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.

Five million years of Antarctic Circumpolar Current strength variability.

The Antarctic Circumpolar Current (ACC) represents the world's largest ocean-current system and affects global ocean circulation, climate and Antarctic ice-sheet stability1-3. Today, ACC dynamics are controlled by atmospheric forcing, oceanic density gradients and eddy activity4. Whereas palaeoceanographic reconstructions exhibit regional heterogeneity in ACC position and strength over Pleistocene glacial-interglacial cycles5-8, the long-term evolution of the ACC is poorly known. Here we document changes in ACC strength from sediment cores in the Pacific Southern Ocean. We find no linear long-term trend in ACC flow since 5.3 million years ago (Ma), in contrast to global cooling9 and increasing global ice volume10. Instead, we observe a reversal on a million-year timescale, from increasing ACC strength during Pliocene global cooling to a subsequent decrease with further Early Pleistocene cooling. This shift in the ACC regime coincided with a Southern Ocean reconfiguration that altered the sensitivity of the ACC to atmospheric and oceanic forcings11-13. We find ACC strength changes to be closely linked to 400,000-year eccentricity cycles, probably originating from modulation of precessional changes in the South Pacific jet stream linked to tropical Pacific temperature variability14. A persistent link between weaker ACC flow, equatorward-shifted opal deposition and reduced atmospheric CO2 during glacial periods first emerged during the Mid-Pleistocene Transition (MPT). The strongest ACC flow occurred during warmer-than-present intervals of the Plio-Pleistocene, providing evidence of potentially increasing ACC flow with future climate warming.

Collection of X-ray micro computed tomography images of shells of planktic foraminifera with curated taxonomy.

Calcite shells of planktic foraminifera (Protista, Rhizaria) constitute a large portion of deep-sea sediments. The shells are constructed by sequential addition of partly overlapping chambers with diverse shapes, resulting in complex shell architectures, which are genetically fixed and diagnostic at the species level. The characterisation of the complete architecture requires three-dimensional imaging of the shell, including the partially or entirely covered juvenile chambers. Here we provide reconstructed x-ray micro computed tomography image stacks of 179 specimens of extant planktic foraminifera collected from plankton tows, sediment traps and surface sediments. The specimens have fully resolved and curated taxonomy and represent 43 of the currently recognised 48 holoplanktic species and subspecies. The image stacks form a basis for further applications, such as the characterisation of the architectural morphospace of the extant taxa, allowing studies of species functional ecology, calcification intensity and reconstructions of phylogenetic relationships.

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.

Amendment with Burkina Faso phosphate rock-enriched composts alters soil chemical properties and microbial structure, and enhances sorghum agronomic performance.

Low soil available phosphorus (P) severely limits crop production in sub-Saharan Africa. The present study evaluated phosphate rock-enriched composts as locally available low-cost fertilizers for sorghum production. The treatments consisted of sorghum straw, compost (COMP), phosphate rock (BPR), BPR-enriched compost (P-COMP), BPR-rhizosphere soil-enriched compost (P-COMP-SOIL), nitrogen-phosphorus-potassium treatment (NPK, 60-39-25), and control (NK, 60-25). Sorghum straw and compost were applied at 1.34 tons ha-1. N, P, and K in all treatments, excluding the control, were adjusted to 60, 39, and 25 kg ha-1, with urea, BPR, and KCl, respectively. Sorghum vr. kapelga was cultivated and soil samples were collected at the S5, S8, and S9 growth stages. P-COMP-SOIL and NPK yielded better sorghum yields than the other treatments. The rhizosphere soil of P-COMP-SOIL had high abundance of soil bacteria and AMF, and genes involved in P solubilization, such as: acid phosphatase (aphA), phosphonatase (phnX), glucose dehydrogenase (gcd), pyrroloquinoline quinone (pqqE), phosphate-specific transporter (pstS). The superior performance of the P-COMP-SOIL was associated with its higher available P content and microbial abundance. Multivariate analysis also revealed vital contributions of N, carbon, and exchangeable cations to sorghum growth. Soils could be amended with phosphate rock-rhizosphere soil-enriched composts, as an alternative to chemical fertilizers.

A case of feline temporal lobe epilepsy with hippocampal sclerosis and dentate gyrus malformation.

A two-months-old, male, mixed breed cat presented with epileptic seizures. The cat was diagnosed with drug-resistant epilepsy, and died at 3-years of age. No gross lesion was found at necropsy. Histopathologically, the dentate gyrus granule cell layer of the hippocampus was irregularly arranged. Granule cells were dispersed and ectopic cells were sporadically observed in the molecular layer. The granule cells had an enlarged cytoplasm and swollen nucleus. Immunohistochemistry for NeuN and GFAP confirmed severe neuronal loss and mild gliosis in CA1. Binucleation and ischemic change were observed in the remaining pyramidal cells. This report describes a case of feline temporal lobe epilepsy and hippocampal sclerosis associated with dentate gyrus malformation.

Adenocarcinoma in situ or early-stage cervical cancer is a risk factor for preterm delivery after cervical conization: a multicenter observational study.

OBJECTIVE: Pregnancy after conization is associated with a high risk of preterm delivery. However, because risk factors for preterm delivery after conization remain unknown, we conducted a multicenter observational study to investigate risk factors associated with preterm delivery. METHODS: We selected patients who had previously undergone conization and reviewed medical records from 18 hospitals in cooperation with Keio University School of Medicine between January 2013 and December 2019. Women were classified as nulliparous and primiparous, and a multiple logistic regression analysis was performed to evaluate the relative contributions of the various maternal risk factors for preterm delivery (i.e. delivery before 37 gestational weeks). RESULTS: Among 409 pregnant women after conization, 68 women delivered preterm (17%). The incidence of nulliparity (p = .014) was higher and a history of preterm delivery (p = .0010) was more common in the preterm delivery group than in the term delivery group. Furthermore, the proportion of women diagnosed with adenocarcinoma in situ (AIS) and cervical cancer in the preterm delivery group was higher than that in the term delivery group (p = .0099 and .0004, respectively). In multiple regression models in nulliparous women, cervical cancer or AIS (Odds ratio [OR]: 4.16, 95% CI: 1.26-13.68, p = .019) and a short cervix in the second trimester (OR: 13.41, 95% CI: 3.88-46.42, p < .0001) increased the risk of preterm delivery. Furthermore, a history of preterm delivery (OR: 7.35, 95% CI: 1.55-34.86, p = .012), cervical cancer or AIS (OR: 5.07, 95% CI: 1.24-20.73, p = .024), and a short cervix in the second trimester (OR: 4.29, 95% CI: 1.11-16.62, p = .035) increased the risk of preterm delivery in the multiple regression models in primiparous women. CONCLUSION: Pregnant women who previously underwent conization are at risk for preterm delivery. The histological type of AIS and cervical cancer was evaluated as a risk factor for preterm delivery. KEY MESSAGESPrior preterm delivery, presence of a short cervix, and cervical cancer or AIS were predictors of preterm delivery after conization.The depth of conization in cervical cancer or AIS group was significantly larger than that in the CIN group.

Site-specific responses of lowland rice to acidulated and calcined phosphate rock fertilizers in the Center-West region of Burkina Faso.

Soil phosphorus (P) deficiency is a major constraint of crop production in Sub-Saharan Africa. In particular, in the Sudano-Sahelian zone of Burkina Faso, P is rarely replenished as fertilizer supplies are limited in rural areas and because of the socio-economic situation of farmers. There is however, an abundance of local phosphate rock resource in the country. The development of local inorganic P fertilizers to improve crop production and replace the nutrients removed after harvesting, as well as to promote to sustainable agriculture, is desired. This study evaluated the efficiency of low-grade Burkina Faso phosphate rock (BPR)-based P fertilizers, produced by acidulation and calcination-the major fertilizer processing methods, on lowland rice production and the soil factors influencing their effectiveness. The results showed that the acidulated P fertilizers were as effective as conventional commercial P fertilizers on various soil types, textures, and fertility. Calcined P fertilizers were consistently effective on fine-textured soils with high basic fertility. It was found that fine soil texture and basic fertility of the initial soils were important factors in agronomic efficiency of BPR-based fertilizers and the resilience of rice production to climatic variability. It is recommended that soil type, with respect to soil texture, soil properties, inherent fertility, and water availability, should be considered when using BPR-based fertilizers for rice cultivation.

Correction to: Sudden onset of syncope and disseminated intravascular coagulation at 14 weeks of pregnancy: a case report.

An amendment to this paper has been published and can be accessed via the original article.

Sudden onset of syncope and disseminated intravascular coagulation at 14 weeks of pregnancy: a case report.

BACKGROUND: Amniotic fluid embolism (AFE), also known as anaphylactoid syndrome of pregnancy (ASP), typically occurs during labor and may result in cardiorespiratory collapse and disseminated intravascular coagulation (DIC). There are reports describing less typical presentations of AFE/ASP in which patients do not necessarily have the classic triad of hypoxia, hypotension, and coagulopathy. AFE/ASP rarely occurs in the absence of labor, but such cases may involve medical or surgical abortion, spontaneous miscarriage, or obstetrical procedures including amniocentesis and amnioinfusion. There are, however, no previously reported cases of AFE/ASP with sudden loss of consciousness and disseminated intravascular coagulation occurring during early pregnancy, in the absence of any intervention or obstetric event. CASE PRESENTATION: A 32-year-old G3P2 Japanese woman had sudden-onset syncope at 14 weeks' gestation. On arrival at our hospital, her level of consciousness was severely disturbed as determined by the Glasgow Coma Scale. Although her vital signs were initially stable, blood samples collected intravenously and by femoral artery puncture did not coagulate. A subchorionic hematoma with active extravasation of blood was apparent on contrast-enhanced computed tomography. Two hours after her arrival, she developed hypovolemic shock with progression of DIC, presumably due to intrauterine and retroperitoneal bleeding. After transfusion of blood products; treatments for DIC including the use of recombinant human soluble thrombomodulin, ulinastatin, and corticosteroids; and hysterectomy, her level of consciousness and physical condition improved remarkably. Later investigation of preoperative blood samples revealed that serum levels of AFE/ASP-associated markers were elevated. Immunohistochemical studies on the excised, unruptured uterus showed that amniotic fluid components were present inside a uterine blood vessel. CONCLUSIONS: This is the first reported patient with sudden-onset syncope and DIC, but without apparent cardiorespiratory collapse, with the highly likely etiology of AFE/ASP occurring at the beginning of the second trimester of pregnancy and in the absence of intervention or delivery. Maternal collapse with DIC during any stage of pregnancy should be considered an AFE/ASP-associated event, even in the absence of labor or obstetric procedures. This event may occur in the presence of subchorionic hematoma alone.

Risk Evaluation for Acute Kidney Injury Induced by the Concomitant Use of Valacyclovir, Analgesics, and Renin-Angiotensin System Inhibitors: The Detection of Signals of Drug-Drug Interactions.

Background: Drug-related acute kidney disease is a common side effect of valacyclovir (VACV) treatment. Although analgesics are frequently administered concomitantly with VACV to treat the pain of herpes zoster, the differences between nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen in relation to VACV-related acute kidney injury (AKI) are unclear. The risk for AKI with concomitant use of VACV and renin-angiotensin system (RAS) inhibitors that can cause AKI via a similar mechanism to NSAIDs is also unknown. We therefore evaluated the association between concomitant use of these drugs and VACV-related AKI, which was characterized according to the Japanese Adverse Drug Event Report (JADER) database. Methods: We analyzed data from the JADER database, which is a spontaneous reporting system. The reporting odds ratio was used to evaluate the signals of AKI. Results: A high proportion of VACV-related AKI cases occurred in summer. There was an increase in AKI signal in cases with concomitant use of VACV and NSAIDs, while no increase was detected in cases with concomitant use of VACV and acetaminophen. AKI events in cases with concomitant use of VACV and NSAIDs were more frequent in older and female patients and those with hypertension. Additionally, a signal increase for VACV-related AKI was observed with concomitant use of RAS inhibitors, with or without NSAIDs. Conclusions: We identified a seasonal variation in VACV-related AKI. Additionally, our findings indicate that acetaminophen might represent a safer analgesic than NSAIDs with respect to VACV-related AKI. We also identified candidate risk factors for AKI with concomitant use of NSAIDs, such as older age, female sex, and hypertension. Although further studies are warranted, our findings highlight the need to consider concomitant drug use and seasonal factors that lead to urinary output loss so that VACV-related AKI can be avoided.

Estimating agro-ecosystem carbon balance of northern Japan, and comparing the change in carbon stock by soil inventory and net biome productivity.

Soil C sequestration in croplands is deemed to be one of the most promising greenhouse gas mitigation options for agriculture. We have used crop-level yields, modeled heterotrophic respiration (Rh) and land use data to estimate spatio-temporal changes in regional scale net primary productivity (NPP), plant C inputs, and net biome productivity (NBP) in northern Japan's arable croplands and grasslands for the period of 1959-2011. We compared the changes in C stocks derived from estimated NBP and using repeated inventory datasets for each individual land use type from 2005 to 2011. For the entire study region of 2193 ha, overall annual plant C inputs to the soil constituted 37% of total region NPP. Plant C inputs in upland areas (excluding bush/fallow) could be predicted by climate variables. Overall NBP for all land use types increased from -1.26MgCha(-1)yr(-1) in 1959-0.26 Mg Cha(-1)yr(-1) in 2011. However, upland and paddy fields showed a decreased in NBP over the period of 1959-2011, under the current C input scenario. From 1988, an increase in agricultural abandonment (bush/fallow) and grassland cover caused a slow increase in the regional C pools. The comparison of carbon budgets using the NBP estimation method and the soil inventory method indicated no significant difference between the two methods. Our results showed C loss in upland crops, paddy fields and sites that underwent land use change from paddy field to upland sites. We also show C gain in grassland from 2005 to 2011. An underestimation of NBP or an overestimation of repeated C inventories cannot be excluded, but either method may be suitable for tracking absolute changes in soil C, considering the uncertainty associated with these methods.

Functional expression of brain neuronal CB2 cannabinoid receptors are involved in the effects of drugs of abuse and in depression.

Major depression and addiction are mental health problems associated with stressful events in life with high relapse and recurrence even after treatment. Many laboratories were not able to detect the presence of CB2 cannabinoid receptors (CB2-Rs) in healthy brains, but CB2-R expression has been demonstrated in rat microglial cells and other brain-associated cells during inflammation. Thus, neuronal expression of CB2-Rs has been ambiguous and controversial, and its role in depression and substance abuse is unknown. In this study we tested the hypothesis that genetic variants of the CB2 gene might be associated with depression in a human population and that alteration in CB2 gene expression may be involved in the effects of abused substances, including opiates, cocaine, and ethanol, in rodents. Here we demonstrate that a high incidence of Q63R but not H316Y polymorphism in the CB2 gene was found in Japanese depressed subjects. CB2-Rs and their gene transcripts are expressed in the brains of naïve mice and are modulated after exposure to stressors and administration of abused drugs. Mice that developed an alcohol preference had reduced CB2 gene expression, and chronic treatment with JWH015 a putative CB2-R agonist, enhanced alcohol consumption in stressed but not in control mice. The direct intracerebroventricular microinjection of CB2 antisense oligonucleotide into the mouse brain reduced mouse aversions in the plus-maze test, indicating the functional presence of CB2-Rs in the brain that modifies behavior. Using electron microscopy we report the subcellular localization of CB2-Rs that are mainly on postsynaptic elements in rodent brain. Our data demonstrate the functional expression of CB2-Rs in the brain that may provide novel targets for the effects of cannabinoids in depression and substance abuse disorders beyond neuroimmunocannabinoid activity.

Brain neuronal CB2 cannabinoid receptors in drug abuse and depression: from mice to human subjects.

BACKGROUND: Addiction and major depression are mental health problems associated with stressful events in life with high relapse and reoccurrence even after treatment. Many laboratories were not able to detect the presence of cannabinoid CB2 receptors (CB2-Rs) in healthy brains, but there has been demonstration of CB2-R expression in rat microglial cells and other brain associated cells during inflammation. Therefore, neuronal expression of CB2-Rs had been ambiguous and controversial and its role in depression and substance abuse is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study we tested the hypothesis that genetic variants of CB2 gene might be associated with depression in a human population and that alteration in CB2 gene expression may be involved in the effects of abused substances including opiates, cocaine and ethanol in rodents. Here we demonstrate that a high incidence of (Q63R) but not (H316Y) polymorphism in the CB2 gene was found in Japanese depressed subjects. CB2-Rs and their gene transcripts are expressed in the brains of naïve mice and are modulated following exposure to stressors and administration of abused drugs. Mice that developed alcohol preference had reduced CB2 gene expression and chronic treatment with JWH015 a putative CB2-R agonist, enhanced alcohol consumption in stressed but not in control mice. The direct intracerebroventricular microinjection of CB2 anti-sense oligonucleotide into the mouse brain reduced mouse aversions in the plus-maze test, indicating the functional presence of CB2-Rs in the brain that modifies behavior. We report for the using electron microscopy the sub cellular localization of CB2-Rs that are mainly on post-synaptic elements in rodent brain. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate the functional expression of CB2-Rs in brain that may provide novel targets for the effects of cannabinoids in depression and substance abuse disorders beyond neuro-immunocannabinoid activity.

Association study between alcoholism and endocannabinoid metabolic enzyme genes encoding fatty acid amide hydrolase and monoglyceride lipase in a Japanese population.

BACKGROUND: Fatty acid amide hydrolase (FAAH) and monoglyceride lipase (MGLL) are the major endocannabinoid metabolic enzymes. Owing to the importance of endocannabinoid system in addiction, the Pro129Thr polymorphism in the FAAH gene has reportedly been associated with substance abuse and dependence in a Caucasian population. OBJECTIVE: To determine whether the single nucleodtide polymorphisms of the FAAH and MGLL genes are associated with alcoholism in a Japanese population. METHODS: We conducted case-control studies for total 14 tag single nucleotide polymorphisms in those two genes using Japanese 729 patients with alcoholism and 799 healthy controls. Genotype and allele frequencies were compared between these groups. RESULTS: None of these genetic markers, however, showed significant association with alcoholism in Japanese. CONCLUSION: Whereas we examined associations in a larger sample size between alcoholism and tag single nucleotide polymorphisms that covered most regions of these endocannabinoid metabolic enzyme genes, we found that these are not associated with susceptibility to alcoholism in a Japanese population.

Discovery of the presence and functional expression of cannabinoid CB2 receptors in brain.

Two well-characterized cannabinoid receptors (CBrs), CB1 and CB2, mediate the effects of cannabinoids and marijuana use, with functional evidence for other CBrs. CB1 receptors are expressed primarily in brain and peripheral tissues. For over a decade several laboratories were unable to detect CB2 receptors in brain and were known to be intensely expressed in peripheral and immune tissues and have traditionally been referred to as peripheral CB2 CBrs. We have reported the discovery and functional presence of CB2 cannabinoid receptors in mammalian brain that may be involved in depression and drug abuse and this was supported by reports of identification of neuronal CB2 receptors that are involved in emesis. We used RT-PCR, immunoblotting, hippocampal cultures, immunohistochemistry, transmission electron microscopy, and stereotaxic techniques with behavioral assays to determine the functional expression of CB2 CBrs in rat brain and mice brain exposed to chronic mild stress (CMS) or those treated with abused drugs. RT-PCR analyses supported the expression of brain CB2 receptor transcripts at levels much lower than those of CB1 receptors. In situ hybridization revealed CB2 mRNA in cerebellar neurons of wild-type but not of CB2 knockout mice. Abundant CB2 receptor immunoreactivity (iCB2) in neuronal and glial processes was detected in brain and CB2 expression was detected in neuron-specific enolase (NSE) positive hippocampal cell cultures. The effect of direct CB2 antisense oligonucleotide injection into the brain and treatment with JWH015 in motor function and plus-maze tests also demonstrated the functional presence of CB2 cannabinoid receptors in the central nervous system (CNS). Thus, contrary to the prevailing view that CB2 CBrs are restricted to peripheral tissues and predominantly in immune cells, we demonstrated that CB2 CBrs and their gene transcripts are widely distributed in the brain. This multifocal expression of CB2 immunoreactivity in brain suggests that CB2 receptors may play broader roles in the brain than previously anticipated and may be exploited as new targets in the treatment of depression and substance abuse.

Melatonin as a local regulator of human placental function.

Melatonin plays a critical role in a variety of mammalian reproductive processes not only acting on the central nervous system but also behaving as a peripheral physiologic regulator. To address the relevance of melatonin to the maintenance of pregnancy at the feto-maternal interface, we investigated the expression of two types of membrane melatonin receptors, MT1 and MT2, as well as arylalkylamine N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT), the two enzymes required for the conversion of serotonin to melatonin, in the human placenta and the effect of melatonin on the release of human chorionic gonadotropin (hCG) from cultured human trophoblast cells. RT-PCR analysis and DNA sequencing revealed that transcripts of MT1, MT2, AA-NAT, and HIOMT were present in the first-trimester human placenta. We also found that melatonin significantly potentiated hCG secretion at optimal concentrations. These results suggest that melatonin may regulate human placental function in a paracrine/autocrine manner, providing evidence for a novel role in human reproduction.