The Marmara Sea Gateway since ~16 ky BP: non-catastrophic causes of paleoceanographic events in the Black Sea at 8.4 and 7.15 ky BP

The Late Quaternary history of connection of the Black Sea to the Eastern Mediterranean has been intensely debated. Ryan, Pitman and coworkers advocate two pulses of outflow from the Black Sea to the world ocean at ~16–14.7 ky BP and ~11–10 ky BP. From ~14.7–11 ky BP and from ~10–8.4 ky BP, they suggest that the level of the Black Sea fell to ~ -100 m. At 8.4 ky BP, they further claim that a catastrophic flood occurred in a geological instant, refilling the Black Sea with saline waters from the Mediterranean. In contrast, we continue to gather evidence from seismic profiles and dated cores in the Marmara Sea which demonstrate conclusively that the proposed flood did not occur. Instead, the Black Sea has been at or above the Bosphorus sill depth and flowing into the world ocean unabated since ~10.5 ky BP. This conclusion is based on continuous Holocene water-column stratification (leading to sapropel deposition in the Marmara Sea and the Aegean Sea), proxy indicators of sea-surface salinity, and migration of endemic species across the Bosphorus in both directions whenever appropriate hydrographic conditions existed in the strait. The two pulses of outflow documented by Ryan, Pitman and coworkers find support in our data, and we have modified our earlier interpretations so that these pulses now coincide with the development of mid-shelf deltas: \Delta 2 (16–14.7 ky BP) and \Delta 1 (10.5–9 ky BP) at the southern end of the Bosphorus Strait. However, continued Black Sea outflow after 9 ky BP prevented the northward advection of Mediterranean water and the entry of open-marine species into the Black Sea for more than 1000 years. Sufficient Mediterranean water to change the Sr-isotopic composition of slope and shelf water masses was not available until ~8.4 ky BP (along with the first arrival of many varieties of marine fauna and flora), whereas euryhaline molluscs did not successfully populate the Black Sea shelves until ~7.15 ky BP. Instead of relying on catastrophic events, we recognize a slow, progressive reconnection of the Black Sea to the world ocean, accompanied by significant time lags

Mechanisms of Zika virus infection and neuropathogenesis

A spotlight has been focused on the mosquito-borne Zika virus (ZIKV) because of its epidemic outbreak in Brazil and Latin America, as well as the severe neurological manifestations of microcephaly and Guillain–Barré syndrome associated with infection. In this review, we discuss the recent literature on ZIKV-host interactions, including new mechanistic insight concerning the basis of ZIKV-induced neuropathogenesis

Derivation of Del180 from sediment core log data\u27 Implications for millennial-scale climate change in the Labrador Sea

Sediment core logs from six sediment cores in the Labrador Sea show millennial-scale climate variability during the last glacial by recording all Heinrich events and several major Dansgaard-Oeschger cycles. The same millennial-scale climate change is documented for surface water δ18O records of Neogloboquadrina pachyderma (left coiled); hence the surface water δ18O record can be derived from sediment core logging by means of multiple linear regression, providing a paleoclimate proxy record at very high temporal resolution (70 years). For the Labrador Sea, sediment core logs contain important information about deepwater current velocities and also reflect the variable input of ice-rafted debris from different sources as inferred from grain-size analysis, the relation of density and P wave velocity, and magnetic susceptibility. For the last glacial, faster deepwater currents, which correspond to highs in sediment physical properties, occurred during iceberg discharge and lasted from several centuries to a few millennia. Those enhanced currents might have contributed to increased production of intermediate waters during times of reduced production of North Atlantic Deep Water. Hudson Strait might have acted as a major supplier of detrital carbonate only during lowered sea level (greater ice extent). During coldest atmospheric temperatures over Greenland, deepwater currents increased during iceberg discharge in the Labrador Sea, then surface water freshened shortly thereafter, while the abrupt atmospheric temperature rise happened after a larger time lag of ≥ 1 kyr. The correlation implies a strong link and common forcing for atmosphere, sea surface, and deep water during the last glacial at millennial timescales but decoupling at orbital timescales

Age-Related Changes of Cystatin C Expression and Polarized Secretion by Retinal Pigment Epithelium: Potential Age-Related Macular Degeneration Links

PURPOSE: Cystatin C, a potent cysteine proteinase inhibitor, is abundantly secreted by the RPE and may contribute to regulating protein turnover in the Bruch's membrane (BrM). A cystatin C variant associated with increased risk of developing AMD and Alzheimer's disease (AD) presents reduced secretion levels from RPE. The purpose of this study was to analyze the effects of age and the accumulation of advanced glycation end-products (AGEs) on the expression and secretion of cystatin C by the RPE.METHODS: Confluent monolayers of human fetal RPE (hfRPE) cells were cultured using an in vitro model mimicking extracellular AGE accumulation. Cystatin C expression, secretion, and its polarity were analyzed following culture on AGE-containing BrM mimics (AGEd versus non-AGEd). Monolayer barrier properties were assessed by transepithelial resistance measurements. The relative level of cystatin C protein expression in human RPE in situ was assessed immunohistochemically in relation to age.RESULTS: Advanced glycation end product-exposed RPE monolayers presented significantly decreased cystatin C expression and secretion. Basolateral secretion was fully established by week 8 in non-AGEd conditions. In AGEd cultures, polarity of secretion was impaired despite maintenance of physiological barrier properties of the monolayer. In the macula region of RPE/choroid segments from human eyes, the level of cystatin C protein was reduced with increasing donor age.CONCLUSIONS: Exposure to AGEs reduces expression of cystatin C and affects its normal secretion in cultured RPE. Age-related changes of cystatin C in the RPE from the posterior pole may compromise its extracellular functions, potentially contributing to AMD pathogenesis.</p

Inhibition of dengue virus replication by novel inhibitors of RNA-dependent RNA polymerase and protease activities

Dengue virus (DENV) is the leading mosquito-transmitted viral infection in the world. With more than 390 million new infections annually, and up to 1 million clinical cases with severe disease manifestations, there continues to be a need to develop new antiviral agents against dengue infection. In addition, there is no approved anti-DENV agents for treating DENV-infected patients. In the present study, we identified new compounds with anti-DENV replication activity by targeting viral replication enzymes – NS5, RNA-dependent RNA polymerase (RdRp) and NS3 protease, using cell-based reporter assay. Subsequently, we performed an enzyme-based assay to clarify the action of these compounds against DENV RdRp or NS3 protease activity. Moreover, these compounds exhibited anti-DENV activity in vivo in the ICR-suckling DENV-infected mouse model. Combination drug treatment exhibited a synergistic inhibition of DENV replication. These results describe novel prototypical small anti-DENV molecules for further development through compound modification and provide potential antivirals for treating DENV infection and DENV-related diseases

Peel and peel again

Aim: To determine if the internal limiting membrane (ILM) was present in the epiretinal membrane (ERM) when we deliberately tried to perform a "double peel" for macular pucker. Methods: Pars-plana vitrectomy and a "double peel" were carried out. The ERM and ILM were stained with Trypan Blue and peeled separately over the same area. The amount of ERM present in ILM specimens and the amount of ILM present in ERM specimens were evaluated by histological examination. Results: Seventeen eyes in 17 patients were included. It was possible to double peel in all cases. Five of 17 ERM specimens (29%) contained ILM fragments. When ILM was present on the ERM, it represented less than 50% of the sample. One ILM specimen was lost as result of an administrative error; of the remaining 16 specimens, residual ERM was found in six, and cellular remnants were observed on the vitreous surface in a further six of the ILMs. Clinically, no recurrence of ERM was found. Conclusion: ILM was present in some ERM specimens seemingly over the same area that an intact ILM was subsequently peel. We speculate that the ILM in the ERM represent a secondary basement membrane and that the surgical plane of dissection for most ERM peel is between the ERM and the native ILM, making it feasible to double peel routinely.published_or_final_versio

Conference Highlights of the 16th International Conference on Human Retrovirology: HTLV and Related Retroviruses, 26–30 June 2013, Montreal, Canada

The 16th International Conference on Human Retrovirology: HTLV and Related Retroviruses was held in Montreal, Québec from June 26 to June 30, 2013 and was therefore hosted by a Canadian city for the first time. The major topic of the meeting was human T-lymphotropic viruses (HTLVs) and was covered through distinct oral and poster presentation sessions: clinical research, animal models, immunology, molecular and cellular biology, human endogenous and emerging exogenous retroviruses and virology. In this review, highlights of the meeting are provided by different experts for each of these research areas

Human Bocavirus NS1 and NS1-70 Proteins Inhibit TNF-α-Mediated Activation of NF-κB by targeting p65.

Human bocavirus (HBoV), a parvovirus, is a single-stranded DNA etiologic agent causing lower respiratory tract infections in young children worldwide. Nuclear factor kappa B (NF-κB) transcription factors play crucial roles in clearance of invading viruses through activation of many physiological processes. Previous investigation showed that HBoV infection could significantly upregulate the level of TNF-α which is a strong NF-κB stimulator. Here we investigated whether HBoV proteins modulate TNF-α-mediated activation of the NF-κB signaling pathway. We showed that HBoV NS1 and NS1-70 proteins blocked NF-κB activation in response to TNF-α. Overexpression of TNF receptor-associated factor 2 (TRAF2)-, IκB kinase alpha (IKKα)-, IκB kinase beta (IKKβ)-, constitutively active mutant of IKKβ (IKKβ SS/EE)-, or p65-induced NF-κB activation was inhibited by NS1 and NS1-70. Furthermore, NS1 and NS1-70 didn't interfere with TNF-α-mediated IκBα phosphorylation and degradation, nor p65 nuclear translocation. Coimmunoprecipitation assays confirmed the interaction of both NS1 and NS1-70 with p65. Of note, NS1 but not NS1-70 inhibited TNF-α-mediated p65 phosphorylation at ser536. Our findings together indicate that HBoV NS1 and NS1-70 inhibit NF-κB activation. This is the first time that HBoV has been shown to inhibit NF-κB activation, revealing a potential immune-evasion mechanism that is likely important for HBoV pathogenesis

Present-day stress orientations and tectonic provinces of the NW Borneo collisional margin

Extent: 15p.Borehole failure observed on image and dipmeter logs from 55 petroleum wells across the NW Borneo collisional margin were used to determine maximum horizontal stress (σH) orientations; combined with seismic and outcrop data, they define seven tectonic provinces. The Baram Delta–Deepwater Fold-Thrust Belt exhibits three tectonic provinces: its inner shelf inverted province (σH is NW-SE, margin-normal), its outer shelf extension province (σH is NE-SW, margin-parallel), and its slope to basin floor compression province (σH is NW-SE, margin-normal). In the inverted province, σH reflects inversion of deltaic normal faults. The σH orientations in the extension and compression provinces reflect deltaic gravitational tectonics. The shale and minibasin provinces have been recognized in offshore Sabah. In the shale province, σH is N010°E, which aligns around the boundary of a massif of mobile shale. Currently, no data are available to determine σH in the minibasin province. In the Balingian province, σH is ESE-WNW, reflecting ESE absolute Sunda plate motions due to the absence of a thick detachment seen elsewhere in NW Borneo. The Central Luconia province demonstrates poorly constrained and variable σH orientations. These seven provinces result from the heterogeneous structural and stratigraphic development of the NW Borneo margin and formed due to complex collisional tectonics and the varied distribution and thicknesses of stratigraphic packages.Rosalind C. King, Mark R. P. Tingay, Richard R. Hillis, Christopher K. Morley, and James Clar