Deciphering social traits and pathophysiological conditions from natural behaviors in common marmosets.

Nonhuman primates (NHPs) are indispensable animal models by virtue of the continuity of behavioral repertoires across primates, including humans. However, behavioral assessment at the laboratory level has so far been limited. Employing the application of three-dimensional (3D) pose estimation and the optimal integration of subsequent analytic methodologies, we demonstrate that our artificial intelligence (AI)-based approach has successfully deciphered the ethological, cognitive, and pathological traits of common marmosets from their natural behaviors. By applying multiple deep neural networks trained with large-scale datasets, we established an evaluation system that could reconstruct and estimate the 3D poses of the marmosets, a small NHP that is suitable for analyzing complex natural behaviors in laboratory setups. We further developed downstream analytic methodologies to quantify a variety of behavioral parameters beyond motion kinematics. We revealed the distinct parental roles of male and female marmosets through automated detections of food-sharing behaviors using a spatial-temporal filter on 3D poses. Employing a recurrent neural network to analyze 3D pose time series data during social interactions, we additionally discovered that marmosets adjusted their behaviors based on others' internal state, which is not directly observable but can be inferred from the sequence of others' actions. Moreover, a fully unsupervised approach enabled us to detect progressively appearing symptomatic behaviors over a year in a Parkinson's disease model. The high-throughput and versatile nature of an AI-driven approach to analyze natural behaviors will open a new avenue for neuroscience research dealing with big-data analyses of social and pathophysiological behaviors in NHPs.

Global oceanic oxygenation controlled by the Southern Ocean through the last deglaciation.

Ocean dissolved oxygen (DO) can provide insights on how the marine carbon cycle affects global climate change. However, the net global DO change and the controlling mechanisms remain uncertain through the last deglaciation. Here, we present a globally integrated DO reconstruction using thallium isotopes, corroborating lower global DO during the Last Glacial Maximum [19 to 23 thousand years before the present (ka B.P.)] relative to the Holocene. During the deglaciation, we reveal reoxygenation in the Heinrich Stadial 1 (~14.7 to 18 ka B.P.) and the Younger Dryas (11.7 to 12.9 ka B.P.), with deoxygenation during the Bølling-Allerød (12.9 to 14.7 ka B.P.). The deglacial DO changes were decoupled from North Atlantic Deep Water formation rates and imply that Southern Ocean ventilation controlled ocean oxygen. The coherence between global DO and atmospheric CO2 on millennial timescales highlights the Southern Ocean's role in deglacial atmospheric CO2 rise.

Surface climate signals transmitted rapidly to deep North Atlantic throughout last millennium.

Instrumental observations of subsurface ocean warming imply that ocean heat uptake has slowed 20th-century surface warming. We present high-resolution records from subpolar North Atlantic sediments that are consistent with instrumental observations of surface and deep warming/freshening and in addition reconstruct the surface-deep relation of the last 1200 years. Sites from ~1300 meters and deeper suggest an ~0.5 degrees celsius cooling across the Medieval Climate Anomaly to Little Ice Age transition that began ~1350 ± 50 common era (CE), whereas surface records suggest asynchronous cooling onset spanning ~600 years. These data suggest that ocean circulation integrates surface variability that is transmitted rapidly to depth by the Atlantic Meridional Ocean Circulation, implying that the ocean moderated Earth's surface temperature throughout the last millennium as it does today.

Fibroblast subtypes in pancreatic cancer and pancreatitis: from mechanisms to therapeutic strategies.

Excessive fibrosis is a predominant feature of pancreatic stroma and plays a crucial role in the development and progression of pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). Emerging evidence showed diversity and heterogeneity of fibroblasts play crucial and somewhat contradictory roles, the interactions between fibroblasts and pancreatic cells or infiltrating immune cells are of great importance during PDAC and CP progression, with some promising therapeutic strategies being tested. Therefore, in this review, we describe the classification of fibroblasts and their functions in PDAC and pancreatitis, the mechanisms by which fibroblasts mediate the development and progression of PDAC and CP through direct or indirect interaction between fibroblast and pancreatic parenchymal cells, or by remodeling the pancreatic immune microenvironment mediates the development and progression of PDAC and CP. Finally, we summarized the current therapeutic strategies and agents that directly target subtypes of fibroblasts or interfere with their essential functions.

Reduction in animal abundance and oxygen availability during and after the end-Triassic mass extinction.

The end-Triassic biodiversity crisis was one of the most severe mass extinctions in the history of animal life. However, the extent to which the loss of taxonomic diversity was coupled with a reduction in organismal abundance remains to be quantified. Further, the temporal relationship between organismal abundance and local marine redox conditions is lacking in carbonate sections. To address these questions, we measured skeletal grain abundance in shallow-marine limestones by point counting 293 thin sections from four stratigraphic sections across the Triassic/Jurassic boundary in the Lombardy Basin and Apennine Platform of western Tethys. Skeletal abundance decreased abruptly across the Triassic/Jurassic boundary in all stratigraphic sections. The abundance of skeletal organisms remained low throughout the lower-middle Hettangian strata and began to rebound during the late Hettangian and early Sinemurian. A two-way ANOVA indicates that sample age (p < .01, η2  = 0.30) explains more of the variation in skeletal abundance than the depositional environment or paleobathymetry (p < .01, η2  = 0.15). Measured I/Ca ratios, a proxy for local shallow-marine redox conditions, show this same pattern with the lowest I/Ca ratios occurring in the early Hettangian. The close correspondence between oceanic water column oxygen levels and skeletal abundance indicates a connection between redox conditions and benthic organismal abundance across the Triassic/Jurassic boundary. These findings indicate that the end-Triassic mass extinction reduced not only the biodiversity but also the carrying capacity for skeletal organisms in early Hettangian ecosystems, adding to evidence that mass extinction of species generally leads to mass rarity among survivors.

Inhibition of lung cancer by vitamin D depends on downregulation of histidine-rich calcium-binding protein.

Introduction: Intrinsic vitamin D affects the proliferation, apoptosis, invasion, metastasis, and tumorigenesis of lung cancer by regulating tumor signaling pathways. Histidine-rich calcium-binding protein (HRC) maintains Ca2+ homeostasis, which plays crucial roles in the occurrence and development of cancer. Objectives: Our study aims to investigate the ability of vitamin D in the regulation of HRC and the role of HRC playing in lung cancer. Methods: We investigated the effects of vitamin D on lung cancer and the underlying mechanisms, by measuring HRC and vitamin D receptor (VDR) expression in lung cancer, paracancer, and normal tissues from patients using immunohistochemistry, western blotting, and real time RT-PCR. We transfected H460 lung cancer cells (supplemented or not with vitamin D) with PX458-HRC and pcDNA3.1-HRC plasmids and injected mice with lung cancer cells harboring pcDNA3.1-vector or pcDNA3.1-HRC plasmids. Results: Vitamin D inhibited HRC expression and H460 cell migration and proliferation, and promoted apoptosis compared with controls. The expression of HRC and VDR was significantly upregulated and downregulated, respectively, in lung cancer versus paracancer or normal tissues. Cell proliferation and migration were reduced, apoptotic cells were more and tumors were smaller in mice treated with vitamin D/cholecalciferol cholesterol emulsion (CCE) than in vitamin D/CCE+HRC+/+ mice. Conclusion: Vitamin D inhibited lung cancer tumor growth, migration, and proliferation by downregulating HRC.

Vitamin D Attenuates Alzheimer-like Pathology Induced by Okadaic Acid.

Many elderly individuals suffer from Alzheimer's disease (AD), which causes a growing concern. We investigated the mechanism underlying the effects of vitamin D (VD) as a prophylactic treatment. A mouse model of okadaic-acid-induced AD-like pathology was used in vivo and in vitro. Morris water maze and field trials were used to assess cognitive function. The expression levels of VDR, MTHFR, LCMT-1, PP2A, p-TAU (Thr396), and T-TAU and the methylation level of PP2A were measured by Western blotting, and a reversal of the increase in the levels of these proteins in an AD cell model was observed. We used MTHFR-knockdown SH-SY5Y cells to further test the effects of VD, treated these cells with cycloheximide and MG132, and used RT-PCR to explore the mechanism underlying MTHFR targeting. We found that the effects of VD on AD were impaired by MTHFR knockdown through a pretranscriptional mechanism. In addition, VD attenuated AD-induced cognitive impairment and significantly suppressed the expression of TAU. Our findings indicated that VD treatment alleviated TAU accumulation and rescued methylated PP2A by increasing the expression of LCMT-1 and MTHFR.

Vitamin D alleviates liver fibrosis by inhibiting histidine-rich calcium binding protein (HRC).

BACKGROUND: Liver fibrosis may progress toward cirrhosis and cancer without effective therapy. Here, we investigated the underlying mechanism of Vitamin D as a therapeutic approach. METHODS: Carbon tetrachloride (CCL4)-induced mice model and transforming growth factor-ß1 (TGF-ß1) induced human hepatic stellate cell line LX-2 were used in vivo and in vitro. The fibrotic profiles, degree of liver injury and HRC expression were assessed by histology, Western blot, immunohistochemistry and Real-Time PCR. The proliferation of cells transfected with HRC +/+ and HRC-/- plasmids was detected by MTS and cell cycle methods. RESULTS: Vitamin D significantly suppressed the expression of HRC in liver fibrosis model both in vivo and in vitro (P < 0.01). The cell with overexpression of HRC significantly increased TGF-ß1/Smad3 expressions and the percentage of the S peak in cell cycle (P < 0.05). However, Vitamin D can significantly reverse the levels of TGF-ß1, Smad3 and p-smad3 caused by HRC in vitro. Furthermore, the overexpression of HRC in cell lines can attenuate the function of Vitamin D, suggesting that VD played a role by regulating HRC. Mechanically, HRC as the target of VDR is detected by CHIP method. CONCLUSIONS: Vitamin D can delay hepatic fibrosis by reducing activation of hepatic stellate cells and TGF-ß/Smad signaling through negative regulation of HRC. The findings revealed the important regulatory effect of Vitamin D in hepatic stellate cells and provided new insights into the therapeutic function of Vitamin D on liver fibrosis.

Late inception of a resiliently oxygenated upper ocean.

Rising oceanic and atmospheric oxygen levels through time have been crucial to enhanced habitability of surface Earth environments. Few redox proxies can track secular variations in dissolved oxygen concentrations around threshold levels for metazoan survival in the upper ocean. We present an extensive compilation of iodine-to-calcium ratios (I/Ca) in marine carbonates. Our record supports a major rise in the partial pressure of oxygen in the atmosphere at ~400 million years (Ma) ago and reveals a step change in the oxygenation of the upper ocean to relatively sustainable near-modern conditions at ~200 Ma ago. An Earth system model demonstrates that a shift in organic matter remineralization to greater depths, which may have been due to increasing size and biomineralization of eukaryotic plankton, likely drove the I/Ca signals at ~200 Ma ago.

Oxygen depletion recorded in upper waters of the glacial Southern Ocean.

Oxygen depletion in the upper ocean is commonly associated with poor ventilation and storage of respired carbon, potentially linked to atmospheric CO2 levels. Iodine to calcium ratios (I/Ca) in recent planktonic foraminifera suggest that values less than ∼2.5 µmol mol(-1) indicate the presence of O2-depleted water. Here we apply this proxy to estimate past dissolved oxygen concentrations in the near surface waters of the currently well-oxygenated Southern Ocean, which played a critical role in carbon sequestration during glacial times. A down-core planktonic I/Ca record from south of the Antarctic Polar Front (APF) suggests that minimum O2 concentrations in the upper ocean fell below 70 µmol kg(-1) during the last two glacial periods, indicating persistent glacial O2 depletion at the heart of the carbon engine of the Earth's climate system. These new estimates of past ocean oxygenation variability may assist in resolving mechanisms responsible for the much-debated ice-age atmospheric CO2 decline.

Are social security policies for Chinese landless farmers really effective on health in the process of Chinese rapid urbanization? A study on the effect of social security policies for Chinese landless farmers on their health-related quality of life.

BACKGROUND: The continuing urbanization in China has resulted in a loss of land and rights among farmers. The social security of landless farmers has attracted considerable research attention. However, only few studies measure the health-related quality of life (HRQOL) of landless farmers by employing scientific standardized scales. By using five-dimensional European quality of life (EQ-5D) scales, this study measures the HRQOL of landless farmers from a new perspective and examines how the social security policies affect their HRQOL. METHODS: This study is based on a 2013 household survey that has been conducted among 1,500 landless famers who are residing in six resettlement areas in three cities within the Yangtze River Delta region, namely, Nanjing, Hangzhou, and Yangzhou. This study adopts EQ-5D scales to measure the HRQOL of these farmers. More than 50% of the respondents are in poor or non-serious health conditions, and over 50% are not satisfied with their current social security policies. The health conditions and social security policies are analyzed by multinomial regression analysis and the relationship between these two factors are analyzed via structural equation modeling (SEM). RESULTS: First, the descriptive statistical analysis shows that more than 50% of the respondents are in poor or non-serious health conditions, and that the largest proportion of these farmers are suffering from anxiety or depression, which is the most serious of the five dimensions. Second, multinomial regression analysis shows that the satisfaction of landless farmers with their social security policies improves their living conditions, particularly in their capacity for self-care, in their ability to perform daily activities, and in the reduction of pain, anxiety, and depression. Third, SEM model analysis shows that the satisfaction of landless farmers with their social security policies positively influences their HRQOL. Among the five dimensions of EQ-5D, daily activities produce the greatest influence on the HRQOL of landless farmers. As regards social security policies, the land acquisition compensation policy and the employment security policy produce the greatest and weakest influences on the HRQOL of landless farmers, respectively. CONCLUSIONS: The rapid urbanization in China has deprived many farmers of their lands and of the benefits of urbanization. These farmers are often in a disadvantaged position in the land acquisition process. Statistic analysis in this paper shows that the satisfaction of landless farmers with their social security policies positively influences their HRQOL. The implementation and improvement of social security policies is very important for the long-term and sustainable development of these landless farmers.