bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of Mutational Hot Spots during Decitabine-Mediated HIV-1 Mutagenesis
Authors: Rawson Jonathan M. O. , Landman Sean R. , Reilly Cavan S. , Bonnac Laurent , Patterson Steven E. , Mansky Louis M.
Published: August 2015

Decitabine has previously been shown to induce lethal mutagenesis of human immunodeficiency virus type 1 (HIV-1). However, the factors that determine the susceptibilities of individual sequence positions in HIV-1 to decitabine have not yet been defined. To investigate this, we performed Illumina high-throughput sequencing of multiple amplicons prepared from proviral DNA that was recovered from decitabine-treated cells infected with HIV-1. We found that decitabine induced an ≈4.1-fold increase in the total mutation frequency of HIV-1, primarily due to a striking ≈155-fold increase in the G-to-C transversion frequency. Intriguingly, decitabine also led to an ≈29-fold increase in the C-to-G transversion frequency. G-to-C frequencies varied substantially (up to ≈80-fold) depending upon sequence position, but surprisingly, mutational hot spots (defined as upper outliers within the mutation frequency distribution) were not observed. We further found that every single guanine position examined was significantly susceptible to the mutagenic effects of decitabine. Taken together, these observations demonstrate for the first time that decitabine-mediated HIV-1 mutagenesis is promiscuous and occurs in the absence of a clear bias for mutational hot spots. These data imply that decitabine-mediated G-to-C mutagenesis is a highly effective antiviral mechanism for extinguishing HIV-1 infectivity.
Interplay among Membrane-Bound Lytic Transglycosylase D1, the CreBC Two-Component Regulatory System, the AmpNG-AmpD
I
-NagZ-AmpR Regulatory Circuit, and L1/L2 β-Lactamase Expression in Stenotrophomonas maltophilia
Authors: Huang Yi-Wei , Wu Chao-Jung , Hu Rouh-Mei , Lin Yi-Tsung , Yang Tsuey-Ching
Published: August 2015

Lytic transglycosylases (LTs) are an important class of enzymes involved in peptidoglycan (PG) cleavage, with the concomitant formation of an intramolecular 1,6-anhydromuramoyl reaction product. There are six annotated LT genes in the
Stenotrophomonas maltophilia
genome, including genes for five membrane-bound LTs (
mltA
,
mltB1
,
mltB2
,
mltD1
, and
mltD2
) and a gene for soluble LT (
slt
). Six LTs of
S. maltophilia
KJ were systematically mutated, yielding the Δ
mltA
, Δ
mltB1
, Δ
mltB2
, Δ
mltD1
, Δ
mltD2
, and Δ
slt
mutants. Inactivation of
mltD1
conferred a phenotype of elevated uninduced β-lactamase activity. The underlying mechanism responsible for this phenotype was elucidated by the construction of several mutants and determination of β-lactamase activity. The expression of the genes assayed was assessed by quantitative reverse transcriptase PCR and a promoter transcription fusion assay. The results demonstrate that Δ
mltD1
mutant-mediated L1/L2 β-lactamase expression involved the
creBC
two-component regulatory system (TCS) and the
ampNG-ampD
I
-
nagZ-ampR
regulatory circuit. The inactivation of
mltD1
resulted in
mltB1
and
mltD2
upexpression in a
creBC
- and
ampNG
-dependent manner. The overexpressed MltB1 and MltD2 activity contributed to the expression of the L1/L2 β-lactamase genes via the
ampNG-ampD
I
-
nagZ-ampR
regulatory circuit. These findings reveal, for the first time, a linkage between LTs, the CreBC TCS, the
ampNG-ampD
I
-
nagZ-ampR
regulatory circuit, and L1/L2 β-lactamase expression in
S. maltophilia
.
Gingipains from the Periodontal Pathogen Porphyromonas gingivalis Play a Significant Role in Regulation of Angiopoietin 1 and Angiopoietin 2 in Human Aortic Smooth Muscle Cells
Authors: Zhang Boxi , Khalaf Hazem , Sirsjö Allan , Bengtsson Torbjörn
Published: August 2015

Angiopoietin 1 (Angpt1) and angiopoietin 2 (Angpt2) are the ligands of tyrosine kinase (Tie) receptors, and they play important roles in vessel formation and the development of inflammatory diseases, such as atherosclerosis.
Porphyromonas gingivalis
is a Gram-negative periodontal bacterium that is thought to contribute to the progression of cardiovascular disease. The aim of this study was to investigate the role of
P. gingivalis
infection in the modulation of Angpt1 and Angpt2 in human aortic smooth muscle cells (AoSMCs). We exposed AoSMCs to wild-type (W50 and 381), gingipain mutant (E8 and K1A), and fimbrial mutant (DPG-3 and KRX-178)
P. gingivalis
strains and to different concentrations of tumor necrosis factor (TNF). The atherosclerosis risk factor TNF was used as a positive control in this study. We found that
P. gingivalis
(wild type, K1A, DPG3, and KRX178) and TNF upregulated the expression of Angpt2 and its transcription factor ETS1, respectively, in AoSMCs. In contrast, Angpt1 was inhibited by
P. gingivalis
and TNF. However, the RgpAB mutant E8 had no effect on the expression of Angpt1, Angpt2, or ETS1 in AoSMCs. The results also showed that ETS1 is critical for
P. gingivalis
induction of Angpt2. Exposure to Angpt2 protein enhanced the migration of AoSMCs but had no effect on proliferation. This study demonstrates that gingipains are crucial to the ability of
P. gingivalis
to markedly increase the expressed Angpt2/Angpt1 ratio in AoSMCs, which determines the regulatory role of angiopoietins in angiogenesis and their involvement in the development of atherosclerosis. These findings further support the association between periodontitis and cardiovascular disease.
MdsABC-Mediated Pathway for Pathogenicity in Salmonella enterica Serovar Typhimurium
Authors: Song Saemee , Lee Boeun , Yeom Ji-Hyun , Hwang Soonhye , Kang Ilnam , Cho Jang-Cheon , Ha Nam-Chul , Bae Jeehyeon , Lee Kangseok , Kim Yong-Hak
Published: August 2015

MdsABC is a
Salmonella
-specific tripartite efflux pump that has been implicated in the virulence of
Salmonella enterica
serovar Typhimurium; however, little is known about the virulence factors associated with this pump. We observed MdsABC expression-dependent alterations in the degree of resistance to extracellular oxidative stress and macrophage-mediated killing. Thin-layer chromatography and tandem mass spectrometry analyses revealed that overexpression of MdsABC led to increased secretion of 1-palmitoyl-2-stearoyl-phosphatidylserine (PSPS), affecting the ability of the bacteria to invade and survive in host cells. Overexpression of MdsABC and external addition of PSPS similarly rendered the
mdsABC
deletion strain resistant to diamide. Diagonal gel analysis showed that PSPS treatment reduced the diamide-mediated formation of disulfide bonds, particularly in the membrane fraction of the bacteria.
Salmonella
infection of macrophages induced the upregulation of MdsABC expression and led to an increase of intracellular bacterial number and host cell death, similar to the effects of MdsABC overexpression and PSPS pretreatment on the
mdsABC
deletion strain. Our study shows that MdsABC mediates a previously uncharacterized pathway that involves PSPS as a key factor for the survival and virulence of
S
. Typhimurium in phagocytic cells.
Campylobacter hyointestinalis Isolated from Pigs Produces Multiple Variants of Biologically Active Cytolethal Distending Toxin
Authors: Kamei Kazumasa , Hatanaka Noritoshi , Asakura Masahiro , Somroop Srinuan , Samosornsuk Worada , Hinenoya Atsushi , Misawa Naoaki , Nakagawa Shinsaku , Yamasaki Shinji
Published: August 2015

Campylobacter hyointestinalisisolated from swine with proliferative enteritis often is considered to be pathogenic. While the precise virulence mechanisms of this species remain unclear, we have recently identified a cytolethal distending toxin (cdt) gene cluster inC. hyointestinalisisolated from a patient with diarrhea (W. Samosornsuk et al., J Med Microbiol, 27 July 2015,http://dx.doi.org/10.1099/jmm.0.000145). However, the sequences of thecdtgenes inC. hyointestinaliswere found to be significantly different and the gene products are immunologically distinct from those of otherCampylobacterspecies. In this study, we demonstrate the presence of a second variant of thecdtgene cluster inC. hyointestinalis, designatedcdt-II, while the former is namedcdt-I. Sequencing of thecdt-IIgene cluster and deduced amino acid sequences revealed that homologies between the subunits CdtA, CdtB, and CdtC of ChCDT-I and ChCDT-II are 25.0, 56.0, and 24.8%, respectively. Furthermore, the CdtB subunit of ChCDT-II was found to be immunologically unrelated to that of ChCDT-I by Ouchterlony double gel diffusion test. Recombinant ChCDT-II also induced cell distention and death of HeLa cells by blocking the cell cycle at G2/M phase. Interestingly, thecdt-IIgenes were detected in all 23 animal isolates and in 1 human isolate ofC. hyointestinalis, and 21 of these strains carried bothcdt-Iandcdt-IIgene clusters. Altogether, our results indicate that ChCDT-II is an important virulence factor ofC. hyointestinalisin animals.
Role of Inflammatory Monocytes in Vaccine-Induced Reduction of Helicobacter felis Infection
Authors: Moyat Mati , Mack Matthias , Bouzourene Hanifa , Velin Dominique
Published: August 2015

Despite the proven ability of immunization to reduce
Helicobacter
infection in mouse models, the precise mechanism of protection has remained elusive. In this study, we evaluated the role of inflammatory monocytes in the vaccine-induced reduction of
Helicobacter felis
infection. We first showed by using flow cytometric analysis that Ly6C
low
major histocompatibility complex class II-positive chemokine receptor type 2 (CCR2)-positive CD64
+
inflammatory monocytes accumulate in the stomach mucosa during the vaccine-induced reduction of
H. felis
infection. To determine whether inflammatory monocytes played a role in the protection, these cells were depleted with anti-CCR2 depleting antibodies. Indeed, depletion of inflammatory monocytes was associated with an impaired vaccine-induced reduction of
H. felis
infection on day 5 postinfection. To determine whether inflammatory monocytes had a direct or indirect role, we studied their antimicrobial activities. We observed that inflammatory monocytes produced tumor necrosis factor alpha and inducible nitric oxide synthase (iNOS), two major antimicrobial factors. Lastly, by using a
Helicobacter
in vitro
killing assay, we showed that mouse inflammatory monocytes and activated human monocytes killed
H. pylori
in an iNOS-dependent manner. Collectively, these data show that inflammatory monocytes play a direct role in the immunization-induced reduction of
H. felis
infection from the gastric mucosa.
A Burkholderia thailandensis Acyl-Homoserine Lactone-Independent Orphan LuxR Homolog That Activates Production of the Cytotoxin Malleilactone
Authors: Truong Thao T. , Seyedsayamdost Mohammad , Greenberg E. Peter , Chandler Josephine R.
Published: August 2015

Burkholderia thailandensis
has three acyl-homoserine lactone (AHL) LuxR-LuxI quorum-sensing circuits and two orphan LuxR homologs. Orphans are LuxR-type transcription factors that do not have cognate LuxI-type AHL synthases. One of the orphans, MalR, is genetically linked to the
mal
gene cluster, which encodes enzymes required for production of the cytotoxic polyketide malleilactone. Under normal laboratory conditions the
mal
gene cluster is silent; however, antibiotics like trimethoprim induce
mal
transcription. We show that trimethoprim-dependent induction of the
mal
genes requires MalR. MalR has all of the conserved amino acid residues characteristic of AHL-responsive LuxR homologs, but in
B. thailandensis
, MalR activation of malleilactone synthesis genes is not responsive to AHLs. MalR can activate transcription from the
mal
promoter in
E. coli
without addition of AHLs or trimethoprim. Expression of
malR
in
B. thailandensis
is induced by trimethoprim. Our data indicate that MalR binds to a
lux
box-like element in the
mal
promoter and activates transcription of the
mal
genes in an AHL-independent manner. Antibiotics like trimethoprim appear to activate
mal
gene expression indirectly by somehow activating
malR
expression. MalR activation of the
mal
genes represents an example of a LuxR homolog that is not a receptor for an AHL quorum-sensing signal. Our evidence is consistent with the idea that
mal
gene activation depends solely on sufficient transcription of the
malR
gene.

IMPORTANCE
LuxR proteins are transcription factors that are typically activated by acyl-homoserine lactone (AHL) signals. We demonstrate that a conserved LuxR family protein, MalR, activates genes independently of AHLs. MalR is required for transcription of genes coding for synthesis of the cytotoxic polyketide malleilactone. These genes are not expressed when cells are grown under normal laboratory conditions. In laboratory culture, MalR induction of malleilactone requires certain antibiotics, such as trimethoprim, which increase
malR
expression by an unknown mechanism. At sufficient levels of
malR
expression, MalR functions independently of any external signal. Our findings show that MalR is an activator of the silent malleilactone biosynthesis genes and that MalR functions independently of AHLs.
The Bacterial Tyrosine Kinase Activator TkmA Contributes to Biofilm Formation Largely Independently of the Cognate Kinase PtkA in Bacillus subtilis
Authors: Gao Tantan , Greenwich Jennifer , Li Yan , Wang Qi , Chai Yunrong
Published: August 2015

In
Bacillus subtilis
, biosynthesis of exopolysaccharide (EPS), a key biofilm matrix component, is regulated at the posttranslational level by the bacterial tyrosine kinase (BY-kinase) EpsB. EpsB, in turn, relies on the cognate kinase activator EpsA for activation. A concerted role of a second BY-kinase–kinase activator pair, PtkA and TkmA, respectively in biofilm formation was also indicated in previous studies. However, the exact functions of PtkA and TkmA in biofilm formation remain unclear. In this work, we show that the kinase activator TkmA contributes to biofilm formation largely independently of the cognate kinase, PtkA. We further show that the biofilm defect caused by a Δ
tkmA
mutation can be rescued by complementation by
epsA
, suggesting a functional overlap between TkmA and EpsA and providing a possible explanation for the role of TkmA in biofilm formation. We also show that the importance of TkmA in biofilm formation depends largely on medium conditions; the biofilm defect of Δ
tkmA
is very severe in the biofilm medium LBGM (lysogenic broth [LB] supplemented with 1% [vol/vol] glycerol and 100 μM MnSO
4
) but marginal in another commonly used biofilm medium, MSgg (5 mM potassium phosphate [pH 7.0], MOPS [100 mM morpholinepropanesulfonic acid] [pH 7.0], 2 mM MgCl
2
, 700 μM CaCl
2
, 50 μM MnCl
2
, 50 μM FeCl
3
, 1 μM ZnCl
2
, 2 μM thiamine, 0.5% glycerol, 0.5% glutamic acid, 50 μg/ml tryptophan, 50 μg/ml threonine, and 50 μg/ml phenylalanine). The molecular basis for the medium dependence is likely due to differential expression of
tkmA
and
epsA
in the two different media and complex regulation of these genes by both Spo0A and DegU. Our studies provide genetic evidence for possible cross talk between a BY-kinase activator (TkmA) and a noncognate kinase (EpsB) and an example of how environmental conditions may influence such cross talk in regulating biofilm formation in
B. subtilis
.

IMPORTANCE
In bacteria, biosynthesis of secreted polysaccharides is often regulated by bacterial tyrosine kinases (BY-kinases). BY-kinases, in turn, rely on cognate kinase activators for activation. In this study, we investigated the role of a BY-kinase activator in biofilm formation in
Bacillus subtilis
. We present evidence that different BY-kinase activators may functionally overlap each other, as well as an example of how activities of the BY-kinase activators may be highly dependent on environmental conditions. Our study broadens the understanding of the complexity of regulation of the BY-kinases/kinase activators and the influence on bacterial cell physiology.
Self-referral psychological treatment centre for young adults: a 2-year observational evaluation of routine practice before and after treatment
Authors: Halje Karin , Timpka Toomas , Tylestedt Petra , Adler Anna-Karin , Fröberg Lena , Schyman Tommy , Johansson Kristoffer , Dahl Katarina
Published: August 2015

Objectives

To examine a self-referral psychological service provided to young adults with regard to effects on anxiety, depression and psychological distress and to explore client factors predicting non-adherence and non-response.

Design

Observational study over a 2-year period.

Setting

Young Adults Centre providing psychological services by self-referral (preprimary care) to Linköping, Åtvidaberg, and Kinda municipalities (combined population 145 000) in Östergötland county, Sweden.

Participants

607 young adults (16–25 years of age); 71% females (n=429).

Intervention

Individually scheduled cognitive behavioural therapy delivered in up to six 45 min sessions structured according to an assessment of the client's mental health problems: anxiety, depression, anxiety and depression combined, or decreased distress without specific anxiety or depression.

Primary outcome measures

Pre–post intervention changes in psychological distress (General Health Questionnaire-12, GHQ-12), Hospital Anxiety and Depression Scale Anxiety/Depression (HADS-A/D).

Results

192 clients (32.5%) discontinued the intervention on their own initiative and 39 clients (6.6%) were referred to a psychiatric clinic during the course of the intervention. Intention-to-treat analyses including all clients showed a medium treatment effect size (d=0.64) with regard to psychological distress, and small effect sizes were observed with regard to anxiety (d=0.58) and depression (d=0.57). Restricting the analyses to clients who adhered to the agreed programme, a large effect size (d=1.26) was observed with regard to psychological distress, and medium effect sizes were observed with regard to anxiety (d=1.18) and depression (d=1.19). Lower age and a high initial HADS-A score were the strongest risk factors for non-adherence, and inability to concentrate and thinking of oneself as a worthless person increased the risk for discontinuation.

Conclusions

We conclude that provision of psychological services to young people through a self-referral centre has potential to improve long-term mental health in communities, but management of non-adherence remains a central challenge.
Diagnostic performance of S100B protein serum measurement in detecting intracranial injury in children with mild head trauma
Authors: Manzano Sergio , Holzinger Iris Bachmann , Kellenberger Christian J , Lacroix Laurence , Klima-Lange Dagmar , Hersberger Martin , La Scala Giorgio , Altermatt Stefan , Staubli Georg
Published: August 2015

Objective

To assess the accuracy of S100B serum level to detect intracranial injury in children with mild traumatic brain injury.

Methods

A multicenter prospective cohort study was carried out in the paediatric emergency departments of three tertiary hospitals in Switzerland between January 2009 and December 2011. Participants included children aged <16 years with a mild traumatic brain injury (GCS ≥13) for whom a head CT was requested by the attending physician. Venous blood was obtained within 6 h of the trauma in all children for S100B measurement before a head CT was performed. As the S100B value was not available during the acute care period, the patient's management was not altered. The main measures were protein S100B value and the CT result.

Results

20/73 (27.4%) included children had an intracranial injury detected on CT. S100B receiver operating characteristics area under the curve was 0.73 (95% CI 0.60 to 0.86). With a 0.14 µg/L cut-off point, S100B reached an excellent sensitivity of 95% (95% CI 77% to 100%) and 100% (95% CI 81% to 100%) in all children and in children aged >2 years, respectively. The specificity, however, was 34% (95% CI 27% to 36%) and 37% (95% CI 30% to 37%), respectively.

Conclusions

S100B has an excellent sensitivity but poor specificity. It is therefore an accurate tool to help rule out an intracranial injury but cannot be used as the sole marker owing to its specificity. Used with clinical decision rules, S100B may help to reduce the number of unnecessary CT scans.
Tissue factor is unregulated in microvascular endothelial cells of patients with heart failure
Authors: Reichman-Warmusz Edyta , Domal-Kwiatkowska Dorota , Matysiak Natalia , Kurek Józef , Spinczyk Dominik , Dudek Damian , Helewski Krzysztof , Wojnicz Romuald
Published: August 2015

Aims

Several lines of evidence point to hypercoagulability as an important factor for heart failure (HF) pathogenesis.

Methods

We hypothesised that endothelial tissue factor (TF) expression reflects altered tissue haemostasis which is related to the severity of HF. Accordingly, we investigated TF expression in the biopsies of 60 patients with HF and 22 without HF. In addition, we assessed the relationship between endothelial TF expression and clinical markers of HF severity.

Results

The control subjects without HF presented absent or weak TF expression in few microvessels, while the endomyocardial biopsies of patients with HF, capillary vessels presented both weak and severe staining patterns by immunohistochemistry usually with regional distribution. This was collaborated by the immune electron microscopic study. The severe microvessel TF antigen expression was found in 11 (18.3%) patients with HF. The endothelial TF expression was inversely associated with left ventricular ejection fraction (r=−0.42, p=0.001) and positively with N-terminal brain natriuretic peptide (r=0.36, p<0.023), markers of HF severity.

Conclusions

Regional upregulation of the TF in the capillary endothelial cells suggests local myocardial thrombogenicity. Furthermore, the relationship between endothelial TF and HF severity would be keeping in line with the hypothesis that an altered tissue haemostasis is most profoundly expressed in patients with severe HF. Weak TF expression found in several microvessels of the biopsy specimens patients without HF pathology might be potentially related to a low basal level of activation of the clotting system in normal individuals.
Risk of recurrence estimates with IHC4+C are tolerant of variations in staining and scoring: an analytical validity study
Authors: Dodson Andrew , Zabaglo Lila , Yeo Belinda , Miller Keith , Smith Ian , Dowsett Mitch
Published: August 2015

Aims

The IHC4+C score combines assessment of oestrogen receptor (ER), progesterone receptor (PgR), HER2 and Ki67 with clinicopathological parameters to identify the risk of distant disease recurrence in patients with breast cancer, so, aiding treatment decision-making on adjuvant chemotherapy. Despite low cost and wide availability, the reported use of IHC4+C remains limited; one explanation for this is the perception that immunohistochemistry (IHC)-based methods and assessment of them lack precision, reproducibility and portability. We examined the effects of decentralised testing and easily reproducible estimate-based scoring methods on IHC4+C scores to determine its suitability for wider adoption.

Methods

Sections from a breast cancer tissue micro-array (TMA) were distributed to three centres undertaking diagnostic breast cancer IHC. Centres stained sections using their standard procedures, and returned them for central assessment. The results were compared with those obtained at IHC4+C's originating hospital (Royal Marsden Hospital (RMH)). In parallel, TMA sections stained at RMH were scored by a variety of simplified non-counting-based methods. The results were compared with those produced using counting.

Results

There was a high degree of correlation between individual IHC results produced by external centres and those of RMH (r: 0.797–0.982), and between risk of distant recurrence scores derived from them (r: 0.972–0.984). Scoring methods for ER and PgR could be adapted to require less precision without significantly affecting correlation with counted results (r: 0.933 and 0.980, respectively), but correlation between estimating and counting for Ki67 was poorer (r: 0.855).

Conclusions

IHC4+C is tolerant of variation in staining and scoring methods. Although additional confirmatory comparative studies are required, these data support use of IHC4+C in clinical practice outside RMH.
Invasive Asian earthworms of the genus Amynthas alter microhabitat use by terrestrial salamanders
Authors: Ziemba Julie L. , Cameron Alex C. , Peterson Kim , Hickerson Cari-Ann M. , Anthony Carl D.
Published: August 2015

Invasive earthworms are rapidly transforming detrital communities in North America. Recent studies have investigated the effects of European earthworms, whereas Asian earthworms, such as species of the genus Amynthas Kinberg, 1867, remain understudied. Amynthas is a surface-dwelling earthworm that voraciously consumes the litter layer of temperate forest floor habitats. The accumulation of detritus is important for the terrestrial Eastern Red-backed Salamanders (Plethodon cinereus (Green, 1818)) because this microhabitat provides the matrix through which salamanders travel when foraging, searching for mates, and dispersing. We examined the effect of Amynthas on the activity of “naïve” (no history of co-occurrence with Amynthas) and “experienced” (recent co-occurrence with Amynthas) salamanders in laboratory microcosms. We hypothesized that earthworms would disturb normal salamander activity through the reduction of leaf litter and physical impediment, with greater negative effects on naïve salamanders encountering this “novel” invasive species. Consistent with published studies, earthworm presence significantly decreased leaf-litter mass over time. Prior experience with earthworms did not appear to influence salamander response. However, earthworm presence had a significant effect on salamander activity, with salamanders exhibiting increased movement, cover-object use, and co-occurrence under cover objects with earthworms as the study progressed. Unnecessary movement has the potential to incur fitness costs to salamanders in the form of energetic expenditure and increased exposure to predators.
The mRNA expression of soluble urokinase plasminogen activator surface receptor in human adipose tissue is positively correlated with body mass index
Authors: Ng Hien Fuh , Chin Kin Fah , Chan Kok-Gan , Ngeow Yun Fong
Published: August 2015

suPLAUR is the transcript variant that encodes the soluble form of the urokinase plasminogen activator surface receptor (suPLAUR). This soluble protein has been shown to enhance leukocyte migration and adhesion, and its circulatory level is increased in inflammatory states. In this pilot study, we used RNA-Seq to examine the splicing pattern of PLAUR in omental adipose tissues from obese and lean individuals. Of the three transcript variants of the PLAUR gene, only the proportion of suPLAUR (transcript variant 2) increases in obesity. After removing the effects of gender and age, the expression of suPLAUR is positively correlated with body mass index. This observation was validated using RT-qPCR with an independent cohort of samples. Additionally, in our RNA-Seq differential expression analysis, we also observed, in obese adipose tissues, an up-regulation of genes encoding other proteins involved in the process of chemotaxis and leukocyte adhesion; of particular interest is the integrin beta 2 (ITGB2) that is known to interact with suPLAUR in leukocyte adhesion. These findings suggest an important role for suPLAUR in the recruitment of immune cells to obese adipose tissue, in the pathogenesis of obesity.
Are Firms with Negative Book Equity in Financial Distress?
Authors: ANG Tze Chuan Chewie
Published: August 2015

This study examines whether negative book equity (BE) firms are in financial distress by analyzing their operating performance, financial characteristics, distress risk, and survivability when they first report negative BE. Firms with small magnitude of negative BE (SNBE firms) suffer from persistent negative earnings and financial distress, while firms with large magnitude of negative BE (LNBE firms) experience a temporary non-distress related earnings shock. LNBE firms report consecutive years of negative BE, but have lower distress risk and failure rate than both SNBE and control firms. However, all negative BE stocks have abysmal returns subsequent to their first report of negative BE.
Architecture of Wireless Vehicle Weight Measurement System for Structural Health Monitoring in Civil Engineering Application
Authors: Andrzejczak Artur , Łęczycki Paweł , Wojtera Michał , Pietrzak Piotr , Pękosławski Bartosz , Napieralski Andrzej
Published: August 2015

The following paper describes architecture of the Wireless Vehicle Weight Measurement System (WVWMS). The challenge was to design a road scale system enabling multipoint vehicle weight with the single network sink. The proposed platform is capable of weight measurement based on electrical strain gauge weight pads and in-node data processing. Communication is wireless, with mesh networking. The developed vehicle weight measurement is one of subsystems applied in the TULCOEMPA project. It is required to cooperate with Structural Health Monitoring and Truck Recognition Systems. Due to the absence of mains line, all installations are powered by Hybrid Power System. The authors propose Energy Harvesting Controller cooperating with both solar panels and wind generators. The controller enables efficient energy harvesting from both power sources as well as monitoring of generated and consumed power levels. Next challenge was a design of vehicle weight data acquisition software architecture. The solution includes application of modern architectural concepts in software design, Representational State Transfer (REST), Model-View-View Model (MVVM) paradigm, and cloud computing. Communication between vehicle weight measurement modules and server application is described.
Dynamic Support Culture of Murine Skeletal Muscle-Derived Stem Cells Improves Their Cardiogenic PotentialIn Vitro
Authors: Neef Klaus , Treskes Philipp , Xu Guoxing , Drey Florian , Srinivasan Sureshkumar Perumal , Saric Tomo , Nembo Erastus , Semmler Judith , Nguemo Filomain , Stamm Christof , Cowan Douglas B. , Deppe Antje-Christin , Scherner Maximilian , Wittwer Thorsten , Hescheler Jürgen , Wahlers Thorsten , Choi Yeong-Hoon
Published: August 2015

Ischemic heart disease is the main cause of death in western countries and its burden is increasing worldwide. It typically involves irreversible degeneration and loss of myocardial tissue leading to poor prognosis and fatal outcome. Autologous cells with the potential to regenerate damaged heart tissue would be an ideal source for cell therapeutic approaches. Here, we compared different methods of conditional culture for increasing the yield and cardiogenic potential of murine skeletal muscle-derived stem cells. A subpopulation of nonadherent cells was isolated from skeletal muscle by preplating and applying cell culture conditions differing in support of cluster formation. In contrast to static culture conditions, dynamic culture with or without previous hanging drop preculture led to significantly increased cluster diameters and the expression of cardiac specific markers on the protein and mRNA level. Whole-cell patch-clamp studies revealed similarities to pacemaker action potentials and responsiveness to cardiac specific pharmacological stimuli. This data indicates that skeletal muscle-derived stem cells are capable of adopting enhanced cardiac muscle cell-like properties by applying specific culture conditions. Choosing this route for the establishment of a sustainable, autologous source of cells for cardiac therapies holds the potential of being clinically more acceptable than transgenic manipulation of cells.
Soft Tissue Reconstruction with Free Gingival Graft Technique following Excision of a Fibroma
Authors: Tezci Nurcan , Meseli Suleyman Emre , Karaduman Burcu , Dogan Serap , Meric Sabri Hasan
Published: August 2015

Background. Oral fibromas are benign, asymptomatic, smooth surfaced, firm structured tumoral lesions that originate from gingival connective tissue or periodontal ligament. Histologically, they are nodular masses characterized by a dense connective tissue, surrounded by stratified squamous epithelium.Case Report. This case report includes the clinical, radiographical, and histological findings and periodontal treatment of a 38-year-old female patient having painless swelling on the gingiva. Intraoral examination revealed a fibrotic, sessile, smooth surfaced gingival overgrowth interdentally between the teeth #13 and #14. Radiographical findings were normal. Initial periodontal treatment (IPT) was applied including oral hygiene instructions, scaling, and root planing. Following IPT, the lesion (0.7 × 0.6 × 0.4 cm) was excised and examined histopathologically. Subsequently, flap operation was performed to have an access to alveolar bone. Surgical site was reconstructed with free gingival graft obtained from hard palate. Hematoxylin-eosin stained sections revealed a nodular mass composed by dense collagen fibers in lamina propria covered by a stratified squamous epithelium, which were consistent with fibroma. Gingival healing was uneventful and without any recurrence during the 12-month follow-up.Conclusions. In order to achieve optimal functional and aesthetical outcomes, free gingival graft can be used for the reconstruction of the wound site after the excision of the fibroma.
The Canadian Cardiac Rehabilitation Registry: Inaugural Report on the Status of Cardiac Rehabilitation in Canada
Authors: Grace Sherry L. , Parsons Trisha L. , Heise Kristal , Bacon Simon L.
Published: August 2015

Introduction. There are over 200 Cardiovascular Rehabilitation (CR) programs in Canada, providing services to more than 50,000 new patients annually. The objective of this study was to describe the impact of CR in Canada.Methods. A retrospective analysis of Canadian CR Registry data is presented. There were 12 programs participating, with 4546 CR participants.Results. The average wait time between patient referral and CR admission was 68 ± 64 days. Participants were 66.3 ± 11.5 years old, 71% male, and 82% White. The three leading referral events were coronary artery bypass graft surgery, percutaneous coronary intervention, and acute coronary syndrome. At discharge, data were available for ~90% of participants. Significant improvements in blood pressure (systolic pre-CR 123.5 ± 17.0, post-CR 121.5 ± 15.8 mmHg;p<.001), lipids, adiposity, and exercise capacity (peak METs pre-CR 6.5 ± 2.8, post-CR 7.2 ± 3.1;p<.001) were observed. However, target attainment for some risk factors was suboptimal.Conclusions. This report provides the first snapshot of the beneficial effects of CR in Canada. Not all patients are equally represented in these programs, however, leaving room for more referral of diverse patients. Greater attainment of risk reduction targets should be pursued.
Curbing Inflammation in Skin Wound Healing: A Review
Authors: Rosique Rodrigo G. , Rosique Marina J. , Farina Junior Jayme A.
Published: August 2015

Wound healing is a complex regulated process that results in skin scar formation in postnatal mammals. Chronic wounds are major medical problems that can confer devastating consequences. Currently, there are no treatments to prevent scarring. In the early fetus wounds heal without scarring and the healing process is characterized by relatively less inflammation compared to adults; therefore, research aimed at reducing the inflammatory process related to wound healing might speed healing and improve the final scar appearance.
Side Effects of Chloroquine and Primaquine and Symptom Reduction in Malaria Endemic Area (Mâncio Lima, Acre, Brazil)
Authors: Braga Cássio Braga e , Martins Antonio Camargo , Cayotopa Athaid David Escalante , Klein Wagner Werner , Schlosser Andreus Roberto , Silva Aline Ferreira da , Souza Mardelson Nery de , Andrade Breno Wilson Benevides , Filgueira-Júnior José Alcântara , Pinto Wagner de Jesus , da Silva-Nunes Mônica
Published: August 2015

Side effects of antimalarial drug can overlap with malaria symptoms. We evaluated 50 patients withvivaxmalaria in Mâncio Lima, Acre, treated with chloroquine and primaquine. Patients were evaluated for the presence of 21 symptoms before and after treatment and for reported side effects of these drugs after treatment was started. The most frequent symptoms before medication were headache, fever, chills, sweating, arthralgia, back pain, and weakness, which were present in between 40% and 76% of respondents. The treatment reduced the occurrence of these symptoms and reduced the lack of appetite, but gastrointestinal symptoms and choluria increased in frequency. There were no reports of pale stools before medication, but 12% reported the occurrence of this symptom after treatment started. Other symptoms such as blurred vision (54%), pruritus (22%), paresthesia (6%), insomnia (46%), and “stings” into the skin (22%) were reported after chloroquine was taken. The antimalarial drugs used to treatP. vivaxmalaria reduce much of the systemic and algic symptoms but cause mainly gastrointestinal side effects that may lead to lack of adherence to drug treatment. It is important to guide the patient for the appearance and the transience of such side effects in order to avoid abandoning treatment.
Preparation and Characterization of Natural Zeolite Modified with Iron Nanoparticles
Authors: Ruíz-Baltazar Alvaro , Esparza Rodrigo , Gonzalez Maykel , Rosas Gerardo , Pérez Ramiro
Published: August 2015

This study is aimed at investigating the structural and morphological characterization of natural and modified zeolite obtained from the state of Oaxaca (Mexico). Iron nanoparticles were used for the zeolite modification. The iron nanoparticles were loaded on the zeolite surface by homogeneous nucleation. Adsorption kinetic models of pseudo first and second order were surveyed. The characterization of pristine and modified zeolite was performed by Fourier transform infrared (FTIR), transmission electron microscopy (TEM), and X‐ray diffraction (XRD). From the results, three main phases were identified: clinoptilolite, mordenite, and feldspar. We could also determine the adsorption capacity of the zeolites by means of adsorption kinetic models.
Prophylactic Subacute Administration of Zinc Increases CCL2, CCR2, FGF2, and IGF-1 Expression and Prevents the Long-Term Memory Loss in a Rat Model of Cerebral Hypoxia-Ischemia
Authors: Blanco-Alvarez Victor Manuel , Soto-Rodriguez Guadalupe , Gonzalez-Barrios Juan Antonio , Martinez-Fong Daniel , Brambila Eduardo , Torres-Soto Maricela , Aguilar-Peralta Ana Karina , Gonzalez-Vazquez Alejandro , Tomás-Sanchez Constantino , Limón I. Daniel , Eguibar Jose R. , Ugarte Araceli , Hernandez-Castillo Jeanett , Leon-Chavez Bertha Alicia
Published: August 2015

Prophylactic subacute administration of zinc decreases lipoperoxidation and cell death following a transient cerebral hypoxia-ischemia, thus suggesting neuroprotective and preconditioning effects. Chemokines and growth factors are also involved in the neuroprotective effect in hypoxia-ischemia. We explored whether zinc prevents the cerebral cortex-hippocampus injury through regulation of CCL2, CCR2, FGF2, and IGF-1 expression following a 10 min of common carotid artery occlusion (CCAO). Male rats were grouped as follows: (1) Zn96h, rats injected with ZnCl2(one dose every 24 h during four days); (2) Zn96h + CCAO, rats treated with ZnCl2before CCAO; (3) CCAO, rats with CCAO only; (4) Sham group, rats with mock CCAO; and (5) untreated rats. The cerebral cortex-hippocampus was dissected at different times before and after CCAO. CCL2/CCR2, FGF2, and IGF-1 expression was assessed by RT-PCR and ELISA. Learning in Morris Water Maze was achieved by daily training during 5 days. Long-term memory was evaluated on day 7 after learning. Subacute administration of zinc increased expression of CCL2, CCR2, FGF2, and IGF-1 in the early and late phases of postreperfusion and prevented the CCAO-induced memory loss in the rat. These results might be explained by the induction of neural plasticity because of the expression of CCL2 and growth factors.
H∞Consensus for Discrete-Time Multiagent Systems
Authors: Wang Xiaoping , Shao Jinliang
Published: August 2015

AnH∞consensus problem of multiagent systems is studied by introducing disturbances into the systems. Based onH∞control theory and consensus theory, a condition is derived to guarantee the systems both reach consensus and have a certainH∞property. Finally, an example is worked out to demonstrate the effectiveness of the theoretical results.
Prognostic Significance of mTOR and PTEN in Patients with Esophageal Squamous Cell Carcinoma
Authors: Lu Jianjun , Pan You , Xia Xin , Gu Yong , Lei Yiyan
Published: August 2015

The prognostic value of mTOR in ESCC is much controversial; this study aimed to determine the prognostic importance of mTOR and PTEN in patients with ESCC. A total of 148 consecutive patients who underwent esophagectomy from 2010 to 2012 were included in this study, tested by western bolt and immunohistochemistry for mTOR and PTEN expression. Correlation coefficient was calculated using Pearson’s correlation test. The 3-year overall survival (OS) and disease-free survival (DFS) were calculated in relation to the two markers. 94 (63.5%) of 148 were mTOR high expression, and PTEN high expression was detected in 46 (31.1%) of the 148 patients with ESCC. The Pearson correlation coefficient revealed a significant negative correlation in two proteins (correlation coefficient = −0.189, P<0.005). The 3-year OS and DFS time in the mTOR-high group was 23.9 and 18.4 months, respectively, and the time in the mTOR-low group was 33.9 months and 31.4 months, respectively. The difference of survival rate between the two groups remained statistically significant. mTOR-low or PTEN-high patients had better 3-year rates of OS and DFS than mTOR-high or PTEN-low group (P<0.001 by the log-rank test). This study also found that mTOR was an independence prognostic factor by multivariate analysis.
Increased Oxidation as an Additional Mechanism Underlying Reduced Clot Permeability and Impaired Fibrinolysis in Type 2 Diabetes
Authors: Lados-Krupa Anna , Konieczynska Malgorzata , Chmiel Artur , Undas Anetta
Published: August 2015

Aims. We sought to investigate whether enhanced oxidation contributes to unfavorable fibrin clot properties in patients with diabetes.Methods. We assessed plasma fibrin clot permeation (Ks, a measure of the pore size in fibrin networks) and clot lysis time induced by recombinant tissue plasminogen activator (CLT) in 163 consecutive type 2 diabetic patients (92 men and 71 women) aged 65 ± 8.8 years with a mean glycated hemoglobin (HbA1c) of 6.8%. We also measured oxidative stress markers, including nitrotyrosine, the soluble form of receptor for advanced glycation end products (sRAGE), 8-iso-prostaglandin F2α(8-iso-PGF2α), oxidized low-density lipoprotein (oxLDL), and advanced glycation end products (AGE).Results. There were inverse correlations betweenKsand nitrotyrosine, sRAGE, 8-iso-PGF2α, and oxLDL. CLT showed a positive correlation with oxLDL and nitrotyrosine but not with other oxidation markers. All these associations remained significant forKsafter adjustment for fibrinogen, disease duration, and HbA1c (allP<0.05), while oxLDL was the only independent predictor of CLT.Conclusions. Our study shows that enhanced oxidative stress adversely affects plasma fibrin clot properties in type 2 diabetic patients, regardless of disease duration and glycemia control.
Effect of Increased Water Intake on Urinary DNA Adduct Levels and Mutagenicity in Smokers: A Randomized Study
Authors: Buendia Jimenez Inmaculada , Richardot Pascaline , Picard Pascaline , Lepicard Eve M. , De Meo Michel , Talaska Glenn
Published: August 2015

The association between fluid intake and bladder cancer risk remains controversial. Very little is known about to which extent the amount of water intake influences the action of excreting toxics upon the urinary system. This proof of concept trial investigates the effect of water intake on mutagenesis in smokers, a high risk population for bladder cancer.Methods. Monocentric randomized controlled trial.Inclusion Criteria.Male subjects aged 2045–45 y/o, smokers, and small drinkers (24-hour urinary volume <1 L and osmolality >700 mOsmol/kg).Outcomes.4-ABP DNA adducts formation in exfoliated bladder cells in 24-hour urine collection and urinary mutagenicity in 24-hour urine.Test Group.Subjects consumed 1.5 L daily of the study product (EVIAN) on top of their usual water intake for 50 days.Control Group.Subjects continued their usual lifestyle habits.Results.65 subjects were randomized. Mean age was 30 y/o and mean cigarettes per day were 20. A slight decrease in adducts formation was observed between baseline and last visit but no statistically significant difference was demonstrated between the groups. Urinary mutagenicity significantly decreased. The study shows that increasing water intake decreases urinary mutagenicity. It is not confirmed by urinary adducts formation. Further research would be necessary.
Influence of Indentation on the Fatigue Strength of Carbonitrided Plain Steel
Authors: Gao Jiewei , Dai Guangze , Zhao Junwen , Li Hengkui , Xu Lei , Zhu Zhenyu
Published: August 2015

To study the influence of indentation on the fatigue strength of untreated and carbonitrided specimens of S38C steel, the fatigue limit of specimens with and without indentations was tested. Fracture surfaces were observed using scanning electron microscopy (SEM). The results show that the fatigue strength of the untreated specimen decreases with increasing dimension of indentation, without significant difference compared to the predicted results. Compared to the fatigue limit of the untreated specimen, those of the carbonitrided specimen and the carbonitrided specimen whose compound layer was polished were improved by 12% and 40%, respectively. The fatigue strength of the carbonitrided specimen decreased sharply with increasing indentation size because of the presence of microcracks in the compound layer. When the compound layer was removed, the fatigue limit was observed to be less sensitive to indentation than that of the carbonitrided specimen.
A Robust Home Alone Faint Detection Based on Wireless Sensor Networks
Authors: Wang Zhen-hai , Xu Bo
Published: August 2015

Target detection and tracking are one of the fundamental problems for wireless sensor networks and play an important role in the safety field. Faint detection is an important problem for the elderly people or patients or even pregnant women. It has wide application in current society. This paper proposed a method to collect information about the behavior and position of faint event in the sensing environment. This method detects and tracks faint person by combining Kalman filter and Camshift tracking algorithm. Experiments showed that the method yields good detection and tracking performance in complex environments.
Caseous Necrosis of Mitral Annulus
Authors: Balci Sinan , Akkaya Selcuk , Ardali Selin , Hazirolan Tuncay
Published: August 2015

Masses or mass-like lesions located in proximity to mitral valve encompass a wide range of differential diagnoses including neoplasias, abscesses, thrombi, and rarely caseous calcification of mitral annulus. Due to asymptomatic presentation, its diagnosis is usually incidental. Echocardiography is the first choice of imaging in evaluation. Cardiac computed tomography (CT) is helpful in establishing diagnosis by showing dense calcifications while cardiac magnetic resonance imaging (MRI) is used primarily as a problem solving tool. Imaging in evaluation of mitral annulus caseous calcification is essential in order to prevent unnecessary operations.