bluuebunny/crossref_metadata_2025 huggingface dataset:
A pilot study evaluating the prognostic utility of platelet indices in dogs with septic peritonitis
Authors: Llewellyn Efa A. , Todd Jeffrey M. , Sharkey Leslie C. , Rendahl Aaron
Published: July 2017

Objective

To characterize platelet indices at time of diagnosis of septic peritonitis in dogs and to assess the relationship between platelet parameter data and survival to discharge in dogs treated surgically.

Design

Retrospective, observational, descriptive pilot study from 2009 to 2014.

Setting

University teaching hospital.

Animals

Forty‐eight dogs diagnosed with septic peritonitis were included in this study. Thirty‐six dogs had surgical source control. Blood samples from 46 healthy control dogs were used for reference interval (RI) generation.

Interventions

None.

Measurements and Main Results

Dogs with septic peritonitis had significantly increased mean values for mean platelet volume (MPV), plateletcrit (PCT), and platelet distribution width (PDW) with increased proportions of dogs having values above the RI compared to healthy dogs. A significantly increased proportion of dogs with septic peritonitis had platelet counts above (12.5%) and below (8.3%) the RI, with no significant difference in mean platelet count compared to healthy dogs. No significant differences in the mean platelet count, MPV, PCT, or PDW were found between survivors and nonsurvivors in dogs with surgical source control; however, dogs with MPV values above the RI had significantly increased mortality compared to dogs within the RI (P = 0.025). Values outside the RI for other platelet parameters were not associated with significant differences in mortality.

Conclusions

Dogs with septic peritonitis have increased frequency of thrombocytosis and thrombocytopenia with increased MPV, PCT, and PDW. An increased MPV may be a useful indicator of increased risk of mortality in dogs treated surgically.
Mathematics Teachers’ Beliefs about Inquiry-based Learning after a Professional Development Course–An International Study
Authors: Maass Katja , Swan Malcolm , Aldorf Anna-Maria
Published: July 2017

Inquiry-based learning (IBL) is a more student-centered approach to mathematics teaching that is recommended by many policy and curriculum documents across Europe. However, it is not easy for teachers to change from a more teacher-centered way of teaching to inquiry-based teaching as this involves a change of their role in class. Professional development courses are one way to help teachers with this endeavor. Within the discussion of effective professional development, beliefs are often named as an important influencing factor. In this respect, much research has been carried out on how beliefs on mathematics teaching impact the outcomes of the course. However, there has been much less research on what beliefs mathematics teachers develop on inquiry-based learning and how this might impact their (perceived) classroom teaching. Therefore, this paper presents an international research study carried out within the European Project Primas, in which professional development courses on inquiry-based learning were conducted in 12 countries. Using the case-study approach, this paper aims at answering the following questions: 1. What kind of beliefs about IBL do mathematics teachers across Europe develop? 2. How do these beliefs relate to teachers’ perceived enactments of IBL?
The effect of different diet on life history parameters and growth of Oppia denticulata (Acari: Oribatida: Oppiidae)
Authors: Seniczak Anna , Seniczak Stanisław , Słowikowska Mariola , Paluszak Zbigniew
Published: July 2017

The effect of different diet on Oppia denticulata was studied during a 4-month laboratory experiment, based on daily observations. This species is known as microphytophagous (i.e. feeding on bacteria and/or fungal hyphae and/or algae), like other species of Oppiidae, but our observations show its wider diet. We tested 11 types of food, including homogenous diet [green algae, lichens, fungi (dry yeasts, Trichoderma viride, Penicillium chrysogenum), nematodes], and combined diet [green algae and nematodes, lichens and nematodes, dry yeasts and nematodes, T. viride and nematodes, P. chrysogenum and nematodes]. The basic population parameters (fertility, mortality, sex ratio), time of development, population growth in four months and body length were compared between all groups. Observations on biology of O. denticulata were also made. The most favourable diet for O. denticulata was a combination of T. viride and nematodes, which allowed the highest population growth (about 50 times higher than the least favourable food, a combination of P. chrysogenum and nematodes), due to highest fertility and shortest development. Good population parameters and largest size were obtained on yeasts (served alone or with nematodes). This species did not do well on P. chrysogenum, probably because it produces penicillin.
‘Scientific wellness’ study divides researchers
Authors: Cross Ryan
Published: July 2017

Famed biologist's spinoff company sells personalized health monitoring and coaching.
Kynurenines: Tryptophan’s metabolites in exercise, inflammation, and mental health
Authors: Cervenka Igor , Agudelo Leandro Z. , Ruas Jorge L.
Published: July 2017

From stomach ache to depression

Our gut hurts and we feel miserable. Such disparate phenomena are mechanistically connected, but how? Cervenka
et al.
review the many pathways taken by dietary tryptophan as it is metabolized into kynurenines. These metabolites distribute into homeostatic networks that integrate diverse aspects of mammalian physiology. Depending on physiological context, kynurenines influence health and disease states ranging from intestinal conditions to inflammation to cancer progression. Further, they can mediate the effects of exercise, mood, and neuronal excitability and, ultimately, communicate with the microbiota.

Science
, this issue p.
eaaf9794
ChromEMT: Visualizing 3D chromatin structure and compaction in interphase and mitotic cells
Authors: Ou Horng D. , Phan Sébastien , Deerinck Thomas J. , Thor Andrea , Ellisman Mark H. , O’Shea Clodagh C.
Published: July 2017

A close-up view inside the nucleus

The nuclei of human cells contain 2 meters of genomic DNA. How does it all fit? Compaction starts with the DNA wrapping around histone octamers to form nucleosomes, but it is unclear how these further compress into mitotic chromosomes. Ou
et al.
describe a DNA-labeling method that allows them to visualize chromatin organization in human cells (see the Perspective by Larson and Misteli). They show that chromatin forms flexible chains with diameters between 5 and 24 nm. In mitotic chromosomes, chains bend back on themselves to pack at high density, whereas during interphase, the chromatin chains are more extended.

Science
, this issue p.
eaag0025
; see also p.
354
CAT-tailing as a fail-safe mechanism for efficient degradation of stalled nascent polypeptides
Authors: Kostova Kamena K. , Hickey Kelsey L. , Osuna Beatriz A. , Hussmann Jeffrey A. , Frost Adam , Weinberg David E. , Weissman Jonathan S.
Published: July 2017

A tale of CAT tails

When protein translation fails, the incomplete nascent polypeptide is targeted for degradation by the highly conserved ribosome-associated quality control complex (RQC). Mutations in RQC components lead to stress at the cellular level and neurodegeneration at the organismal level. Recent studies have shown that RQC tags partially synthesize proteins with C-terminal alanine and threonine (CAT) tails in an unusual elongation reaction. Working in yeast, Kostova
et al.
elucidated the role of this process. CAT-tailing is a fail-safe mechanism to ensure the degradation of partially synthesized proteins. The elongation process appears to “push” lysines out of the ribosome exit tunnel, which allows them to be marked by ubiquitin degradation signals.

Science
, this issue p.
414
Direct optical lithography of functional inorganic nanomaterials
Authors: Wang Yuanyuan , Fedin Igor , Zhang Hao , Talapin Dmitri V.
Published: July 2017

Patterning without polymers

Nanoscale patterning usually requires multiple steps to mask, pattern, and develop sequential layers. One overriding concern is to obtain compatibility between all the materials, as well as the patterning techniques used, to ensure accurate and clean processing. Wang
et al.
use light-responsive ligands to change the solubility of nanocrystals in specific solvents, so that development can be done by simple redispersion of nanocrystals in dark regions (see the Perspective by Striccoli). The process can fully utilize the advantages of conventional semiconductor processing, but without the need for photoresists, because the nanocrystals are only deposited where they are exposed to light.

Science
, this issue p.
385
; see also p.
353
Reconfiguration of DNA molecular arrays driven by information relay
Authors: Song Jie , Li Zhe , Wang Pengfei , Meyer Travis , Mao Chengde , Ke Yonggang
Published: July 2017

Relaying information on DNA tiles

Arrays of modular DNA units can relay information by transforming their internal shape in response to binding of DNA trigger strands. Song
et al.
synthesized rectangular arrays of double-stranded DNA (see the Perspective by Yang and Lin). Transient square configurations transform into two stable rectangular structures by pinching across a pair of opposing vertices. Binding of DNA trigger strands causes switching into the alternative stable configuration. The tiles thus create a cascade of transformations along a particular pathway, thereby transmitting information about where binding occurred.

Science
, this issue p.
eaan3377
; see also p.
352
Al Gore's inconvenient update
An Inconvenient Sequel: Truth to Power
Bonni Cohen and Jon Shenk, directors
Actual Films and Participant Media, 2017. In theaters 4 August 2017.
Authors: Thompson Valerie
Published: July 2017

The former vice president's climate activism takes center stage once again
N-Terminal Pfs230 Domain Produced in Baculovirus as a Biological Active Transmission-Blocking Vaccine Candidate
Authors: Lee Shwu-Maan , Wu Chia-Kuei , Plieskatt Jordan L. , Miura Kazutoyo , Hickey John M. , King C. Richter
Published: July 2017

Transmission-blocking vaccines have the potential to accelerate malaria parasite elimination by inducing antibodies that block parasite transmission from humans to mosquitoes. Pfs230, a gametocyte surface protein involved in gamete function, has long been a promising candidate. Due to the large size (3,135 amino acids), complex domains, and repeating 6-cysteine (6-Cys) motifs with a multitude of disulfide bonds, the feasibility of expression of a full-length protein has been difficult. A priority focus, therefore, has been on the generation of single domains, including N-terminal fragments. Here we utilized a heterologous expression system, baculovirus, to produce an N-terminal domain of Pfs230 (Pfs230C1). Pfs230C1 (amino acids 443 to 731) with a polyhistidine affinity tag was expressed in Super Sf9 cells. Since the native host lacks glycosylation machinery, a single N585Q mutation was made to eliminate potential N-linked glycosylation. The expressed protein, purified by nickel affinity, ion exchange, and size exclusion chromatography to >90% purity, was present in monomeric form with an observed mass of 33,510 Da (matching oxidized form). Peptide mapping and disulfide analysis confirmed the proper formation of predicted disulfide bonds. Antibodies, generated against Pfs230C1 in mice, bound to the gametocyte in an immunofluorescence assay (IFA) and demonstrated functional activity in both the standard membrane feeding assay (SMFA) and the exflagellation assay (EXA). The biochemical, biophysical, and immunological results reported herein support the continued advancement of an N-terminal Pfs230 antigen (Pfs230C1) as a component of a transmission-blocking vaccine. Our results also support the continued use of the scalable baculovirus expression system for the generation of complex
Plasmodium
proteins.
Fusarium Keratitis in Germany
Authors: Walther Grit , Stasch Serena , Kaerger Kerstin , Hamprecht Axel , Roth Mathias , Cornely Oliver A. , Geerling Gerd , Mackenzie Colin R. , Kurzai Oliver , von Lilienfeld-Toal Marie
Published: July 2017

Fusarium
keratitis is a destructive eye infection that is difficult to treat and results in poor outcome. In tropical and subtropical areas, the infection is relatively common and associated with trauma or chronic eye diseases. However, in recent years, an increased incidence has been reported in temperate climate regions. At the German National Reference Center, we have observed a steady increase in case numbers since 2014. Here, we present the first German case series of eye infections with
Fusarium
species. We identified
Fusarium
isolates from the eye or eye-related material from 22 patients in 2014 and 2015. Thirteen isolates belonged to the
Fusarium solani
species complex (FSSC), 6 isolates belonged to the
Fusarium oxysporum
species complex (FOSC), and three isolates belonged to the
Fusarium fujikuroi
species complex (FFSC). FSSC was isolated in 13 of 15 (85%) definite infections and FOSC in 3 of 4 (75%) definite contaminations. Furthermore, diagnosis from contact lens swabs or a culture of contact lens solution turned out to be highly unreliable. FSSC isolates differed from FOSC and FFSC by a distinctly higher MIC for terbinafine. Outcome was often adverse, with 10 patients requiring keratoplasty or enucleation. The use of natamycin as the most effective agent against keratitis caused by filamentous fungi was rare in Germany, possibly due to restricted availability. Keratitis caused by
Fusarium
spp. (usually FSSC) appears to be a relevant clinical problem in Germany, with the use of contact lenses as the predominant risk factor. Its outcome is often adverse.
Survival, Persistence, and Isolation of the Emerging Multidrug-Resistant Pathogenic Yeast Candida auris on a Plastic Health Care Surface
Authors: Welsh Rory M. , Bentz Meghan L. , Shams Alicia , Houston Hollis , Lyons Amanda , Rose Laura J. , Litvintseva Anastasia P.
Published: July 2017

The emerging multidrug-resistant pathogenic yeast
Candida auris
represents a serious threat to global health. Unlike most other
Candida
species, this organism appears to be commonly transmitted within health care facilities and causes health care-associated outbreaks. To better understand the epidemiology of this emerging pathogen, we investigated the ability of
C. auris
to persist on plastic surfaces common in health care settings compared with that of
Candida parapsilosis
, a species known to colonize the skin and plastics. Specifically, we compiled comparative and quantitative data essential to understanding the vehicles of spread and the ability of both species to survive and persist on plastic surfaces under controlled conditions (25°C and 57% relative humidity), such as those found in health care settings. When a test suspension of 10
4
cells was applied and dried on plastic surfaces,
C. auris
remained viable for at least 14 days and
C. parapsilosis
for at least 28 days, as measured by CFU. However, survival measured by esterase activity was higher for
C. auris
than
C. parapsilosis
throughout the 28-day study. Given the notable length of time
Candida
species survive and persist outside their host, we developed methods to more effectively culture
C. auris
from patients and their environment. Using our enrichment protocol, public health laboratories and researchers can now readily isolate
C. auris
from complex microbial communities (such as patient skin, nasopharynx, and stool) as well as environmental biofilms, in order to better understand and prevent
C. auris
colonization and transmission.
Evaluation of the Rapid Polymyxin NP Test for Polymyxin B Resistance Detection Using Enterobacter cloacae and Enterobacter aerogenes Isolates
Authors: Simar Shelby , Sibley Diane , Ashcraft Deborah , Pankey George
Published: July 2017

Polymyxin resistance is an increasing problem worldwide. Currently, determining susceptibility to polymyxins is problematic and lengthy. Polymyxins diffuse poorly into agar, potentially giving inaccurate disk diffusion and Etest results. A rapid screening test (2 h) for the detection of polymyxin resistance in
Enterobacteriaceae
, developed by P. Nordmann and L. Poirel (rapid polymyxin NP test) in 2016, detects glucose metabolization in the presence of polymyxin E (PE) and PB via pH-induced color change. The sensitivity and specificity were 99.3 and 95.4%, respectively, with results obtained in ≤2 h. Our goal was to evaluate this test using PB against larger numbers of
Enterobacter
. A total of 143 nonduplicate
Enterobacter
isolates (102
E. cloacae
complex, 41
E. aerogenes
) were tested, including 136 collected from Ochsner Health System patients from March to May 2016 and 7 previously determined PB-resistant
E. cloacae
isolates from JMI Laboratories. MICs were determined via broth microdilution. For the rapid polymyxin NP test, a color change from orange to yellow is positive; a weak/no color change is deemed negative after 4 h. Of 143
Enterobacter
isolates, 25 were determined to be PB resistant by broth microdilution (MIC > 2 μg/ml), including all 7 JMI isolates. Of these 25, 7 were positive by the rapid polymyxin NP test (included 3/7 JMI isolates). All 118 isolates determined to be PB susceptible by broth microdilution were NP test negative. The sensitivity and specificity for the rapid polymyxin NP test were 25 and 100%, respectively, compared to broth microdilution. Although the rapid polymyxin NP test is a much faster method (2 to 4 h) for polymyxin resistance determination compared to broth microdilution (16 to 20 h), our study indicates that it may be subject to limitations when testing
Enterobacter
.
Designing HIV Testing Algorithms Based on 2015 WHO Guidelines Using Data from Six Sites in Sub-Saharan Africa
Authors: Kosack Cara S. , Shanks Leslie , Beelaert Greet , Benson Tumwesigye , Savane Aboubacar , Ng'ang'a Anne , Bita André , Zahinda Jean-Paul B. N. , Fransen Katrien , Page Anne-Laure
Published: July 2017

Our objective was to evaluate the performance of HIV testing algorithms based on WHO recommendations, using data from specimens collected at six HIV testing and counseling sites in sub-Saharan Africa (Conakry, Guinea; Kitgum and Arua, Uganda; Homa Bay, Kenya; Douala, Cameroon; Baraka, Democratic Republic of Congo). A total of 2,780 samples, including 1,306 HIV-positive samples, were included in the analysis. HIV testing algorithms were designed using Determine as a first test. Second and third rapid diagnostic tests (RDTs) were selected based on site-specific performance, adhering where possible to the WHO-recommended minimum requirements of ≥99% sensitivity and specificity. The threshold for specificity was reduced to 98% or 96% if necessary. We also simulated algorithms consisting of one RDT followed by a simple confirmatory assay. The positive predictive values (PPV) of the simulated algorithms ranged from 75.8% to 100% using strategies recommended for high-prevalence settings, 98.7% to 100% using strategies recommended for low-prevalence settings, and 98.1% to 100% using a rapid test followed by a simple confirmatory assay. Although we were able to design algorithms that met the recommended PPV of ≥99% in five of six sites using the applicable high-prevalence strategy, options were often very limited due to suboptimal performance of individual RDTs and to shared falsely reactive results. These results underscore the impact of the sequence of HIV tests and of shared false-reactivity data on algorithm performance. Where it is not possible to identify tests that meet WHO-recommended specifications, the low-prevalence strategy may be more suitable.
Role of Viral Hemorrhagic Septicemia Virus Matrix (M) Protein in Suppressing Host Transcription
Authors: Ke Qi , Weaver Wade , Pore Adam , Gorgoglione Bartolomeo , Wildschutte Julia Halo , Xiao Peng , Shepherd Brian S. , Spear Allyn , Malathi Krishnamurthy , Stepien Carol A. , Vakharia Vikram N. , Leaman Douglas W.
Published: July 2017

Viral hemorrhagic septicemia virus (VHSV) is a pathogenic fish rhabdovirus found in discrete locales throughout the Northern Hemisphere. VHSV infection of fish cells leads to upregulation of the host's virus detection response, but the virus quickly suppresses interferon (IFN) production and antiviral gene expression. By systematically screening each of the six VHSV structural and nonstructural genes, we identified matrix protein (M) as the virus' most potent antihost protein. Only M of VHSV genotype IV sublineage b (VHSV-IVb) suppressed mitochondrial antiviral signaling protein (MAVS) and type I IFN-induced gene expression in a dose-dependent manner. M also suppressed the constitutively active simian virus 40 (SV40) promoter and globally decreased cellular RNA levels. Chromatin immunoprecipitation (ChIP) studies illustrated that M inhibited RNA polymerase II (RNAP II) recruitment to gene promoters and decreased RNAP II C-terminal domain (CTD) Ser2 phosphorylation during VHSV infection. However, transcription directed by RNAP I to III was suppressed by M. To identify regions of functional importance, M proteins from a variety of VHSV strains were tested in cell-based transcriptional inhibition assays. M of a particular VHSV-Ia strain, F1, was significantly less potent than IVb M at inhibiting SV40/luciferase (Luc) expression yet differed by just 4 amino acids. Mutation of D62 to alanine alone, or in combination with an E181-to-alanine mutation (D62A E181A), dramatically reduced the ability of IVb M to suppress host transcription. Introducing either M D62A or D62A E181A mutations into VHSV-IVb via reverse genetics resulted in viruses that replicated efficiently but exhibited less cytotoxicity and reduced antitranscriptional activities, implicating M as a primary regulator of cytopathicity and host transcriptional suppression.

IMPORTANCE
Viruses must suppress host antiviral responses to replicate and spread between hosts. In these studies, we identified the matrix protein of the deadly fish novirhabdovirus VHSV as a critical mediator of host suppression during infection. Our studies indicated that M alone could block cellular gene expression at very low expression levels. We identified several subtle mutations in M that were less potent at suppressing host transcription. When these mutations were engineered back into recombinant viruses, the resulting viruses replicated well but elicited less toxicity in infected cells and activated host innate immune responses more robustly. These data demonstrated that VHSV M plays an important role in mediating both virus-induced cell toxicity and viral replication. Our data suggest that its roles in these two processes can be separated to design effective attenuated viruses for vaccine candidates.
Effects of Inner Nuclear Membrane Proteins SUN1/UNC-84A and SUN2/UNC-84B on the Early Steps of HIV-1 Infection
Authors: Schaller Torsten , Bulli Lorenzo , Pollpeter Darja , Betancor Gilberto , Kutzner Juliane , Apolonia Luis , Herold Nikolas , Burk Robin , Malim Michael H.
Published: July 2017

Human immunodeficiency virus type 1 (HIV-1) infection of dividing and nondividing cells involves regulatory interactions with the nuclear pore complex (NPC), followed by translocation to the nucleus and preferential integration into genomic areas in proximity to the inner nuclear membrane (INM). To identify host proteins that may contribute to these processes, we performed an overexpression screen of known membrane-associated NE proteins. We found that the integral transmembrane proteins SUN1/UNC84A and SUN2/UNC84B are potent or modest inhibitors of HIV-1 infection, respectively, and that suppression corresponds to defects in the accumulation of viral cDNA in the nucleus. While laboratory strains (HIV-1
NL4.3
and HIV-1
IIIB
) are sensitive to SUN1-mediated inhibition, the transmitted founder viruses RHPA and ZM247 are largely resistant. Using chimeric viruses, we identified the HIV-1 capsid (CA) protein as a major determinant of sensitivity to SUN1, and
in vitro
-assembled capsid-nucleocapsid (CANC) nanotubes captured SUN1 and SUN2 from cell lysates. Finally, we generated
SUN1
−/−
and
SUN2
−/−
cells by using CRISPR/Cas9 and found that the loss of SUN1 had no effect on HIV-1 infectivity, whereas the loss of SUN2 had a modest suppressive effect. Taken together, these observations suggest that SUN1 and SUN2 may function redundantly to modulate postentry, nuclear-associated steps of HIV-1 infection.

IMPORTANCE
HIV-1 causes more than 1 million deaths per year. The life cycle of HIV-1 has been studied extensively, yet important steps that occur between viral capsid release into the cytoplasm and the expression of viral genes remain elusive. We propose here that the INM components SUN1 and SUN2, two members of the linker of nucleoskeleton and cytoskeleton (LINC) complex, may interact with incoming HIV-1 replication complexes and affect key steps of infection. While overexpression of these proteins reduces HIV-1 infection, disruption of the individual
SUN2
and
SUN1
genes leads to a mild reduction or no effect on infectivity, respectively. We speculate that SUN1/SUN2 may function redundantly in early HIV-1 infection steps and therefore influence HIV-1 replication and pathogenesis.
Bam35 Tectivirus Intraviral Interaction Map Unveils New Function and Localization of Phage ORFan Proteins
Authors: Berjón-Otero Mónica , Lechuga Ana , Mehla Jitender , Uetz Peter , Salas Margarita , Redrejo-Rodríguez Modesto
Published: July 2017

The family
Tectiviridae
comprises a group of tailless, icosahedral, membrane-containing bacteriophages that can be divided into two groups by their hosts, either Gram-negative or Gram-positive bacteria. While the first group is composed of PRD1 and nearly identical well-characterized lytic viruses, the second one includes more variable temperate phages, like GIL16 or Bam35, whose hosts are
Bacillus cereus
and related Gram-positive bacteria. In the genome of Bam35, nearly half of the 32 annotated open reading frames (ORFs) have no homologs in databases (ORFans), being putative proteins of unknown function, which hinders the understanding of their biology. With the aim of increasing knowledge about the viral proteome, we carried out a comprehensive yeast two-hybrid analysis of all the putative proteins encoded by the Bam35 genome. The resulting protein interactome comprised 76 unique interactions among 24 proteins, of which 12 have an unknown function. These results suggest that the P17 protein is the minor capsid protein of Bam35 and P24 is the penton protein, with the latter finding also being supported by iterative threading protein modeling. Moreover, the inner membrane transglycosylase protein P26 could have an additional structural role. We also detected interactions involving nonstructural proteins, such as the DNA-binding protein P1 and the genome terminal protein (P4), which was confirmed by coimmunoprecipitation of recombinant proteins. Altogether, our results provide a functional view of the Bam35 viral proteome, with a focus on the composition and organization of the viral particle.

IMPORTANCE
Tailless viruses of the family
Tectiviridae
can infect commensal and pathogenic Gram-positive and Gram-negative bacteria. Moreover, they have been proposed to be at the evolutionary origin of several groups of large eukaryotic DNA viruses and self-replicating plasmids. However, due to their ancient origin and complex diversity, many tectiviral proteins are ORFans of unknown function. Comprehensive protein-protein interaction (PPI) analysis of viral proteins can eventually disclose biological mechanisms and thus provide new insights into protein function unattainable by studying proteins one by one. Here we comprehensively describe intraviral PPIs among tectivirus Bam35 proteins determined using multivector yeast two-hybrid screening, and these PPIs were further supported by the results of coimmunoprecipitation assays and protein structural models. This approach allowed us to propose new functions for known proteins and hypothesize about the biological role of the localization of some viral ORFan proteins within the viral particle that will be helpful for understanding the biology of tectiviruses infecting Gram-positive bacteria.
Potential markers and metabolic processes involved in the mechanism of radiation-induced heart injury
Authors: Slezak Jan , Kura Branislav , Babal Pavel , Barancik Miroslav , Ferko Miroslav , Frimmel Karel , Kalocayova Barbora , Kukreja Rakesh C. , Lazou Antigone , Mezesova Lucia , Okruhlicova Ludmila , Ravingerova Tanya , Singal Pawan K. , Szeiffova Bacova Barbara , Viczenczova Csilla , Vrbjar Norbert , Tribulova Narcis
Published: July 2017

Irradiation of normal tissues leads to acute increase in reactive oxygen/nitrogen species that serve as intra- and inter-cellular signaling to alter cell and tissue function. In the case of chest irradiation, it can affect the heart, blood vessels, and lungs, with consequent tissue remodelation and adverse side effects and symptoms. This complex process is orchestrated by a large number of interacting molecular signals, including cytokines, chemokines, and growth factors. Inflammation, endothelial cell dysfunction, thrombogenesis, organ dysfunction, and ultimate failing of the heart occur as a pathological entity — “radiation-induced heart disease” (RIHD) that is major source of morbidity and mortality. The purpose of this review is to bring insights into the basic mechanisms of RIHD that may lead to the identification of targets for intervention in the radiotherapy side effect. Studies of authors also provide knowledge about how to select targeted drugs or biological molecules to modify the progression of radiation damage in the heart. New prospective studies are needed to validate that assessed factors and changes are useful as early markers of cardiac damage.
Population structure in two geographically sympatric and congeneric ectoparasites (Cimex adjunctusandCimex lectularius) in the North American Great Lakes region
Authors: Talbot Benoit , Vonhof Maarten J. , Broders Hugh G. , Fenton M. Brock , Keyghobadi Nusha
Published: July 2017

Subdivided populations can be described by different models of population structure that reflect population organization, dynamics, and connectivity. We used genetic data to investigate population structure in two geographically sympatric, congeneric species of generalist ectoparasites of warm-blooded animals. We characterized the spatial genetic structure of the eastern bat bug (Cimex adjunctus Barber, 1939), an understudied and fairly abundant species, using microsatellite markers at a spatial scale representing contemporary dispersal of the species. We found seven genetic clusters, global [Formula: see text] of 0.2, 33% of genetic variation among sites, and nonsignificant isolation-by-distance. We compared these results with the common bed bug (Cimex lectularius L., 1758), a closely related but conversely well-known species, in the same geographic area. We found stronger genetic structuring in C. lectularius than in C. adjunctus, with 11 genetic clusters, [Formula: see text] of 0.7, 57% of genetic variation among sites, and significant but weak isolation-by-distance (R2= 0.09). These results suggest that while both species can be described as having classic metapopulation structure, C. adjunctus leans more towards a patchy population and C. lectularius leans more towards a nonequilibrium metapopulation. The difference in population structure between these species may be attributable to differences in movement potential and extinction–colonization dynamics.
Body-size and growth-rate divergence among populations of threespine stickleback (Gasterosteus aculeatus) in Cook Inlet, Alaska, USA
Authors: Rollins J.L.
Published: July 2017

Body size is one of the most perceptible traits of organisms and is an important fitness proxy in evolutionary studies. Oceanic threespine stickleback (Gasterosteus aculeatus L., 1758) have colonized and adapted to numerous freshwater habitats throughout the Holarctic since the most recent glacial retreat, giving us natural “replicates” of both convergent and divergent evolution. I observed considerable body-size variation among 22 threespine stickleback populations within a small region surrounding Cook Inlet, Alaska, USA. Larger bodied populations tended to have bimodal size-frequency distributions, whereas most smaller bodied populations had unimodal distributions. Bimodal distributions suggested the presence of at least two age classes within large-bodied populations. I used a Bayesian approach to infer mean size of presumed age-1 and age-2+ fish from bimodal size-frequency distributions; I found significant differences in size among populations within ages and sexes, suggesting significant divergence in growth rate among populations. I did not find significant correlations between growth rates (age-specific size) and geographic distances among populations, drainage affiliation, or distance to the sea. Thus, historical processes like isolation by distance, gene flow, or recent common ancestry did not explain differences in growth among populations, suggesting a role for local adaptation or phenotypic plasticity in size divergence.
Degradation and Recovery in Changing Forest Landscapes: A Multiscale Conceptual Framework
Authors: Ghazoul Jaboury , Chazdon Robin
Published: July 2017

Conceptual confusion revolves around how to define, assess, and overcome land, ecosystem, and landscape degradation. Common elements link degradation and recovery processes, offering ways to advance local, regional, and global initiatives to reduce degradation and promote the recovery of ecosystems and landscapes in forest biomes. Biophysical attributes of degradation and recovery can be measured, but the relevance of selected attributes across scales is subject to values that determine preferred states. Degradation defined in the context of a resilience-based approach is a state where the capacity for regeneration is greatly reduced or lost, recovery is arrested, core interactions and feedbacks are broken, and human intervention is required to initiate a trajectory of recovery. Another approach combines degradation and recovery processes through the concept of recovery debt, the cumulative lost benefits incurred, relative to a target state during phases of degradation and recovery. Degradation and recovery can also be described in terms of societal willingness to invest in improved management or restoration. Interventions can facilitate recovery to new stable or persistent states that provide multiple social and ecological benefits at land, ecosystem, and landscape scales. Multiple trajectories of recovery, as well as historic and ongoing chronic environmental change, might, however, mean that recovery to an original reference state is not possible.
Metabolic acidosis stimulates the production of the antimicrobial peptide cathelicidin in rabbit urine
Authors: Peng Hu , Purkerson Jeffrey M. , Schwaderer Andy L. , Schwartz George J.
Published: July 2017

Intercalated cells of the collecting duct (CD) are critical for acid-base homeostasis and innate immune defense of the kidney. Little is known about the impact of acidosis on innate immune defense in the distal nephron. Urinary tract infections are mainly due to Escherichia coli and are an important risk factor for development of chronic kidney disease. While the effect of urinary pH on growth of E. coli is well established, in this study, we demonstrate that acidosis increases urine antimicrobial activity due, at least in part, to induction of cathelicidin expression within the CD. Acidosis was induced in rabbits by adding NH4Cl to the drinking water and reducing food intake over 3 days or by casein supplementation. Microdissected CDs were examined for cathelicidin mRNA expression and antimicrobial activity, and cathelicidin protein levels in rabbit urine were measured. Cathelicidin expression in CD cells was detected in kidney sections. CDs from acidotic rabbits expressed three times more cathelicidin mRNA than those isolated from normal rabbits. Urine from acidotic rabbits had significantly more antimicrobial activity (vs. E. coli) than normal urine, and most of this increased activity was blocked by cathelicidin antibody. The antibody had little effect on antimicrobial activity of normal urine. Urine from acidotic rabbits had at least twice the amount of cathelicidin protein as did normal urine. We conclude that metabolic acidosis not only stimulates CD acid secretion but also induces expression of cathelicidin and, thereby, enhances innate immune defense against urinary tract infections via induction of antimicrobial peptide expression.
Heat shock protein 90 contributes to cutaneous vasodilation through activating nitric oxide synthase in young male adults exercising in the heat
Authors: Fujii Naoto , Zhang Sarah Y. , McNeely Brendan D. , Nishiyasu Takeshi , Kenny Glen P.
Published: July 2017

While the mechanisms underlying the control of cutaneous vasodilation have been extensively studied, there remains a lack of understanding of the different factors that may modulate cutaneous perfusion during an exercise-induced heat stress. We evaluated the hypothesis that heat shock protein 90 (HSP90) contributes to the heat loss response of cutaneous vasodilation via the activation of nitric oxide synthase (NOS) during exercise in the heat. In 11 young males (25 ± 5 yr), cutaneous vascular conductance (CVC) was measured at four forearm skin sites that were continuously treated with 1) lactated Ringer solution (control), 2) NOS inhibition with 10 mM NG-nitro-l-arginine methyl ester (l-NAME), 3) HSP90 inhibition with 178 μM geldanamycin, or 4) a combination of 10 mM l-NAME and 178 μM geldanamycin. Participants rested in a moderate heat stress (35°C) condition for 70 min. Thereafter, they performed a 50-min bout of moderate-intensity cycling (~52% V̇o2peak) followed by a 30-min recovery period. We showed that NOS inhibition attenuated CVC (~40–50%) relative to the control site during pre- and postexercise rest in the heat ( P ≤ 0.05); however, no effect of HSP90 inhibition was observed ( P > 0.05). During exercise, we observed an attenuation of CVC with the separate inhibition of NOS (~40–50%) and HSP90 (~15–20%) compared with control (both P ≤ 0.05). However, the effect of HSP90 inhibition was absent in the presence of the coinhibition of NOS ( P > 0.05). We show that HSP90 contributes to cutaneous vasodilation in young men exposed to the heat albeit during exercise only. We also show that the HSP90 contribution is due to NOS-dependent mechanisms.

NEW & NOTEWORTHY We show that heat shock protein 90 functionally contributes to the heat loss response of cutaneous vasodilation during exercise in the heat, and this response is mediated through the activation of nitric oxide synthase. Therefore, interventions that may activate heat shock protein 90 may facilitate an increase in heat dissipation through an augmentation of cutaneous perfusion. In turn, this may attenuate or reduce the increase in core temperature and therefore the level of heat strain.
Associations between motor unit action potential parameters and surface EMG features
Authors: Del Vecchio Alessandro , Negro Francesco , Felici Francesco , Farina Dario
Published: July 2017

The surface interference EMG signal provides some information on the neural drive to muscles. However, the association between neural drive to muscle and muscle activation has long been debated with controversial indications due to the unavailability of motor unit population data. In this study, we clarify the potential and limitations of interference EMG analysis to infer motor unit recruitment strategies with an experimental investigation of several concurrently active motor units and of the associated features of the surface EMG. For this purpose, we recorded high-density surface EMG signals during linearly increasing force contractions of the tibialis anterior muscle, up to 70% of maximal force. The recruitment threshold (RT), conduction velocity (MUCV), median frequency (MDFMU), and amplitude (RMSMU) of action potentials of 587 motor units from 13 individuals were assessed and associated with features of the interference EMG. MUCV was positively associated with RT ( R2 = 0.64 ± 0.14), whereas MDFMU and RMSMU showed a weaker relation with RT ( R2 = 0.11 ± 0.11 and 0.39 ± 0.24, respectively). Moreover, the changes in average conduction velocity estimated from the interference EMG predicted well the changes in MUCV ( R2 = 0.71), with a strong association to ankle dorsiflexion force ( R2 = 0.81 ± 0.12). Conversely, both the average EMG MDF and RMS were poorly associated with motor unit recruitment. These results clarify the limitations of EMG spectral and amplitude analysis in inferring the neural strategies of muscle control and indicate that, conversely, the average conduction velocity could provide relevant information on these strategies.

NEW & NOTEWORTHY The surface EMG provides information on the neural drive to muscles. However, the associations between EMG features and neural drive have been long debated due to unavailability of motor unit population data. Here, by using novel highly accurate decomposition of the EMG, we related motor unit population behavior to a wide range of voluntary forces. The results fully clarify the potential and limitation of the surface EMG to provide estimates of the neural drive to muscles.
Isoflurane, ketamine-xylazine, and urethane markedly alter breathing even at subtherapeutic doses
Authors: Massey Cory A. , Richerson George B.
Published: July 2017

Anesthetics are widely used for animal research on respiratory control in vivo, but their effect on breathing and CO2chemoreception has not been well characterized in mice, a species now often used for these studies. We previously demonstrated that 1% isoflurane markedly reduces the hypercapnic ventilatory response (HCVR) in adult mice in vivo and masks serotonin [5-hydroxytryptamine (5-HT)] neuron chemosensitivity in vitro. Here we investigated effects of 0.5% isoflurane on breathing in adult mice and also found a large reduction in the HCVR even at this subanesthetic concentration. We then tested the effects on breathing of ketamine-xylazine and urethane, anesthetics widely used in research on breathing. We found that these agents altered baseline breathing and blunted the HCVR at doses within the range typically used experimentally. At lower doses ventilation was decreased, but mice appropriately matched their ventilation to metabolic demands due to a parallel decrease in O2consumption. Neither ketamine nor urethane decreased chemosensitivity of 5-HT neurons. These results indicate that baseline breathing and/or CO2chemoreception in mice are decreased by anesthetics widely viewed as not affecting respiratory control, and even at subtherapeutic doses. These effects of anesthetics on breathing may alter the interpretation of studies of respiratory physiology in vivo.

NEW & NOTEWORTHY Anesthetics are frequently used in animal research, but their effects on physiological functions in mice have not been well defined. Here we investigated the effects of commonly used anesthetics on breathing in mice. We found that all tested anesthetics significantly reduced the hypercapnic ventilatory response (HCVR), even at subtherapeutic doses. In addition, ketamine-xylazine and urethane anesthesia altered baseline breathing. These data indicate that breathing and the HCVR in mice are highly sensitive to anesthetic modulation.
Numerical and Experimental Investigation on the Structural Behaviour of a Horizontal Stabilizer under Critical Aerodynamic Loading Conditions
Authors: Sepe R. , Citarella R. , De Luca A. , Armentani E.
Published: July 2017

The aim of the proposed research activity is to investigate the mechanical behaviour of a part of aerospace horizontal stabilizer, made of composite materials and undergoing static loads. The prototype design and manufacturing phases have been carried out in the framework of this research activity. The structural components of such stabilizer are made of composite sandwich panels (HTA 5131/RTM 6) with honeycomb core (HRH-10-1/8-4.0); the sandwich skins have been made by means of Resin Transfer Moulding (RTM) process. In order to assess the mechanical strength of this stabilizer, experimental tests have been performed. In particular, the most critical inflight recorded aerodynamic load has been experimentally reproduced and applied on the stabilizer. A numerical model, based on the Finite Element Method (FEM) and aimed at reducing the experimental effort, has been preliminarily developed to calibrate amplitude, direction, and distribution of an equivalent and simpler load vector to be used in the experimental test. The FEM analysis, performed by using NASTRAN code, has allowed modelling the skins of the composite sandwich plates by definition of material properties and stack orientation of each lamina, while the honeycomb core has been modelled by using an equivalent orthotropic plate. Numerical and experimental results have been compared and a good agreement has been achieved.
Antagonistic Properties of Some Halophilic Thermoactinomycetes Isolated from Superficial Sediment of a Solar Saltern and Production of Cyclic Antimicrobial Peptides by the Novel Isolate Paludifilum halophilum
Authors: Frikha Dammak Donyez , Zarai Ziad , Najah Soumaya , Abdennabi Rayed , Belbahri Lassaad , Rateb Mostafa E. , Mejdoub Hafedh , Maalej Sami
Published: July 2017

This study has focused on the isolation of twenty-three halophilic actinomycetes from two ponds of different salinity and the evaluation of their ability to exert an antimicrobial activity against both their competitors and several other pathogens. From the 23 isolates, 18 strains showed antagonistic activity, while 19 showed activities against one or more of the seven pathogen strains tested. Six strains exhibited consistent antibacterial activity against Gram-negative and Gram-positive pathogens characterized at the physiological and molecular levels. These strains shared only 94-95% 16S rRNA sequence identity with the closely related species of the Thermoactinomycetaceae family. Among them, the potent strain SMBg3 was further characterized and assigned to a new genus in the family for which the name Paludifilum halophilum (DSM 102817T) is proposed. Sequential extraction of the antimicrobial compounds with ethyl acetate revealed that the crude extract from SMBg3 strain had inhibitory effect on the growth of the plant pathogen Agrobacterium tumefaciens and the human pathogens Staphylococcus aureus, Salmonella enterica, Escherichia coli, and Pseudomonas aeruginosa. Based on the HRESI-MS spectral data, the cyclic lipopeptide Gramicidin S and four cyclic dipeptides (CDPs) named cyclo(L-4-OH-Pro-L-Leu), cyclo(L-Tyr-L-Pro), cyclo(L-Phe-L-Pro), and cyclo(L-Leu-L-Pro) were detected in the fermentation broth of Paludifilum halophilum. To our knowledge, this is the first report on the isolation of these compounds from members of the Thermoactinomycetaceae family.