bluuebunny/crossref_metadata_2025_split huggingface dataset:
An assessment of linkage disequilibrium in Holstein cattle using a Bayesian network
Authors: Morota G. , Valente B.D. , Rosa G.J.M. , Weigel K.A. , Gianola D. 
Published: September 2012

SummaryLinkage disequilibrium (LD) is defined as a non‐random association of the distributions of alleles at different loci within a population. This association between loci is valuable in prediction of quantitative traits in animals and plants and in genome‐wide association studies. A question that arises is whether standard metrics such as D′ and r2 reflect complex associations in a genetic system properly. It seems reasonable to take the view that loci associate and interact together as a system or network, as opposed to in a simple pairwise manner. We used a Bayesian network (BN) as a representation of choice for an LD network. A BN is a graphical depiction of a probability distribution and can represent sets of conditional independencies. Moreover, it provides a visual display of the joint distribution of the set of random variables in question. The usefulness of BN for linkage disequilibrium was explored and illustrated using genetic marker loci found to have the strongest effects on milk protein in Holstein cattle based on three strategies for ranking marker effect estimates: posterior means, standardized posterior means and additive genetic variance. Two different algorithms, Tabu search (a local score–based algorithm) and incremental association Markov blanket (a constraint‐based algorithm), coupled with the chi‐square test, were used for learning the structure of the BN and were compared with the reference r2 metric represented as an LD heat map. The BN captured several genetic markers associated as clusters, implying that markers are inter‐related in a complicated manner. Further, the BN detected conditionally dependent markers. The results confirm that LD relationships are of a multivariate nature and that r2 gives an incomplete description and understanding of LD. Use of an LD Bayesian network enables inferring associations between loci in a systems framework and provides a more accurate picture of LD than that resulting from the use of pairwise metrics.
L1CAM and its cell‐surface mutants: new mechanisms and effects relevant to the physiology and pathology of neural cells
Authors: Tagliavacca Luigina , Colombo Federico , Racchetti Gabriella , Meldolesi Jacopo 
Published: September 2012

AbstractThe L1 syndrome, a genetic disease that affects 1/30 000 newborn males, is sustained by numerous missense mutations of L1 cell adhesion molecule (L1CAM), an adhesion surface protein active also in transmembrane signaling, essential for the development and function of neurons. To investigate the cell biology of L1CAM, we employed a high RE1‐silencing transcription (factor) clone of the pheochromocytoma PC12 line, defective in L1CAM expression and neurite outgrowth. The clone was transfected with wild‐type L1CAM and four missense, disease‐inducing point mutants encoding proteins distributed to the cell surface. The mutant‐expressing cells, defective in adhesion to extracellular matrix proteins and in migration, exhibited unchanged proliferation. The nerve growth factor (NGF)‐induced neurite outgrowth was re‐established in defective clone cells transfected with the wild‐type and the H210Q and I219T L1CAMs mutants, but not in the others. The stimulated outgrowth was confirmed in a second defective PC12 clone over‐expressing the NGF receptor TrkA, treated with NGF and/or a recombinant L1CAM chimera. These results revealed a new function of L1CAM, a positive, robust and dose‐dependent modulation of the TrkA receptor activated spontaneously or by NGF. The variable effects observed with the different L1CAM mutants suggest that this function contributes to the marked heterogeneity of symptoms and severity observed in the patients affected by the L1 syndrome.
Pen‐2 is dispensable for endoproteolysis of presenilin 1, and nicastrin‐Aph subcomplex is important for both γ‐secretase assembly and substrate recruitment
Authors: Mao Guozhang , Cui Mei‐Zhen , Li Tong , Jin Yipeng , Xu Xuemin 
Published: September 2012

Abstractγ‐secretase is a protease complex with at least four components: presenilin, nicastrin (NCT), anterior pharynx‐defective 1 (Aph‐1), and presenilin enhancer 2 (Pen‐2). In this study, using knockout cell lines and small interfering RNA technology, our data demonstrated that the disappeared presenilin 1 C‐terminal fragment (PS1C) caused by knockdown of pen‐2 or knockout of NCT or Aph‐1 was recovered by the addition of proteasome inhibitors, indicating that Pen‐2, as well as NCT and Aph‐1α, is dispensable for presenilin endoproteolysis. Our data also demonstrate that the formation of the nicastrin‐Aph‐1 subcomplex plays not only an important role in γ‐secretase complex assembly but also in recruiting substrate C‐terminal fragment of amyloid precursor protein generated by β‐cleavage. Ablating any one component resulted in the instability of other components of the γ‐secretase complex, and the presence of all three of the other components is required for full maturation of NCT.
Impact of Grapes Heterogeneity According to Sugar Level on both Physical and Mechanical Berries Properties and Their Anthocyanins Extractability at Harvest
Authors: Zouid I. , Siret R. , Jourjon F. , Mehinagic E. , Rolle L. 
Published: September 2012

AbstractCabernet Franc grapes belonging to six different classes of sugar level content (from 176.5 to 258.5 g/L) at harvest were studied. Their physical proprieties and mechanical behavior were measured using compression and puncture tests. The evolution of anthocyanins extractability was determined. Significant differences were found in grape textural properties and anthocyanins content due to the sugar level content in the different samples of berries tested. It appears that the sweetest berries are characterized by a higher extraction yield of anthocyanins (up to +3.55%) with respect to those with more low sugar content. Furthermore, significant relationships exist between the extractability of anthocyanins and the mechanical and physical attributes of the grape berries. The best correlations were obtained with physical parameters such as the berry weight and the surface : volume ratio (r = −0.99 and 0.97, respectively) and with double compression test parameters such as hardness, chewiness and springiness (r = −0.90, −0.91 and 0.92, respectively).Practical ApplicationsThe purpose and the originality of this work were to determine the real impact of the heterogeneity of grapes at harvest. Among the berries with different sugar contents, were assessed the real differences in anthocyanin contents and extractability at harvest. The results acquired, also in function of different distribution percentage of the berries after floatation, suggest that each class of berries may influence in unlike way the final quality of wine. Therefore, automatic densimetric berry‐sorting machines recently developed and proposed for use in wineries could be indeed useful to select the grapes after the harvest.
ArchaealJAB1/MPN/MOV34 metalloenzyme (HvJAMM1) cleaves ubiquitin‐like small archaeal modifier proteins (SAMPs) from protein‐conjugates
Authors: Hepowit Nathaniel L. , Uthandi Sivakumar , Miranda Hugo V. , Toniutti Micaela , Prunetti Laurence , Olivarez Oliver , De Vera Ian Mitchelle S. , Fanucci Gail E. , Chen Sixue , Maupin‐Furlow Julie A. 
Published: September 2012

SummaryProteins withJAB1/MPN/MOV34 metalloenzyme (JAMM/MPN+) domains are widespread among all domains of life, yet poorly understood. Here we report the purification and characterization of an archaealJAMM/MPN+ domain protein (HvJAMM1) fromHaloferax volcaniithat cleaves ubiquitin‐like small archaeal modifier proteins (SAMP1/2) from protein conjugates.HvJAMM1 cleavedSAMP1/2 conjugates generated inH. volcaniias well as isopeptide‐ and linear‐linkedSAMP1–MoaEin purified form. Cleavage of linear linkedSAMP1–MoaEwas dependent on the presence of theSAMPdomain and theC‐terminalVSGGmotif of this domain. WhileHvJAMM1 was inhibited by size exclusion chromatography and metal chelators, its activity could be restored by addition of excessZnCl2.HvJAMM1 residues (Glu31,His88,His90,Ser98 andAsp101) that were conserved with theJAMM/MPN+ active‐site motif were required for enzyme activity. Together, these results provide the first example of aJAMM/MPN+ zinc metalloprotease that independently catalyses the cleavage of ubiquitin‐like (isopeptide and linear) bonds from target proteins. In archaea,HvJAMM1 likely regulates sampylation and the pools of ‘free’SAMPavailable for protein modification.HvJAMM1‐type proteins are thought to release theSAMPs from proteins modified post‐translationally as well as those synthesized as domain fusions.
Inflammatory histopathogenesis of nasopalatine duct cyst: a clinicopathological study of 41 cases
Authors: Tsuneki M , Maruyama S , Yamazaki M , Abé T , Adeola HA , Cheng J , Nishiyama H , Hayashi T , Kobayashi T , Takagi R , Funayama A , Saito C , Saku T 
Published: September 2012

ObjectiveThe aim of this study is to characterize immunohistochemical profiles of lining epithelia of nasopalatine duct cyst (NPC) as well as to correlate those findings with their clinicopathological features to understand the histopathogenesis of NPC.Materials and methodsForty‐one surgical specimens from NPC were examined for clinical profiles and expression of keratin‐7, 13, MUC‐1, and P63 by immunohistochemistry, compared to radicular cyst (RC) and maxillary sinusitis.ResultsNasopalatine duct cyst was clinically characterized by male predominant occurrence: 44% of the cases involved tooth roots, and 70% with inflammatory backgrounds. Lining epithelia of NPCs without daughter cysts were immunohistochemically distinguished into three layers: a keratin 7‐positive (+) ciliated cell layer in the surface, a keratin‐13+ middle layer, and a MUC‐1+/P63+ lower half, indicating that they were not respiratory epithelia, and the same layering pattern was observed in RC. However, those immunolocalization patterns of the main cyst lining with daughter cyst were exactly the same as those of daughter cyst linings as well as duct epithelia of mucous glands.ConclusionsTwo possible histopathogeneses of NPC were clarified: one was inflammatory cyst like RC and the other was salivary duct cyst‐like mucocele.
An evaluation of vitamin E and pycnogenol in children suffering from oral mucositis during cancer chemotherapy
Authors: Khurana H , Pandey RK , Saksena AK , Kumar A 
Published: September 2012

ObjectiveThe purpose of the present study was to evaluate and compare the effectiveness of Vitamin E (E) and Pycnogenol (P) in treatment of Chemotherapy‐Related Oral Mucositis (ChROM) in children.Materials and MethodsA total of 72 children, aged between 6 and 15 years, with ChROM were selected and randomly divided into three groups after assessment of oral mucositis (OM) by WHO grading system. Glycerine (control), E, and P were topically applied in group I, II, and III, respectively, and the prognosis of OM was assessed by functional, objective, and subjective parameters.ResultsPatients of group II and III showed significant improvement when ChROM was analyzed through scoring systems – WHO grading, Oral Mucositis Assessment Scale (OMAS), and Children's International Mucositis Evaluation Scale (ChIMES) as compared to group I (P < 0.001); however, there was no significant difference between groups II and III.ConclusionBoth the drugs E and P per se are effective for treatment of OM with P being not effective for the treatment of severe mucositis (grade 4). Combination of E and P and additional agents may be tried for better results.
A randomized trial comparing the Ambu®Aura‐i™ with the air‐Q™ intubating laryngeal airway as conduits for tracheal intubation in children
Authors: Jagannathan Narasimhan , Sohn Lisa E. , Sawardekar Amod , Gordon Jason , Shah Ravi D. , Mukherji Isabella I. , Roth Andrew G. , Suresh Santhanam 
Published: September 2012

SummaryObjectivesTo assess the clinical performance of the Ambu Aura‐i (Aura‐i) in children.AimTo compare the Aura‐i with the air‐Q intubating laryngeal airway (air‐Q) for the purposes of fiberoptic‐guided tracheal intubation.BackgroundThe Aura‐i is a new supraglottic airway designed for tracheal intubation.Materials/MethodsOne hundred twenty children, ages 1 month to 6 years, were randomized to receive either the Aura‐i or air‐Q, and divided into three equal subgroups (Group 1, 2, 3) based on weight. The time for successful tracheal intubation was primarily assessed. The ease, time, and number of attempts for successful device insertion, leak pressures, fiberoptic grade of laryngeal view, number of attempts time for removal of the device after tracheal intubation, and complications were secondarily assessed.ResultsDevice placement, tracheal intubation, and removal after tracheal intubation were successful in all patients. There were no differences in the time to successful tracheal intubation through the Aura‐i (32.9 ± 13.3 s), and the air‐Q (33.9 ± 13 s; P = 0.68), or fiberoptic grade of view between devices. There was not a statistically significant correlation between the time to intubation and the fiberoptic grade of laryngeal view in any of the groups. There were no statistically significant differences in the overall leak pressures, air‐Q (18.3 ± 6.1 cm H2O) vs Aura‐i (16 ± 5.1 cm H2O; P = 0.05). In Group 1 (5–10 kg), leak pressures were higher with the air‐Q (23.4 ± 7.2 cm H2O) than the Aura‐i (16.1 ± 5.2 cm H2O; P = 0.001). There were no statistically significant differences in the time for removal between the two devices (P = 0.11). However, with the size 1.5 Aura‐i, the pilot balloon of the tracheal tube was removed in order to facilitate the removal of the device after tracheal intubation.ConclusionsBoth devices served as effective conduits for fiberoptic‐guided tracheal intubation. The limitation of the narrower proximal airway tube of the size 1.5 Aura‐i should be considered if cuffed tracheal tubes are to be utilized.
Mitophagy or how to control the Jekyll and Hyde embedded in mitochondrial metabolism: implications for melanoma progression and drug resistance
Authors: Soengas María S. 
Published: September 2012

SummaryProteins and pathways that control cell fate are placed under intense scrutiny. The same tight regulation applies to essential organelles that can both sustain cell survival or promote self‐degradation programs. Mitochondria are perhaps the prime example of cellular machineries with split functions (personalities). As a main source of ATP, mitochondria represent the main powerhouse of eukaryotic cells. However, mitochondrial respiration has the hidden complication of the production of potentially harmful reactive oxygen species (ROS). Moreover, mitochondria holds an armamentarium of stress‐response factors, which depending on the context, may lead to pro‐inflammatory signals, and to various forms of cell death, ranging from apoptosis to necrosis. A main clearance mechanism to eliminate superfluous, damaged or hyperactive mitochondria is selective mitophagy. Mitophagy, in fact, is emerging as a key quality‐control mechanism in cancer cells. Specifically, malignant transformation has been found to induce marked changes in mitochondrial dynamics and structure. Moreover, a key hallmark of tumor progression is metabolic reprogramming, which further deregulates ROS content and renders cells more susceptible to mitochondrial perturbations. Despite its increasing relevance in cancer biology, the field of mitophagy remains virtually unexplored in melanoma. However, given unique antioxidant mechanisms in melanocytic cells (e.g., linked to melanin) and the idiosyncratic interplay between ROS and hypoxia (both mitophagy inducers) in melanoma, this tumor type represents an ideal scenario for physiological studies of mitochondrial turnover. This perspective summarizes proof of concept for in‐depth basic and translational studies of mitophagy in melanoma. Particular emphasis is dedicated to new opportunities for gene discovery and drug design in this still aggressive disease.
LBD18 acts as a transcriptional activator that directly binds to the EXPANSIN14 promoter in promoting lateral root emergence of Arabidopsis
Authors: Lee Han Woo , Kim Min‐Jung , Kim Nan Young , Lee Sung Haeng , Kim Jungmook 
Published: September 2012

SummaryLateral root formation, a developmental process under the control of the plant hormone auxin, is a major determinant of root architecture, and defines the ability of a plant to acquire nutrients and water. The LATERAL ORGAN BOUNDARIES DOMAIN/ASYMMETRIC LEAVES2‐LIKE (LBD/ASL) proteins play an important role in the lateral organ development of plants, including lateral root formation. However, their downstream components and signalling mechanisms are largely unknown. Here, we show that auxin‐responsive LBD18/ASL20 acts as a specific DNA‐binding transcriptional activator that directly regulates EXPANSIN14 (EXP14), a gene encoding a cell wall‐loosening factor that promotes lateral root emergence in Arabidopsis thaliana. We showed that LBD18 possesses transcription‐activating function in both yeast and Arabidopsis protoplasts. We isolated putative LBD18 target genes by microarray analysis, and identified EXP14 as a direct target of LBD18. Dexamethasone‐induced expression of LBD18 under the CaMV 35S promoter in transgenic Arabidopsis resulted in enhanced expression of GUS fused to the EXP14 promoter in primordium and overlaying tissues. In contrast, GUS expression under the EXP14 promoter in the lbd18 mutant background was significantly reduced in the same tissues. Experiments using a variety of molecular techniques demonstrated that LBD18 activates EXP14 by directly binding to a specific promoter element in vitro and in vivo. Overexpression of EXP14 in Arabidopsis resulted in the stimulation of emerged lateral roots, but not primordia, whereas EXP14 loss‐of‐function plants had reduced auxin‐stimulated lateral root formation. This study revealed the molecular function of LBD18 as a specific DNA‐binding transcription factor that activates EXP14 expression by directly binding to its promoter.
Activation of R‐mediated innate immunity and disease susceptibility is affected by mutations in a cytosolic O‐acetylserine (thiol) lyase in Arabidopsis
Authors: Tahir Jibran , Watanabe Mutsumi , Jing Hai‐Chun , Hunter Donald A. , Tohge Takayuki , Nunes‐Nesi Adriano , Brotman Yariv , Fernie Alisdair R. , Hoefgen Rainer , Dijkwel Paul P. 
Published: September 2012

SummaryO‐acetylserine (thiol) lyases (OASTLs) are evolutionarily conserved proteins among many prokaryotes and eukaryotes that perform sulfur acquisition and synthesis of cysteine. A mutation in the cytosolic OASTL‐A1 protein ONSET OF LEAF DEATH3 (OLD3) was previously shown to reduce the OASTL activity of the old3‐1 protein in vitro and cause auto‐necrosis in specific Arabidopsis accessions. Here we investigated why a mutation in this protein causes auto‐necrosis in some but not other accessions. The auto‐necrosis was found to depend on Recognition of Peronospora Parasitica 1 (RPP1)‐like disease resistance R gene(s) from an evolutionarily divergent R gene cluster that is present in Ler‐0 but not the reference accession Col‐0. RPP1‐like gene(s) show a negative epistatic interaction with the old3‐1 mutation that is not linked to reduced cysteine biosynthesis. Metabolic profiling and transcriptional analysis further indicate that an effector triggered‐like immune response and metabolic disorder are associated with auto‐necrosis in old3‐1 mutants, probably activated by an RPP1‐like gene. However, the old3‐1 protein in itself results in largely neutral changes in primary plant metabolism, stress defence and immune responses. Finally, we showed that lack of a functional OASTL‐A1 results in enhanced disease susceptibility against infection with virulent and non‐virulent Pseudomonas syringae pv. tomato DC3000 strains. These results reveal an interaction between the cytosolic OASTL and components of plant immunity.
A proteomics approach to investigate the process of Zn hyperaccumulation in Noccaea caerulescens (J & C. Presl) F.K. Meyer
Authors: Schneider Thomas , Persson Daniel Pergament , Husted Søren , Schellenberg Maja , Gehrig Peter , Lee Youngsook , Martinoia Enrico , Schjoerring Jan K. , Meyer Stefan 
Published: September 2012

SummaryZinc (Zn) is an essential trace element in all living organisms, but is toxic in excess. Several plant species are able to accumulate Zn at extraordinarily high concentrations in the leaf epidermis without showing any toxicity symptoms. However, the molecular mechanisms of this phenomenon are still poorly understood. A state‐of‐the‐art quantitative 2D liquid chromatography/tandem mass spectrometry (2D‐LC‐MS/MS) proteomics approach was used to investigate the abundance of proteins involved in Zn hyperaccumulation in leaf epidermal and mesophyll tissues of Noccaea caerulescens. Furthermore, the Zn speciation in planta was analyzed by a size‐exclusion chromatography/inductively coupled plasma mass spectrometer (SEC‐ICP‐MS) method, in order to identify the Zn‐binding ligands and mechanisms responsible for Zn hyperaccumulation. Epidermal cells have an increased capability to cope with the oxidative stress that results from excess Zn, as indicated by a higher abundance of glutathione S‐transferase proteins. A Zn importer of the ZIP family was more abundant in the epidermal tissue than in the mesophyll tissue, but the vacuolar Zn transporter MTP1 was equally distributed. Almost all of the Zn located in the mesophyll was stored as Zn–nicotianamine complexes. In contrast, a much lower proportion of the Zn was found as Zn–nicotianamine complexes in the epidermis. However, these cells have higher concentrations of malate and citrate, and these organic acids are probably responsible for complexation of most epidermal Zn. Here we provide evidence for a cell type‐specific adaptation to excess Zn conditions and an increased ability to transport Zn into the epidermal vacuoles.
Arabidopsis RABA1 GTPases are involved in transport between the trans‐Golgi network and the plasma membrane, and are required for salinity stress tolerance
Authors: Asaoka Rin , Uemura Tomohiro , Ito Jun , Fujimoto Masaru , Ito Emi , Ueda Takashi , Nakano Akihiko 
Published: September 2012

SummaryRAB GTPases are key regulators of membrane traffic. Among them, RAB11, a widely conserved sub‐group, has evolved in a unique way in plants; plant RAB11 members show notable diversity, whereas yeast and animals have only a few RAB11 members. Fifty‐seven RAB GTPases are encoded in the Arabidopsis thaliana genome, 26 of which are classified in the RAB11 group (further divided into RABA1–RABA6 sub‐groups). Although several plant RAB11 members have been shown to play pivotal roles in plant‐unique developmental processes, including cytokinesis and tip growth, molecular and physiological functions of the majority of RAB11 members remain unknown. To reveal precise functions of plant RAB11, we investigated the subcellular localization and dynamics of the largest sub‐group of Arabidopsis RAB11, RABA1, which has nine members. RABA1 members reside on mobile punctate structures adjacent to the trans‐Golgi network and co‐localized with VAMP721/722, R‐SNARE proteins that operate in the secretory pathway. In addition, the constitutive‐active mutant of RABA1b, RABA1bQ72L , was present on the plasma membrane. The RABA1b ‐containing membrane structures showed actin‐dependent dynamic motion . Vesicles labeled by GFP–RABA1b moved dynamically, forming queues along actin filaments. Interestingly, Arabidopsis plants whose four major RABA1 members were knocked out, and those expressing the dominant‐negative mutant of RABA1B, exhibited hypersensitivity to salinity stress. Altogether, these results indicate that RABA1 members mediate transport between the trans‐Golgi network and the plasma membrane, and are required for salinity stress tolerance.