bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multifaceted approach to modeling the immune response in tuberculosis
Authors: Marino Simeone , Linderman Jennifer J. , Kirschner Denise E. 
Published: December 2010

AbstractTuberculosis (TB) is a deadly infectious disease caused byMycobacterium tuberculosis(Mtb). No available vaccine is reliable and, although treatment exists, approximately 2 million people still die each year. The hallmark of TB infection is the granuloma, a self‐organizing structure of immune cells forming in the lung and lymph nodes in response to bacterial invasion. Protective immune mechanisms play a role in granuloma formation and maintenance; these act over different time/length scales (e.g., molecular, cellular, and tissue scales). The significance of specific immune factors in determining disease outcome is still poorly understood, despite incredible efforts to establish several animal systems to track infection progression and granuloma formation. Mathematical and computational modeling approaches have recently been applied to address open questions regarding host–pathogen interaction dynamics, including the immune response to Mtb infection and TB granuloma formation. This provides a unique opportunity to identify factors that are crucial to a successful outcome of infection in humans. These modeling tools not only offer an additional avenue for exploring immune dynamics at multiple biological scales but also complement and extend knowledge gained via experimental tools. We review recent modeling efforts in capturing the immune response to Mtb, emphasizing the importance of a multiorgan and multiscale approach that has tuneable resolution. Together with experimentation, systems biology has begun to unravel key factors driving granuloma formation and protective immune response in TB.WIREs Syst Biol Med2011 3 479–489 DOI: 10.1002/wsbm.131This article is categorized under:Models of Systems Properties and Processes > Cellular ModelsModels of Systems Properties and Processes > Mechanistic ModelsPhysiology > Mammalian Physiology in Health and Disease
Layers of epistasis: genome‐wide regulatory networks and network approaches to genome‐wide association studies
Authors: Cowper‐Sal·lari Richard , Cole Michael D. , Karagas Margaret R. , Lupien Mathieu , Moore Jason H. 
Published: December 2010

AbstractThe conceptual foundation of the genome‐wide association study (GWAS) has advanced unchecked since its conception. A revision might seem premature as the potential of GWAS has not been fully realized. Multiple technical and practical limitations need to be overcome before GWAS can be fairly criticized. But with the completion of hundreds of studies and a deeper understanding of the genetic architecture of disease, warnings are being raised. The results compiled to date indicate that risk‐associated variants lie predominantly in noncoding regions of the genome. Additionally, alternative methodologies are uncovering large and heterogeneous sets of rare variants underlying disease. The fear is that, even in its fulfillment, the current GWAS paradigm might be incapable of dissecting all kinds of phenotypes. In the following text, we review several initiatives that aim to overcome these limitations. The overarching theme of these studies is the inclusion of biological knowledge to both the analysis and interpretation of genotyping data. GWAS is uninformed of biology by design and although there is some virtue in its simplicity, it is also its most conspicuous deficiency. We propose a framework in which to integrate these novel approaches, both empirical and theoretical, in the form of a genome‐wide regulatory network (GWRN). By processing experimental data into networks, emerging data types based on chromatin immunoprecipitation are made computationally tractable. This will give GWAS re‐analysis efforts the most current and relevant substrates, and root them firmly on our knowledge of human disease.WIREs Syst Biol Med2011 3 513–526 DOI: 10.1002/wsbm.132This article is categorized under:Laboratory Methods and Technologies > Genetic/Genomic Methods
Ischemic kidney injury and mechanisms of tissue repair
Authors: Sabbahy Marwa El , Vaidya Vishal S. 
Published: December 2010

AbstractAcute kidney injury (AKI) may result from ischemia or by the use of nephrotoxic agents. The incidence of AKI is variable, depends on comorbidities, and ranges from 5 to 35% in all hospitalized patients. The mechanisms of kidney injury exist within a large network of signaling pathways driven by interplay of inflammatory cytokines/chemokines, reactive oxygen species (ROS), and apoptotic factors. The effects and progression of injury overlap extensively with the remarkable ability of the kidney to repair itself both by intrinsic and extrinsic mechanisms that involve specific cell receptors/ligands as well as possible paracrine influences. The fact that kidney injury is usually part of a generalized comorbid condition makes it all the more challenging in terms of assessment of severity. In this review, we attempt to analyze the mechanisms of ischemic injury and repair in acute and chronic kidney disease from the perspectives of both preclinical and human studies.WIREs Syst Biol Med2011 3 606–618 DOI: 10.1002/wsbm.133This article is categorized under:Physiology > Mammalian Physiology in Health and Disease
Whole transcriptome analysis: what are we still missing?
Authors: Saxena Alka , Carninci Piero 
Published: December 2010

AbstractNew technologies such as tag‐based sequencing and tiling arrays have provided unique insights into the transcriptional output of cells. Many new RNA classes have been uncovered in the past decade, despite limitations in current technologies. Even as the repertoire of known functional elements of the transcriptome increases and contemporary technologies become mainstream, inadequacies in conventional protocols for library preparation, sequencing and mapping continue to hamper revelation of the entire transcriptome of cells. In this article, we review current protocols and outline their deficiencies. We also provide our view on what we may be overlooking in the transcriptome, despite exhaustive investigations, and indicate future areas of technological development and research. WIREs Syst Biol Med 2011 3 527–543 DOI: 10.1002/wsbm.135This article is categorized under:

Laboratory Methods and Technologies > Genetic/Genomic Methods
Functional genomics of the brain: uncovering networks in the CNS using a systems approach
Authors: Konopka Genevieve 
Published: December 2010

AbstractThe central nervous system (CNS) is undoubtedly the most complex human organ system in terms of its diverse functions, cellular composition, and connections. Attempts to capture this diversity experimentally were the foundation on which the field of neurobiology was built. Until now though, techniques were either painstakingly slow or insufficient in capturing this heterogeneity. In addition, the combination of multiple layers of information needed for a complete picture of neuronal diversity from the epigenome to the proteome requires an even more complex compilation of data. In this era of high‐throughput genomics though, the ability to isolate and profile neurons and brain tissue has increased tremendously and now requires less effort. Both microarrays and next‐generation sequencing have identified neuronal transcriptomes and signaling networks involved in normal brain development, as well as in disease. However, the expertise needed to organize and prioritize the resultant data remains substantial. A combination of supervised organization and unsupervised analyses are needed to fully appreciate the underlying structure in these datasets. When utilized effectively, these analyses have yielded striking insights into a number of fundamental questions in neuroscience on topics ranging from the evolution of the human brain to neuropsychiatric and neurodegenerative disorders. Future studies will incorporate these analyses with behavioral and physiological data from patients to more efficiently move toward personalized therapeutics. WIREs Syst Biol Med 2011 3 628–648 DOI: 10.1002/wsbm.139This article is categorized under:

Laboratory Methods and Technologies > Genetic/Genomic Methods
Human cardiomyogenesis and the need for systems biology analysis
Authors: Adam Young D. , DeQuach Jessica A. , Christman Karen L. 
Published: December 2010

AbstractCardiovascular disease remains the leading cause of death in the Western world and myocardial infarction is one of the primary facets of this disease. The limited natural self‐renewal of cardiac muscle following injury and restricted supply of heart transplants has encouraged researchers to investigate other means to stimulate regeneration of damaged myocardium. The plasticity of stem cells toward multiple lineages offers the potential to repair the heart following injury. Embryonic stem cells have been extensively studied for their ability to differentiate into early cardiomyocytes, however, the pathway has only been partially defined and inadequate efficiency limits their clinical applicability. Some studies have shown cardiomyogenesis from adult mesenchymal stem cells, from both bone marrow and adipose tissue, but their differentiation pathway remains poorly detailed and these results remain controversial. Despite promising results using stem cells in animal models of cardiac injury, the driving mechanisms behind their differentiation down a cardiomyogenic pathway have yet to be determined. Currently, there is a paucity of information regarding cardiomyogenesis on the systemic level. Stem cell differentiation results from multiple signaling parameters operating in a tightly regulated spatiotemporal pattern. Investigating this phenomenon from a systems biology perspective could unveil the abstruse mechanisms controlling cardiomyogenesis that would otherwise require extensive in vitro testing. WIREs Syst Biol Med 2011 3 666–680 DOI: 10.1002/wsbm.141This article is categorized under:

Developmental Biology > Stem Cell Biology and Regeneration
Synthesis, Structure, Luminescent and Thermal Properties of Ytterbium(III) and Dysprosium(III) Complexes with 5‐Sulfoisophthalic Acid Sodium Salt
Authors: Wu Gang , Yin Fu‐Jun , Wei Hao , Liu Zhen‐Feng , Yin Gui 
Published: January 2011

AbstractTwo rare earth metal‐organic framework compounds [Ybsip(H2O)5]·3H2O (1) and [Dysip(H2O)4] (2) (NaH2sip: 5‐sulfoisophthalic acid sodium salt) were synthesized hydrothermally, and characterized by single‐crystal X‐ray diffraction, elemental analysis, and FT‐IR spectroscopy. In complex 1, each YbIII atom is nine‐coordinate with a distorted monocapped tetragonal prismatic arrangement. Two carboxylate groups of each sip3– molecule adopt the same μ1‐η1:η1 chelating coordination model connecting two YbIII atoms. The oxygen atoms of the sulfonate group do not participate in coordination with YbIII. The whole sip3– molecule acts as a μ2 bridge to form an one‐dimensional (1D) chain structure. The 1D chains are linked by hydrogen bonding to generate two‐dimensional layers, and are further combined together to form a three‐dimensional structure. In complex 2, the DyIII atom is nine‐coordinate with a distorted monocapped tetragonal antiprismatic arrangement. In each sip3– anion, two carboxylate groups take the same μ1‐η1:η1 chelating coordination mode, only an oxygen atom of sulfonate group bond to DyIII ion. The whole ligand sip3– acts as a μ3 bridge linking three different DyIII ions to generate a wave‐like two‐dimensional network with (6,3) topological structure. The two‐dimensional networks are further linked by O–H···O hydrogen bonds to form a three‐dimensional structure. The thermal and luminescent properties of both complexes are investigated.
A 3D Nickel(II) Coordination Polymer with cds Nets Constructed from 3‐Pyridin‐4‐yl‐benzoic Acid
Authors: Tang Long , Fu Feng , Gao Loujun , Wu Yapan , Liu Quirui , Gao Xiaoming 
Published: January 2011

AbstractA new coordination polymer, [Ni(3,4‐pybz)2(H2O)]n (1), was hydrothermally synthesized from Ni(NO3)2·6H2O and an unsymmetrical 3‐pyridin‐4‐yl‐benzoic acid (3,4‐Hpybz). It was characterized by IR spectroscopy, elemental analysis, thermogravimetric analysis, and single‐crystal X‐ray diffraction. In complex 1, the 3,4‐pybz ligands act as linear linkers to join 4‐connected nickel(II) ion nodes, to build a 3D 4‐connected twofold interpenetrated 658‐cds coordination framework. In addition, the magnetic and thermal properties of complex 1 were also investigated.
Synthesis of Dimeric Methylzinc N,N‐Bis(2‐pyridylmethyl)carbamate via Addition of CO2 to a Methylzinc Amide
Authors: Kahnes Marcel , Görls Helmar , Westerhausen Matthias 
Published: January 2011

AbstractExposure of a THF solution of bis(methylzinc) tert‐butylamide bis(2‐pyridylmethyl)amide (1) to a carbon dioxide atmosphere leads to formation of dimeric methylzinc bis(2‐pyridylmethyl)carbamate (2). The preparation of 2 from 1 and CO2 is a two‐step reaction and affords ligand redistribution after insertion of CO2 into the Zn–N bonds. The central structural fragment is an eight‐membered (ZnO2C)2 ring with tetracoordinate zinc atoms and planar C2N–CO2 carbamate units in a boat conformation.
Palm Olein and Olive Oil Cause a Higher Increase in Postprandial Lipemia Compared with Lard but Had No Effect on Plasma Glucose, Insulin and Adipocytokines
Authors: Teng Kim‐Tiu , Nagapan Gowri , Cheng Hwee Ming , Nesaretnam Kalanithi 
Published: December 2010

AbstractPostprandial lipemia impairs insulin sensitivity and triggers the pro‐inflammatory state which may lead to the progression of cardiovascular diseases. A randomized, crossover single‐blind study (n= 10 healthy men) was designed to compare the effects of a high‐fat load (50 g fat), rich in palmitic acid from both plant (palm olein) or animal source (lard) versus an oleic acid‐rich fat (virgin olive oil) on lipemia, plasma glucose, insulin and adipocytokines. Serum triacylglycerol (TAG) concentrations were significantly lower after the lard meal than after the olive oil and palm olein meals (meal effectP= 0.003; time effectP< 0.001). The greater reduction in the plasma non‐esterified free fatty acids levels in the lard group compared to the olive oil meal was mirrored by the changes observed for serum TAG levels (P< 0.05). The magnitude of response for plasma glucose, insulin and adipocytokines [interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β) and leptin] were not altered by the type of dietary fats. A significant difference in plasma IL‐1β was found over time following the three high fat loads (time effectP= 0.036). The physical characteristics and changes in TAG structure of lard may contribute to the smaller increase in postprandial lipemia compared with palm olein. A high fat load but not the type of fats influences concentrations of plasma IL‐1β over time but had no effect on other pro‐inflammatory markers tested in the postprandial state.
Lumbopelvic fusion with a new fixation technique in lumbosacral agenesis: Three cases
Authors: Yazici Muharrem , Akel Ibrahim , Demirkiran Halil Gokhan 
Published: December 2010

Purpose Patients with lumbosacral agenesis characteristically sit on their iliac wings with their torsos bent forward, which yields an increase in intra-abdominal pressure and, subsequently, negative effects on their diaphragm. The sacrum is not available as an anchor point for instrumentation. Dunn-McCarthy rods or Galveston fixations cannot be performed due to these limited anatomic properties. On the other hand, the absence of necessary bone mass for fusion anteriorly limits the fusion interventions to the posterior. Therefore, a secure and rigid fixation is essential to preclude the need for an external support. There are limited publications discussing different techniques due to the relatively rare incidence of the disease. We report the clinical and radiological results of a new technique applied to three patients in which previously recommended methods are modified. Methods Two 6-year-old female patients and one 5-year-old male patient with lumbosacral agenesis underwent posterior lumbopelvic instrumentation and fusion. Together with standard pedicle screw spinal instrumentation, pelvic fixation is obtained with a combination of supero-inferior directed rod and/or screw to overcome deforming forces created at the flexion–extension pivot points of the lumbopelvic junction. Autogenic anterior tibial cortical structural graft is used for laminopelvic bridging, and demineralized bone matrix is used for the augmentation of osteoinduction. A single leg hip spica is applied for 4 months to protect the fixation. Results Total correction yielded an aligned spine with a posture that allows for sitting on the ischial spines for all three patients. Solid fusion was observed to maintain this correction at the final follow-up. Conclusion The use of new-generation pediatric spinal instrumentation systems with a new technique without knee disarticulation provides a safe and effective fixation and fusion in lumbosacral agenesis.
The function of bone morphogenetic proteins in the human ovary
Authors: Yoshino Osamu , Shi Jia , Osuga Yutaka , Harada Miyuki , Nishii Osamu , Yano Tetsu , Taketani Yuji 
Published: January 2011

AbstractThe gonadotropins, follicle‐stimulating hormone (FSH), and luteinizing hormone (LH), are of particular importance in ovarian physiology. However, FSH receptors and LH receptors are not expressed until the secondary follicle stage, indicating that initiation of follicular growth is independent of the gonadotropins. Among many intra‐ovarian growth factors, many studies have shown that bone morphogenetic proteins (BMPs) play pivotal roles in regulating the early phases of follicular growth. The BMP system induces the gonadotropin system by modulating gonadotropin receptors in early‐stage follicles. Interestingly, the BMP system also prevents precocious maturation of the follicle by suppressing luteinization. Signals provoked by the preovulatory LH surge eliminate BMPs, enabling luteinization to progress. Thus, the BMP system and the gonadotropin system seem to cooperate in regulating follicular development, maturation, and luteinization.
Does minimal access major surgery in the newborn hurt less? An evaluation of cumulative opioid doses
Authors: Ceelie I. , van Dijk M. , Bax N.M.A. , de Wildt S.N. , Tibboell D. 
Published: December 2010

AbstractBackground: Minimal access surgery (MAS) in adults is associated with less postoperative pain in comparison to conventional ‘open’ surgery. It is not known whether this holds true for neonates as well. Less pain would imply that opioid consumption can be reduced, which has a beneficial effect on morbidity.Aim: To evaluate potential differences in' opioid consumption between neonates undergoing thoracoscopic minimal access surgery or conventional surgery of esophageal atresia (EA) and congenital diaphragmatic hernia (CDH).Methods: In this retrospective cohort study we included two controls for each MAS patient, matched on diagnosis, sex and age at surgery. Opioid dose titration was based on validated pain scores (VAS and COMFORT behaviour), applied by protocol. Cumulative opioid doses at 12, 24, 48 h and 7 days postoperatively were compared between groups with the Mann—Whitney test.Results: The study group consisted of 24 MAS patients (14 EA; 10 CDH). These were matched to 48 control patients (28 EA; 20 CDH). At none of the time points cumulative opioid (median in mg/kg (IQR)) doses significantly differed between MAS patients and controls, both with CDH and EA. For example at 24 h postoperative for CDH patients cumulative opioid doses were [0.84(0.61–1.83) MAS vs. 1.06(0.60–1.36) p =1.0] controls, For EA patients at 24 h the cumulative opioid doses were [0.48(0.30–0.75) MAS vs. 0.49(0.35–0.79) p =0.83] controls. This held true for the postoperative pain scores as well.Conclusions: Minimal access surgery for the repair of esophageal atresia or congenital diaphragmatic hernia is not associated with less cumulative opioid doses.
Self‐reported sleep duration associated with distraction analgesia, hyperemia, and secondary hyperalgesia in the heat‐capsaicin nociceptive model
Authors: Campbelll Claudia M. , Boundsl Sara C. , Simangol Mpepera B. , Witmerl Kenneth R. , Campbelll James N. , Edwardsl Robert R. , Haythornthwaitel Jennifer A. , Smithl Michael T. 
Published: December 2010

AbstractAlthough sleep deprivation is known to heighten pain sensitivity, the mechanisms by which sleep modifies nociception are largely unknown. Few studies of sleep—pain interactions have utilized quantitative sensory testing models that implicate specific underlying physiologic mechanisms. One possibility, which is beginning to receive attention, is that differences in sleep may alter the analgesic effects of distraction. We utilized the heat‐capsaicin nociceptive model to examine whether self‐reported habitual sleep duration is associated with distraction analgesia, the degree of secondary hyperalgesia and skin flare, markers implicating both central and peripheral processes that heighten pain. Twenty‐eight healthy participants completed three experimental sessions in a randomized within subjects design. In the pain only condition, pain was induced for approximately 70‐min via application of heat and capsaicin to the dorsum of the non‐dominant hand. Verbal pain ratings were obtained at regular intervals. In the distraction condition, identical procedures were followed, but during heat‐capsaicin pain, subjects played a series of video games. The third session involved assessing performance on the video games (no capsaicin). Participants indicated their normal self‐reported habitual sleep duration over the past month. Individuals who slept less than 6.5 h/night in the month prior to the study experienced significantly less behavioral analgesia, increased skin flare and augmented secondary hyperalgesia. These findings suggest that reduced sleep time is associated with diminished analgesic benefits from distraction and/or individuals obtaining less sleep have a reduced ability to disengage from pain‐related sensations. The secondary hyperalgesia finding may implicate central involvement, whereas enhanced skin flare response suggests that sleep duration may also impact peripheral inflammatory mechanisms.
Differences in activity‐related behaviour among patients with chronic low back pain
Authors: Huijnenl Ivan P.J. , Verbuntl Jeanine A. , Petersl Madelon L. , Smeetsl Rob J.E.M. , Kindermansl Hanne P.J. , Roelofsl Jeffrey , Goossensl Marielle , Seelenl Henk A.M. 
Published: December 2010

AbstractThe aim of the present study was to compare the subjectively reported and objectively assessed activity‐related characteristics of patients with Chronic Low Back Pain (CLBP) who were classified according to their scores on the Patterns of Activity Measure‐Pain (POAM‐P) into avoiders, persisters, mixed performers (i.e. high scores on both avoidance and persistence behaviour) or functional performers (i.e. low scores on avoidance and persistence behaviour).Patients carried an electronic diary during 14 days to assess the self‐reported activity and pain intensity levels in daily life. An accelerometer was used to objectively assess their activity level during the same time period.Results were available for 79 patients. Avoiders, persisters and mixed performers showed a higher level of self‐reported disability than functional performers. Avoiders were characterized by a low level of self‐reported habitual activities and persisters by long objectively measured daily uptime. The objectively assessed level of physical activity did not differ between the four groups. A further analysis tested the association between pain intensity levels and self‐reported and objectively assessed daily life activity levels in avoiders and persisters. In persisters, a higher level of self‐reported activities in daily life was related to increased pain. The objectively assessed activity level was not associated with pain intensity.