The cytoplasmic filaments of the nuclear pore complex are dispensable for selective nuclear protein import

The nuclear pore complex (NPC) mediates bidirectional macromolecular traffic between the nucleus and cytoplasm in eukaryotic cells. Eight filaments project from the NPC into the cytoplasm and are proposed to function in nuclear import. We investigated the localization and function of two nucleoporins on the cytoplasmic face of the NPC, CAN/Nup214 and RanBP2/Nup358. Consistent with previous data, RanBP2 was localized at the cytoplasmic filaments. In contrast, CAN was localized near the cytoplasmic coaxial ring. Unexpectedly, extensive blocking of RanBP2 with gold-conjugated antibodies failed to inhibit nuclear import. Therefore, RanBP2-deficient NPCs were generated by in vitro nuclear assembly in RanBP2-depleted Xenopus egg extracts. NPCs were formed that lacked cytoplasmic filaments, but that retained CAN. These nuclei efficiently imported nuclear localization sequence (NLS) or M9 substrates. NPCs lacking CAN retained RanBP2 and cytoplasmic filaments, and showed a minor NLS import defect. NPCs deficient in both CAN and RanBP2 displayed no cytoplasmic filaments and had a strikingly immature cytoplasmic appearance. However, they showed only a slight reduction in NLS-mediated import, no change in M9-mediated import, and were normal in growth and DNA replication. We conclude that RanBP2 is the major nucleoporin component of the cytoplasmic filaments of the NPC, and that these filaments do not have an essential role in importin /ß– or transportin-dependent import

Resting electrocardiographic and echocardiographic findings in an urban community in the Gambia

The presence of Left Ventricular Hypertrophy (LVH) in a patient with systemic hypertension deserves serious attention and makes its clinical diagnosis a priority. Over the years various criteriahave been proposed for the electrographic (ECG) diagnosis of LVH and the sensitivity and specificity of these criteria have been extensively studied in Caucasians. Recent evidence indicates that they areinapplicable to people of African descent. Unlike echocardiography (ECHO), the ECG is generally available, cheap but has a lower sensitivity in detecting LVH compared to echocardiography. Thisstudy was conducted to evaluate ECG criteria against 2-dimensional (2-D) guided M-mode echocardiography in the diagnosis of LVH in adult Gambians. Secondly, to determine the ECG criteria usingthe Minnesota, Araoye, Sokolow and Lyon or Wolff criteria with the overall best accuracy for the diagnosis of LVH. Two hundred and eight (208) consecutive patients with systemic hypertension (BP.140/90mmHg) with or without treatment and an age matched group of 108 non-hypertensive patients were enrolled from outpatient clinics. A questionnaire was filled. All patients were investigated with 2-D guided M-mode echocardiography and a standard 12-1ead ECG. Anthropometric measurements were also taken. The gold standard was the Penn formula to determine the left ventricular mass index (of 125 g/m2 in males and 110 g/m2 in females as the cut-off for LVH). Using this gold standard the prevalence of echocardiographic LVH was 47.5% and 27.8 % in the hypertensives and non-hypertensives respectively (P 0.05). Sokolow and Lyon criterion had overall best accuracy for the electrocardiographic diagnosis of left ventricular hypertrophyin hypertensives and is further recommended for use as such. But for non-hypertensives, the Wolff criterion had overall best accuracy

Characterising loss and damage from climate change

Policy-makers are creating mechanisms to help developing countries cope with loss and damage from climate change, but the negotiations are largely neglecting scientific questions about what the impacts of climate change actually are. Mitigation efforts have failed to prevent the continued increase of anthropogenic greenhouse gas (GHG) emissions. Adaptation is now unlikely to be sufficient to prevent negative impacts from current and future climate change1. In this context, vulnerable nations argue that existing frameworks to promote mitigation and adaptation are inadequate, and have called for a third international mechanism to deal with residual climate change impacts, or “loss and damage”2. In 2013, the United Nations Framework Convention on Climate Change (UNFCCC) responded to these calls and established the Warsaw International Mechanism (WIM) to address loss and damage from the impacts of climate change in developing countries3. An interim Executive Committee of party representatives has been set up, and is currently drafting a two-year workplan comprising meetings, reports, and expert groups; and aiming to enhance knowledge and understanding of loss and damage, strengthen dialogue among stakeholders, and promote enhanced action and support. Issues identified as priorities for the WIM thus far include: how to deal with non-economic losses, such as loss of life, livelihood, and cultural heritage; and linkages between loss and damage and patterns of migration and displacement2. In all this, one fundamental issue still demands our attention: which losses and damages are relevant to the WIM? What counts as loss and damage from climate change

Mapping the shoreface of coastal sediment compartments to improve shoreline change forecasts in New South Wales, Australia

The potential response of shoreface depositional environments to sea level rise over the present century and beyond remains poorly understood. The shoreface is shaped by wave action across a sedimentary seabed and may aggrade or deflate depending on the balance between time-averaged wave energy and the availability and character of sediment, within the context of the inherited geological control. For embayed and accommodation-dominated coastal settings, where shoreline change is particularly sensitive to cross-shore sediment transport, whether the shoreface is a source or sink for coastal sediment during rising sea level may be a crucial determinant of future shoreline change. While simple equilibrium-based models (e.g. the Bruun Rule) are widely used in coastal risk planning practice to predict shoreline change due to sea level rise, the relevance of fundamental model assumptions to the shoreface depositional setting is often overlooked due to limited knowledge about the geomorphology of the nearshore seabed. We present high-resolution mapping of the shoreface-inner shelf in southeastern Australia from airborne lidar and vessel-based multibeam echosounder surveys, which reveals a more complex seabed than was previously known. The mapping data are used to interpret the extent, depositional character and morphodynamic state of the shoreface, by comparing the observed geomorphology to theoretical predictions from wave-driven sediment transport theory. The benefits of high-resolution seabed mapping for improving shoreline change predictions in practice are explored by comparing idealised shoreline change modelling based on our understanding of shoreface geomorphology and morphodynamics before and after the mapping exercise

Specific cortical and subcortical grey matter regions are associated with insomnia severity

BACKGROUND: There is an increasing awareness that sleep disturbances are a risk factor for dementia. Prior case-control studies suggested that brain grey matter (GM) changes involving cortical (i.e, prefrontal areas) and subcortical structures (i.e, putamen, thalamus) could be associated with insomnia status. However, it remains unclear whether there is a gradient association between these regions and the severity of insomnia in older adults who could be at risk for dementia. Since depressive symptoms and sleep apnea can both feature insomnia-related factors, can impact brain health and are frequently present in older populations, it is important to include them when studying insomnia. Therefore, our goal was to investigate GM changes associated with insomnia severity in a cohort of healthy older adults, taking into account the potential effect of depression and sleep apnea as well. We hypothesized that insomnia severity is correlated with 1) cortical regions responsible for regulation of sleep and emotion, such as the orbitofrontal cortex and, 2) subcortical regions, such as the putamen. METHODS: 120 healthy subjects (age 74.8±5.7 years old, 55.7% female) were recruited from the Hillblom Healthy Aging Network at the Memory and Aging Center, UCSF. All participants were determined to be cognitively healthy following a neurological evaluation, neuropsychological assessment and informant interview. Participants had a 3T brain MRI and completed the Insomnia Severity Index (ISI), Geriatric Depression Scale (GDS) and Berlin Sleep Questionnaire (BA) to assess sleep apnea. Cortical thickness (CTh) and subcortical volumes were obtained by the CAT12 toolbox within SPM12. We studied the correlation of CTh and subcortical volumes with ISI using multiple regressions adjusted by age, sex, handedness and MRI scan type. Additional models adjusting by GDS and BA were also performed. RESULTS: ISI and GDS were predominantly mild (4.9±4.2 and 2.5±2.9, respectively) and BA was mostly low risk (80%). Higher ISI correlated with lower CTh of the right orbitofrontal, right superior and caudal middle frontal areas, right temporo-parietal junction and left anterior cingulate cortex (p<0.001, uncorrected FWE). When adjusting by GDS, right ventral orbitofrontal and temporo-parietal junction remained significant, and left insula became significant (p<0.001, uncorrected FWE). Conversely, BA showed no effect. The results were no longer significant following FWE multiple comparisons. Regarding subcortical areas, higher putamen volumes were associated with higher ISI (p<0.01). CONCLUSIONS: Our findings highlight a relationship between insomnia severity and brain health, even with relatively mild insomnia, and independent of depression and likelihood of sleep apnea. The results extend the previous literature showing the association of specific GM areas (i.e, orbitofrontal, insular and temporo-parietal junction) not just with the presence of insomnia, but across the spectrum of severity itself. Moreover, our results suggest subcortical structures (i.e., putamen) are involved as well. Longitudinal studies are needed to clarify how these insomnia-related brain changes in healthy subjects align with an increased risk of dementia

Pulmonary contusion in a collegiate diver: a case report

Abstract Introduction Pulmonary contusions typically occur after high-energy trauma and have rarely been reported as occurring during participation in sports. This is the first reported case of a pulmonary contusion occurring in a sport other than football. Case Presentation A 19-year-old Caucasian man impacted the water awkwardly after diving off a one-meter springboard. He complained of chest discomfort and produced immediate hemoptysis. Computed tomography confirmed the diagnosis of pulmonary contusion. The athlete recovered without complications and returned to activity one week after injury. Conclusion Immediate hemoptysis following blunt chest trauma during sports activity may indicate an underlying pulmonary contusion. No specific guidelines exist for return to athletic competition following pulmonary contusion, but a progressive return to activities once symptoms resolve appears to be a reasonable approach.</p

The Surgical Infection Society revised guidelines on the management of intra-abdominal infection

Background: Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the time the most recent guideline was released, the plan was to update the guideline every five years to ensure the timeliness and appropriateness of the recommendations. Methods: Based on the previous guidelines, the task force outlined a number of topics related to the treatment of patients with IAI and then developed key questions on these various topics. All questions were approached using general and specific literature searches, focusing on articles and other information published since 2008. These publications and additional materials published before 2008 were reviewed by the task force as a whole or by individual subgroups as to relevance to individual questions. Recommendations were developed by a process of iterative consensus, with all task force members voting to accept or reject each recommendation. Grading was based on the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) system; the quality of the evidence was graded as high, moderate, or weak, and the strength of the recommendation was graded as strong or weak. Review of the document was performed by members of the SIS who were not on the task force. After responses were made to all critiques, the document was approved as an official guideline of the SIS by the Executive Council. Results: This guideline summarizes the current recommendations developed by the task force on the treatment of patients who have IAI. Evidence-based recommendations have been made regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy. Additional recommendations related to the treatment of pediatric patients with IAI have been included. Summary: The current recommendations of the SIS regarding the treatment of patients with IAI are provided in this guideline