bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein-like proton exchange in a synthetic host cavity
Authors: Hart-Cooper William M. , Sgarlata Carmelo , Perrin Charles L. , Toste F. Dean , Bergman Robert G. , Raymond Kenneth N. 
Published: December 2015

Significance
Water drives molecular interactions central to the chemistry of life. Critical to life’s metabolic machinery, enzymes catalyze reactions with remarkable selectivities and efficiencies resulting from noncovalent interactions between water, substrate, and the enzyme active site. Here, amide hydrogen–deuterium exchange kinetics provide quantification of the electronic and steric factors that influence exchange between water and a highly charged host molecule whose protective outer shell and hydrophobic cavity allow it to function like an enzyme. Investigations suggest that the host’s interior microenvironment reacts with encapsulated water in a manner that is correlated to the host’s ability to mediate acid catalysis, thereby providing a tool for developing enzyme-like microenvironments to mediate acid- or base catalysis.
Biological soil crusts accelerate the nitrogen cycle through large NO and HONO emissions in drylands
Authors: Weber Bettina , Wu Dianming , Tamm Alexandra , Ruckteschler Nina , Rodríguez-Caballero Emilio , Steinkamp Jörg , Meusel Hannah , Elbert Wolfgang , Behrendt Thomas , Sörgel Matthias , Cheng Yafang , Crutzen Paul J. , Su Hang , Pöschl Ulrich 
Published: December 2015

Significance
Biological soil crusts (biocrusts), occurring on ground surfaces in drylands throughout the world, are among the oldest life forms consisting of cyanobacteria, lichens, mosses, and algae plus heterotrophic organisms in varying proportions. They prevent soil erosion and nurture ecosystems by fixing carbon and nitrogen from the atmosphere. Here, we show that the fixed nitrogen is processed within the biocrusts, and during this metabolic activity, nitrogen oxide and nitrous acid are released to the atmosphere. Both of these gases are highly relevant, as they influence the radical formation and oxidizing capacity of the lower atmosphere, also interacting with climate change. In drylands, biocrusts appear to play a key role both in nitrogen fixation and the release of atmospheric reactive nitrogen.
Role of protein dynamics in ion selectivity and allosteric coupling in the NaK channel
Authors: Brettmann Joshua B. , Urusova Darya , Tonelli Marco , Silva Jonathan R. , Henzler-Wildman Katherine A. 
Published: December 2015

Significance
Pore domains of ion channels form the ion conduction pathway and thus control the identity and flux of ions across the membrane. Flux-dependent inactivation suggests that these two functions are connected, with allosteric linkage between the selectivity filter and inner gate. This study uses solution NMR to investigate structural and dynamic features of ion selectivity and coupling between the gates in the small bacterial channel NaK. NaK is a nonselective cation channel and is homologous to several eukaryotic channels that are not well modeled by KcsA. Our results show a previously unexpected dynamic coupling between the selectivity filter and inner gate in NaK. This suggests that such transmembrane communication is widespread and occurs through distinct mechanisms in diverse channels.
Genomic data do not support comb jellies as the sister group to all other animals
Authors: Pisani Davide , Pett Walker , Dohrmann Martin , Feuda Roberto , Rota-Stabelli Omar , Philippe Hervé , Lartillot Nicolas , Wörheide Gert 
Published: December 2015

SignificanceClarifying the phylogeny of animals is fundamental to understanding their evolution. Traditionally, sponges have been considered the sister group of all other extant animals, but recent genomic studies have suggested comb jellies occupy that position instead. Here, we analyzed the current genomic evidence from comb jellies and found no convincing support for this hypothesis. Instead, when analyzed with appropriate methods, recent genomic data support the traditional hypothesis. We conclude that the alternative scenario of animal evolution according to which ctenophores evolved morphological complexity independently from cnidarians and bilaterians or, alternatively, sponges secondarily lost a nervous system, muscles, and other characters, is not supported by the available evidence.
Translational profiling identifies a cascade of damage initiated in motor neurons and spreading to glia in mutant SOD1-mediated ALS
Authors: Sun Shuying , Sun Ying , Ling Shuo-Chien , Ferraiuolo Laura , McAlonis-Downes Melissa , Zou Yiyang , Drenner Kevin , Wang Yin , Ditsworth Dara , Tokunaga Seiya , Kopelevich Alex , Kaspar Brian K. , Lagier-Tourenne Clotilde , Cleveland Don W. 
Published: December 2015

Significance
Amyotrophic lateral sclerosis can be caused by a mutation in superoxide dismutase. Ubiquitously expressed, disease mechanism involves damage within motor neurons (whose degeneration is responsible for progressive paralysis) and glia. By combining ribosome affinity purification from each of three cell types, a temporal cascade of damage is identified that initiates within motor neurons, with subsequent damage within glia driving disease propagation. Mutant-dependent damage to motor neurons, which are shown to express very low levels of endoplasmic reticulum chaperones, includes synapse and metabolic abnormalities and selective activation of the PERK arm of the unfolded protein response. Early changes in astrocytes are to genes involved in inflammation and metabolism, while dysregulation of myelination and lipid signaling pathways in oligodendrocytes occurs only after disease initiation.
Human autoreactive T cells recognize CD1b and phospholipids
Authors: Van Rhijn Ildiko , van Berlo Twan , Hilmenyuk Tamara , Cheng Tan-Yun , Wolf Benjamin J. , Tatituri Raju V. V. , Uldrich Adam P. , Napolitani Giorgio , Cerundolo Vincenzo , Altman John D. , Willemsen Peter , Huang Shouxiong , Rossjohn Jamie , Besra Gurdyal S. , Brenner Michael B. , Godfrey Dale I. , Moody D. Branch 
Published: December 2015

Significance
Peptides are known to be targets of autoreactive T cells that can cause autoimmune diseases. Here we show that human T cells recognize self-lipids displayed on the surface of cells by CD1b proteins. A particular lipid that is recognized by CD1b autoreactive cells, phosphatidylglycerol, is present in mammalian mitochondria and in bacteria. Therefore, these data define a phospholipid autoantigen that is released during mitochondrial stress and bacterial infection.
Amyloid fibrils activate B-1a lymphocytes to ameliorate inflammatory brain disease
Authors: Kurnellas Michael Phillip , Ghosn Eliver Eid Bou , Schartner Jill M. , Baker Jeanette , Rothbard Jesse J. , Negrin Robert S. , Herzenberg Leonore A. , Fathman C. Garrison , Steinman Lawrence , Rothbard Jonathan B. 
Published: December 2015

SignificanceIL-10–secreting B lymphocytes and peritoneal macrophages are activated by immunization with amyloid fibrils composed of short peptides resulting in reduction of paralysis and inflammation in mice with experimental autoimmune encephalomyelitis. B-cell–deficient μMT mice and IL-10 knockout animals were used to establish the critical role of regulatory B cells in the therapeutic mode of action. Reintroduction of B-1a lymphocytes into the μMT animals reconstituted the ability of the fibrils to ameliorate the paralytic signs, leading to the trafficking of both populations of cells from the peritoneum to secondary lymph organs and not to the CNS. The reduction in CNS inflammation, combined with successful intranasal administration, provides support that this strategy could be translated into an effective human therapeutic.
Functional screen identifies kinases driving prostate cancer visceral and bone metastasis
Authors: Faltermeier Claire M. , Drake Justin M. , Clark Peter M. , Smith Bryan A. , Zong Yang , Volpe Carmen , Mathis Colleen , Morrissey Colm , Castor Brandon , Huang Jiaoti , Witte Owen N. 
Published: December 2015

Significance
Therapies are urgently needed to treat metastatic prostate cancer. Mutationally activated and wild-type kinases such as BCR-ABL and BTK are effective therapeutic targets in multiple cancers. Genetically altered kinases are rare in prostate cancer. Wild-type kinases may be implicated in prostate cancer progression, but their therapeutic potential in metastatic prostate cancer remains unknown. Using phosphoproteomics and gene expression datasets, we selected 125 wild-type kinases implicated in human prostate cancer metastasis to screen for metastatic ability in vivo. The RAF family, MERTK, and NTRK2 drove prostate cancer bone and visceral metastasis and were highly expressed in human metastatic prostate cancer tissues. These studies reveal that wild-type kinases can drive metastasis and that the RAF family, MERTK, and NTRK2 may represent important therapeutic targets.
Paediatric meningococcaemia in northwestern Ontario, Canada: a case for publicly funded meningococcal B vaccination
Authors: Eton Vic , Tsang Raymond S. W. , Ulanova Marina 
Published: December 2015

Introduction:

Neisseria meningitidis serogroup B is an important infectious agent in developed countries, including Canada. Infants are particularly susceptible to infection with serogroup B because of immature immune systems, pathogen virulence factors and changing serogroup dynamics in the post-vaccination era. Currently, the Ontario provincial government does not include serogroup B in its routine publicly funded meningococcal vaccination program.

Case Presentation:
A formerly well 14-month-old male presented to a tertiary hospital emergency department with fever, minor respiratory problems, diffuse purpuric rash, distended abdomen, tachycardia, and history of one episode of vomiting and melena each. Meningococcaemia was immediately suspected, and he was treated with ceftriaxone, cefotaxime and vancomycin before transfer to a different acute care facility within 12 h. N. meningitidis serogroup B, sensitive to ceftriaxone and penicillin, was identified in his blood. The patient developed gangrene of the lower legs and underwent bilateral below-knee amputation 8 days post-admission.

Conclusion:
This instance of meningococcaemia with extensive sequelae is an example of the various serious outcomes of meningococcal infection. It provides persuasive reason for routine publicly funded vaccination against N. meningitidis serogroup B in Ontario.
Efficient sequence-specific isolation of DNA fragments and chromatin byin vitroenChIP technology using recombinant CRISPR ribonucleoproteins
Authors: Fujita Toshitsugu , Yuno Miyuki , Fujii Hodaka 
Published: December 2015

AbstractThe clustered regularly interspaced short palindromic repeat (CRISPR) system is widely used for various biological applications, including genome editing. We developed engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) using CRISPR to isolate target genomic regions from cells for their biochemical characterization. In this study, we developed“in vitroenChIP” using recombinant CRISPR ribonucleoproteins (RNPs) to isolate target genomic regions.in vitroenChIP has the great advantage over conventional enChIP of not requiring expression of CRISPR complexes in cells. We first demonstrate thatin vitroenChIP using recombinant CRISPR RNPs can be used to isolate target DNA from mixtures of purified DNA in a sequence-specific manner. In addition, we show that this technology can be employed to efficiently isolate target genomic regions, while retaining their intracellular molecular interactions, with negligible contamination from irrelevant genomic regions. Thus,in vitroenChIP technology is of potential use for sequence-specific isolation of DNA, as well as for identification of molecules interacting with genomic regions of interestin vivoin combination with downstream analysis.
MARDI GRAS: A GIFT ECONOMY
Authors: PHILLIPS HAL , KINNEY MEG 
Published: December 2015

To residents of New Orleans, there is a special brand of pageantry and community surrounding the Mardi Gras ritual. At the center of it all are Parades – the heartbeat of Mardi Gras. Each Krewe (social club) puts on a huge parade sometime during Carnivale Season. They each have their own personality, costumes and “throws”. Throws can be as simple as the iconic beads we all know, or elaborate handcrafted items that are highly sought after prizes.During parades, a strange thing happens – objects that have little commercial value become incredibly valuable, even for a few moments. People jockey for position to catch beads, toys, custom medallions, and above all the prized throws of each Krewe. There is a whole system of value attached to each parade, which the city celebrates. We will explore how the gift economy of the Mardi Gras parade unites old and young, and bridges racial boundaries in a shared ritual.
DataTaxi: Applied Ethnography for Connecting the Feeling of the Streets and Communication Messages
Authors: SILVA SERGIO 
Published: December 2015

The urban environment has created a multiplication of stimulus that causes people to pay less attention to message content. In an attempt to understand what really interests them, the author found the taxi cab –a traditional mobile scenario– as way to explore aspects and encounter feelings of the population. By applying ethnographic approach and training taxi drivers this tool collects information from participant and consumers while traveling through São Paulo streets.Ethnography, methodology development, research innovation, marketing research.
TEST performance of a myositis panel in a clinical immunology laboratory in New South Wales, Australia
Authors: Tan Teck Choon , Wienholt Louise , Adelstein Stephen 
Published: December 2015

AbstractBackgroundThere is increasing recognition of a clinico‐serological correlation between the idiopathic inflammatory myopathies and myositis‐specific autoantibodies (MSA). We review the use of a line immunoassay‐based myositis panel incorporating both MSA and myositis‐associated autoantibodies (MAA) in a selected population of patients.MethodsA retrospective analysis of patients with myositis panel assays performed in 2013 were reviewed and compared against clinical diagnoses.ResultsA total of 96 patient samples were evaluated, the clinical indications include 60 patients with suspected idiopathic inflammatory myositis (IIM), 24 patients with suspected interstitial lung disease (ILD) and 12 patients with suspected systemic autoimmune disease (SAD). In the myositis group, there were 21 patients diagnosed with IIM and 18 patients diagnosed with IIM had a positive myositis panel. Of the 39 patients without IIM, nine of these patients had a positive myositis panel. In the ILD group, 10 of 24 patients had a positive myositis panel; of these, two were diagnosed anti‐synthetase syndrome (ASS) and five patients with ILD. In the suspected SAD group, three had positive myositis panel and all did not appear associated with their final diagnoses. In patients with a clinical diagnosis of IIM or ILD‐associated SAD, four patients with anti‐PL‐12 were detected, three patients with anti‐signal recognition protein, two patients with anti‐Jo‐1, and two patients with anti‐Mi2.ConclusionsThe myositis panel is an objective investigative modality with a sensitivity of 80.00% and a specificity of 75.76% in a setting of high pretest clinical suspicion.
Pulmonary IgG4‐related disease and colon adenocarcinoma: possible paraneoplastic syndrome
Authors: Krause Megan L. , Yi Eunhee S. , Warrington Kenneth J. 
Published: December 2015

AbstractMalignancy has a complicated association with immunoglobulin G4‐related disease (IgG4‐RD) both being an item in the differential diagnosis as well as malignancy occurring in the background of IgG4‐RD in the same organ. However, recently there is evidence of higher rates of distant malignancy in patients with IgG4‐RD. Here we report a case of pulmonary IgG4‐RD potentially consistent with a paraneoplastic phenomenon which improved with treatment of the underlying colon adenocarcinoma.
Synergistic antitumor activity of pro‐apoptotic agent PAC‐1 with cisplatinum by the activation of CASP3 in pulmonary adenocarcinoma cell line H1299
Authors: Huang Jian‐qing , Liang Hong‐ling , Zhang Xu‐chao , Xie Zhi , Jin Tian‐en 
Published: December 2015

AbstractAimEvasion of apoptosis is a hallmark of human cancer cells. We sought to explore the potential synergistic antitumor activity and underlying mechanisms of the pro‐apoptotic agent PAC‐1 plus cisplatinum (Cis) in non‐small cell lung cancer (NSCLC) cell lines.MethodsThe adenocarcinoma cell lines H1299, A549, PC9, H1650 and H1975 were used as in vitro models. Colorimetric MTT assays, Western blotting and flow cytometry were used to evaluate the anti‐growth effects of PAC‐1 and/or Cis and apoptosis status. The activated form of CASP3 (C‐CASP3) was assessed by immunofluorescent staining.ResultsSingle‐agent Cis and PAC‐1 were able to inhibit the cancer cell growth in certain dose ranges, with IC50 values of 1.9–11.7 and 5.6–14.8 μM, respectively. Sequential Cis→PAC‐1 or concurrent Cis + PAC‐1, but not PAC‐1→Cis combinations showed synergistic effects on cell growth inhibition in H1299 cells (combination index, CI ≤ 0.6). In contrast, other combination modes mostly showed seemingly antagonistic effects (CI > 1.0). Flow cytometric analysis showed that Cis→PAC‐1 sequential combination showed strong pro‐apoptotic effects in H1299 cells. Western blots showed that in H1299, PC9 and H1975 cells, PAC‐1 promoted the C‐CASP3, but only in H1299 cells was there a synergistic effect with Cis on the CASP3 activation.ConclusionsPAC‐1 showed anti‐tumor activity in NSCLCs in vitro and a synergistic effect with cisplatin in EGFRwtKRASwt H1299 cells. Our data suggest a potential treatment approach using cisplatin plus a pro‐apoptotic agent acting via CASP3 activation for this subgroup of pulmonary adenocarcinomas.
Peri‐operative cardiac protection for non‐cardiac surgery
Authors: Wong S. S. C. , Irwin M. G. 
Published: December 2015

SummaryCardiovascular complications are an important cause of morbidity and mortality after non‐cardiac surgery. Pre‐operative identification of high‐risk individuals and appropriate peri‐operative management can reduce cardiovascular risk. It is important to continue chronic beta‐blocker and statin therapy. Statins are relatively safe and peri‐operative initiation may be beneficial in high‐risk patients and those scheduled for vascular surgery. The pre‐operative introduction of beta‐blockers reduces myocardial injury but increases rates of stroke and mortality, possibly due to hypotension. They should only be considered in high‐risk patients and the dose should be titrated to heart rate. Alpha‐2 agonists may also contribute to hypotension. Aspirin continuation can increase the risk of major bleeding and offset the benefit of reduced myocardial risk. Contrary to the initial ENIGMA study, nitrous oxide does not seem to increase the risk of myocardial injury. Volatile anaesthetic agents and opioids have been shown to be cardioprotective in animal laboratory studies but these effects have, so far, not been conclusively reproduced clinically.
Peri‐operative pulmonary dysfunction and protection
Authors: Marseu K. , Slinger P. 
Published: December 2015

SummaryPulmonary complications are a major cause of peri‐operative morbidity and mortality, but have been researched less thoroughly than cardiac complications. It is important to try and predict which patients are at risk of peri‐operative pulmonary complications and to intervene to reduce this risk. Anaesthetists are in a unique position to do this during the whole peri‐operative period. Pre‐operative training, smoking cessation and lung ventilation with tidal volumes of 6–8 ml.kg−1 and low positive end‐expiratory pressure probably reduce postoperative pulmonary complications.
Twenty‐Year Outcome After Right Ventricular Outflow Tract Repair Using Heterotopic Pulmonary Conduits in Infants and Children
Authors: Hoxha Stiljan , Torre Salvatore , Rungatscher Alessio , Sandrini Camilla , Rossetti Lucia , Barozzi Luca , Faggian Giuseppe , Luciani Giovanni Battista 
Published: December 2015

AbstractDurability of pulmonary conduits (PCs) used for reconstruction of the right ventricular outflow tract (RVOT) may be affected by a variety of factors. Among these, the technique used for PC implantation, whether in orthotopic or heterotopic position, strictly dependent upon the underlying anatomy, has been suggested to influence long‐term outcome after RVOT repair. To determine the outcome of heterotopic implantation in infants and children treated at our institution, late results of heterotopic PC in non‐Ross patients were analyzed and compared with data of orthotopic PC in age‐matched pediatric Ross patients operated during the same time period. Between November 1991 and January 2015, 58 infants and children, 32 male and 26 female, with a median age of 9.4 years (range 1 day–18 years) underwent implantation of heterotopic PC (31 homografts [HG] and 27 xenografts [XG]) for reconstruction of RVOT. Median age in the XG group was significantly lower than in the HG group (0.9 vs. 13.4 years, P = 0.01), while male/female ratio was similar. Fifty (86%) patients had undergone one or more prior cardiac operations, while 32 (55%) required associated procedures during PC implantation. Comparison with data in 305 children and with a median age of 9.4 years, receiving orthotopic PC between 1990 and 2012 (Italian Pediatric Ross Registry), was undertaken. Descriptive, univariate, and Kaplan–Meier analysis defined outcome. There were three (5.2%) early and five (9.0%) late deaths, during a median follow‐up of 7.6 years (range 2 months–23 years). Patients having XG had trend toward higher hospital mortality (2/27 vs. 1/31, P = 0.2), but similar late mortality (2/24 vs. 3/30, P = 0.3). Overall survival was 88 and 62%, while freedom from PC replacement was 49 and 21%, at 10 and 20 years, respectively. The latter proved significantly worse than freedom from orthotopic PC replacement, which was 94 ± 2 and 70 ± 9% at 10 and 20 years (P = 0.02). When stratified for type of heterotopic PC, late survival proved comparable (81 and 81% for XG vs. 92 and 60% for HG, at 10 and 20 years, respectively, P = 0.7). However, freedom from PC replacement was significantly higher in patients with heterotopic HG (21 and 5% for XG vs. 63 and 48% for HG, at 10 and 20 years, respectively, P = 0.001). RVOT repair using either XG or HG in heterotopic position is a safe procedure associated with low hospital mortality and satisfactory late survival. Freedom from reoperation is significantly lower than that observed in age‐matched children having orthotopic HG. Freedom from reoperation in heterotopic XG is poorer than in HG, although different baseline demography may have influenced this finding.