bluuebunny/crossref_metadata_2025 huggingface dataset:
Polycyclovorans algicola gen. nov., sp. nov., an Aromatic-Hydrocarbon-Degrading Marine Bacterium Found Associated with Laboratory Cultures of Marine Phytoplankton
Authors: Gutierrez Tony , Green David H. , Nichols Peter D. , Whitman William B. , Semple Kirk T. , Aitken Michael D.
Published: October 2012

A strictly aerobic, halotolerant, rod-shaped bacterium, designated strain TG408, was isolated from a laboratory culture of the marine diatom
Skeletonema costatum
(CCAP1077/1C) by enrichment with polycyclic aromatic hydrocarbons (PAHs) as the sole carbon source. 16S rRNA gene sequence analysis placed this organism within the order
Xanthomonadales
of the class
Gammaproteobacteria
. Its closest relatives included representatives of the
Hydrocarboniphaga-Nevskia-Sinobacter
clade (<92% sequence similarity) in the family
Sinobacteraceae
. The strain exhibited a narrow nutritional spectrum, preferring to utilize aliphatic and aromatic hydrocarbon compounds and small organic acids. Notably, it displayed versatility in degrading two- and three-ring PAHs. Moreover, catechol 2,3-dioxygenase activity was detected in lysates, indicating that this strain utilizes the
meta
-cleavage pathway for aromatic compound degradation. Cells produced surface blebs and contained a single polar flagellum. The predominant isoprenoid quinone of strain TG408 was Q-8, and the dominant fatty acids were C
16:0
, C
16:1
ω7
c
, and C
18:1
ω7
c
. The G+C content of the isolate's DNA was 64.3 mol% ± 0.34 mol%. On the basis of distinct phenotypic and genotypic characteristics, strain TG408 represents a novel genus and species in the class
Gammaproteobacteria
for which the name
Polycyclovorans algicola
gen. nov., sp. nov., is proposed. Quantitative PCR primers targeting the 16S rRNA gene of this strain were developed and used to show that this organism is found associated with other species of marine phytoplankton. Phytoplankton may be a natural biotope in the ocean where new species of hydrocarbon-degrading bacteria await discovery and which contribute significantly to natural remediation processes.
VeA Regulates Conidiation, Gliotoxin Production, and Protease Activity in the Opportunistic Human Pathogen Aspergillus fumigatus
Authors: Dhingra Sourabh , Andes David , Calvo Ana M.
Published: October 2012

Invasive aspergillosis byAspergillus fumigatusis a leading cause of infection-related mortality in immunocompromised patients. In this study, we show thatveA, a major conserved regulatory gene that is unique to fungi, is necessary for normal morphogenesis in this medically relevant fungus. Although deletion ofveAresults in a strain with reduced conidiation, overexpression of this gene further reduced conidial production, indicating thatveAhas a major role as a regulator of development inA. fumigatusand that normal conidiation is only sustained in the presence of wild-type VeA levels. Furthermore, our studies revealed thatveAis a positive regulator in the production of gliotoxin, a secondary metabolite known to be a virulent factor inA. fumigatus. Deletion ofveAresulted in a reduction of gliotoxin production with respect to that of the wild-type control. This reduction in toxin coincided with a decrease ingliZandgliPexpression, which is necessary for gliotoxin biosynthesis. Interestingly,veAalso influences protease activity in this organism. Specifically, deletion ofveAresulted in a reduction of protease activity; this is the first report of aveAhomolog with a role in controlling fungal hydrolytic activity. AlthoughveAaffects several cellular processes inA. fumigatus, pathogenicity studies in a neutropenic mouse infection model indicated thatveAis dispensable for virulence.
Mutants in the Candida glabrata Glycerol Channels Are Sensitized to Cell Wall Stress
Authors: Beese-Sims Sara E. , Pan Shih-Jung , Lee Jongmin , Hwang-Wong Elizabeth , Cormack Brendan P. , Levin David E.
Published: October 2012

Many fungal species use glycerol as a compatible solute with which to maintain osmotic homeostasis in response to changes in external osmolarity. In
Saccharomyces cerevisiae
, intracellular glycerol concentrations are regulated largely by the
h
igh
o
smolarity
g
lycerol (HOG) response pathway, both through induction of glycerol biosynthesis and control of its flux through the plasma membrane Fps1 glycerol channel. The channel activity of Fps1 is also controlled by a pair of positive regulators, Rgc1 and Rgc2. In this study, we demonstrate that
Candida glabrata
, a fungal pathogen that possesses two Fps1 orthologs and two Rgc1/-2 orthologs, accumulates glycerol in response to hyperosmotic stress. We present an initial characterization of mutants with deletions in the
C. glabrata FPS1
(CAGL0C03267 [
www.candidagenome.org
]) and
FPS2
(CAGL0E03894) genes and find that a double mutant accumulates glycerol, experiences constitutive cell wall stress, and is hypersensitive to treatment by caspofungin, an antifungal agent that targets the cell wall. This mutant is cleared more efficiently in mouse infections than is wild-type
C. glabrata
by caspofungin treatment. Finally, we demonstrate that one of the
C. glabrata RGC
orthologs complements an
S. cerevisiae rgc1 rgc2
null mutant, supporting the conclusion that this regulatory assembly is conserved between these species.
Cryptococcus neoformans Phosphoinositide-Dependent Kinase 1 (PDK1) Ortholog Is Required for Stress Tolerance and Survival in Murine Phagocytes
Authors: Chabrier-Roselló Yeissa , Gerik Kimberly J. , Koselny Kristy , DiDone Louis , Lodge Jennifer K. , Krysan Damian J.
Published: October 2012

Cryptococcus neoformans
PKH2-01
and
PKH2-02
are orthologous to mammalian PDK1 kinase genes. Although orthologs of these kinases have been extensively studied in
S. cerevisiae
, little is known about their function in pathogenic fungi. In this study, we show that
PKH2-02
but not
PKH2-01
is required for
C. neoformans
to tolerate cell wall, oxidative, nitrosative, and antifungal drug stress. Deletion of
PKH2-02
leads to decreased basal levels of Pkc1 activity and, consequently, reduced activation of the cell wall integrity mitogen-activated protein kinase (MAPK) pathway in response to cell wall, oxidative, and nitrosative stress.
PKH2-02
function also is required for tolerance of fluconazole and amphotericin B, two important drugs for the treatment of cryptococcosis. Furthermore, OSU-03012, an inhibitor of human PDK1, is synergistic and fungicidal in combination with fluconazole. Using a
Galleria mellonella
model of low-temperature cryptococcosis, we found that
PKH2-02
is also required for virulence in a temperature-independent manner. Consistent with the hypersensitivity of the
pkh2-02
Δ mutant to oxidative and nitrosative stress, this mutant shows decreased survival in murine phagocytes compared to that of wild-type (WT) cells. In addition, we show that deletion of
PKH2-02
affects the interaction between
C. neoformans
and phagocytes by decreasing its ability to suppress production of tumor necrosis factor alpha (TNF-α) and reactive oxygen species. Taken together, our studies demonstrate that Pkh2-02-mediated signaling in
C. neoformans
is crucial for stress tolerance, host-pathogen interactions, and both temperature-dependent and -independent virulence.
New Functions for the Ancient DedA Membrane Protein Family
Authors: Doerrler William T. , Sikdar Rakesh , Kumar Sujeet , Boughner Lisa A.
Published: October 2012

The DedA protein family is a highly conserved and ancient family of membrane proteins with representatives in most sequenced genomes, including those of bacteria, archaea, and eukarya. The functions of the DedA family proteins remain obscure. However, recent genetic approaches have revealed important roles for certain bacterial DedA family members in membrane homeostasis. Bacterial DedA family mutants display such intriguing phenotypes as cell division defects, temperature sensitivity, altered membrane lipid composition, elevated envelope-related stress responses, and loss of proton motive force. The DedA family is also essential in at least two species of bacteria:
Borrelia burgdorferi
and
Escherichia coli
. Here, we describe the phylogenetic distribution of the family and summarize recent progress toward understanding the functions of the DedA membrane protein family.
CspR, a Cold Shock RNA-Binding Protein Involved in the Long-Term Survival and the Virulence of Enterococcus faecalis
Authors: Michaux Charlotte , Martini Cecilia , Shioya Koki , Ahmed Lecheheb Sandra , Budin-Verneuil Aurélie , Cosette Pascal , Sanguinetti Maurizio , Hartke Axel , Verneuil Nicolas , Giard Jean-Christophe
Published: October 2012

By coprecipitation, we identified RNA-binding proteins in the Gram-positive opportunistic pathogen
Enterococcus faecalis
known to be deficient of the RNA chaperone Hfq. In particular, we characterized one belonging to the cold shock protein (Csp) family (Ef2925) renamed CspR for cold shock protein RNA binding. Compared to the wild-type strain, the Δ
cspR
mutant was less virulent in an insect infection model (
Galleria mellonella
) and exhibited a decreased persistence in mouse kidneys and a low survival rate in peritoneal macrophages. As expected, we found that the Δ
cspR
mutant strain was more impaired in its growth than the parental strain under cold conditions and in its long-term survival under nutrient starvation. All these phenotypes were restored after complementation of the Δ
cspR
mutant. In addition, Western blot analysis showed that CspR was overexpressed under cold shock conditions and in the stationary phase. Since CspR may act as an RNA chaperone, putative targets were identified using a global proteomic approach completed with transcriptomic assays. This study revealed that 19 proteins were differentially expressed in the Δ
cspR
strain (9 upregulated, 10 downregulated) and that CspR mainly acted at the posttranscriptional level. These data highlight for the first time the role of the RNA-binding protein CspR as a regulator in
E. faecalis
and its requirement in stress response and virulence in this important human pathogen.
Thomas Kuhn's ‘Structure of Scientific Revolutions’ applied to exercise science paradigm shifts: example including the Central Governor Model
Authors: Pires Flávio de Oliveira
Published: October 2012

According to Thomas Kuhn, the scientific progress of any discipline could be distinguished by a pre-paradigm phase, a normal science phase and a revolution phase. The science advances when a scientific revolution takes place after silent period of normal science and the scientific community moves ahead to a paradigm shift. I suggest there has been a recent change of course in the direction of the exercise science. According to the ‘current paradigm’, exercise would be probably limited by alterations in either central command or peripheral skeletal muscles, and fatigue would be developed in a task-dependent manner. Instead, the central governor model (GCM) has proposed that all forms of exercise are centrally-regulated, the central nervous system would calculate the metabolic cost required to complete a task in order to avoid catastrophic body failure. Some have criticized the CGM and supported the traditional interpretation, but recently the scientific community appears to have begun an intellectual trajectory to accept this theory. First, the increased number of citations of articles that have supported the CGM could indicate that the community has changed the focus. Second, relevant journals have devoted special editions to promote the debate on subjects challenged by the CGM. Finally, scientists from different fields have recognized mechanisms included in the CGM to understand the exercise limits. Given the importance of the scientific community in demarcating a Kuhnian paradigm shift, I suggest that these three aspects could indicate an increased acceptance of a centrally-regulated effort model, to understand the limits of exercise.
Systematic review of SGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetes
Authors: Clar Christine , Gill James Alexander , Court Rachel , Waugh Norman
Published: October 2012

Background

Despite the number of medications for type 2 diabetes, many people with the condition do not achieve good glycaemic control. Some existing glucose-lowering agents have adverse effects such as weight gain or hypoglycaemia. Type 2 diabetes tends to be a progressive disease, and most patients require treatment with combinations of glucose-lowering agents. The sodium glucose co-transporter 2 (SGLT2) receptor inhibitors are a new class of glucose-lowering agents.

Objective

To assess the clinical effectiveness and safety of the SGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetes.

Data sources

MEDLINE, Embase, Cochrane Library (all sections); Science Citation Index; trial registries; conference abstracts; drug regulatory authorities; bibliographies of retrieved papers.

Inclusion criteria

Randomised controlled trials of SGLT2 receptor inhibitors compared with placebo or active comparator in type 2 diabetes in dual or combination therapy.

Methods

Systematic review. Quality assessment used the Cochrane risk of bias score.

Results

Seven trials, published in full, assessed dapagliflozin and one assessed canagliflozin. Trial quality appeared good. Dapagliflozin 10 mg reduced HbA1c by −0.54% (weighted mean differences (WMD), 95% CI −0.67 to −0.40) compared to placebo, but there was no difference compared to glipizide. Canagliflozin reduced HbA1c slightly more than sitagliptin (up to −0.21% vs sitagliptin). Both dapagliflozin and canagliflozin led to weight loss (dapagliflozin WMD −1.81 kg (95% CI −2.04 to −1.57), canagliflozin up to −2.3 kg compared to placebo).

Limitations

Long-term trial extensions suggested that effects were maintained over time. Data on canagliflozin are currently available from only one paper. Costs of the drugs are not known so cost-effectiveness cannot be assessed. More data on safety are needed, with the Food and Drug Administration having concerns about breast and bladder cancers.

Conclusions

Dapagliflozin appears effective in reducing HbA1c and weight in type 2 diabetes, although more safety data are needed.
Frequency and consequences of violence and aggression towards employees in the German healthcare and welfare system: a cross-sectional study
Authors: Schablon Anja , Zeh Annett , Wendeler Dana , Peters Claudia , Wohlert Claudia , Harling Melanie , Nienhaus Albert
Published: October 2012

Objectives

In this study, the frequency and consequences of aggressive assaults on employees in the German healthcare and welfare system were investigated.

Design

A retrospective cross-sectional study.

Setting

Employees in the German healthcare system and their experiences of violence and aggression were examined in this study.

Participants

The sample consisted of 1973 employees from 39 facilities (6 facilities for the disabled, 6 hospitals and 27 outpatient and inpatient geriatric care facilities) who have regular contact with patients or clients.

Main outcome measures

The frequency of physical and verbal violence towards employees and the consequences of aggressive assaults were analysed.

Results

56% of respondents had experienced physical violence and 78% verbal aggression. The highest frequency of physical violence was in inpatient geriatric care (63%) (p=0.000). Younger workers run a higher risk of being affected by physical violence than older colleagues (OR 1.8, 95% CI 1.3 to 2.4). There is also an increased risk of experiencing physical violence in inpatient geriatric care (OR 1.6, 95% CI 1.2 to 2.0). Around a third of workers feel seriously stressed by the violence experienced. The better the facility trained employees for dealing with aggressive and violent clients, the less risk employees ran of experiencing either verbal aggression (OR 0.5, 95% CI 0.4 to 0.7) or physical violence (OR 0.7, 95% CI 0.6 to 0.9). Training by the facility has a positive effect on experienced stress (OR 0.6, 95% CI 0.4 to 0.8).

Conclusions

Violence towards nursing and healthcare personnel occurs frequently. Every third respondent feels severely stressed by violence and aggression. Occupational support provisions to prevent and provide aftercare for cases of violence and aggression reduce the risk of incidents and of perceived stress. Research is needed on occupational support provisions that reduce the risk of staff experiencing verbal and physical violence and the stress that is associated with it.
Type 2 diabetes: a cohort study of treatment, ethnic and social group influences on glycated haemoglobin
Authors: James Gareth D , Baker Peter , Badrick Ellena , Mathur Rohini , Hull Sally , Robson John
Published: October 2012

Objectives

To assess whether in people with poorly controlled type 2 diabetes (HbA1c>7.5%) improvement in HbA1c varies by ethnic and social group.

Design

Prospective 2-year cohort of type 2 diabetes treated in general practice.

Setting and participants

All patients with type 2 diabetes in 100 of the 101 general practices in two London boroughs. The sample consisted of an ethnically diverse group with uncontrolled type 2 diabetes aged 37–71 years in 2007 and with HbA1c recording in 2008–2009.

Outcome measure

Change from baseline HbA1c in 2007 and achievement of HbA1c control in 2008 and 2009 were estimated for each ethnic, social and treatment group using multilevel modelling.

Results

The sample consisted of 6104 people; 18% were white, 63% south Asian, 16% black African/Caribbean and 3% other ethnic groups. HbA1c was lower after 1 and 2 years in all ethnic groups but south Asian people received significantly less benefit from each diabetes treatment. After adjustment, south Asian people were found to have 0.14% less reduction in HbA1c compared to white people (95% CI 0.04% to 0.24%) and white people were 1.6 (95% CI 1.2 to 2.0) times more likely to achieve HbA1c controlled to 7.5% or less relative to south Asian people. HbA1c reduction and control in black African/Caribbean and white people did not differ significantly. There was no evidence that social deprivation influenced HbA1c reduction or control in this cohort.

Conclusions

In all treatment groups, south Asian people with poorly controlled diabetes are less likely to achieve controlled HbA1c, with less reduction in mean HbA1c than white or black African/Caribbean people.
High risk medicolegal autopsies: is a full postmortem examination necessary?
Authors: Fryer Eve Patricia , Traill Zoe C , Benamore Rachel E , Roberts Ian S D
Published: October 2012

Aims

Aiming to reduce the numbers of high risk autopsies, we use a minimally invasive approach. HIV/hepatitis C virus (HCV)-positive coronial referrals, mainly intravenous drug abusers, have full autopsy only if external examination, toxicology and/or postmortem CT scan do not provide the cause of death. In this study, we review and validate this protocol.

Methods and results

62 HIV/HCV-positive subjects were investigated. All had external examination, 59 toxicology and 24 CT. In 42/62, this minimally invasive approach provided a cause of death. Invasive autopsy was required in 20/62, CT/toxicology being inconclusive, giving a potential rather than definite cause of death. Autopsy findings provided the cause of death in 6/20; in the remainder, a negative autopsy allowed more weight to be given to toxicological results previously regarded as inconclusive. In order to validate selection of cases for invasive autopsy using history, external examination and toxicology, a separate group of 57 non-infectious full autopsies were analysed. These were consecutive cases in which there was a history that suggested drug abuse. A review pathologist, provided only with clinical summary, external findings and toxicology, formulated a cause of death. This formulation was compared with the original cause of death, based on full autopsy. The review pathologist correctly identified a drug-related death or requirement for full autopsy in 56/57 cases. In one case, diagnosed as cocaine toxicity by the review pathologist, autopsy additionally revealed subarachnoid haemorrhage and Berry aneurysm.

Conclusions

These findings support the use of minimally invasive techniques in high risk autopsies, which result in a two-thirds reduction in full postmortems.
Endovascular treatment of paraclinoid aneurysms: 142 aneurysms in one centre
Authors: Wang Yang , Li Youxiang , Jiang Chuhan , Jiang Fan , Meng Hui , Siddiqui Adnan H , Yang Xinjian
Published: October 2012

Background

Current endovascular techniques have been widely used to treat paraclinoid aneurysms.

Methods

From January 2009 to December 2011, 126 consecutive patients with 142 saccular paraclinoid aneurysms were treated with endovascular embolization at our institute. A retrospective review of the clinical and imaging data was performed.

Results

Of the 142 aneurysms, 121 (86.2%) had small while 21 (14.8%) had large fundus size. 83 aneurysms (58.5%) were narrow necked and 59 (41.5%) were wide necked. The dome–neck ratio was favorable in 26 aneurysms (18.3%) and unfavorable in 116 (81.7%). 24 aneurysms (16.9%) were managed with coil embolization and 118 (83.1%) with a stent assisted coiling technique. Immediate angiography demonstrated complete occlusion in 62 (43.7%), neck remnant occlusion in 47 (33.1%), and residual aneurysm occlusion in 33 (23.2%) aneurysms. The overall recurrence rate in the 112 aneurysms with angiographic follow-up (8.88±3.40 months, mean±SD) was 12.5%. Of the 14 recurrent aneurysms, 10 were managed with endovascular treatment (six by stent assisted coiling, four by coiling) while four are under observation. There were six (4.3%) procedural complications during 137 procedures. Clinical follow-up was available for 119 patients (94%) with a follow-up time of 16.6±13.6 months, and the majority (98%) had a modified Rankin scale score of 0–1.

Conclusions

The stent assisted coiling technique is effective for the treatment of paraclinoid aneurysms. Small paraclinoid aneurysms (≤10 mm) are suitable for endovascular treatment, with a low rate of recurrence. In contrast, large paraclinoid aneurysms (>10 mm) treated with current endovascular techniques exhibited a high rate of recurrence.
Modelling the embedment process during offshore pipe-laying on fine-grained soils
Authors: Westgate Z.J. , White D.J. , Randolph M.F.
Published: October 2012

Subsea pipelines are becoming an increasingly significant element of offshore hydrocarbon developments as exploration moves into deep-water environments further from shore. During the lay process, pipelines are subject to small amplitude vertical and horizontal oscillations, driven by the sea state and lay vessel motions. Centrifuge model tests have been used to simulate these small-amplitude lay effects, with varying degrees of idealization relative to the real lay process. In the soft soils found in deep water, pipe embedment can exceed a diameter or more, thus significantly affecting the lateral pipe–soil interaction, axial resistance, and thermal insulation. In this paper, results from centrifuge model tests are used to calibrate a model for calculating the dynamic embedment of a subsea pipeline. The model uses elements of plasticity theory to capture the effects of combined vertical and horizontal loading, and incorporates the softening of the surrounding soil as it is remoulded due to the pipeline motions. Influences from the lay rate, lay geometry, and sea state are included in the calculation process. The model is compared with observed as-laid pipeline embedment data from field surveys at three different offshore sites. Using site-specific soil parameters obtained from in situ testing and idealized pipe loads and motions to represent the load and displacement patterns during offshore pipe-laying, respectively, the model is shown to capture well the final as-laid embedment measured in the field surveys.
Cellular therapy promotes endogenous stem cell repair
Authors: Kamdar Forum , Jameel Mohammad Nurulqadr , Score Paul , Zhang Jianyi
Published: October 2012

Cellular transplantation for cardiac repair has emerged as an exciting treatment option for patients with myocardial infarction (MI) and heart failure. Animal models of post-infarction left ventricular remodeling have demonstrated an improvement in left ventricular (LV) function, decrease in scar size, and amelioration of adverse cardiac remodeling after stem cell transplantation. These beneficial effects occur despite minimal engraftment and negligible differentiation of transplanted cells. Evidence of the heart capability to self-renew continues to mount; however, the extent to which this occurs is still unclear. Although there is a specific population of cardiac stem cells capable of differentiating into cardiomyocytes, they alone are not capable of fully regenerating tissue damaged by MI. Therefore, paracrine mechanisms may be responsible for activating endogenous stem cells to promote regeneration and prevent apoptosis. These structural beneficial effects may reduce regional wall stresses, consequently leading to long-term host myocardium gene/protein expression changes, which may subsequently result in improvement in LV function.
SPIN-DEPENDENT SHOT NOISE IN APERIODIC SEMICONDUCTOR MULTILAYERS HETEROSTRUCTURES
Authors: QIN AILI , LIU DE
Published: October 2012

We investigated the spin-dependent shot noise in aperiodic semiconductor multilayers heterostructures in the presence of the Rashba spin-orbit interaction and an electric field. The results indicate that the shot noise and Fano factor are strongly spin-dependent and can be greatly modulated not only by the external bias voltage and Rashba spin-orbit interaction but also by the thicknesses of block A and B. Our investigations may provide away to design the detection system electronic devices.
Finding Usability Bugs with Automated Tests
Authors: Harty Julian
Published: October 2012

Ideally, all software should be easy to use and accessible for a wide range of people; however, even software that appears to be modern and intuitive often falls short of the most basic usability and accessibility goals. Why does this happen? One reason is that sometimes our designs
look
appealing so we skip the step of testing their usability and accessibility; all in the interest of speed, reducing costs, and competitive advantage.
Testable System Administration
Authors: Burgess Mark
Published: October 2012

The methods of system administration have changed little in the past 20 years. While core IT technologies have improved in a multitude of ways, for many if not most organizations system administration is still based on production-line build logistics (aka provisioning) and reactive incident handling. As we progress into an information age, humans will need to work less like the machines they use and embrace knowledge-based approaches. That means exploiting simple (hands-free) automation that leaves us unencumbered to discover patterns and make decisions. This goal is reachable if IT itself opens up to a core challenge of automation that is long overdue: namely, how to abandon the myth of determinism and expect the unexpected.
Hierarchies in Dependence Logic
Authors: Durand Arnaud , Kontinen Juha
Published: October 2012

We study fragments
D
(
k
∀) and
D
(
k
-dep) of dependence logic defined either by restricting the number
k
of universal quantifiers or the width of dependence atoms in formulas. We find the sublogics of existential second-order logic corresponding to these fragments of dependence logic. We also show that, for any fixed signature, the fragments
D
(
k
∀) give rise to an infinite hierarchy with respect to expressive power. On the other hand, for the fragments
D
(
k
-dep), a hierarchy theorem is otained only in the case the signature is also allowed to vary. For any fixed signature, this question is open and is related to the so-called Spectrum Arity Hierarchy Conjecture.
SART
Authors: Sioutas Spyros , Tsoumakos Dimitrios , Panaretos Alexandros , Tzimas Giannis , Karydis Ioannis , Tsolis Dimitrios
Published: October 2012

We consider the problem of constructing efficient P2P overlays for sensornets providing "Energy-Level Application and Services". In this context, assuming that a sensor is responsible for executing some program task but unfortunately it's energy-level is lower than a pre-defined threshold. Then, this sensor should be able to introduce a query to the whole system in order to discover efficiently another sensor with the desired energy level, in which the task overhead must be eventually forwarded. In this way, the "Life-Expectancy" of the whole network could be increased. Sensor nodes are mapped to peers based on their energy level. As the energy levels change, the sensor nodes would have to move from one peer to another and this operation is very crucial for the efficient scalability of the proposed system. Similarly, as the energy level of a sensor node becomes extremely low, that node may want to forward it's task to another node with the desired energy level. The method presented in presents a novel P2P overlay for Energy Level discovery in a sensornet. However, this solution is not dynamic, since requires periodical restructuring. In particular, it is not able to support neither join of sensor_nodes with energy level out of the ranges supported by the existing p2p overlay nor leave of
empty
overlay_peers to which no sensor_nodes are currently associated. On this purpose and based on the efficient P2P method presented in [16], we design a dynamic P2P overlay for Energy Level discovery in a sensornet, the so-called SART (Sensors' Autonomous Range Tree). The adaptation of the P2P index presented in guarantees the best-known dynamic query performance of the above operation. We experimentally verify this performance, via the D-P2P-Sim simulator.
Innate immune responses involving natural killer and natural killer T cells promote liver regeneration after partial hepatectomy in mice
Authors: Hosoya Satoko , Ikejima Kenichi , Takeda Kazuyoshi , Arai Kumiko , Ishikawa Sachiko , Yamagata Hisafumi , Aoyama Tomonori , Kon Kazuyoshi , Yamashina Shunhei , Watanabe Sumio
Published: October 2012

To clarify the roles of innate immune cells in liver regeneration, here, we investigated the alteration in regenerative responses after partial hepatectomy (PH) under selective depletion of natural killer (NK) and/or NKT cells. Male, wild-type (WT; C57Bl/6), and CD1d-knockout (KO) mice were injected with anti-NK1.1 or anti-asialo ganglio- N-tetraosylceramide (GM1) antibody and then underwent the 70% PH. Regenerative responses after PH were evaluated, and hepatic expression levels of cytokines and growth factors were measured by real-time RT-PCR and ELISA. Phosphorylation of STAT3 was detected by Western blotting. Depletion of both NK and NKT cells with an anti-NK1.1 antibody in WT mice caused drastic decreases in bromodeoxyuridine uptake, expression of proliferating cell nuclear antigen, and cyclin D1, 48 h after PH. In mice given NK1.1 antibody, increases in hepatic TNF-α, IL-6/phospho-STAT3, and hepatocyte growth factor (HGF) levels following PH were also blunted significantly, whereas IFN-γ mRNA levels were not different. CD1d-KO mice per se showed normal liver regeneration; however, pretreatment with an antiasialo GM1 antibody to CD1d-KO mice, resulting in depletion of both NK and NKT cells, also blunted regenerative responses. Collectively, these observations clearly indicated that depletion of both NK and NKT cells by two different ways results in impaired liver regeneration. NK and NKT cells most likely upregulate TNF-α, IL-6/STAT3, and HGF in a coordinate fashion, thus promoting normal regenerative responses in the liver.
3-D imaging and illustration of mouse intestinal neurovascular complex
Authors: Fu Ya-Yuan , Peng Shih-Jung , Lin Hsin-Yao , Pasricha Pankaj J. , Tang Shiue-Cheng
Published: October 2012

Because of the dispersed nature of nerves and blood vessels, standard histology cannot provide a global and associated observation of the enteric nervous system (ENS) and vascular network. We prepared transparent mouse intestine and combined vessel painting and three-dimensional (3-D) neurohistology for joint visualization of the ENS and vasculature. Cardiac perfusion of the fluorescent wheat germ agglutinin (vessel painting) was used to label the ileal blood vessels. The pan-neuronal marker PGP9.5, sympathetic neuronal marker tyrosine hydroxylase (TH), serotonin, and glial markers S100B and GFAP were used as the immunostaining targets of neural tissues. The fluorescently labeled specimens were immersed in the optical clearing solution to improve photon penetration for 3-D confocal microscopy. Notably, we simultaneously revealed the ileal microstructure, vasculature, and innervation with micrometer-level resolution. Four examples are given: 1) the morphology of the TH-labeled sympathetic nerves: sparse in epithelium, perivascular at the submucosa, and intraganglionic at myenteric plexus; 2) distinct patterns of the extrinsic perivascular and intrinsic pericryptic innervation at the submucosal-mucosal interface; 3) different associations of serotonin cells with the mucosal neurovascular elements in the villi and crypts; and 4) the periganglionic capillary network at the myenteric plexus and its contact with glial fibers. Our 3-D imaging approach provides a useful tool to simultaneously reveal the nerves and blood vessels in a space continuum for panoramic illustration and analysis of the neurovascular complex to better understand the intestinal physiology and diseases.
TRPV4 activation in mouse submandibular gland modulates Ca2+influx and salivation
Authors: Zhang Yan , Catalán Marcelo A. , Melvin James E.
Published: October 2012

Transient receptor potential vanilloid subtype 4 (TRPV4) is a ligand-gated nonselective cation channel that participates in the transduction of mechanical and osmotic stimuli in different tissues. TRPV4 is activated by endogenous arachidonic acid metabolites, 4α-phorbol-12,13 didecanoate, GSK1016790A, moderate heat, and mechanical stress. TRPV4 is expressed in the salivary glands, but its expression pattern and function are poorly understood. The aim of this study was to evaluate the functional role of TRPV4 channels in the mouse submandibular gland. Using RT-PCR and Western blot analysis, we detected expression of TRPV4 message and protein, respectively, in the submandibular gland. Immunolocalization studies showed that TRPV4 targeted to the basolateral membrane of mouse submandibular gland acinar cells. Pharmacological TRPV4 activation using the selective agonist GSK1016790A caused Ca2+influx in isolated acinar cells in a basal-to-apical wave. Consistent with these observations, GSK1016790A elicited salivation in the perfused submandibular gland that was dependent on extracellular Ca2+. In summary, we report that activation of TRPV4 channels induced Ca2+influx and salivation and, thus, may contribute a novel nonadrenergic, noncholinergic secretion pathway in the mouse submandibular gland.
Butyrate increases IL-23 production by stimulated dendritic cells
Authors: Berndt Bradford E. , Zhang Min , Owyang Stephanie Y. , Cole Tyler S. , Wang Teresa W. , Luther Jay , Veniaminova Natalia A. , Merchant Juanita L. , Chen Chun-Chia , Huffnagle Gary B. , Kao John Y.
Published: October 2012

The gut microbiota is essential for the maintenance of intestinal immune homeostasis and is responsible for breaking down dietary fiber into short-chain fatty acids (SCFAs). Butyrate, the most abundant bioactive SCFA in the gut, is a histone deacetylase inhibitor (HDACi), a class of drug that has potent immunomodulatory properties. This characteristic of butyrate, along with our previous discovery that conventional dendritic cells (DCs) are required for the development of experimental colitis, led us to speculate that butyrate may modulate DC function to regulate gut mucosal homeostasis. We found that butyrate, in addition to suppressing LPS-induced bone marrow-derived DC maturation and inhibiting DC IL-12 production, significantly induced IL-23 expression. The upregulation of mRNA subunit IL-23p19 at the pretranslational level was consistent with the role of HDACi on the epigenetic modification of gene expression. Furthermore, the mechanism of IL-23p19 upregulation was independent of Stat3 and ZBP89. Coculture of splenocytes with LPS-stimulated DCs pretreated with or without butyrate was performed and showed a significant induction of IL-17 and IL-10. We demonstrated further the effect of butyrate in vivo using dextran sulfate sodium (DSS)-induced colitis and found that the addition of butyrate in the drinking water of mice worsened DSS-colitis. This is in contrast to the daily intraperitoneal butyrate injection of DSS-treated mice, which mildly improved disease severity. Our study highlights a novel effect of butyrate in upregulating IL-23 production of activated DCs and demonstrates a difference in the host response to the oral vs. systemic route of butyrate administration.
Melatonin inhibits nitric oxide signaling by increasing PDE5 phosphorylation in coronary arteries
Authors: Shukla Praveen , Sun Chengwen , O'Rourke Stephen T.
Published: October 2012

Melatonin inhibits nitric oxide (NO)-induced relaxation of coronary arteries. We tested the hypothesis that melatonin increases the phosphorylation of phosphodiesterase 5 (PDE5), which increases the activity of the enzyme and thereby decreases intracellular cGMP accumulation in response to NO and inhibits NO-induced relaxation. Sodium nitroprusside (SNP) and 8-Br-cGMP caused concentration-dependent relaxation of isolated coronary arteries suspended in organ chambers for isometric tension recording. In the presence of melatonin, the concentration-response curve to SNP, but not 8-Br-cGMP, was shifted to the right. The effect of melatonin on SNP-induced relaxation was abolished in the presence of the PDE5 inhibitors zaprinast and sildenafil. Melatonin markedly inhibited the SNP-induced increase in intracellular cGMP in coronary arteries, an effect that was also abolished by zaprinast. Treatment of coronary arteries with melatonin caused a nearly fourfold increase in the phosphorylation of PDE5, which increased the catalytic activity of the enzyme and thereby increased the degradation of cGMP to inactive 5′-GMP. Melatonin-induced PDE5 phosphorylation was markedly attenuated in the presence of the PKG1 inhibitors DT-2 or Rp-8-Br-PET-cGMPS and in those arteries in which PKG1 expression was first downregulated by 24-h incubation with SNP before exposure to melatonin. The selective MT2receptor antagonist 4-phenyl-2-propionamidotetralin completely blocked the stimulatory effect of melatonin on PDE5 phosphorylation as well as the inhibitory effect of melatonin on SNP-induced relaxation and intracellular cGMP. Thus, in coronary arteries, melatonin acts via MT2receptors and PKG1 to increase PDE5 phosphorylation, resulting in decreased cGMP accumulation in response to NO and impaired NO-induced vasorelaxation.
H2O2-induced endothelial NO production contributes to vascular cell apoptosis and increased permeability in rat venules
Authors: Zhou Xueping , Yuan Dong , Wang Mingxia , He Pingnian
Published: October 2012

Although elevated levels of H2O2 have been implicated to play important roles in the pathogenesis of various cardiovascular diseases, the underlying mechanisms remain unclear. This study aims to examine the effect of H2O2 on endothelial nitric oxide (NO) production in intact venules, and elucidate the role and mechanisms of NO in H2O2-induced increases in microvessel permeability. Experiments were conducted on individually perfused rat mesenteric venules. Microvessel permeability was determined by measuring hydraulic conductivity (Lp), and endothelial [Ca2+]i was measured on fura-2-loaded vessels. Perfusion of H2O2 (10 μM) caused a delayed and progressively increased endothelial [Ca2+]i and Lp, a pattern different from inflammatory mediator-induced immediate and transient response. Under the same experimental conditions, measuring endothelial NO via DAF-2 and the spatial detection of cell apoptosis by fluorescent markers revealed that H2O2 induced two phases of NO production followed by caspase activation, intracellular Ca2+ accumulation, and vascular cell apoptosis. The initial NO production was correlated with increased endothelial NO synthase (eNOS) Ser1177 phosphorylation in the absence of elevated endothelial [Ca2+]i, whereas the second phase of NO depended on increased [Ca2+]i and was associated with Thr495 dephosphorylation without increased Ser1177 phosphorylation. Inhibition of NOS prevented H2O2-induced caspase activation, cell apoptosis, and increases in endothelial [Ca2+]i and Lp. Our results indicate that H2O2 at micromolar concentration is able to induce a large magnitude of NO in intact venules, causing caspase activation-mediated endothelial Ca2+ accumulation, cell apoptosis, and increases in permeability. The mechanisms revealed from intact microvessels may contribute to the pathogenesis of oxidant-related cardiovascular diseases.
Left atrial and ventricular function during dobutamine and glycopyrrolate stress in healthy young and elderly as evaluated by cardiac magnetic resonance
Authors: Ahtarovski Kiril A. , Iversen Kasper K. , Lønborg Jacob T. , Madsen Per L. , Engstrøm Thomas , Vejlstrup Niels
Published: October 2012

The aim of this study is to describe phasic volume changes of the left atrium (LA) in healthy young and elderly subjects at rest and during pharmacological stress (PS). LA maximum size is related to cardiovascular mortality. LA has passive, active, and conduit function for left ventricular (LV) filling. We hypothesized that changes in LV compliance from normal aging are reflected in LA volume changes and that PS will augment these differences. We enrolled twenty young (20–30 yr) and twenty elderly (60–70 yr) healthy subjects and measured their LV and LA volumes by cardiac magnetic resonance imaging at rest and during dobutamine and glycopyrrolate stress. We identified LA minimum, maximum, and middiastolic volumes and the volume before atrial contraction. LA emptying volumes were calculated as LA passive and active emptying volumes and LA conduit volume. We also calculated LV peak filling rates (LVPFRs). Both at rest and during PS, LA maximum and minimum volumes were similar in the groups, whereas middiastolic volume was higher in the elderly. During PS, a marked decrease in LA passive emptying function and a corresponding increase in LA active emptying function were seen in the elderly but not in the young. At rest, LVPFR was lower in the elderly, and during PS this difference was augmented. The aging heart has reduced LVPFR, which is reflected in reduced LA passive and compensatory increased LA active volumetric contribution to LV stroke volume. These age-related differences are evident at rest and highly augmented during both dobutamine and glycopyrrolate stress.
Modulation of cardiac Na+,K+-ATPase cell surface abundance by simulated ischemia-reperfusion and ouabain preconditioning
Authors: Belliard Aude , Sottejeau Yoann , Duan Qiming , Karabin Jessa L. , Pierre Sandrine V.
Published: October 2012

Na+,K+-ATPase and cell survival were investigated in a cellular model of ischemia-reperfusion (I/R)-induced injury and protection by ouabain-induced preconditioning (OPC). Rat neonatal cardiac myocytes were subjected to 30 min of substrate and coverslip-induced ischemia followed by 30 min of simulated reperfusion. This significantly compromised cell viability as documented by lactate dehydrogenase release and Annexin V/propidium iodide staining. Total Na+,K+-ATPase α1- and α3-polypeptide expression remained unchanged, but cell surface biotinylation and immunostaining studies revealed that α1-cell surface abundance was significantly decreased. Na+,K+-ATPase-activity in crude homogenates and86Rb+transport in live cells were both significantly decreased by about 30% after I/R. OPC, induced by a 4-min exposure to 10 μM ouabain that ended 8 min before the beginning of ischemia, increased cell viability in a PKCε-dependent manner. This was comparable with the protective effect of OPC previously reported in intact heart preparations. OPC prevented I/R-induced decrease of Na+,K+-ATPase activity and surface expression. This model also revealed that Na+,K+-ATPase-mediated86Rb+uptake was not restored to control levels in the OPC group, suggesting that the increased viability was not conferred by an increased Na+,K+-ATPase-mediated ion transport capacity at the cell membrane. Consistent with this observation, transient expression of an internalization-resistant mutant form of Na+,K+-ATPase α1known to have increased surface abundance without increased ion transport activity successfully reduced I/R-induced cell death. These results suggest that maintenance of Na+,K+-ATPase cell surface abundance is critical to myocyte survival after an ischemic attack and plays a role in OPC-induced protection. They further suggest that the protection conferred by increased surface expression of Na+,K+-ATPase may be independent of ion transport.
Oxidative stress exaggerates skeletal muscle contraction-evoked reflex sympathoexcitation in rats with hypertension induced by angiotensin II
Authors: Koba Satoshi , Watanabe Ryosuke , Kano Naoko , Watanabe Tatsuo
Published: October 2012

Muscle contraction stimulates thin fiber muscle afferents and evokes reflex sympathoexcitation. In hypertension, this reflex is exaggerated. ANG II, which is elevated in hypertension, has been reported to trigger the production of superoxide and other reactive oxygen species. In the present study, we tested the hypothesis that increased ANG II in hypertension exaggerates skeletal muscle contraction-evoked reflex sympathoexcitation by inducing oxidative stress in the muscle. In rats, subcutaneous infusion of ANG II at 450 ng·kg−1·min−1 for 14 days significantly ( P < 0.05) elevated blood pressure compared with sham-operated (sham) rats. Electrically induced 30-s hindlimb muscle contraction in decerebrate rats with hypertension evoked larger renal sympathoexcitatory and pressor responses [+1,173 ± 212 arbitrary units (AU) and +35 ± 5 mmHg, n = 10] compared with sham normotensive rats (+419 ± 103 AU and +13 ± 2 mmHg, n = 11). Tempol, a SOD mimetic, injected intra-arterially into the hindlimb circulation significantly reduced responses in hypertensive rats, whereas this compound had no effect on responses in sham rats. Tiron, another SOD mimetic, also significantly reduced reflex renal sympathetic and pressor responses in a subset of hypertensive rats ( n = 10). Generation of muscle superoxide, as evaluated by dihydroethidium staining, was increased in hypertensive rats. RT-PCR and immunoblot experiments showed that mRNA and protein for gp91 phox, a NADPH oxidase subunit, in skeletal muscle tissue were upregulated in hypertensive rats. Taken together, hese results suggest that increased ANG II in hypertension induces oxidative stress in skeletal muscle, thereby exaggerating the muscle reflex.