Increased demand for NAD+ relative to ATP drives aerobic glycolysis

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Cardiac Fibroblasts Contribute to Myocardial Dysfunction in Mice with Sepsis: The Role of NLRP3 Inflammasome Activation

Myocardial contractile dysfunction in sepsis is associated with the increased morbidity and mortality. Although the underlying mechanisms of the cardiac depression have not been fully elucidated, an exaggerated inflammatory response is believed to be responsible. Nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome is an intracellular platform that is involved in the maturation and release of interleukin (IL)-1β. The aim of the present study is to evaluate whether sepsis activates NLRP3 inflammasome/caspase-1/IL-1β pathway in cardiac fibroblasts (CFs) and whether this cytokine can subsequently impact the function of cardiomyocytes (cardiac fibroblast-myocyte cross-talk). We show that treatment of CFs with lipopolysaccharide (LPS) induces upregulation of NLRP3, activation of caspase-1, as well as the maturation (activation) and release of IL-1β. In addition, the genetic (small interfering ribonucleic acid [siRNA]) and pharmacological (glyburide) inhibition of the NLRP3 inflammasome in CFs can block this signaling pathway. Furthermore, the inhibition of the NLRP3 inflammasome in cardiac fibroblasts ameliorated the ability of LPS-chalenged CFs to impact cardiomyocyte function as assessed by intracellular cyclic adenosine monophosphate (cAMP) responses in cardiomyocytes. Salient features of this the NLP3 inflammasome/ caspase-1 pathway were confirmed in in vivo models of endotoxemia/sepsis. We found that inhibition of the NLRP3 inflammasome attenuated myocardial dysfunction in mice with LPS and increased the survival rate in mice with feces-induced peritonitis. Our results indicate that the activation of the NLRP3 inflammasome in cardiac fibroblasts is pivotal in the induction of myocardial dysfunction in sepsis.     

Scale sensitivity of synthetic long‐term vegetation time series derived through overlay of short‐term field records

Questions: Is change in cover of dominant species driving the velocity of succession or is it species turnover (1)? Is the length of the time‐step chosen in sampling affecting our recognition of the long‐term rate of change (2)1 Location: 74 permanent plots located in the Swiss National Park, SE Switzerland, ca. 1900 m a.s.l. Methods: We superimpose several time‐series from permanent plots to one single series solely based on compositional dissimilarity. As shown earlier (Wildi & Schütz 2000) this results in a synthetic series covering about 400 to 650 yr length. Continuous power transformation of cover‐percentage scores is used to test if the dominance or the presence‐absence of species is governing secondary succession from pasture to forest. The effect of time step length is tested by sub‐samples of the time series. Results: Altering the weight of presence‐absence versus dominance of species affects the emerging time frame, while altering time step length is uncritical. Where species turnover is fast, different performance scales yield similar results. When cover change in dominant species prevails, the solutions vary considerably. Ordinations reveal that the synthetic time series seek for shortest paths of the temporal pattern whereas in the real system longer lasting alternatives exist. Conclusions: Superimposing time series differs from the classical space‐for‐time substitution approach. It is a computation‐based method to investigate temporal patterns of hundreds of years fitting between direct monitoring (usually limited to decades) and the analysis of proxy‐data (for time spans of thousands of years and more).     

On the Photosynthetic Potential in the Very Early Archean Oceans

In this work we apply a mathematical model of photosynthesis to quantify the potential for photosynthetic life in the very Early Archean oceans. We assume the presence of oceanic blockers of ultraviolet radiation, specifically ferrous ions. For this scenario, our results suggest a potential for photosynthetic life greater than or similar to that in later eras/eons, such as the Late Archean and the current Phanerozoic eon.     

The CR3 motif of Rrp44p is important for interaction with the core exosome and exosome function

The 10-subunit RNA exosome is involved in a large number of diverse RNA processing and degradation events in eukaryotes. These reactions are carried out by the single catalytic subunit, Rrp44p/Dis3p, which is composed of three parts that are conserved throughout eukaryotes. The exosome is named for the 3′ to 5′ exoribonuclease activity provided by a large C-terminal region of the Rrp44p subunit that resembles other exoribonucleases. Rrp44p also contains an endoribonuclease domain. Finally, the very N-terminus of Rrp44p contains three Cys residues (CR3 motif) that are conserved in many eukaryotes but have no known function. These three conserved Cys residues cluster with a previously unrecognized conserved His residue in what resembles a metal-ion-binding site. Genetic and biochemical data show that this CR3 motif affects both endo- and exonuclease activity in vivo and both the nuclear and cytoplasmic exosome, as well as the ability of Rrp44p to associate with the other exosome subunits. These data provide the first direct evidence that the exosome-Rrp44p interaction is functionally important and also provides a molecular explanation for the functional defects when the conserved Cys residues are mutated.     

Osteoderm histology of the Pampatheriidae (Cingulata,Xenarthra, Mammalia): Implications for systematics,osteoderm growth,and biomechanical adaptation

Pampatheres are extinct, large‐bodied cingulates, which share morphological characters with both armadillos and glyptodonts but are considered to be more closely related to the latter. The osteoderm histology of six pampathere taxa was examined and compared to the histology of other cingulate osteoderms. This study investigates the development and functional adaptation of pampathere osteoderms as well as the phylogenetic relationships of the Pampatheriidae within the Cingulata. We found that pampathere osteoderms share a uniform histological organization based on a basic diploe‐like structure. After initial stages of intramembranous growth, metaplastic ossification, that is, the direct incorporation and mineralization of pre‐existing protein fibers, plays an important role in osteoderm development and provides information on various kinds of soft tissue otherwise not preserved. The latest stages of osteoderm growth are dominated by periosteal bone formation especially in the superficial cortex. Movable band osteoderms show regular arrangements of incorporated fibers that may increase the resistance of particularly weak areas against strain. The histological composition of pampathere osteoderms is plesiomorphic in its basic structure but shows a number of derived features. A unique array of Sharpey's fibers that are incorporated into the bone matrix at sutured osteoderm margins is interpreted as a synapomorphy of pampatheres. The arrangement of dermal fibers in the deep and superficial cortexes supports the close relationship between pampatheres and glyptodonts. J. Morphol., 2012. © 2011 Wiley Periodicals, Inc.     

Characterization of Vibrio cholerae O1 isolates responsible for cholera outbreaks in Kenya between 1975 and 2017

Kenya is endemic for cholera with different waves of outbreaks having been documented since 1971. In recent years, new variants of Vibrio cholerae O1 have emerged and have replaced most of the traditional El Tor biotype globally. These strains also appear to have increased virulence, and it is important to describe and document their phenotypic and genotypic traits. This study characterized 146 V. cholerae O1 isolates from cholera outbreaks that occurred in Kenya between 1975 and 2017. Our study reports that the 1975–1984 strains had typical classical or El Tor biotype characters. New variants of V. cholerae O1 having traits of both classical and El Tor biotypes were observed from 2007 with all strains isolated between 2015 and 2017 being sensitive to polymyxin B and carrying both classical and El Tor type ctxB. All strains were resistant to Phage IV and harbored rstR, rtxC, hlyA, rtxA and tcpA genes specific for El Tor biotype indicating that the strains had an El Tor backbone. Pulsed field gel electrophoresis (PFGE) genotyping differentiated the isolates into 14 pulsotypes. The clustering also corresponded with the year of isolation signifying that the cholera outbreaks occurred as separate waves of different genetic fingerprints exhibiting different genotypic and phenotypic characteristics. The emergence and prevalence of V. cholerae O1 strains carrying El Tor type and classical type ctxB in Kenya are reported. These strains have replaced the typical El Tor biotype in Kenya and are potentially more virulent and easily transmitted within the population.