bluuebunny/crossref_metadata_2025_split huggingface dataset:
Environmental Factors Shape the Community of Symbionts in the Hoopoe Uropygial Gland More than Genetic Factors
Authors: Ruiz-Rodríguez Magdalena , Soler Juan J. , Martín-Vivaldi Manuel , Martín-Platero Antonio M. , Méndez María , Peralta-Sánchez Juan M. , Ananou Samir , Valdivia Eva , Martínez-Bueno Manuel 
Published: August 2014

ABSTRACTExploring processes of coevolution of microorganisms and their hosts is a new imperative for life sciences. If bacteria protect hosts against pathogens, mechanisms facilitating the intergenerational transmission of such bacteria will be strongly selected by evolution. By disentangling the diversity of bacterial strains from the uropygium of hoopoes (Upupa epops) due to genetic relatedness or to a common environment, we explored the importance of horizontal (from the environment) and vertical (from parents) acquisition of antimicrobial-producing symbionts in this species. For this purpose, we compared bacterial communities among individuals in nonmanipulated nests; we also performed a cross-fostering experiment using recently hatched nestlings before uropygial gland development and some nestlings that were reared outside hoopoe nests. The capacity of individuals to acquire microbial symbionts horizontally during their development was supported by our results, since cross-fostered nestlings share bacterial strains with foster siblings and nestlings that were not in contact with hoopoe adults or nests also developed the symbiosis. Moreover, nestlings could change some bacterial strains over the course of their stay in the nest, and adult females changed their bacterial community in different years. However, a low rate of vertical transmission was inferred, since genetic siblings reared in different nests shared more bacterial strains than they shared with unrelated nestlings raised in different nests. In conclusion, hoopoes are able to incorporate new symbionts from the environment during the development of the uropygium, which could be a selective advantage if strains with higher antimicrobial capacity are incorporated into the gland and could aid hosts in fighting against pathogenic and disease-causing microbes.
The High-Capacity Specific Fructose Facilitator ZrFfz1 Is Essential for the Fructophilic Behavior of Zygosaccharomyces rouxii CBS 732T
Authors: Leandro Maria José , Cabral Sara , Prista Catarina , Loureiro-Dias Maria C. , Sychrová Hana 
Published: August 2014

ABSTRACTZygosaccharomyces rouxiiis a fructophilic yeast that consumes fructose preferably to glucose. This behavior seems to be related to sugar uptake. In this study, we constructedZ. rouxiisingle-, double-, and triple-deletion mutants in the UL4 strain background (aura3strain derived from CBS 732T) by deleting the genes encoding the specific fructose facilitatorZ. rouxiiFfz1 (ZrFfz1), the fructose/glucose facilitator ZrFfz2, and/or the fructose symporter ZrFsy1. We analyzed the effects on the growth phenotype, on kinetic parameters of fructose and glucose uptake, and on sugar consumption profiles. No growth phenotype was observed on fructose or glucose upon deletion ofFFZgenes. Deletion of ZrFFZ1drastically reduced fructose transport capacity, increased glucose transport capacity, and eliminated the fructophilic character, while deletion of ZrFFZ2had almost no effect. The strain in which bothFFZgenes were deleted presented even higher consumption of glucose than strain Zrffz1Δ, probably due to a reduced repressing effect of fructose. This study confirms the molecular basis of theZ. rouxiifructophilic character, demonstrating that ZrFfz1 is essential forZ. rouxiifructophilic behavior. The gene is a good candidate to improve the fructose fermentation performance of industrialSaccharomyces cerevisiaestrains.
Sequential Logic of Polarity Determination during the Haploid-to-Diploid Transition in Saccharomyces cerevisiae
Authors: Zapanta Rinonos Serendipity , Rai Urvashi , Vereb Sydney , Wolf Kyle , Yuen Eric , Lin Cindy , Tartakoff Alan Michael 
Published: August 2014

ABSTRACT

In many organisms, the geometry of encounter of haploid germ cells is arbitrary. In
Saccharomyces cerevisiae
, the resulting zygotes have been seen to bud asymmetrically in several directions as they produce diploid progeny. What mechanisms account for the choice of direction, and do the mechanisms directing polarity change over time? Distinct subgroups of cortical “landmark” proteins guide budding by haploid versus diploid cells, both of which require the Bud1/Rsr1 GTPase to link landmarks to actin. We observed that as mating pairs of haploid cells form zygotes, bud site specification progresses through three phases. The first phase follows disassembly and limited scattering of proteins that concentrated at the zone of cell contact, followed by their reassembly to produce a large medial bud. Bud1 is not required for medial placement of the initial bud. The second phase produces a contiguous bud(s) and depends on axial landmarks. As the titer of the Axl1 landmark diminishes, the third phase ultimately redirects budding toward terminal sites and is promoted by bipolar landmarks. Thus, following the initial random encounter that specifies medial budding, sequential spatial choices are orchestrated by the titer of a single cortical determinant that determines whether successive buds will be contiguous to their predecessors.
Nobel Laureate Roy Glauber on Physics and His Personal Experience
Authors: Good Michael 
Published: September 2014

Roy Jay Glauber, Lee Kong Chian Distinguished Professor; Mallinckrodt Professor of Physics, Harvard University. Professor Glabuer was awarded the 2005 Nobel Prize in Physics for his contribution to the quantum theory of optical coherence. He was invited to Singapore by Institute of Advanced Studies@ Nanyang Technological University in 2014. During his stay in Singapore, he gave several talks to the local physics community members and the general public. In one of his public lectures on "Some Recollections of Los Alamos — and the Nuclear Era", he shared his personal experiences, feelings, and interpretations, regarding wartime science. The editorial team of Asia Pacific Physics Newsletter interviewed Professor Glauber at the Centre for Quantum Technologies, National University of Singapore on 6 May 2014.
Stress Signaling from Human Mammary Epithelial Cells Contributes to Phenotypes of Mammographic Density
Authors: DeFilippis Rosa Anna , Fordyce Colleen , Patten Kelley , Chang Hang , Zhao Jianxin , Fontenay Gerald V. , Kerlikowske Karla , Parvin Bahram , Tlsty Thea D. 
Published: August 2014

Abstract
Telomere malfunction and other types of DNA damage induce an activin A–dependent stress response in mortal nontumorigenic human mammary epithelial cells that subsequently induces desmoplastic-like phenotypes in neighboring fibroblasts. Some characteristics of this fibroblast/stromal response, such as reduced adipocytes and increased extracellular matrix content, are observed not only in tumor tissues but also in disease-free breast tissues at high risk for developing cancer, especially high mammographic density tissues. We found that these phenotypes are induced by repression of the fatty acid translocase CD36, which is seen in desmoplastic and disease-free high mammographic density tissues. In this study, we show that epithelial cells from high mammographic density tissues have more DNA damage signaling, shorter telomeres, increased activin A secretion and an altered DNA damage response compared with epithelial cells from low mammographic density tissues. Strikingly, both telomere malfunction and activin A expression in epithelial cells can repress CD36 expression in adjacent fibroblasts. These results provide new insights into how high mammographic density arises and why it is associated with breast cancer risk, with implications for the definition of novel invention targets (e.g., activin A and CD36) to prevent breast cancer. Cancer Res; 74(18); 5032–44. ©2014 AACR.
The Cytokinesis-Blocked Micronucleus Assay as a Strong Predictor of Lung Cancer: Extension of a Lung Cancer Risk Prediction Model
Authors: El-Zein Randa A. , Lopez Mirtha S. , D'Amelio Anthony M. , Liu Mei , Munden Reginald F. , Christiani David , Su Li , Tejera-Alveraz Paula , Zhai Rihong , Spitz Margaret R. , Etzel Carol J. 
Published: August 2014

Abstract
Background: There is an urgent need to improve lung cancer outcome by identifying and validating markers of risk. We previously reported that the cytokinesis-blocked micronucleus assay (CBMN) is a strong predictor of lung cancer risk. Here, we validate our findings in an independent external lung cancer population and test discriminatory power improvement of the Spitz risk prediction model upon extension with this biomarker.
Methods: A total of 1,506 participants were stratified into a test set of 995 (527 cases/468 controls) from MD Anderson Cancer Center (Houston, TX) and a validation set of 511 (239 cases/272 controls) from Massachusetts General Hospital (Boston, MA). An epidemiologic questionnaire was administered and genetic instability was assessed using the CBMN assay.
Results: Excellent concordance was observed between the two populations in levels and distribution of CBMN endpoints [binucleated-micronuclei (BN-MN), binucleated-nucleoplasmic bridges (BN-NPB)] with significantly higher mean BN-MN and BN-NPB values among cases (P &lt; 0.0001). Extension of the Spitz model led to an overall improvement in the AUC (95% confidence intervals) from 0.61 (55.5–65.7) with epidemiologic variables to 0.92 (89.4–94.2) with addition of the BN-MN endpoint. The most dramatic improvement was observed with the never-smokers extended model followed by the former and current smokers.
Conclusions: The CBMN assay is a sensitive and specific predictor of lung cancer risk, and extension of the Spitz risk prediction model led to an AUC that may prove useful in population screening programs to identify the “true” high-risk individuals.
Impact: Identifying high-risk subgroups that would benefit from screening surveillance has immense public health significance. Cancer Epidemiol Biomarkers Prev; 23(11); 2462–70. ©2014 AACR.
On-Target Effect of FK866, a Nicotinamide Phosphoribosyl Transferase Inhibitor, by Apoptosis-Mediated Death in Chronic Lymphocytic Leukemia Cells
Authors: Gehrke Iris , Bouchard Eric D.J. , Beiggi Sara , Poeppl Armando G. , Johnston James B. , Gibson Spencer B. , Banerji Versha 
Published: August 2014

Abstract
Purpose: Chronic lymphocytic leukemia (CLL) remains incurable despite advances in therapy. In this study, we characterize the effect of nicotinamide phosphoribosyltransferase (NAMPT) inhibition by FK866 in primary CLL cells from patients with various clinical prognostic markers.
Experimental Design: CLL cells were treated with FK866 to assess viability by Annexin V/PI staining. Functional analysis of FK866 included time- and concentration-dependent evaluation of cellular NAD, ATP, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and apoptotic signaling. Chemosensitization potential by FK866 to fludarabine was also assessed. Prognostic markers were correlated with drug response.
Results: FK866 induced CLL cell death by depleting cellular NAD content by day 1, followed by a drop in ATP on day 2. We observed loss of MMP, ROS increase, and induction of apoptotic signaling at day 3. On-target activity of FK866 was confirmed by NAD-mediated rescue of NAD and ATP loss, apoptotic signaling, and viability. The response to FK866 was independent of most prognostic markers. Higher doses were required with short lymphocyte doubling time and positive CD38 status, whereas CLL cells resistant to fludarabine in vitro and from patients with del17p13.1 were equally sensitive to FK866. FK866 did not upregulate the p53-target p21, nor did the p53 activator Nutlin improve FK866-mediated cell death. Furthermore, fludarabine and FK866 were synergistic at clinically relevant concentrations.
Conclusions: NAMPT inhibition by FK866 may be a potential treatment for CLL, including patients with del17p13.1 or other high-risk features. FK866 may complement standard agents to enhance their efficacy and/or allow dose reduction for improved tolerability. Clin Cancer Res; 20(18); 4861–72. ©2014 AACR.
Deletion of Chromosome 9p21 Noncoding Cardiovascular Risk Interval in Mice Alters Smad2 Signaling and Promotes Vascular Aneurysm
Authors: Loinard Céline , Basatemur Gemma , Masters Leanne , Baker Lauren , Harrison James , Figg Nichola , Vilar José , Sage Andrew P. , Mallat Ziad 
Published: September 2014

Background—
Vascular aneurysm is an abnormal local dilatation of an artery that can lead to vessel rupture and sudden death. The only treatment involves surgical or endovascular repair or exclusion. There is currently no approved medical therapy for this condition. Recent data established a strong association between genetic variants in the 9p21 chromosomal region in humans and the presence of cardiovascular diseases, including aneurysms. However, the mechanisms linking this 9p21 DNA variant to cardiovascular risk are still unknown.

Methods and Results—

Here, we show that deletion of the orthologous 70-kb noncoding interval on mouse chromosome 4 (chr4
Δ70kb/Δ70kb
mice) is associated with reduced aortic expression of cyclin-dependent kinase inhibitor genes
p19Arf
and
p15Inkb
. Vascular smooth muscle cells from chr4
Δ70kb/Δ70kb
mice show reduced transforming growth factor-β–dependent canonical Smad2 signaling but increased cyclin-dependent kinase–dependent Smad2 phosphorylation at linker sites, a phenotype previously associated with tumor growth and consistent with the mechanistic link between reduced canonical transforming growth factor-β signaling and susceptibility to vascular diseases. We also show that targeted deletion of the 9p21 risk interval promotes susceptibility to aneurysm development and rupture when mice are subjected to a validated model of aneurysm formation. The vascular disease of chr4
Δ70kb/Δ70kb
mice is prevented by treatment with a cyclin-dependent kinase inhibitor.

Conclusions—
The results establish a direct mechanistic link between 9p21 noncoding risk interval and susceptibility to aneurysm and may have important implications for the understanding and treatment of vascular diseases.
The omohyoid muscle entrapment of the internal jugular vein. A still unclear pathogenetic mechanism
Authors: Gianesini Sergio , Menegatti Erica , Mascoli Francesco , Salvi Fabrizio , Bastianello Stefano , Zamboni Paolo 
Published: September 2014

Objectives: To evaluate the role of the omohyoid muscle anatomic variants as a possible reversible cause of internal jugular vein extrinsic compression. Method: We describe a chronic cerebro-spinal venous insufficiency patient, who presented a omohyoid muscle entrapment of the internal jugular vein, confirmed by both magnetic resonance venography and ultrasound investigation. A omohyoid muscle surgical transection together with a patch angioplasty was performed. Results: The surgical procedure led to both IJV flow restoration and neurological improvement. Conclusions: The omohyoid muscle compression on the internal jugular vein seems to be a possible cause of venous obstruction, but several anatomical and patho-physiological aspects need further investigations. Such picture might cause balloon venous angioplasty inefficacy and needs to be preoperatively considered.
Mast cells in human airways: the culprit?
Authors: Erjefält Jonas S. 
Published: September 2014

By virtue of their undisputed role in allergy, the study of airway mast cells has focused on nasal and bronchial mast cells and their involvement in allergic rhinitis and asthma. However, recent mechanistic and human studies suggest that peripheral mast cells also have an important role in asthma, as well as chronic obstructive pulmonary disease, respiratory infections and lung fibrosis. Pathogenic roles include immune-modulatory, pro-inflammatory and pro-fibrotic activities. Importantly, mast cells also actively downregulate inflammation and participate in the defence against respiratory infections. Another complicating factor is the notorious mast cell heterogeneity, where each anatomical compartment of the lung harbours site-specific mast cell populations.Alveolar mast cells stand out as they lack the cardinal expression of the high affinity IgE receptor. Supporting the emerging concept of alveolar inflammation in asthma, alveolar mast cells shift to a highly FcϵRI-expressing phenotype in uncontrolled asthma. Site-specific and disease-associated mast cell changes have also recently been described in most other inflammatory conditions of the lung. Thus, in the exploration of new anti-mast cell treatment strategies the search has widened to include the lung periphery and the delicate task of identifying which of the countless potential roles are the critical disease modifying ones in a given clinical situation.
Depression and anxiety in patients with COPD
Authors: Yohannes Abebaw M. , Alexopoulos George S. 
Published: September 2014

Under-recognised and untreated depression and anxiety symptoms have deleterious effects on physical functioning and social interaction increasing fatigue and healthcare utilisation in patients with chronic obstructive pulmonary disease (COPD). Depression and anxiety are challenging to identify and treat because their symptoms often overlap with those of COPD. The cause(s) of depression and anxiety symptoms are multifactorial and include behavioural, social and biological factors. Less than one-third of COPD patients with comorbid depression or anxiety symptoms are receiving appropriate treatment. Factors that contribute to the lack of provision of treatment are varied, they include patient perceived barriers, for example lack of knowledge and reluctance to receive antidepressant drug therapy; poor treatment compliance and lack of a standardised diagnostic approach; and scarcity of adequate resources for mental health treatment.The evidence for the efficacy of antidepressant drug therapy in patients with COPD with comorbid depression and anxiety is inconclusive. There are some promising findings regarding pulmonary rehabilitation, psychological therapy and the collaborative care model in reducing depression and anxiety symptoms in patients with COPD, but these findings are limited by short-term follow-up periods. Further work is required to examine the efficacy of these interventions in randomised controlled trials with larger samples and long-term follow-up.
Diagnostic and therapeutic errors in cluster headache: a hospital-based study
Authors: Voiticovschi-Iosob Cristina , Allena Marta , De Cillis Ilaria , Nappi Giuseppe , Sjaastad Ottar , Antonaci Fabio 
Published: September 2014

Abstract

Background
Cluster headache (CH) is a severe, disabling form of headache. Even though CH has a typical clinical picture it seems that its diagnosis is often missed or delayed in clinical practice. CH patients may thus face: misdiagnosis, unnecessary investigations and delays in accessing adequate treatment. This study was conducted to investigate the occurrence of diagnostic and therapeutic errors with a view to improving the clinical and instrumental work-up in affected patients.

Methods
Our study comprised 144 episodic CH patients: 116 from Italy and 28 from Eastern European countries (Moldova, Ukraine, Bulgaria). One hundred six patients (73.6%) were examined personally and 38 (26.4%) were evaluated through telephone interviews conducted by headache specialists using an ad hoc questionnaire developed by the authors.

Results
The sample was predominantly male (M:F ratio 2.79:1) and had a mean age of 42.4 ± 9.8 years; approximately 76% of the patients had already consulted a physician about their CH at the onset of the disease. The mean interval between onset of the disease and first consultation at a headache center was 4.1 ± 5.6 years. The patients had consulted different specialists prior to receiving their CH diagnosis: neurologists (49%), primary care physicians (35%), ENT specialists (10%), dentists (3%), etc. Misdiagnoses at first consultation were recorded in 77% of the cases: trigeminal neuralgia (22%), migraine without aura (19%), sinusitis (15%), etc. The average “diagnostic delay” was 5.3 ± 6.4 years and the condition was diagnosed approximately (“doctor delay”: one year). Instrumental and laboratory investigations were carried out in 93% of the patients prior to diagnosis of CH. Some of the patients had never received abortive or preventive medications, either before or after diagnosis. Medical prescription compliance: 88% of the cases.

Conclusions
Our results emphasize the need to improve specialist education in this field in order to improve recognition of the clinical picture of CH and increase knowledge of the proper medical treatments for de novo CH. Continuous medical education on CH should target general neurologists, primary care physicians, ENT specialists and dentists. A study on a larger population of CH patients may further improve error-avoidance strategies.
Fractal-based analysis of optical coherence tomography data to quantify retinal tissue damage
Authors: Somfai Gábor Márk , Tátrai Erika , Laurik Lenke , Varga Boglárka E , Ölvedy Vera , Smiddy William E , Tchitnga Robert , Somogyi Anikó , DeBuc Delia Cabrera 
Published: September 2014

Abstract

Background
The sensitivity of Optical Coherence Tomography (OCT) images to identify retinal tissue morphology characterized by early neural loss from normal healthy eyes is tested by calculating structural information and fractal dimension. OCT data from 74 healthy eyes and 43 eyes with type 1 diabetes mellitus with mild diabetic retinopathy (MDR) on biomicroscopy was analyzed using a custom-built algorithm (OCTRIMA) to measure locally the intraretinal layer thickness. A power spectrum method was used to calculate the fractal dimension in intraretinal regions of interest identified in the images. ANOVA followed by Newman-Keuls post-hoc analyses were used to test for differences between pathological and normal groups. A modified p value of <0.001 was considered statistically significant. Receiver operating characteristic (ROC) curves were constructed to describe the ability of each parameter to discriminate between eyes of pathological patients and normal healthy eyes.

Results
Fractal dimension was higher for all the layers (except the GCL + IPL and INL) in MDR eyes compared to normal healthy eyes. When comparing MDR with normal healthy eyes, the highest AUROC values estimated for the fractal dimension were observed for GCL + IPL and INL. The maximum discrimination value for fractal dimension of 0.96 (standard error =0.025) for the GCL + IPL complex was obtained at a FD ≤ 1.66 (cut off point, asymptotic 95% Confidence Interval: lower-upper bound = 0.905-1.002). Moreover, the highest AUROC values estimated for the thickness measurements were observed for the OPL, GCL + IPL and OS. Particularly, when comparing MDR eyes with control healthy eyes, we found that the fractal dimension of the GCL + IPL complex was significantly better at diagnosing early DR, compared to the standard thickness measurement.

Conclusions
Our results suggest that the GCL + IPL complex, OPL and OS are more susceptible to initial damage when comparing MDR with control healthy eyes. Fractal analysis provided a better sensitivity, offering a potential diagnostic predictor for detecting early neurodegeneration in the retina.