Birth intervention and non-maternal infant-handling during parturition in a nonhuman primate

Direct intervention in infant delivery by non-parturient individuals is a rare phenomenon in nonhuman primates. In contrast, birth assistance by other individuals, or the practice of midwifery, is universal among human societies and generally believed to be a behavior unique to our species. It has been proposed that the enlarged head of the human fetus and the relatively narrow birth canal constrained by bipedalism has made human parturition more difficult than in nonhuman primates, and these anatomic challenges have led to the rotation of the fetus in the birth canal and an occiput anterior (i.e., backward-facing) orientation of emergence. These characteristics have hindered the mother’s ability to self-assist the delivery of the infant, therefore necessitating assistance by other individuals or midwives for successful birth. Here we report the first high-definition video recordings of birth intervention behavior in a wild nonhuman primate, the white-headed langur (Trachypithecus leucocephalus). We observed that while a primiparous female gave birth to an infant in an occiput posterior (i.e., forward-facing) orientation, a multiparous female intervened in the delivery by manually pulling the infant out of the birth canal and cared for it in the following hours. Our finding shows extensive social interactions throughout parturition, and presents an unequivocal case of non-maternal intervention with infant birth in a nonhuman primate.     

Activation of STAT3 stimulates AHSP expression in K562 cells

Studies on the chaperone proteinα-hemoglobin stabilizing protein(AHSP)reveal that abundant AHSP in erythroid cells enhance the cells’tolerance to oxidative stress imposed by excessα-hemoglobin in pathological conditions.However,the potential intracellular modulation of AHSP expression itself in response to oxidative stress is still unknown.The present study examined the effect and molecular mechanism of STAT3,an oxidative regulator,on the expression of AHSP.AHSP expression increased in K562 cells upon cytokine IL-6-induced STAT3 activation and decreased in STAT3 knock-down K562 cells.Regulation of AHSP in oxidative circumstance was then examined inα-globin-overloaded K562 cells,and real-time PCR showed strengthened expression of both AHSP and STAT3.ChIP analysis showed binding of STAT3 to AHSP promoter and binding was significantly augmented with IL6 stimulation and uponα-globin overexpression.Dual luciferase reporter assays of the wildtype and mutated SB3 element,an IL-6RE site,in the AHSP promoter in K562 cells highlighted the direct regulatory effect of STAT3 on AHSP gene.Finally,direct binding of STAT3 to SB3 site of AHSP promoter was confirmed with EMSA assays.Our work reveals an adaptive AHSP regulation mediated by the redox-sensitive STAT3 signaling pathway,and provides clues to the therapeutic strategy for AHSP enhancement.     

A B3LYP and MP2(full) theoretical investigation into cooperativity effects,aromaticity and thermodynamic properties in the Na+⋯benzonitrile⋯H2O ternary complex

In this work the growth of a graphene monolayer on copper substrate, as typically achieved via chemical vapor deposition of propene (C₃H₆), was investigated by first-principles and kinetic Monte Carlo calculations. A comparison between calculated C1s core-level binding energies and electron spectroscopy measurements showed that graphene nucleates from isolated carbon atoms adsorbed on surface defects or sub-superficial layers upon hydrocarbon fragmentation. In this respect, ab initio nudged elastic band simulations yield the energetic barriers characterizing the diffusion of elemental carbon on the Cu(111) surface and atomic carbon uptake by the growing graphene film. Our calculations highlight a strong interaction between the growing film edges and the copper substrate, indicative of the importance of the grain boundaries in the epitaxy process. Furthermore, we used activation energies to compute the reaction rates for the different mechanisms occurring at the carbon–copper interface via harmonic transition state theory. Finally, we simulated the long-time system growth evolution through a kinetic Monte Carlo approach for different temperatures and coverage. Our ab initio and Monte Carlo simulations of the out-of-equilibrium system point towards a growth model strikingly different from that of standard film growth. Graphene growth on copper turns out to be a catalytic, thermally-activated process that nucleates from carbon monomers, proceeds by adsorption of carbon atoms, and is not self-limiting. Furthermore, graphene growth seems to be more effective at carbon supersaturation of the surface—a clear fingerprint of a large activation barrier for C attachment. Our growth model and computational results are in good agreement with recent X-ray photoelectron spectroscopy experimental measurements.     

Uncovering the pathogenesis and identifying novel targets of pancreatic cancer using bioinformatics approach

Pancreatic cancer is a uniformly lethal disease that can be difficult to diagnose at its early stage. Thus, our present study aimed to explore the underlying mechanism and identify new targets for this disease. The data GSE16515, including 36 tumor and 16 normal samples were available from Gene Expression Omnibus. Differentially expressed genes (DEGs) were screened out using Robust Multichip Averaging and LIMMA package. Moreover, gene ontology and pathway enrichment analyses were performed to DEGs. Followed with protein–protein interaction (PPI) network construction by STRING and Cytoscape, module analysis was conducted using ClusterONE. Finally, based on PubMed, text mining about these DEGs was carried out. Total 274 up-regulated and 93 down-regulated genes were identified as the common DEGs and these genes were discovered significantly enriched in cell adhesion and extracellular region terms, as well as ECM-receptor interaction pathway. In addition, five modules were screened out from the up-regulated PPI network with none in down-regulated network. Finally, the up-regulated genes, including MIA, MET and CEACAMS, and down-regulated genes, such as FGF, INS and LAPP, had the most references in text mining analysis. Our findings demonstrate that the up- and down-regulated genes play important roles in pancreatic cancer development and might be new targets for the therapy.     

Pierisformotoxins A – D,Polyesterified Grayanane Diterpenoids from Pieris formosa and Their cAMP‐Decreasing Activities

Four highly acylated diterpenoids, designated as pierisformotoxins A–D ( 1 – 4 , resp.), along with 26 known compounds, were isolated from the flowers of Pieris formosa. Among them, pierisformotoxins A and B ( 1 and 2 , resp.) were new highly acylated grayanane diterpenoids, of which the five‐membered ring A has undergone an oxidative cleavage between C(3) and C(4), followed by lactonization, to give rise to a five‐membered lactone ring between C(3) and C(5), differing from the previously reported grayanane diterpenoids with a 5/7/6/5 ring system. Results of the cAMP‐regulation‐activity assay showed that pierisformotoxin C ( 3 ) at 10 μM (inhibitory ratio (IR): 10.1%) or 2 μM (9.8%), and pierisformotoxin B ( 2 ) at 50 μM (13.9%) significantly decreased the cAMP level in N1E‐115 neuroblastoma cells (p<0.05).     

The Possible Structural Models for Polyglutamine Aggregation: A Molecular Dynamics Simulations Study

Abstract

Huntington's disease is a neurodegenerative disorder caused by a polyglutamine (polyQ) expansion near the N-terminus of huntingtin. Previous studies have suggested that polyQ aggregation occurs only when the number of glutamine (Q) residues is more than 36-40, the disease threshold. However, the structural characteristics of polyQ nucleation in the very early stage of aggregation still remain elusive. In this study, we designed 18 simulation trials to determine the possible structural models for polyQ nucleation and aggregation with various shapes and sizes of initial β-helical structures, such as left-handed circular, right-handed rectangular, and left- and right-handed triangular. Our results show that the stability of these models significantly increases with increasing the number of rungs, while it is rather insensitive to the number of Qs in each rung. In particular, the 3-rung β-helical models are stable when they adopt the left-handed triangular and right-handed rectangular conformations due to the fact that they preserve high β-turn and β-sheet contents, respectively, during the simulation courses. Thus, we suggested that these two stable β-helical structures with at least 3 rungs might serve as the possible nucleation seeds for polyQ depending on how the structural elements of β-turn and β-sheet are sampled and preserved during the very early stage of aggregation.     

Blocking OLFM4/HIF-1α axis alleviates hypoxia-induced invasion,epithelial–mesenchymal transition,and chemotherapy resistance in non-small-cell lung cancer

Hypoxia is a common biological hallmark of solid cancers, which has been proposed to be associated with oncogenesis and chemotherapy resistance. The purpose of the present study was to investigate the role and underlying mechanisms of olfactomedin 4 (OLFM4) in the hypoxia-induced invasion, epithelial–mesenchymal transition (EMT), and chemotherapy resistance of non-small-cell lung cancer (NSCLC). We observed dramatically upregulated expression of OLFM4 in several NSCLC cell lines, and this effect was more pronounced in A549 and H1299 cells. In addition, our data revealed that OLFM4 expression was remarkably increased in both A549 and H1299 cells under hypoxic microenvironment, accompanied by enhanced levels of hypoxia-inducible factor (HIF)-1α protein. The HIF-1α level was elevated in response to hypoxia, resulting in the regulation of OLFM4. Interestingly, OLFM4 was a positive regulator of hypoxia-driven HIF-1α production. Moreover, depletion of OLFM4 modulated multiple EMT-associated proteins, as evidenced by the enhanced E-cadherin levels along with the diminished expression of N-cadherin and vimentin in response to hypoxia, and thus blocked invasion ability of A549 and H1299 cells following exposure to hypoxia. Furthermore, ablation of OLFM4 accelerated the sensitivity of A549 cells to cisplatin under hypoxic conditions, implying that OLFM4 serves as a key regulator in chemotherapeutic resistance under hypoxia. In conclusion, OLFM4/HIF-1α axis might be a potential therapeutic strategy for NSCLC.     

Heterotrophic carbon metabolism and energy acquisition in Candidatus Thioglobus singularis strain PS1, a member of the SUP05 clade of marine Gammaproteobacteria

A hallmark of the SUP05 clade of marine Gammaproteobacteria is the ability to use energy obtained from reduced inorganic sulfur to fuel autotrophic fixation of carbon using RuBisCo. However, some SUP05 also have the genetic potential for heterotrophic growth, raising questions about the roles of SUP05 in the marine carbon cycle. We used genomic reconstructions, physiological growth experiments and proteomics to characterize central carbon and energy metabolism in Candidatus Thioglobus singularis strain PS1, a representative from the SUP05 clade that has the genetic potential for autotrophy and heterotrophy. Here, we show that the addition of individual organic compounds and 0.2 μm filtered diatom lysate significantly enhanced the growth of this bacterium. This positive growth response to organic substrates, combined with expression of a complete TCA cycle, heterotrophic pathways for carbon assimilation, and methylotrophic pathways for energy conversion demonstrate strain PS1's capacity for heterotrophic growth. Further, our inability to verify the expression of RuBisCO suggests that carbon fixation was not critical for growth. These results highlight the metabolic diversity of the SUP05 clade that harbours both primary producers and consumers of organic carbon in the oceans and expand our understanding of specific pathways of organic matter oxidation by the heterotrophic SUP05.