bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective bacterial quorum sensing inhibitors from Indian medicinal plant extracts
Authors: Tiwary B.K. , Ghosh R. , Moktan S. , Ranjan V.K. , Dey P. , Choudhury D. , Dutta S. , Deb D. , Das A.P. , Chakraborty R. 
Published: April 2017

Abstract
As virulence of many pathogenic bacteria is regulated by the phenomenon of quorum sensing (QS), the present study aimed to find the QS-inhibiting (QS-I) property (if any) in 61 Indian medicinal plants. The presence of QS-I compound in the leaf extract was evaluated by its ability to inhibit production of pigment in Chromobacterium violaceum MTCC 2656 (violacein) and Pseudomonas aeruginosa MTCC 2297 (pyocyanin) or swarming of P. aeruginosa MTCC 2297. Extracts of three plants, Astilbe rivularis, Fragaria nubicola and Osbeckia nepalensis, have shown a dose-dependent inhibition of violacein production with no negative effect on bacterial growth. Inhibition of pyocyanin pigment production and swarming motility in P. aeruginosa MTCC 2297 was also shown. Based on the results obtained by gas chromatography–mass spectroscopy (GC-MS) and thin-layer chromatography–direct bioautography (TLC-DB), it was concluded that triterpenes and flavonoid compounds found in the three plant extracts could have QS-I activity.

Significance and Impact of the Study
A novel alternative prospect to prevent bacterial infections without inhibiting the growth is to apply chemicals that inhibit quorum sensing mechanism of the pathogens. Antiquorum property of 61 medicinal plants was evaluated by the ability of their leaf extract(s) to inhibit production of pigment (violacein in Chromobacterium violaceum MTCC 2656, pyocyanin in Pseudomonas aeruginosa MTCC 2297) or swarming in P. aeruginosa MTCC 2297. The most prospective plants (for the development of quorum sensing inhibitor), showing inhibition of violacein production without affecting bacterial growth, were Astilbe rivularis, Fragaria nubicola and Osbeckia nepalensis.
Backward Control from Possessors
Authors: Funakoshi Kenshi 
Published: April 2017

AbstractThis article presents an argument that Japanese (and Korean) has a previously unattested type of external‐possession constructions (EPCs) (Payne & Barshi ): EPC with a backward‐control structure (Polinsky & Potsdam ). It has been attested in the literature that there are EPCs that have forward‐raising structures, backward‐raising structures, and forward‐control structures. Only the backward‐control type has not been attested. Thus, if the argument in this article is correct, the relevant construction fills in the missing piece of the typology of EPCs. This adds plausibility to the Movement Theory of Control (Hornstein ) and the Copy Theory of Movement (Chomsky ) because this typology is expected under these theories. Furthermore, I argue that Nunes's () mechanism of copy deletion (chain reduction, in his terms) can explain why the pronounce‐the‐original‐copy strategy is available in backward‐control EPCs.
Multiunit Sequences in First Language Acquisition
Authors: Theakston Anna , Lieven Elena 
Published: April 2017

AbstractTheoretical and empirical reasons suggest that children build their language not only out of individual words but also out of multiunit strings. These are the basis for the development of schemas containing slots. The slots are putative categories that build in abstraction while the schemas eventually connect to other schemas in terms of both meaning and form. Evidence comes from the nature of the input, the ways in which children construct novel utterances, the systematic errors that children make, and the computational modeling of children's grammars. However, much of this research is on English, which is unusual in its rigid word order and impoverished inflectional morphology. We summarize these results and explore their implications for languages with more flexible word order and/or much richer inflectional morphology.
Dissecting virulence function from recognition: cell death suppression in Nicotiana benthamiana by XopQ/HopQ1‐family effectors relies on EDS1‐dependent immunity
Authors: Adlung Norman , Bonas Ulla 
Published: April 2017

SummaryMany Gram‐negative plant pathogenic bacteria express effector proteins of the XopQ/HopQ1 family which are translocated into plant cells via the type III secretion system during infection. In Nicotiana benthamiana, recognition of XopQ/HopQ1 proteins induces an effector‐triggered immunity (ETI) reaction which is not associated with strong cell death but renders plants immune against Pseudomonas syringae and Xanthomonas campestris pv. vesicatoria strains. Additionally, XopQ suppresses cell death in N. benthamiana when transiently co‐expressed with cell death inducers. Here, we show that representative XopQ/HopQ1 proteins are recognized similarly, likely by a single resistance protein of the TIR‐NB‐LRR class. Extensive analysis of XopQ derivatives indicates the recognition of structural features. We performed Agrobacterium‐mediated protein expression experiments in wild‐type and EDS1‐deficient (eds1) N. benthamiana leaves, not recognizing XopQ/HopQ1. XopQ recognition limits multiplication of Agrobacterium and attenuates levels of transiently expressed proteins. Remarkably, XopQ fails to suppress cell death reactions induced by different effectors in eds1 plants. We conclude that XopQ‐mediated cell death suppression in N. benthamiana is due to the attenuation of Agrobacterium‐mediated protein expression rather than the cause of the genuine XopQ virulence activity. Thus, our study expands our understanding of XopQ recognition and function, and also challenges the commonly used co‐expression assays for elucidation of in planta effector activities, at least under conditions of ETI induction.
Role of mucosa in generating spontaneous activity in the guinea pig seminal vesicle
Authors: Takeya Mitsue , Hashitani Hikaru , Hayashi Tokumasa , Higashi Ryuhei , Nakamura Kei‐ichiro , Takano Makoto 
Published: April 2017

Key points
The mucosa may have neuron‐like functions as urinary bladder mucosa releases bioactive substances that modulate sensory nerve activity as well as detrusor muscle contractility. However, such mucosal function in other visceral organs remains to be established.
The role of mucosa in generating spontaneous contractions in seminal vesicles (SVs), a paired organ in the male reproductive tract, was investigated.
The intact mucosa is essential for the generation of spontaneous phasic contractions of SV smooth muscle arising from electrical slow waves and corresponding increases in intracellular Ca2+. These spontaneous events primarily depend on Ca2+ handling by sarco‐endoplasmic reticulum Ca2+ stores.
A population of mucosal cells developed spontaneous rises in intracellular Ca2+ relying on sarco‐endoplasmic reticulum Ca2+ handling.
The spontaneously active cells in the SV mucosa appear to drive spontaneous activity in smooth muscle either by sending depolarizing signals and/or by releasing humoral substances.
AbstractThe role of the mucosa in generating the spontaneous activity of guinea‐pig seminal vesicle (SV) was explored. Changes in contractility, membrane potential and intracellular Ca2+ dynamics of SV smooth muscle cells (SMCs) were recorded using isometric tension recording, intracellular microelectrode recording and epi‐fluorescence Ca2+ imaging, respectively. Mucosa‐intact but not mucosa‐denuded SV preparations generated TTX‐ (1 μm) resistant spontaneous phasic contractions that were abolished by nifedipine (3 μm). Consistently, SMCs developed mucosa‐dependent slow waves (SWs) that triggered action potentials and corresponding Ca2+ flashes. Nifedipine (10 μm) abolished the action potentials and spontaneous contractions, while suppressing the SWs and Ca2+ flashes. Both the residual SWs and spontaneous Ca2+ transients were abolished by cyclopiazonic acid (CPA, 10 μm), a sarco‐endoplasmic reticulum Ca2+‐ATPase (SERCA) inhibitor. DIDS (300 μm) and niflumic acid (100 μm), blockers for Ca2+‐activated Cl− channels (CACCs), or low Cl− solution also slowed or prevented the generation of SWs. In SV mucosal preparations detached from the muscle layer, a population of mucosal cells generated spontaneous Ca2+ transients that were blocked by CPA but not nifedipine. These results suggested that spontaneous contractions and corresponding Ca2+ flashes in SV SMCs arise from action potential generation due to the opening of L‐type voltage‐dependent Ca2+ channels. Spontaneous Ca2+ transients appear to primarily result from Ca2+ release from sarco‐endoplasmic reticulum Ca2+ stores to activate CACCs to develop SWs. The mucosal cells firing spontaneous Ca2+ transients may play a critical role in driving spontaneous activity of SV smooth muscle either by sending depolarizing signals or by releasing humoral substances.
Effect of Comprehensive School Physical Activity Programming on Cardiometabolic Health Markers in Children From Low-Income Schools
Authors: Burns Ryan D. , Brusseau Timothy A. , Hannon James C. 
Published: April 2017

Background:The purpose of this study was to examine the effect of a 36-week Comprehensive School Physical Activity Program (CSPAP) on cardiometabolic health markers in children from low-income schools.Methods:Participants were 217 school-aged children (mean age = 10.1 ± 1.1 years; 114 girls, 103 boys) recruited from 5 low-income elementary schools. Cardiometabolic health markers were collected in a fasted state at 2 time-points, before commencement of the CSPAP for classroom and school level clustering and the modifying effects of grade level and sex, there were statistically significant improvements in HDL cholesterol (Δ = 3.6 mg/dL, 95% CI: 1.4 mg/dL to 5.8 mg/dL, P = .039), triglycerides (Δ = –14.1 mg/dL, 95% CI: –21.4 mg/dL to –6.8 mg/dL, P = .022), and mean arterial pressure (Δ = –4.3 mmHg, 95% CI: –8.5 mmHg to –0.1 mmHg, P = .041) following the 36-week CSPAP intervention. Sixth-grade children showed decreases in LDL cholesterol (Δ = –15.3 mg/dL, 95% CI: –30.5 mg/dL to –0.1 mg/dL, P = .033).Conclusions:Improvements in specific cardiometabolic health markers were found following a 36-week CSPAP in children from low-income schools.
Effects of Anterior Knee Displacement During Squatting on Patellofemoral Joint Stress
Authors: Kernozek Thomas W. , Gheidi Naghmeh , Zellmer Matthew , Hove Jordan , Heinert Becky L. , Torry Michael R. 
Published: April 2017

Context:Squatting is a common rehabilitation training exercise for patellofemoral pain syndrome (PFPS). Patellofemoral joint stress (PFJS) during squatting with more anterior knee displacement has not been systematically investigated.Objective:To compare PFJS during squatting using 2 techniques: squat while keeping the knees behind the toes (SBT) and squat while allowing the knees to go past the toes (SPT).Setting:University research laboratory.Participants:Twenty-five healthy females (age: 22.69 (0.74) y; height: 169.39 (6.44) cm; mass: 61.55 (9.74) kg) participated.Main Outcome Measures:Three-dimensional kinematic and kinetic data were collected at 180 and 1800 Hz, respectively. A musculoskeletal model was used to calculate muscle forces through static optimization. These muscle forces were used in a patellofemoral joint model to estimate PFJS.Results:The magnitudes of PFJS, reaction force, and quadriceps force were higher (P < .001) during SPT compared with the SBT technique. Knee flexion, hip flexion, and ankle dorsiflexion angles were reduced when using the SBT technique.Conclusions:Findings provide some general support for minimizing forward knee translation during squats for patients that may have patellofemoral pain syndrome.
The DnaK Chaperone Uses Different Mechanisms To Promote and Inhibit Replication of
Vibrio cholerae
Chromosome 2
Authors: Jha Jyoti K. , Li Mi , Ghirlando Rodolfo , Miller Jenkins Lisa M. , Wlodawer Alexander , Chattoraj Dhruba 
Published: April 2017

ABSTRACT

Replication of
Vibrio cholerae
chromosome 2 (Chr2) depends on molecular chaperone DnaK to facilitate binding of the initiator (RctB) to the replication origin. The binding occurs at two kinds of site, 12-mers and 39-mers, which promote and inhibit replication, respectively. Here we show that DnaK employs different mechanisms to enhance the two kinds of binding. We found that mutations in
rctB
that reduce DnaK binding also reduce 12-mer binding and initiation. The initiation defect is suppressed by second-site mutations that increase 12-mer binding only marginally. Instead, they reduce replication inhibitory mechanisms: RctB dimerization and 39-mer binding. One suppressing change was in a dimerization domain which is folded similarly to the initiator of an iteron plasmid—the presumed progenitor of Chr2. In plasmids, DnaK promotes initiation by reducing dimerization. A different mutation was in the 39-mer binding domain of RctB and inactivated it, indicating an alternative suppression mechanism. Paradoxically, although DnaK increases 39-mer binding, the increase was also achieved by inactivating the DnaK binding site of RctB. This result suggests that the site inhibits the 39-mer binding domain (via autoinhibition) when prevented from binding DnaK. Taken together, our results reveal an important feature of the transition from plasmid to chromosome: the Chr2 initiator retains the plasmid-like dimerization domain and its control by chaperones but uses the chaperones in an unprecedented way to control the inhibitory 39-mer binding.

IMPORTANCE
The capacity of proteins to undergo remodeling provides opportunities to control their function. However, remodeling remains a poorly understood aspect of the structure-function paradigm due to its dynamic nature. Here we have studied remodeling of the initiator of replication of
Vibrio cholerae
Chr2 by the molecular chaperone, DnaK. We show that DnaK binds to a site on the Chr2 initiator (RctB) that promotes initiation by reducing the initiator’s propensity to dimerize. Dimerization of the initiator of the putative plasmid progenitor of Chr2 is also reduced by DnaK, which promotes initiation. Paradoxically, the DnaK binding also promotes replication inhibition by reducing an autoinhibitory activity of RctB. In the plasmid-to-chromosome transition, it appears that the initiator has acquired an autoinhibitory activity and along with it a new chaperone activity that apparently helps to control replication inhibition independently of replication promotion.
Loss and recovery of functional connectivity in cultured cortical networks exposed to hypoxia
Authors: le Feber Joost , Erkamp Niels , van Putten Michel J. A. M. , Hofmeijer Jeannette 
Published: April 2017

In the core of a brain infarct, loss of neuronal function is followed by neuronal death within minutes. In an area surrounding the core (penumbra), some perfusion remains. Here, neurons initially remain structurally intact, but massive synaptic failure strongly reduces neural activity. Activity in the penumbra may eventually recover or further deteriorate toward massive cell death. Besides activity recovery, return of brain functioning requires restoration of connectivity. However, low activity has been shown to initiate compensatory mechanisms that affect network connectivity. We investigated the effect of transient hypoxia and compensatory mechanisms on activity and functional connectivity using cultured cortical networks on multielectrode arrays. Networks were exposed to hypoxia of controlled depth (10–90% of normoxia) and duration (6–48 h). First, we determined how hypoxic depth and duration govern activity recovery. Then, we investigated connectivity changes during and after hypoxic incidents, mild enough for activity to recover. Shortly after hypoxia onset, activity and connectivity decreased. Following 4–6 h of ongoing hypoxia, we observed partial recovery. Only if the hypoxic burden was limited did connectivity show further recovery upon return to normoxia. Partial recovery during hypoxia was dominated by restored baseline connections, rather than newly formed ones. Baseline strengths of surviving (persisting or recovered) and lost connections did not differ nor did baseline activity at their “presynaptic” electrodes. However, “postsynaptic” electrodes of surviving connections were significantly more active during baseline than those of lost connections. This implies that recovery during hypoxia reflects an effective mechanism to restore network activity, which does not necessarily conserve prehypoxia connectivity. NEW & NOTEWORTHY Hypoxia reduced the firing rates of cultured neurons. Depending on hypoxic depth and duration, activity recovered during hypoxia and upon return to normoxia. Recovery (partial) during hypoxia was associated with restored baseline connections rather than newly formed ones. Predominantly, baseline connections with most active postsynaptic electrodes recovered, supporting the notion of effective activity homeostasis. This compensatory mechanism remained effective during ~20 h of hypoxia. Beyond 20 h of compensation, loss of activity and connectivity became irreversible.
A Phase I Study of ABC294640, a First-in-Class Sphingosine Kinase-2 Inhibitor, in Patients with Advanced Solid Tumors
Authors: Britten Carolyn D. , Garrett-Mayer Elizabeth , Chin Steven H. , Shirai Keisuke , Ogretmen Besim , Bentz Tricia A. , Brisendine Alan , Anderton Kate , Cusack Susan L. , Maines Lynn W. , Zhuang Yan , Smith Charles D. , Thomas Melanie B. 
Published: April 2017

Abstract
Purpose: Sphingosine kinases (SK1 and SK2) regulate tumor growth by generating the mitogenic and proinflammatory lipid sphingosine 1-phosphate (S1P). This phase I study investigated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of ABC294640, a first-in-class orally available inhibitor of SK2.
Experimental Design: Escalating doses of ABC294640 were administered orally to patients with advanced solid tumors in sequential cohorts at the following dose levels: 250 mg qd, 250 mg bid, 500 mg bid, and 750 mg bid, continuously in cycles of 28 days. Serial blood samples were obtained to measure ABC294640 concentrations and sphingolipid profiles.
Results: Twenty-two patients were enrolled, and 21 received ABC294640. The most common drug-related toxicities were nausea, vomiting, and fatigue. Among the 4 patients at 750 mg bid, one had dose-limiting grade 3 nausea and vomiting, and 2 were unable to complete cycle 1 due to diverse drug-related toxicities. The 500 mg bid dose level was established as the recommended phase II dose. ABC294640 administration resulted in decreases in S1P levels over the first 12 hours, with return to baseline at 24 hours. The best response was a partial response in a patient with cholangiocarcinoma at 250 mg qd, and stable disease was observed in 6 patients with various solid tumors across dose levels.
Conclusions: At 500 mg bid, ABC294640 is well tolerated and achieves biologically relevant plasma concentrations. Changes in plasma sphingolipid levels may provide a useful pharmacodynamic biomarker for ABC294640. Clin Cancer Res; 23(16); 4642–50. ©2017 AACR.
Ortognaisse Morro do Resende: mineralogia, petrografia, geoquímica e geocronologia
Authors: Vasconcelos Fabiana Franco de , Ávila Ciro Alexandre , Neumann Reiner , Teixeira Wilson , Bongiolo Everton Marques , Barbosa Natali , Camara Beatriz de Oliveira , Menezes Victor Hugo Riboura , Cunha Fernanda Caetano de Mattos 
Published: April 2017

O ortognaisse Morro do Resende aflora próximo à mina da Volta Grande, no município de Nazareno, estado de Minas Gerais, e corresponde a um corpo hololeucocrático a leucocrático, fino e de composição monzogranítica a granodiorítica. Apresenta xenólitos de rochas metamáficas da sequência metavulcano-sedimentar Rio das Mortes e possui idade de cristalização U-Pb SHRIMP de 2174 ± 4 Ma, possibilitando sua correlação a um dos pulsos magmáticos do cinturão Mineiro. Sua mineralogia primária é representada por quartzo, albita, microclínio, biotita, allanita, zircão, magnetita, titanita e apatita, enquanto os minerais metamórficos correspondem a sericita, epidoto, zoisita, clinozoisita, carbonato e clorita. Maghemita, barita, fluorita, monazita, xenotímio, granada e fluoretos de elementos de terras raras (ETR) (possivelmente gagarinita) são minerais de origem hidrotermal, pois ocorrem preenchendo fraturas, intercrescidos ou substituindo os minerais primários e metamórficos, sendo que a percolação desse fluido não ocorreu de forma homogênea ao longo de todo o corpo. A paragênese metamórfica indica condições de fácies xisto verde, que pode estar correlacionada ao evento paleproterozoico II do cinturão Mineiro, com idade entre 2131 e 2101 Ma. Esse corpo apresenta acentuado enriquecimento no conteúdo de ETR, anomalia negativa de Eu associada ao processo de cristalização magmática e anomalia negativa de Ce correlacionada à circulação de fluidos hidrotermais oxidantes.
Association Between Chronic Kidney Disease and Rates of Transfusion and Progression to End‐Stage Renal Disease in Patients Undergoing Transradial Versus Transfemoral Cardiac Catheterization—An Analysis From the Veterans Affairs Clinical Assessment Reporting and Tracking (CART) Program
Authors: Vora Amit N. , Stanislawski Maggie , Grunwald Gary K. , Plomondon Mary E. , Rumsfeld John S. , Maddox Thomas M. , Vidovich Mladen I. , Woody Walter , Nallamothu Brahmajee K. , Gurm Hitinder S. , Rao Sunil V. 
Published: April 2017

Background

Patients with chronic kidney disease (
CKD
) are at increased risk for bleeding, transfusion, and dialysis after cardiac catheterization. Whether rates of these complications are increased in this high‐risk population undergoing transradial access compared with transfemoral access is unknown.

Methods and Results

From the Veterans Affairs (VA) Clinical Assessment Reporting and Tracking program, we identified 229 108 patients undergoing cardiac catheterization between 2007 and 2014, of which 48 155 (21.0%) had baseline glomerular filtration rate (
GFR
) between 15 and 59 mL/min. We used multivariable Cox modeling to determine the independent association between transradial access and postprocedure transfusion as well as progression to new dialysis by degree of renal dysfunction. Overall, 35 979 (15.7%) of patients underwent Transradial access. Transradial patients tended to be slightly younger, but, overall, had similar rates of
CKD
compared to transfemoral patients (24.3% vs 27.1%). Transradial patients had longer fluoroscopy times (7.2 vs 6.0 minutes;
P
<0.001), but lower contrast use (85.0 vs 100.0 mL;
P
<0.001). The estimated rate of blood transfusion within 48 hours was lower among transradial patients (0.85% vs 1.01%) as were rates of new dialysis at 1 year (0.58% vs 0.71%). After multivariable adjustment, transradial access was associated with lower rates of progression to dialysis at 1 year overall (hazard ratio [
HR],
0.83; 95%
CI,
0.70–0.98), with no trend of increased risk for dialysis by degree of
CKD
compared with transfemoral access. Transradial access was associated with greater reduction in transfusion rates with increasing degree of
CKD
(
P
value for trend=0.04: non‐
CKD
:
HR,
0.99; 95%
CI,
0.73–1.34;
GFR
45–59 mL/min:
HR,
0.93; 95%
CI,
0.70–1.23;
GFR
30–44 mL/min:
HR,
0.73; 95%
CI,
0.51–1.03;
GFR
15–29 mL/min:
HR,
0.43; 95%
CI,
0.20–0.90).

Conclusions

Among patients undergoing cardiac catheterization in the
VA
health system, transradial access was associated with lower risk for postprocedure transfusion within 48 hours among patients with more‐severe
CKD
, and with lower risk of progression to end‐stage renal disease at 1 year compared with transfemoral access. These data provide additional evidence that transradial access may provide significant benefit in this high‐risk population.