A marine record of Patagonian ice sheet changes over the past 140,000 years.

Terrestrial glacial records from the Patagonian Andes and New Zealand Alps document quasi-synchronous Southern Hemisphere-wide glacier advances during the late Quaternary. However, these records are inherently incomplete. Here, we provide a continuous marine record of western-central Patagonian ice sheet (PIS) extent over a complete glacial-interglacial cycle back into the penultimate glacial (~140 ka). Sediment core MR16-09 PC03, located at 46°S and ~150 km offshore Chile, received high terrestrial sediment and meltwater input when the central PIS extended westward. We use biomarkers, foraminiferal oxygen isotopes, and major elemental data to reconstruct terrestrial sediment and freshwater input related to PIS variations. Our sediment record documents three intervals of general PIS marginal fluctuations, during Marine Isotope Stage (MIS) 6 (140 to 135 ka), MIS 4 (~70 to 60 ka), and late MIS 3 to MIS 2 (~40 to 18 ka). These higher terrigenous input intervals occurred during sea-level low stands, when the western PIS covered most of the Chilean fjords, which today retain glaciofluvial sediments. During these intervals, high-amplitude phases of enhanced sediment supply occur at millennial timescales, reflecting increased ice discharge most likely due to a growing PIS. We assign the late MIS 3 to MIS 2 phases and, by inference, older advances to Antarctic cold stages. We conclude that the increased sediment/meltwater release during Southern Hemisphere millennial-scale cold phases was likely related to higher precipitation caused by enhanced westerly winds at the northwestern margin of the PIS. Our records complement terrestrial archives and provide evidence for PIS climate sensitivity.

[Diffuse large B cell lymphoma with HIV infection presented with disseminated thromboembolism during antiretroviral therapy].

Patients with HIV are at higher risk of developing thrombosis than the general population. We present a rare case of a 57-year-old Japanese man with HIV infection and a malignant lymphoma. He had fever with unknown origin and cervical lymph node swelling 2 months before his hospital visit. Because he was positive for the HIV antibody, he was referred to our HIV special outpatient section. HIV RNA level was found to be 846,680 copies/ml. Therefore, antiretroviral therapy of DTG/ABC/3TC was initiated. However, the high fever continued for 7 days after treatment initiation; moreover, renal dysfunction was progressive. After admission, antibiotic therapy was initiated, due to which the fever subsided. However, renal dysfunction continued to progress. Fourteen days later, he died due to acute renal failure with hyperkalemia. An autopsy revealed a large mass in the spleen, and histological findings revealed a diffuse large B cell lymphoma (DLBCL). Furthermore, thrombi were detected in the right and left ventricles, right atrium, iliac artery, and renal artery. Pathological findings revealed that the thrombus induced the renal failure. These thrombi contained fibrin with inflammatory cell infiltration but not tumor cells. Patients with HIV and malignant lymphoma are at a higher risk of thrombosis. It is important to consider thrombosis during the treatment of patients with HIV.

Byproduct-Free Intact Modification of Insulin by Cholesterol End-Modified Poly(ethylene glycol) for in Vivo Protein Delivery.

Insulin is a key peptide hormone used for the treatment of both type I and type II diabetes. To maximize the effect of the treatment of these diseases, the addition of poly(ethylene glycol) (PEGylation) methods for the insulin are widely developed. Here, to make these PEGylation methods the simplest, we report the byproduct-free intact modification of insulin by cholesterol end-modified poly(ethylene glycol) with urethane, propyl, and methoxy groups (that is, Chol-U-Pr-mPEG). The noncovalent PEGylation by the Chol-U-Pr-mPEG has been achieved by the simple mixing of insulin with the Chol-U-Pr-mPEG in aqueous solution, followed by freeze-drying. The formation of the Chol-U-Pr-mPEG/insulin complex has proceeded without byproducts, such as N-hydroxysuccinimide, formed by the conventional covalent PEGylation using an active ester group. The byproduct-free PEGylation has preserved insulin conformation as well as primary structure. The intact PEGylation has protected insulin from hydrolysis by protease. The resulting insulin modified by the Chol-U-Pr-mPEG has sustainably suppressed the level of blood glucose, as compared to naked insulin, in mice. Consequently, the Chol-U-Pr-mPEG/insulin complex formation offers the byproduct-free intact PEGylation of insulin for in vivo protein delivery.

Asian dust-deposition flux to the subarctic Pacific estimated using single quartz particles.

Iron availability limits marine ecosystem activities in large areas of the ocean. However, the sources and seasonal supply of iron, critically important for controlling surface ocean biogeochemistry and carbon cycling, are poorly understood. The western subarctic Pacific is a high-nutrient and low-chlorophyll region, and despite high concentrations of macronutrients, iron limits phytoplankton production in summer. Here, we determine the seasonal deposition flux of Asian dust using scanning electron microscope-cathodoluminescence analysis of single quartz particles derived from the western subarctic Pacific during 2003-2022 to trace provenance. We found a high (up to 6.9 mg m-2 day-1) deposition flux of Asian dust in May, June, and early July, with an annual average of 1.0 ± 0.2 mg m-2 day-1. The supply of dissolved-iron flux calculated from Asian dust was 0.9 ± 0.3 µg m-2 day-1 during the high productivity season (April-July), which is approximately half that from the deeper part of the ocean, calculated from vertical profiles of dissolved iron. Our study provides a reliable approach for estimating iron supply from dust to the surface ocean that may be critical for sustaining biological productivity under future ocean stratification, which suppresses nutrient supply from the subsurface ocean.

Evidence for late-glacial oceanic carbon redistribution and discharge from the Pacific Southern Ocean.

Southern Ocean deep-water circulation plays a vital role in the global carbon cycle. On geological time scales, upwelling along the Chilean margin likely contributed to the deglacial atmospheric carbon dioxide rise, but little quantitative evidence exists of carbon storage. Here, we develop an X-ray Micro-Computer-Tomography method to assess foraminiferal test dissolution as proxy for paleo-carbonate ion concentrations ([CO32-]). Our subantarctic Southeast Pacific sediment core depth transect shows significant deep-water [CO32-] variations during the Last Glacial Maximum and Deglaciation (10-22 ka BP). We provide evidence for an increase in [CO32-] during the early-deglacial period (15-19 ka BP) in Lower Circumpolar Deepwater. The export of such low-carbon deep-water from the Pacific to the Atlantic contributed to significantly lowered carbon storage within the Southern Ocean, highlighting the importance of a dynamic Pacific-Southern Ocean deep-water reconfiguration for shaping late-glacial oceanic carbon storage, and subsequent deglacial oceanic-atmospheric CO2 transfer.

Possible clinical outcomes using early enteral nutrition in individuals with allogeneic hematopoietic stem cell transplantation: A single-center retrospective study.

OBJECTIVES: Intensive nutritional support during allogeneic hematopoietic stem cell transplantation (allo-HSCT) yields improved clinical outcomes. However, the clinical implications of early enteral nutrition (EN) in allo-HSCT remain unclear. This retrospective study was conducted to determine the significance of early EN in individuals who underwent allo-HSCT, and the association between early nutritional intervention and clinical outcomes, including the status of the intestinal microbiome. METHODS: Thirty-one participants received EN before conditioning. The intestinal microbiota was examined by meta 16S rRNA gene sequencing of fecal samples. RESULTS: The median body mass variation was only -0.35 kg on day 60. The probability of 2-y overall survival was 61.1%. The cumulative incidence of treatment-related mortality was 17.4%, and those of acute graft-versus-host disease were 32.3% (grades II-IV) and 3.2% (grades III-IV). Chronic graft-versus-host disease was observed in four participants. Dysbiosis of the intestines and acute graft-versus-host disease occurred simultaneously, and Enterococcus species were abundant. CONCLUSIONS: Our results suggest that early nutritional support can improve the outcomes for individuals who have undergone allo-HSCT and can maintain homeostasis of their intestinal microbiome. Future prospective clinical trials are required to elucidate the role of EN in allo-HSCT and the association between the intestinal microbiome and EN.

Successful brentuximab vedotin monotherapy against late relapse of classical Hodgkin lymphoma 6 years after first remission.

Brentuximab vedotin monotherapy for late-relapse CHL is a promising therapeutic with sustained CR benefit and avoiding potential toxicities caused by aPBSCT/HDT.

Facile Method of Protein PEGylation by a Mono-Ion Complex.

Diethylaminoethyl end-modified poly(ethylene glycol) (DEAE-PEG) has been synthesized for the noncovalent PEGylation of proteins. The resulting DEAE-PEG and catalase formed an ion complex, that is, a protein mono-ion complex (MIC). The formation of the protein MIC was confirmed by native poly(acrylamide) gel electrophoresis and gel-filtration chromatography. The resulting catalase MIC preserved the catalase activity, confirmed by monitoring the O2 concentration with a Clark-type oxygen electrode, in spite of MIC formation. The catalase activity of the protein MIC was protected in the presence of a protease, trypsin, or 10% fetal bovine serum. Furthermore, less change in the circular dichroism measurements of the catalase MIC was observed as compared to those of a catalase-PEG conjugate (covalent PEGylation), suggesting less influence of the protein conformation. Consequently, the formation of the MIC is considered to be a facile method of protein PEGylation.