bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-throughput platform for the discovery of elicitors of silent bacterial gene clusters
Authors: Seyedsayamdost Mohammad R. 
Published: May 2014

Significance
Most clinically used antibiotics are derived from bacterial small molecules produced by dedicated biosynthetic gene clusters. Recent investigations have indicated that the majority of these biosynthetic genes are inactive or “silent.” Identifying the triggers that lead to activation of silent clusters would greatly expand our repertoire of therapeutic molecules. Described herein is a new, high-throughput approach for identifying activators of silent gene clusters. Application of this method to two bacterial clusters revealed that both could be efficiently activated and uncovered a new metabolite. Surprisingly, almost all elicitors discovered were antibiotics, suggesting they play an important role in modulating silent biosynthetic pathways. This approach promises to reveal useful small molecules and the biological regulatory mechanisms underlying silent gene clusters.
Botanical view of the use of plants in medieval medicine in the Eastern Mediterranean according to the Cairo Genizah
Authors: Lev Efraim 
Published: May 2014

This article presents the medicinal plants that were used by the inhabitants of the medieval Eastern Mediterranean (mainly tenth to thirteenth centuries AD) and analyzes their geographical/phyto-botanical origin and their frequency of use at the medieval time. It also discusses various issues such as their historical trade and the continuation of their use in present-day Middle Eastern traditional medicine.The Cairo Genizah is an historical source containing about 250,000 documents, found in a semi-archeological context (synagogue and graves). Since Cairo became the capital and consequently the economic and administrative center of the Muslim empire, the Jewish community had close connections with the Jewish communities of the Middle East, North Africa, Southern Europe, Sicily and India. Therefore, these highly valued documents record every aspect of life and reflect on the whole Mediterranean region and beyond.The inventory of the practicalmateria medicawas reconstructed thanks to hundreds of documents such as prescriptions, list of drugs, and medical letters. It consists of 278 drugs, 223 of which are of plant origin. Asian medicinal plants became highly used in medieval Mediterranean medicine; the vast majority of them are still sold in Middle Eastern markets, although not with the same importance. It is important to note that some of them are sold today mainly for their other uses as spices, perfumes, incense, etc.
Survey of Infection Control Practices in Hemodialysis Units: Preventing Vascular Access–Associated Bloodstream Infections
Authors: Trépanier Pascale , Quach Caroline , Gonzales Milagros , Fortin Élise , Kaouache Mohammed , Desmeules Simon , Rocher Isabelle , Ngenda-Muadi Muleka , Frenette Charles , Tremblay Claude ,   on behalf of the Quebec Healthcare-Associated Infections Surveillance Program Hemodialysis Group
Published: May 2014

ObjectiveDespite surveillance, the Quebec Healthcare-Associated Infections Surveillance Program saw no improvement in vascular access–associated bloodstream infections in hemodialysis (HD). We aimed to determine the infection control measures recommended and implemented in Quebec’s HD units, compliance of local protocols to infection control practice guidelines, and reasons behind the low prevalence of arteriovenous fistulas.MethodsAn online survey was elaborated on the basis of the Centers for Disease Control and Prevention (CDC) and National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines. The questionnaire was validated (construct, content, face validity, and reliability) and sent to all HD units in Quebec (n = 40). Results were analyzed using descriptive statistics, linear regression, and Poisson regression.ResultsThirty-seven (93%) of 40 HD units participated. Thirty (94%) of the 32 centers where central catheters are inserted have written insertion protocols. Compliance with practice guidelines is good, except for full-body draping during catheter insertion (79%) and ointment use at insertion site (3%). Prevention measures for catheter maintenance are in accordance with guidelines, except for skin disinfection with at least 0.5% chlorhexidine and 70% alcohol (67% compliance) and regular antiseptic ointment use at the insertion site (3%). Before fistula cannulation, skin preparation is suboptimal; forearm hygiene is performed in only 61% of cases. Several factors explain the low rate of fistulas, including patient preference (69%) and lack of surgical resources (39%; P = .01).ConclusionsImprovement in standardization of care according to practice guidelines is necessary. Fistula rate could be increased by improving access to surgical resources and patient education. Strategies are now being elaborated to address these findings.
Neurosteroids Allopregnanolone Sulfate and Pregnanolone Sulfate Have Diverse Effect on the α Subunit of the Neuronal Voltage-gated Sodium Channels Nav1.2, Nav1.6, Nav1.7, and Nav1.8 Expressed in Xenopus Oocytes
Authors: Horishita Takafumi , Yanagihara Nobuyuki , Ueno Susumu , Sudo Yuka , Uezono Yasuhito , Okura Dan , Minami Tomoko , Kawasaki Takashi , Sata Takeyoshi 
Published: May 2014

Abstract

Background:
The neurosteroids allopregnanolone and pregnanolone are potent positive modulators of γ-aminobutyric acid type A receptors. Antinociceptive effects of allopregnanolone have attracted much attention because recent reports have indicated the potential of allopregnanolone as a therapeutic agent for refractory pain. However, the analgesic mechanisms of allopregnanolone are still unclear. Voltage-gated sodium channels (Nav) are thought to play important roles in inflammatory and neuropathic pain, but there have been few investigations on the effects of allopregnanolone on sodium channels.

Methods:
Using voltage-clamp techniques, the effects of allopregnanolone sulfate (APAS) and pregnanolone sulfate (PAS) on sodium current were examined in Xenopus oocytes expressing Nav1.2, Nav1.6, Nav1.7, and Nav1.8 α subunits.

Results:
APAS suppressed sodium currents of Nav1.2, Nav1.6, and Nav1.7 at a holding potential causing half-maximal current in a concentration-dependent manner, whereas it markedly enhanced sodium current of Nav1.8 at a holding potential causing maximal current. Half-maximal inhibitory concentration values for Nav1.2, Nav1.6, and Nav1.7 were 12 ± 4 (n = 6), 41 ± 2 (n = 7), and 131 ± 15 (n = 5) μmol/l (mean ± SEM), respectively. The effects of PAS were lower than those of APAS. From gating analysis, two compounds increased inactivation of all α subunits, while they showed different actions on activation of each α subunit. Moreover, two compounds showed a use-dependent block on Nav1.2, Nav1.6, and Nav1.7.

Conclusion:
APAS and PAS have diverse effects on sodium currents in oocytes expressing four α subunits. APAS inhibited the sodium currents of Nav1.2 most strongly.
Withdrawal of Immunosuppression Following Pediatric Liver Transplantation
Authors: Mohammad Saeed , Li Zhe , Englesbe Michael , Skaro Anton , Alonso Estella 
Published: May 2014

ABSTRACTObjectives:Survivors of pediatric liver transplantation are at risk for developing complications related to posttransplant immunosuppressive medications. Withdrawal is possible in selected patients but carries the risk of graft rejection and loss. We modeled the effect of withdrawing immunosuppressive medications on survival, cost, and quality‐adjusted life‐years (QALYs) in a hypothetical cohort of pediatric patients who received transplantation for biliary atresia with stable liver enzymes and no recent episodes of rejection, and who were free from immunosuppression‐related adverse effects.Methods:A decision analysis tree was developed, and Monte Carlo simulations were used to track patients through the model during a 10‐year time course with 1‐year cycles. Data from the literature were used to assign probabilities to major clinical events and preference‐based utility scores to the values of health outcomes. One‐way and probabilistic sensitivity analyses were used to evaluate the impact of uncertainty.Results:Patients following the withdrawal strategy had a 10‐year survival rate of 95.8% and experienced 8.61 QALYs versus 88.6% survival and 8.01 QALYs for those taking immunosuppressive medications. Each additional QALY is attained at a cost of −$18,992.41 and was therefore cost saving.Conclusions:Patients in our model who had their immunosuppression withdrawn had improved survival and QALYs with lower costs. Although every effort was made to validate the model, it is limited by the accuracy of the underlying assumptions. Therefore, clinical trials are needed to determine predictors of successful immunosuppression withdrawal to allow for personalization of medication regimens.
Intraepithelial Lymphocyte Eotaxin‐2 Expression and Perineural Mast Cell Degranulation Differentiate Allergic/Eosinophilic Colitis From Classic IBD
Authors: Torrente Franco , Barabino Arrigo , Bellini Tommaso , Murch Simon H. 
Published: May 2014

ABSTRACTObjectives:Allergic colitis shows overlap with classic inflammatory bowel disease (IBD). Clinically, allergic colitis is associated with dysmotility and abdominal pain, and mucosal eosinophilia is characteristic. We thus aimed to characterise mucosal changes in children with allergic colitis compared with normal tissue and classic IBD, focusing on potential interaction between eosinophils and mast cells with enteric neurones.Methods:A total of 15 children with allergic colitis, 10 with Crohn disease (CD), 10 with ulcerative colitis (UC), and 10 histologically normal controls were studied. Mucosal biopsies were stained for CD3 T cells, Ki‐67, eotaxin‐1, and eotaxin‐2. Eotaxin‐2, IgE, and tryptase were localised compared with mucosal nerves, using neuronal markers neurofilament protein, neuron‐specific enolase, and nerve growth factor receptor.Results:Overall inflammation was greater in patients with CD and UC than in patients with allergic colitis. CD3 T‐cell density was increased in patients with allergic colitis, similar to that in patients with CD but lower than in patients with UC, whereas eosinophil density was higher than in all other groups. Eotaxin‐1 and ‐2 were localised to basolateral crypt epithelium in all specimens, with eotaxin‐1+ lamina propria cells found in all of the colitis groups. Eotaxin‐2+ intraepithelial lymphocyte (IEL) density was significantly higher in allergic colitis specimens than in all other groups. Mast cell degranulation was strikingly increased in patients with allergic colitis (12/15) compared with that in patients with UC (1/10) and CD (0/1). Tryptase and IgE colocalised on enteric neurons in patients with allergic colitis but rarely in patients with IBD.Conclusions:Eotaxin‐2+ IELs may contribute to the periepithelial eosinophil accumulation characteristic of allergic colitis. The colocalisation of IgE and tryptase with mucosal enteric nerves is likely to promote the dysmotility and visceral hyperalgesia classically seen in allergic gastrointestinal inflammation.
The Plant Membrane-Associated REMORIN1.3 Accumulates in Discrete Perihaustorial Domains and Enhances Susceptibility to Phytophthora infestans
Authors: Bozkurt Tolga O. , Richardson Annis , Dagdas Yasin F. , Mongrand Sébastien , Kamoun Sophien , Raffaele Sylvain 
Published: May 2014

Abstract
Filamentous pathogens such as the oomycete Phytophthora infestans infect plants by developing specialized structures termed haustoria inside the host cells. Haustoria are thought to enable the secretion of effector proteins into the plant cells. Haustorium biogenesis, therefore, is critical for pathogen accommodation in the host tissue. Haustoria are enveloped by a specialized host-derived membrane, the extrahaustorial membrane (EHM), which is distinct from the plant plasma membrane. The mechanisms underlying the biogenesis of the EHM are unknown. Remarkably, several plasma membrane-localized proteins are excluded from the EHM, but the remorin REM1.3 accumulates around P. infestans haustoria. Here, we used overexpression, colocalization with reporter proteins, and superresolution microscopy in cells infected by P. infestans to reveal discrete EHM domains labeled by REM1.3 and the P. infestans effector AVRblb2. Moreover, SYNAPTOTAGMIN1, another previously identified perihaustorial protein, localized to subdomains that are mainly not labeled by REM1.3 and AVRblb2. Functional characterization of REM1.3 revealed that it is a susceptibility factor that promotes infection by P. infestans. This activity, and REM1.3 recruitment to the EHM, require the REM1.3 membrane-binding domain. Our results implicate REM1.3 membrane microdomains in plant susceptibility to an oomycete pathogen.
CYTOKININ OXIDASE/DEHYDROGENASE4 Integrates Cytokinin and Auxin Signaling to Control Rice Crown Root Formation
Authors: Gao Shaopei , Fang Jun , Xu Fan , Wang Wei , Sun Xiaohong , Chu Jinfang , Cai Baodong , Feng Yuqi , Chu Chengcai 
Published: May 2014

Abstract
Crown roots constitute the majority of the rice (Oryza sativa) root system and play an important role in rice growth and development. However, the molecular mechanism of crown root formation in rice is not well understood. Here, we characterized a rice dominant mutant, root enhancer1 (ren1-D), which was observed to exhibit a more robust root system, increased crown root number, and reduced plant height. Molecular and genetic analyses revealed that these phenotypes are caused by the activation of a cytokinin oxidase/dehydrogenase (CKX) family gene, OsCKX4. Subcellular localization demonstrated that OsCKX4 is a cytosolic isoform of CKX. OsCKX4 is predominantly expressed in leaf blades and roots. It is the dominant CKX, preferentially expressed in the shoot base where crown root primordia are produced, underlining its role in root initiation. OsCKX4 is induced by exogenous auxin and cytokinin in the roots. Furthermore, one-hybrid assays revealed that OsCKX4 is a direct binding target of both the auxin response factor OsARF25 and the cytokinin response regulators OsRR2 and OsRR3. Overexpression and RNA interference of OsCKX4 confirmed that OsCKX4 plays a positive role in crown root formation. Moreover, expression analysis revealed a significant alteration in the expression of auxin-related genes in the ren1-D mutants, indicating that the OsCKX4 mediates crown root development by integrating the interaction between cytokinin and auxin. Transgenic plants harboring OsCKX4 under the control of the root-specific promoter RCc3 displayed enhanced root development without affecting their shoot parts, suggesting that this strategy could be a powerful tool in rice root engineering.
Phosphoproteomic Analyses Reveal Early Signaling Events in the Osmotic Stress Response
Authors: E. Stecker Kelly , Minkoff Benjamin B. , Sussman Michael R. 
Published: May 2014

AbstractElucidating how plants sense and respond to water loss is important for identifying genetic and chemical interventions that may help sustain crop yields in water-limiting environments. Currently, the molecular mechanisms involved in the initial perception and response to dehydration are not well understood. Modern mass spectrometric methods for quantifying changes in the phosphoproteome provide an opportunity to identify key phosphorylation events involved in this process. Here, we have used both untargeted and targeted isotope-assisted mass spectrometric methods of phosphopeptide quantitation to characterize proteins in Arabidopsis (Arabidopsis thaliana) whose degree of phosphorylation is rapidly altered by hyperosmotic treatment. Thus, protein phosphorylation events responsive to 5 min of 0.3 m mannitol treatment were first identified using 15N metabolic labeling and untargeted mass spectrometry with a high-resolution ion-trap instrument. The results from these discovery experiments were then validated using targeted Selected Reaction Monitoring mass spectrometry with a triple quadrupole. Targeted Selected Reaction Monitoring experiments were conducted with plants treated under nine different environmental perturbations to determine whether the phosphorylation changes were specific for osmosignaling or involved cross talk with other signaling pathways. The results indicate that regulatory proteins such as members of the mitogen-activated protein kinase family are specifically phosphorylated in response to osmotic stress. Proteins involved in 5′ messenger RNA decapping and phosphatidylinositol 3,5-bisphosphate synthesis were also identified as targets of dehydration-induced phosphoregulation. The results of these experiments demonstrate the utility of targeted phosphoproteomic analysis in understanding protein regulation networks and provide new insight into cellular processes involved in the osmotic stress response.
Strigolactone Hormones and Their Stereoisomers Signal through Two Related Receptor Proteins to Induce Different Physiological Responses in Arabidopsis
Authors: Scaffidi Adrian , Waters Mark T. , Sun Yueming K. , Skelton Brian W. , Dixon Kingsley W. , Ghisalberti Emilio L. , Flematti Gavin R. , Smith Steven M. 
Published: May 2014

AbstractTwo α/β-fold hydrolases, KARRIKIN INSENSITIVE2 (KAI2) and Arabidopsis thaliana DWARF14 (AtD14), are necessary for responses to karrikins (KARs) and strigolactones (SLs) in Arabidopsis (Arabidopsis thaliana). Although KAI2 mediates responses to KARs and some SL analogs, AtD14 mediates SL but not KAR responses. To further determine the specificity of these proteins, we assessed the ability of naturally occurring deoxystrigolactones to inhibit Arabidopsis hypocotyl elongation, regulate seedling gene expression, suppress outgrowth of secondary inflorescences, and promote seed germination. Neither 5-deoxystrigol nor 4-deoxyorobanchol was active in KAI2-dependent seed germination or hypocotyl elongation, but both were active in AtD14-dependent hypocotyl elongation and secondary shoot growth. However, the nonnatural enantiomer of 5-deoxystrigol was active through KAI2 in growth and gene expression assays. We found that the four stereoisomers of the SL analog GR24 had similar activities to their deoxystrigolactone counterparts. The results suggest that AtD14 and KAI2 exhibit selectivity to the butenolide D ring in the 2′R and 2′S configurations, respectively. However, we found, for nitrile-debranone (CN-debranone, a simple SL analog), that the 2′R configuration is inactive but that the 2′S configuration is active through both AtD14 and KAI2. Our results support the conclusion that KAI2-dependent signaling does not respond to canonical SLs. Furthermore, racemic mixtures of chemically synthesized SLs and their analogs, such as GR24, should be used with caution because they can activate responses that are not specific to naturally occurring SLs. In contrast, the use of specific stereoisomers might provide valuable information about the specific perception systems operating in different plant tissues, parasitic weed seeds, and arbuscular mycorrhizae.
Favre–Racouchot syndrome concurrent with chronic granulomatous reaction
Authors: Zheng Li‐qiang , Han Xiang‐chun , Huang Yong , Li Hong‐wei , Niu Xiao‐dong 
Published: May 2014

AbstractFavre–Racouchot syndrome (FRS) is a disorder consisting of solar elastosis with the presence of multiple cysts and open comedones. Although the exact mechanism of the condition is not known, FRS has been specifically connected to sun exposure, smoking and radiation exposure. The histological changes present in FRS reveal an atrophic epidermis and large masses of keratinous material, causing follicular plugging, as well as solar elastotic changes and possible basophilic degeneration of connective tissue. Herein, we report an unusual case of FRS concurrent with chronic granulomatous reaction and review relevant published works.
Warming decreases thermal heterogeneity of leaf surfaces: implications for behavioural thermoregulation by arthropods
Authors: Caillon Robin , Suppo Christelle , Casas Jérôme , Arthur Woods H. , Pincebourde Sylvain 
Published: May 2014

Summary

Ectotherms rely heavily on the spatial variance of environmental conditions to thermoregulate. Theoretically, their fitness is maximized when they can find suitable microhabitats by moving over short distances – this condition is met when spatial variance is high at fine spatial scales. Strikingly, despite the diversity of organisms living in leaf microhabitats, little is known about the impact of warming on the spatial variance of climatic conditions at the scale of individual leaf surfaces.

Here, we used experimental manipulation of ambient conditions to quantify the effects of environmental change on the thermal heterogeneity within individual leaf surfaces. We also explored the implications for behavioural thermoregulation by arthropods at a single leaf surface.

Using thermography, we characterized the apple leaf microclimate in terms of span and spatial aggregation of surface temperatures across a range of air temperatures and relative humidities. Then, we assessed how thermal heterogeneity within individual leaves affected behavioural thermoregulation by the two‐spotted spider mite (Tetranychus urticae Koch) under both near‐optimal and sublethal conditions in this microhabitat. We measured the upper lethal temperature threshold of the mite to define sublethal exposure.

Thermal heterogeneity of individual leaves was driven mainly by ambient air temperature. Higher air temperatures gave both smaller ranges and higher spatial aggregation of temperatures at the leaf surface, such that the leaf microclimate was homogenized.

Tetranychus urticae used behavioural thermoregulation at moderate air temperature, when thermal heterogeneity was high at the leaf surface. At higher air temperature, however, heterogeneity declined and spider mites did not perform behavioural thermoregulation.

Warming decreases thermal heterogeneity of leaf surfaces with critical implications for arthropods – behavioural thermoregulation alone is not sufficient to escape the heat in the leaf microhabitat. Information on spatial variance of microclimatic conditions is critical for estimating how readily organisms can buffer global warming by moving.
Functional Properties of Vinegar
Authors: Budak Nilgün H. , Aykin Elif , Seydim Atif C. , Greene Annel K. , Guzel‐Seydim Zeynep B. 
Published: May 2014

AbstractA variety of natural vinegar products are found in civilizations around the world. A review of research on these fermented products indicates numerous reports of health benefits derived by consumption of vinegar components. Therapeutic effects of vinegar arising from consuming the inherent bioactive components including acetic acid, gallic acid, catechin, ephicatechin, chlorogenic acid, caffeic acid, p‐coumaric acid, and ferulic acid cause antioxidative, antidiabetic, antimicrobial, antitumor, antiobesity, antihypertensive, and cholesterol‐lowering responses. The aims of this article are to discuss vinegar history, production, varieties, acetic acid bacteria, and functional properties of vinegars.