bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kalrnplays key roles within and outside of the nervous system
Authors: Mandela Prashant , Yankova Maya , Conti Lisa H , Ma Xin-Ming , Grady James , Eipper Betty A , Mains Richard E 
Published: November 2012

Abstract

Background
The human KALRN gene, which encodes a complex, multifunctional Rho GDP/GTP exchange factor, has been linked to cardiovascular disease, psychiatric disorders and neurodegeneration. Examination of existing Kalrn knockout mouse models has focused only on neuronal phenotypes. However, Kalirin was first identified through its interaction with an enzyme involved in the synthesis and secretion of multiple bioactive peptides, and studies in C.elegans revealed roles for its orthologue in neurosecretion.

Results
We used a broad array of tests to evaluate the effects of ablating a single exon in the spectrin repeat region of Kalrn (KalSRKO/KO); transcripts encoding Kalrn isoforms containing only the second GEF domain can still be produced from the single remaining functional Kalrn promoter. As expected, KalSRKO/KO mice showed a decrease in anxiety-like behavior and a passive avoidance deficit. No changes were observed in prepulse inhibition of acoustic startle or tests of depression-like behavior. Growth rate, parturition and pituitary secretion of growth hormone and prolactin were deficient in the KalSRKO/KO mice. Based on the fact that a subset of Kalrn isoforms is expressed in mouse skeletal muscle and the observation that muscle function in C.elegans requires its Kalrn orthologue, KalSRKO/KO mice were evaluated in the rotarod and wire hang tests. KalSRKO/KO mice showed a profound decrease in neuromuscular function, with deficits apparent in KalSR+/KO mice; these deficits were not as marked when loss of Kalrn expression was restricted to the nervous system. Pre- and postsynaptic deficits in the neuromuscular junction were observed, along with alterations in sarcomere length.

Conclusions
Many of the widespread and diverse deficits observed both within and outside of the nervous system when expression of Kalrn is eliminated may reflect its role in secretory granule function and its expression outside of the nervous system.
Expression of flavonoid 3’-hydroxylase is controlled by P1, the regulator of 3-deoxyflavonoid biosynthesis in maize
Authors: Sharma Mandeep , Chai Chenglin , Morohashi Kengo , Grotewold Erich , Snook Maurice E , Chopra Surinder 
Published: November 2012

Abstract

Background
The maize (Zea mays) red aleurone1 (pr1) encodes a CYP450-dependent flavonoid 3’-hydroxylase (ZmF3’H1) required for the biosynthesis of purple and red anthocyanin pigments. We previously showed that Zmf3’h1 is regulated by C1 (Colorless1) and R1 (Red1) transcription factors. The current study demonstrates that, in addition to its role in anthocyanin biosynthesis, the Zmf3’h1 gene also participates in the biosynthesis of 3-deoxyflavonoids and phlobaphenes that accumulate in maize pericarps, cob glumes, and silks. Biosynthesis of 3-deoxyflavonoids is regulated by P1 (Pericarp color1) and is independent from the action of C1 and R1 transcription factors.

Results
In maize, apiforol and luteoforol are the precursors of condensed phlobaphenes. Maize lines with functional alleles of pr1 and p1 (Pr1;P1) accumulate luteoforol, while null pr1 lines with a functional or non-functional p1 allele (pr1;P1 or pr1;p1) accumulate apiforol. Apiforol lacks a hydroxyl group at the 3’-position of the flavylium B-ring, while luteoforol has this hydroxyl group. Our biochemical analysis of accumulated compounds in different pr1 genotypes showed that the pr1 encoded ZmF3’H1 has a role in the conversion of mono-hydroxylated to bi-hydroxylated compounds in the B-ring. Steady state RNA analyses demonstrated that Zmf3’h1 mRNA accumulation requires a functional p1 allele. Using a combination of EMSA and ChIP experiments, we established that the Zmf3’h1 gene is a direct target of P1. Highlighting the significance of the Zmf3’h1 gene for resistance against biotic stress, we also show here that the p1 controlled 3-deoxyanthocyanidin and C-glycosyl flavone (maysin) defence compounds accumulate at significantly higher levels in Pr1 silks as compared to pr1 silks. By virtue of increased maysin synthesis in Pr1 plants, corn ear worm larvae fed on Pr1; P1 silks showed slower growth as compared to pr1; P1 silks.

Conclusions
Our results show that the Zmf3’h1 gene participates in the biosynthesis of phlobaphenes and agronomically important 3-deoxyflavonoid compounds under the regulatory control of P1.
Dissecting tocopherols content in maize (Zea mays L.), using two segregating populations and high-density single nucleotide polymorphism markers
Authors: Shutu Xu , Dalong Zhang , Ye Cai , Yi Zhou , Shah Trushar , Ali Farhan , Qing Li , Zhigang Li , Weidong Wang , Jiansheng Li , Xiaohong Yang , Jianbing Yan 
Published: November 2012

Abstract

Background
Tocopherols, which are vitamin E compounds, play an important role in maintaining human health. Compared with other staple foods, maize grains contain high level of tocopherols.

Results
Two F2 populations (K22/CI7 and K22/Dan340, referred to as POP-1 and POP-2, respectively), which share a common parent (K22), were developed and genotyped using a GoldenGate assay containing 1,536 single nucleotide polymorphism (SNP) markers. An integrated genetic linkage map was constructed using 619 SNP markers, spanning a total of 1649.03 cM of the maize genome with an average interval of 2.67 cM. Seventeen quantitative trait loci (QTLs) for all the traits were detected in the first map and 13 in the second. In these two maps, QTLs for different traits were localized to the same genomic regions and some were co-located with candidate genes in the tocopherol biosynthesis pathway. Single QTL was responsible for 3.03% to 52.75% of the phenotypic variation and the QTLs in sum explained23.4% to 66.52% of the total phenotypic variation. A major QTL (qc5-1/qd5-1) affecting α-tocopherol (αT) was identified on chromosome 5 between the PZA03161.1 and PZA02068.1 in the POP-2. The QTL region was narrowed down from 18.7 Mb to 5.4 Mb by estimating the recombination using high-density markers of the QTL region. This allowed the identification of the candidate gene VTE4 which encodes γ-tocopherol methyltransferase, an enzyme that transforms γ-tocopherol (γT)to αT.

Conclusions
These results demonstrate that a few QTLs with major effects and several QTLs with medium to minor effects might contribute to the natural variation of tocopherols in maize grain. The high-density markers will help to fine map and identify the QTLs with major effects even in the preliminary segregating populations. Furthermore, this study provides a simple guide line for the breeders to improve traits that minimize the risk of malnutrition, especially in developing countries.
Methicillin-resistant Staphylococcus aureus nasal carriage among patients receiving hemodialysis in Taiwan: prevalence rate, molecular characterization and de-colonization
Authors: Kang Yu-Chuan , Tai Wei-Chen , Yu Chun-Chen , Kang Je-Ho , Huang Yhu-Chering 
Published: November 2012

Abstract

Background

Staphylococcus aureus, particularly methicillin resistant (MRSA), is a common pathogen among patients receiving hemodialysis. To evaluate nasal carriage, molecular characterization and effectiveness of decolonization of MRSA among patients receiving hemodialysis in Taiwan, we conducted this study.

Methods
From January to June 2011, two nasal samplings with a 3-month interval were obtained from patients undergoing hemodialysis in a medical center (CGMH), and in a local hospital (YMH) and sent for detection of MRSA. For MRSA carriers, decolonization procedures were administered. All patients in CGMH were observed if MRSA infections occurred during the study period.

Results
A total of 529 nasal specimens (265 from CGMH and 264 from YMH) were collected from 296 patients (161 from CGMH and 135 from YMH). 233 patients participated in both surveys. Average one-time point MRSA carriage rate was 3.8%, and the rate was up to 6.9% for those with two-time point surveys. No additional significant factor for MRSA carriage was identified. Seventy percent of the 20 colonizing MRSA isolates, though categorized as healthcare-associated strains epidemiologically, shared common molecular characteristics of the local community-associated strains. Only one of the 20 MRSA-colonized patients failed decolonization and had persistent colonization, while without any intervention, 17 (61%) of 28 patients with methicillin-sensitive S. aureus colonization in the first survey had persistent colonization of a genetically indistinguishable strain. Within the study period, two patients (1.24%) in CGMH, one with MRSA colonization (9.1%), developed MRSA infection.

Conclusion
A substantial proportion of patients receiving hemodialysis in Taiwan had MRSA colonization, mostly genetically community strains. Decolonization procedures may effectively eliminate MRSA colonization and might reduce subsequent MRSA infection in these patients.
Risk factors associated with brachial–ankle pulse wave velocity among peritoneal dialysis patients in Macao
Authors: Kuang Ding-Wei , Li Chiu-Leong , Kuok Un-I , Cheung Kin , Lio Weng-In , Xin Jing 
Published: November 2012

Abstract

Background
Cardiovascular disease is the leading cause of mortality among peritoneal dialysis (PD) patients in Macao. Increased arterial stiffness determined by pulse wave velocity (PWV) has been established as an independent predictor of cardiovascular mortality in end-stage renal disease patients. The present study aims to investigate the relationship between arterial stiffness and its associated risk factors in chronic PD patients.

Methods
A total of 96 chronic PD patients (48 males/48 females) were included in the cross-sectional study. Arterial stiffness was assessed by brachial-ankle PWV (baPWV). Patients were divided into two subgroups according to mean baPWV value. On enrollment, clinical characteristics and biochemical parameters were collected.

Results
Compared with low baPWV group patients, high baPWV group patients were significant older (p<0.001) and more likely to have a high proportion of female gender (p=0.004) as well as previous CVD history (p=0.008). Serum albumin, pre-albumin levels and residual renal creatinine clearance (CCr) were significantly lower but the serum ferritin level was significantly higher in high baPWV group patients than in low baPWV group patients (all p<0.01). BaPWV was positively associated with age (r=0.534, p<0.001), Charlson comorbidity index (r=0.350, p<0.001) and serum ferritin level (r=0.340, p=0.001). Meanwhile, baPWV negatively correlated with serum albumin (r=−0.479, p<0.001), pre-albumin levels (r=−0.320, p=0.003) and residual renal CCr (r=−0.177, p=0.048). Age-adjusted partial correlation test found a significant correlation between baPWV and CRP (r=0.462, p<0.001). Multivariate regression analysis showed that baPWV was independently associated with age (p<0.001), serum albumin level (p=0.015), CRP (p=0.019) and residual renal CCr (p=0.045).

Conclusion
Arterial stiffness, assessed by baPWV, had an independent correlation with age, serum albumin level, CRP level and residual renal CCr among PD patients in Macao.
Rationale for short course primaquine in Africa to interrupt malaria transmission
Authors: Eziefula Alice C , Gosling Roly , Hwang Jimee , Hsiang Michelle S , Bousema Teun , von Seidlein Lorenz , Drakeley Chris 
Published: November 2012

Abstract
Following the recent successes of malaria control in sub-Saharan Africa, the gametocytocidal drug primaquine needs evaluation as a tool to further reduce the transmission of Plasmodium falciparum malaria. The drug has scarcely been used in Africa because of concerns about its safety in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency. The evidence base for the use of primaquine as a transmission blocker is limited by a lack of comparable clinical and parasitological endpoints between trials. In March 2012, a group of experts met in London to discuss the existing evidence on the ability of primaquine to block malaria transmission, to define the roadblocks to the use of primaquine in Africa and to develop a roadmap to enable its rapid, safe and effective deployment. The output of this meeting is a strategic plan to optimize trial design to reach desired goals efficiently. The roadmap includes suggestions for a series of phase 1, 2, 3 and 4 studies to address specific hurdles to primaquine’s deployment. These include ex-vivo studies on efficacy, primaquine pharmacokinetics and pharmacodynamics and dose escalation studies for safety in high-risk groups. Phase 3 community trials are proposed, along with Phase 4 studies to evaluate safety, particularly in pregnancy, through pharmacovigilance in areas where primaquine is already deployed. In parallel, efforts need to be made to address issues in drug supply and regulation, to map G6PD deficiency and to support the evaluation of alternative gametocytocidal compounds.
The DEAD/DEAH box helicase, DDX11, is essential for the survival of advanced melanomas
Authors: Bhattacharya Chitralekha , Wang Xiaolei , Becker Dorothea 
Published: November 2012

Abstract

Background
Despite continuous efforts to identify genes that are pivotal regulators of advanced melanoma and closely related to it, to determine which of these genes have to be blocked in their function to keep this highly aggressive disease in check, it is far from clear which molecular pathway(s) and specific genes therein, is the Achilles’ heel of primary and metastatic melanoma. In this report, we present data, which document that the DEAD-box helicase DDX11, which is required for sister chromatid cohesion, is a crucial gatekeeper for melanoma cell survival.

Methods
Performing immunohistochemistry and immunoblot analysis, we determined expression of DDX11 in melanoma tissues and cell lines. Following transfection of melanoma cells with a DDX11-specific siRNA, we conducted a qPCR analysis to determine downregulation of DDX11 in the transfected melanoma cells. In subsequent studies, which focused upon an analysis of fluorescently labeled as well as Giesma-stained chromosome spreads, a proliferation analysis and apoptosis assays, we determined the impact of suppressing DDX11 expression on melanoma cells representing advanced melanoma.

Result
The findings of the study presented herein document that DDX11 is upregulated with progression from noninvasive to invasive melanoma, and that it is expressed at high levels in advanced melanoma. Furthermore, and equally important, we demonstrate that blocking the expression of DDX11 leads not only to inhibition of melanoma cell proliferation and severe defects in chromosome segregation, but also drives melanoma cells rapidly into massive apoptosis.

Conclusion
To date, little is known as to whether helicases play a role in melanoma development and specifically, in the progression from early to advanced melanoma. In this report, we show that the helicase DDX11 is expressed at high levels in primary and metastatic melanoma, and that interfering with its expression leads to severe chromosome segregation defects, telomere shortening, and massive melanoma cell apoptosis. These findings suggest that DDX11 could be an important candidate for molecular targeted therapy for advanced melanoma.
Interference mitigation in an LTE femtocell base station using uplink antenna selection
Authors: Soler-Garrido Josep , Sandell Magnus , Chin Woon Hau 
Published: November 2012

Abstract
Antenna selection represents an attractive technique that allows to improve performance of wireless systems due to its simplicity and ease of implementation. Antenna selection is able to provide diversity through the use of multiple antennas while keeping low cost and energy consumption by selecting only a subset of the available elements at any given time, hence requiring a smaller number of RF transmitter and receiver chains. This makes it especially suitable for femtocell or small-cell base stations, typically employed by cellular operators to provide indoor radio coverage in customer premises. This article presents an analysis and validation of antenna selection using a LTE-FDD femtocell prototype. The effects on antenna selection performance of different antenna training schedules and channel variation rates are investigated under realistic propagation conditions. It is observed that antenna selection is able to provide substantial gains in terms of channel quality and reliability in interference-limited scenarios, attesting its suitability for large-scale femtocell deployments.
High genetic diversity and predominance of Rhinovirus A and C from Panamanian hospitalized children under five years with respiratory infections
Authors: Franco Danilo , Delfraro Adriana , Abrego Leyda , Cano Maria , Castillo Celedonio , Castillo Marlene , Castillo Juan , Pascale Juan , Arbiza Juan 
Published: November 2012

Abstract

Background
Human Rhinoviruses (HRVs) have high genetic diversity and three species have been described: HRV-A, HRV-B, and the recently recognized HRV-C, which has been rapidly identified worldwide.

Findings
In the present study, we report the frequency and diversity of Human Rhinovirus (HRV) strains circulating in Panama from children hospitalized with respiratory infections.

Conclusions
HRVs of species A, B and C have been identified with a predominance of HRV-A and HRV-C over HRV-B, and marked genetic diversity within each species.
Reply to comment on Fisichella et al. (2012), “Intestinal toxicity evaluation of TiO2 degraded surface-treated nanoparticles: a combined physico-chemical and toxicogenomics approach in Caco-2 cells” by Faust et al.
Authors: Fisichella Matthieu , Bérenguer Frédéric , Steinmetz Gérard , Auffan Mélanie , Rose Jérôme , Prat Odette 
Published: November 2012

Abstract
In this response, we discuss the major differences that clearly distinguish our results from those mentioned by Faust et al. In particular, the experiments have been conducted on nanoparticles of different nature, what mainly explains the observed discrepancies. This is a reply to http://www.particleandfibretoxicology.com/content/pdf/1743-8977-9-39.pdf.
Cutaneous Nociceptors Lack Sensitisation, but Reveal μ-Opioid Receptor-Mediated Reduction in Excitability to Mechanical Stimulation in Neuropathy
Authors: Schmidt Yvonne , Labuz Dominika , Heppenstall Paul A , Machelska Halina 
Published: November 2012

Background: Peripheral nerve injuries often trigger a hypersensitivity to tactile stimulation. Behavioural studies demonstrated efficient and side effect-free analgesia mediated by opioid receptors on peripheral sensory neurons. However, mechanistic approaches addressing such opioid properties in painful neuropathies are lacking. Here we investigated whether opioids can directly inhibit primary afferent neuron transmission of mechanical stimuli in neuropathy. We analysed the mechanical thresholds, the firing rates and response latencies of sensory fibres to mechanical stimulation of their cutaneous receptive fields. Results: Two weeks following a chronic constriction injury of the saphenous nerve, mice developed a profound mechanical hypersensitivity in the paw innervated by the damaged nerve. Using an in vitro skin-nerve preparation we found no changes in the mechanical thresholds and latencies of sensory fibres from injured nerves. The firing rates to mechanical stimulation were unchanged or reduced following injury. Importantly, μ-opioid receptor agonist [D-Ala2, N-Me-Phe4,Gly5]-ol-enkephalin (DAMGO) significantly elevated the mechanical thresholds of nociceptive Aδ and C fibres. Furthermore, DAMGO substantially diminished the mechanically evoked discharges of C nociceptors in injured nerves. These effects were blocked by DAMGO washout and pre-treatment with the selective μ-opioid receptor antagonist Cys2-Tyr3-Orn5-Pen7-amide. DAMGO did not alter the responses of sensory fibres in uninjured nerves. Conclusions: Our findings suggest that behaviourally manifested neuropathy-induced mechanosensitivity does not require a sensitised state of cutaneous nociceptors in damaged nerves. Yet, nerve injury renders nociceptors sensitive to opioids. Prevention of action potential generation or propagation in nociceptors might represent a cellular mechanism underlying peripheral opioid-mediated alleviation of mechanical hypersensitivity in neuropathy.
Italian Biological Prosthesis Work-Group (IBPWG): proposal for a decisional model in using biological prosthesis
Authors: Coccolini Federico , Agresta Ferdinando , Bassi Andrea , Catena Fausto , Crovella Feliciano , Ferrara Roberto , Gossetti Francesco , Marchi Domenico , Munegato Gabriele , Negro Paolo , Piccoli Micaela , Melotti Gianluigi , Sartelli Massimo , di Visconte Michele Schiano , Testini Mario , Bertoli Paolo , Capponi Michela Giulii , Lotti Marco , Manfredi Roberto , Pisano Michele , Poiasina Elia , Poletti Eugenio , Ansaloni Luca 
Published: November 2012

Abstract

Introduction
Indications for repair of abdominal hernia are well established and widely diffused. Controversies still exist about the indication in using the different prosthetic materials and principally about the biological ones.

Material and methods
In February 2012, the Italian Biological Prosthesis Work-Group (IBPWG), counting a background of 264 biologic implants, met in Bergamo (Italy) for 1-day meeting with the aim to elaborate a decisional model on biological prosthesis use in abdominal surgery.

Results
A diagram to simplify the decisional process in using biologics has been elaborated.

Conclusion
The present score represents a first attempt to combine scientific knowledge and clinical expertise in order to offer precise indications about the kind of biological mesh to use.
The mQTL hotspot on linkage group 16 for phenolic compounds in apple fruits is probably the result of a leucoanthocyanidin reductase gene at that locus
Authors: Khan Sabaz Ali , Schaart Jan G , Beekwilder Jules , Allan Andrew C , Tikunov Yury M , Jacobsen Evert , Schouten Henk J 
Published: November 2012

Abstract

Background
Our previous study on ripe apples from a progeny of a cross between the apple cultivars ‘Prima’ and ‘Fiesta’ showed a hotspot of mQTLs for phenolic compounds at the top of LG16, both in peel and in flesh tissues. In order to find the underlying gene(s) of this mQTL hotspot, we investigated the expression profiles of structural and putative transcription factor genes of the phenylpropanoid and flavonoid pathways during different stages of fruit development in progeny genotypes.

Results
Only the structural gene leucoanthocyanidin reductase (MdLAR1) showed a significant correlation between transcript abundance and content of metabolites that mapped on the mQTL hotspot. This gene is located on LG16 in the mQTL hotspot. Progeny that had inherited one or two copies of the dominant MdLAR1 alleles (Mm, MM) showed a 4.4- and 11.8-fold higher expression level of MdLAR1 respectively, compared to the progeny that had inherited the recessive alleles (mm). This higher expression was associated with a four-fold increase of procyanidin dimer II as one representative metabolite that mapped in the mQTL hotspot. Although expression level of several structural genes were correlated with expression of other structural genes and with some MYB and bHLH transcription factor genes, only expression of MdLAR1 was correlated with metabolites that mapped at the mQTL hotspot. MdLAR1 is the only candidate gene that can explain the mQTL for procyanidins and flavan-3-ols. However, mQTLs for other phenylpropanoids such as phenolic esters, dihydrochalcones and flavonols, that appear to map at the same locus, have so far not been considered to be dependent on LAR, as their biosynthesis does not involve LAR activity. An explanation for this phenomenon is discussed.

Conclusions
Transcript abundances and genomic positions indicate that the mQTL hotspot for phenolic compounds at the top of LG16 is controlled by the MdLAR1 gene. The dominant allele of the MdLAR1 gene, causing increased content of metabolites that are potentially health beneficial, could be used in marker assisted selection of current apple breeding programs and for cisgenesis.