High mobility group box-1 in hypothalamic paraventricular nuclei attenuates sympathetic tone in rats at post-myocardial infarction

Background: Inflammation is associated with increased sympathetic drive in cardiovascular diseases. The paraventricular nucleus (PVN) of the hypothalamus is a key regulator of sympathetic nerve activity at post-myocardial infarction (MI). High mobility group box-1 (HMGB1) exhibits inflammatory cytokine like activity in the extracellular space. Inflammation is associated with increased sympathetic drive in cardiovscular diseases. However, the role of HMGB1 in sympathetic nerve activity at post-MI remains unknown. The aim of the present study is to determine the role and mechanism of HMGB1 in the PVN, in terms of sympathetic activity and arrhythmia after MI. Methods: Sprague-Dawley rats underwent left anterior descending coronary artery ligation to induce MI. Anti-HMGB1 polyclonal antibody or control IgG was bilaterally microinjected into the PVN (5 μL every second day for seven consecutive days). Then, renal sympathetic nerve activity (RSNA) was recorded. The association between ventricular arrhythmias (VAs) and MI was evaluated using programmedelectrophysiological stimulation. After performing electrophysiological experiments in vivo, immunohistochemistry was used to detect the distribution of HMGB1, while Western blot was used to detect the expression of HMGB1 and p-ERK in the PVN of MI rats. Results: HMGB1 and p-ERK were upregulated in the PVN in rats at post-MI. Moreover, bilateral PVN microinjection of anti-HMGB1 polyclonal antibody reversed the expression of HMGB1 and p-ERK, and consequently decreased the baseline RSNA and inducible VAs, when compared to those in sham rats. Conclusions: These results suggest that MI causes the translocation of HMGB1 in the PVN, which leads to sympathetic overactivation through the ERK1/2 signaling pathway. The bilateral PVN microinjection of anti-HMGB1 antibody can be an effective therapy for MI-induced arrhythmia

Testing a hypothesis of unidirectional hybridization in plants: Observations on Sonneratia, Bruguiera and Ligularia

<p>Abstract</p> <p>Background</p> <p>When natural hybridization occurs at sites where the hybridizing species differ in abundance, the pollen load delivered to the rare species should be predominantly from the common species. Previous authors have therefore proposed a hypothesis on the direction of hybridization: interspecific hybrids are more likely to have the female parent from the rare species and the male parent from the common species. We wish to test this hypothesis using data of plant hybridizations both from our own experimentation and from the literature.</p> <p>Results</p> <p>By examining the maternally inherited chloroplast DNA of 6 cases of F1 hybridization from four genera of plants, we infer unidirectional hybridization in most cases. In all 5 cases where the relative abundance of the parental species deviates from parity, however, the direction is predominantly in the direction opposite of the prediction based strictly on numerical abundance.</p> <p>Conclusion</p> <p>Our results show that the observed direction of hybridization is almost always opposite of the predicted direction based on the relative abundance of the hybridizing species. Several alternative hypotheses, including unidirectional postmating isolation and reinforcement of premating isolation, were discussed.</p

Large-gap quantum anomalous Hall states induced by functionalizing buckled Bi-III monolayer/Al2_{2}O3_{3}

Chiral edge modes inherent to the topological quantum anomalous Hall (QAH) effect are a pivotal topic of contemporary condensed matter research aiming at future quantum technology and application in spintronics. A large topological gap is vital to protecting against thermal fluctuations and thus enabling a higher operating temperature. From first-principle calculations, we propose Al$_{2}$O$_{3}$ as an ideal substrate for atomic monolayers consisting of Bi and group-III elements, in which a large-gap quantum spin Hall effect can be realized. Additional half-passivation with nitrogen then suggests a topological phase transition to a large-gap QAH insulator. By effective tight-binding modelling, we demonstrate that Bi-III monolayer/Al$_{2}$O$_{3}$ is dominated by $p_{x}, p_{y}$ orbitals, with subdominant $p_z$ orbital contributions. The topological phase transition into the QAH is induced by Zeeman splitting, where the off-diagonal spin exchange does not play a significant role. The effective model analysis promises utility far beyond Bi-III monolayer/Al$_{2}$O$_{3}$, as it should generically apply to systems dominated by $p_{x}, p_{y}$ orbitals with a band inversion at $\Gamma$.Comment: 9 pages with 4 figure

Ancient geograpical barriers drive differentiation among Sonneratia caseolaris populations and recent divergence from S. Ianceolata

Glacial vicariance is thought to influence population dynamics and speciation of many marine organisms. Mangroves, a plant group inhabiting intertidal zones, were also profoundly influenced by Pleistocene glaciations. In this study, we investigated phylogeographic patterns of a widespread mangrove species Sonneratia caseolaris and a narrowly distributed, closely related species S. lanceolata to infer their divergence histories and related it to historical geological events. We sequenced two chloroplast fragments and five nuclear genes for one population of S. lanceolata and 12 populations of S. caseolaris across the Indo-West Pacific (IWP) region to evaluate genetic differentiation and divergence time among them. Phylogenetic analysis based on sequences of nuclear ribosomal internal transcribed spacer and a nuclear gene rpl9 for all Sonneratia species indicate that S. lanceolata individuals are nested within S. caseolaris. We found strong genetic structure among geographic regions (South China Sea, the Indian Ocean, and eastern Australia) inhabited by S. caseolaris. We estimated that divergence between the Indo-Malesia and Australasia populations occurred 4.035 million years ago (MYA), prior to the onset of Pleistocene. BARRIERS analysis suggested that complex geographic features in the IWP region had largely shaped the phylogeographic patterns of S. caseolaris. Furthermore, haplotype analyses provided convincing evidence for secondary contact of the South China Sea and the Indian Ocean lineages at the Indo-Pacific boundary. Demographic history inference under isolation and migration (IM) model detected substantial gene flow from the Sri Lanka populations to the populations in the Java Island. Moreover, multi-locus sequence analysis indicated that S. lanceolata was most closely related to the Indian Ocean populations of S. caseolaris and the divergence time between them was 2.057 MYA, coinciding with the onset of the Pleistocene glaciation. Our results suggest that geographic isolation driven by the Pleistocene ice age resulted in the recent origin of S. lanceolata

Speciation with gene flow via cycles of isolation and migration: insights from multiple mangrove taxa

Allopatric speciation requiring an unbroken period of geographical isolation has been the standard model of neo-Darwinism. While doubts have been repeatedly raised, strict allopatry without any gene flow remains a plausible mechanism in most cases. To rigorously reject strict allopatry, genomic sequences superimposed on the geological records of a well-delineated geographical barrier are necessary. The Strait of Malacca, narrowly connecting the Pacific and Indian Ocean coasts, serves at different times either as a geographical barrier or a conduit of gene flow for coastal/marine species. We surveyed 1,700 plants from 29 populations of five common mangrove species by large scale DNA sequencing and added several whole-genome assemblies. Speciation between the two oceans is driven by cycles of isolation and gene flow due to the fluctuations in sea level leading to the opening/closing of the Strait to ocean currents. Because the time required for speciation in mangroves is longer than the isolation phases, speciation in these mangroves has proceeded through many cycles of mixing-isolation-mixing, or MIM cycles. The MIM mechanism, by relaxing the condition of no gene flow, can promote speciation in many more geographical features than strict allopatry can. Finally, the MIM mechanism of speciation is also efficient, potentially yielding mn (m>1) species after n cycles

STUDY ON THE ANTIBACTERIAL ACTIVITY OF BERGENIA PURPURASCENS EXTRACT

Background: Bergenia purpurascens has tonic, haemostatic and anti-tussive actions. Anti-inflammatory and anti-bacterial activities of Bergenia purpurascens have not been reported so far. The objective of this paper is to provide experimental basis for the clinical application of Bergenia purpurascens through the pharmacodynamic study on its anti-inflammatory and anti-bacterial effects. Methods: Experimental models of xylene-induced ear edema in mice, cotton pellet granuloma in rats, and acetic acid-induced peritoneal capillary permeability in mice were used to investigate the anti-inflammatory effect of Bergenia purpurascens; bacteriostatic and bactericidal effects of Bergenia purpurascens extract on Staphylococcus aureus (SA), methicillin-resistant Staphylococcus aureus (MRSA), and β-lactamase positive Staphylococcus aureus (ESBLs-SA), were observed in vitro. Results: The results show that Bergenia purpurascens extract could markedly inhibit xylene-induced mouse ear edema, cotton pellet granulation tissue hyperplasia, and increased capillary permeability. Bergenia purpurascens extract has an inhibitory effect on SA, MRSA and ESBLs-SA. Conclusion: We conclude that Bergenia purpurascens extract has certain anti-inflammatory and anti-bacterial effects

Genomic Variation in Rice: Genesis of Highly Polymorphic Linkage Blocks during Domestication

Genomic regions that are unusually divergent between closely related species or racial groups can be particularly informative about the process of speciation or the operation of natural selection. The two sequenced genomes of cultivated Asian rice, Oryza sativa, reveal that at least 6% of the genomes are unusually divergent. Sequencing of ten unlinked loci from the highly divergent regions consistently identified two highly divergent haplotypes with each locus in nearly complete linkage disequilibrium among 25 O. sativa cultivars and 35 lines from six wild species. The existence of two highly divergent haplotypes in high divergence regions in species from all geographical areas (Africa, Asia, and Oceania) was in contrast to the low polymorphism and low linkage disequilibrium that were observed in other parts of the genome, represented by ten reference loci. While several natural processes are likely to contribute to this pattern of genomic variation, domestication may have greatly exaggerated the trend. In this hypothesis, divergent haplotypes that were adapted to different geographical and ecological environments migrated along with humans during the development of domesticated varieties. If true, these high divergence regions of the genome would be enriched for loci that contribute to the enormous range of phenotypic variation observed among domesticated breeds.</p

Identification of novel driver mutations of the discoidin domain receptor 2 (DDR2) gene in squamous cell lung cancer of Chinese patients

BACKGROUND: Although many of the recently approved genomically targeted therapies have improved outcomes for patients in non–small-cell lung cancer (NSCLC) with lung adenocarcinoma, little is known about the genomic alterations that drive lung squamous cell cancer (SCC) and development of effective targeted therapies in lung SCC is a promising area to be further investigated. Discoidin domain receptor 2 (DDR2), is a novel receptor tyrosine kinases that respond to several collagens and involved in tissue repair, primary and metastatic cancer progression. METHODS: Expression of DDR2 mRNA was analyzed in 54 lung SCC tissues by qRT-PCR. Over-expression approaches were used to investigate the biological functions of DDR2 and its’ mutations in lung SCC cells. Conventional Sanger sequencing was used to investigate the mutations of DDR2 gene in 86 samples. The effect of DDR2 and its’ mutations on proliferation was evaluated by MTT and colony formation assays; cell migration and invasion was evaluated by trasnwell assays. Lung SCC cells stably transfected with pEGFP-DDR2 WT, pEGFP-DDR2-S131C or empty vector were injection into nude mice to study the effect of DDR2 and its’ mutation on tumorigenesis in vivo. Protein and mRNA expression levels of E-cadherin and MMP2 were determined by qRT-PCR and western blot analysis. Differences between groups were tested for significance using Student’s t-test (two-tailed). RESULTS: In this study, we found that DDR2 mRNA levels were significantly decreased in 54 lung SCC tissues compared with normal lung tissues. Moreover, there were 3 novel DDR2 mutations (G531V, S131C, T681I) in 4 patients and provide the mutation rate of 4.6% in the 86 patients with lung SCC. The mutation of S131C in DDR2 could promote lung SCC cells proliferation, migration and invasion via inducing MMP-2, but reducing E-cadherin expression. CONCLUSIONS: These data indicated that the novel DDR2 mutation may contribute to the development and progression of lung SCC and this effect may be associated with increased proliferation and invasiveness, at least in part, via regulating E-cadherin expression