Natural History, Microbes and Sequences: Shouldn't We Look Back Again to Organisms?

The discussion on the existence of prokaryotic species is reviewed. The demonstration that several different mechanisms of genetic exchange and recombination exist has led some to a radical rejection of the possibility of bacterial species and, in general, the applicability of traditional classification categories to the prokaryotic domains. However, in spite of intense gene traffic, prokaryotic groups are not continuously variable but form discrete clusters of phenotypically coherent, well-defined, diagnosable groups of individual organisms. Molecularization of life sciences has led to biased approaches to the issue of the origins of biodiversity, which has resulted in the increasingly extended tendency to emphasize genes and sequences and not give proper attention to organismal biology. As argued here, molecular and organismal approaches that should be seen as complementary and not opposed views of biology

Operative versus non-operative management of pediatric medial epicondyle fractures: a systematic review

There is ongoing debate about the management of medial epicondyle fractures in the pediatric population. This systematic review evaluated non-operative versus operative treatment of medial epicondyle fractures in pediatric and adolescent patients over the last six decades. A systematic review of the available literature was performed. Frequency-weighted mean union times were used to compare union rates for closed versus open treatments. Moreover, functional outcomes and range-of-motion variables were correlated with varying treatment modalities. Any complications, including ulnar nerve symptoms, pain, instability, infection, and residual deformity, were cataloged. Fourteen studies, encompassing 498 patients, met the inclusion/exclusion criteria. There were 261 males and 132 female patients; the frequency-weighted average age was 11.93 years. The follow-up range was 6–216 months. Under the cumulative random effects model, the odds of union with operative fixation was 9.33 times the odds of union with non-operative treatment (P < 0.0001). There was no significant difference between operative and non-operative treatments in terms of pain at final follow-up (P = 0.73) or ulnar nerve symptoms (P = 0.412). Operative treatment affords a significantly higher union rate over the non-operative management of medial epicondyle fractures. There was no difference in pain at final follow-up between operative and non-operative treatments. As surgical indications evolve, and the functional demands of pediatric patients increase, surgical fixation should be strongly considered to achieve stable fixation and bony union

Global distribution maps of the leishmaniases

The leishmaniases are vector-borne diseases that have a broad global distribution throughout much of the Americas, Africa, and Asia. Despite representing a significant public health burden, our understanding of the global distribution of the leishmaniases remains vague, reliant upon expert opinion and limited to poor spatial resolution. A global assessment of the consensus of evidence for leishmaniasis was performed at a sub-national level by aggregating information from a variety of sources. A database of records of cutaneous and visceral leishmaniasis occurrence was compiled from published literature, online reports, strain archives, and GenBank accessions. These, with a suite of biologically relevant environmental covariates, were used in a boosted regression tree modelling framework to generate global environmental risk maps for the leishmaniases. These high-resolution evidence-based maps can help direct future surveillance activities, identify areas to target for disease control and inform future burden estimation efforts. DOI: http://dx.doi.org/10.7554/eLife.02851.00

Host-parasite co-metabolic activation of antitrypanosomal aminomethyl-benzoxaboroles

<div><p>Recent development of benzoxaborole-based chemistry gave rise to a collection of compounds with great potential in targeting diverse infectious diseases, including human African Trypanosomiasis (HAT), a devastating neglected tropical disease. However, further medicinal development is largely restricted by a lack of insight into mechanism of action (MoA) in pathogenic kinetoplastids. We adopted a multidisciplinary approach, combining a high-throughput forward genetic screen with functional group focused chemical biological, structural biology and biochemical analyses, to tackle the complex MoAs of benzoxaboroles in <i>Trypanosoma brucei</i>. We describe an oxidative enzymatic pathway composed of host semicarbazide-sensitive amine oxidase and a trypanosomal aldehyde dehydrogenase TbALDH3. Two sequential reactions through this pathway serve as the key underlying mechanism for activating a series of 4-aminomethylphenoxy-benzoxaboroles as potent trypanocides; the methylamine parental compounds as pro-drugs are transformed first into intermediate aldehyde metabolites, and further into the carboxylate metabolites as effective forms. Moreover, comparative biochemical and crystallographic analyses elucidated the catalytic specificity of TbALDH3 towards the benzaldehyde benzoxaborole metabolites as xenogeneic substrates. Overall, this work proposes a novel drug activation mechanism dependent on both host and parasite metabolism of primary amine containing molecules, which contributes a new perspective to our understanding of the benzoxaborole MoA, and could be further exploited to improve the therapeutic index of antimicrobial compounds.</p></div

Ebola Zaire Virus Blocks Type I Interferon Production by Exploiting the Host SUMO Modification Machinery

Ebola Zaire virus is highly pathogenic for humans, with case fatality rates approaching 90% in large outbreaks in Africa. The virus replicates in macrophages and dendritic cells (DCs), suppressing production of type I interferons (IFNs) while inducing the release of large quantities of proinflammatory cytokines. Although the viral VP35 protein has been shown to inhibit IFN responses, the mechanism by which it blocks IFN production has not been fully elucidated. We expressed VP35 from a mouse-adapted variant of Ebola Zaire virus in murine DCs by retroviral gene transfer, and tested for IFN transcription upon Newcastle Disease virus (NDV) infection and toll-like receptor signaling. We found that VP35 inhibited IFN transcription in DCs following these stimuli by disabling the activity of IRF7, a transcription factor required for IFN transcription. By yeast two-hybrid screens and coimmunoprecipitation assays, we found that VP35 interacted with IRF7, Ubc9 and PIAS1. The latter two are the host SUMO E2 enzyme and E3 ligase, respectively. VP35, while not itself a SUMO ligase, increased PIAS1-mediated SUMOylation of IRF7, and repressed Ifn transcription. In contrast, VP35 did not interfere with the activation of NF-κB, which is required for induction of many proinflammatory cytokines. Our findings indicate that Ebola Zaire virus exploits the cellular SUMOylation machinery for its advantage and help to explain how the virus overcomes host innate defenses, causing rapidly overwhelming infection to produce a syndrome resembling fulminant septic shock

Thermal Adaptation and Diversity in Tropical Ecosystems: Evidence from Cicadas (Hemiptera, Cicadidae)

The latitudinal gradient in species diversity is a central problem in ecology. Expeditions covering approximately 16°54′ of longitude and 21°4′ of latitude and eight Argentine phytogeographic regions provided thermal adaptation data for 64 species of cicadas. We test whether species diversity relates to the diversity of thermal environments within a habitat. There are general patterns of the thermal response values decreasing in cooler floristic provinces and decreasing maximum potential temperature within a habitat except in tropical forest ecosystems. Vertical stratification of the plant communities leads to stratification in species using specific layers of the habitat. There is a decrease in thermal tolerances in species from the understory communities in comparison to middle level or canopy fauna. The understory Herrera umbraphila Sanborn & Heath is the first diurnally active cicada identified as a thermoconforming species. The body temperature for activity in H. umbraphila is less than and significantly different from active body temperatures of all other studied species regardless of habitat affiliation. These data suggest that variability in thermal niches within the heterogeneous plant community of the tropical forest environments permits species diversification as species adapt their physiology to function more efficiently at temperatures different from their potential competitors

Direct and Inverse Computation of Jacobi Matrices of Infinite Homogeneous Affine I.F.S

We introduce a new set of algorithms to compute Jacobi matrices associated with measures generated by infinite systems of iterated functions. We demonstrate their relevance in the study of theoretical problems, such as the continuity of these measures and the logarithmic capacity of their support. Since our approach is based on a reversible transformation between pairs of Jacobi matrices, we also discuss its application to an inverse / approximation problem. Numerical experiments show that the proposed algorithms are stable and can reliably compute Jacobi matrices of large order.Comment: 20 pages 6 figure