requirement for cdc10+ function by sct1-1 mutations leads to pleiotropic defects, including microtubule, microfilament and nuclear structural abnormalities. Our data suggest that sct1 encodes a protein that is dependent upon cdc10+ either for its normal function or expression, or is a component of a checkpoint that monitors execution of p85cdc10 function.

Forma Tarraconis: GIS aplicado a la arqueología urbana

Desde aquel incipiente interés renacentista del siglo XVI hasta la profesionalización de la arqueología en la actualidad, la ingente actividad realizada en Tarragona ha necesitado de formas de registrarla y organizarla, a fin de ser estudiada en el contexto diacrónico general de la ciudad. Esta tarea se ha visto favorecida en el último decenio del siglo pasado por la aparición y adopción de una herramienta informática que no fue diseñada específicamente para la Arqueología. El GIS o SIG, se ha convertido en un instrumento básico e indispensable para cualquier ciudad que tenga un mínimo bagaje patrimonial. Prueba de ello son las publicaciones de Cartas Arqueológicas obtenidas a partir de este software, o sin ir mucho más lejos, los trabajos presentados en este simposio. Presentamos a continuación la experiencia de Tarragona en la creación de un programa, bajo soporte GIS, para la gestión de la actividad arqueológica. Previamente contextualizaremos esta experiencia ya que es justa heredera de iniciativas individuales y de equipos y proyectos previos que trataron, con mucha menor suerte que no éxito, de organizar y poner orden en la maltrecha documentación arqueológica de nuestra ciudad. Describiremos posteriormente las funcionalidades básicas de este programa, su arquitectura y las aplicaciones realizadas en el desarrollo de sendos proyectos de estudio de la ciudad. En este último caso nos centraremos, principalmente, en el proyecto Planimetria Arqueològica de Tàrraco, impulsado por el Museu d’Història del Ayuntamiento de Tarragona y el Institut Català d’Arqueologia Clàssica, y que ha contado con la colaboración de la Generalitat de Catalunya para su edición. Seguidamente veremos como el uso de la información en capas registrada en el GIS combinada con la inclusión de la cartografía histórica de una ciudad permiten el análisis de problemas arqueológicos irresolubles sólo con los datos estrictamente arqueológicos. En este caso se aplicará sobre la validación de la morfología urbana de Tarraco propuesta por Macias (2000a). Por último se hará una reflexión sobre cuales podrían ser las mejoras aplicables sobre el programa, en previsión de futuras revisiones del mismo.

Use of anisotropic modelling in electrical impedance tomography: description of method and preliminary assessment of utility in imaging brain function in the adult human head.

Electrical Impedance Tomography (EIT) is an imaging method which enables a volume conductivity map of a subject to be produced from multiple impedance measurements. It has the potential to become a portable non-invasive imaging technique of particular use in imaging brain function. Accurate numerical forward models may be used to improve image reconstruction but, until now, have employed an assumption of isotropic tissue conductivity. This may be expected to introduce inaccuracy, as body tissues, especially those such as white matter and the skull in head imaging, are highly anisotropic. The purpose of this study was, for the first time, to develop a method for incorporating anisotropy in a forward numerical model for EIT of the head and assess the resulting improvement in image quality in the case of linear reconstruction of one example of the human head. A realistic Finite Element Model (FEM) of an adult human head with segments for the scalp, skull, CSF, and brain was produced from a structural MRI. Anisotropy of the brain was estimated from a diffusion tensor-MRI of the same subject and anisotropy of the skull was approximated from the structural information. A method for incorporation of anisotropy in the forward model and its use in image reconstruction was produced. The improvement in reconstructed image quality was assessed in computer simulation by producing forward data, and then linear reconstruction using a sensitivity matrix approach. The mean boundary data difference between anisotropic and isotropic forward models for a reference conductivity was 50%. Use of the correct anisotropic FEM in image reconstruction, as opposed to an isotropic one, corrected an error of 24 mm in imaging a 10% conductivity decrease located in the hippocampus, improved localisation for conductivity changes deep in the brain and due to epilepsy by 4-17 mm, and, overall, led to a substantial improvement on image quality. This suggests that incorporation of anisotropy in numerical models used for image reconstruction is likely to improve EIT image quality.

Tolerance to preharvest sprouting and yield of wheat genotypes from different breeding programs

Abstract:The objective of this work was to characterize the performance of elite wheat genotypes from different Brazilian breeding programs for traits associated with grain yield and preharvest sprouting. The study was conducted in 2010 and 2011 in the municipality of Capão do Leão, in the state of Rio Grande do Sul, Brazil, in a randomized complete block design with three replicates. Thirty-three wheat genotypes were evaluated for traits related to preharvest sprouting and grain yield. The estimate of genetic distance was used to predict potential combinations for selection of plants with high grain yield and tolerance to preharvest sprouting. The combined analysis of sprouted grains and falling number shows that the TBIO Alvorada, TBIO Mestre, Frontana, Fundacep Raízes, Fundacep Cristalino, and BRS Guamirim genotypes are tolerant to preharvest sprouting. Combinations of TBIO Alvorada and TBIO Mestre with Fundacep Cristalino show high potential for recovering superior genotypes for high grain yield and tolerance to preharvest sprouting.

Cigarette, cigar, and pipe smoking and the risk of head and neck cancers: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium.

Cigar and pipe smoking are considered risk factors for head and neck cancers, but the magnitude of effect estimates for these products has been imprecisely estimated. By using pooled data from the International Head and Neck Cancer Epidemiology (INHANCE) Consortium (comprising 13,935 cases and 18,691 controls in 19 studies from 1981 to 2007), we applied hierarchical logistic regression to more precisely estimate odds ratios and 95% confidence intervals for cigarette, cigar, and pipe smoking separately, compared with reference groups of those who had never smoked each single product. Odds ratios for cigar and pipe smoking were stratified by ever cigarette smoking. We also considered effect estimates of smoking a single product exclusively versus never having smoked any product (reference group). Among never cigarette smokers, the odds ratio for ever cigar smoking was 2.54 (95% confidence interval (CI): 1.93, 3.34), and the odds ratio for ever pipe smoking was 2.08 (95% CI: 1.55, 2.81). These odds ratios increased with increasing frequency and duration of smoking (Ptrend ≤ 0.0001). Odds ratios for cigar and pipe smoking were not elevated among ever cigarette smokers. Head and neck cancer risk was elevated for those who reported exclusive cigar smoking (odds ratio = 3.49, 95% CI: 2.58, 4.73) or exclusive pipe smoking (odds ratio = 3.71, 95% CI: 2.59, 5.33). These results suggest that cigar and pipe smoking are independently associated with increased risk of head and neck cancers.

Software SMEs asStrategic Partners in the Partner Programs of Large International Companies

Tutkielman tavoitteena oli tutkia pienten- ja keskisuurten (PK) ohjelmistoyritysten kansainvälisiä kumppanuuksia. Päätavoitteena oli löytää keinoja kuinka PK-ohjelmistoyritykset voisivat tulla strategisiksi kumppaneksi suurten kansainvälisten yritysten kumppanuusohjelmissa. Lisäksi tutkielmassa oli tavoitteena selvittää kuinka kumppaneiden välistä sitoutumista voitaisiin vahvistaa, jotta PK-ohjelmistoyritykset voisivat saavuttaa todellista lisäarvoa ja kansainvälistä kasvua kumppanuusohjelmien kautta. Tutkielma jakaantuu teoreettiseen ja empiiriseen osaan. Teoreettinen osa keskittyy tarkastelemaan korkean teknologian markkinointia ohjelmistoalalla sekä kansainvälisiä kumppanuuksia. Suurten yritystenkumppanuusohjelmia ei ole tutkittu suomalaisten PK-ohjelmistoyritysten näkökulmasta, minkä vuoksi empiirinen tutkimus on perusteltua. Empiirinen tutkimus toteutettiin laadullisena case-tutkimuksena ja tutkimusmenetelmänä käytettiin puolistrukturoitua haastattelua. Tutkimustulokset osoittavat, että strategisen kumppanin aseman saavuttaminen on pitkä ja haastava matka PK-yrityksille. Suurten kansainvälisten yritysten kumppanuusohjelmat ovat useimmiten monimutkaisia ja todellisen lisäarvon saavuttaminen kumppanuusohjelman kautta vaatii paljon resursseja PK-yrityksiltä. Jotta PK-yritykset voisivat saavuttaa ja säilyttää strategisen kumppanin aseman kumppanuusohjelmassa, vaatii se aktiivista ja päivittäistä vuorovaikutusta kumppaneiden kesken. Erityisesti tiiviit henkilösuhteet oikeiden avainhenkilöiden kanssa ovat välttämättömyys. Läheiset kontaktit mahdollistavat sen, että PK-yritykset voivat ainakin osittain ohittaa kumppanuusohjelman byrokratian, mikä lisää luottamusta ja sitoutumista kumppanuussuhteessa sekä edistää kansainvälistä kasvua ja menestystä liiketoiminnassa.

Global transcriptional programs in peripheral nerve endoneurium and DRG are resistant to the onset of type 1 diabetic neuropathy in Ins2 mice.

While the morphological and electrophysiological changes underlying diabetic peripheral neuropathy (DPN) are relatively well described, the involved molecular mechanisms remain poorly understood. In this study, we investigated whether phenotypic changes associated with early DPN are correlated with transcriptional alterations in the neuronal (dorsal root ganglia [DRG]) or the glial (endoneurium) compartments of the peripheral nerve. We used Ins2(Akita/+) mice to study transcriptional changes underlying the onset of DPN in type 1 diabetes mellitus (DM). Weight, blood glucose and motor nerve conduction velocity (MNCV) were measured in Ins2(Akita/+) and control mice during the first three months of life in order to determine the onset of DPN. Based on this phenotypic characterization, we performed gene expression profiling using sciatic nerve endoneurium and DRG isolated from pre-symptomatic and early symptomatic Ins2(Akita/+) mice and sex-matched littermate controls. Our phenotypic analysis of Ins2(Akita/+) mice revealed that DPN, as measured by reduced MNCV, is detectable in affected animals already one week after the onset of hyperglycemia. Surprisingly, the onset of DPN was not associated with any major persistent changes in gene expression profiles in either sciatic nerve endoneurium or DRG. Our data thus demonstrated that the transcriptional programs in both endoneurial and neuronal compartments of the peripheral nerve are relatively resistant to the onset of hyperglycemia and hypoinsulinemia suggesting that either minor transcriptional alterations or changes on the proteomic level are responsible for the functional deficits associated with the onset of DPN in type 1 DM.

Action Research : the first steps to start up a pilot experiment in heritage education

Peer-reviewed

The Role and Measurement of Social Capital in New Technology-Based Start-up Context

Tämän Pro gradu-tutkielman tavoitteena olirakentaa esiymmärrys sosiaalisen pääoman roolista ja mittaamisesta uuden teknologian start-up yrityksissä. Pääasiallisena tarkoituksena tässä tutkimuksessa olilöytää sosiaalisen pääoman ja start-up yrityksen tuloksellisuuden välille yhdistävä tekijä. Tutkimuksen empiirinen aineisto kerättiin pääasiallisesti kuuden OKO Venture Capitalin sijoitusportfolioon sisältyvien case-yritysten kvalitatiivisten teemahaastatteluiden sekä kvantitatiivisten kyselylomakkeiden avulla. Kvalitatiivisten haastatteluiden tulosten perusteella sosiaalisen pääoman ja tuloksellisuuden välille löytyi yhdistävä tekijä, jota käytettiin myöhemmin hyväksi kvantitatiivisessa kyselylomakkeessa. Tämän tutkielman tulokset osoittivat, että startegisen päätöksenteon kautta sosiaalinen pääoma vaikuttaa osittain start-up yritysten tuloksellisuuteen. Manageriaalisesti tärkempi löydös tässä tutkimuksessa oli kuitenkin se, että sosiaalista pääomaa voidaan käyttää hyväksi ennustettaessa uuden teknologian start-up yritysten tulevaisuuden kassavirtoja.

A prospective, randomized, and controlled study of fluid management in children with severe head injury: lactated Ringer's solution versus hypertonic saline.

OBJECTIVES: Resuscitation in severe head injury may be detrimental when given with hypotonic fluids. We evaluated the effects of lactated Ringer's solution (sodium 131 mmol/L, 277 mOsm/L) compared with hypertonic saline (sodium 268 mmol/L, 598 mOsm/L) in severely head-injured children over the first 3 days after injury. DESIGN: An open, randomized, and prospective study. SETTING: A 16-bed pediatric intensive care unit (ICU) (level III) at a university children's hospital. PATIENTS: A total of 35 consecutive children with head injury. INTERVENTIONS: Thirty-two children with Glasgow Coma Scores of <8 were randomly assigned to receive either lactated Ringer's solution (group 1) or hypertonic saline (group 2). Routine care was standardized, and included the following: head positioning at 30 degrees; normothermia (96.8 degrees to 98.6 degrees F [36 degrees to 37 degrees C]); analgesia and sedation with morphine (10 to 30 microg/kg/hr), midazolam (0.2 to 0.3 mg/kg/hr), and phenobarbital; volume-controlled ventilation (PaCO2 of 26.3 to 30 torr [3.5 to 4 kPa]); and optimal oxygenation (PaO2 of 90 to 105 torr [12 to 14 kPa], oxygen saturation of >92%, and hematocrit of >0.30). MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure and intracranial pressure (ICP) were monitored continuously and documented hourly and at every intervention. The means of every 4-hr period were calculated and serum sodium concentrations were measured at the same time. An ICP of 15 mm Hg was treated with a predefined sequence of interventions, and complications were documented. There was no difference with respect to age, male/female ratio, or initial Glasgow Coma Score. In both groups, there was an inverse correlation between serum sodium concentration and ICP (group 1: r = -.13, r2 = .02, p < .03; group 2: r = -.29, r2 = .08, p < .001) that disappeared in group 1 and increased in group 2 (group 1: r = -.08, r2 = .01, NS; group 2: r = -.35, r2 =.12, p < .001). Correlation between serum sodium concentration and cerebral perfusion pressure (CPP) became significant in group 2 after 8 hrs of treatment (r = .2, r2 = .04, p = .002). Over time, ICP and CPP did not significantly differ between the groups. However, to keep ICP at <15 mm Hg, group 2 patients required significantly fewer interventions (p < .02). Group 1 patients received less sodium (8.0 +/- 4.5 vs. 11.5 +/- 5.0 mmol/kg/day, p = .05) and more fluid on day 1 (2850 +/- 1480 vs. 2180 +/- 770 mL/m2, p = .05). They also had a higher frequency of acute respiratory distress syndrome (four vs. 0 patients, p = .1) and more than two complications (six vs. 1 patient, p = .09). Group 2 patients had significantly shorter ICU stay times (11.6 +/- 6.1 vs. 8.0 +/- 2.4 days; p = .04) and shorter mechanical ventilation times (9.5 +/- 6.0 vs. 6.9 +/- 2.2 days; p = .1). The survival rate and duration of hospital stay were similar in both groups. CONCLUSIONS: Treatment of severe head injury with hypertonic saline is superior to that treatment with lactated Ringer's solution. An increase in serum sodium concentrations significantly correlates with lower ICP and higher CPP. Children treated with hypertonic saline require fewer interventions, have fewer complications, and stay a shorter time in the ICU.