bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intermediates in the assembly of mitotic checkpoint complexes and their role in the regulation of the anaphase-promoting complex
Authors: Kaisari Sharon , Sitry-Shevah Danielle , Miniowitz-Shemtov Shirly , Hershko Avram 
Published: January 2016

Significance
The mitotic checkpoint system has important roles to ensure accurate segregation of chromosomes in mitosis. This system regulates the activity of the ubiquitin ligase Anaphase-Promoting Complex/Cyclosome (APC/C) by the formation of inhibitors including the Mitotic Checkpoint Complex (MCC). The mode of the assembly of MCC is not sufficiently understood, and it is also not known whether checkpoint complexes different from MCC also inhibit the APC/C. We find that complexes lacking Mad2, a protein component of MCC, have greatly reduced APC/C inhibitory action. On the other hand, a previously unknown species of MCC that contains an additional molecule of Cdc20 is a strong inhibitor of APC/C. These results reveal important molecular mechanisms in the action of the mitotic checkpoint system.
Calcium sensor regulation of the Ca
V
2.1 Ca
2+
channel contributes to short-term synaptic plasticity in hippocampal neurons
Authors: Nanou Evanthia , Sullivan Jane M. , Scheuer Todd , Catterall William A. 
Published: January 2016

Significance
Information processing in the brain is mediated through synaptic connections between neurons, where neurotransmitter molecules released from presynaptic nerve terminals stimulate postsynaptic cells. Strength of synaptic transmission is increased transiently by short-term synaptic facilitation in response to repeated stimulation of nerve fibers. Synaptic transmission is initiated by calcium influx through calcium channels in presynaptic nerve terminals, which are regulated by calcium sensor proteins. We found that genetically modified mice in which we introduced a mutation in the binding site for calcium sensor proteins in presynaptic calcium channels have substantially altered facilitation in hippocampal synapses in response to pairs or trains of repetitive high-frequency stimuli. Our results show that disruption of calcium channel regulation by calcium sensor proteins impairs short-term facilitation in native synapses.
Altered short-term synaptic plasticity and reduced muscle strength in mice with impaired regulation of presynaptic Ca
V
2.1 Ca
2+
channels
Authors: Nanou Evanthia , Yan Jin , Whitehead Nicholas P. , Kim Min Jeong , Froehner Stanley C. , Scheuer Todd , Catterall William A. 
Published: January 2016

Significance
Muscle contraction begins with release of neurotransmitter molecules from motor-nerve terminals onto muscle fibers. Strength of contraction depends on high-frequency stimulation of the nerve, which induces short-term increases in neurotransmitter release through presynaptic facilitation. Neurotransmitter release is initiated via calcium influx through voltage-gated calcium channels, which are regulated by calcium sensor (CaS) proteins. We found that genetically modified mice with a mutation in the binding site for CaS proteins on presynaptic calcium channels have reduced synaptic facilitation during high-frequency stimulation, resulting in reduced muscle strength, endurance, and coordination. Our results demonstrate critical roles for the regulation of calcium channels by CaS proteins in short-term presynaptic facilitation, with important consequences for motor control and muscle function in vivo.
Formation of nanosized grain structure in martensitic 100Cr6 bearing steels upon rolling contact loading studied by atom probe tomography
Authors: Li Y. J. , Herbig M. , Goto S. , Raabe D. 
Published: January 2016

To understand the origin of white etching cracks (WECs), a systematic microstructural characterisation in the regions affected from the near-surface region down to the subsurface layers where WECs occur is necessary. As a starting point, we focus on the near-surface region of an axial thrust bearing, made of martensitic 100Cr6 steel, to study the influence of rolling contact loading on the microstructure and the resulting distributions of the major alloying elements C and Cr using atom probe tomography. We find that upon rolling contact loading the original plate-like martensitic structure evolves into a nanosized equiaxed grain structure with C segregation up to 5 at.-% at the grain boundaries. Cementite particles, located at grain boundaries and triple junctions, undergo spheroidisation. The originally homogeneously distributed Cr becomes enriched in spheroidised cementite particles. The microstructural changes give strong hints that rolling contact loading induces plastic deformation and an increased temperature on the near-surface region. This paper is part of a Themed Issue on Recent developments in bearing steels.
Loss of the smallest subunit of cytochrome c oxidase, COX8A, causes Leigh-like syndrome and epilepsy
Authors: Hallmann Kerstin , Kudin Alexei P. , Zsurka Gábor , Kornblum Cornelia , Reimann Jens , Stüve Burkhard , Waltz Stephan , Hattingen Elke , Thiele Holger , Nürnberg Peter , Rüb Cornelia , Voos Wolfgang , Kopatz Jens , Neumann Harald , Kunz Wolfram S. 
Published: January 2016

Abstract
Isolated cytochrome c oxidase (complex IV) deficiency is one of the most frequent respiratory chain defects in humans and is usually caused by mutations in proteins required for assembly of the complex. Mutations in nuclear-encoded structural subunits are very rare. In a patient with Leigh-like syndrome presenting with leukodystrophy and severe epilepsy, we identified a homozygous splice site mutation in COX8A, which codes for the ubiquitously expressed isoform of subunit VIII, the smallest nuclear-encoded subunit of complex IV. The mutation, affecting the last nucleotide of intron 1, leads to aberrant splicing, a frame-shift in the highly conserved exon 2, and decreased amount of the COX8A transcript. The loss of the wild-type COX8A protein severely impairs the stability of the entire cytochrome c oxidase enzyme complex and manifests in isolated complex IV deficiency in skeletal muscle and fibroblasts, similar to the frequent c.845_846delCT mutation in the assembly factor SURF1 gene. Stability and activity of complex IV could be rescued in the patient’s fibroblasts by lentiviral expression of wild-type COX8A. Our findings demonstrate that COX8A is indispensable for function of human complex IV and its mutation causes human disease.
Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America
Authors: Pappas Peter G. , Kauffman Carol A. , Andes David R. , Clancy Cornelius J. , Marr Kieren A. , Ostrosky-Zeichner Luis , Reboli Annette C. , Schuster Mindy G. , Vazquez Jose A. , Walsh Thomas J. , Zaoutis Theoklis E. , Sobel Jack D. 
Published: January 2016

AbstractIt is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.
Human Cytomegalovirus Up-Regulates Endothelin Receptor Type B: Implication for Vasculopathies?
Authors: Yaiw Koon-Chu , Mohammad Abdul-Aleem , Costa Helena , Taher Chato , Badrnya Sigrun , Assinger Alice , Wilhelmi Vanessa , Ananthaseshan Sharan , Estekizadeh Atosa , Davoudi Belghis , Ovchinnikova Olga , Shlyakhto Eugene , Rafnsson Arnar , Khan Zahidul , Butler Lynn , Rahbar Afsar , Pernow John , Söderberg-Nauclér Cecilia 
Published: January 2016

Abstract
Background.  Both endothelin receptor type B ([ETBR], a G protein-coupled receptor that mediates the vascular effects of the potent vasoconstrictor endothelin-1) and human cytomegalovirus ([HCMV], a ubiquitous herpesvirus) have been implicated in the pathogenesis of cardiovascular disease (CVD). The effects of HCMV infection on ETBR expression are unknown. We hypothesized that HCMV may contribute to the pathogenesis of CVD via ETBR modulation.
Methods.  Human CMV effects on ETBR were studied in vitro in endothelial cells (ECs) and smooth muscle cells (SMCs) and ex vivo in human carotid plaque tissue specimens. Expression of ETBR and viral immediate-early were quantified using quantitative polymerase chain reaction. Functional consequences after ETBR blockade in ECs were examined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide proliferation, wound healing, tube formation, and flow adhesion assays.
Results.  Human CMV is capable of upregulating both ETBR mRNA and protein expression in ECs and SMCs. The ETBR was also abundantly expressed in ECs, foam cells, and SMCs, and, more importantly, in HCMV-positive cells in human carotid plaques. Endothelin receptor type B blockade led to decreased proliferation and reduced tumor necrosis factor α-mediated leukocyte recruitment in both uninfected and HCMV-infected ECs. Direct HCMV infection was antimigratory and antiangiogenic in ECs.
Conclusions.  Human CMV may contribute to CVD via ETBR induction.
The Effect of Rosuvastatin on Markers of Immune Activation in Treatment-Naive Human Immunodeficiency Virus-Patients
Authors: Weijma Robyn G. M. , Vos Eric R. A. , Ten Oever Jaap , Van Schilfgaarde Muriel , Dijksman Lea M. , Van Der Ven André , Van Den Berk Guido E. L. , Brinkman Kees , Frissen Jos P. H. J. , Leyte Anja , Schouten Ineke W. E. M. , Netea Mihai G. , Blok Willem L. 
Published: January 2016

AbstractBackground.  Immune activation has been implicated in the excess mortality in human immunodeficiency virus (HIV)-infected patients, due to cardiovascular diseases and malignancies. Statins may modulate this immune activation. We assessed the capacity of rosuvastatin to mitigate immune activation in treatment-naive HIV-infected patients.Methods.  In a randomized double-blind placebo-controlled crossover study, we explored the effects of 8 weeks of rosuvastatin 20 mg in treatment-naive male HIV-infected patients (n = 28) on immune activation markers: neopterin, soluble Toll-like receptor (TLR)2, sTLR4, interleukin (IL)-6, IL-1Ra, IL-18, d-dimer, highly sensitive C-reactive protein, and CD38 and/or human leukocyte antigen-DR expression on T cells. Baseline data were compared with healthy male controls (n = 10). Furthermore, the effects of rosuvastatin on HIV-1 RNA, CD4/CD8 T-cell count, and low-density lipoprotein cholesterol were examined and side effects were registered.Results.  T-cell activation levels were higher in patients than in controls. Patients had higher levels of circulating IL-18, sTLR2, and neopterin (all P &lt; .01). Twenty patients completed the study. Rosuvastatin increased the CD4/CD8 T-cell ratio (P = .02). No effect on other markers was found.Conclusions.  Patients infected with HIV had higher levels of circulating neopterin, IL-18, sTLR2, and T-cell activation markers. Rosuvastatin had a small but significant positive effect on CD4/CD8 T-cell ratio, but no influence on other markers of T-cell activation and innate immunity was identified (The Netherlands National Trial Register [NTR] NTR 2349, http://www.trialregister.nl/trialreg/index.asp).
A Cumulative Spore Killing Approach: Synergistic Sporicidal Activity of Dilute Peracetic Acid and Ethanol at Low pH Against Clostridium difficile and Bacillus subtilis Spores
Authors: Nerandzic Michelle M. , Sankar C Thriveen , Setlow Peter , Donskey Curtis J. 
Published: January 2016

Abstract
Background.  Alcohol-based hand sanitizers are the primary method of hand hygiene in healthcare settings, but they lack activity against bacterial spores produced by pathogens such as Clostridium difficile and Bacillus anthracis. We previously demonstrated that acidification of ethanol induced rapid sporicidal activity, resulting in ethanol formulations with pH 1.5–2 that were as effective as soap and water washing in reducing levels of C difficile spores on hands. We hypothesized that the addition of dilute peracetic acid (PAA) to acidified ethanol would enhance sporicidal activity while allowing elevation of the pH to a level likely to be well tolerated on skin (ie, &gt;3).
Methods.  We tested the efficacy of acidified ethanol solutions alone or in combination with PAA against C difficile and Bacillus subtilis spores in vitro and against nontoxigenic C difficile spores on hands of volunteers.
Results.  Acidification of ethanol induced rapid sporicidal activity against C difficile and to a lesser extent B subtilis. The addition of dilute PAA to acidified ethanol resulted in synergistic enhancement of sporicidal activity in a dose-dependent fashion in vitro. On hands, the addition of 1200–2000 ppm PAA enhanced the effectiveness of acidified ethanol formulations, resulting in formulations with pH &gt;3 that were as effective as soap and water washing.
Conclusions.  Acidification and the addition of dilute PAA induced rapid sporicidal activity in ethanol. Our findings suggest that it may be feasible to develop effective sporicidal ethanol formulations that are safe and tolerable on skin.
Clinical Liver Disease Progression Among Hepatitis C-Infected Drug Users With CD4 Cell Count Less Than 200 Cells/mm3 Is More Pronounced Among Women Than Men
Authors: Baranoski Amy S. , Cotton Deborah , Heeren Timothy , Nunes David , Kubiak Rachel W. , Horsburgh C. Robert 
Published: January 2016

Abstract
Background.  Hepatitis C virus (HCV) infection is a leading cause of liver-related morbidity and mortality in the United States, and injection drug users are at particularly high risk.
Methods.  This prospective observational cohort study assessed the rate of, and risk factors for, clinical liver disease progression in a cohort of HCV monoinfected and human immunodeficiency virus (HIV)/HCV coinfected drug users using unadjusted and multivariate Cox proportional hazards regression analyses.
Results.  Of 564 subjects including 421 (75%) with HIV/HCV coinfection and 143 with HCV monoinfection, 55 (10%) had clinical liver disease progression during follow-up with a rate of 25.3 events per 1000 person-years. In unadjusted analysis, there was an interaction between sex and HIV status. In sex-stratified multivariate analysis, HIV/HCV-coinfected women with CD4 &lt;200 cells/mm3 had 9.99 times the risk of liver disease progression as HCV-monoinfected women (confidence interval [CI], 1.84–54.31; P = .008), and white women had a trend towards increased risk of liver disease progression compared with non-white women (hazard ratio, 2.84; CI, .93–8.68; P = .07). Human immunodeficiency virus/HCV-coinfected men with CD4 &lt;200 cells/mm3 had 2.86 times the risk of liver disease progression as HCV-monoinfected men (CI, 1.23-6.65; P = .01).
Conclusions.  Hepatitis C virus-monoinfected and HIV/HCV-coinfected drug users had high rates of clinical liver disease progression. In those with HIV infection, liver disease progression was associated with advanced immune suppression. This effect was strikingly more pronounced in women than in men.
Completion Rate and Side-Effect Profile of Three-Month Isoniazid and Rifapentine Treatment for Latent Tuberculosis Infection in an Urban County Jail
Authors: Juarez-Reyes Maria , Gallivan Mark , Chyorny Alexander , O'Keeffe Linda , Shah Neha S. 
Published: January 2016

Abstract
In an urban jail population, 3 months of isoniazid and rifapentine (3HP) was associated with an 85% latent tuberculosis infection treatment completion rate compared with 18% in a standard 9-month isoniazid treatment group. Among the 91 patients who started 3HP therapy, there were 2 treatment discontinuations from adverse drug reactions.
Observational constraint on Pluto's atmospheric CO with ASTE
Authors: Iino Takahiro , Hirahara Yasuhiro , Hidemori Takehiro , Tsukagoshi Takashi , Nakajima Taku , Nakamoto Satoru , Kato Chihaya 
Published: January 2016

Abstract
To confirm the previous observational results of Pluto's atmospheric CO in the J = 2–1 rotational transition, we conducted a new observation of CO (J = 3–2) in Pluto's atmosphere in 2014 August with the Atacama Submillimeter Telescope Experiment 10 m single-dish telescope. In contrast to the previous observational result obtained with the James Clerk Maxwell Telescope in 2009 and 2010 by using the J = 2–1 transition, no emission structure was observed near the rest frequency in our attempt. Possible explanations for the nondetection result of the J = 3–2 transition are discussed.
Activation of Peripheral μ-opioid Receptors by Dermorphin [d-Arg2, Lys4] (1–4) Amide Leads to Modality-preferred Inhibition of Neuropathic Pain
Authors: Tiwari Vinod , Yang Fei , He Shao-Qiu , Shechter Ronen , Zhang Chen , Shu Bin , Zhang Tong , Tiwari Vineeta , Wang Yun , Dong Xinzhong , Guan Yun , Raja Srinivasa N. 
Published: January 2016

AbstractAbstract
By using a model of male and female rats with spinal nerve ligation–induced neuropathic pain, the authors demonstrated that systemic administration of dermorphin [d-Arg2, Lys4] (1-4) amide, a highly selective μ-receptor agonist, attenuated both neuropathic mechanical and heat hypersensitivity through activation of μ-receptor at peripheral but not central sites. Further, the efficacy of dermorphin [d-Arg2, Lys4] (1-4) amide to inhibit heat hypersensitivity is greater than that to inhibit mechanical hypersensitivity.

Background
Opioids have long been regarded as the most effective drugs for the treatment of severe acute and chronic pain. Unfortunately, their therapeutic efficacy and clinical utility have been limited because of central and peripheral side effects.

Methods
To determine the therapeutic value of peripheral μ-opioid receptors as a target for neuropathic pain treatment, the authors examined the effects of dermorphin [d-Arg2, Lys4] (1–4) amide (DALDA), a hydrophilic, peripherally acting μ-opioid receptor agonist, in male and female rats with spinal nerve ligation–induced neuropathic pain. The authors also utilized behavioral, pharmacologic, electrophysiologic, and molecular biologic tools to characterize DALDA’s possible mechanisms of action in male rats.

Results
DALDA, administered subcutaneously, had 70 times greater efficacy for inhibiting thermal (n = 8 to 11/group) than mechanical hypersensitivity (n = 6 to 8/group) in male rats. The pain inhibitory effects of DALDA on mechanical and heat hypersensitivity were abolished in animals pretreated with systemic methylnaltrexone (n = 7 to 9/group), a peripheral μ-opioid receptor antagonist. In the spinal wide-dynamic range neurons, systemic DALDA inhibited C-fiber–mediated, but not A-fiber–mediated, response in neuropathic male rats (n = 13). In primary sensory neurons, DALDA inhibited the capsaicin-induced [Ca2+] increase more than the β-alanine–induced [Ca2+] increase (n = 300); capsaicin and β-alanine activate subpopulations of neurons involved in the signaling of heat and mechanical pain, respectively. DALDA-treated rats (n = 5 to 8/group) did not exhibit motor deficits and locomotor impairment suggesting that it does not induce central side effects.

Conclusions
These findings suggest that DALDA may represent a potential alternative to current opioid therapy for the treatment of neuropathic pain and is likely to be associated with minimal adverse effects.
A Randomized Controlled Trial Studying the Role of Dexamethasone in Scalp Nerve Blocks for Supratentorial Craniotomy
Authors: Jose Riya , Chakravarthy Kalyana , Nair Shalini , Joseph Mathew , Jeyaseelan Visalakshi , Korula Grace 
Published: January 2016

Background:
The aim of this double-blinded randomized control study was to examine the role of the steroid dexamethasone as an adjuvant to lignocaine and ropivacaine in scalp nerve blocks in adults undergoing supratentorial craniotomy under general anesthesia. We compared the intraoperative anesthetic and postoperative analgesic requirement with and without the addition of dexamethasone to the local anesthetics.

Methods:
The consented 90 patients were randomized into 2 groups: one group received 8 mg (2 mL) of dexamethasone, whereas the other received 2 mL of normal saline along with the local anesthetics in the scalp nerve block administered soon after induction of general anesthesia. All patients received oral/intravenous dexamethasone perioperatively to decrease cerebral edema. The general anesthetic technique for induction, maintenance, and recovery was standardized in the 2 groups. The primary outcome assessed was the time to administration of the first dose of analgesic postoperatively. The secondary outcomes included intraoperative opioid requirement, time to emergence, and incidence of postoperative nausea and vomiting.

Results:
There was no significant difference between the dexamethasone and saline groups with respect to time to first analgesic requirement, intraoperative fentanyl requirements, time to emergence from general anesthesia, and incidence of postoperative nausea and vomiting.

Conclusions:
Addition of dexamethasone as an adjuvant to local anesthetics in scalp nerve blocks in the setting of perioperative steroid therapy does not appear to provide any additional benefit with respect to prolongation of the duration of the block.
Cortical Atrophy Related to Tumor Prosthesis in Skeletally Immature Osteosarcoma Patients
Authors: Kim Wanlim , Han Ilkyu , Cho Hwan-Seong , Kang Seungcheol , Kim Han-Soo 
Published: January 2016

Background:
Cortical atrophy is commonly observed after prosthetic reconstruction for bone sarcomas. However, relevant literature regarding this phenomenon in skeletally immature patients is limited. Therefore, in this study, we evaluated the incidence and patterns of cortical atrophy. We then assessed its predisposing factors. Finally, we analyzed whether cortical atrophy was associated with poor prosthesis survival.

Methods:
We retrospectively reviewed 31 stems in 19 skeletally immature osteosarcoma patients who were treated with resection and tumor prosthesis surgery. We measured the cortical thickness using plain radiographs annually. The mean patient age was 11 years (range, 6 to 14 y) and the mean follow-up period was 10 years (range, 2 to 14 y).

Results:
Cortical atrophy developed in 13 stems, all within 3 years. There were 3 gross types of cortical atrophy: hourglass in 5, sharpening in 4, and shortening atrophy in 4. On multivariate analysis, stem-cortex diameter ratio of ≥0.5 and age of less than 10 years were significantly associated with cortical atrophy (P=0.002 and P=0.019, respectively). Cortical atrophy was significantly associated with eventual prosthesis failure (9/13 in the cortical atrophy group vs. 4/18 in the nonatrophy group, P=0.035).

Conclusions:
Cortical atrophy is common in the skeletally immature patients with tumor prosthesis and is associated with prosthesis failure. Patients with cortical atrophy should be closely monitored for prosthesis failure and appropriately managed to prevent failures.

Level of Evidence:
Level IV—therapeutic study.