Biological evidence supports an early and complex emergence of the Isthmus of Panama.

The linking of North and South America by the Isthmus of Panama had major impacts on global climate, oceanic and atmospheric currents, and biodiversity, yet the timing of this critical event remains contentious. The Isthmus is traditionally understood to have fully closed by ca. 3.5 million years ago (Ma), and this date has been used as a benchmark for oceanographic, climatic, and evolutionary research, but recent evidence suggests a more complex geological formation. Here, we analyze both molecular and fossil data to evaluate the tempo of biotic exchange across the Americas in light of geological evidence. We demonstrate significant waves of dispersal of terrestrial organisms at approximately ca. 20 and 6 Ma and corresponding events separating marine organisms in the Atlantic and Pacific oceans at ca. 23 and 7 Ma. The direction of dispersal and their rates were symmetrical until the last ca. 6 Ma, when northern migration of South American lineages increased significantly. Variability among taxa in their timing of dispersal or vicariance across the Isthmus is not explained by the ecological factors tested in these analyses, including biome type, dispersal ability, and elevation preference. Migration was therefore not generally regulated by intrinsic traits but more likely reflects the presence of emergent terrain several millions of years earlier than commonly assumed. These results indicate that the dramatic biotic turnover associated with the Great American Biotic Interchange was a long and complex process that began as early as the Oligocene-Miocene transition.

Cerebral Hypoperfusion in Posterior Reversible Encephalopathy Syndrome is Different from Transient Ischemic Attack on CT Perfusion.

BACKGROUND: PRES is a reversible neurotoxic state presenting with headache, altered mental status, visual loss, and seizures. Delayed diagnosis can be avoided if radiological patterns could distinguish PRES from cerebral ischemia. METHODS: Clinical and radiological data were collected on all hospitalized patients who had (1) discharge diagnosis of PRES and (2) acute CTP/CTA. Data were compared with 10 TIA patients with proven cytotoxic edema on MRI. RESULTS: Of the four PRES patients found, three were correlated with acute blood pressure and one with chemotherapy. At the radiological level, quantitative analyses of the CTP parameters showed that 2 out of 4 patients had bilaterally reduced CBF-values (23.2-47.1 ml/100g/min) in occipital regions, as seen in the pathological regions of TIA patients (27.3 ± 13.5 ml/100g/min). When compared with TIA patients, the pathological ROI's demonstrated decreased CBV-values (3.4-5.6 ml/100g). Vasogenic edema on MRI FLAIR imaging was seen in only one PRES patient, and cytotoxic edema on DWI-imaging was never found. CT angiography showed in one PRES patient a vasospasm-like unilateral posterior cerebral artery. CONCLUSIONS: If confirmed by other groups, CTP and CTA imaging in patients with acute visual loss and confusion may help to distinguish PRES from bi-occipital ischemia. These radiological parameters may identify PRES patients at risk for additional tissue infarction.

Multiple supernumerary teeth not associated with complex syndromes: a retrospective study

Objectives: To determine the epidemiology and describe the clinical and radiographic characteristics, the type of treatment, and the possible delayed appearance of new supernumerary teeth in patients with non-syndromic multiple hyperdontia. Patients and Methods: We conducted a small retrospective observational study of 8 patients diagnosed with nonsyndromic multiple hyperdontia. Multiple hyperdontia not associated to complex syndromes was defined as apparently generally healthy patients with one or more supernumerary teeth in two or more areas. Results: The average patient age was 16.23 years; males predominated (3:1). Multiple hyperodontia with a minimum of 2 and a maximum of 9 supernumerary teeth was found (total: 34 mean: 4.25). The most frequent location was the upper jaw (76.47%). Eumorphic teeth were seen at lower premolar level, while the rest were all heteromorphic. There was altered eruption of the contiguous teeth of 4 of the impacted supernumerary teeth all the rest being asymptomatic. Extraction was the treatment in all patients, and in one of them the delayed appearance of 4 supernumerary teeth was detected. Conclusions: Multiple hyperodontia rarely occurs without being associated with complex syndromes. Prophylactic surgical removal of the supernumerary teeth is generally the treatment of choice.

Complex regulation of CREB-binding protein by homeodomain-interacting protein kinase 2.

CREB-binding protein (CBP) and p300 are transcriptional coactivators involved in numerous biological processes that affect cell growth, transformation, differentiation, and development. In this study, we provide evidence of the involvement of homeodomain-interacting protein kinase 2 (HIPK2) in the regulation of CBP activity. We show that HIPK2 interacts with and phosphorylates several regions of CBP. We demonstrate that serines 2361, 2363, 2371, 2376, and 2381 are responsible for the HIPK2-induced mobility shift of CBP C-terminal activation domain. Moreover, we show that HIPK2 strongly potentiates the transcriptional activity of CBP. However, our data suggest that HIPK2 activates CBP mainly by counteracting the repressive action of cell cycle regulatory domain 1 (CRD1), located between amino acids 977 and 1076, independently of CBP phosphorylation. Our findings thus highlight a complex regulation of CBP activity by HIPK2, which might be relevant for the control of specific sets of target genes involved in cellular proliferation, differentiation and apoptosis.

The Strategic Intent and Launching of a Knowledge Management Tool in a Complex Organisation, case Stora Enso Consumer Boards

Informaatiotulva ja organisaation monimutkaisuus luoneet tarpeen tietämyksen hallinnalle. Tämän tutkimuksen tavoitteena on tunnistaa muutostarpeet, jotka portaalin käyttöönotto tietämyksenhallintatyökaluna luo. Tutkimuksessa verrataan myös uusia työkaluja olemassa oleviin sekä arvioidaan organisaation kykyä siirtää tietämystä virtuaalisesti. Kirjallisuutta vastaavanlaisista projekteista ei ole ollut saatavilla, sillä käyttöönotettava teknologia on melko uutta. Samaa teknologiaa on käytössä hieman eri alueella, kuin tässä projektissa on tavoitteena. Tutkimus on tapaustutkimus, jonka pääasialliset lähteet ovat erilaisissa kokouksissa tuotettuja dokumentteja. Tutkija on osallistunut aktiivisesti projektityöhön, joten osa taustatiedoista perustuu tutkijan huomioihin sekä vielä keskusteluihin. Teoriaosassa käsitellään tietämyksen jakamista tietämyksen hallinnan ja virtuaalisuuden näkökulmasta. Muutoksen hallintaa on käsitelty lyhyesti tietämyksenhallintatyökalun käyttöönotossa. Tutkimus liittyy Stora Enso Consumer Boardsin tietämyksen hallintaprojektiin.

Controlling complexity: the clinical relevance of mouse complex genetics.

Experimental animal models are essential to obtain basic knowledge of the underlying biological mechanisms in human diseases. Here, we review major contributions to biomedical research and discoveries that were obtained in the mouse model by using forward genetics approaches and that provided key insights into the biology of human diseases and paved the way for the development of novel therapeutic approaches.

Added value of acute multimodal CT-based imaging (MCTI) : a comprehensive analysis

Introduction: MCTI is used to assess acute ischemic stroke (AIS) patients.We postulated that use of MCTI improves patient outcome regardingindependence and mortality.Methods: From the ASTRAL registry, all patients with an AIS and a non-contrast-CT (NCCT), angio-CT (CTA) or perfusion-CT (CTP) within24 h from onset were included. Demographic, clinical, biological, radio-logical, and follow-up caracteristics were collected. Significant predictorsof MCTI use were fitted in a multivariate analysis. Patients undergoingCTA or CTA&CTP were compared with NCCT patients with regards tofavourable outcome (mRS ≤ 2) at 3 months, 12 months mortality, strokemechanism, short-term renal function, use of ancillary diagnostic tests,duration of hospitalization and 12 months stroke recurrence.

Pathomorphological and CT-angiographical characteristics of coronary atherosclerotic plaques in cases of sudden cardiac death.

The goal of this study was to assess the localization and types of thrombosed plaques in cases of sudden cardiac death attributed to coronary artery disease and to evaluate possible correlations with body mass index (BMI) and increased heart weight. This retrospective study was performed on forensic cases for which the cause of death was attributed to coronary artery disease. A complete autopsy and a multi-phase postmortem computed tomography (CT) angiography (MPMCTA) were performed in all cases. Eighty-five cases were selected (mean age, 55.18 ± 11.04 years; 72 men and 13 women). MPMCTA performed prior to autopsy enabled an evaluation of coronary artery perfusion before dissection of the body and helped therefore to guide sampling for histology. An acute coronary thrombosis was found in 57 cases, which included plaque erosion in 26 cases (mean age, 46.73 ± 8.33 years) and rupture or intra-plaque hemorrhage in 31 cases (mean age, 58.23 ± 10.62 years). Erosions were most frequently found in the left anterior descending artery (61.5 %), while only 35.48 % of ruptures were observed in this artery. Chronic coronary pathology was considered as the main cause of death in 28 cases (mean age, 59.64 ± 9.47 years). Sixty-two of the cases (72.94 %) had a BMI in the overweight category (BMI ≥25), with the highest mean BMI in patients with chronic coronary pathology without acute thrombosis found at autopsy. The heart weight was above the predicted reference values in 52 cases (61.18 %). Our results are in accordance with previously published studies on the spatial distribution of vulnerable plaques. We observed a higher percentage of eroded plaques than previously reported. Patients with coronary erosions were significantly younger than those with plaque rupture or those without an acute coronary thrombosis (p values <0.0001). BMI and heart weight were significantly higher for cases without thrombosis in comparison with those with plaque rupture (p values 0.028 and 0.003, respectively). Our results indicating that increased BMI and overweight hearts are associated with chronic ischemic heart disease are compatible with clinical studies. Performing more postmortem studies on forensic autopsies, including modern radiological examinations with MPMCTA, can enhance the detection of vulnerable plaques in living patients and prevent sudden cardiac death.

Meeting report of the European mouse complex genetics network SYSGENET.

The second scientific meeting of the European systems genetics network for the study of complex genetic human disease using genetic reference populations (SYSGENET) took place at the Center for Cooperative Research in Biosciences in Bilbao, Spain, December 10-12, 2012. SYSGENET is funded by the European Cooperation in the Field of Scientific and Technological Research (COST) and represents a network of scientists in Europe that use mouse genetic reference populations (GRPs) to identify complex genetic factors influencing disease phenotypes (Schughart, Mamm Genome 21:331-336, 2010). About 50 researchers working in the field of systems genetics attended the meeting, which consisted of 27 oral presentations, a poster session, and a management committee meeting. Participants exchanged results, set up future collaborations, and shared phenotyping and data analysis methodologies. This meeting was particularly instrumental for conveying the current status of the US, Israeli, and Australian Collaborative Cross (CC) mouse GRP. The CC is an open source project initiated nearly a decade ago by members of the Complex Trait Consortium to aid the mapping of multigenetic traits (Threadgill, Mamm Genome 13:175-178, 2002). In addition, representatives of the International Mouse Phenotyping Consortium were invited to exchange ongoing activities between the knockout and complex genetics communities and to discuss and explore potential fields for future interactions.

Systematics and phylogeography of the Dysdera erythrina species complex (Araneae, Dysderidae) in Sardinia

Sardinia is the second largest island in the Mediterranean and, together with Corsica and nearby mainland areas, one of the top biodiversity hotspots in the region. The origin of Sardinia traces back to the opening of the western Mediterranean in the late Oligocene. This geological event and the subsequent Messinian Salinity Crisis and Pleistocene glacial cycles have had a major impact on local biodiversity. The Dysdera woodlouse hunter spiders are one of the most diverse ground-dweller groups in the Mediterranean. Here we describe the first two species of this genus endemic to Sardinia: Dysdera jana sp. n. and Dysdera shardana sp. n. The two species show contrasting allopatric distribution: D. jana sp. n. is a narrow endemic while D. shardana sp. n. is distributed throughout most of the island. A multi-gene DNA sequence phylogenetic analys based on mitochondrial and nuclear genes supports the close relationships of the new species to the type species of the genus Dysdera erythrina. Age estimates reject Oligocene origin of the new Dysdera species and identify the Messinian Salinity Crises as the most plausible period for the split between Sardinian endemics and their closest relatives. Phylogeographic analysis reveals deep genetic divergences and population structure in Dysdera shardana sp. n., suggesting that restriction to gene flow probably due to environmental factors could explain local speciation events. Taxonomy, phylogeny, DNA sequencing, Mediterranean biogeography, phylogeography