The Local Origin of the Tibetan Pig and Additional Insights into the Origin of Asian Pigs

BACKGROUND: The domestic pig currently indigenous to the Tibetan highlands is supposed to have been introduced during a continuous period of colonization by the ancestors of modern Tibetans. However, there is no direct genetic evidence of either the local origin or exotic migration of the Tibetan pig. METHODS AND FINDINGS: We analyzed mtDNA hypervariable segment I (HVI) variation of 218 individuals from seven Tibetan pig populations and 1,737 reported mtDNA sequences from domestic pigs and wild boars across Asia. The Bayesian consensus tree revealed a main haplogroup M and twelve minor haplogroups, which suggested a large number of small scale in situ domestication episodes. In particular, haplogroups D1 and D6 represented two highly divergent lineages in the Tibetan highlands and Island Southeastern Asia, respectively. Network analysis of haplogroup M further revealed one main subhaplogroup M1 and two minor subhaplogroups M2 and M3. Intriguingly, M2 was mainly distributed in Southeastern Asia, suggesting for a local origin. Similar with haplogroup D6, M3 was mainly restricted in Island Southeastern Asia. This pattern suggested that Island Southeastern Asia, but not Southeastern Asia, might be the center of domestication of the so-called Pacific clade (M3 and D6 here) described in previous studies. Diversity gradient analysis of major subhaplogroup M1 suggested three local origins in Southeastern Asia, the middle and downstream regions of the Yangtze River, and the Tibetan highlands, respectively. CONCLUSIONS: We identified two new origin centers for domestic pigs in the Tibetan highlands and in the Island Southeastern Asian region

SETDB1 Is Involved in Postembryonic DNA Methylation and Gene Silencing in Drosophila

DNA methylation is fundamental for the stability and activity of genomes. Drosophila melanogaster and vertebrates establish a global DNA methylation pattern of their genome during early embryogenesis. Large-scale analyses of DNA methylation patterns have uncovered revealed that DNA methylation patterns are dynamic rather than static and change in a gene-specific fashion during development and in diseased cells. However, the factors and mechanisms involved in dynamic, postembryonic DNA methylation remain unclear. Methylation of lysine 9 in histone H3 (H3-K9) by members of the Su(var)3–9 family of histone methyltransferases (HMTs) triggers embryonic DNA methylation in Arthropods and Chordates. Here, we demonstrate that Drosophila SETDB1 (dSETDB1) can mediate DNA methylation and silencing of genes and retrotransposons. We found that dSETDB1 tri-methylates H3-K9 and binds methylated CpA motifs. Tri-methylation of H3-K9 by dSETDB1 mediates recruitment of DNA methyltransferase 2 (Dnmt2) and Su(var)205, the Drosophila ortholog of mammalian “Heterochromatin Protein 1”, to target genes for dSETDB1. By enlisting Dnmt2 and Su(var)205, dSETDB1 triggers DNA methylation and silencing of genes and retrotransposons in Drosophila cells. DSETDB1 is involved in postembryonic DNA methylation and silencing of Rt1b{} retrotransposons and the tumor suppressor gene retinoblastoma family protein 1 (Rb) in imaginal discs. Collectively, our findings implicate dSETDB1 in postembryonic DNA methylation, provide a model for silencing of the tumor suppressor Rb, and uncover a role for cell type-specific DNA methylation in Drosophila development

Funktionelle Charakterisierung von Histon-Methyltransferase und Methyl-DNA-Bindeprotein MDU sowie seine Rolle bei der epigenetischen Regulierung des Rbf-Gens in Drosophila melanogaster

Die Methylierung der genomischen DNA und Histonen im Kern eukaryotischer Zellen spielt eine wichtige Rolle in epigenetischen Prozessen wie z. B. Imprinting, Gene Dosage Compensation , und epigenetische Repression der Genexpression. Studien in Pilzen, Pflanzen und Vertebraten unterstützen ein Model, wonach die Methylierung von Histonen, insbesondere die Methylierung der Lysinreste 9 (H3K9) und/oder 27 im Histon 3, die de novo Methylierung von DNA auslöst. Im Gegensatz dazu, ist nur wenig über die Mechanismen bekannt, die für de novo Methylierung in Modelorganismen wie z. B. Drosophila melanogaster verantwortlich sind. Drosophila exprimiert Schlüsselfaktoren für die Methylierung von Histonen and DNA: a.) Histonmethyltransferasen (HMT), die H3K9 methylieren und entscheidende Rollen für die Etablierung and Aufrechterhaltung von Heterochromatin und Genrepression spielen; b.) Eine DNA-Methyltransferase (dDNMT2), die überwiegend CpA und CpT-Motive im Drosophila Genom methyliert; c.) Methyl-CpG binding domain (MBD) Proteine, die methylierte DNA binden und DNA Methylierung in biologische Aktivität übersetzen. Ein Mitglied der Drosophila MBD-Proteinfamilie ist Medusa (MDU), welches sowohl ein MBD- als auch ein SET-Motiv enthält. Das SET-Motiv methyliert H3K9 in vitro und In Drosophila. Die Anwesenheit eines MBD und Set Motivs in MDU unterstützt die Hypothese, dass MDU an der Methylierung von H3K9 und DNA in Drosophila beteiligt ist. In dieser Arbeit habe ich die funktionale Beduetung von MDU bezüglich der Genexpression and DNA Methylierung untersucht. In vitro HMT-Experimente gekoppelt mit Western blot and Chromatin Immunpräzipitationsexperimenten ergaben, dass MDU H3K9 in vitro und in vivo tri-methyliert. MDU-vermittellte Methylierung von H3K9 resultiert in Repression der Zielgentranskription in Drosophila Zellkultur, woraus abgeleitet werden kann, dass MDU als Repressor der Transkription wirkt. Das MBD-Motiv von MDU bindet methylierte CpA DNA Sequenzen in vitro, und besitzt eine intrinsische methylierte-DNA Binding saffinität. Die Ergebnisse molekularer and genetischer Studien zeigen, dass MDU die Transkription des Tumorsuppressor Gens retinoblastoma family protein (Rbf), einem Schlüsselregulator der Zellproliferation und differenzierung, reprimiert. Die Untersuchungen zur Funktion von MDU in der Regulation der Expression von Rbf unterstützen ein Model wonach tri-methylierung von H3K9 durch MDU die dDNMT2-abhängige de novo Methylierung in der cis-regulatorischen enhancer Region von Rbf auslöst. Sobald DNA Methylierung platziert ist, bindet das MBD-Motif von MDU an methylierte DNA und induziert eine selbstangetriebene DNA-Histone Mehtylierungskaskade, die zur Ausbreitung von DNA und H3K9 Methylierung auf dem Rbf Genlocus führt und letztendlich Repression der Rbf Transkription bewirkt. Die Ergebnisse dieser Arbeit entschlüsseln die Funktion von MDU in der Repression der Genexpression, ergeben einen Mechanismus für die Etablierung der de novo DNA Methylierung in Drosophila, und deuten auf eine wichtige Rolle der bifunktionalen MBD/SET Proteine für die Kontrolle der Proliferation und Differenzierung von Zellen hin

Decompensated liver disease complicated by acute stroke caused by multiple factors: a clinical analysis of 15 cases

Objective To investigate the clinical features of patients with decompensated liver disease complicated by acute stroke. Methods A retrospective analysis was performed for the clinical data of 15 patients who were hospitalized in Beijing You'an Hospital, Capital Medical University and diagnosed with decompensated liver disease complicated by acute stroke from January 2011 to December 2015, including medical history, neurological manifestations, treatment, and prognostic features. Results Among the 15 patients, 11 had acute hemorrhagic stroke (AHS), and 4 had acute ischemic stroke (AIS); among the 11 patients with AHS, 4 (36.36%) had hemorrhage caused by brain metastatic tumor of liver cancer (tumor-associated stroke), and 3 (27.27%) were complicated by liver failure. Among the 15 patients, 12 (80%) had disturbance of consciousness as the early neurological manifestation, and the confirmed diagnosis was made based on head CT findings; the treatment mainly included symptomatic support and rehabilitation training. The patients with AHS had poor prognosis. Four (26.67%) of the 15 AHS patients died, among these patients, 2 had liver failure complicated by AHS, 1 had liver cirrhosis complicated by AHS, and 1 had brain metastases complicated by AHS. Conclusion Patients with decompensated liver disease complicated by acute stroke tend to develop the manifestations of AHS, which may be related to a poor clotting mechanism and brain metastasis of liver cancer, and have poor prognosis. Head CT scan should be performed for patients with decompensated liver disease accompanied by neuropsychiatric abnormalities as early as possible to help with early diagnosis and timely treatment

Structural, electronic and magnetic properties of metal–organic-framework perovskites [AmH] [Mn(HCOO)3]: a first-principles study

International audienceWe calculate the structural, electronic and magnetic properties of the subgroup of Metal–Organic-Frameworks (MOFs) [AmH][M(HCOO)3] (in which AmH+ ¼ organic ammonium cation, M ¼ divalent metalion) using density functional theory with GGA+U approximation. The optimized structures and magneticground states are in good agreement with available experimental results. The electronic structures ofthese MOFs are obtained at their magnetic ground states. Using hybrid functional method (HSE06), theband gap is 4.33 eV, 4.12 eV, 4.15 eV and 4.78 eV for NH2NH3+, HONH3+, CH3CH2NH3+ and NH4+compounds, respectively. The band gap of NH2NH3+ varies from 2.63 eV (5% compressive strain) to3.50 eV (+5% tensile strain) at Ueff ¼ 4 eV. It is demonstrated that the band gap of such MOFs can beeasily tuned by applying external strain and the AmH+ ligand for the first time. These MOFs all showinsulating properties. In addition, such strain engineering may also be useful for enhancing the Neeltemperature by changing the distance of magnetic Mn ions. Interestingly, Bader charge analysis indicatesthat AmH+ is fully ionic suggesting that appropriate arrangement may give rise to polar order associatedwith the magnetic ordering, these MOFs materials can be considered as potential multiferroics. Finally,this work reveals that both strain and chemical modification are efficient approaches for designingimproved and novel MOFs for future applications in photocatalytic, optoelectronic, ferroelectric ormultiferroic and electronic device

Gene Co-Expression Network Analysis Unraveling Transcriptional Regulation of High-Altitude Adaptation of Tibetan Pig

<div><p>Tibetan pigs have survived at high altitude for millennia and they have a suite of adaptive features to tolerate the hypoxic environment. However, the molecular mechanisms underlying the regulation of hypoxia-adaptive phenotypes have not been completely elucidated. In this study, we analyzed differentially expressed genes (DEGs), biological pathways and constructed co-expression regulation networks using whole-transcriptome microarrays from lung tissues of Tibetan and Duroc pigs both at high and low altitude. A total of 3,066 DEGs were identified and this list was over-represented for the ontology terms including metabolic process, catalytic activity, and KEGG pathway including metabolic pathway and PI3K-Akt signaling pathway. The regulatory (RIF) and phenotypic (PIF) impact factor analysis identified several known and several potentially novel regulators of hypoxia adaption, including: <i>IKBKG</i>, <i>KLF6</i> and <i>RBPJ</i> (RIF1), <i>SF3B1</i>, <i>EFEMP1</i>, <i>HOXB6</i> and <i>ATF6</i> (RIF2). These findings provide new details of the regulatory architecture of hypoxia-adaptive genes and also insight into which genes may undergo epigenetic modification for further study in the high-altitude adaptation.</p></div

Adenovirus Small E1A Employs the Lysine Acetylases p300/CBP and Tumor Suppressor Rb to Repress Select Host Genes and Promote Productive Virus Infection

Oncogenic transformation by adenovirus small e1a depends on simultaneous interactions with the host lysine acetylases p300/CBP and the tumor suppressor RB. How these interactions influence cellular gene expression remains unclear. We find that e1a displaces RBs from E2F transcription factors and promotes p300 acetylation of RB1 K873/K874 to lock it into a repressing conformation that interacts with repressive chromatin-modifying enzymes. These repressing p300-e1a-RB1 complexes specifically interact with host genes that have unusually high p300 association within the gene body. The TGF-β, TNF-, and interleukin-signaling pathway components are enriched among such p300-targeted genes. The p300-e1a-RB1 complex condenses chromatin in a manner dependent on HDAC activity, p300 lysine acetylase activity, the p300 bromodomain, and RB K873/K874 and e1a K239 acetylation to repress host genes that would otherwise inhibit productive virus infection. Thus, adenovirus employs e1a to repress host genes that interfere with viral replication

Diagram summarizing experiments and analyses conducted in the whole study.

<p>Abbreviations: TH = Tibetan pigs at high altitude, DH = Duroc pigs at high altitude, TL = Tibetan pigs at low altitude, DL = Duroc pigs at low altitude, DEGs = Differential Expression Genes, PCIT = Partial Correlation and Information Theory, RIF = Regulatory Impact Factor, PIF = Phenotype Impact Factor.</p