bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell surface‐associated aggregation‐promoting factor from Lactobacillus gasseri SBT2055 facilitates host colonization and competitive exclusion of Campylobacter jejuni
Authors: Nishiyama Keita , Nakazato Akiko , Ueno Shintaro , Seto Yasuyuki , Kakuda Tsutomu , Takai Shinji , Yamamoto Yuji , Mukai Takao
Published: August 2015

Campylobacter jejuni, one of the most common causes of gastroenteritis worldwide, is transmitted to humans through poultry. We previously reported that Lactobacillus gasseri SBT2055 (LG2055) reduced C. jejuni infection in human epithelial cells in vitro and inhibited pathogen colonization of chickens in vivo. This suggested that the LG2055 adhesion and/or co‐aggregation phenotype mediated by cell‐surface aggregation‐promoting factors (APFs) may be important for the competitive exclusion of C. jejuni. Here, we show that cell surface‐associated APF1 promoted LG2055 self‐aggregation and adhesion to human epithelial cells and exhibited high affinity for the extracellular matrix component fibronectin. These effects were absent in the apf1 knockout mutant, indicating the role of APF1 in LG2055‐mediated inhibition of C. jejuni in epithelial cells and chicken colonization. Similar to APF1, APF2 promoted the co‐aggregation of LG2055 and C. jejuni but did not inhibit C. jejuni infection. Our data suggest a pivotal role for APF1 in mediating the interaction of LG2055 with human intestinal cells and in inhibiting C. jejuni colonization of the gastrointestinal tract. We thus provide new insight into the health‐promoting effects of probiotics and mechanisms of competitive exclusion in poultry. Further research is needed to determine whether the probiotic strains reach the epithelial surface.
Identification and selection of normalization controls for quantitative transcript analysis in Blumeria graminis
Authors: Pennington Helen G. , Li Linhan , Spanu Pietro D.
Published: August 2015

The investigation of obligate biotrophic pathogens, for example Blumeria graminis, presents a number of challenges. The sensitivity of many assays is reduced because of the presence of host material. Furthermore, the fungal structures inside and outside of the plant possess very different characteristics. Normalization genes are used in quantitative real‐time polymerase chain reaction (qPCR) to compensate for changes as a result of the quantity and quality of template material. Such genes are used as references against which genes of interest are compared, enabling true quantification. Here, we identified six potential B. graminis and five barley genes for qPCR normalization. The relative changes in abundance of the transcripts were assayed across an infection time course in barley epidermis, in B. graminis epiphytic structures and haustoria. The B. graminis glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH), actin (ACT) and histone 3 (H3) genes and the barley GAPDH, ubiquitin (UBI) and α‐tubulin 2B (TUBA2B) genes were optimal normalization controls for qPCR during the infection cycle. These genes were then used for normalization in the quantification of the members of a Candidate Secreted Effector Protein (CSEP) family 21, a conidia‐specific gene and barley genes encoding putative interactors of CSEP0064. The analysis demonstrates the importance of identifying which reference genes are appropriate for each investigation.
Cell‐mediated and humoral acute vascular rejection and graft loss: A registry study
Authors: Teo Rachel ZC , Wong Germaine , Russ Graeme R , Lim Wai H
Published: August 2015

Aims

Rejection of renal allografts following transplantation continues to be a major impediment to long‐term graft survival. Although acute vascular rejection (AVR) is associated with a high risk of graft loss, it remains unclear whether AVR with accompanied cellular or acute humoral rejection (AHR) have dissimilar outcomes. The aim of this registry study was to examine the association between subtypes of AVR and graft loss.

Methods

Using Australia and New Zealand Dialysis and Transplant registry, primary kidney transplant recipients between 2005 and 2012 whose first rejection episode was AVR were included and categorized into AVR‐none (AVR without other rejections), AVR‐CG (AVR with cellular and/or glomerular rejections), and AVR‐AHR (AVR with AHR). Association between AVR groups and graft loss was examined using logistic and Cox regression models.

Results

Of the 274 recipients, 61 (22.3%) experienced AVR‐none, 79 (28.8%) AVR‐AHR and 134 (48.9%) AVR‐CG. Compared with AVR‐none and AVR‐CG, AVR‐AHR was associated with the highest incidence of overall graft loss at 3 months (12%, 10% and 27%, respectively, χ2 = 11.88, P = 0.003). AVR‐AHR was associated with almost a threefold greater risk of death‐censored graft loss compared with AVR‐none (adjusted hazard ratio 2.84, 95% confidence interval 1.22–2.62, P < 0.01).

Conclusion

AVR‐AHR is associated with the poorest outcome with over 25% of grafts being lost 3 months after transplantation. Future studies evaluating factors that predict graft loss in AVR‐AHR may help determine prognosis and inform treatment practices.
Alterations of the blood‐spinal cord barrier in sporadic amyotrophic lateral sclerosis
Authors: Sasaki Shoichi
Published: August 2015

The blood‐spinal cord barrier (BSCB) of the spinal cord capillary consists of non‐fenestrated endothelial cells with tight junctions, basal laminae, pericytes and astrocyte feet processes, referred to as a “neurovascular unit.” The primary function of the BSCB is the maintenance and control of homeostasis of the spinal cord parenchyma by the selective transport of molecules and cells from the systemic compartment. Dysfunction of the BSCB shows important function in the etiology or progression of several pathological conditions of the spinal cord, including amyotrophic lateral sclerosis (ALS). However, the role of BSCB in the pathogenesis of ALS is still unclear. Here the changes of BSCB in sporadic ALS patients were studied by electron microscopy to determine whether the BSCB is disrupted and involved in the pathogenesis of motor neuron degeneration. A total of 358 and 366 cross‐sectioned capillaries were quantitatively examined in controls and ALS patients, respectively. The frequency of degenerated endothelia and pericytes, vacuolar changes of the cytoplasm in the endothelia and pericytes, and the replication of basement membranes was significantly higher in ALS patients than in the controls (P = 0.0175). The areas of the capillaries with diameters of ≤ 5 µm in the ALS patients were significantly smaller than those in the controls (P = 0.0124). The frequency of collagen fiber content of more than a moderate degree around the perivascular space was significantly higher in the ALS patients compared to the controls (P = 0.048), although there was no significant difference in the mild degree of accumulation of collagen fibers. Thus, the BSCB may be disrupted in sporadic ALS patients due to increased permeability and reduced microcirculation, leading to motor neuron degeneration and to the progression of the disease.
Successful use of ultrasound‐guided caudal catheter in a child with a very low termination of dural sac and Opitz–GBBB syndrome: a case report
Authors: Mislovic Branislav
Published: August 2015

We report a 2‐year‐old patient with Opitz–GBBB syndrome scheduled for a posterior sagittal anorectoplasty (PSARP). The ultrasound scan revealed the inferior end of dural sac just below sacrococcygeal membrane, although the patient had previously two successful caudal epidural blocks. Consequently, the epidural catheter was inserted under a real‐time ultrasound guidance without dural puncture. Our patient had excellent pain relief without any side effects.
Current prescription pattern of maintenance treatments for bipolar patients in Korea: A focus on the transition from acute treatments
Authors: Song Hoo Rim , Kwon Young‐Joon , Bahk Won‐Myong , Woo Young Sup , Lee Hwang‐Bin , Lee Jonghun , Lee Dae‐Bo , Lee Sang‐Yeol , Kim Moon‐Doo , Won Seunghee , Lee Kwanghun , Sohn Inki , Lee Jung Goo , Shin Young‐Chul , Chung Sangkeun , Jang Saeheon , Jae Young Myo , Yoon Bo‐Hyun
Published: August 2015

Aims

We examined prescription patterns in maintenance treatment for recovered bipolar patients and compared these with acute treatments.

Methods

Using retrospective methods, the bipolar patients in clinical recovery (Clinical Global Impression Bipolar Version score ≤ 2 for 6 months) after acute episode were selected. We reviewed differences between prescription patterns at remission and after a maintenance period of at least 6 months.

Results

A total of 340 bipolar disorder patients were selected. During the maintenance period, more than half of the patients (192, 56.5%) took a mood stabilizer (MS) + antipsychotic (AP) combination. Among the MS, valproate (149, 43.8%) was most prescribed, and lithium (98, 28.8%) was second, but as patients moved into maintenance treatment, lithium use decreased, and the use of lamotrigine (86, 25.3%) increased. Preferred AP were quetiapine (125, 36.8%), aripiprazole (67, 19.7%), risperidone (48, 14.1%), and olanzapine (39, 11.5%). The use of olanzapine in maintenance was greatly decreased compared with that during acute treatment (67, 19.7%). Most patients did not take an antidepressant (AD), but the proportion using one or more AD was increased during maintenance (17.9% to 30.3%), and bupropion (28, 8.2%) was the preferred AD. Doses were decreased in all drugs, but lamotrigine was maintained at a dose of 133.2 ± 68.5 mg/day.

Conclusions

The most common prescription combination for bipolar maintenance treatment was MS + AP. The use of AP was decreased, whereas the use of AD in combination with MS and/or AP was increased. The doses of MS and AP were generally decreased during the maintenance periods, with the exception of lamotrigine.
Identification of a flavin‐containing S‐oxygenating monooxygenase involved in alliin biosynthesis in garlic
Authors: Yoshimoto Naoko , Onuma Misato , Mizuno Shinya , Sugino Yuka , Nakabayashi Ryo , Imai Shinsuke , Tsuneyoshi Tadamitsu , Sumi Shin‐ichiro , Saito Kazuki
Published: August 2015

S‐Alk(en)yl‐l‐cysteine sulfoxides are cysteine‐derived secondary metabolites highly accumulated in the genus Allium. Despite pharmaceutical importance, the enzymes that contribute to the biosynthesis of S‐alk‐(en)yl‐l‐cysteine sulfoxides in Allium plants remain largely unknown. Here, we report the identification of a flavin‐containing monooxygenase, AsFMO1, in garlic (Allium sativum), which is responsible for the S‐oxygenation reaction in the biosynthesis of S‐allyl‐l‐cysteine sulfoxide (alliin). Recombinant AsFMO1 protein catalyzed the stereoselective S‐oxygenation of S‐allyl‐l‐cysteine to nearly exclusively yield (RCSS)‐S‐allylcysteine sulfoxide, which has identical stereochemistry to the major natural form of alliin in garlic. The S‐oxygenation reaction catalyzed by AsFMO1 was dependent on the presence of nicotinamide adenine dinucleotide phosphate (NADPH) and flavin adenine dinucleotide (FAD), consistent with other known flavin‐containing monooxygenases. AsFMO1 preferred S‐allyl‐l‐cysteine to γ‐glutamyl‐S‐allyl‐l‐cysteine as the S‐oxygenation substrate, suggesting that in garlic, the S‐oxygenation of alliin biosynthetic intermediates primarily occurs after deglutamylation. The transient expression of green fluorescent protein (GFP) fusion proteins indicated that AsFMO1 is localized in the cytosol. AsFMO1 mRNA was accumulated in storage leaves of pre‐emergent nearly sprouting bulbs, and in various tissues of sprouted bulbs with green foliage leaves. Taken together, our results suggest that AsFMO1 functions as an S‐allyl‐l‐cysteine S‐oxygenase, and contributes to the production of alliin both through the conversion of stored γ‐glutamyl‐S‐allyl‐l‐cysteine to alliin in storage leaves during sprouting and through the de novo biosynthesis of alliin in green foliage leaves.
A Highly Efficient Thin Film CuInGaSe2 Solar Cell
Authors: Doriani M. , Dehdashti Jahromi H. , Sheikhi M. H.
Published: August 2015

A new structure for CuIn1−xGaxSe2 (CIGS) solar cell is investigated. The structure consists of an absorber layer with constant bandgap placed next to the cadmium sulfide (CdS) buffer layer and a graded bandgap absorber layer positioned near the molybdenum (Mo) back contact. This leads to a reduced recombination rate at the back contact and enhances collection of generated carriers by additional induced drift field. The structure provides higher efficiency than previous structures. Optimum value of bandgap, thickness, and doping level of the layers are determined to reach maximum efficiency. Moreover, a trap density model is interpolated and applied in the simulations.
Effect of Pressure Drop and Reheating on Thermal and Exergetic Performance of Supercritical Carbon Dioxide Brayton Cycles Integrated With a Solar Central Receiver
Authors: Padilla Ricardo Vasquez , Too Yen Chean Soo , Beath Andrew , McNaughton Robbie , Stein Wes
Published: August 2015

Concentrated solar power using supercritical carbon dioxide (S-CO2) Brayton cycles offers advantages of similar or higher overall thermal efficiencies than conventional Rankine cycles using superheated or supercritical steam. The high efficiency and compactness of S-CO2, as compared with steam Rankine cycles operating at the same temperature, make this cycle attractive for solar central receiver applications. In this paper, S-CO2 Brayton cycle is integrated with a solar central receiver that provides heat input to the power cycle. Three configurations were analyzed: simple, recompression (RC), and recompression with main intercooling (MC). The effect of pressure drop in heat exchangers and solar receiver and solar receiver surface temperature on the thermal and exergetic performance of the CO2 Brayton cycle with and without reheat condition was studied. Energy, exergy, and mass balance were carried out for each component and the cycle first law and exergy efficiencies were calculated. In order to obtain optimal operating conditions, optimum pressure ratios were obtained by maximizing the cycle thermal efficiency under different pressure drops and solar receiver temperature conditions. Optimization of the cycle first law efficiency was carried out in python 2.7 by using sequential least squares programing (SLSQP). The results showed that under low pressure drops, adding reheat to the S-CO2 Brayton cycle has a favorable effect on the thermal and exergy efficiencies. Increasing pressure drop reduces the gap between efficiencies for reheat and no reheat configuration, and for pressure drop factors in the solar receiver above 2.5%, reheat has a negligible or detrimental effect on thermal and exergy performance of S-CO2 Brayton cycles. Additionally, the results showed that the overall exergy efficiency has a bell shape, reaching a maximum value between 18.3% and 25.1% at turbine inlet temperatures in the range of 666–827 °C for different configurations. This maximum value is highly dependent on the solar receiver surface temperature, the thermal performance of the solar receiver, and the solar field efficiency. As the solar receiver surface temperature increases, more exergy destruction associated with heat transfer losses to the environment takes place in the solar receiver and therefore the overall exergy efficiency decreases. Recompression with main intercooling (MC) showed the best thermal (ηI,cycle > 47% at Tin,turbine > 700 °C) and exergy performance followed by RC configuration.
A one-two punch for CML
Authors: Nusinovich Yevgeniya
Published: August 2015

Increased CD70 induced by tyrosine kinase inhibitors mediates drug resistance in leukemia stem cells.
A little toxin can do a lot
Authors: Hurtley Stella M.
Published: August 2015

An actin-specific toxin employs actin oligomers to subvert cellular functions at very low doses.
Lumefantrine and Desbutyl-Lumefantrine Population Pharmacokinetic-Pharmacodynamic Relationships in Pregnant Women with Uncomplicated Plasmodium falciparum Malaria on the Thailand-Myanmar Border
Authors: Kloprogge Frank , McGready Rose , Hanpithakpong Warunee , Blessborn Daniel , Day Nicholas P. J. , White Nicholas J. , Nosten François , Tarning Joel
Published: August 2015

Artemether-lumefantrine is the most widely used antimalarial artemisinin-based combination treatment. Recent studies have suggested that day 7 plasma concentrations of the potent metabolite desbutyl-lumefantrine correlate better with treatment outcomes than those of lumefantrine. Low cure rates have been reported in pregnant women with uncomplicated falciparum malaria treated with artemether-lumefantrine in northwest Thailand. A simultaneous pharmacokinetic drug-metabolite model was developed based on dense venous and sparse capillary lumefantrine and desbutyl-lumefantrine plasma samples from 116 pregnant patients on the Thailand-Myanmar border. The best model was used to evaluate therapeutic outcomes with a time-to-event approach. Lumefantrine and desbutyl-lumefantrine concentrations, implemented in an
E
max
model, both predicted treatment outcomes, but lumefantrine provided better predictive power. A combined model including both lumefantrine and desbutyl-lumefantrine did not improve the model further. Simulations suggested that cure rates in pregnant women with falciparum malaria could be increased by prolonging the treatment course. (These trials were registered at controlled-trials.com [ISRCTN 86353884].)
MALDI-TOF MS as a Tool To Detect a Nosocomial Outbreak of Extended-Spectrum-β-Lactamase- and ArmA Methyltransferase-Producing Enterobacter cloacae Clinical Isolates in Algeria
Authors: Khennouchi Nour Chems el Houda , Loucif Lotfi , Boutefnouchet Nafissa , Allag Hamoudi , Rolain Jean-Marc
Published: August 2015

Enterobacter cloacae
is among the most important pathogens responsible for nosocomial infections and outbreaks. In this study, 77
Enterobacter
isolates were collected: 27 isolates from Algerian hospitals (in Constantine, Annaba, and Skikda) and 50 isolates from Marseille, France. All strains were identified by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS). Antibiotic susceptibility testing was performed by the disk diffusion method. PCR was used to detect extended-spectrum-beta-lactamase (ESBL)-encoding, fluoroquinolone resistance-encoding, and aminoglycoside-modifying enzyme (AME) genes. Epidemiological typing was performed using MALDI-TOF MS with data mining approaches, along with multilocus sequence typing (MLST). Sixty-eight isolates (27 from Algeria, 41 from Marseille) were identified by MALDI-TOF MS as
E. cloacae
. Resistance to antibiotics in the Algerian isolates was significantly higher than that in the strains from Marseille, especially for beta-lactams and aminoglycosides. Eighteen of the 27 Algerian isolates and 11 of the 41 Marseille isolates possessed at least one ESBL-encoding gene:
bla
CTX-M
and/or
bla
TEM
. AME genes were detected in 20 of the 27 Algerian isolates and 8 of the 41 Marseille isolates [
ant(2″)
-
Ia
,
aac(6′)
-
Ib-cr
,
aadA1
,
aadA2
, and
armA
]. Conjugation experiments showed that
armA
was carried on a transferable plasmid. MALDI-TOF typing showed three separate clusters according to the geographical distribution and species level. An MLST-based phylogenetic tree showed a clade of 14
E. cloacae
isolates from a urology unit clustering together in the MALDI-TOF dendrogram, suggesting the occurrence of an outbreak in this unit. In conclusion, the ability of MALDI-TOF to biotype strains was confirmed, and surveillance measures should be implemented, especially for Algerian patients hospitalized in France.
Rapid, Semiquantitative Assay To Discriminate among Compounds with Activity against Replicating or Nonreplicating Mycobacterium tuberculosis
Authors: Gold Ben , Roberts Julia , Ling Yan , Quezada Landys Lopez , Glasheen Jou , Ballinger Elaine , Somersan-Karakaya Selin , Warrier Thulasi , Warren J. David , Nathan Carl
Published: August 2015

The search for drugs that can kill replicating and nonreplicating
Mycobacterium tuberculosis
faces practical bottlenecks. Measurement of CFU and discrimination of bacteriostatic from bactericidal activity are costly in compounds, supplies, labor, and time. Testing compounds against
M. tuberculosis
under conditions that prevent the replication of
M. tuberculosis
often involves a second phase of the test in which conditions are altered to permit the replication of bacteria that survived the first phase. False-positive determinations of activity against nonreplicating
M. tuberculosis
may arise from carryover of compounds from the nonreplicating stage of the assay that act in the replicating stage. We mitigate these problems by carrying out a 96-well microplate liquid MIC assay and then transferring an aliquot of each well to a second set of plates in which each well contains agar supplemented with activated charcoal. After 7 to 10 days—about 2 weeks sooner than required to count CFU—fluorometry reveals whether
M. tuberculosis
bacilli in each well have replicated extensively enough to reduce a resazurin dye added for the final hour. This charcoal agar resazurin assay (CARA) distinguishes between bacterial biomasses in any two wells that differ by 2 to 3 log
10
CFU. The CARA thus serves as a pretest and semiquantitative surrogate for longer, more laborious, and expensive CFU-based assays, helps distinguish bactericidal from bacteriostatic activity, and identifies compounds that are active under replicating conditions, nonreplicating conditions, or both. Results for 14 antimycobacterial compounds, including tuberculosis (TB) drugs, revealed that PA-824 (pretomanid) and TMC207 (bedaquiline) are largely bacteriostatic.
Antibacterial Action of Nitric Oxide-Releasing Chitosan Oligosaccharides against Pseudomonas aeruginosa under Aerobic and Anaerobic Conditions
Authors: Reighard Katelyn P. , Schoenfisch Mark H.
Published: August 2015

Chitosan oligosaccharides were modified with
N
-diazeniumdiolates to yield biocompatible nitric oxide (NO) donor scaffolds. The minimum bactericidal concentrations and MICs of the NO donors against
Pseudomonas aeruginosa
were compared under aerobic and anaerobic conditions. Differential antibacterial activities were primarily the result of NO scavenging by oxygen under aerobic environments and not changes in bacterial physiology. Bacterial killing was also tested against nonmucoid and mucoid biofilms and compared to that of tobramycin. Smaller NO payloads were required to eradicate
P. aeruginosa
biofilms under anaerobic versus aerobic conditions. Under oxygen-free environments, the NO treatment was 10-fold more effective at killing biofilms than tobramycin. These results demonstrate the potential utility of NO-releasing chitosan oligosaccharides under both aerobic and anaerobic environments.
Protective Effect of Qnr on Agents Other than Quinolones That Target DNA Gyrase
Authors: Jacoby George A. , Corcoran Marian A. , Hooper David C.
Published: August 2015

Qnr is a plasmid-encoded and chromosomally determined protein that protects DNA gyrase and topoisomerase IV from inhibition by quinolones. Despite its prevalence worldwide and existence prior to the discovery of quinolones, its native function is not known. Other synthetic compounds and natural products also target bacterial topoisomerases. A number were studied as molecular probes to gain insight into how Qnr acts. Qnr blocked inhibition by synthetic compounds with somewhat quinolone-like structure that target the GyrA subunit, such as the 2-pyridone ABT-719, the quinazoline-2,4-dione PD 0305970, and the spiropyrimidinetrione pyrazinyl-alkynyl-tetrahydroquinoline (PAT), indicating that Qnr is not strictly quinolone specific, but Qnr did not protect against GyrA-targeting simocyclinone D8 despite evidence that both simocyclinone D8 and Qnr affect DNA binding to gyrase. Qnr did not affect the activity of tricyclic pyrimidoindole or pyrazolopyridones, synthetic inhibitors of the GyrB subunit, or nonsynthetic GyrB inhibitors, such as coumermycin A1, novobiocin, gyramide A, or microcin B17.Thus, in this set of compounds the protective activity of Qnr was confined to those that, like quinolones, trap gyrase on DNA in cleaved complexes.
Toll-Like Receptor 9 Contributes to Defense against Acinetobacter baumannii Infection
Authors: Noto Michael J. , Boyd Kelli L. , Burns William J. , Varga Matthew G. , Peek Richard M. , Skaar Eric P.
Published: August 2015

Acinetobacter baumannii
is a common nosocomial pathogen capable of causing severe diseases associated with significant morbidity and mortality in impaired hosts. Pattern recognition receptors, such as the Toll-like receptors (TLRs), play a key role in pathogen detection and function to alert the immune system to infection. Here, we examine the role for TLR9 signaling in response to
A. baumannii
infection. In a murine model of
A. baumannii
pneumonia, TLR9
−/−
mice exhibit significantly increased bacterial burdens in the lungs, increased extrapulmonary bacterial dissemination, and more severe lung pathology compared with those in wild-type mice. Following systemic
A. baumannii
infection, TLR9
−/−
mice have significantly increased bacterial burdens in the lungs, as well as decreased proinflammatory cytokine and chemokine production. These results demonstrate that TLR9-mediated pathogen detection is important for host defense against the opportunistic pathogen
Acinetobacter baumannii
.
Fibronectin Binding Proteins SpsD and SpsL Both Support Invasion of Canine Epithelial Cells by Staphylococcus pseudintermedius
Authors: Pietrocola Giampiero , Gianotti Valentina , Richards Amy , Nobile Giulia , Geoghegan Joan A. , Rindi Simonetta , Monk Ian R. , Bordt Andrea S. , Foster Timothy J. , Fitzgerald J. Ross , Speziale Pietro
Published: August 2015

In this study, we investigated the cell wall-anchored fibronectin-binding proteins SpsD and SpsL from the canine commensal and pathogen
Staphylococcus pseudintermedius
for their role in promoting bacterial invasion of canine progenitor epidermal keratinocytes (CPEK). Invasion was examined by the gentamicin protection assay and fluorescence microscopy. An Δ
spsD ΔspsL
mutant of strain ED99 had a dramatically reduced capacity to invade CPEK monolayers, while no difference in the invasion level was observed with single mutants.
Lactococcus lactis
transformed with plasmids expressing SpsD and SpsL promoted invasion, showing that both proteins are important. Soluble fibronectin was required for invasion, and an RGD-containing peptide or antibodies recognizing the integrin α
5
β
1
markedly reduced invasion, suggesting an important role for the integrin in this process. Src kinase inhibitors effectively blocked internalization, suggesting a functional role for the kinase in invasion. In order to identify the minimal fibronectin-binding region of SpsD and SpsL involved in the internalization process, recombinant fragments of both proteins were produced. The SpsD
520–846
and SpsL
538–823
regions harboring the major fibronectin-binding sites inhibited
S. pseudintermedius
internalization. Finally, the effects of staphylococcal invasion on the integrity of different cell lines were examined. Because SpsD and SpsL are critical factors for adhesion and invasion, blocking these processes could provide a strategy for future approaches to treating infections.
Streptolysin S Promotes Programmed Cell Death and Enhances Inflammatory Signaling in Epithelial Keratinocytes during Group A Streptococcus Infection
Authors: Flaherty Rebecca A. , Puricelli Jessica M. , Higashi Dustin L. , Park Claudia J. , Lee Shaun W.
Published: August 2015

Streptococcus pyogenes, or group AStreptococcus(GAS), is a pathogen that causes a multitude of human diseases from pharyngitis to severe infections such as toxic shock syndrome and necrotizing fasciitis. One of the primary virulence factors produced by GAS is the peptide toxin streptolysin S (SLS). In addition to its well-recognized role as a cytolysin, recent evidence has indicated that SLS may influence host cell signaling pathways at sublytic concentrations during infection. We employed an antibody array-based approach to comprehensively identify global host cell changes in human epithelial keratinocytes in response to the SLS toxin. We identified key SLS-dependent host responses, including the initiation of specific programmed cell death and inflammatory cascades with concomitant downregulation of Akt-mediated cytoprotection. Significant signaling responses identified by our array analysis were confirmed using biochemical and protein identification methods. To further demonstrate that the observed SLS-dependent host signaling changes were mediated primarily by the secreted toxin, we designed a Transwell infection system in which direct bacterial attachment to host cells was prevented, while secreted factors were allowed access to host cells. The results using this approach were consistent with our direct infection studies and reveal that SLS is a bacterial toxin that does not require bacterial attachment to host cells for activity. In light of these findings, we propose that the production of SLS by GAS during skin infection promotes invasive outcomes by triggering programmed cell death and inflammatory cascades in host cells to breach the keratinocyte barrier for dissemination into deeper tissues.
Chitinase 3-Like 1 Promotes Candida albicans Killing and Preserves Corneal Structure and Function by Controlling Host Antifungal Responses
Authors: Gao Nan , Yu Fu-Shin X.
Published: August 2015

Chitinase 3-like 1 (CHI3L1) has been shown to play a role in promoting antibacterial responses, decreasing tissue injury, and enhancing pulmonary repair. This study sought to elucidate the role of CHI3L1 in augmenting the corneal innate immune response to
Candida albicans
infection in an animal model of fungal keratitis. Flagellin applied topically 24 h prior to
C. albicans
inoculation significantly protected the corneal from
C. albicans
and induced CHI3L1 expression in C57BL/6 mouse corneas. CHI3L1, however, played a detectable but minor role in flagellin-induced protection. While
C. albicans
keratitis was more severe in the corneas treated with
Chi3l1
small interfering RNA (siRNA), corneas treated with recombinant CHI3L1 before
C. albicans
inoculation had markedly ameliorated keratitis, reduced fungal load, and decreased polymorphonucleocyte (PMN) infiltration in an interleukin 13 receptor α2 (IL-13Rα2)-dependent manner. CHI3L1 treatment resulted in the induction of the antimicrobial peptides β-defensin 3, CRAMP, and chemokine CXCL10 and its receptor CXCR3 in corneal epithelial cells. Importantly, CHI3L1 administered after
C. albicans
inoculation also had strong protection against fungal keratitis, suggesting a therapeutic window. This is the first report demonstrating that CHI3L1 is induced during fungal infection, where it acts as an immunomodulator to promote fungal clearance and to regulate antifungal innate immune responses in the cornea.
An unusual presentation of herpes simplex encephalitis with negative PCR
Authors: Buerger Kelly J , Zerr Kayleigh , Salazar Richard
Published: August 2015

A 74-year-old man presented with acute right-sided hemiparesis and epilepsia partialis continua in association with fever and confusion. Initial workup revealed possible cerebritis in the left medial frontal lobe without involvement of the temporal lobes. Cerebrospinal fluid (CSF) analysis revealed minimal lymphocytic pleocytosis but negative real-time herpes simplex virus (HSV) PCR. Acyclovir was discontinued on day 5 due to a negative infectious workup and clinical improvement. On day 9 his condition deteriorated and he was transferred to a higher level of acuity for advanced supportive care. Worsening encephalopathy and refractory status epilepticus ensued despite medical care. Repeat CSF analysis showed mild lymphocytic pleocytosis with negative real-time HSV PCR. Brain MRI revealed progression of cortical enhancement. Immunosuppressive therapy and plasma exchange were attempted without clinical response. On day 24, another lumbar puncture showed only mild lymphocytic pleocytosis. Brain MRI showed involvement of the right medial temporal lobe. Subsequently, acyclovir was resumed. The HSV-1 PCR result was positive on day 30. Unfortunately, the patient expired.
Even a low-dose of moderate-to-vigorous physical activity reduces mortality by 22% in adults aged ≥60 years: a systematic review and meta-analysis
Authors: Hupin David , Roche Frédéric , Gremeaux Vincent , Chatard Jean-Claude , Oriol Mathieu , Gaspoz Jean-Michel , Barthélémy Jean-Claude , Edouard Pascal
Published: August 2015

Background

The health benefits of 150 min a week of moderate-to-vigorous-intensity physical activity (MVPA) in older adults, as currently recommended, are well established, but the suggested dose in older adults is often not reached.

Objectives

We aimed to determine whether a lower dose of MVPA was effective in reducing mortality, in participants older than 60 years.

Methods

The PubMed and Embase databases were searched from inception to February 2015. Only prospective cohorts were included. Risk ratios of death were established into four doses based on weekly Metabolic Equivalent of Task (MET)-minutes, defined as inactive (reference), low (1–499), medium (500–999) or high (≥1000). Data were pooled and analysed through a random effects model using comprehensive meta-analysis software.

Results

Of the 835 reports screened, nine cohort studies remained, totalling 122 417 participants, with a mean follow-up of 9.8±2.7 years and 18 122 reported deaths (14.8%). A low dose of MVPA resulted in a 22% reduction in mortality risk (RR=0.78 (95% CI 0.71 to 0.87) p<0.0001). MVPA beyond this threshold brought further benefits, reaching a 28% reduction in all-cause mortality in older adults who followed the current recommendations (RR=0.72 (95% CI 0.65 to 0.80) p<0.0001) and a 35% reduction beyond 1000 MET-min per week (RR=0.65 (95% CI 0.61 to 0.70) p<0.0001).

Conclusions

A dose of MVPA below current recommendations reduced mortality by 22% in older adults. A further increase in physical activity dose improved these benefits in a linear fashion. Older adults should be encouraged to include even low doses of MVPA in their daily lives.
Impact of preoperative serum albumin on 30-day mortality following surgery for colorectal cancer: a population-based cohort study
Authors: Montomoli Jonathan , Erichsen Rune , Antonsen Sussie , Nilsson Tove , Sørensen Henrik Toft
Published: August 2015

Objective

Surgery is the only potentially curable treatment for colorectal cancer (CRC), but it is hampered by high mortality. Human serum albumin (HSA) below 35 g/L is associated with poor overall prognosis in patients with CRC, but evidence regarding the impact on postoperative mortality is sparse.

Methods

We performed a population-based cohort study including patients undergoing CRC surgery in North and Central Denmark (1997–2011). We categorised patients according to HSA concentration measured 1–30 days prior to surgery date. We used the Kaplan-Meier method to compute 30-day mortality and Cox regression model to compute HRs as measures of the relative risk of death, controlling for potential confounders. We further stratified patients by preoperative conditions, including cancer stage, comorbidity level, and C reactive protein concentration.

Results

Of the 9339 patients undergoing first-time CRC surgery with preoperative HSA measurement, 26.4% (n=2464) had HSA below 35 g/L. 30-day mortality increased from 4.9% among patients with HSA 36–40 g/L to 26.9% among patients with HSA equal to or below 25 g/L, compared with 2.0% among patients with HSA above 40 g/L. The corresponding adjusted HRs increased from 1.75 (95% CI 1.25 to 2.45) among patients with HSA 36–40 g/L to 7.59 (95% CI 4.95 to 11.64) among patients with HSA equal to or below 25 g/L, compared with patients with HSA above 40 g/L. The negative impact associated with a decrement of HSA was found in all subgroups.

Conclusions

A decrement in preoperative HSA concentration was associated with substantial concentration-dependent increased 30-day mortality following CRC surgery.
Natriuretic peptides for the detection of paroxysmal atrial fibrillation
Authors: Seegers Joachim , Zabel Markus , Grüter Timo , Ammermann Antje , Weber-Krüger Mark , Edelmann Frank , Gelbrich Götz , Binder Lutz , Herrmann-Lingen Christoph , Gröschel Klaus , Hasenfuß Gerd , Feltgen Nicolas , Pieske Burkert , Wachter Rolf
Published: August 2015

Background and purpose

Silent atrial fibrillation (AF) and tachycardia (AT) are considered precursors of ischaemic stroke. Therefore, detection of paroxysmal atrial rhythm disorders is highly relevant, but is clinically challenging. We aimed to evaluate the diagnostic value of natriuretic peptide levels in the detection of paroxysmal AT/AF in a pilot study.

Methods

Natriuretic peptide levels were analysed in two independent patient cohorts (162 patients with arterial hypertension or other cardiovascular risk factors and 82 patients with retinal vessel disease). N-terminal-pro-brain natriuretic peptide (NT-proBNP) and BNP were measured before the start of a 7-day Holter monitoring period carefully screened for AT/AF.

Results

244 patients were included; 16 had paroxysmal AT/AF. After excluding patients with a history of AT/AF (n=5), 14 patients had newly diagnosed AT/AF (5.8%) NT-proBNP and BNP levels were higher in patients with paroxysmal AT/AF in both cohorts: (1) 154.4 (IQR 41.7; 303.6) versus 52.8 (30.4; 178.0) pg/mL and 70.0 (31.9; 142.4) versus 43.9 (16.3; 95.2) and (2) 216.9 (201.4; 277.1) versus 90.8 (42.3–141.7) and 96.0 (54.7; 108.2) versus 29.1 (12.0; 58.1). For the detection of AT/AF episodes, NT-proBNP and BNP had an area under the curve in receiver operating characteristic analysis of 0.76 (95% CI, 0.64 to 0.88; p=0.002) and 0.75 (0.61 to 0.89; p=0.004), respectively.

Conclusions

NT-proBNP and BNP levels are elevated in patients with silent AT/AF as compared with sinus rhythm. Thus, screening for undiagnosed paroxysmal AF using natriuretic peptide level initiated Holter monitoring may be a useful strategy in prevention of stroke or systemic embolism.
Nutrient availability, the microbiome, and intestinal transport during pregnancy
Authors: Astbury Stuart , Mostyn Alison , Symonds Michael E. , Bell Rhonda C.
Published: August 2015

Adequate adaptation of the gastrointestinal tract is important during pregnancy to ensure that the increased metabolic demands by the developing fetus are met. These include changes in surface area mediated by villus hypertrophy and enhanced functional capacity of individual nutrient receptors, including those transporting glucose, fructose, leucine, and calcium. These processes are regulated either by the enhanced nutrient demand or are facilitated by changes in the secretion of pregnancy hormones. Our review also covers recent research into the microbiome, and how pregnancy could lead to microbial adaptations, which are beneficial to the mother, yet are also similar to those seen in the metabolic syndrome. The potential role of diet in modulating the microbiome during pregnancy, as well as the potential for the intestinal microbiota to induce pregnancy complications, are examined. Gaps in the current literature are highlighted, including those where only historical evidence is available, and we suggest areas that should be a priority for further research. In summary, although a significant degree of adaptation has been described, there are both well-established processes and more recent discoveries, such as changes within the maternal microbiome, that pose new questions as to how the gastrointestinal tract effectively adapts to pregnancy, especially in conjunction with maternal obesity.
Physiological and perceptual responses to incremental exercise testing in healthy men: effect of exercise test modality
Authors: Muscat Kristina M. , Kotrach Houssam G. , Wilkinson-Maitland Courtney A. , Schaeffer Michele R. , Mendonca Cassandra T. , Jensen Dennis
Published: August 2015

In a randomized cross-over study of 15 healthy men aged 20–30 years, we compared physiological and perceptual responses during treadmill and cycle exercise test protocols matched for increments in work rate — the source of increased locomotor muscle metabolic and contractile demands. The rates of O2 consumption and CO2 production were higher at the peak of treadmill versus cycle testing (p ≤ 0.05). Nevertheless, work rate, minute ventilation, tidal volume (VT), breathing frequency (fR), inspiratory capacity (IC), inspiratory reserve volume (IRV), tidal esophageal (Pes,tidal) and transdiaphragmatic pressure swings (Pdi,tidal), peak expiratory gastric pressures (Pga,peak), the root mean square of the diaphragm electromyogram (EMGdi,rms) expressed as a percentage of maximum EMGdi,rms (EMGdi,rms%max), and dyspnea ratings were similar at the peak of treadmill versus cycle testing (p > 0.05). Ratings of leg discomfort were higher at the peak of cycle versus treadmill exercise (p ≤ 0.05), even though peak O2 consumption was lower during cycling. Oxygen consumption, CO2 production, minute ventilation, fR, Pes,tidal, Pdi,tidal and Pga,peak were higher (p ≤ 0.05), while VT, IC, IRV, EMGdi,rms%max, and ratings of dyspnea and leg discomfort were similar (p > 0.05) at all or most submaximal work rates during treadmill versus cycle exercise. Our findings highlight important differences (and similarities) in physiological and perceptual responses at maximal and submaximal work rates during incremental treadmill and cycle exercise testing protocols. The lack of effect of exercise test modality on peak work rate advocates for the use of this readily available parameter to optimize training intensity determination, regardless of exercise training mode.
Experimental observation of saline underflows and turbidity currents, flowing over rough beds
Authors: Varjavand Peyman , Ghomeshi Mehdi , Dalir Ali Hosseinzadeh , Farsadizadeh Davood , Gorgij Alireza Docheshmeh
Published: August 2015

Density currents are formed when gravity acts upon a density difference between two different fluids, and the driving force is the buoyancy force. These currents are the most important transport mechanisms and deposition of noncohesive sediments in narrow and deep reservoirs. In this research, 126 experiments were performed to investigate the effects of artificial bed roughness on saline and sediment-laden density currents. Conic and cylindrical shapes of roughness were used with three different heights. Velocity and concentration profiles were measured in 4 and 3 cross-sections, respectively. Presence of roughness causes increasing density current body thickness, decreasing maximum value of velocity and increasing distance of peak value of velocity point from the bed in the normal velocity profile. Coefficient of entrainment in the rough beds was more than in smooth beds and increased for greater roughness heights. A special behavior, referred to as “lifting phenomenon”, was present in some of the tests and which had an effect on the velocity profiles.
Total and epiphytic litter under the canopy of Acer macrophyllum in an old-growth temperate rainforest, Washington State, USA
Authors: Tejo Camila F. , Zabowski Darlene , Nadkarni Nalini M.
Published: August 2015

The amounts and ecological importance of epiphytic litterfall has often been overlooked in forest ecosystem studies. However, epiphytes participate in whole-ecosystem dynamics by capturing and retaining nutrients from atmospheric sources and transferring these nutrients to other ecosystem components. We quantified epiphytic litterfall under the canopy of mature bigleaf maples (Acer macrophyllum Pursh) and compared it with other litter components in an old-growth temperate rainforest in Washington State. Total litterfall during one year was 4760 kg·ha−1, with the greatest contribution from bigleaf maple leaves. Of the total litter input, 546 kg·ha−1 consisted of epiphytic litter, equivalent to 12% of total fine litter input, the highest contribution of epiphyte litterfall documented for this type of forest. Compared with other studies in the Pacific Northwest, our estimations of conifer needle inputs relate to the location of the littertraps. Bigleaf maple leaves dominated carbon (C) and nitrogen (N) returns in litter; epiphytic litterfall contributed 240 kg·ha−1·year−1 of C (∼11% of total C inputs) and 5.7 kg·ha−1·year−1 of N (∼11% of total N inputs) to the forest floor. Inputs of N from epiphytes and bigleaf maple litter under the canopy of this tree could be important in augmenting N in this old-growth ecosystem.
Deforestation mapping sampling designs for Canadian landscapes
Authors: Leckie Donald G. , Paradine Dennis , Kurz Werner A. , Magnussen Steen
Published: August 2015

Deforestation is the direct human-induced conversion of forest to nonforest land uses. It is important for nations to understand and report the extent of their deforestation. Because of the vastness of Canada’s forest and the rare and spatially diverse nature of its deforestation, a sampling approach in which deforestation is mapped and then scaled up to represent deforestation for different regions was needed. The effectiveness of different sample designs in capturing the area of deforestation was evaluated using a Monte Carlo approach in which alternate sample designs were applied to simulated forest landscapes representative of different regions and deforestation patterns in Canada. Sampling error as expressed by the standard error in the estimated deforestation level for the sample divided by actual deforestation of the simulated landscape was used as a measure of sample design performance. Results indicated that sampling error was dependent on the characteristics of the deforestation (e.g., amount, shape, size, and distribution). For example, as mean event size increases or the proportion of linear deforestation events (e.g., roads and corridors) decreases, the required sampling intensity to reach a certain level of sampling error increases, and landscapes with a small number of very large events required the largest sampling intensity. To achieve a relative sampling error target (standard error / sample mean) of 10%, given sample designs of square plots on a systematic grid, a sample of 15%–25% of a landscape will be required for most Canadian landscapes, given a 10-year mapping time frame (interval between samples) and assuming a deforestation rate of 0.025% per annum. With mapping over a 5-year period, the required sampling intensity rises to 20%–40%. Also discussed are the consequences of the sampling error of different designs on the uncertainty in estimated greenhouse gas emission resulting from deforestation.