bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis on multi-domain cooperation for predicting protein-protein interactions
Authors: Wang Rui-Sheng , Wang Yong , Wu Ling-Yun , Zhang Xiang-Sun , Chen Luonan 
Published: October 2007

Abstract

Background
Domains are the basic functional units of proteins. It is believed that protein-protein interactions are realized through domain interactions. Revealing multi-domain cooperation can provide deep insights into the essential mechanism of protein-protein interactions at the domain level and be further exploited to improve the accuracy of protein interaction prediction.

Results
In this paper, we aim to identify cooperative domains for protein interactions by extending two-domain interactions to multi-domain interactions. Based on the high-throughput experimental data from multiple organisms with different reliabilities, the interactions of domains were inferred by a Linear Programming algorithm with Multi-domain pairs (LPM) and an Association Probabilistic Method with Multi-domain pairs (APMM). Experimental results demonstrate that our approach not only can find cooperative domains effectively but also has a higher accuracy for predicting protein interaction than the existing methods. Cooperative domains, including strongly cooperative domains and superdomains, were detected from major interaction databases MIPS and DIP, and many of them were verified by physical interactions from the crystal structures of protein complexes in PDB which provide intuitive evidences for such cooperation. Comparison experiments in terms of protein/domain interaction prediction justified the benefit of considering multi-domain cooperation.

Conclusion
From the computational viewpoint, this paper gives a general framework to predict protein interactions in a more accurate manner by considering the information of both multi-domains and multiple organisms, which can also be applied to identify cooperative domains, to reconstruct large complexes and further to annotate functions of domains. Supplementary information and software are provided in http://intelligent.eic.osaka-sandai.ac.jp/chenen/MDCinfer.htm and http://zhangroup.aporc.org/bioinfo/MDCinfer.
Improved human disease candidate gene prioritization using mouse phenotype
Authors: Chen Jing , Xu Huan , Aronow Bruce J , Jegga Anil G 
Published: October 2007

Abstract

Background
The majority of common diseases are multi-factorial and modified by genetically and mechanistically complex polygenic interactions and environmental factors. High-throughput genome-wide studies like linkage analysis and gene expression profiling, tend to be most useful for classification and characterization but do not provide sufficient information to identify or prioritize specific disease causal genes.

Results
Extending on an earlier hypothesis that the majority of genes that impact or cause disease share membership in any of several functional relationships we, for the first time, show the utility of mouse phenotype data in human disease gene prioritization. We study the effect of different data integration methods, and based on the validation studies, we show that our approach, ToppGene http://toppgene.cchmc.org, outperforms two of the existing candidate gene prioritization methods, SUSPECTS and ENDEAVOUR.

Conclusion
The incorporation of phenotype information for mouse orthologs of human genes greatly improves the human disease candidate gene analysis and prioritization.
Sequences conserved by selection across mouse and human malaria species
Authors: Imamura Hideo , Persampieri Jason H , Chuang Jeffrey H 
Published: October 2007

Abstract

Background
Little is known, either experimentally or computationally, about the genomic sequence features that regulate malaria genes. A sequence conservation analysis of the malaria species P. falciparum, P. berghei, P. yoelii, and P. chabaudi could significantly advance knowledge of malaria gene regulation.

Results
We computationally identify intergenic sequences conserved beyond neutral expectations, using a conservation algorithm that accounts for the strong compositional biases in malaria genomes. We first quantify the composition-specific divergence at silent positions in coding sequence. Using this as a background, we examine gene 5' regions, identifying 610 blocks conserved far beyond neutral expectations across the three mouse malariae, and 81 blocks conserved as strongly across all four species (p < 10-6). Detailed analysis of these blocks indicates that only a minor fraction are likely to be previously unknown coding sequences. Analogous noncoding conserved blocks have been shown to regulate adjacent genes in other phylogenies, making the predicted blocks excellent candidates for novel regulatory functions. We also find three potential transcription factor binding motifs which exhibit strong conservation and overrepresentation among the rodent malariae.

Conclusion
A broader finding of our analysis is that less malaria intergenic sequence has been conserved by selection than in yeast or vertebrate genomes. This supports the hypothesis that transcriptional regulation is simpler in malaria than other eukaryotic species. We have built a public database containing all sequence alignments and functional predictions, and we expect this to be a valuable resource to the malaria research community.
Experimental optimization of probe length to increase the sequence specificity of high-density oligonucleotide microarrays
Authors: Suzuki Shingo , Ono Naoaki , Furusawa Chikara , Kashiwagi Akiko , Yomo Tetsuya 
Published: October 2007

Abstract

Background
High-density oligonucleotide arrays are widely used for analysis of genome-wide expression and genetic variation. Affymetrix GeneChips – common high-density oligonucleotide arrays – contain perfect match (PM) and mismatch (MM) probes generated by changing a single nucleotide of the PMs, to estimate cross-hybridization. However, a fraction of MM probes exhibit larger signal intensities than PMs, when the difference in the amount of target specific hybridization between PM and MM probes is smaller than the variance in the amount of cross-hybridization. Thus, pairs of PM and MM probes with greater specificity for single nucleotide mismatches are desirable for accurate analysis.

Results
To investigate the specificity for single nucleotide mismatches, we designed a custom array with probes of different length (14- to 25-mer) tethered to the surface of the array and all possible single nucleotide mismatches, and hybridized artificially synthesized 25-mer oligodeoxyribonucleotides as targets in bulk solution to avoid the effects of cross-hybridization. The results indicated the finite availability of target molecules as the probe length increases. Due to this effect, the sequence specificity of the longer probes decreases, and this was also confirmed even under the usual background conditions for transcriptome analysis.

Conclusion
Our study suggests that the optimal probe length for specificity is 19–21-mer. This conclusion will assist in improvement of microarray design for both transcriptome analysis and mutation screening.
ADAM15 gene structure and differential alternative exon use in human tissues
Authors: Kleino Iivari , Ortiz Rebekka M , Huovila Ari-Pekka J 
Published: October 2007

Abstract

Background
ADAM15 is a metalloprotease-disintegrin implicated in ectodomain shedding and cell adhesion. Aberrant ADAM15 expression has been associated with human cancer and other disorders. We have previously shown that the alternative splicing of ADAM15 transcripts is mis-regulated in cancer cells. To gain a better understanding of ADAM15 regulation, its genomic organization and regulatory elements as well as the alternative exon use in human tissues were characterized.

Results
Human ADAM15, flanked by the FLJ32785/DCST1 and ephrin-A4 genes, spans 11.4 kb from the translation initiation codon to the polyadenylation signal, being the shortest multiple-exon ADAM gene. The gene contains 23 exons varying from 63 to 316 bp and 22 introns from 79 to 1283 bp. The gene appeared to have several transcription start sites and their location suggested the promoter location within a CpG island proximal to the translation start. Reporter expression experiments confirmed the location of functional GC-rich, TATAless and CAATless promoter, with the most critical transcription-supporting elements located -266 to -23 bp relative to the translation start. Normal human tissues showed different complex patterns of at least 13 different ADAM15 splice variants arising from the alternative use of the cytosolic-encoding exons 19, 20a/b, and 21a/b. The deduced ADAM15 protein isoforms have different combinations of cytosolic regulatory protein interaction motifs.

Conclusion
Characterization of human ADAM15 gene and identification of elements involved in the regulation of transcription and alternative splicing provide important clues for elucidation of physiological and pathological roles of ADAM15. The present results also show that the alternative exon use is a physiological post-transcriptional mechanism regulating ADAM15 expression in human tissues.
Prehospital score for acute disease: a community-based observational study in Japan
Authors: Toyoda Yasuhiro , Matsuo Yoshio , Tanaka Hiroyuki , Fujiwara Hidekazu , Takatorige Toshio , Iso Hiroyasu 
Published: October 2007

Abstract

Background
Ambulance usage in Japan has increased consistently because it is free under the national health insurance system. The introduction of refusal for ambulance transfer is being debated nationally. The purpose of the present study was to investigate the relationship between prehospital data and hospitalization outcome for acute disease patients, and to develop a simple prehospital evaluation tool using prehospital data for Japan's emergency medical service system.

Methods
The subjects were 9,160 consecutive acute disease patients aged ≥ 15 years who were transferred to hospital by Kishiwada City Fire Department ambulance between July 2004 and March 2006. The relationship between prehospital data (age, systolic blood pressure, pulse rate, respiration rate, level of consciousness, SpO2 level and ability to walk) and outcome (hospitalization or non-hospitalization) was analyzed using logistic regression models. The prehospital score component of each item of prehospital data was determined by beta coefficients. Eligible patients were scored retrospectively and the distribution of outcome was examined. For patients transported to the two main hospitals, outcome after hospitalization was also confirmed.

Results
A total of 8,330 (91%) patients were retrospectively evaluated using a prehospital score with a maximum value of 14. The percentage of patients requiring hospitalization rose from 9% with score = 0 to 100% with score = 14. With a cut-off point score ≥ 2, the sensitivity, specificity, positive predictive value and negative predictive value were 97%, 16%, 39% and 89%, respectively. Among the 6,498 patients transported to the two main hospitals, there were no deaths at scores ≤ 1 and the proportion of non-hospitalization was over 90%. The proportion of deaths increased rapidly at scores ≥ 11.

Conclusion
The prehospital score could be a useful tool for deciding the refusal of ambulance transfer in Japan's emergency medical service system.
Metabolic phenotype of methylmalonic acidemia in mice and humans: the role of skeletal muscle
Authors: Chandler Randy J , Sloan Jennifer , Fu Hong , Tsai Matthew , Stabler Sally , Allen Robert , Kaestner Klaus H , Kazazian Haig H , Venditti Charles P 
Published: October 2007

AbstractBackgroundMutations in methylmalonyl-CoA mutase cause methylmalonic acidemia, a common organic aciduria. Current treatment regimens rely on dietary management and, in severely affected patients, liver or combined liver-kidney transplantation. For undetermined reasons, transplantation does not correct the biochemical phenotype.MethodsTo study the metabolic disturbances seen in this disorder, we have created a murine model with a null allele at the methylmalonyl-CoA mutase locus and correlated the results observed in the knock-out mice to patient data. To gain insight into the origin and magnitude of methylmalonic acid (MMA) production in humans with methylmalonyl-CoA mutase deficiency, we evaluated two methylmalonic acidemia patients who had received different variants of combined liver-kidney transplants, one with a complete liver replacement-kidney transplant and the other with an auxiliary liver graft-kidney transplant, and compared their metabolite production to four untransplanted patients with intact renal function.ResultsEnzymatic, Western and Northern analyses demonstrated that the targeted allele was null and correctable by lentiviral complementation. Metabolite studies defined the magnitude and tempo of plasma MMA concentrations in the mice. Before a fatal metabolic crisis developed in the first 24–48 hours, the methylmalonic acid content per gram wet-weight was massively elevated in the skeletal muscle as well as the kidneys, liver and brain. Near the end of life, extreme elevations in tissue MMA were present primarily in the liver. The transplant patients studied when well and on dietary therapy, displayed massive elevations of MMA in the plasma and urine, comparable to the levels seen in the untransplanted patients with similar enzymatic phenotypes and dietary regimens.ConclusionThe combined observations from the murine metabolite studies and patient investigations indicate that during homeostasis, a large portion of circulating MMA has an extra-heptorenal origin and likely derives from the skeletal muscle. Our studies suggest that modulating skeletal muscle metabolism may represent a strategy to increase metabolic capacity in methylmalonic acidemia as well as other organic acidurias. This mouse model will be useful for further investigations exploring disease mechanisms and therapeutic interventions in methylmalonic acidemia, a devastating disorder of intermediary metabolism.
Immunohistochemical study of N-epsilon-carboxymethyl lysine (CML) in human brain: relation to vascular dementia
Authors: Southern Louise , Williams Jonathan , Esiri Margaret M 
Published: October 2007

Abstract

Background
Advanced glycation end-products (AGEs) and their receptor (RAGE) occur in dementia of the Alzheimer's type and diabetic microvascular disease. Accumulation of AGEs relates to risk factors for vascular dementia with ageing, including hypertension and diabetes. Cognitive dysfunction in vascular dementia may relate to microvascular disease resembling that in diabetes. We tested if, among people with cerebrovascular disease, (1) those with dementia have higher levels of neuronal and vascular AGEs and (2) if cognitive dysfunction depends on neuronal and/or vascular AGE levels.

Methods
Brain Sections from 25 cases of the OPTIMA (Oxford Project to Investigate Memory and Ageing) cohort, with varying degrees of cerebrovascular pathology and cognitive dysfunction (but only minimal Alzheimer type pathology) were immunostained for N
ε
-(carboxymethyl)-lysine (CML), the most abundant AGE. The level of staining in vessels and neurons in the cortex, white matter and basal ganglia was compared to neuropsychological and other clinical measures.

Results
The probability of cortical neurons staining positive for CML was higher in cases with worse cognition (p = 0.01) or a history of hypertension (p = 0.028). Additionally, vascular CML staining related to cognitive impairment (p = 0.02) and a history of diabetes (p = 0.007). Neuronal CML staining in the basal ganglia related to a history of hypertension (p = 0.002).

Conclusion
CML staining in cortical neurons and cerebral vessels is related to the severity of cognitive impairment in people with cerebrovascular disease and only minimal Alzheimer pathology. These findings support the possibility that cerebral accumulation of AGEs may contribute to dementia in people with cerebrovascular disease.
A novel emergency department based prevention intervention program for people living with HIV: evaluation of early experiences
Authors: Lyons Michael S , Raab Dana L , Lindsell Christopher J , Trott Alexander T , Fichtenbaum Carl J 
Published: October 2007

Abstract
Background
HIV prevention is increasingly focused on people living with HIV (PLWH) and the role of healthcare settings in prevention. Emergency Departments (EDs) frequently care for PLWH, but do not typically endorse a prevention mission. We conducted a pilot exploratory evaluation of the first reported ED program to address the prevention needs of PLWH.

Methods
This retrospective observational cohort evaluation reviewed program records to describe the first six months of participants and programmatic operation. Trained counselors provided a risk assessment and counseling intervention combined with three linkage interventions: i) linkage to health care, ii) linkage to case management, and iii) linkage to partner counseling and referral.

Results
Of 81 self-identified PLWH who were approached, 55 initially agreed to participate. Of those completing risk assessment, 17/53 (32%, 95 CI 20% to 46%) reported unprotected anal/vaginal intercourse or needle sharing in the past six months with a partner presumed to be HIV negative. Counseling was provided to 52/53 (98%). For those requesting services, 11/15 (73%) were linked to healthcare, 4/23 (17%) were coordinated with case management, and 1/4 (25%) completed partner counseling and referral.

Conclusion
Given base resources of trained counselors, it was feasible to implement a program to address the prevention needs for persons living with HIV in an urban ED. ED patients with HIV often have unmet needs which might be addressed by improved linkage with existing community resources. Healthcare and prevention barriers for PLWH may be attenuated if EDs were to incorporate CDC recommended prevention measures for healthcare providers.
Analytical and numerical quantification and comparison of the local electric field in the tissue for different electrode configurations
Authors: Čorović Selma , Pavlin Mojca , Miklavčič Damijan 
Published: October 2007

Abstract

Background
Electrochemotherapy and gene electrotransfer are novel promising treatments employing locally applied high electric pulses to introduce chemotherapeutic drugs into tumor cells or genes into target cells based on the cell membrane electroporation. The main focus of this paper was to calculate analytically and numerically local electric field distribution inside the treated tissue in two dimensional (2D) models for different plate and needle electrode configurations and to compare the local electric field distribution to parameter U/d, which is widely used in electrochemotherapy and gene electrotransfer studies. We demonstrate the importance of evaluating the local electric field distribution in electrochemotherapy and gene electrotransfer.

Methods
We analytically and numerically analyze electric field distribution based on 2D models for electrodes and electrode configurations which are most widely used in electrochemotherapy and gene electrotransfer. Analytical calculations were performed by solving the Laplace equation and numerical calculations by means of finite element method in two dimensions.

Results
We determine the minimal and maximal E inside the target tissue as well as the maximal E over the entire treated tissue for the given electrode configurations. By comparing the local electric field distribution calculated for different electrode configurations to the ratio U/d, we show that the parameter U/d can differ significantly from the actual calculated values of the local electric field inside the treated tissue. By calculating the needed voltage to obtain E > U/d inside the target tissue, we showed that better electric field distribution can be obtained by increasing the number and changing the arrangement of the electrodes.

Conclusion
Based on our analytical and numerical models of the local electric field distribution we show that the applied voltage, configuration of the electrodes and electrode position need to be chosen specifically for each individual case, and that numerical modeling can be used to optimize the appropriate electrode configuration and adequate voltage. Using numerical models we further calculate the needed voltage for a specific electrode configuration to achieve adequate E inside the target tissue while minimizing damages of the surrounding tissue. We present also analytical solutions, which provide a convenient, rapid, but approximate method for a pre-analysis of electric field distribution in treated tissue.
Stress induced cardiomyopathy presenting as acute coronary syndrome: Tako-Tsubo in Mercogliano, Southern Italy
Authors: Cangella F , Medolla A , De Fazio G , Iuliano C , Curcio N , Salemme L , Mottola G , Agrusta Marco 
Published: October 2007

Abstract

Background
Tako-tsubo syndrome (TTS) in its typical (apical) and atypical (non-apical) forms is being increasingly recognized in the West owing to early systematic coronary angiography in acute coronary syndromes (ACS).

Aim of the study
To assess the incidence, the clinical characteristics and the outcome of TTS in a single high volume cath lab in Southern Italy over the last 6 years.

Methods
Among 1674 consecutive patients (pts) referred to our coronary care units in the last 6 years (2001–2006) for ACS we selected 6 (0.5%) pts (6 women; age 57 ± 6 years) who fulfilled the following 4 criteria: 1) transient left ventricular wall motion abnormalities resulting in ballooning at contrast ventricolographic or echocardiographic evaluation; 2) normal coronary artery on coronary angiography performed 5 ± 9 hours from hospitalization; 3) new electrocardiographic ischemic-like abnormalities (either ST-segment elevation or T-wave inversion) and 4) emotional or physical trigger event.

Results
At admission all pts had presumptive diagnosis of ACS and ECG revealed ST elevation in 3 (50%) and T wave inversion with QT elongation in 3 (50%). In the acute phase cardiogenic shock occurred in 2 (33%) and heart failure in 1(16%). Presenting symptoms were chest pain in 6 (100%), dyspnoea in 2 (33%) and lipotimia in 1 (16%). At echocardiographic-ventricolographic assessment, the mechanical dysfunction (ballooning) was apical in all 6 pts ("classic" TTS). In all patients wall motion abnormalities completely reversed within 4.5 ± 1.5 days. The region of initial recovery was the anterior and lateral wall in 4 cases and the lateral wall in 2 cases. Ejection fraction was 35 ± 8% in the acute phase and increased progressively at discharge (55 ± 6%) and at 41 ± 20 months follow-up (60 ± 4%, p < 0.001 vs. baseline). All patients remained asymptomatic with minimal (aspirin, beta blockers, antihypertensive and antidislipidemic therapy) treatment.

Conclusion
Classic TTS is a frequent serendipitous diagnosis after coronary angiography showed "surprisingly" normal findings in a clinical setting mimicking an ACS. Despite its long-term good prognosis life threatening complications in the acute phase can occur.