29 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2018/06/15

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

21 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2018/06/15

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

27 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2018/06/14

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

26 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2018/06/14

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

34 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2018/06/13

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

33 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2018/06/13

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

34 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2018/06/12

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Short exposure to low concentrations of alcohol during embryonic development has only subtle and strain- dependent effect on the levels of five amino acid neurotransmitters in zebrafish.

Neurotoxicol Teratol. 2018 Jun 07;:

Authors: Mahabir S, Chatterjee D, Gerlai R

Abstract
The zebrafish has been successfully employed to model and study the effects of embryonic alcohol exposure. Short exposure to low alcohol concentrations during embryonic development has been shown to significantly disrupt social behavior as well as the dopaminergic and serotoninergic systems in zebrafish. However, analysis of potential effects of embryonic alcohol exposure on other amino acid neurotransmitter systems has not been performed. Here we analyzed neurochemicals obtained from adult AB and TU strain zebrafish that were immersed in 0.00% (control), 0.25%, 0.50%, 0.75% or 1.00% alcohol solution (vol/vol%) at 24 h post-fertilization for 2 h. From whole brain extracts, we quantified glutamate, aspartate, glycine, taurine and GABA levels using high performance liquid chromatography (HPLC). We found embryonic alcohol exposure not to have any significant effect on the levels of glutamate, aspartate, glycine and GABA in both AB and TU zebrafish. AB zebrafish showed a significant elevation of taurine levels, but only in the highest alcohol dose group compared to control. These results, albeit mainly negative, together with prior findings suggest that behavioral abnormalities resulting from embryonic alcohol exposure described before for AB zebrafish may primarily be due to altered dopaminergic and serotoninergic mechanisms. Furthermore, a Principal Component Analysis conducted with all neurochemicals tested in this and in our prior study, found a strain-dependent correlation structure response to embryonic alcohol treatment, confirming that embryonic alcohol effects may be genotype dependent.

PMID: 29886245 [PubMed - as supplied by publisher]

Encoding Growth Factor Identity in the Temporal Dynamics of FOXO3 under the Combinatorial Control of ERK and AKT Kinases.

Cell Syst. 2018 May 31;:

Authors: Sampattavanich S, Steiert B, Kramer BA, Gyori BM, Albeck JG, Sorger PK

Abstract
Extracellular growth factors signal to transcription factors via a limited number of cytoplasmic kinase cascades. It remains unclear how such cascades encode ligand identities and concentrations. In this paper, we use live-cell imaging and statistical modeling to study FOXO3, a transcription factor regulating diverse aspects of cellular physiology that is under combinatorial control. We show that FOXO3 nuclear-to-cytosolic translocation has two temporally distinct phases varying in magnitude with growth factor identity and cell type. These phases comprise synchronous translocation soon after ligand addition followed by an extended back-and-forth shuttling; this shuttling is pulsatile and does not have a characteristic frequency, unlike a simple oscillator. Early and late dynamics are differentially regulated by Akt and ERK and have low mutual information, potentially allowing the two phases to encode different information. In cancer cells in which ERK and Akt are dysregulated by oncogenic mutation, the diversity of states is lower.

PMID: 29886111 [PubMed - as supplied by publisher]

Micropapillary urothelial carcinoma: evaluation of HER2 status and immunohistochemical characterization of the molecular subtype.

Hum Pathol. 2018 Jun 06;:

Authors: Zinnall U, Weyerer V, Compérat E, Camparo P, Gaisa NT, Knuechel-Clarke R, Perren A, Lugli A, Toma M, Baretton G, Kristiansen G, Wirtz RM, Cheng L, Wullich B, Stoehr R, Hartmann A, Bertz S

Abstract
Comprehensive molecular analyses of urothelial bladder cancer (UBC) have defined distinct subtypes with potential therapeutic implications. In this study, we focused on micropapillary urothelial carcinoma (MPUC), an aggressive, histomorphologically defined rare variant. Apart from genetic alterations shared with conventional UBC alterations of the HER2 gene have been reported in higher frequencies. However, only small cohorts of MPUCs have been analyzed and the real impact is still unclear. We collected a cohort of 94 MPUCs and immunohistochemically tested HER2, basal (CD44, CK5, EGFR, p63) and luminal (CD24, FOXA1, GATA3, CK20) markers to allocate MPUC to a molecular subtype. Additionally, HER2 amplification status was assigned by chromogenic in-situ-hybridization. Sanger sequencing of Exon 4 and 8 was used to test for HER2 mutations. Kruskal-Wallis test was calculated to compare marker distribution between proportions of the MPUC component. 2+/3+ HER2 staining scores were identified in 39.6% of 91 analyzed MPUCs and were not differentially distributed among the proportion of the MPUC component (P=.89). Additionally, CISH analysis revealed 30% of HER2 amplified tumors independently of the MPUC fraction. In 6/90 evaluable MPUCs a p.S310F HER2 mutation was detected. Overexpression of luminal markers was observed in the majority of MPUC. Our investigations of the largest cohort of analyzed MPUC demonstrate that HER2 overexpression and amplifications are common genetic alterations and identification of overexpressed luminal markers allows sub-classification to the luminal subtype. These findings highlight the need of histomorphological recognition of MPUC and analysis of HER2 status and the luminal molecular subtype for potential targeted therapeutic strategies.

PMID: 29885409 [PubMed - as supplied by publisher]

Are there general laws for digit evolution in squamates? The loss and re-evolution of digits in a clade of fossorial lizards (Brachymeles, Scincinae).

J Morphol. 2018 Jun 08;:

Authors: Wagner GP, Griffith OW, Bergmann PJ, Bello-Hellegouarch G, Kohlsdorf T, Bhullar A, Siler CD

Abstract
Evolutionary simplification of autopodial structures is a major theme in studies of body-form evolution. Previous studies on amniotes have supported Morse's law, that is, that the first digit reduced is Digit I, followed by Digit V. Furthermore, the question of reversibility for evolutionary digit loss and its implications for "Dollo's law" remains controversial. Here, we provide an analysis of limb and digit evolution for the skink genus Brachymeles. Employing phylogenetic, morphological, osteological, and myological data, we (a) test the hypothesis that digits have re-evolved, (b) describe patterns of morphological evolution, and (c) investigate whether patterns of digit loss are generalizable across taxa. We found strong statistical support for digit, but not limb re-evolution. The feet of pentadactyl species of Brachymeles are very similar to those of outgroup species, while the hands of these lineages are modified (2-3-3-3-2) and a have a reduced set of intrinsic hand muscles. Digit number variation suggests a more labile Digit V than Digit I, contrary to Morse's law. The observed pattern of digit variation is different from that of other scincid lizards (Lerista, Hemiergis, Carlia). Our results present the first evidence of clade-specific modes of digit reduction.

PMID: 29884998 [PubMed - as supplied by publisher]

Metallomics: The Science of Biometals and Biometalloids.

Adv Exp Med Biol. 2018;1055:1-20

Authors: Maret W

Abstract
Metallomics, a discipline integrating sciences that address the biometals and biometalloids, provides new opportunities for discoveries. As part of a systems biology approach, it draws attention to the importance of many chemical elements in biochemistry. Traditionally, biochemistry has treated life as organic chemistry, separating it from inorganic chemistry, considered a field reserved for investigating the inanimate world. However, inorganic chemistry is part of the chemistry of life, and metallomics contributes by showing the importance of a neglected fifth branch of building blocks in biochemistry. Metallomics adds chemical elements/metals to the four building blocks of biomolecules and the fields of their studies: carbohydrates (glycome), lipids (lipidome), proteins (proteome), and nucleotides (genome). The realization that non-essential elements are present in organisms in addition to essential elements represents a certain paradigm shift in our thinking, as it stipulates inquiries into the functional implications of virtually all the natural elements. This article discusses opportunities arising from metallomics for a better understanding of human biology and health. It looks at a biological periodic system of the elements as a sum of metallomes and focuses on the major roles of metals in about 30-40% of all proteins, the metalloproteomes. It emphasizes the importance of zinc and iron biology and discusses why it is important to investigate non-essential metal ions, what bioinformatics approaches can contribute to understanding metalloproteins, and why metallomics has a bright future in the many dimensions it covers.

PMID: 29884959 [PubMed - in process]

Dephosphorylation of the HIV-1 restriction factor SAMHD1 is mediated by PP2A-B55α holoenzymes during mitotic exit.

Nat Commun. 2018 Jun 08;9(1):2227

Authors: Schott K, Fuchs NV, Derua R, Mahboubi B, Schnellbächer E, Seifried J, Tondera C, Schmitz H, Shepard C, Brandariz-Nuñez A, Diaz-Griffero F, Reuter A, Kim B, Janssens V, König R

Abstract
SAMHD1 is a critical restriction factor for HIV-1 in non-cycling cells and its antiviral activity is regulated by T592 phosphorylation. Here, we show that SAMHD1 dephosphorylation at T592 is controlled during the cell cycle, occurring during M/G1 transition in proliferating cells. Using several complementary proteomics and biochemical approaches, we identify the phosphatase PP2A-B55α responsible for rendering SAMHD1 antivirally active. SAMHD1 is specifically targeted by PP2A-B55α holoenzymes during mitotic exit, in line with observations that PP2A-B55α is a key mitotic exit phosphatase in mammalian cells. Strikingly, as HeLa or activated primary CD4+ T cells enter the G1 phase, pronounced reduction of RT products is observed upon HIV-1 infection dependent on the presence of dephosphorylated SAMHD1. Moreover, PP2A controls SAMHD1 pT592 level in non-cycling monocyte-derived macrophages (MDMs). Thus, the PP2A-B55α holoenzyme is a key regulator to switch on the antiviral activity of SAMHD1.

PMID: 29884836 [PubMed - in process]

Metformin induces FOXO3-dependent fetal hemoglobin production in human primary erythroid cells.

Blood. 2018 Jun 08;:

Authors: Zhang Y, Paikari A, Sumazin P, Ginter Summarell CC, Crosby JR, Boerwinkle E, Weiss MJ, Sheehan VA

Abstract
Induction of red blood cell fetal hemoglobin (HbF, α2γ2) ameliorates the pathophysiology of sickle cell disease (SCD) by reducing the concentration of sickle hemoglobin (HbS, α2βS2) to inhibit its polymerization. Hydroxyurea (HU), the only FDA-approved drug for SCD, acts in part by inducing HbF, but is not fully effective, reflecting the need for new therapies. Whole exome sequence analysis of rare genetic variants in SCD patients identified FOXO3 as a candidate regulator of RBC HbF. We validated these genomic findings through loss and gain of function studies in normal human CD34+ hematopoietic stem and progenitor cells (HSPCs) induced to undergo erythroid differentiation. FOXO3 gene silencing reduced γ-globin RNA levels and HbF levels in erythroblasts, while overexpression of FOXO3 produced the opposite effect. Moreover, treatment of primary CD34+ cell-derived erythroid cultures with metformin, an FDA-approved drug known to enhance FOXO3 activity in non-erythroid cells, caused dose-related, FOXO3-dependent, increases in both percentage (%) HbF protein and the fraction of HbF-immunostaining cells (F-cells). Combined HU and metformin treatment induced HbF additively and reversed the erythroid maturation arrested caused by HU treatment alone. HbF induction in erythroid precursors by metformin was dependent on FOXO3 expression and did not alter expression of BCL11A, MYB or KLF1. Collectively, our data implicate FOXO3 as a positive regulator of γ-globin expression and identify metformin as a potential therapeutic agent for SCD.

PMID: 29884740 [PubMed - as supplied by publisher]

PDGF-A suppresses contact inhibition during directional collective cell migration.

Development. 2018 Jun 08;:

Authors: Nagel M, Winklbauer R

Abstract
The leading edge mesendoderm (LEM) of the Xenopus gastrula moves as an aggregate by collective migration. However, LEM cells on fibronectin in vitro show contact inhibition of locomotion by quickly retracting lamellipodia upon mutual contact. We found that a fibronectin-integrin-syndecan module acts between p21-activated kinase-1 upstream and ephrinB1 downstream to promote the contact-induced collapse of lamellipodia. To function in this module, fibronectin has to be present as puncta on the surface of LEM cells. To overcome contact inhibition in LEM cell aggregates, PDGF-A deposited in the endogenous substratum of LEM migration blocks the fibronectin-integrin-syndecan module at the integrin level. This stabilizes lamellipodia preferentially in the direction of normal LEM movement and supports cell orientation and the directional migration of the coherent LEM cell mass.

PMID: 29884673 [PubMed - as supplied by publisher]

A Dual sgRNA Approach for Functional Genomics in Arabidopsis thaliana.

G3 (Bethesda). 2018 Jun 08;:

Authors: Pauwels L, De Clercq R, Goossens J, Iñigo S, Williams C, Ron M, Britt A, Goossens A

Abstract
Reverse genetics uses loss-of-function alleles to interrogate gene function. The advent of CRISPR/Cas9-based gene editing now allows the generation of knock-out alleles for any gene and entire gene families. Even in the model plant Arabidopsis thaliana, gene editing is welcomed as T-DNA insertion lines do not always generate null alleles. Here, we show efficient generation of heritable mutations in Arabidopsis using CRISPR/Cas9 with a workload similar to generating overexpression lines. We obtain for several different genes Cas9 null-segregants with bi-allelic mutations in the T2 generation. While somatic mutations were predominantly generated by the canonical non-homologous end joining (cNHEJ) pathway, we observed inherited mutations that were the result of synthesis-dependent microhomology-mediated end joining (SD-MMEJ), a repair pathway linked to polymerase θ (PolQ). We also demonstrate that our workflow is compatible with a dual sgRNA approach in which a gene is targeted by two sgRNAs simultaneously. This paired nuclease method results in more reliable loss-of-function alleles that lack a large essential part of the gene. The ease of the CRISPR/Cas9 workflow should help in the eventual generation of true null alleles of every gene in the Arabidopsis genome, which will advance both basic and applied plant research.

PMID: 29884615 [PubMed - as supplied by publisher]

23 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2018/06/09

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

20 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2018/06/09

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

28 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2018/06/08

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

24 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2018/06/08

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.