Gene tree parsimony vs uninode coding for phylogenetic reconstruction

have suggested that there are important weaknesses of gene tree parsimony in reconstructing phylogeny in the face of gene duplication, weaknesses that are addressed by method of uninode coding. Here, we discuss Simmons and Freudenstein's criticisms and suggest a number of reasons why gene tree parsimony is preferable to uninode coding. During this discussion we introduce a number of recent developments of gene tree parsimony methods overlooked by Simmons and Freudenstein. Finally, we present a re-analysis of data from that produces a more reasonable phylogeny than that found by Simmons and Freudenstein, suggesting that gene tree parsimony outperforms uninode coding, at least on these data.     

P450 BM3: the very model of a modern flavocytochrome

Flavocytochrome P450 BM3 is a bacterial P450 system in which a fatty acid hydroxylase P450 is fused to a mammalian-like diflavin NADPH-P450 reductase in a single polypeptide. The enzyme is soluble (unlike mammalian P450 redox systems) and its fusion arrangement affords it the highest catalytic activity of any P450 mono-oxygenase. This article discusses the fundamental properties of P450 BM3 and how progress with this model P450 has affected our comprehension of P450 systems in general.     

The induction of preterm labor in rhesus macaques is determined by the strength of immune response to intrauterine infection

Intrauterine infection/inflammation (IUI) is a major contributor to preterm labor (PTL). However, IUI does not invariably cause PTL. We hypothesized that quantitative and qualitative differences in immune response exist in subjects with or without PTL. To define the triggers for PTL, we developed rhesus macaque models of IUI driven by lipopolysaccharide (LPS) or live Escherichia coli. PTL did not occur in LPS challenged rhesus macaques, while E. coli–infected animals frequently delivered preterm. Although LPS and live E. coli both caused immune cell infiltration, E. coli–infected animals showed higher levels of inflammatory mediators, particularly interleukin 6 (IL-6) and prostaglandins, in the chorioamnion-decidua and amniotic fluid (AF). Neutrophil infiltration in the chorio-decidua was a common feature to both LPS and E. coli. However, neutrophilic infiltration and IL6 and PTGS2 expression in the amnion was specifically induced by live E. coli. RNA sequencing (RNA-seq) analysis of fetal membranes revealed that specific pathways involved in augmentation of inflammation including type I interferon (IFN) response, chemotaxis, sumoylation, and iron homeostasis were up-regulated in the E. coli group compared to the LPS group. Our data suggest that the intensity of the host immune response to IUI may determine susceptibility to PTL.     

Effects of a retaining wall and an artificial embankment on nearshore littoral habitats and biota in a large Alpine lake

Hydrobiologia - The littoral zones of many Central European lakes are severely altered by lake-side retaining walls. These are suspected to impair littoral biota due to the reflection of incoming...     

Synthesis and evaluation of 4-(1-aminoalkyl)-N-(4-pyridyl)cyclohexanecarboxamides as Rho kinase inhibitors and neurite outgrowth promoters

The influence of stereochemistry and alkyl side chain length on the bioactivity of the Rho kinase inhibitor Y-27632 [(+)-1, R=Me] was examined by the synthesis of (+)- and (-)-1, and two alkyl chain analogs (+)- and (-)-2 (R=n-propyl) and (-)-3 (R=n-octyl) as well as their evaluation in enzymatic and neurite outgrowth assays.     

Dolichol and N-linked oligosaccharide synthesis in the rat testis: interaction between Sertoli and spermatogenic cells, evidence for paracrine effects.

The relative contribution of the Sertoli cell and the pachytene spermatocyte to dolichol and N-linked oligosaccharide biosynthesis within the seminiferous tubule was investigated. Evidence is presented to show that the interaction between these two cell types affects dolichol and N-linked oligosaccharide biosynthesis. Analysis of the dolichol content of Sertoli cultures confirms earlier data suggesting that the Sertoli cell constitutes the major pool of dolichols within the seminiferous tubule. [14C]Acetate incorporation studies suggest that the Sertoli cell in culture synthesizes dolichol much more rapidly than does the isolated pachytene spermatocyte. This information, in addition to previous data in the literature, infers an interactive effect whereby the presence of the spermatogenic cell in the tubule stimulates dolichol synthesis in the Sertoli cell. The absence of normal Sertoli-spermatocyte interactions in in vitro incubations may also limit dolichol synthesis in the pachytene spermatocyte. The distribution of dolichol kinase between the Sertoli and the pachytene spermatocyte was also examined. The concentration of this enzyme in the Sertoli cell suggests the presence of an active salvage pathway within that cell. The correlation between the appearance of the pachytene spermatocyte and the previously described peak of dolichol kinase activity in the seminiferous tubules of the prepubertal animal implies cell-cell interactions. Radiolabelling studies of N-linked oligosaccharides were conducted using [3H]mannose and concanavalin A affinity chromatography to identify multiantennary, biantennary, and high-mannose oligosaccharide pools. An in vitro bicameral coculture system was used to demonstrate that pachytene spermatocytes stimulate incorporation of [3H]mannose into Sertoli cell oligosaccharides.(ABSTRACT TRUNCATED AT 250 WORDS)     

The empowerment of translational research: lessons from laminopathies

The need for a collaborative approach to complex inherited diseases collectively referred to as laminopathies, encouraged Italian researchers, geneticists, physicians and patients to join in the Italian Network for Laminopathies, in 2009. Here, we highlight the advantages and added value of such a multidisciplinary effort to understand pathogenesis, clinical aspects and try to find a cure for Emery-Dreifuss muscular dystrophy, Mandibuloacral dysplasia, Hutchinson-Gilford Progeria and forms of lamin-linked cardiomyopathy, neuropathy and lipodystrophy.     

Cysteine Oxidation Targets Peroxiredoxins 1 and 2 for Exosomal Release through a Novel Mechanism of Redox-Dependent Secretion

Nonclassical protein secretion is of major importance as a number of cytokines and inflammatory mediators are secreted via this route. Current evidence indicates that there are several mechanistically distinct methods of nonclassical secretion. We have shown recently that peroxiredoxin (Prdx) 1 and Prdx2 are released by various cells upon exposure to inflammatory stimuli such as lipopolysaccharide (LPS) or tumor necrosis factor alpha (TNF-α). The released Prdx then acts to induce production of inflammatory cytokines. However, Prdx1 and 2 do not have signal peptides and therefore must be secreted by alternative mechanisms, as has been postulated for the inflammatory mediators interleukin-1β (IL-1β) and high mobility group box-1 (HMGB1). We show here that circulating Prdx1 and 2 are present exclusively as disulfide-linked homodimers. Inflammatory stimuli also induce in vitro release of Prdx1 and 2 as disulfide-linked homodimers. Mutation of cysteines Cys51 or Cys172 (but not Cys70) in Prdx2, and Cys52 or Cys173 (but not Cys71 or Cys83) in Prdx1 prevented dimer formation and this was associated with inhibition of their TNF-α-induced release. Thus, the presence and oxidation of key cysteine residues in these proteins are a prerequisite for their secretion in response to TNF-α, and this release can be induced with an oxidant. By contrast, the secretion of the nuclear-associated danger signal HMGB1 is independent of cysteine oxidation, as shown by experiments with a cysteine-free HMGB1 mutant. Release of Prdx1 and 2 is not prevented by inhibitors of the classical secretory pathway, instead, both Prdx1 and 2 are released in exosomes from both human embryonic kidney (HEK) cells and monocytic cells. Serum Prdx1 and 2 also are associated with the exosomes. These results describe a novel pathway of protein secretion mediated by cysteine oxidation that underlines the importance of redox-dependent signaling mechanisms in inflammation.     

A genetically distinct hybrid zone occurs for two globally invasive mosquito fish species with striking phenotypic resemblance

Hybrid zones allow for the investigation of incipient speciation and related evolutionary processes of selection, gene flow, and migration. Interspecific dynamics, like competition, can impact the size, shape, and directional movement of species in hybrid zones. Hybrid zones contribute to a paradox for the biological species concept because interbreeding between species occurs while parental forms remain distinct. A long‐standing zone of intergradation or introgression exists for eastern and western mosquito fish (Gambusia holbrooki and G. affinis) around Mobile Bay, AL. The region has been studied episodically, over decades, making it perfect for addressing temporal dynamics and for providing a deeper understanding of the genetics of these periodically reclassified fishes (as species or subspecies). We used six microsatellite markers to assess the current population structure and gene flow patterns across 19 populations of mosquito fish and then compared our results with historical data. Genetic evidence demonstrates that the current hybrid zone is located in a similar geographic region as the historical one, even after three decades. Hybrid fish, however, demonstrate relatively low heterozygosity and are genetically distinct from western and eastern mosquito fish populations. Fin ray counts, sometimes used to distinguish the two species from one another, demonstrate more eastern (G. holbrooki) phenotype fish within the molecular genetic hybrid zone today. Mosquito fish are globally invasive, often found on the leading edge of flooded waters that they colonize, so the impact of hurricanes in the wake of climate change was also evaluated. An increase in the frequency and intensity of hurricanes in the hybrid region has occurred, and this point warrants further attention since hurricanes are known to move these aggressive, invasive species into novel territory. This work contributes to our classical understanding of hybrid zone temporal dynamics, refines our understanding of mosquito fish genetics in their native range, evaluates important genotype–phenotype relationships, and identifies a potential new impact of climate change.