bluuebunny/crossref_metadata_2025_split huggingface dataset:
The N-terminal loop of IRAK-4 death domain regulates ordered assembly of the Myddosome signalling scaffold
Authors: Dossang Anthony C. G. , Motshwene Precious G. , Yang Yang , Symmons Martyn F. , Bryant Clare E. , Borman Satty , George Julie , Weber Alexander N. R. , Gay Nicholas J. 
Published: November 2016

AbstractActivation of Toll-like receptors induces dimerization and the recruitment of the death domain (DD) adaptor protein MyD88 into an oligomeric post receptor complex termed the Myddosome. The Myddosome is a hub for inflammatory and oncogenic signaling and has a hierarchical arrangement with 6–8 MyD88 molecules assembling with exactly 4 of IRAK-4 and 4 of IRAK-2. Here we show that a conserved motif in IRAK-4 (Ser8-X-X-X-Arg12) is autophosphorylated and that the phosphorylated DD is unable to form Myddosomes. Furthermore a mutant DD with the phospho-mimetic residue Asp at this position is impaired in both signalling and Myddosome assembly. IRAK-4 Arg12 is also essential for Myddosome assembly and signalling and we propose that phosphorylated Ser8 induces the N-terminal loop to fold into an α-helix. This conformer is stabilised by an electrostatic interaction between phospho-Ser8 and Arg12 and would destabilise a critical interface between IRAK-4 and MyD88. Interestingly IRAK-2 does not conserve this motif and has an alternative interface in the Myddosome that requires Arg67, a residue conserved in paralogues, IRAK-1 and 3(M).
Experienced migratory songbirds do not display goal-ward orientation after release following a cross-continental displacement: an automated telemetry study
Authors: Kishkinev Dmitry , Heyers Dominik , Woodworth Bradley K. , Mitchell Greg W. , Hobson Keith A. , Norris D. Ryan 
Published: November 2016

AbstractThe ability to navigate implies that animals have the capability to compensate for geographical displacement and return to their initial goal or target. Although some species are capable of adjusting their direction after displacement, the environmental cues used to achieve this remain elusive. Two possible cues are geomagnetic parameters (magnetic map hypothesis) or atmospheric odour-forming gradients (olfactory map hypothesis). In this study, we examined both of these hypotheses by surgically deactivating either the magnetic or olfactory sensory systems in experienced white-throated sparrows (Zonotrichia albicollis) captured in southern Ontario, Canada, during spring migration. Treated, sham-treated, and intact birds were then displaced 2,200 km west to Saskatchewan, Canada. Tracking their initial post-displacement migration using an array of automated VHF receiving towers, we found no evidence in any of the groups for compensatory directional response towards their expected breeding grounds. Our results suggest that white-throated sparrows may fall back to a simple constant-vector orientation strategy instead of performing true navigation after they have been geographically displaced to an unfamiliar area during spring migration. Such a basic strategy may be more common than currently thought in experienced migratory birds and its occurrence could be determined by habitat preferences or range size.
Multiple crosstalk between TOR and the cell integrity MAPK signaling pathway in fission yeast
Authors: Madrid Marisa , Vázquez-Marín Beatriz , Franco Alejandro , Soto Teresa , Vicente-Soler Jero , Gacto Mariano , Cansado José 
Published: November 2016

AbstractIn eukaryotic cells, the highly conserved Target of Rapamycin (TOR) and the Mitogen Activated Protein Kinase (MAPK) signaling pathways elicit adaptive responses to extra- and intracellular conditions by regulating essential cellular functions. However, the nature of the functional relationships between both pathways is not fully understood. In the fission yeast Schizosaccharomyces pombe the cell integrity MAPK pathway (CIP) regulates morphogenesis, cell wall structure and ionic homeostasis. We show that the Rab GTPase Ryh1, a TORC2 complex activator, cross-activates the CIP and its core member, the MAPK Pmk1, by two distinct mechanisms. The first one involves TORC2 and its downstream effector, Akt ortholog Gad8, which together with TORC1 target Psk1 increase protein levels of the PKC ortholog Pck2 during cell wall stress or glucose starvation. Also, Ryh1 activates Pmk1 in a TORC2-independent fashion by prompting plasma membrane trafficking and stabilization of upstream activators of the MAPK cascade, including PDK ortholog Ksg1 or Rho1 GEF Rgf1. Besides, stress-activated Pmk1 cross-inhibits Ryh1 signaling by decreasing the GTPase activation cycle, and this ensures cell growth during alterations in phosphoinositide metabolism. Our results reveal a highly intricate cross-regulatory relationship between both pathways that warrants adequate cell adaptation and survival in response to environmental changes.
Novel structure in sciaenid fish skulls indicates continuous production of the cephalic neuromast cupula
Authors: Pombo Maíra , Turra Alexander 
Published: November 2016

AbstractThe presence of a conspicuous and frequent but never-described structure in the skull cavities of sciaenid fish was noted during population studies in an urbanized bay. The ultrastructure closely resembles the cupula of neuromasts, an organ associated with the perception of the environment in teleost fish. The bodies were recorded detached in both preserved and freshly sampled individuals and without associated cilia. Prominent characteristics are acellularity, the elliptic-conic shape composed of stack-like protein lamellas, and a mesh-like appearance in cross section. These acellular lamellar cephalic bodies (ALCBs) were more abundant in larger individuals and showed temporal peaks of abundance independently of the fish size. The conic and lamellar features suggest that the deposition of protein layers follows fish growth, and the bimodality of the size of these structures in individuals indicates temporal peaks of production. These results indicate that these ALCBs are a consequence of the accretion of the cupula of neuromasts at a faster rate than they degrade. Given the novelty of this structure and the increasing records of diseases of marine organisms worldwide, an important question is whether these bodies occur subsequently to some environmental change and whether their accumulation in the skull cavities has consequences to fish health.
The measurement of lung volumes using body plethysmography and helium dilution methods in COPD patients: a correlation and diagnosis analysis
Authors: Tang Yongjiang , Zhang Mingke , Feng Yulin , Liang Binmiao 
Published: November 2016

AbstractChronic obstructive pulmonary disease (COPD) is a chronic airway disease characterized by persistent airflow limitation. Moreover, lung hyperinflation evaluated by lung volumes is also the key pathophysiologic process during COPD progression. Nevertheless, there is still no preferred method to evaluate lung volumes. For this study, we recruited 170 patients with stable COPD to assess lung volumes stratified by airflow limitation severity. Lung volumes including residual volume (RV) and total lung capacity (TLC) were determined by both body plethysmography and helium dilution methods. The discrepancies between these two methods were recorded as ΔRV%pred, ΔTLC%pred, and ΔRV/TLC. We found that ΔRV%pred, ΔTLC%pred, and ΔRV/TLC increased significantly with the severity of COPD. The differences of lung capacity between these two methods were negatively correlated with FEV1%pred, and diffusing capacity for carbon monoxide (DLCO%pred). Moreover, the receiver operating characteristic (ROC) for ΔTLC%pred to distinguish severe COPD from non-severe COPD had an area under curve (AUC) of 0.886. The differences of lung volume parameters measured by body plethysmography and helium dilution methods were associated with airflow limitation and can effectively differentiate COPD severity, which may be a supportive method to assess the lung function of stable COPD patients.
In Silico Exploration for Novel Type-I Inhibitors of Tie-2/TEK: The Performance of Different Selection Strategy in Selecting Virtual Screening Candidates
Authors: Pan Peichen , Sun Huiyong , Liu Hui , Li Dan , Zhou Wenfang , Kong Xiaotian , Li Youyong , Yu Huidong , Hou Tingjun 
Published: November 2016

AbstractThe receptor tyrosine kinase Tie-2 is involved in vessel remodeling and maturation, and has been regarded as a potential target for the treatment of various solid tumors. The absence of novel, potent and selective inhibitors severely hampers the understanding of the therapeutic potential of Tie-2. In the present work, we describe the discovery of novel type-I inhibitors of Tie-2 by structure-based virtual screening. Preliminary SAR was also performed based on one active compound, and several novel inhibitors with low micro-molar affinity were discovered. To directly compare the efficiency between different filtering strategies in selecting VS candidates, two methods were separately carried out to screen the same chemical library, and the selected VS candidates were then experimentally assessed by in vitro enzymatic assays. The results demonstrate that the hit rate is improved when stricter drug-likeness criteria and less number of molecules for clustering analysis are used, and meanwhile, the molecular diversity of the compounds still maintains. As a case study of TIE-2, the information presented in this work underscores the importance of selecting an appropriate selection strategy in VS campaign, and the novel inhibitors identified and the detailed binding modes of action provide a starting point for further hit-to-lead optimization process.
ENSO’s far reaching connection to Indian cold waves
Authors: Ratnam J. V. , Behera Swadhin K. , Annamalai H. , Ratna Satyaban B. , Rajeevan M. , Yamagata Toshio 
Published: November 2016

AbstractDuring boreal winters, cold waves over India are primarily due to transport of cold air from higher latitudes. However, the processes associated with these cold waves are not yet clearly understood. Here by diagnosing a suite of datasets, we explore the mechanisms leading to the development and maintenance of these cold waves. Two types of cold waves are identified based on observed minimum surface temperature and statistical analysis. The first type (TYPE1), also the dominant one, depicts colder than normal temperatures covering most parts of the country while the second type (TYPE2) is more regional, with significant cold temperatures only noticeable over northwest India. Quite interestingly the first (second) type is associated with La Niña (El Niño) like conditions, suggesting that both phases of ENSO provide a favorable background for the occurrence of cold waves over India. During TYPE1 cold wave events, a low-level cyclonic anomaly generated over the Indian region as an atmospheric response to the equatorial convective anomalies is seen advecting cold temperatures into India and maintaining the cold waves. In TYPE2 cold waves, a cyclonic anomaly generated over west India anomalously brings cold winds to northwest India causing cold waves only in those parts.
The Reproductive Toxicity of CdSe/ZnS Quantum Dots on the in vivo Ovarian Function and in vitro Fertilization
Authors: Xu Gaixia , Lin Guimiao , Lin Suxia , Wu Na , Deng Yueyue , Feng Gang , Chen Qiang , Qu Junle , Chen Danni , Chen Siping , Niu Hanben , Mei Shujiang , Yong Ken-Tye , Wang Xiaomei 
Published: November 2016

AbstractDespite the usefulness of quantum dots (QDs) in biomedicine and optoelectronics, their toxicity risks remain a major obstacle for clinical usages. Hence, we studied the reproductive toxicity of CdSe/ZnS QDs on two aspects, (i) in vivo ovarian functions and (ii) in vitro fertilization process. The body weight, estrous cycles, biodistribution of QDs, and oocyte maturation are evaluated on female mice treated with QDs. The mRNA level of the follicle-stimulating hormone receptor (FSHr) and luteinizing hormone receptor (LHr) in ovaries are assayed. Then, the matured cumulus-oocyte-complexes are harvested to co-culture with in vitro capacitated sperms, and the in vitro fertilization is performed. The result revealed that QDs are found in the ovaries, but no changes are detected on the behavior and estrous cycle on the female mice. The mRNA downregulations of FSHr and LHr are observed and the number of matured oocytes has shown a significant decrease when the QDs dosage was above 1.0 pmol/day. Additionally, we found the presence of QDs has reduced the in vitro fertilization success rate. This study highly suggests that the exposure of CdSe/ZnS QDs to female mice can cause adverse effects to the ovary functions and such QDs may have limited applications in clinical usage.
Fabrication of functional hollow microspheres constructed from MOF shells: Promising drug delivery systems with high loading capacity and targeted transport
Authors: Gao Xuechuan , Hai Xiao , Baigude Huricha , Guan Weihua , Liu Zhiliang 
Published: November 2016

AbstractAn advanced multifunctional, hollow metal-organic framework (MOF) drug delivery system with a high drug loading level and targeted delivery was designed and fabricated for the first time and applied to inhibit tumour cell growth. This hollow MOF targeting drug delivery system was prepared via a simple post-synthetic surface modification procedure, starting from hollow ZIF-8 successfully obtained for the first time via a mild phase transformation under solvothermal conditions. As a result, the hollow ZIF-8 exhibits a higher loading capacity for the model anticancer drug 5-fluorouracil (5-FU). Subsequently, 5-FU-loaded ZIF-8 was encapsulated into polymer layers (FA-CHI-5-FAM) with three components: a chitosan (CHI) backbone, the imaging agent 5-carboxyfluorescein (5-FAM), and the targeting reagent folic acid (FA). Thus, an advanced drug delivery system, ZIF-8/5-FU@FA-CHI-5-FAM, was fabricated. A cell imaging assay demonstrated that ZIF-8/5-FU@FA-CHI-5-FAM could target and be taken up by MGC-803 cells. Furthermore, the as-prepared ZIF-8/5-FU@FA-CHI-5-FAM exhibited stronger cell growth inhibitory effects on MGC-803 cells because of the release of 5-FU, as confirmed by a cell viability assay. In addition, a drug release experiment in vitro indicated that ZIF-8/5-FU@FA-CHI-5-FAM exhibited high loading capacity (51%) and a sustained drug release behaviour. Therefore, ZIF-8/5-FU@FA-CHI-5-FAM could provide targeted drug transportation, imaging tracking and localized sustained release.
Possible generation of heat from nuclear fusion in Earth’s inner core
Authors: Fukuhara Mikio 
Published: November 2016

AbstractThe cause and source of the heat released from Earth’s interior have not yet been determined. Some research groups have proposed that the heat is supplied by radioactive decay or by a nuclear georeactor. Here we postulate that the generation of heat is the result of three-body nuclear fusion of deuterons confined in hexagonal FeDx core-centre crystals; the reaction rate is enhanced by the combined attraction effects of high-pressure (~364 GPa) and high-temperature (~5700 K) and by the physical catalysis of neutral pions: 2D + 2D + 2D → 21H + 4He + 2 "Equation missing" + 20.85 MeV. The possible heat generation rate can be calculated as 8.12 × 1012 J/m3, based on the assumption that Earth’s primitive heat supply has already been exhausted. The H and He atoms produced and the anti-neutrino "Equation missing" are incorporated as Fe-H based alloys in the H-rich portion of inner core, are released from Earth’s interior to the universe, and pass through Earth, respectively.
Evaluation of the efficacy of Myco/F lytic system, MGIT960 system and Lowenstein-Jensen medium for recovery of Mycobacterium tuberculosis from sterile body fluids
Authors: Wang Guirong , Yang Xinting , Zhu Junping , Dong Weijie , Huang Mailing , Jiang Guanglu , Zhao Liping , Qin Sibing , Chen Xiaoyou , Huang Hairong 
Published: November 2016

AbstractThe diagnosis of extrapulmonary tuberculosis (EPTB) is challenging due to non-specific symptoms, invasive approach for specimen collection and most importantly, the paucibacillary status. The objective of this assay was to evaluate the efficacy of Myco/F lytic system, BACTEC Mycobacteria Growth Indicator Tube (MGIT) 960 system and Lowenstein-Jensen (L-J) medium for recovery of bacilli from sterile body fluids. 214 specimens (114 pleural fluid and 100 pus) from clinically diagnosed EPTB patients were collected and subjected to Ziehl-Neelsen (ZN) smear microscopy, L-J culture, MGIT 960 culture and Myco/F lytic culture.103 out of the 214 sterile body fluid samples yielded positive culture outcomes by any of the three methods. Among all the culture positive specimens, the recovery rate was 86.41% for Myco/F lytic, 75.73% for MGIT 960, and 42.72% for L-J medium. The mean time to positivity (TTP) was 27.06 ± 8.03 days for Myco/F lytic, 22.20 ± 7.84 days for MGIT960 and 42 ± 8.84 days for L-J medium. The rates of contamination were 6.54%, 3.74% and 2.80% for Myco/F lytic, MGIT960 and L-J medium respectively. Both Myco/F lytic and MGIT960 system were superior to L-J medium for recovery of bacilli from sterile body fluids. Myco/F lytic system was more favorable than MGIT960 regarding recovery rate and cost-effectiveness, thus can be considered as a promising alternative to MGIT960 system for diagnosing EPTB.
Goodness and Accentedness Ratings of /hVt/ Tokens by Aware and Naive Listeners
Authors: Franklin Amber D. , Oksanen Kara A. , Gilfert Kaitlyn E. 
Published: November 2016

Purpose
This study compares goodness and accentedness ratings of speech tokens rated by listeners who are naive to and aware of speakers' native language backgrounds. Listener responses to open-ended questions regarding goodness and accentedness ratings are also examined.

Method
Twenty-eight monolingual speakers of U.S. English served as listeners. Listeners were presented with 5 blocks of /hVt/ tokens. Each block represented a different vowel target and comprised correct and incorrect productions from English, Spanish, Korean, and Japanese speakers. Listeners rated goodness and accentedness using a 9-point Likert scale and explained their decision-making criteria when judging goodness versus accentedness.

Results
There is a high positive correlation between goodness and accentedness. Both naive and aware listeners assigned poorer ratings when judging goodness compared with accentedness, but results varied on the basis of target accuracy. Aware listeners assigned better goodness and accentedness ratings compared with naive listeners. This difference was highly statistically significant. Both accentedness and goodness ratings are susceptible to listener bias.

Conclusions
Goodness and accentedness are highly correlated yet distinct measures. Goodness is more reflective of target accuracy than is accentedness. Native English tokens were affected by listener bias to a greater extent than nonnative English tokens.
Simultaneous determination of opioid drugs in urine with high‐performance liquid chromatography–ultraviolet after supramolecular based magnetic NP solid‐phase extraction
Authors: Zabardasti Abedien , Afrouzi Hossein , Kakanejadifard Ali , Amoli‐Diva Mitra 
Published: November 2016

A simple and rapid extraction/preconcentration procedure using supramolecular based magnetic nanoparticle (MNP) solid‐phase extraction method by sodium dodecyl sulphate (SDS)‐coated MNPs has been developed for both removal and preconcentration of three important opioid drugs named morphine, codeine and methadone before their high‐performance liquid chromatography–ultraviolet determination. To get insight conﬁguration of SDS molecules on the surface of the MNPs, zeta potential measurements were performed in different SDS (mg)/mg of MNPs ratios. Parameters affecting the extraction and preconcentration efficiency of the opioids were optimised as recovery by one variable at‐a‐time methodology and the obtained recoveries were 91, 94 and 98% for morphine, codeine and methadone, respectively. Under optimum conditions (such as pH = 3.5; adsorbent amount = 60 mg; eluent solvent volume = 2 ml of acetonitrile, sample volume = 200 ml etc.), the method was linear in the range of 1–200 ng ml−1 with enrichment factors (EFs) of 91, 94 and 98 for morphine, codeine and methadone, respectively, and the limits of detection were <0.27 ng ml−1. Finally, the proposed method was successfully applied for both removal and trace determination of the targeted drugs in urine samples.
The Risk Factors of Postoperative Delirium after Total Knee Arthroplasty
Authors: Wang Lih , Kim Sungsoo , Kim Kyungtaek , Lee Seunghyun , Lee Kyungho , Seok Sangyun 
Published: November 2016

AbstractWe investigated the results of delirium which developed after total knee arthroplasty (TKA) and the risk factors for delirium in the patients who are older than 65 years. From March 2008 to March 2012, we performed a retrospective study on 296 knees of 265 patients who were treated with TKA. They were divided into two groups: 216 patients without delirium and 49 patients diagnosed with delirium by psychiatry. We analyzed the risk factors into three categories: First, the preoperative factors including gender, age, body mass index (BMI), clinical and functional knee joint score (Knee Society Knee Score and Knee Society Function Score) and the number of underlying diseases and associations with each disease; Second, the operative factors including the anesthesia method, amount of blood loss, operating time, laboratory factors, and transfusion count; Third, the postoperative factors such as start time of walking and duration of hospital stay were analyzed. There were significant statistical difference between two groups just in age, history of dementia, cerebrovascular disease, difference of hemoglobin and albumin, start time of walking, and duration of hospital stay. The delirium after TKA delays the postoperative ambulation and extends the hospital stay, which causes functional and socioeconomic loss of patients. Therefore, the risk factors for delirium should be assessed and proper prevention and management should be conducted.
Necrotizing Otitis Externa: A Disease Barely Known to Neurosurgeons
Authors: Cançado Sérgio Augusto Vieira , Souza Lucídio Duarte de , Faleiro Rodrigo Moreira , Siqueira José Maurício 
Published: November 2016

AbstractNecrotizing otitis externa (NOE), also known as malignant otitis externa (MOE), is a severe and rare infectious disease of the external auditory canal (EAC). Without treatment, it may progress to skull base involvement. The bacteria Pseudomonas aeruginosa is the most common causative agent (∼ 90% of the cases), and affects immunocompromised subjects, particularly diabetic patients. Severe chronic otalgia, otorrhea, and cranial nerve palsy are the most common clinical presentations. Patients with NOE are frequently referred to neurosurgery because of the neurological impairment and skull base compromise. The definitive diagnosis is frequently elusive, requiring a high index of suspicion. Several laboratorial tests, imaging modalities, and the histologic exclusion of malignancy may be required. An early diagnosis and aggressive treatment reduce morbidity and mortality. We present four NOE cases to illustrate the spectrum of clinical presentation and complementary exams. According to the literature, more effort for early diagnosis and treatment is required, and neurosurgeons play an important role in this task.