bluuebunny/crossref_metadata_2025 huggingface dataset:
Deciphering the Interplay between Two Independent Functions of the Small RNA Regulator SgrS in Salmonella
Authors: Balasubramanian Divya , Vanderpool Carin K.
Published: August 2013

Bacterial dual-function small RNAs regulate gene expression by RNA-RNA base pairing and also code for small proteins. SgrS is a dual-function small RNA in
Escherichia coli
and
Salmonella
that is expressed under stress conditions associated with accumulation of sugar-phosphates, and its activity is crucial for growth during stress. The base-pairing function of SgrS regulates a number of mRNA targets, resulting in reduced uptake and enhanced efflux of sugars. SgrS also encodes the SgrT protein, which reduces sugar uptake by a mechanism that is independent of base pairing. While SgrS base-pairing activity has been characterized in detail, little is known about how base pairing and translation of
sgrT
are coordinated. In the current study, we utilized a series of mutants to determine how translation of
sgrT
affected the efficiency of base pairing-dependent regulation and vice versa. Mutations that abrogated
sgrT
translation had minimal effects on base-pairing activity. Conversely, mutations that impaired base-pairing interactions resulted in increased SgrT production. Furthermore, while ectopic overexpression of
sgrS
mutant alleles lacking only one of the two functions rescued cell growth under stress conditions, the SgrS base-pairing function alone was indispensable for growth rescue when alleles were expressed from the native locus. Collectively, the results suggest that during stress, repression of sugar transporter synthesis via base pairing with sugar transporter mRNAs is the first priority of SgrS. Subsequently, SgrT is made and acts on preexisting transporters. The combined action of these two functions produces an effective stress response.
Diverse Functions for Six Glycosyltransferases in Caulobacter crescentus Cell Wall Assembly
Authors: Yakhnina Anastasiya A. , Gitai Zemer
Published: August 2013

The essential process of peptidoglycan synthesis requires two enzymatic activities, transpeptidation and transglycosylation. While the PBP2 and PBP3 transpeptidases perform highly specialized functions that are widely conserved, the specific roles of different glycosyltransferases are poorly understood. For example,
Caulobacter crescentus
encodes six glycosyltransferase paralogs of largely unknown function. Using genetic analyses, we found that
Caulobacter
glycosyltransferases are primarily redundant but that PbpX is responsible for most of the essential glycosyltransferase activity. Cells containing PbpX as their sole glycosyltransferase are viable, and the loss of
pbpX
leads to a general defect in the integrity of the cell wall structure even in the presence of the other five glycosyltransferases. However, neither PbpX nor any of its paralogs is required for the specific processes of cell elongation or division, while the cell wall synthesis required for stalk biogenesis is only partially disrupted in several of the glycosyltransferase mutants. Despite their genetic redundancy,
Caulobacter
glycosyltransferases exhibit different subcellular localizations. We suggest that these enzymes have specialized roles and normally function in distinct subcomplexes but retain the ability to substitute for one another so as to ensure the robustness of the peptidoglycan synthesis process.
Identification and Characterization of RibN, a Novel Family of Riboflavin Transporters from Rhizobium leguminosarum and Other Proteobacteria
Authors: García Angulo Víctor A. , Bonomi Hernán R. , Posadas Diana M. , Serer María I. , Torres Alfredo G. , Zorreguieta Ángeles , Goldbaum Fernando A.
Published: August 2013

Rhizobia are symbiotic bacteria able to invade and colonize the roots of legume plants, inducing the formation of nodules, where bacteria reduce atmospheric nitrogen (N
2
) to ammonia (NH
3
). Riboflavin availability influences the capacity of rhizobia to survive in the rhizosphere and to colonize roots. In this study, we identified the
RL1692
gene of
Rhizobium leguminosarum
downstream of a flavin mononucleotide (FMN) riboswitch.
RL1692
encodes a putative transmembrane permease with two EamA domains. The presence of an FMN riboswitch regulating a transmembrane protein is usually observed in riboflavin transporters, suggesting that RL1692 may be involved in riboflavin uptake. The product of
RL1692
, which we named RibN, is conserved in members of the alpha-, beta-, and gammaproteobacteria and shares no significant identity with any riboflavin transporter previously identified. In this work, we show that RibN is localized in the membrane cellular fraction and its expression is downregulated by riboflavin. By heterologous expression in a
Brucella abortus
mutant auxotrophic for riboflavin, we demonstrate that RibN possesses flavin transport activity. Similarly, we also demonstrate that RibN orthologues from
Ochrobactrum anthropi
and
Vibrio cholerae
(which lacks the FMN riboswitch) are able to transport riboflavin. An
R. leguminosarum ribN
null mutant exhibited lower nodule occupancy levels in pea plants during symbiosis assays. Thus, we propose that RibN and its homologues belong to a novel family of riboflavin transporters. This work provides the first experimental description of riboflavin transporters in Gram-negative bacteria.
Control of the Escherichia coli Sialoregulon by Transcriptional Repressor NanR
Authors: Kalivoda Kathryn A. , Steenbergen Susan M. , Vimr Eric R.
Published: August 2013

NanR, one of >8,500 GntR superfamily helix-turn-helix transcriptional regulators, controls expression of the genes required for catabolism of sialic acids in
Escherichia coli
. It is predicted to do the same in related bacteria harboring orthologs of
nanR
. The sialic acids are a family of over 40 naturally occurring nine-carbon keto-sugar acids found mainly in the animal lineage, which includes starfish to humans in the deuterostome lineage. Sialic acids function in development, immunity, protein localization and stability, and homeostasis. They also serve as microbial carbon and nitrogen sources and ligands for cell recognition during host colonization. The importance of microbial sialic acid metabolism for host-microbe interactions has made it a target for therapeutic development. Exploiting this target depends on understanding sialometabolic pathways in a wide range of evolutionarily distinct bacteria. Here, we show by transcriptome, genetic, and biochemical analyses that the most common sialic acid,
N
-acetylneuraminate, induces the
nanATEK-yhcH
,
yjhATS
(
nanCMS
), and
yjhBC
operons by directly inactivating NanR, converting the predominantly dimeric form of the repressor to an inactive monomer of approximately 30-kDa. Additionally, other results identify critical amino acid residues and nucleotides in the regulator and operator, respectively. The combined results better define how sialic acids, acting through NanR, affect the metabolic flux of an important group of host-derived metabolites. Thus,
E. coli
serves as a valuable model for understanding sialocatabolic pathways in bacteria.
Nitrite Reductase NirBD Is Induced and Plays an Important Role during
In Vitro
Dormancy of Mycobacterium tuberculosis
Authors: Akhtar Shamim , Khan Arshad , Sohaskey Charles D. , Jagannath Chinnaswamy , Sarkar Dhiman
Published: August 2013

Mycobacterium tuberculosis
is one of the strongest reducers of nitrate among all mycobacteria. Reduction of nitrate to nitrite, mediated by nitrate reductase (NarGHJI) of
M. tuberculosis
, is induced during the dormant stage, and the enzyme has a respiratory function in the absence of oxygen. Nitrite reductase (NirBD) is also functional during aerobic growth when nitrite is the sole nitrogen source. However, the role of NirBD-mediated nitrite reduction during the dormancy is not yet characterized. Here, we analyzed nitrite reduction during aerobic growth as well as in a hypoxic dormancy model of
M. tuberculosis in vitro
. When nitrite was used as the sole nitrogen source in the medium, the organism grew and the reduction of nitrite was evident in both hypoxic and aerobic cultures of
M. tuberculosis
. Remarkably, the hypoxic culture of
M. tuberculosis
, compared to the aerobic culture, showed 32- and 4-fold-increased expression of nitrite reductase (NirBD) at the transcription and protein levels, respectively. More importantly, a
nirBD
mutant of
M. tuberculosis
was unable to reduce nitrite and compared to the wild-type (WT) strain had a >2-log reduction in viability after 240 h in the Wayne model of hypoxic dormancy. Dependence of
M. tuberculosis
on nitrite reductase (NirBD) was also seen in a human macrophage-based dormancy model where the
nirBD
mutant was impaired for survival compared to the WT strain. Overall, the increased expression and essentiality of nitrite reductase in the
in vitro
dormancy models suggested that NirBD-mediated nitrite reduction could be critical during the persistent stage of
M. tuberculosis
.
The Putative Enoyl-Coenzyme A Hydratase DspI Is Required for Production of the Pseudomonas aeruginosa Biofilm Dispersion Autoinducer
cis
-2-Decenoic Acid
Authors: Amari Diana T. , Marques Cláudia N. H. , Davies David G.
Published: August 2013

In the present study, we report the identification of a putative enoyl-coenzyme A (CoA) hydratase/isomerase that is required for synthesis of the biofilm dispersion autoinducer
cis
-2-decenoic acid in the human pathogen
Pseudomonas aeruginosa
. The protein is encoded by PA14_54640 (PA0745), named
dspI
for
d
i
sp
ersion
i
nducer. The gene sequence for this protein shows significant homology to RpfF in
Xanthomonas campestris
. Inactivation of
dspI
was shown to abolish biofilm dispersion autoinduction in continuous cultures of
P. aeruginosa
and resulted in biofilms that were significantly greater in thickness and biomass than those of the parental wild-type strain. Dispersion was shown to be inducible in
dspI
mutants by the exogenous addition of synthetic
cis
-2-decenoic acid or by complementation of Δ
dspI in trans
under the control of an arabinose-inducible promoter. Mutation of
dspI
was also shown to abolish
cis
-2-decenoic acid production, as revealed by gas chromatography-mass spectrometry (GC-MS) analysis of cell-free spent culture medium. The transcript abundance of
dspI
correlated with cell density, as determined by quantitative reverse transcriptase (RT) PCR. This regulation is consistent with the characterization of
cis
-2-decenoic acid as a cell-to-cell communication molecule that regulates biofilm dispersion in a cell density-dependent manner.
ppGpp Metabolism Is Involved in Heterocyst Development in the Cyanobacterium Anabaena sp. Strain PCC 7120
Authors: Zhang Shao-Ran , Lin Gui-Ming , Chen Wen-Li , Wang Li , Zhang Cheng-Cai
Published: August 2013

When deprived of a combined-nitrogen source in the growth medium, the filamentous cyanobacterium
Anabaena
sp. PCC 7120 (
Anabaena
) can form heterocysts capable of nitrogen fixation. The process of heterocyst differentiation takes about 20 to 24 h, during which extensive metabolic and morphological changes take place. Guanosine tetraphosphate (ppGpp) is the signal of the stringent response that ensures cell survival by adjusting major cellular activities in response to nutrient starvation in bacteria, and ppGpp accumulates at the early stage of heterocyst differentiation (J. Akinyanju, R. J. Smith, FEBS Lett. 107:173–176, 1979; J Akinyanju, R. J. Smith, New Phytol. 105:117–122, 1987). Here we show that
all1549
(here designated

rel
ana

) in
Anabaena
, homologous to
relA/spoT
, is upregulated in response to nitrogen deprivation and predominantly localized in vegetative cells. The disruption of

rel
ana

strongly affects the synthesis of ppGpp, and the resulting mutant,
all1549
Ωsp/sm, fails to form heterocysts and to grow in the absence of a combined-nitrogen source. This phenotype can be complemented by a wild-type copy of

rel
ana

. Although the upregulation of
hetR
is affected in the mutant, ectopic overexpression of
hetR
cannot rescue the phenotype. However, we found that the mutant rapidly loses its viability, within a time window of 3 to 6 h, following the deprivation of combined nitrogen. We propose that ppGpp plays a major role in rebalancing the metabolic activities of the cells in the absence of the nitrogen source supply and that this regulation is necessary for filament survival and consequently for the success of heterocyst differentiation.
Interaction of Streptococcus mutans YidC1 and YidC2 with Translating and Nontranslating Ribosomes
Authors: Wu Zht Cheng , de Keyzer Jeanine , Berrelkamp-Lahpor Greetje A. , Driessen Arnold J. M.
Published: August 2013

The YidC/OxaI/Alb3 family of membrane proteins is involved in the biogenesis of integral membrane proteins in bacteria, mitochondria, and chloroplasts. Gram-positive bacteria often contain multiple YidC paralogs that can be subdivided into two major classes, namely, YidC1 and YidC2. The
Streptococcus mutans
YidC1 and YidC2 proteins possess C-terminal tails that differ in charges (+9 and + 14) and lengths (33 and 61 amino acids). The longer YidC2 C terminus bears a resemblance to the C-terminal ribosome-binding domain of the mitochondrial OxaI protein and, in contrast to the shorter YidC1 C terminus, can mediate the interaction with mitochondrial ribosomes. These observations have led to the suggestion that YidC1 and YidC2 differ in their abilities to interact with ribosomes. However, the interaction with bacterial translating ribosomes has never been addressed. Here we demonstrate that
Escherichia coli
ribosomes are able to interact with both YidC1 and YidC2. The interaction is stimulated by the presence of a nascent membrane protein substrate and abolished upon deletion of the C-terminal tail, which also abrogates the YidC-dependent membrane insertion of subunit c of the F
1
F
0
-ATPase into the membrane. It is concluded that both YidC1 and YidC2 interact with ribosomes, suggesting that the modes of membrane insertion by these membrane insertases are similar.
The MerR-Like Regulator BrlR Impairs Pseudomonas aeruginosa Biofilm Tolerance to Colistin by Repressing PhoPQ
Authors: Chambers Jacob R. , Sauer Karin
Published: August 2013

While the MerR-like transcriptional regulator BrlR has been demonstrated to contribute to
Pseudomonas aeruginosa
biofilm tolerance to antimicrobial agents known as multidrug efflux pump substrates, the role of BrlR in resistance to cationic antimicrobial peptides (CAP), which is based on reduced outer membrane susceptibility, is not known. Here, we demonstrate that inactivation of
brlR
coincided with increased resistance of
P. aeruginosa
to colistin, while overexpression of
brlR
resulted in increased susceptibility.
brlR
expression correlated with reduced transcript abundances of
phoP
,
phoQ
,
pmrA
,
pmrB
, and
arnC
. Inactivation of
pmrA
and
pmrB
had no effect on the susceptibility of
P. aeruginosa
biofilms to colistin, while inactivation of
phoP
and
phoQ
rendered biofilms more susceptible than the wild type. The susceptibility phenotype of Δ
phoP
biofilms to colistin was comparable to that of
P. aeruginosa
biofilms overexpressing
brlR
. BrlR was found to directly bind to
oprH
promoter DNA of the
oprH-phoPQ
operon. BrlR reciprocally contributed to colistin and tobramycin resistance in
P. aeruginosa
PAO1 and CF clinical isolates, with overexpression of
brlR
resulting in increased tobramycin MICs and increased tobramycin resistance but decreased colistin MICs and increased colistin susceptibility. The opposite trend was observed upon
brlR
inactivation. The difference in susceptibility to colistin and tobramycin was eliminated by combination treatment of biofilms with both antibiotics. Our findings establish BrlR as an unusual member of the MerR family, as it not only functions as a multidrug transport activator, but also acts as a repressor of
phoPQ
expression, thus suppressing colistin resistance.
A Novel Protein Protects Bacterial Iron-Dependent Metabolism from Nitric Oxide
Authors: Stern Andrew M. , Liu Binbin , Bakken Lars R. , Shapleigh James P. , Zhu Jun
Published: August 2013

Reactive nitrogen species (RNS), in particular nitric oxide (NO), are toxic to bacteria, and bacteria have mechanisms to allow growth despite this stress. Understanding how bacteria interact with NO is essential to understanding bacterial physiology in many habitats, including pathogenesis; however, many targets of NO and enzymes involved in NO resistance remain uncharacterized. We performed for the first time a metabolomic screen on NO-treated and -untreated bacteria to define broadly the effects of NO on bacterial physiology, as well as to identify the function of NnrS, a previously uncharacterized enzyme involved in defense against NO. We found many known and novel targets of NO. We also found that iron-sulfur cluster enzymes were preferentially inhibited in a strain lacking NnrS due to the formation of iron-NO complexes. We then demonstrated that NnrS is particularly important for resistance to nitrosative stress under anaerobic conditions. Our data thus reveal the breadth of the toxic effects of NO on metabolism and identify the function of an important enzyme in alleviating this stress.
Bilateral medial medullary syndrome secondary to Takayasu arteritis
Authors: Deshpande Anirudda , Chandran Vijay , Pai Aparna , Rao Suryanarayana , Shetty Ranjan
Published: August 2013

Medial medullary syndrome (MMS) is a rare type of stroke which results due to occlusion of the anterior spinal artery or vertebral artery or its branches. In this case report we present a patient who developed MMS secondary to Takayasu arteritis (TA). TA is a chronic inflammatory arteritis primarily involving the arch of aorta and its branches, which in our patient resulted in occlusion of subclavian arteries as well as infarction of the medial medulla bilaterally. To our knowledge this is the first time that MMS has been found to occur secondary to TA.
Predictive accuracy of triage nurses evaluation in risk stratification of syncope in the emergency department
Authors: Bonzi M , Fiorelli E M , Angaroni L , Furlan L , Solbiati M , Colombo C , Dipaola F , Montano N , Furlan R , Costantino G
Published: August 2013

Background

Syncope is a common clinical problem that accounts for 1–3% of all emergency department (ED) visits. Its prognosis is extremely variable with a 1-year mortality that may reach 30%. There are no available data about the accuracy of nursing triage in identifying high-risk syncope. The aim of our study was to evaluate the predictive accuracy of nursing triage in identifying high-risk syncope.

Methods

We conducted a retrospective study on 678 consecutive patients who presented with syncope at four EDs. For each patient, nursing triage, comorbidities, clinical features and adverse events that occurred both in the ED and at 10-day follow-up were assessed. Adverse events included death, readmission to ED, need for major therapeutic procedures, cardiopulmonary resuscitation, intensive care unit admittance, acute antiarrhythmic therapy and major causes of syncope identified during the ED evaluation. Predictive accuracy of nursing triage was evaluated.

Results

We observed a total of 55 (8.1%) adverse events. Eight of them (9.4%) occurred among the 85 patients who were identified as high priority by nursing triage. Sensitivity (Sn) and specificity (Sp) of urgent nursing triage in identifying adverse outcomes in the ED (19 patients) were 21% (95% CI 3% to 39%) and 88% (95% CI 85% to 90%), while the positive likelihood ratio (LR+) and negative likelihood ratio (LR−) were 1.7 and 0.9, respectively. Sn and Sp for 10-day adverse events were 15% (95% CI 5% to 24%) and 88% (95% CI 85% to 90%), respectively, with a LR+ of 1.18 and a LR− of 0.98.

Conclusions

Nursing triage was characterised by a low predictive accuracy in identifying high-risk individuals.
Clinical significance of micropapillary urothelial carcinoma of the upper urinary tract
Authors: Sung Hyun Hwan , Cho Junhun , Kwon Ghee Young , Jeon Hwang Gyun , Jeong Byong Chang , Seo Seong Il , Jeon Seong Soo , Choi Han-Yong , Lee Hyun Moo
Published: August 2013

Background

The aim of this study was to improve understanding of the characteristics of micropapillary urothelial carcinoma (MPUC) in the renal pelvis and ureter, and to compare oncological outcomes between MPUC and non-MPUC.

Methods

From September 1994 to October 2010, 418 patients underwent nephroureterectomy with bladder excision due to presumed urothelial carcinoma. Pathological review of all specimens was done by one uropathologist. Perioperative data from these patients were reviewed retrospectively. Patients were divided into MPUC and non-MPUC groups. Oncological outcomes were compared between the two groups via progression-free survival (PFS) and cancer-specific survival (CSS) rates.

Results

A total of 386 patients were included in the study. Of these, seven patients (1.81%) had MPUC. The median follow-up duration was 39.0 months (IQR range 21.1–70.6). All MPUC patients were men and had lymphovascular invasion, and six patients (85.7%) had grade III and T3 disease. On univariable analysis, MPUC showed significantly worse prognosis with regard to disease progression (p<0.001). In the subgroup analysis confined to T3 or T4 disease, MPUC showed worse prognosis than non-MPUC in terms of PFS and CSS, respectively (p<0.05). In the multivariable model, MPUC still remained a statistically significant independent predictor for PFS (HR (95% CI)=3.85 (1.59–9.32), p=0.003). MPUC was associated with poorer CSS than non-MPUC (p<0.001).

Conclusions

We have observed that upper tract MPUC is associated with poor oncological outcomes in terms of PFS and CSS. MPUC was an independent prognostic factor for PFS in multivariable analysis.
Validating the 5Fs mnemonic for cholelithiasis: time to include family history
Authors: Bass Gary , Gilani S Nadia S , Walsh Thomas N , Leader Frank
Published: August 2013

Background

The time-honoured mnemonic of ‘5Fs’ is a reminder to students that patients with upper abdominal pain and who conform to a profile of ‘fair, fat, female, fertile and forty’ are likely to have cholelithiasis. We feel, however, that a most important ‘F’—that for ‘family history’—is overlooked and should be introduced to enhance the value of a useful aide memoire.

Methods

To assess the usefulness of each of the existing factors of a popular mnemonic, 398 patients admitted with upper abdominal pain between March 2009 and April 2010 were studied. The clinical features expressed in the cholelithiasis mnemonic in patients with sonographic evidence of cholelithiasis were compared with those of patients without.

Findings

In the cholelithiasis group, significantly more patients were women (150/198 (75.8%) vs 111/200 (55.5%), p<0.001), fair (144/198 (62.9%) vs 54/200 (32.1%), (p<0.001)), fertile (135/198 (68.2%) vs 50/200 (25%) (p<0.001)) and had a body mass index >30 (56/198 (28.3%) vs 19/200 (9.5%) (p<0.001)) compared with controls; but age over 40 years did not predict cholelithiasis (82/198 (41.4%) vs 79/200 (39.5%) (p=0.697)). In the cholelithiasis group, 78/198 (39.4%) had a family history in at least one first-degree relative, compared with 27/200 (13.5%) of controls, (p<0.001). Where the phenotypic elements of the history existed in combination, that patient was found to be at an increased risk of cholelithiasis.

Interpretation

Our study found that the validated ‘students’ 5Fs’ mnemonic retains a role in clinical diagnosis of patients suspected of cholelithiasis but the factor ‘familial’ should be substituted for ‘forty’ in recognition of the role of inheritance and the changing demographics of gallstone incidence.
Pathogen profile in men with inflammation of paraurethral glands
Authors: Fan Wenge , Zhang Qingsong , Jiang Tingwang
Published: August 2013

Objective

To investigate the pathogen profile in men with inflammation of the paraurethral glands.

Methods

We enrolled 40 patients with first-onset, drug-naive inflammation of the paraurethral glands. Discharge from the lesions was collected for Gram staining. Microscopy was performed for screening for trichomonads and detecting Gram-negative intracellular diplococci within phagocytes. Cultures for detection ofNeisseria gonorrhoeae,Ureaplasma urealyticumand other bacteria, andChlamydia-trachomatis-associated antigens were performed. PCR was conducted for herpes simplex virus type 1 or 2.

Results

From these 40 patients, there were nine microbial species, which included Gram-negative bacteria (23 cases, 54.8%), Gram-positive bacteria (15 cases, 35.7%) and other pathogens (4 cases, 9.5%). The top three pathogens were gonococci (38.1%),Staphylococcus aureus(16.7%) andEscherichia coli(14.3%).

Conclusions

Inflammation of paraurethral glands in men may be caused by a variety of pathogens and not just by gonococcal infection.
Computational study on the reaction of atomic chlorine with 1,2-dibromoethane (CH2BrCH2Br)
Authors: Yu Ang-yang
Published: August 2013

In this work, the reaction mechanism and kinetics of Cl + CH2BrCH2Br → products are theoretically investigated for the first time. The optimized geometries and frequencies of all of the stationary points and selected points along the minimum-energy path for the three hydrogen abstraction channels and two bromine abstraction channels are calculated at the BH&H-LYP level with the 6-311G** basis set and the energy profiles are further calculated at the CCSD(T) level of theory. The rate constants are evaluated using the conventional transition-state theory, the canonical variational transition-state theory, and the canonical variational transition-state theory with a small-curvature tunneling correction over the temperature range 200–1000 K. The results show that reaction channel 3 is the primary channel and the calculated rate constants are in good agreement with available experimental values. The three-parameter Arrhenius expression for the total rate constants over 200–1000 K is provided.
Initial turnover rates of two standard wood substrates following land-use change in subalpine ecosystems in the Swiss Alps
Authors: Risch Anita C. , Jurgensen Martin F. , Page-Dumroese Deborah S. , Schütz Martin
Published: August 2013

Forest cover has increased in mountainous areas of Europe over the past decades because of the abandonment of agricultural areas (land-use change). For this reason, understanding how land-use change affects carbon (C) source–sink strength is of great importance. However, most studies have assessed mountainous systems C stocks, and less is known about C turnover rates, especially of “fresh” organic material (OM). We studied the decomposition of wood stakes of trembling aspen (Populus tremuloides Michx.) and loblolly pine (Pinus taeda L.) placed on the litter layer and in the mineral soil of five ecosystem types (pastures and forests) — representing the successional development after land abandonment in the eastern Swiss Alps — for 6 years. Wood stake decomposition rates were generally highest in pastures and lowest in early successional forests. Aspen stakes decomposed more rapidly than pine stakes, especially in the mineral soil. Soil temperature (and to a smaller extent soil phosphorus (P) concentration) best explained the differences in decomposition among the ecosystem types. Initial wood decay is temperature-sensitive, and therefore would likely increase under future climate change scenarios.
Prediction of bioactive compound activity against wood contaminant fungi using artificial neural networks
Authors: Vicente Henrique , Roseiro José C. , Arteiro José M. , Neves José , Caldeira A. Teresa
Published: August 2013

Biopesticides based on natural endophytic bacteria to control plant diseases are an ecological alternative to chemical treatments. Bacillus species produce a wide variety of metabolites with biological activity like iturinic lipopeptides. This work addresses the production of biopesticides based on natural endophytic bacteria isolated from Quercus suber L. Artificial neural networks were used to maximize the percentage of inhibition triggered by the antifungal activity of bioactive compounds produced by Bacillus amyloliquefaciens. The active compounds, produced in liquid cultures, inhibited the growth of 15 fungi and exhibited a broader spectrum of antifungal activity against surface contaminant fungi, blue stain fungi, and phytopathogenic fungi. A 19-7-6-1 neural network was selected to predict the percentage of inhibition produced by antifungal bioactive compounds. A good match among the observed and predicted values was obtained with the R2values varying between 0.9965–0.9971 and 0.9974–0.9989 for training and test sets. The 19-7-6-1 neural network was used to establish the dilution rates that maximize the production of antifungal bioactive compounds, namely, 0.25 h−1for surface contaminant fungi, 0.45 h−1for blue stain fungi, and between 0.30 and 0.40 h−1for phytopathogenic fungi. Artificial neural networks show great potential in the modelling and optimization of these bioprocesses.
THE ENERGY SPACES OF THE TANGENT POINT ENERGIES
Authors: BLATT SIMON
Published: August 2013

In this note, we will give a necessary and sufficient condition under which the tangent point energies introduced by von der Mosel and Strzelecki in [J. Geom. Anal., pp. 1–55 (2011), J. Knot Theory Ramifications21 (2012) 1250044] are bounded. We show that an admissible submanifold has bounded 𝔈q-energy if and only if it is injective and locally agrees with the graph of functions that belong to Sobolev–Slobodeckij space [Formula: see text]. The known Morrey embedding theorems of von der Mosel and Strzelecki can then be interpreted as standard Morrey embedding theorems for these spaces. Especially, this shows that the Hölder exponents for the embeddings in [J. Geom. Anal., pp. 1–55 (2011)] are sharp.
Diverse regulation of IP3 and ryanodine receptors by pentazocine through σ1-receptor in cardiomyocytes
Authors: Tagashira Hideaki , Bhuiyan Md. Shenuarin , Fukunaga Kohji
Published: August 2013

Although pentazocine binds to σ1-receptor (σ1R) with high affinity, the physiological relevance of its binding remains unclear. We first confirmed that σ1R stimulation with pentazocine rescues contractile dysfunction following pressure overload (PO)-induced cardiac hypertrophy ovariectomized (OVX) female rats. In in vivo studies, vehicle, pentazocine (0.5–1.0 mg/kg ip), and NE-100 (1.0 mg/kg po), a σ1R antagonist, were administered for 4 wk (once daily) starting from the onset of aortic banding after OVX. We also examined antihypertrophic effects of pentazocine (0.5–1 μM) in cultured cardiomyocytes exposed to angiotensin II. Pentazocine administration significantly inhibited PO-induced cardiac hypertrophy and rescued hypertrophy-induced impairment of cardiac dysfunctions such as left ventricular end-diastolic pressure, left ventricular developed pressure, and left ventricular contraction and relaxation (±dp/dt) rates. Coadministration of NE-100 with pentazocine eliminated pentazocine-induced amelioration of heart dysfunction. Interestingly, pentazocine administration inhibited PO-induced σ1R reduction and inositol-1,4,5-trisphosphate (IP3) receptor type 2 (IP3R2) upregulation in heart. Therefore, the reduced mitochondrial ATP production following PO was restored by pentazocine administration. Furthermore, we found that σ1R binds to the ryanodine receptor (RyR) in addition to IP3 receptor (IP3R) in cardiomyocytes. The σ1R/RyR complexes were decreased following OVX-PO and restored by pentazocine administration. We noticed that pentazocine inhibits the ryanodine-induced Ca2+ release from sarcoplasmic reticulum (SR) in cultured cardiomyocytes. Taken together, the stimulation of σ1R by pentazocine rescues cardiac dysfunction by restoring IP3R-mediated mitochondrial ATP production and by suppressing RyR-mediated Ca2+ leak from SR in cardiomyocytes.
Shear stress modulates VCAM-1 expression in response to TNF-α and dietary lipids via interferon regulatory factor-1 in cultured endothelium
Authors: DeVerse J. Sherrod , Sandhu Angad S. , Mendoza Natalie , Edwards Christina M. , Sun Chongxiu , Simon Scott I. , Passerini Anthony G.
Published: August 2013

Dyslipidemia is a primary risk factor for cardiovascular disease, but the specific mechanisms that determine the localization of atherosclerotic plaques in arteries are not well defined. Triglyceride-rich lipoproteins (TGRL) isolated from human plasma after a high-fat meal modulate TNF-α-induced VCAM-1 expression in cultured human aortic endothelial cells (HAECs) via an interferon regulatory factor (IRF)-1-dependent transcriptional mechanism. We examined whether fluid shear stress acts as a mediator of IRF-1-dependent VCAM-1 expression in response to cytokine and dietary lipids. IRF-1 and VCAM-1 were examined by immunofluorescence in TNF-α-stimulated HAEC monolayers exposed to TGRL and a linear gradient of shear stress ranging from 0 to 16 dyn/cm2 in a microfluidic device. Shear stress alone modulated TNF-α-induced VCAM-1 expression, eliciting a 150% increase at low shear stress (2 dyn/cm2) and a 70% decrease at high shear stress (12 dyn/cm2) relative to static. These differences correlated with a 60% increase in IRF-1 expression under low shear stress and a 40% decrease under high shear stress. The addition of TGRL along with cytokine activated a fourfold increase in VCAM-1 expression and a twofold increase in IRF-1 expression. The combined effect of shear stress and TGRL on the upregulation of membrane VCAM-1 was abolished by transfection of HAECs with IRF-1-specific small interfering RNA. In a healthy swine model, elevated levels of endothelial IRF-1 were also observed within atherosusceptible regions of the aorta by Western blot analysis and immunohistochemistry, implicating arterial hemodynamics in the regulation of IRF-1 expression. These data demonstrate direct roles for fluid shear stress and postprandial TGRL from human serum in the regulation of IRF-1 expression and downstream inflammatory responses in HAECs.
Aspirate from human stented native coronary arteries vs. saphenous vein grafts: more endothelin but less particulate debris
Authors: Kleinbongard Petra , Baars Theodor , Möhlenkamp Stefan , Kahlert Philipp , Erbel Raimund , Heusch Gerd
Published: August 2013

Stent implantation into atherosclerotic coronary arteries releases particulate debris and soluble substances that contribute to impaired microvascular perfusion. Here we addressed the potential for microvascular obstruction in patients with stenotic native right coronary arteries (nRCA) compared with saphenous vein grafts on right coronary arteries (SVG-RCA). We enrolled symptomatic, male patients with stable angina pectoris and a flow-limiting stenosis in their nRCA or SVG-RCA ( n = 18/18). Plaque volume and composition were analyzed using intravascular ultrasound before stent implantation. Coronary aspirate was retrieved during stent implantation under protection with a distal occlusion/aspiration device and divided into particulate debris and plasma. The release of catecholamines, endothelin, serotonin, thromboxane B2, and tumor necrosis factor-α was measured. The response of rat mesenteric arteries with intact (+E) and denuded (−E) endothelium to aspirate plasma (without and with selective endothelin receptor blockade) was normalized to that by potassium chloride (KClmax = 100%). Plaque volume and composition were not different between nRCA and SVG-RCA. There was less particulate debris (65 ± 8 vs. 146 ± 23 mg; P < 0.05) and more endothelin release (5.8 ± 0.8 vs. 1.3 ± 0.7 pg/ml; P < 0.05) in nRCA than in SVG-RCA, whereas the release of the other mediators was not different. Aspirate from nRCA induced stronger vasoconstriction than that from SVG-RCA [nRCA, 78 ± 6% (+E)/84 ± 5% (−E); SVG-RCA, 59 ± 6% (+E)/68 ± 3% (−E); P < 0.05 nRCA vs. SVG-RCA], which was attenuated by a nonspecific endothelin and a specific endothelin receptor A antagonist. Thus coronary aspirate from stented nRCA is characterized by less debris but more endothelin and stronger vasoconstrictor response than that from SVG-RCA.
Disruption of phase synchronization between blood pressure and muscle sympathetic nerve activity in postural vasovagal syncope
Authors: Schwartz Christopher E. , Lambert Elisabeth , Medow Marvin S. , Stewart Julian M.
Published: August 2013

Withdrawal of muscle sympathetic nerve activity (MSNA) may not be necessary for the precipitous fall of peripheral arterial resistance and arterial pressure (AP) during vasovagal syncope (VVS). We tested the hypothesis that the MSNA-AP baroreflex entrainment is disrupted before VVS regardless of MSNA withdrawal using the phase synchronization between blood pressure and MSNA during head-up tilt (HUT) to measure reflex coupling. We studied eight VVS subjects and eight healthy control subjects. Heart rate, AP, and MSNA were measured during supine baseline and at early, mid, late, and syncope stages of HUT. Phase synchronization indexes, measuring time-dependent differences between MSNA and AP phases, were computed. Directionality indexes, indicating the influence of AP on MSNA (neural arc) and MSNA on AP (peripheral arc), were computed. Heart rate was greater in VVS compared with control subjects during early, mid, and late stages of HUT and significantly declined at syncope ( P = 0.04). AP significantly decreased during mid, late, and syncope stages of tilt in VVS subjects only ( P = 0.001). MSNA was not significantly different between groups during HUT ( P = 0.700). However, the phase synchronization index significantly decreased during mid and late stages in VVS subjects but not in control subjects ( P < .001). In addition, the neural arc was significantly affected more than the peripheral arc before syncope. In conclusion, VVS is accompanied by a loss of the synchronous AP-MSNA relationship with or without a loss in MSNA at faint. This provides insight into the mechanisms behind the loss of vasoconstriction and drop in AP independent of MSNA at the time of vasovagal faint.
Autonomic modulation of repolarization instability in patients with heart failure prone to ventricular tachycardia
Authors: Nayyar Sachin , Roberts-Thomson Kurt C. , Hasan Muhammad A. , Sullivan Thomas , Harrington Judith , Sanders Prashanthan , Baumert Mathias
Published: August 2013

QT variability (QTV) signifies repolarization lability, and increased QTV is a risk predictor for sudden cardiac death. The aim of the present study was to investigate the role of autonomic nervous system activity on QTV. This study was performed in 29 subjects: 10 heart failure (HF) patients with spontaneous ventricular tachycardia [HFVT(+)], 10 HF patients without spontaneous VT [HFVT(−)], and 9 subjects with structurally normal hearts (HNorm). The beat-to-beat QT interval was measured on 3-min records of surface ECGs at baseline and during interventions (atrial pacing and esmolol, isoprenaline, and atropine infusion). Variability in QT intervals was expressed as the SD of all QT intervals (SDQT). The ratio of the SDQT to SD of RR intervals (SDRR) was calculated as an index of QTV normalized to heart rate variability. There was a trend toward a higher baseline SDQT-to-SDRR ratio in the HFVT(+) group compared with the HFVT(−) and HNorm groups ( P = 0.09). SDQT increased significantly in the HFVT(+) and HFVT(−) groups compared with the HNorm group during fixed-rate atrial pacing ( P = 0.008). Compared with baseline, isoprenaline infusion increased SDQT in HNorm subjects ( P = 0.02) but not in HF patients. SDQT remained elevated in the HFVT(+) group relative to the HNorm group despite acute β-adrenoceptor blockade with esmolol ( P = 0.02). In conclusion, patients with HF and spontaneous VT have larger fluctuations in beat-to-beat QT intervals. This appears to be a genuine effect that is not solely a consequence of heart rate variation. The effect of acute autonomic nervous system modulation on QTV appears to be limited in HF patients.
Cathepsin G deficiency decreases complexity of atherosclerotic lesions in apolipoprotein E-deficient mice
Authors: Rafatian Naimeh , Karunakaran Denuja , Rayner Katey J. , Leenen Frans H. H. , Milne Ross W. , Whitman Stewart C.
Published: August 2013

Cathepsin G is a serine protease with a broad range of catalytic activities, including production of angiotensin II, degradation of extracellular matrix and cell-cell junctions, modulation of chemotactic responses, and induction of apoptosis. Cathepsin G mRNA expression is increased in human coronary atheroma vs. the normal vessel. To assess whether cathepsin G modulates atherosclerosis, cathepsin G knockout ( Cstg−/−) mice were bred with apolipoprotein E knockout ( Apoe−/−) mice to obtain Ctsg+/−Apoe−/−and Ctsg+/+Apoe−/−mice. Heterozygous cathepsin G deficiency led to a 70% decrease in cathepsin G activity in bone marrow cells, but this reduced activity did not impair generation of angiotensin II in bone marrow-derived macrophages (BMDM). Atherosclerotic lesions were compared in male Cstg+/−Apoe−/−and Cstg+/+Apoe−/−mice after 8 wk on a high-fat diet. Plasma cholesterol levels and cholesterol distribution within serum lipoprotein fractions did not differ between genotypes nor did the atherosclerotic lesion areas in either the aortic root or aortic arch. Cstg+/−Apoe−/−mice, however, showed a lower percentage of complex lesions within the aortic root and a smaller number of apoptotic cells compared with Cstg+/+Apoe−/−littermates. Furthermore, apoptotic Cstg−/−BMDM were more efficiently engulfed by phagocytic BMDM than were apoptotic Ctsg+/+BMDM. Thus cathepsin G activity may impair efferocytosis, which could lead to an accumulation of lesion-associated apoptotic cells and the accelerated progression of early atherosclerotic lesions to more complex lesions in Apoe−/−mice.
Apurinic/apyrimidinic endonucelase 1 maintains adhesion of endothelial progenitor cells and reduces neointima formation
Authors: Yamauchi Atsushi , Kawabe Jun-ichi , Kabara Maki , Matsuki Motoki , Asanome Akira , Aonuma Tatsuya , Ohta Hisanobu , Takehara Naofumi , Kitagawa Taku , Hasebe Naoyuki
Published: August 2013

Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional protein that processes DNA-repair function and controls cellular response to oxidative stress. Endothelial progenitor cells (EPCs) are recruited to oxidative stress-rich injured vascular walls and positively contribute to vascular repair and endothelialization. We hypothesized that APE1 functions for EPCs-mediated inhibition of neointima formation in injured vasculature. EPCs isolated from bone marrow cells of C57BL6 mice (12–16 wk old) were able to survive in the presence of hydrogen peroxide (H2O2; up to 1,000 μM) due to the highly expressed reactive oxygen species (ROS) scavengers. However, adhesion capacity of EPCs was significantly inhibited by H2O2 (100 μM) even though an intracellular ROS was retained at small level. An APE1-selective inhibitor or RNA interference-mediated knockdown of endogenous APE1 in EPCs aggravated the H2O2-mediated inhibition of EPCs-adhesion. In contrast, when APE1 was overexpressed in EPCs using an adenovirus harboring the APE1 gene (APE-EPCs), adhesion was significantly improved during oxidative stress. To examine in vivo effects of APE1 in EPCs, APE-EPCs were transplanted via the tail vein after wire-mediated injury of the mouse femoral artery. The number of adherent EPCs at injured vascular walls and the vascular repair effect of EPCs were enhanced in APE-EPCs compared with control EPCs. Among the cellular functions of EPCs, adhesion is especially sensitive to oxidative stress. APE1 enhances in vivo vascular repair effects of EPCs in part through the maintenance of adhesion properties of EPCs. APE1 may be a novel and useful target gene for effective cellular transplantation therapy.
Cigarette smoke and CFTR: implications in the pathogenesis of COPD
Authors: Rab Andras , Rowe Steven M. , Raju S. Vamsee , Bebok Zsuzsa , Matalon Sadis , Collawn James F.
Published: August 2013

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder consisting of chronic bronchitis and/or emphysema. COPD patients suffer from chronic infections and display exaggerated inflammatory responses and a progressive decline in respiratory function. The respiratory symptoms of COPD are similar to those seen in cystic fibrosis (CF), although the molecular basis of the two disorders differs. CF is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR) gene encoding a chloride and bicarbonate channel (CFTR), leading to CFTR dysfunction. The majority of COPD cases result from chronic oxidative insults such as cigarette smoke. Interestingly, environmental stresses including cigarette smoke, hypoxia, and chronic inflammation have also been implicated in reduced CFTR function, and this suggests a common mechanism that may contribute to both the CF and COPD. Therefore, improving CFTR function may offer an excellent opportunity for the development of a common treatment for CF and COPD. In this article, we review what is known about the CF respiratory phenotype and discuss how diminished CFTR expression-associated ion transport defects may contribute to some of the pathological changes seen in COPD.
Soluble guanylate cyclase modulates alveolarization in the newborn lung
Authors: Bachiller Patricia R. , Cornog Katherine H. , Kato Rina , Buys Emmanuel S. , Roberts Jesse D.
Published: August 2013

Nitric oxide (NO) regulates lung development through incompletely understood mechanisms. NO controls pulmonary vascular smooth muscle cell (SMC) differentiation largely through stimulating soluble guanylate cyclase (sGC) to produce cGMP and increase cGMP-mediated signaling. To examine the role of sGC in regulating pulmonary development, we tested whether decreased sGC activity reduces alveolarization in the normal and injured newborn lung. For these studies, mouse pups with gene-targeted sGC-α1 subunit truncation were used because we determined that they have decreased pulmonary sGC enzyme activity. sGC-α1 knockout (KO) mouse pups were observed to have decreased numbers of small airway structures and lung volume compared with wild-type (WT) mice although lung septation and body weights were not different. However, following mild lung injury caused by breathing 70% O2, the sGC-α1 KO mouse pups had pronounced inhibition of alveolarization, as evidenced by an increase in airway mean linear intercept, reduction in terminal airway units, and decrease in lung septation and alveolar openings, as well as reduced somatic growth. Because cGMP regulates SMC phenotype, we also tested whether decreased sGC activity reduces lung myofibroblast differentiation. Cellular markers revealed that vascular SMC differentiation decreased, whereas myofibroblast activation increased in the hyperoxic sGC-α1 KO pup lung. These results indicate that lung development, particularly during hyperoxic injury, is impaired in mouse pups with diminished sGC activity. These studies support the investigation of sGC-targeting agents as therapies directed at improving development in the newborn lung exposed to injury.
Aggressive Angiomyxoma of the Vulva: A Précis for Primary Care Providers
Authors: Elkattah R. , Sarkodie O. , Otteno H. , Fletcher A.
Published: August 2013

Vulvar aggressive angiomyxoma (AA) is a rare mesenchymal tumor of the vulva. Due to its slow-growing nature, it is often overlooked and misdiagnosed by primary care providers (PCPs). We describe a case report of vulvar AA in a 38-year-old woman who underwent complete surgical excision of the neoplasm with no evidence of recurrence on a 5-year followup. A literature review follows to provide PCPs with the clinical, radiologic, and pathologic features that this tumor displays.