bluuebunny/crossref_metadata_2025_split huggingface dataset:
Solution structure and binding specificity of the p63 DNA binding domain
Authors: Enthart Andreas , Klein Christian , Dehner Alexander , Coles Murray , Gemmecker Gerd , Kessler Horst , Hagn Franz 
Published: May 2016

Abstractp63 is a close homologue of p53 and, together with p73, is grouped into the p53 family of transcription factors. p63 is known to be involved in the induction of controlled apoptosis important for differentiation processes, germ line integrity and development. Despite its high homology to p53, especially within the DNA binding domain (DBD), p63-DBD does not show cooperative DNA binding properties and is significantly more stable against thermal and chemical denaturation. Here, we determined the solution structure of p63-DBD and show that it is markedly less dynamic than p53-DBD. In addition, we also investigate the effect of a double salt bridge present in p53-DBD, but not in p63-DBD on the cooperative binding behavior and specificity to various DNA sites. Restoration of the salt bridges in p63-DBD by mutagenesis leads to enhanced binding affinity to p53-specific, but not p63-specific response elements. Furthermore, we show that p63-DBD is capable of binding to anti-apoptotic BclxL via its DNA binding interface, a feature that has only been shown for p53 so far. These data suggest that all p53 family members - despite alterations in the specificity and binding affinity - are capable of activating pro-apoptotic pathways in a tissue specific manner.
Phage selection restores antibiotic sensitivity in MDR Pseudomonas aeruginosa
Authors: Chan Benjamin K. , Sistrom Mark , Wertz John E. , Kortright Kaitlyn E. , Narayan Deepak , Turner Paul E. 
Published: May 2016

AbstractIncreasing prevalence and severity of multi-drug-resistant (MDR) bacterial infections has necessitated novel antibacterial strategies. Ideally, new approaches would target bacterial pathogens while exerting selection for reduced pathogenesis when these bacteria inevitably evolve resistance to therapeutic intervention. As an example of such a management strategy, we isolated a lytic bacteriophage, OMKO1, (family Myoviridae) of Pseudomonas aeruginosa that utilizes the outer membrane porin M (OprM) of the multidrug efflux systems MexAB and MexXY as a receptor-binding site. Results show that phage selection produces an evolutionary trade-off in MDR P. aeruginosa, whereby the evolution of bacterial resistance to phage attack changes the efflux pump mechanism, causing increased sensitivity to drugs from several antibiotic classes. Although modern phage therapy is still in its infancy, we conclude that phages, such as OMKO1, represent a new approach to phage therapy where bacteriophages exert selection for MDR bacteria to become increasingly sensitive to traditional antibiotics. This approach, using phages as targeted antibacterials, could extend the lifetime of our current antibiotics and potentially reduce the incidence of antibiotic resistant infections.
Discovery and small RNA profile of Pecan mosaic-associated virus, a novel potyvirus of pecan trees
Authors: Su Xiu , Fu Shuai , Qian Yajuan , Zhang Liqin , Xu Yi , Zhou Xueping 
Published: May 2016

AbstractA novel potyvirus was discovered in pecan (Carya illinoensis) showing leaf mosaic symptom through the use of deep sequencing of small RNAs. The complete genome of this virus was determined to comprise of 9,310 nucleotides (nt), and shared 24.0% to 58.9% nucleotide similarities with that of other Potyviridae viruses. The genome was deduced to encode a single open reading frame (polyprotein) on the plus strand. Phylogenetic analysis based on the whole genome sequence and coat protein amino acid sequence showed that this virus is most closely related to Lettuce mosaic virus. Using electron microscopy, the typical Potyvirus filamentous particles were identified in infected pecan leaves with mosaic symptoms. Our results clearly show that this virus is a new member of the genus Potyvirus in the family Potyviridae. The virus is tentatively named Pecan mosaic-associated virus (PMaV). Additionally, profiling of the PMaV-derived small RNA (PMaV-sRNA) showed that the most abundant PMaV-sRNAs were 21-nt in length. There are several hotspots for small RNA production along the PMaV genome; two 21-nt PMaV-sRNAs starting at 811 nt and 610 nt of the minus-strand genome were highly repeated.
Intestinal APCs of the endogenous nanomineral pathway fail to express PD-L1 in Crohn’s disease
Authors: Robertson Jack , Haas Carolin T. , Pele Laetitia C. , Monie Tom P. , Charalambos Charles , Parkes Miles , Hewitt Rachel E. , Powell Jonathan J. 
Published: May 2016

AbstractCrohn’s disease is a chronic inflammatory condition most commonly affecting the ileum and colon. The aetiology of Crohn’s disease is complex and may include defects in peptidoglycan recognition, and/or failures in the establishment of intestinal tolerance. We have recently described a novel constitutive endogenous delivery system for the translocation of nanomineral-antigen-peptidoglycan (NAP) conjugates to antigen presenting cells (APCs) in intestinal lymphoid patches. In mice NAP conjugate delivery to APCs results in high surface expression of the immuno-modulatory molecule programmed death receptor ligand 1 (PD-L1). Here we report that NAP conjugate positive APCs in human ileal tissues from individuals with ulcerative colitis and intestinal carcinomas, also have high expression of PD-L1. However, NAP-conjugate positive APCs in intestinal tissue from patients with Crohn’s disease show selective failure in PD-L1 expression. Therefore, in Crohn’s disease intestinal antigen taken up by lymphoid patch APCs will be presented without PD-L1 induced tolerogenic signalling, perhaps initiating disease.
Quasi-freestanding graphene on Ni(111) by Cs intercalation
Authors: Alattas M. , Schwingenschlögl U. 
Published: May 2016

AbstractA possible approach to achieve quasi-freestanding graphene on a substrate for technological purpose is the intercalation of alkali metal atoms. Cs intercalation between graphene and Ni(111) therefore is investigated using density functional theory, incorporating van der Waals corrections. It is known that direct contact between graphene and Ni(111) perturbs the Dirac states. We find that Cs intercalation restores the linear dispersion characteristic of Dirac fermions, which agrees with experiments, but the Dirac cone is shifted to lower energy, i.e., the graphene sheet is n-doped. Cs intercalation therefore decouples the graphene sheet from the substrate except for a charge transfer. On the other hand, the spin polarization of Ni(111) does not extend through the intercalated atoms to the graphene sheet, for which we find virtually spin-degeneracy.
Radiocarbon dating of prehistoric phytoliths: a preliminary study of archaeological sites in China
Authors: Zuo Xinxin , Lu Houyuan , Zhang Jianping , Wang Can , Sun Guoping , Zheng Yunfei 
Published: May 2016

AbstractPhytoliths can occlude some organic carbon during their deposition in plants. This carbon fraction is recognised as an ideal dating material because of its high resistance to decomposition and post-deposition contamination at the time of phytolith formation. However, the reliability of phytolith radiocarbon dating has recently been questioned. The development of a new extraction protocol for phytoliths, with paired dating between phytoliths and other materials from the same sediment, may provide further evidence for the reliability of phytolith dating. We present an improved method for extracting phytoliths from soils. We compared the dating of phytoliths and other materials (e.g., charcoal and plant seeds) recovered at the same depth from seven pits at six archaeological sites in China. The estimated ages of the phytoliths and other materials were generally consistent, except for one outlier. We attribute this inconsistency to the post-depositional processes of phytoliths in soil, rather than to the uptake of old carbon from the soil. Our results clearly show the potential for phytolith carbon dating at archaeological sites in the absence of other dating materials.
Design strategy of surface decoration for efficient delivery of nanoparticles by computer simulation
Authors: Ding Hong-ming , Ma Yu-qiang 
Published: May 2016

AbstractUnderstanding the role of surface decoration of nanoparticles in protein adsorption and cellular uptake is of great importance in biomedicine. Here, by using dissipative particle dynamics simulations, we take two typical coating polymers (i.e., hydrophilic and zwitterionic polymers) as an example and systematically investigate their effect on cellular delivery of hydrophobic and charged nanoparticles (in the presence of serum protein). Our results show that though two types of polymers are charge-neutral and can both reduce the protein adsorption, there exist some differences between their ability of protein resistance, especially in the case of positively charged nanoparticles. Besides, it is found that the coating polymers may also greatly decrease the cellular uptake efficiency of nanoparticles. Nevertheless and importantly, since the zwitterionic polymers may become positively charged under low pH environments, the nanoparticle can attach onto cell membrane more firmly than that coated with hydrophilic polymers, which can further enhance the active targeting of nanoparticles. Finally, we also provide the design maps for surface decoration to achieve efficient cellular delivery. These results can help better understand how to keep the balance between protein resistance and cell targeting, which may give some useful guidelines on optimal design of future nanomaterials in drug delivery.
Vaginal Dysbiosis from an Evolutionary Perspective
Authors: Schlabritz-Loutsevitch Natalia , Gygax Scott E , Dick Edward , Smith William L. , Snider Cathy , Hubbard Gene , Ventolini Gary 
Published: May 2016

AbstractEvolutionary approaches are powerful tools for understanding human disorders. The composition of vaginal microbiome is important for reproductive success and has not yet been characterized in the contexts of social structure and vaginal pathology in non-human primates (NHPs). We investigated vaginal size, vulvovaginal pathology and the presence of the main human subtypes ofLactobacillusspp./ BV-related species in the vaginal microflora of baboons (Papio spp.). We performed morphometric measurements of external and internal genitalia (group I, n = 47), analyzed pathology records of animals from 1999–2015 (group II, n = 64 from a total of 12,776), and evaluated vaginal swabs using polymerase chain reaction (PCR) (group III, n = 14). A total of 68 lesions were identified in 64 baboons.Lactobacillus iners, Gardnerella vaginalis, Atopobium vaginae, Megasphaera I, andMegasphaera IIwere not detected.L. jensenii, L. crispatus, andL. gasseriwere detected in 2/14 (14.2%), 1/14 (7.1%), and 1/14 (7.1%) samples, respectively.BVAB2was detected in 5/14 (35.7%) samples. The differences in the vaginal milieu between NHP and humans might be the factor associated with human-specific pattern of placental development and should be taken in consideration in NHP models of human pharmacology and microbiology.
A novel approach of chemical mechanical polishing for cadmium zinc telluride wafers
Authors: Zhang Zhenyu , Wang Bo , Zhou Ping , Kang Renke , Zhang Bi , Guo Dongming 
Published: May 2016

AbstractA novel approach of chemical mechanical polishing (CMP) is developed for cadmium zinc telluride (CdZnTe or CZT) wafers. The approach uses environment-friendly slurry that consists of mainly silica, hydrogen peroxide and citric acid. This is different from the previously reported slurries that are usually composed of strong acid, alkali and bromine methanol and are detrimental to the environment and operators. Surface roughness 0.5 nm and 4.7 nm are achieved for Ra and peak-to-valley (PV) values respectively in a measurement area of 70 × 50 μm2, using the developed novel approach. Fundamental polishing mechanisms are also investigated in terms of X-ray photoelectron spectroscopy (XPS) and electrochemical measurements. Hydrogen peroxide dominates the passivating process during the CMP of CZT wafers, indicating by the lowest passivation current density among silica, citric acid and hydrogen peroxide solution. Chemical reaction equations are proposed during CMP according to the XPS and electrochemical measurements.
MicroRNA-126 contributes to Niaspan treatment induced vascular restoration after diabetic retinopathy
Authors: Wang Yang , Yan Hua 
Published: May 2016

AbstractDiabetic retinopathy (DR) is a serious microvascular complication of diabetes and a major cause of blindness in the developing world. Early diabetic retinopathy is characterized by a loss of pericytes and vascular endothelial cells, a breakdown of the blood–retinal barrier, vascular dysfunction and vascular-neuroinflammation. However, optimal treatment options and related mechanisms are still unclear. MicroRNA-126 (miR-126) plays a potential role in the pathogenesis in DR, which may regulate VEGF, Ang-1 and VCAM-1 expressions. This study investigated the therapeutic effects and mechanisms of Niaspan treatment of DR in diabetes (DM) rats. DM rats exhibits significantly decreased miR-126 and tight junction Claudin-5/Occludin/ZO-1 genes expression and increased Blood retinal-barrier (BRB) breakdown, retinal apoptosis and VEGF/VEGFR, as well as VCAM-1/CD45 expressions in the retina compared to normal control group. Niaspan treatment significantly improved clinical and histopathological outcomes; decreased the expressions of VEGF/VEGFR, VCAM-1/CD45, apoptosis and BRB breakdown, significantly increased tight junction proteins and Ang-1/Tie-2 expressions, as well as increased retinal miR-126 expression compared to non-treatment diabetic rats. These data are the first to show that Niaspan treatment ameliorates DR through its repair vascular and inhibits inflammatory effects and also suggest that the miR-126 pathway may contribute to Niaspan treatment induced benefit effects.
Transcriptional regulator Bhlhe40 works as a cofactor of T-bet in the regulation of IFN-γ production iniNKT cells
Authors: Kanda Masatoshi , Yamanaka Hiroyuki , Kojo Satoshi , Usui Yuu , Honda Hiroaki , Sotomaru Yusuke , Harada Michishige , Taniguchi Masaru , Suzuki Nao , Atsumi Tatsuya , Wada Haruka , Baghdadi Muhammad , Seino Ken-ichiro 
Published: May 2016

SignificanceA unique characteristic of invariant natural killer T (iNKT) cells is their ability to immediately produce large amounts of interferon-gamma (IFN-γ) upon activation, which enables these cells to play critical roles in initiating immune responses in various pathological conditions. In this study, we demonstrate a previously unidentified mechanism mediated by basic helix–loop–helix transcription factor family, member e40 (Bhlhe40) for accelerating IFN-γ production iniNKT cells. Bhlhe40 is required for normal physiological functions iniNKT cells, where it positively regulates IFN-γ production. Bhlhe40 also contributes to acetylating histone H3-lysine 9 of theIfnglocus iniNKT cells. These findings may help in understanding the molecular mechanisms related to the biology ofiNKT cells.
Lévy-Khintchine random matrices and the Poisson weighted infinite skeleton tree
Authors: Jung Paul 
Published: May 2016

We study a class of Hermitian random matrices which includes Wigner matrices, heavy-tailed random matrices, and sparse random matrices such as adjacency matrices of Erdős-Rényi random graphs with

p
n

∼

1
n

p_n\sim \frac 1 n

. Our

n
×
n

n\times n

random matrices have real entries which are i.i.d. up to symmetry. The distribution of entries depends on

n
n

, and we require row sums to converge in distribution. It is then well-known that the limit distribution must be infinitely divisible.

We show that a limiting empirical spectral distribution (LSD) exists and, via local weak convergence of associated graphs, that the LSD corresponds to the spectral measure associated to the root of a graph which is formed by connecting infinitely many Poisson weighted infinite trees using a backbone structure of special edges called “cords to infinity”. One example covered by the results are matrices with i.i.d. entries having infinite second moments but normalized to be in the Gaussian domain of attraction. In this case, the limiting graph is

N

\mathbb {N}

rooted at

1
1

, so the LSD is the semicircle law.
Acute Encephalitis and Abnormal MRI
Authors: Wijdicks Eelco F. M. , Rabinstein Alejandro A. , Hocker Sara E. , Fugate Jennifer E. 
Published: May 2016

Abstract
The diagnosis of encephalitis is easy, finding the cause is not. Clinicians should always consider the diagnosis of encephalitis in a febrile and confused patient, regardless of the presence of meningeal signs or focal deficits. In this chapter, the differential diagnosis of the main forms of acute encephalitis is discussed. Polymerase chain reaction for herpes simplex virus 1 (HSV-1) should be performed in all cerebrospinal fluid samples of patients with presumed encephalitis. MRI with gadolinium is the most informative neuroimaging modality for patients with suspected encephalitis. Medical therapy and indications for brain biopsy are also mentioned in the chapter.
Acutely Progressive Dyspnea and Limb Weakness
Authors: Wijdicks Eelco F. M. , Rabinstein Alejandro A. , Hocker Sara E. , Fugate Jennifer E. 
Published: May 2016

Abstract
Paradoxical breathing is the most characteristic sign of neuromuscular respiratory failure. How to confidently assess the need for respiratory support in acute neuromuscular disease is difficult. This chapter discusses indications of triage to the intensive care unit, the benefits and risks of noninvasive mechanical ventilation, and indications of intubation in acute neuromuscular disorders such as Guillain-Barré syndrome and myasthenia gravis. Patients with Guillain-Barré syndrome should be intubated electively when they develop their first signs of ventilatory failure. Patients with myasthenic crisis are best treated with noninvasive ventilation if this support is initiated before the development of hypercapnia.
Prior Cancer and a Worrisome MRI of the Spine
Authors: Wijdicks Eelco F. M. , Rabinstein Alejandro A. , Hocker Sara E. , Fugate Jennifer E. 
Published: May 2016

Abstract
For patients with spinal cord compression, from metastasis in the patient presented in this chapter, there is an immediate urgency to prevent permanent paralysis. For many physicians this is one of the most uncomfortable situations. The medical treatment with corticosteroids and indications for acute neurosurgical decompression are discussed in this chapter. Aggressive pain management with opioids and corticosteroids may provide adequate palliation. The treatment modality that is best for the patient is determined on the basis of severity and acuity of the neurological deficit, nature of the tumor, instability of the spine, and general performance status and life expectancy of the patient.
Treatable Toxicity After Chemotherapy
Authors: Wijdicks Eelco F. M. , Rabinstein Alejandro A. , Hocker Sara E. , Fugate Jennifer E. 
Published: May 2016

Abstract
This chapter discusses how to manage a comatose patient with a serious intoxication. Intoxications often present with prominent neurological features, most notably depressed consciousness, delirium, abnormal movements, and seizures. None of these manifestations are specific for any single toxin. Recognition of the most common toxidromes can guide management and predict complications. Early management focuses on securing the airway, ensuring adequate oxygenation, achieving hemodynamic stabilization, excluding hypoglycemia, and considering gastrointestinal decontamination. Options for antidotes, dialysis, and other measures to correct laboratory abnormalities are concisely reviewed in the chapter.
Rigidity After Experimenting with Drugs
Authors: Wijdicks Eelco F. M. , Rabinstein Alejandro A. , Hocker Sara E. , Fugate Jennifer E. 
Published: May 2016

Abstract
Abnormal involuntary movements described variably as twitching, jerking, shaking or convulsing are a common reason for neurological consultation in intensive care units. While many of the abnormal movements in critical illness may simply be observed, certain acute movement disorders represent potentially lethal emergencies and require prompt recognition and treatment. Often these movements indicate some toxicity of some newly introduced drug. An overview of potential causes is presented in this chapter. The majority of acute movement disorders are drug-induced, such as serotonin syndrome, or result from severe metabolic derangements. The triad of acute encephalopathy, fever, and increased tone in association with involuntary movements should prompt consideration of a serious cause.
Sweaty, Febrile, and Tachypneic After Traumatic Brain Injury
Authors: Wijdicks Eelco F. M. , Rabinstein Alejandro A. , Hocker Sara E. , Fugate Jennifer E. 
Published: May 2016

Abstract
Paroxysmal sympathetic hyperactivity after traumatic brain injury is an underappreciated and undertreated condition. It may cause potentially life-threatening complications, such as intracranial hypertension, dehydration, hyperthermia, refractory surges of hypertension, and muscle contractures. The differential diagnosis is broad, but it can be sorted out quickly by a focused evaluation. The difficulties with management and short- and long-term pharmacological approaches are discussed in this chapter. These include boluses of morphine sulfate for aborting the episodes, propranolol and clonidine for control of the tachycardia and hypertension, and baclofen and diazepam for improving increased muscle tone. Gabapentin is useful for achieving control of the sympathetic dysfunction in the long term.
Hypertension and Bradycardia in Severe Guillain-Barré Syndrome
Authors: Wijdicks Eelco F. M. , Rabinstein Alejandro A. , Hocker Sara E. , Fugate Jennifer E. 
Published: May 2016

Abstract
Dysautonomia is common in severe forms of Guillain-Barré syndrome. Paralytic ileus is a concern in all immobilized bedridden patients with this syndrome. Marked blood pressure fluctuations or sustained hypertension are the most concerning manifestations. Treatment of these autonomic disorders is provided in this chapter. Hypertensive surges can be treated with morphine, clonidine, or, if necessary, an infusion of a calcium channel blocker, such as nicardipine. Vagal spells may lead to prolonged episodes of asystole, and a transcutaneous pacemaker might be needed. Every bedridden patient with severe Guillain-Barré syndrome is at risk of developing severe adynamic ileus, and treatment may require a period of parenteral nutrition or colonoscopic decompression.
Struggling to Get a Patient with Myasthenia Gravis off the Ventilator
Authors: Wijdicks Eelco F. M. , Rabinstein Alejandro A. , Hocker Sara E. , Fugate Jennifer E. 
Published: May 2016

Abstract
Weaning from the mechanical ventilator after intubation following treatment for myasthenic crisis is difficult. There is a high probability of reintubation, especially in patients with bronchial hypersecretion and atelectasis. Long-term management with placement of a tracheostomy is needed after reintubation. Strategies for successful weaning and extubation are discussed in this chapter. Plasma exchange is the preferred treatment in myasthenic patients with severe neuromuscular respiratory muscle weakness. Plasma exchange may not be sufficient, however, to wean a patient off the ventilator, and pyridostigmine is needed to improve respiratory muscle function. Finding an optimal dose of pyridostigmine after treatment of myasthenic crisis is difficult. There is a fine line between minimizing secretions and optimizing the strength of oropharyngeal and respiratory muscles.