bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic deletion of CNGB3 is identical by descent in multiple canine breeds and causes achromatopsia
Authors: Yeh Connie Y , Goldstein Orly , Kukekova Anna V , Holley Debbie , Knollinger Amy M , Huson Heather J , Pearce-Kelling Susan E , Acland Gregory M , Komáromy András M 
Published: April 2013

Abstract

Background
Achromatopsia is an autosomal recessive disease characterized by the loss of cone photoreceptor function that results in day-blindness, total colorblindness, and decreased central visual acuity. The most common causes for the disease are mutations in the CNGB3 gene, coding for the beta subunit of the cyclic nucleotide-gated channels in cones. CNGB3-achromatopsia, or cone degeneration (cd), is also known to occur in two canine breeds, the Alaskan malamute (AM) and the German shorthaired pointer.

Results
Here we report an in-depth characterization of the achromatopsia phenotype in a new canine breed, the miniature Australian shepherd (MAS). Genotyping revealed that the dog was homozygous for a complete genomic deletion of the CNGB3 gene, as has been previously observed in the AM. Identical breakpoints on chromosome 29 were identified in both the affected AM and MAS with a resulting deletion of 404,820 bp. Pooled DNA samples of unrelated purebred Australian shepherd, MAS, Siberian husky, Samoyed and Alaskan sled dogs were screened for the presence of the affected allele; one Siberian husky and three Alaskan sled dogs were identified as carriers. The affected chromosomes from the AM, MAS, and Siberian husky were genotyped for 147 SNPs in a 3.93 Mb interval within the cd locus. An identical shared affected haplotype, 0.5 Mb long, was observed in all three breeds and defined the minimal linkage disequilibrium (LD) across breeds. This supports the idea that the mutated allele was identical by descent (IBD).

Conclusion
We report the occurrence of CNGB3-achromatopsia in a new canine breed, the MAS. The CNGB3-deletion allele previously described in the AM was also observed in a homozygous state in the affected MAS, as well as in a heterozygous carrier state in a Siberian husky and Alaskan sled dogs. All affected alleles were shown to be IBD, strongly suggesting an affected founder effect. Since the MAS is not known to be genetically related to the AM, other breeds may potentially carry the same cd-allele and be affected by achromatopsia.
The association between serious upper gastrointestinal bleeding and incident bisphosphonate use: a population-based nested cohort study
Authors: Knopp-Sihota Jennifer A , Cummings Greta G , Homik Joanne , Voaklander Don 
Published: April 2013

Abstract

Background
Oral bisphosphonates are commonly used to prevent / treat osteoporosis. However, bisphosphonate treatment is not without risk and serious adverse effects, including upper gastrointestinal bleeding (UGIB) have been described. We sought to determine if new users of bisphosphonate drugs were more likely to suffer a serious UGIB within 120 days of drug initiation.

Methods
This was a population-based nested cohort study utilizing administrative healthcare data in British Columbia, Canada. Community based individuals ≥ 65 years with a new prescription for a bisphosphonate between 1991 and 2007 were included. A multivariate logistic regression model was used to examine the relationship between older age and the development of a serious UGIB within 120 days of new exposure to oral bisphosphonate drugs.

Results
Within the exposure cohort (n = 26,223), 117 individuals had suffered a serious UGIB within 120 days of incident bisphosphonate use. Cases tended to be > 80 years old, and were significantly more likely to have had a past history of gastric ulcer disease, a remote history of serious UGIB, and had been dispensed proton pump inhibitor (PPI) medications (p < 0.001 for all comparisons). After adjustment for confounding covariates, those > 80 years were more than twice as likely to suffer a UGIB when compared to those ≤ 80 years (adjusted OR = 2.03; 95% CI 1.40–2.94). A past history of serious UGIB was the strongest predictor of UGIB within 120 days of incident bisphosphonate use (adjusted OR = 2.28; 95% CI = 1.29–4.03) followed by PPI use (adjusted OR = 2.04; 95% CI = 1.35–3.07). Males were 70% more likely to suffer an UGIB compared to females (adjusted OR = 1.69; 95% CI = 1.05–2.72).

Conclusions
Upper GIB is a rare, but serious, side effect of bisphosphonate therapy more often afflicting older individuals. At the same time, concern about potential rare adverse events should not discourage clinicians from prescribing bisphosphonate drugs, particularly in older patients who have already sustained a fragility fracture. Clinicians must remain cognizant of potential adverse events associated with bisphosphonate use and should routinely ask about pre-existing GI disorders and concurrent medication history prior to prescribing these drugs.
Quantitative threefold allele-specific PCR (QuanTAS-PCR) for highly sensitive JAK2V617F mutant allele detection
Authors: Zapparoli Giada V , Jorissen Robert N , Hewitt Chelsee A , McBean Michelle , Westerman David A , Dobrovic Alexander 
Published: April 2013

Abstract

Background
The JAK2 V617F mutation is the most frequent somatic change in myeloproliferative neoplasms, making it an important tumour-specific marker for diagnostic purposes and for the detection of minimal residual disease. Sensitive quantitative assays are required for both applications, particularly for the monitoring of minimal residual disease, which requires not only high sensitivity but also very high specificity.

Methods
We developed a highly sensitive probe-free quantitative mutant-allele detection method, Quantitative Threefold Allele-Specific PCR (QuanTAS-PCR), that is performed in a closed-tube system, thus eliminating the manipulation of PCR products. QuantTAS-PCR uses a threefold approach to ensure allele-specific amplification of the mutant sequence: (i) a mutant allele-specific primer, (ii) a 3′dideoxy blocker to suppress false-positive amplification from the wild-type template and (iii) a PCR specificity enhancer, also to suppress false-positive amplification from the wild-type template. Mutant alleles were quantified relative to exon 9 of JAK2.

Results
We showed that the addition of the 3′dideoxy blocker suppressed but did not eliminate false-positive amplification from the wild-type template. However, the addition of the PCR specificity enhancer near eliminated false-positive amplification from the wild-type allele. Further discrimination between true and false positives was enabled by using the quantification cycle (Cq) value of a single mutant template as a cut-off point, thus enabling robust distinction between true and false positives. As 10,000 JAK2 templates were used per replicate, the assay had a sensitivity of 1/10-4 per replicate. Greater sensitivity could be reached by increasing the number of replicates analysed. Variation in replicates when low mutant-allele templates were present necessitated the use of a statistics-based approach to estimate the load of mutant JAK2 copies. QuanTAS-PCR showed comparable quantitative results when validated against a commercial assay.

Conclusions
QuanTAS-PCR is a simple, cost-efficient, closed-tube method for JAK2 V617F mutation quantification that can detect very low levels of the mutant allele, thus enabling analysis of minimal residual disease. The approach can be extended to the detection of other recurrent single nucleotide somatic changes in cancer.
Discrimination in relation to parenthood reported by community psychiatric service users in the UK: a framework analysis
Authors: Jeffery Debra , Clement Sarah , Corker Elizabeth , Howard Louise M , Murray Joanna , Thornicroft Graham 
Published: April 2013

Abstract

Background
Experienced discrimination refers to an individual’s perception that they have been treated unfairly due to an attribute and is an important recent focus within stigma research. A significant proportion of mental health service users report experiencing mental illness-based discrimination in relation to parenthood. Existing studies in this area have not gone beyond prevalence, therefore little is known about the nature of experienced discrimination in relation to parenthood, and how is it constituted. This study aims to generate a typology of community psychiatric service users’ reports of mental illness-based discrimination in relation to becoming or being a parent. A secondary aim is to assess the prevalence of these types of experienced discrimination.

Methods
In a telephone survey 2026 community psychiatric service users in ten UK Mental Health service provider organisations (Trusts) were asked about discrimination experienced in the previous 12 months using the Discrimination and Stigma Scale (DISC). The sample were asked if, due to their mental health problem, they had been treated unfairly in starting a family, or in their role as a parent, and gave examples of this. Prevalence is reported and the examples of experienced discrimination in relation to parenthood were analysed using the framework method of qualitative analysis.

Results
Three hundred and four participants (73% female) reported experienced discrimination, with prevalences of 22.5% and 28.3% for starting a family and for the parenting role respectively. Participants gave 89 examples of discrimination about starting a family and 228 about parenting, and these occurred in social and professional contexts. Ten themes were identified. These related to being seen as an unfit parent; people not being understanding; being stopped from having children; not being allowed to see their children; not getting the support needed; children being affected; children avoiding their parents; children’s difficulties being blamed on the parent’s mental health problem; not being listened to; and being undermined as a parent.

Conclusions
This research highlights the need for: greater support for parents with mental illness, those wishing to have children, and those who lose access or custody; services to better meet the needs of children with a mentally ill parent; training about discrimination for professionals; and parenting issues to be included in anti-stigma programmes.
Multicore-based 3D-DWT video encoder
Authors: Galiano Vicente , López-Granado Otoniel , Malumbres Manuel P. , Migallón Hector 
Published: April 2013

Abstract
Three-dimensional wavelet transform (3D-DWT) encoders are good candidates for applications like professional video editing, video surveillance, multi-spectral satellite imaging, etc. where a frame must be reconstructed as quickly as possible. In this paper, we present a new 3D-DWT video encoder based on a fast run-length coding engine. Furthermore, we present several multicore optimizations to speed-up the 3D-DWT computation. An exhaustive evaluation of the proposed encoder (3D-GOP-RL) has been performed, and we have compared the evaluation results with other video encoders in terms of rate/distortion (R/D), coding/decoding delay, and memory consumption. Results show that the proposed encoder obtains good R/D results for high-resolution video sequences with nearly in-place computation using only the memory needed to store a group of pictures. After applying the multicore optimization strategies over the 3D DWT, the proposed encoder is able to compress a full high-definition video sequence in real-time.
Mathematical models for the Notch and Wnt signaling pathways and the crosstalk between them during somitogenesis
Authors: Wang Hong-yan , Huang Yan-xin , Qi Yun-feng , Zhang Yu , Bao Yong-li , Sun Lu-guo , Zheng Li-hua , Zhang Yu-wei , Ma Zhi-qiang , Li Yu-xin 
Published: April 2013

Abstract

Background
Somitogenesis is a fundamental characteristic feature of development in various animal embryos. Molecular evidence has proved that the Notch and Wnt pathways play important roles in regulating the process of somitogenesis and there is crosstalk between these two pathways. However, it is difficult to investigate the detailed mechanism of these two pathways and their interactions in somitogenesis through biological experiments. In recent years some mathematical models have been proposed for the purpose of studying the dynamics of the Notch and Wnt pathways in somitogenesis. Unfortunately, only a few of these models have explored the interactions between them.

Results
In this study, we have proposed three mathematical models for the Notch signalling pathway alone, the Wnt signalling pathway alone, and the interactions between them. These models can simulate the dynamics of the Notch and Wnt pathways in somitogenesis, and are capable of reproducing the observations derived from wet experiments. They were used to investigate the molecular mechanisms of the Notch and Wnt pathways and their crosstalk in somitogenesis through the model simulations.

Conclusions
Three mathematical models are proposed for the Notch and Wnt pathways and their interaction during somitogenesis. The simulations demonstrate that the extracellular Notch and Wnt signals are essential for the oscillating expressions of both Notch and Wnt target genes. Moreover, the internal negative feedback loops and the three levels of crosstalk between these pathways play important but distinct roles in maintaining the system oscillation. In addition, the results of the parameter sensitivity analysis of the models indicate that the Notch pathway is more sensitive to perturbation in somitogenesis.
A common mechanism of clinical HIV-1 resistance to the CCR5 antagonist maraviroc despite divergent resistance levels and lack of common gp120 resistance mutations
Authors: Roche Michael , Salimi Hamid , Duncan Renee , Wilkinson Brendan L , Chikere Kelechi , Moore Miranda S , Webb Nicholas E , Zappi Helena , Sterjovski Jasminka , Flynn Jacqueline K , Ellett Anne , Gray Lachlan R , Lee Benhur , Jubb Becky , Westby Mike , Ramsland Paul A , Lewin Sharon R , Payne Richard J , Churchill Melissa J , Gorry Paul R 
Published: April 2013

Abstract

Background
The CCR5 antagonist maraviroc (MVC) inhibits human immunodeficiency virus type 1 (HIV-1) entry by altering the CCR5 extracellular loops (ECL), such that the gp120 envelope glycoproteins (Env) no longer recognize CCR5. The mechanisms of HIV-1 resistance to MVC, the only CCR5 antagonist licensed for clinical use are poorly understood, with insights into MVC resistance almost exclusively limited to knowledge obtained from in vitro studies or from studies of resistance to other CCR5 antagonists. To more precisely understand mechanisms of resistance to MVC in vivo, we characterized Envs isolated from 2 subjects who experienced virologic failure on MVC.

Results
Envs were cloned from subjects 17 and 24 before commencement of MVC (17-Sens and 24-Sens) and after virologic failure (17-Res and 24-Res). The Envs cloned during virologic failure showed broad divergence in resistance levels, with 17-Res Env exhibiting a relatively high maximal percent inhibition (MPI) of ~90% in NP2-CD4/CCR5 cells and peripheral blood mononuclear cells (PBMC), and 24-Res Env exhibiting a very low MPI of ~0 to 12% in both cell types, indicating relatively “weak” and “strong” resistance, respectively. Resistance mutations were strain-specific and mapped to the gp120 V3 loop. Affinity profiling by the 293-Affinofile assay and mathematical modeling using VERSA (Viral Entry Receptor Sensitivity Analysis) metrics revealed that 17-Res and 24-Res Envs engaged MVC-bound CCR5 inefficiently or very efficiently, respectively. Despite highly divergent phenotypes, and a lack of common gp120 resistance mutations, both resistant Envs exhibited an almost superimposable pattern of dramatically increased reliance on sulfated tyrosine residues in the CCR5 N-terminus, and on histidine residues in the CCR5 ECLs. This altered mechanism of CCR5 engagement rendered both the resistant Envs susceptible to neutralization by a sulfated peptide fragment of the CCR5 N-terminus.

Conclusions
Clinical resistance to MVC may involve divergent Env phenotypes and different genetic alterations in gp120, but the molecular mechanism of resistance of the Envs studied here appears to be related. The increased reliance on sulfated CCR5 N-terminus residues suggests a new avenue to block HIV-1 entry by CCR5 N-terminus sulfopeptidomimetic drugs.
LocARNAscan: Incorporating thermodynamic stability in sequence and structure-based RNA homology search
Authors: Will Sebastian , Siebauer Michael F , Heyne Steffen , Engelhardt Jan , Stadler Peter F , Reiche Kristin , Backofen Rolf 
Published: April 2013

Abstract

Background
The search for distant homologs has become an import issue in genome annotation. A particular difficulty is posed by divergent homologs that have lost recognizable sequence similarity. This same problem also arises in the recognition of novel members of large classes of RNAs such as snoRNAs or microRNAs that consist of families unrelated by common descent. Current homology search tools for structured RNAs are either based entirely on sequence similarity (such as or ) or combine sequence and secondary structure. The most prominent example of the latter class of tools is . Alternatives are descriptor-based methods. In most practical applications published to-date, however, the information contained in covariance models or manually prescribed search patterns is dominated by sequence information. Here we ask two related questions: (1) Is secondary structure alone informative for homology search and the detection of novel members of RNA classes? (2) To what extent is the thermodynamic propensity of the target sequence to fold into the correct secondary structure helpful for this task?

Results
Sequence-structure alignment can be used as an alternative search strategy. In this scenario, the query consists of a base pairing probability matrix, which can be derived either from a single sequence or from a multiple alignment representing a set of known representatives. Sequence information can be optionally added to the query. The target sequence is pre-processed to obtain local base pairing probabilities. As a search engine we devised a semi-global scanning variant of ’s algorithm for sequence-structure alignment. The tool is optimized for speed and low memory consumption. In benchmarking experiments on artificial data we observe that the inclusion of thermodynamic stability is helpful, albeit only in a regime of extremely low sequence information in the query. We observe, furthermore, that the sensitivity is bounded in particular by the limited accuracy of the predicted local structures of the target sequence.

Conclusions
Although we demonstrate that a purely structure-based homology search is feasible in principle, it is unlikely to outperform tools such as in most application scenarios, where a substantial amount of sequence information is typically available. The approach will profit, however, from high throughput methods to determine RNA secondary structure. In transcriptome-wide applications, such methods will provide accurate structure annotations on the target side.

Availability
Source code of the free software 1.0 and supplementary data are available athttp://www.bioinf.uni-leipzig.de/Software/LocARNAscan.
Intra-partum fever and cerebral palsy in Khartoum, Sudan
Authors: Abdullahi Hala , Satti Mohamed , Rayis Duria A , Imam Abdulmutalab M , Adam Ishag 
Published: April 2013

Abstract

Background
Cerebral palsy (CP) is a major cause of childhood disability. There are various maternal and neonatal predictors associated with the development of CP, and they are variable across different populations. This case–control study was designed to investigate maternal and neonatal predictors of CP at Khartoum pediatric neurology clinics. Data (maternal sociodemographic characteristics and neonatal expected predictors) were collected from mothers of children with CP and healthy controls using questionnaires.

Results
One hundred and eleven cases of CP and 222 controls were included. Spastic CP was the most common type (69.4%). In logistic regression, maternal age, parity, birth weight, and sex were not associated with CP. However, maternal fever (OR = 8.4, CI = 2.3–30.5; P = 0.001), previous neonatal death (OR = 5.4, CI = 1.8–16.2; P = 0.003), and poor sucking (OR = 30.5, CI = 10.0–93.1; P < 0.001) were predictors of CP.

Conclusions
Fever during labor is a significant risk factor for developing CP in children. Further efforts are required for labor management to prevent CP in this setting.
Polymeric immunoglobulin receptor traffics through two distinct apically targeted pathways in primary lacrimal gland acinar cells
Authors: Xu Shi , Ma Linlin , Evans Eunbyul , Okamoto Curtis T. , Hamm-Alvarez Sarah F. 
Published: April 2013

SummaryThe polymeric immunoglobulin receptor (pIgR) mediates transcytosis of dimeric immunoglobulin A (dIgA) and its release into mucosal secretions. The present study reveals the complexity of the trafficking of pIgR to the apical plasma membrane in epithelial cells with exocrine secretory functions; in rabbit lacrimal gland acinar cells (LGACs), trafficking of pIgR involves both the transcytotic pathway and one arm of the regulated secretory pathway. By specifically tracking pIgR endocytosed from the basolateral membrane, we show here that the Rab11a-regulated transcytotic pathway mediates the basal-to-apical transport of pIgR, and that pIgR sorted into the transcytotic pathway does not access the regulated secretory pathway. However, previous work in LGACs expanded in the present study has shown that some pIgR is localized to Rab3D-enriched mature secretory vesicles (SVs). Myosin Vb and myosin Vc motors modulate release of proteins from the Rab11a-regulated transcytotic pathway and the Rab3D-enriched secretory pathway in LGACs, respectively. Confocal fluorescence microscopy and biochemical assays showed that inhibition of myosin Vb and myosin Vc activity by overexpression of their dominant-negative mutants each significantly but differentially impaired aspects of apically targeted pIgR trafficking and secretory component release, suggesting that these motors function to regulate pIgR trafficking in both the transcytotic and exocytotic pathways. Intriguingly, a second mature SV population enriched in Rab27b was devoid of pIgR cargo, suggesting the specialization of Rab3D-enriched mature SVs to carry a particular subset of cargo proteins from the trans-Golgi network to the apical plasma membrane.