Late pleistocene sedimentation history of the Shirshov Ridge, Bering Sea

The analysis of the lithology, grain-size distribution, clay minerals, and geochemistry of Upper Pleistocene sediments from the submarine Shirshov Ridge (Bering Sea) showed that the main source area was the Yukon–Tanana terrane of Central Alaska. The sedimentary materials were transported by the Yukon River through Beringia up to the shelf break, where they were entrained by a strong northwestward-flowing sea current. The lithological data revealed several pulses of ice-rafted debris deposition, roughly synchronous with Heinrich events, and periods of weaker bottom-current intensity. Based on the geochemical results, we distinguished intervals of an increase in paleoproductivity and extension of the oxygen minimum zone. The results suggest that there were three stages of deposition driven by glacioeustatic sea-level fluctuations and glacial cycles in Alaska

Late quaternary sea-ice and sedimentary redox conditions in the eastern Bering Sea – Implications for ventilation of the mid-depth North Pacific and an Atlantic-Pacific seesaw mechanism

On glacial-interglacial and millennial timescales, sea ice is an important player in the circulation and primary productivity of high latitude oceans, affecting regional and global biogeochemical cycling. In the modern North Pacific, brine rejection during sea-ice freezing in the Sea of Okhotsk drives the formation of North Pacific Intermediate Water (NPIW) that ventilates the North Pacific Ocean at 300 m to 1000 m water depth. Glacial intervals of the late Quaternary, however, experienced a deepening of glacial NPIW to at least 2000 m, with the strongest ventilation observed during cold stadial conditions of the last deglaciation. However, the origin of the shifts in NPIW ventilation is poorly understood. Numerical simulations suggest an atmospheric teleconnection between the North Atlantic and the North Pacific, in response to a slowdown or shutdown of the Atlantic meridional overturning circulation. This leads to a build-up of salinity in the North Pacific surface ocean, triggering deep ventilation. Alternatively, increased sea-ice formation in the North Pacific and its marginal seas may have caused strengthened overturning in response to enhanced brine rejection. Here we use a multi-proxy approach to explore sea-ice dynamics, sedimentary redox chemistry, and benthic ecology at Integrated Ocean Drilling Program Site U1343 in the eastern Bering Sea across the last 40 ka. Our results suggest that brine rejection from enhanced sea-ice formation during early Heinrich Stadial 1 locally weakened the halocline, aiding in the initiation of deep overturning. Additionally, deglacial sea-ice retreat likely contributed to increased primary productivity and expansion of mid-depth hypoxia at Site U1343 during interstadials, confirming a vital role of sea ice in the deglacial North Pacific carbon cycle

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

First stage of medical rehabilitation of patients after spontaneous miscarriage

The article presents a discussion of the issue of management of patients after spontaneous abortion to prevent inflammatory complications. The condition of 165 patients distributed randomly in two groups is analyzed. Attention was paid to a full-fledged microbiological examination, including bacterioscopy and modern methods of PCR-diagnostics: «Inbioflor(4+MHC)» and «Femoflor-16». Patients of the first group (85 people) were prescribed antibacterial therapy (doxycycline, metronidazole, povidoniodine), as well as modern methods of physiotherapy: magnetoinfrared laser and ozone therapy. The second group (80 people) received similar antibacterial therapy, without physiotherapy. The study showed that the best effect can be achieved with complex therapy, including antibacterial drugs and modern methods of physiotherapy