bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bringing order to protein disorder through comparative genomics and genetic interactions
Authors: Bellay Jeremy , Han Sangjo , Michaut Magali , Kim TaeHyung , Costanzo Michael , Andrews Brenda J , Boone Charles , Bader Gary D , Myers Chad L , Kim Philip M 
Published: February 2011

Abstract
Background
Intrinsically disordered regions are widespread, especially in proteomes of higher eukaryotes. Recently, protein disorder has been associated with a wide variety of cellular processes and has been implicated in several human diseases. Despite its apparent functional importance, the sheer range of different roles played by protein disorder often makes its exact contribution difficult to interpret.

Results
We attempt to better understand the different roles of disorder using a novel analysis that leverages both comparative genomics and genetic interactions. Strikingly, we find that disorder can be partitioned into three biologically distinct phenomena: regions where disorder is conserved but with quickly evolving amino acid sequences (flexible disorder); regions of conserved disorder with also highly conserved amino acid sequences (constrained disorder); and, lastly, non-conserved disorder. Flexible disorder bears many of the characteristics commonly attributed to disorder and is associated with signaling pathways and multi-functionality. Conversely, constrained disorder has markedly different functional attributes and is involved in RNA binding and protein chaperones. Finally, non-conserved disorder lacks clear functional hallmarks based on our analysis.

Conclusions
Our new perspective on protein disorder clarifies a variety of previous results by putting them into a systematic framework. Moreover, the clear and distinct functional association of flexible and constrained disorder will allow for new approaches and more specific algorithms for disorder detection in a functional context. Finally, in flexible disordered regions, we demonstrate clear evolutionary selection of protein disorder with little selection on primary structure, which has important implications for sequence-based studies of protein structure and evolution.
Biphasic activity of CD137 ligand-stimulated monocytes on T cell apoptosis and proliferation
Authors: Shaqireen Kwajah M M , Mustafa Nurulhuda , Holme Andrea L , Pervaiz Shazib , Schwarz Herbert 
Published: February 2011

ABSTRACTCD137L (4-1BBL) is a member of the TNFSF and is expressed on APCs as a transmembrane protein. Reverse signaling by CD137L in monocytes causes cell activation and differentiation to mature inflammatory DCs that can stimulate T cell proliferation. However, CD137L agonists have also been reported to induce apoptosis in PBMCs. This study aimed at clarifying these seemingly opposing activities. We find that the dying cells within PBMCs are T cells and that this T cell death is dependent on monocytes and correlates with the monocyte:T cell ratio. This CD137L-induced, monocyte-mediated T cell apoptosis is reminiscent of MDCD, and both are cell contact-dependent. T cell death is not mediated by CD95 or DR4 or -5 but by ROS produced by the T cells. T cell apoptosis is restricted to the first 24 h of stimulation, and at later time-points, the monocytes differentiate to inflammatory DCs under the influence of CD137L signaling and acquire the capacity to stimulate T cell proliferation from Day 4 onward. This biphasic activity may contribute to infection-induced T cell attrition, where in the early phase (&lt;24 h) of an infection, massive T cell apoptosis occurs before the antigen-specific T cells expand.
Autoinflammation: translating mechanism to therapy
Authors: Doherty Taylor A , Brydges Susannah D , Hoffman Hal M 
Published: February 2011

ABSTRACTAutoinflammatory syndromes are a clinically heterogeneous collection of diseases characterized by dysregulation of the innate immune system. The hereditary recurrent fever disorders were the first to be defined as autoinflammatory. Several of the responsible genes are now known to encode proteins forming multimeric complexes called inflammasomes, which are intracellular “danger sensors” that respond to a variety of different signals by activating caspase-1, responsible for cleavage and subsequent release of bioactive IL-1β. This discovery of the causative link between autoinflammation and IL-1β maturation has led to a significantly improved understanding of the mechanisms of innate immunity, as well as life-altering treatments for patients. Targeting IL-1β for the treatment of autoinflammatory syndromes is an excellent example of the power of translational research. Given the central role of inflammation in many complex multigenic diseases, these treatments may benefit larger numbers of patients in the future. Here, we review current treatment strategies of autoinflammatory diseases with a focus on IL-1 antagonism.
Leptin Deficiency and Diet-Induced Obesity Reduce Hypothalamic Kisspeptin Expression in Mice
Authors: Quennell Janette H. , Howell Christopher S. , Roa Juan , Augustine Rachael A. , Grattan David R. , Anderson Greg M. 
Published: February 2011

Abstract
The hormone leptin modulates a diverse range of biological functions, including energy homeostasis and reproduction. Leptin promotes GnRH function via an indirect action on forebrain neurons. We tested whether leptin deficiency or leptin resistance due to a high-fat diet (HFD) can regulate the potent reproductive neuropeptide kisspeptin. In mice with normalized levels of estradiol, leptin deficiency markedly reduced kisspeptin gene expression, particularly in the arcuate nucleus (ARC), and kisspeptin immunoreactive cell numbers in the rostral periventricular region of the third ventricle (RP3V). The HFD model was used to determine the effects of diet-induced obesity and central leptin resistance on kisspeptin cell number and gene expression. DBA/2J mice, which are prone to HFD-induced infertility, showed a marked decrease in kisspeptin expression in both the RP3V and ARC and cell numbers in the RP3V after HFD. This is the first evidence that kisspeptin can be regulated by HFD and/or increased body weight. Next we demonstrated that leptin does not signal (via signal transducer and activator of transcription 3 or 5, or mammalian target of rapamycin) directly on kisspeptin-expressing neurons in the RP3V. Lastly, in leptin receptor-deficient mice, neither GnRH nor kisspeptin neurons were activated during a preovulatory-like GnRH/LH surge induction regime, indicating that leptin's actions on GnRH may be upstream of kisspeptin neurons. These data provide evidence that leptin's effects on reproductive function are regulated by kisspeptin neurons in both the ARC and RP3V, although in the latter site the effects are likely to be indirect.
Essential Role for Protein Kinase Cζ in Oleic Acid-Induced Glucagon-Like Peptide-1 Secretion in Vivo in the Rat
Authors: Iakoubov Roman , Ahmed Ausma , Lauffer Lina M. , Bazinet Richard P. , Brubaker Patricia L. 
Published: February 2011

AbstractLuminal monounsaturated long-chain fatty acids [e.g. oleic acid (OA)] increase secretion of the incretin, glucagon-like peptide-1 (GLP-1) from the ileocolonic L cell. However, it is not known whether OA ingestion causes a sufficient increase in distal luminal concentrations to directly enhance GLP-1 secretion. Furthermore, we have demonstrated that protein kinase Cζ (PKCζ) is required for OA-induced GLP-1 secretion in vitro; however, the physiological relevance of this finding remains unknown. Therefore, we have determined luminal OA concentrations in OA-fed rats and examined the effects of direct OA stimulation on GLP-1 secretion using a novel model of intestinal-specific PKCζ knockdown. Murine GLUTag L cells express numerous fatty acid transport proteins and take up OA in a saturable manner. Oral administration of OA increased the ileal chyme content of OA by 140-fold over 60–120 min (P &lt; 0.05–0.01), peaking at 105 ± 50 μmol/g. To evaluate the direct effects of OA on GLP-1 secretion, 125 mm OA was rectally infused into the colon and terminal ileum of rats. Plasma bioactive GLP-1 increased from 20 ± 6 to 102 ± 21 pg/ml at 60 min (P &lt; 0.01). However, pretreatment with ileocolonic adenoviral PKCζ small interfering RNA resulted in a 68 ± 8% reduction in the GLP-1 response to rectal OA (P &lt; 0.001). The results of these studies indicate that OA levels in the rat terminal gut after oral ingestion are sufficient to induce GLP-1 secretion and that PKCζ is necessary for the effects of OA on GLP-1 secretion in vivo. PKCζ may therefore serve as a novel therapeutic target to enhance GLP-1 levels in patients with type 2 diabetes.
Estradiol Down-Regulates RF-Amide-Related Peptide (RFRP) Expression in the Mouse Hypothalamus
Authors: Molnár C. S. , Kalló I. , Liposits Z. , Hrabovszky E. 
Published: February 2011

Abstract
In most mammals, RF-amide-related peptides are synthesized in the dorsomedial hypothalamic nucleus and regulate reproduction via inhibiting GnRH neurons and, possibly, adenohypophyseal gonadotrophs. In the present study, we investigated the possibility that RFRP-synthesizing neurons are involved in estrogen feedback signaling to the reproductive axis in mice. First, we used quantitative in situ hybridization and compared the expression of prepro-RFRP mRNA of ovariectomized mice, with and without 17β-estradiol (E2) replacement. Subcutaneous administration of E2 via silastic capsules for 4 d significantly down-regulated prepro-RFRP mRNA expression. The underlying receptor mechanism was investigated with immunohistochemistry. In ovariectomized mice, low levels of nuclear estrogen receptor (ER)-α immunoreactivity were detectable in 18.7 ± 3.8% of RFRP neurons. The majority of RFRP neurons showed no ER-α signal, and RFRP neurons did not exhibit ER-β immunoreactivity. Results of these studies indicate that RFRP is a negatively estradiol-regulated neurotransmitter/neuromodulator in mice. The estrogenic down-regulation of RFRP expression may contribute to estrogen feedback to the reproductive axis. The issue of whether E2 regulates RFRP neurons directly or indirectly remains open given that ER-α immunoreactivity is present only at low levels in a subset of these cells.
Selection of Treatment for Patients with Carotid Artery Disease: Medication, Carotid Endarterectomy, or Carotid Artery Stenting
Authors: Bosiers Marc , Peeters Patrick , Deloose Koen , Verbist Jürgen , Sprouse L. Richard 
Published: February 2011

Patients presenting with atherosclerosis of the extracranial carotid arteries may be offered carotid endarterectomy (CEA), carotid artery stenting (CAS), or medical therapy to reduce their risk of stroke. In many cases, the choice between treatment modalities remains controversial. An algorithm based on patients' neurologic symptoms, comorbidities, limiting factors for CAS and CEA, and personal preferences was developed to determine the optimal treatment in each case. This algorithm was then employed to determine therapy in 308 consecutive patients presenting to a single institution during one calendar year. Ninety-five (30.8%) patients presented with an asymptomatic carotid stenosis of more than 80% and 213 (69.2%) with a symptomatic stenosis of more than 50%. According to our algorithm, 59 (62.1%) of the 95 asymptomatic patients received CAS, 20 (21.1%) received CEA, and 16 (16.8%) received medical therapy. All symptomatic patients underwent intervention; 153 (71.8%) were treated with CAS and 60 (28.2%) with CEA. Combined 30-day stroke and death rates after CAS were 1.7% in asymptomatic patients and 2.6% in symptomatic patients. After CEA, these rates were 0% and 3.3%, respectively. Careful selection of treatment modality according to predetermined criteria can result in improved outcomes.
Experimental Force Measurements on a Bifurcated Endoluminal Stent Graft Model: Comparison with Theory
Authors: Šutalo Ilija D. , Liffman Kurt , Lawrence-Brown Michael M.D. , Semmens James B. 
Published: February 2011

The goal of this study was to experimentally validate a steady-state mathematical model, which can be used to compute the forces acting on a bifurcated endoluminal stent graft. To accomplish this task, an acrylic model of a bifurcated graft was used for the force measurements. The graft model was connected to the inlet piping with a flexible rubber membrane that allowed the graft model to move. This allowed us to measure the force owing to the movement of the graft model with a calibrated load cell. Steady-state blood flow was assumed, and the working fluid was water. The experimental data were found to be consistent with the results from a previously published mathematical model: the graft force is strongly dependent on the proximal or inlet pressure and the inlet area. The force tends to be weakly dependent on flow rate. More research work will be required to determine whether the steady-state force model examined in this article provides a realistic determination of the forces on an endoluminal stent graft that is subject to pulsatile blood flow.
Clinical Outcome and Technical Considerations of Late Removal of Abdominal Aortic Endografts: 8-Year Single-Center Experience
Authors: de Vries Jean-Paul P. M. , van Herwaarden Joost A. , Overtoom Tim Th. , Vos Jan Albert , Moll Frans L. , van de Pavoordt Eric D. W. M. 
Published: February 2011

During an 8-year period, 355 patients underwent endovascular repair of mainly true (97%) infrarenal aneurysms. After a mean follow-up of 48 months, 11 (3.1%) patients required conversion to open repair and 10 were eligible for open surgical intervention. Via a midline incision, explantation of the endograft was performed by using an infrarenal aortotomy. Explantation was done for rupture in four patients (40%), with a marked difference in mortality rates between acute (50%) and elective (0%) explantations. The main reason for explantation was proximal type I endoleak caused by (1) malposition of the device, (2) proximal migration of the endograft, and (3) dislodgment of a tube endograft that followed former central reconstruction. Proximal migration is most worrisome and demands preventive endovascular reintervention. The mortality and morbidity rates of elective explantation are acceptable. When delayed conversion is indicated, priority has to be given to operate on these patients.
Carotid Artery Stenting: Which Stent for Which Lesion?
Authors: Bosiers Marc , Deloose Koen , Verbist Jürgen , Peeters Patrick 
Published: February 2011

The different geometries and working principles of carotid stents (nitinol or cobalt chromium, open- or closed-cell configuration) provide each product with unique functional properties. The individual characteristics of each device may make it an attractive choice in one circumstance but render it less desirable in other situations. In approximately 75% of all procedures, all types of stents will achieve similar outcomes, making adequate device selection unnecessary. For the remaining quarter, careful preoperative screening is mandatory. In addition to eventual access issues, the choice of the optimal carotid stent depends mainly on arterial anatomy and lesion morphology. When treating a tortuous anatomy, stents with a flexible and comformable open-cell configuration are preferred. In arteries with a significant mismatch between common carotid artery and internal carotid artery diameter, cobalt chromium (Elgiloy) or tapered nitinol stents are selected. Lesions with suspected high emboligenicity are best covered with stents with a closed-cell configuration, whereas highly calcified lesions need treatment with nitinol stents. Thorough knowledge of the characteristics, advantages and disadvantages, and working principles of the different available stents is mandatory to optimally select the materials to be used for patients eligible for carotid revascularization.
In Vivo Comparison of the Inflammatory Response Induced by Different Vascular Biomaterials
Authors: Busuttil Steven J. , Drumm Carla , Plow Edward F. 
Published: February 2011

Biomaterial implants induce a local inflammatory response. A comparison of the inflammatory cell response was made between several biomaterials commonly used as vascular prostheses. Disks of polyethylene terephthalate (PET), polytetrafluoroethylene (PTFE), aluminum, titanium, copper, and stainless steel were surgically placed into the peritoneum of mice. Recruited macrophage and neutrophil populations were measured after recovery from the disk surface and peritoneal lavage. Following peritoneal biomaterial implants, there was no difference in total neutrophil or macrophage recruitment between mice implanted with PET, PTFE, aluminum, or titanium disks. However, there was significant attenuation of total neutrophil and macrophage recruitment to stainless steel compared with the other implants. Similarly, there was no significant difference in the percentage of leukocytes adherent to the PET, aluminum, or titanium disks. Macrophage adherence to the stainless steel disks was attenuated by 19.1%, and the number of neutrophils was attenuated by 69.1% when compared with PET implant mice. Mice implanted with copper disks universally expired. Leukocyte recruitment did not differ between PET, PTFE, aluminum, or titanium disks, suggesting that these materials stimulate similar inflammatory responses. Stainless steel disks recruited both fewer neutrophils and fewer macrophages and support lower adherence of these cells than the other biomaterials. Copper incited an overwhelming and fatal response.
Nonoperative Management of Lower Extremity Claudication Caused by a Baker's Cyst: Case Report and Review of the Literature
Authors: Zhang Wayne W. , Lukan James K. , Dryjski Maciej L. 
Published: February 2011

A Baker's or popliteal cyst is a synovial cyst in the popliteal fossa arising from the knee joint. The majority of patients develop a popliteal mass that is asymptomatic, but in a small percentage of patients, complications and symptoms occur; these may not only encompass the popliteal veins and arteries but may also include cyst leakage, infection, hemorrhage, and compartment syndrome. Severe lower limb ischemia caused by a Baker's cyst is extremely rare, having been reported only six times since 1960; all patients were treated with surgical intervention. We report the case of a 29-year-old male presenting with right calf claudication caused by a Baker's cyst. The patient was managed nonoperatively with nonsteroidal anti-inflammatory agents, proper exercises, and close observation. His claudication improved progressively and had completely disappeared at 12 months of follow-up. A repeat duplex arterial study showed that increased blood flow to the right foot and the right ankle/brachial index improved to 0.97 from 0.67. Repeat ultrasonography demonstrated that the size of the cyst decreased from 4.5 × 1.5 cm to 2.8 × 0.9 cm. The patient had been followed for 20 months and remained asymptomatic in the last 8 months. We will continue to follow the patient to evaluate the long-term outcome. In summary, our own data and literature review suggest that the limb ischemia caused by Baker's cyst may be a transient condition and can be managed nonoperatively in selected patients.
Aortic Arch Aneurysm and Patent Left Internal Mammary Artery: Technique of Transposition of Supra-aortic Vessels and Embolization of the Subclavian Artery
Authors: Mangialardi Nicola , Costa Pierluigi , Serrao Eugenia , Cavazzini Carlo , Bergeron Patrice 
Published: February 2011

Endovascular treatment of aortic arch aneurysms poses unique problems because of vascularization of the carotid arteries. Transposition of supra-aortic vessels is becoming an established and accepted strategy for expanding the applicability of stent graft repair. left subclavian artery (LSA) is not usually transposed because its overstenting does not produce relevant complications. Nevertheless, some selected cases need high-pressure revascularization of the LSA, such as in the presence of a patent left internal mammary artery. We present a technique of revascularization of supra-aortic vessels and “balloon protected” embolization of the origin of the LSA.
Does Conversion of Intended Remote Iliac Artery Endarterectomy Alter the Early and Long-Term Outcome?
Authors: Smeets Luuk , van der Horn Garmt , Gisbertz Suzanne S. , Ho Gwan , Moll Frans 
Published: February 2011

The purpose of this study was to compare the perioperative and long-term results of initial successful remote iliac artery endarterectomies (RIAEs) with converted procedures. From April 1994 to September 2003, 63 remote endarterectomies of the external and/or common iliac artery were planned in 62 patients (41 males, 42 procedures). The median age was 65 years (range 39–83 years), and the indication for operation was severe claudication in 37 (59%), rest pain in 16 (25%), and gangrene in 10 (16%) procedures. Initial technical success was achieved in 56 (89%) procedures (group 1); seven conversions (group 2) were necessary. In group 1, the 5-year primary patency rate improved from 64 ± 15% to a primary assisted patency of 88 ± 9.3% after percutaneous transluminal angioplasty in 11 patients, with 7 requiring stent placement. The 5-year secondary patency rate was 94 ± 7.4%. The primary and secondary patency rates in group 2 were 86 ± 19% and 100%, respectively. RIAE can be offered to patients with long occlusions of the iliac arteries as a first treatment option. The inherent risk of a possible conversion of an intended RIAE to a more invasive surgical procedure has no significant adverse clinical effect on the early and 5-year clinical outcomes.
Structural Control with Multi-Subnet Wireless Sensing Feedback: Experimental Validation of Time-Delayed Decentralized H* Control Design
Authors: Wang Yang , Law Kincho H. 
Published: February 2011

This study investigates the feasibility of deploying wireless communication and embedded computing for structural control applications. A feedback structural control system involves a network of sensors and control devices. As control devices are becoming smaller, more cost effective and reliable, opportunities are now available to instrument a structure with large number of control devices. However, instrumenting a large scale centralized control system with cables can be time consuming, labor intensive, and difficult to maintain and reconfigure. This study explores decentralized feedback control using wireless sensors incorporated with a computational core and a signal generation module. Decentralized control architectures are designed to make control decisions based on data acquired from sensors located in the vicinity of a control device. Specifically, this paper describes the experimental validation of a time-delayed decentralized structural control strategy that aims to minimize the H* norm of a closed-loop control system. The decentralized controller design employs a homotopy method that gradually transforms a centralized controller into multiple decentralized controllers. Linear matrix inequality constraints are included in the homotopic transformation to ensure optimal control performance. The paper also describes our first implementation of a real-time wireless sensing and control system that achieves simultaneous communication within multiple wireless subnets. Different decentralized H* control architectures are implemented with a network of wireless sensing and control units instrumented on a six-story scaled steel frame structure controlled by magnetorheological dampers. Shake table experiments are conducted to demonstrate the performance of the wireless decentralized control architectures.