Description: The last deglaciation was characterized by a sequence of abrupt climate events thought to be linked to rapid changes in Atlantic meridional overturning circulation (AMOC). The sequence includes a weakening of the AMOC after the Last Glacial Maximum (LGM) during Heinrich Stadial 1 (HS1), which ends with an abrupt AMOC amplification at the transition to the Bølling/Allerød (B/A). This transition occurs despite persistent deglacial meltwater fluxes that counteract vigorous North Atlantic deep-water formation. Using the Earth system model COSMOS with a range of deglacial boundary conditions and reconstructed deglacial meltwater fluxes, we show that deglacial CO2 rise and ice sheet decline modulate the sensitivity of the AMOC to these fluxes. While declining ice sheets increase the sensitivity, increasing atmospheric CO2 levels tend to counteract this effect. Therefore, the occurrence of a weaker HS1 AMOC and an abrupt AMOC increase in the presence of meltwater, might be explained by these effects, as an alternative to or in combination with changes in the magnitude or routing of meltwater discharge.

Description: The cause of rapid hydrological changes in the tropical West Pacific during the last deglaciation remains controversial. In order to test whether these changes were triggered by abrupt climate change events in the North Atlantic Ocean, variations in precipitation during the last deglaciation (18–10 ka) were extracted from proxy records of chemical weathering and terrigenous input in the western Philippine Sea (WPS). The evolution of chemical weathering and terrigenous input since 27 ka was reconstructed using the chemical index of alteration (CIA), elemental ratios (K/Al, TOC/TN and Ti/Ca), δ13Corg, terrigenous fraction abundance and flux data from International Marine Global Change Study Program (IMAGES) core MD06-3054 collected on the upper continental slope of eastern Luzon (northern Philippines). Sediment deposited during the Last Glacial Maximum (LGM) shows weathering equal to or slightly greater than Holocene sediment in the WPS. This unusual state of chemical weathering, which is inconsistent with lower air temperatures and decreased precipitation in Luzon during the LGM, may be due to reworking of poorly consolidated sediments on the eastern Luzon continental shelf during the LGM sea-level lowstand. Rapid changes in chemical weathering, characterized by higher intensity during the Heinrich event 1 (H1) and Younger Dryas (YD) and lower intensity during the Bølling-Allerød (B/A), were linked to rapid variations in precipitation in the WPS during the last deglaciation. The higher terrigenous inputs during the LGM relative to those of the Holocene were controlled by sea-level changes rather than precipitation. The terrigenous inputs show a long-term decline during the last deglaciation, punctuated by brief spikes during the H1 and YD related to sea-level rises and rapid precipitation changes in the WPS, respectively. The proxy records of chemical weathering and terrigenous input from eastern Luzon suggest high rainfall during the H1 and YD events, consistent with inferred rainfall patterns based on Fe/Ca records from offshore Mindanao. Rapid precipitation changes in the WPS did not coincide with migrations of the Intertropical Convergence Zone (ITCZ) but, rather, were related to state shifts of the El Niño-Southern Oscillation (ENSO) during the last deglaciation. Based on proxy records and modeling results, we argue that the Atlantic meridional overturning circulation (AMOC) controlled rapid precipitation changes in the tropical West Pacific through zonal shifts of ENSO or meridional migration of the ITCZ during the last deglaciation. Our findings highlight the dominant role of the North Atlantic Ocean in the tropical hydrologic cycle during the last deglaciation.

Description: Climate models are potentially useful tools for addressing human dispersals and demographic change. The Arabian Peninsula is becoming increasingly significant in the story of human dispersals out of Africa during the Late Pleistocene. Although characterised largely by arid environments today, emerging climate records indicate that the peninsula was wetter many times in the past, suggesting that the region may have been inhabited considerably more than hitherto thought. Explaining the origins and spatial distribution of increased rainfall is challenging because palaeoenvironmental research in the region is in an early developmental stage. We address environmental oscillations by assembling and analysing an ensemble of five global climate models (CCSM3, COSMOS, HadCM3, KCM, and NorESM). We focus on precipitation, as the variable is key for the development of lakes, rivers and savannas. The climate models generated here were compared with published palaeoenvironmental data such as palaeolakes, speleothems and alluvial fan records as a means of validation. All five models showed, to varying degrees, that the Arabia Peninsula was significantly wetter than today during the Last Interglacial (130 ka and 126/125 ka timeslices), and that the main source of increased rainfall was from the North African summer monsoon rather than the Indian Ocean monsoon or from Mediterranean climate patterns. Where available, 104 ka (MIS 5c), 56 ka (early MIS 3) and 21 ka (LGM) timeslices showed rainfall was present but not as extensive as during the Last Interglacial. The results favour the hypothesis that humans potentially moved out of Africa and into Arabia on multiple occasions during pluvial phases of the Late Pleistocene.

Description: Background: Staphylococcus aureus is the major cause of hospital-acquired and community-acquired pneumonia. Host defense to S.aureus infection is largely mediated by the innate immune system. gammadelta T cells play an important role in innate immunity to many infectious diseases. However, less is known about the role of these cells during S.aureus-induced pneumonia. In this study, we examined the response and the role of gammadelta T cells to pulmonary S.aureusinfection. Results: Mice infected with S. aureus intranasally showed rapid gammadelta T cells accumulation in the lung. Deficiency of gammadelta T cells led to attenuated bacterial clearance and less tissue damage in lung compared with WT mice. Moreover, TCR-delta/mice exhibited impaired neutrophilrecruitment and reduced cytokine production at the site of infection. The gammadelta T cells in response to pulmonary S. aureus infection mainly secreted IL-17 and gammadelta T cells deficiency reduced IL-17 production, which might regulate the production of neutrophil-inducingcytokine/chemokine in the S. aureus-infected lungs Conclusions: Accumulation of gammadelta T cells in the lungs to S. aureus infection is beneficial for bacteria clearance and also contributes to the tissue damage. These cells were the primary source of IL-17, which might influence the recruitment of neutrophils at the early stage of infection.

Description: Background: The mechanisms that underlie autophagy in cerebral ischemia remain poorly defined. Myeloid cell leukemia-1 (Mcl1), an anti-apoptotic member of the Bcl-2 family of proteins, regulates the balance between autophagy and apoptosis. However, little is known regarding its expression profile and contribution to cell fate in the brain following ischemic stroke. Results: In this study, we investigated the expression profile and cellular distribution of Mcl1 in brains from transient middle cerebral artery occlusion (MCAO) model rats. Brain slices from sham-operated control rats showed minimal immunoreactivity for Mcl1. Mcl1 was mainly produced in neurons. Immunoreactivity for Mcl1 increased as early as 4 hours after MCAO, peaked at 24 hours, and then declined, but still remained high, at 72 hours. Mcl1 positive cells never colocalized with either cleaved caspase-3 or terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells. Both microtubule-associated protein 1 light chain 3 (LC3) and beclin-1 were evident in ischemic brain between 4 and 72 hours after MCAO. Most cells with strong LC3 staining were also labeled with beclin-1. Beclin-1 did colocalize with caspase-3 or Mcl1. Beclin-1/caspase-3 positive cells displayed the characteristic features of apoptosis including cell shrinkage and pyknotic nuclei, whereas beclin-1/Mcl1 positive cells had normal morphology. Pretreatment with 3-methyladenine attenuated autophagy without affecting the level of Mcl1 protein. Conclusions: These findings demonstrate that the expression of Mcl1 is involved in the survival of neuronal cells. In addition, the coexpression of Mcl1 with beclin-1 may attenuate beclin-1-dependent autophagy during ischemic stroke in rats.

Description: Background: High-resolution cytogenetic map can provide not only important biological information on genome organization but also solid foundation for genetic and genomic research. The progress in the molecular and cytogenetic studies has created the basis for developing the cytogenetic map in cucumber (Cucumis sativus L.). Results: Here, the cytogenetic maps of four cucumber chromosomes (chromosomes 1, 3--5) were constructed by fluorescence in situ hybridization (FISH) analysis on cucumber pachytene chromosomes. Together with our previously constructed cytogenetic maps of three cucumber chromosomes (chromosomes 2, 6--7), cucumber has a complete cytogenetic map with 76 anchoring points between the genetic, the cytogenetic and the draft genome assembly maps. To compare our pachytene FISH map directly to the genetic linkage and draft genome assembly maps, we used a standardized map unit---relative map position (RMP) to produce the comparative map alignments. The alignments allowed a global view of the relationship of genetic and physical distances along each cucumber chromosome, and accuracy and coverage of the draft genome assembly map. Conclusions: We demonstrated a good correlation between positions of the markers in the linkage and physical maps, and essentially complete coverage of chromosome arms by the draft genome assembly. Our study not only provides essential information for the improvement of sequence assembly but also offers molecular tools for cucumber genomics research, comparative genomics and evolutionary study.

Description: Highlights: • Climate model sensitivity experiments are performed using state-of-the-art ice sheet and freshwater reconstructions • Declining Northern Hemisphere ice sheets increase the sensitivity of the AMOC to North Atlantic meltwater discharge • Deglacial rise in atmospheric CO2 concentration decreases the sensitivity of the AMOC to North Atlantic meltwater discharge • Both effects provide a complementary perspective to existing explanations for abrupt AMOC transitions Abstract: The last deglaciation was characterized by a sequence of abrupt climate events thought to be linked to rapid changes in Atlantic meridional overturning circulation (AMOC). The sequence includes a weakening of the AMOC after the Last Glacial Maximum (LGM) during Heinrich Stadial 1 (HS1), which ends with an abrupt AMOC amplification at the transition to the Bølling/Allerød (B/A). This transition occurs despite persistent deglacial meltwater fluxes that counteract vigorous North Atlantic deep-water formation. Using the Earth system model COSMOS with a range of deglacial boundary conditions and reconstructed deglacial meltwater fluxes, we show that deglacial CO2 rise and ice sheet decline modulate the sensitivity of the AMOC to these fluxes. While declining ice sheets increase the sensitivity, increasing atmospheric CO2 levels tend to counteract this effect. Therefore, the occurrence of a weaker HS1 AMOC and an abrupt AMOC increase in the presence of meltwater, might be explained by these effects, as an alternative to or in combination with changes in the magnitude or routing of meltwater discharge.

Description: Background: We have recovered one bla NDM-1-harboring bacterial strain, designated as XM1570, from a sputum sample obtained from a fatal case of pneumonia in China. Methods: Biochemical profiling, 16S rRNA sequencing and antimicrobial susceptibility testing were performed. Conjugation experiments were conducted to determine transmissibility of resistance. Pulsed-field gel electrophoresis and whole genome sequencing were performed to identify strain-specific features. Results: The isolate XM1570 was identified as Acinetobacter calcoaceticus. Whole genome sequencing identified two plasmids, pXM1 and pXM2. Comparative analysis showed 〉99% similarity between XM1570 and A. calcoaceticus PHEA-2. Plasmid pXM1 carried the carbapenemase gene bla NDM-1 and displayed high homology with previously described plasmids isolated from different Acinetobacter spp., which were collected from human or livestock distributed in China and worldwide. The bla NDM-1 gene was located on this conjugative plasmid in a transposon-like region flanked by two copies of the insertion sequence ISAba125; and resistance to all tested β-lactams was observed. Transferability of resistance from pXM1 to the transconjugants was identified. Plasmid pXM2 had an insertion sequence ISAba125 and a −35 region of the bla NDM-1 gene promoter but the bla NDM-1 gene was not present. A chromosomally located carbapenemase-encoding gene bla OXA-75 was detected; however, this gene was interrupted by an insertion sequence ISAba22 belonging to IS3 family. Conclusions: Location of bla NDM-1 on different self-transmissible plasmids could facilitate geographically broad dissemination and host range expansion of the bla NDM-1 gene via horizontal gene transfer. Our findings of this normally environmental species A. calcoaceticus XM1570 further underline the significant clinical challenge and the essential need for surveillance including molecular methods and plasmid analyses.

Description: Background: Breast cancer stem cells (BCSCs) have been reported as the origin of breast cancer and the radical cause of drug resistance, relapse and metastasis in breast cancer. BCSCs could be derived from mutated mammary epithelial stem cells (MaSCs). Therefore, comparing the molecular differences between BCSCs and MaSCs may clarify the mechanism underlying breast carcinogenesis and the targets for gene therapy. Specifically, the distinct miRNome data of BCSCs and MaSCs need to be analyzed to find out the key miRNAs and reveal their roles in regulating the stemness of BCSCs. Methods: MUC1 − ESA + cells were isolated from normal mammary epithelial cell line MCF-10A by fluorescence-activated cell sorting (FACS) and tested for stemness by clonogenic assay and multi-potential differentiation experiments. The miRNA profiles of MaSCs, BCSCs and breast cancer MCF-7 cells were compared to obtain the candidate miRNAs that may regulate breast tumorigenesis. An miRNA consecutively upregulated from MaSCs to BCSCs to MCF-7 cells, miR-200c, was chosen to determine its role in regulating the stemness of BCSCs and MaSCs in vitro and in vivo. Based on bioinformatics, the targets of miR-200c were validated by dual-luciferase report system, western blot and rescue experiments. Results: In a 2-D clonogenic assay, MUC1 − ESA + cells gave rise to multiple morphological colonies, including luminal colonies, myoepithelial colonies and mixed colonies. The clonogenic potential of MUC1 − ESA + (61.5 ± 3.87 %) was significantly higher than that of non-stem MCF-10A cells (53.5 ± 3.42 %) (P 

Description: Acute diarrhea is a leading cause of morbidity and mortality in children, particularly in those under the age of 5 years. Rotavirus is recognized as the leading cause of acute diarrhea in children, however, the c...