Environmental controls on the interannual variability in chlorophyll and phytoplankton community structure within the seasonal sub surface chlorophyll maximum in the western English channel

The subsurface chlorophyll maximum (SCM) is increasingly recognised as an important but understudied locus of primary production particularly in shelf seas. Here we report the results of a 4 year, repeat station, summer sampling programme (2013–2016) of a seasonally recurrent SCM in the Western English Channel. Interannual variability in phytoplankton community structure and chlorophyll distribution and intensity was strongly related to water column stability at the depth interval of the SCM and also to water temperature. The phytoplankton community was statistically distinct in each year. High stability, as evidenced by large Richardson numbers and a well-developed strong thermocline appeared to favour the growth of larger dinoflagellates (autotrophs or mixotrophs) and diatoms. Such conditions led to development of the most intense SCMs and these were sometimes dominated by a single or a few key species most prominently in 2015 with near monospecific concentrations of the dinoflagellate Tripos fusus with average peak SCM chlorophyll concentrations of 7.3 ± 4.4 μg l−1. By contrast, in years with low water column stability and intermittent turbulence at the thermocline (2014, 2016) there was greater chlorophyll dispersal and less intense SCM. In these low stability conditions, red fluorescent nano-phytoplankton, such as naked dinoflagellates, chlorophytes and prymnesiophytes, made a greater contribution to the community, possibly as a result of the advantages that motility and enhanced light utilisation efficiency confer within an SCM exposed to turbulence. It is also likely that turbulence disrupted the stability required by the larger dinoflagellates and diatoms. Several of the key SCM taxa were absent from surface waters including the dinoflagellates Tripos fusus, Tripos lineatus, and most of the Rhizosolenia/Proboscia diatoms, consistent with adaptations more suited to survival at depth in stratified waters. These traits include luxury nutrient uptake and storage and survival in low light (both groups) and mixotrophy (dinoflagellates). On the other hand, in 2013, diatoms including Pseudo-nitzschia spp. were abundant in both surface, SCM and bottom waters. The relatively cooler waters (11.6–12.1 °C on average in 2013 and 2016) were characterised by smaller diatoms (Chaetoceros spp. and Pseudo-nitzschia spp.) whereas the warmer waters (13.1 °C on average in 2014) contained larger diatoms (large Rhizosolenia spp., Lauderia annulata and Leptocylindrus danicus). There did not appear to be continuity of key species between years, other than for the dinoflagellate Tripos lineatus, which was significant in both 2013 and 2014 and present in 2015. In any given year, there was no correspondence between the key spring bloom phytoplankton species as monitored in the nearby Western Channel Observatory L4 station and the key SCM taxa

Management of ruptured brain arteriovenous malformations

Item does not contain fulltextIntracranial arteriovenous malformations (AVMs) are a common cause of stroke in younger patients, and often present as intracerebral hemorrhages (ICH), associated with 10 % to 30 % mortality. Patients who present with a hemorrhage from an AVM should be initially stabilized according to acute management guidelines for ICH. The characteristics of a lesion including its size, location in eloquent tissue, and high-risk features will influence risk of rupture, prognosis, as well as help guide management decisions. Given that rupture is associated with an increased risk of 6 % re-rupture in the year following the initial hemorrhage, versus 1 % to 3 % predicted annual risk in non-ruptured lesions only, definitive treatment is encouraged after ICH stabilization. A rest period of 2 to 6 weeks after hemorrhage is recommended before definitive treatment to avoid disrupting friable parenchyma and the hematoma. Treatment may consist of endovascular embolization, surgical resection, radiosurgery, or a combination of these three interventions based on the lesion

Apaf-1 is a transcriptional target for E2F and p53

Loss of function of the retinoblastoma protein, pRB, leads to lack of differentiation, hyperproliferation and apoptosis. Inactivation of pRB results in deregulated E2F activity, which in turn induces entry to S-phase and apoptosis. Induction of apoptosis by either the loss of pRB or the deregulation of E2F activity occurs via both p53-dependent and p53-independent mechanisms. The mechanism by which E2F induces apoptosis is still unclear. Here we show that E2F1 directly regulates the expression of Apaf-1, the gene for apoptosis protease-activating factor 1. These results provide a direct link between the deregulation of the pRB pathway and apoptosis. Furthermore, because the pRB pathway is functionally inactivated in most cancers, the identification of Apaf-1 as a transcriptional target for E2F might explain the increased sensitivity of tumour cells to chemotherapy. We also show that, independently of the pRB pathway, Apaf-1 is a direct transcriptional target of p53, suggesting that p53 might sensitize cells to apoptosis by increasing Apaf-1 levels

Linking indirect effects of cytomegalovirus to modulation of monocyte innate immune function

Cytomegalovirus (CMV) is an important cause of morbidity and mortality in the immunocompromised host. In transplant recipients, a variety of clinically important "indirect effects" are attributed to immune modulation by CMV, including increased mortality from fungal disease, allograft dysfunction and rejection in solid organ transplantation, and graft-versus-host-disease in stem cell transplantation. Monocytes, key cellular targets of CMV, are permissive to primary, latent and reactivated CMV infection. Here, pairing unbiased bulk and single cell transcriptomics with functional analyses we demonstrate that human monocytes infected with CMV do not effectively phagocytose fungal pathogens, a functional deficit which occurs with decreased expression of fungal recognition receptors. Simultaneously, CMV-infected monocytes upregulate antiviral, pro-inflammatory chemokine, and inflammasome responses associated with allograft rejection and graft-versus-host disease. Our study demonstrates that CMV modulates both immunosuppressive and immunostimulatory monocyte phenotypes, explaining in part, its paradoxical "indirect effects" in transplantation. These data could provide innate immune targets for the stratification and treatment of CMV disease.</p