bluuebunny/crossref_metadata_2025_split huggingface dataset:
Error-Prone Processing of Apurinic/Apyrimidinic (AP) Sites by PolX Underlies a Novel Mechanism That Promotes Adaptive Mutagenesis in Bacillus subtilis
Authors: Barajas-Ornelas Rocío del Carmen , Ramírez-Guadiana Fernando H. , Juárez-Godínez Rafael , Ayala-García Victor M. , Robleto Eduardo A. , Yasbin Ronald E. , Pedraza-Reyes Mario 
Published: June 2014

ABSTRACT

In growing cells, apurinic/apyrimidinic (AP) sites generated spontaneously or resulting from the enzymatic elimination of oxidized bases must be processed by AP endonucleases before they compromise cell integrity. Here, we investigated how AP sites and the processing of these noncoding lesions by the AP endonucleases Nfo, ExoA, and Nth contribute to the production of mutations (
hisC952
,
metB5
, and
leuC427
) in starved cells of the
Bacillus subtilis
YB955 strain. Interestingly, cells from this strain that were deficient for Nfo, ExoA, and Nth accumulated a greater amount of AP sites in the stationary phase than during exponential growth. Moreover, under growth-limiting conditions, the triple
nfo exoA nth
knockout strain significantly increased the amounts of adaptive
his
,
met
, and
leu
revertants produced by the
B. subtilis
YB955 parental strain. Of note, the number of stationary-phase-associated reversions in the
his
,
met
, and
leu
alleles produced by the
nfo exoA nth
strain was significantly decreased following disruption of
polX
. In contrast, during growth, the reversion rates in the three alleles tested were significantly increased in cells of the
nfo exoA nth
knockout strain deficient for polymerase X (PolX). Therefore, we postulate that adaptive mutations in
B. subtilis
can be generated through a novel mechanism mediated by error-prone processing of AP sites accumulated in the stationary phase by the PolX DNA polymerase.
Selection of
dinB
Alleles Suppressing Survival Loss upon
dinB
Overexpression in Escherichia coli
Authors: Benson Ryan W. , Cafarelli Tiziana M. , Rands Thomas J. , Lin Ida , Godoy Veronica G. 
Published: June 2014

ABSTRACT

Escherichia coli
strains overproducing DinB undergo survival loss; however, the mechanisms regulating this phenotype are poorly understood. Here we report a genetic selection revealing DinB residues essential to effect this loss-of-survival phenotype. The selection uses strains carrying both an antimutator allele of DNA polymerase III (Pol III) α-subunit (
dnaE915
) and either chromosomal or plasmid-borne
dinB
alleles. We hypothesized that
dnaE915
cells would respond to DinB overproduction differently from
dnaE

+

cells because the
dnaE915
allele is known to have an altered genetic interaction with
dinB

+

compared to its interaction with
dnaE

+

. Notably, we observe a loss-of-survival phenotype in
dnaE915
strains with either a chromosomal catalytically inactive
dinB
(
D103N
) allele or a low-copy-number plasmid-borne
dinB

+

upon DNA damage treatment. Furthermore, we find that the loss-of-survival phenotype occurs independently of DNA damage treatment in a
dnaE915
strain expressing the catalytically inactive
dinB
(
D103N
) allele from a low-copy-number plasmid. The selective pressure imposed resulted in suppressor mutations that eliminated growth defects. The
dinB
intragenic mutations examined were either base pair substitutions or those that we inferred to be loss of function (i.e., deletions and insertions). Further analyses of selected novel
dinB
alleles, generated by single-base-pair substitutions in the
dnaE915
strain, indicated that these no longer effect loss of survival upon overproduction in
dnaE

+

strains. These mutations are mapped to specific areas of DinB; this permits us to gain insights into the mechanisms underlying the DinB-mediated overproduction loss-of-survival phenotype.
A Model for the Evolution of Biological Specificity: a Cross-Reacting DNA-Binding Protein Causes Plasmid Incompatibility
Authors: Hyland Edel M. , Wallace Edward W. J. , Murray Andrew W. 
Published: June 2014

ABSTRACT

Few biological systems permit rigorous testing of how changes in DNA sequence give rise to adaptive phenotypes. In this study, we sought a simplified experimental system with a detailed understanding of the genotype-to-phenotype relationship that could be altered by environmental perturbations. We focused on plasmid fitness, i.e., the ability of plasmids to be stably maintained in a bacterial population, which is dictated by the plasmid's replication and segregation machinery. Although plasmid replication depends on host proteins, the type II plasmid partitioning (Par) machinery is entirely plasmid encoded and relies solely on three components:
parC
, a centromere-like DNA sequence, ParR, a DNA-binding protein that interacts with
parC
, and ParM, which forms actin-like filaments that push two plasmids away from each other at cell division. Interactions between the Par operons of two related plasmids can cause incompatibility and the reduced transmission of one or both plasmids. We have identified segregation-dependent plasmid incompatibility between the highly divergent Par operons of plasmids pB171 and pCP301. Genetic and biochemical studies revealed that the incompatibility is due to the functional promiscuity of the DNA-binding protein ParR
pB171
, which interacts with both
parC
DNA sequences to direct plasmid segregation, indicating that the lack of DNA binding specificity is detrimental to plasmid fitness in this environment. This study therefore successfully utilized plasmid segregation to dissect the molecular interactions between genotype, phenotype, and fitness.
Association of birth of girls with postnatal depression and exclusive breastfeeding: an observational study
Authors: Jain Akanksha , Tyagi Prashant , Kaur Prabhjeet , Puliyel Jacob , Sreenivas Vishnu 
Published: June 2014

Objectives and hypothesisTo examine the influence of gender of the baby on exclusive breastfeeding and incidence of postnatal depression (PND). We hypothesise that in a society with a male gender bias there may be more PND and less exclusive breastfeeding of the girl child.DesignProspective study.SettingThe study was conducted in an urban, tertiary hospital in Delhi.ParticipantsMothers delivering normally with their babies roomed-in.1537 eligible women participated in the study.Primary and secondary outcome measuresExclusive breastfeeding within the first 48 h of life and score on the Edinburgh Postnatal Depression Scale (EPDS) were recorded.Results3466 babies were born in the hospital. There were 792 girls for every 1000 boys. Among primiparous women, the sex ratio was 901 girls per 1000 boys. For second babies, the sex ratio was 737:1000. If the first child was a girl the birth ratio fell to 632. 1026 mothers were exclusively breastfeeding. Exclusive breastfeeding of boys was significantly higher (70.8% vs 61.5%, p<0.001). The EPDS score was significantly higher with the birth of girls (EPDS 6.0±3.39 vs 5.4±2.87, p<0.01). Women with an EPDS score >11 were less likely to exclusively breastfeed (p<0.01).ConclusionsThe results point to a pro-male gender bias evidenced by a low sex ratio at birth, higher EPDS score in mothers of girls and less breastfeeding of female children.
A multidisciplinary, multifaceted improvement initiative to eliminate mislabelled laboratory specimens at a large tertiary care hospital
Authors: Seferian Edward G , Jamal Salima , Clark Kathleen , Cirricione Mary , Burnes-Bolton Linda , Amin Mahul , Romanoff Neil , Klapper Ellen 
Published: June 2014

ObjectivesTo sustainably reduce the rate of mislabelled laboratory specimens through implementation of a series of interventions as led and coordinated by a multidisciplinary performance improvement team.MethodsThe quality improvement project was performed at Cedars-Sinai Medical Center in Los Angeles, an academic care tertiary care hospital. Phlebotomy services are provided by unit-based nursing and dedicated laboratory-based phlebotomists. Baseline mislabelled specimen rate was obtained for a 6-month period prior to the first improvement intervention. Included in the rate of mislabelled specimens were inpatient blood and body fluid specimens. Anatomic pathology and cytological specimens and outpatient specimens were excluded. Mislabelled specimens were identified preanalytically, analytically or postanalytically. A specimen was considered mislabelled under the following circumstances: (1) specimen/requisition mismatch; (2) incorrect patient identifiers and (3) unlabelled specimen. Specimen mislabels were identified and validated monthly by a multidisciplinary team composed of personnel from nursing, laboratory and performance improvement. Performance improvement initiatives were implemented over a 2-year period with control charts used to assess improvement over time.ResultsThe rate of mislabelled specimens varied by clinical area and decreased significantly over a 24-month time period during the initiative from 4.39 per 10 000 specimens to 1.97 per 10 000 specimens. All clinical areas achieved a significant decrease in the rate of mislabelled specimens except for the operating room and labour and delivery.ConclusionsA multidisciplinary unit specific approach using performance improvement methodologies focusing on human factors can reliably and sustainably reduce the rate of mislabelled laboratory specimens in a large tertiary care hospital.
Value of repeat biopsy in lupus nephritis flares
Authors: Greloni G , Scolnik M , Marin J , Lancioni E , Quiroz C , Zacariaz J , De la Iglesia Niveyro P , Christiansen S , Pierangelo M A , Varela C F , Rosa-Diez G J , Catoggio L J , Soriano E R 
Published: June 2014

ObjectivesRenal flares are common in lupus nephritis (LN), and class switch is thought to be characteristic. There is no agreement on indications for performing a repeat renal biopsy. Our objective was to retrospectively review patients who had more than one renal biopsy performed on clinical indications, and analyse clinical, pathological and treatment changes after successive biopsies.MethodsForty-five patients with LN and one or more repeat renal biopsies were included, with a total of 116 biopsies.ResultsOf the 71 repeat biopsies, pathological transition occurred in 39 (54.9%). When having a previous biopsy with a proliferative lesion, class switch occurred in 55.6%, with 24.4% evolving into non-proliferative classes. When previous biopsy was class V, transition to other classes occurred in 58.3% and changes were all into proliferative classes. Conversion from one pure proliferative form to another (class III to class IV or vice versa) happened in 11.3% of the rebiopsies, with 62 rebiopsies (87.3%) leading to a change in the treatment regimen.ConclusionsHistological transformations were common, and they occurred when the previous biopsy had non-proliferative lesions as well as when lesions were proliferative. Treatments were modified after repeat renal biopsy in the majority of patients. In this experience, kidney repeat biopsies were useful in guiding treatment of LN flares.
Vitamin D deficiency is common and associated with increased C-reactive protein in children and young adults with lupus: an Atherosclerosis Prevention in Pediatric Lupus Erythematosus substudy
Authors: Robinson Angela Byun , Tangpricha Vin , Yow Eric , Gurion Reut , McComsey Grace A , Schanberg Laura E 
Published: June 2014

ObjectiveEpidemiological associations suggest vitamin D may play a role in inflammation and atherosclerosis. Using frozen serum and data from the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial, we assessed associations between 25-hydroxyvitamin D [25(OH)D] and measures of systemic lupus erythematosus (SLE) disease activity and cardiovascular risk.MethodsBaseline APPLE serum samples were used to measure 25(OH)D levels. Logistic regression models for vitamin D deficiency [25(OH)D levels <20 ng/mL] were constructed using baseline variables collected as part of the trial, including race, season, latitude, disease duration, disease activity, high-sensitivity C-reactive protein (hsCRP), proteinuria, fasting lipids and carotid intima medial thickness (CIMT).ResultsSamples were available from 201 of 221 APPLE subjects; 61/201 (30%) had vitamin D deficiency at baseline. In univariable analysis, baseline vitamin D deficiency was associated with season (p<0.01), minority status (p<0.01), body mass index (p=0.04), duration of SLE (p<0.01), SLICC damage index (p=0.04), hsCRP (p<0.01), mean–max CIMT (p=0.01), LDL-cholesterol (p=0.03) and timed urine protein (p=0.03). In multivariable modelling, vitamin D deficiency was associated with age, latitude, season, minority status, proteinuria and hsCRP.ConclusionsVitamin D deficiency is common in paediatric lupus and is independently associated with elevated hsCRP, a marker of inflammation that predicts cardiovascular disease risk. Although association is not proof of causation, this association is novel in the paediatric SLE population and suggests that vitamin D deficiency may contribute to heightened inflammation and cardiovascular risk in this population.Trial register numberNCT00065806.
Ultrasonographic features of the liver with cystic echinococcosis in sheep
Authors: Hussein Hussein Awad , Elrashidy Mohammed 
Published: June 2014

ObjectivesThe present study was designed to gain information about the ultrasonographic features of livers with cystic echinococcosis, as well as to evaluate the use of ultrasonography for diagnosis of such disease in sheep.DesignThis was a retrospective study during the period April 2011 to March 2013.ParticipantsA total of 22 Baladi sheep (aged three to six years) were included in this study. Based on clear hepatic ultrasonographic findings, all animals were classified into two groups: those with hepatic cysts (n=9) and without liver cysts (healthy liver, n=13).ResultsBiochemically, serum concentrations of γ‐glutamyl transferase, aspartate aminotransferase, total bilirubin and globulins were significantly increased (P<0.01), while albumin was lowered (P<0.01) in sheep with cystic livers. Ultrasonographic findings of diseased sheep livers revealed the presence of rounded, anechoic and unilocular hydatid cysts with ellipse circumference ranged from 6–10 cm. The borders of cysts were mostly well defined. The interior of cysts contained echogenic particulate materials, septations, or fine echoes. At the 10th intercostal space, the ventral margin, size, thickness and angle of livers were higher (P<0.01), while the diameter of portal vein was lower (P<0.01) in sheep with liver cysts than control ones. Furthermore, at the 9th intercostal space, the circumference of the gall bladder was decreased in sheep with hepatic cysts (P<0.01). The sensitivity, specificity, and positive and negative predictive values of ultrasonography for diagnosis of hepatic hydatid cysts were 80 per cent and 100 per cent, and 100 per cent and 83 per cent, respectively.ConclusionsCystic echinococcosis is associated with a number of anatomical alterations in the liver tissues that can be easily recognised by ultrasound. Furthermore, ultrasonography alone or in combination with analysis of biochemical parameters reflecting liver function could be helpful for diagnosis of hepatic hydatid cysts in sheep.
Alterations in sclerostin protein in lesions of equine osteochondrosis
Authors: Power Jonathon , Hernandez Paula , Wardale John , Henson Frances M. D. 
Published: June 2014

Osteochondrosis (OC) is a common and clinically important joint disease that occurs in many species, including humans, pigs, chickens and horses. It has been described as a focal failure of endochondral ossification (EO), but no cellular/molecular mechanisms are fully described that explain the cause of this condition. Recently a Wnt signalling inhibitor, sclerostin, has been described in osteoarthritic cartilage, where it has been proposed to protect damaged cartilage from degradation. Cartilage degradation is a key event in EO, thus, abnormalities of sclerostin in growth cartilage could, potentially, lead to a failure of EO and, thus, OC. The aim of this study was to describe the distribution of sclerostin protein in normal and OC growth cartilage.Immunohistochemistry (IHC) was used to localise sclerostin protein in normal and OC growth cartilage. Growth cartilage was harvested from the distal femur of horses aged between 6 and 18 months. Cartilage was classified as normal or having lesions consistent with a diagnosis of early OC. IHC was used to identify sclerostin protein in cartilage sections. Sclerostin protein distribution was semiquantified using a grading system and shown to be upregulated throughout all three zones of cartilage in lesions of OC (IHC score 8.1 compared to IHC score of 0.88). These results indicate that sclerostin may be contributing to the development of OC lesions by inhibiting extracellular matrix remodelling or may reflect the response of damaged cartilage. Clearly, further work is required to fully characterise this observation but, with antisclerostin antibodies used to treat human osteoporosis, the possibility of development of a systemic treatment of OC remains a potential goal.
Robust Polylines Tracing for N-Symmetry Direction Field on Triangulated Surfaces
Authors: Ray Nicolas , Sokolov Dmitry 
Published: June 2014

We are proposing an algorithm for tracing polylines that are oriented by a direction field defined on a triangle mesh. The challenge is to ensure that two such polylines cannot cross or merge. This property is fundamental for mesh segmentation and is impossible to enforce with existing algorithms.
The core of our contribution is to determine how polylines cross each triangle. Our solution is inspired by EdgeMaps where each triangle boundary is decomposed into inflow and outflow intervals such that each inflow interval is mapped onto an outflow interval. To cross a triangle, we find the inflow interval that contains the entry point, and link it to the corresponding outflow interval, with the same barycentric coordinate. To ensure that polylines cannot merge or cross, we introduce a new direction field representation, we resolve the inflow/outflow interval pairing with a guaranteed combinatorial algorithm, and propagate the barycentric positions with arbitrary precision number representation. Using these techniques, two streamlines crossing the same triangle cannot merge or cross, but only locally overlap when all streamline extremities are located on the same edge.
Cross-free and merge-free polylines can be traced on the mesh by iteratively crossing triangles. Vector field singularities and polyline/vertex crossing are characterized and consistently handled.
Loss of miR125a Expression in a Model of K-ras–Dependent Pulmonary Premalignancy
Authors: Liclican Elvira L. , Walser Tonya C. , Hazra Saswati , Krysan Kostyantyn , Park Stacy J. , Pagano Paul C. , Gardner Brian K. , Larsen Jill E. , Minna John D. , Dubinett Steven M. 
Published: June 2014

Abstract
Understanding the molecular pathogenesis of lung cancer is necessary to identify biomarkers/targets specific to individual airway molecular profiles and to identify options for targeted chemoprevention. Herein, we identify mechanisms by which loss of microRNA (miRNA)125a-3p (miR125a) contributes to the malignant potential of human bronchial epithelial cells (HBEC) harboring an activating point mutation of the K-ras proto-oncogene (HBEC K-ras). Among other miRNAs, we identified significant miR125a loss in HBEC K-ras lines and determined that miR125a is regulated by the PEA3 transcription factor. PEA3 is upregulated in HBEC K-ras cells, and genetic knockdown of PEA3 restores miR125a expression. From a panel of inflammatory/angiogenic factors, we identified increased CXCL1 and vascular endothelial growth factor (VEGF) production by HBEC K-ras cells and determined that miR125a overexpression significantly reduces K-ras–mediated production of these tumorigenic factors. miR125a overexpression also abrogates increased proliferation of HBEC K-ras cells and suppresses anchorage-independent growth (AIG) of HBEC K-ras/P53 cells, the latter of which is CXCL1-dependent. Finally, pioglitazone increases levels of miR125a in HBEC K-ras cells via PEA3 downregulation. In addition, pioglitazone and miR125a overexpression elicit similar phenotypic responses, including suppression of both proliferation and VEGF production. Our findings implicate miR125a loss in lung carcinogenesis and lay the groundwork for future studies to determine whether miR125a is a possible biomarker for lung carcinogenesis and/or a chemoprevention target. Moreover, our studies illustrate that pharmacologic augmentation of miR125a in K-ras–mutated pulmonary epithelium effectively abrogates several deleterious downstream events associated with the mutation. Cancer Prev Res; 7(8); 845–55. ©2014 AACR.
Robust Seasonality of Arctic Warming Processes in Two Different Versions of the MIROC GCM
Authors: Yoshimori Masakazu , Abe-Ouchi Ayako , Watanabe Masahiro , Oka Akira , Ogura Tomoo 
Published: June 2014

Abstract
It is one of the most robust projected responses of climate models to the increase of atmospheric CO2 concentration that the Arctic experiences a rapid warming with a magnitude larger than the rest of the world. While many processes are proposed as important, the relative contribution of individual processes to the Arctic warming is not often investigated systematically. Feedbacks are quantified in two different versions of an atmosphere–ocean GCM under idealized transient experiments based on an energy balance analysis that extends from the surface to the top of the atmosphere. The emphasis is placed on the largest warming from late autumn to early winter (October–December) and the difference from other seasons. It is confirmed that dominating processes vary with season. In autumn, the largest contribution to the Arctic surface warming is made by a reduction of ocean heat storage and cloud radiative feedback. In the annual mean, on the other hand, it is the albedo feedback that contributes the most, with increasing ocean heat uptake to the deeper layers working as a negative feedback. While the qualitative results are robust between the two models, they differ quantitatively, indicating the need for further constraint on each process. Ocean heat uptake, lower tropospheric stability, and low-level cloud response probably require special attention.
On the Representation of High-Latitude Boundary Layer Mixed-Phase Cloud in the ECMWF Global Model
Authors: Forbes Richard M. , Ahlgrimm Maike 
Published: June 2014

AbstractSupercooled liquid water (SLW) layers in boundary layer clouds are abundantly observed in the atmosphere at high latitudes, but remain a challenge to represent in numerical weather prediction (NWP) and climate models. Unresolved processes such as small-scale turbulence and mixed-phase microphysics act to maintain the liquid layer at cloud top, directly affecting cloud radiative properties and prolonging cloud lifetimes. This paper describes the representation of supercooled liquid water in boundary layer clouds in the European Centre for Medium-Range Weather Forecasts (ECMWF) global NWP model and in particular the change from a diagnostic temperature-dependent mixed phase to a prognostic representation with separate cloud liquid and ice variables. Data from the Atmospheric Radiation Measurement site in Alaska and from the CloudSat/Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) satellite missions are used to evaluate the model parameterizations. The prognostic scheme shows a more realistic cloud structure, with an SLW layer at cloud top and ice falling out below. However, because of the limited vertical and horizontal resolution and uncertainties in the parameterization of physical processes near cloud top, the change leads to an overall reduction in SLW water with a detrimental impact on shortwave and longwave radiative fluxes, and increased 2-m temperature errors over land. A reduction in the ice deposition rate at cloud top significantly improves the SLW occurrence and radiative impacts, and highlights the need for improved understanding and parameterization of physical processes for mixed-phase cloud in large-scale models.