bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crystal structure of the DNA‐binding domain of the LysR‐type transcriptional regulator CbnR in complex with a DNA fragment of the recognition‐binding site in the promoter region
Authors: Koentjoro Maharani Pertiwi , Adachi Naruhiko , Senda Miki , Ogawa Naoto , Senda Toshiya 
Published: January 2018

LysR‐type transcriptional regulators (LTTRs) are among the most abundant transcriptional regulators in bacteria. CbnR is an LTTR derived from Cupriavidus necator (formerly Alcaligenes eutrophus or Ralstonia eutropha) NH9 and is involved in transcriptional activation of the cbnABCD genes encoding chlorocatechol degradative enzymes. CbnR interacts with a cbnA promoter region of approximately 60 bp in length that contains the recognition‐binding site (RBS) and activation‐binding site (ABS). Upon inducer binding, CbnR seems to undergo conformational changes, leading to the activation of the transcription. Since the interaction of an LTTR with RBS is considered to be the first step of the transcriptional activation, the CbnR–RBS interaction is responsible for the selectivity of the promoter to be activated. To understand the sequence selectivity of CbnR, we determined the crystal structure of the DNA‐binding domain of CbnR in complex with RBS of the cbnA promoter at 2.55 Å resolution. The crystal structure revealed details of the interactions between the DNA‐binding domain and the promoter DNA. A comparison with the previously reported crystal structure of the DNA‐binding domain of BenM in complex with its cognate RBS showed several differences in the DNA interactions, despite the structural similarity between CbnR and BenM. These differences explain the observed promoter sequence selectivity between CbnR and BenM. Particularly, the difference between Thr33 in CbnR and Ser33 in BenM appears to affect the conformations of neighboring residues, leading to the selective interactions with DNA.DatabaseAtomic coordinates and structure factors for the DNA‐binding domain of Cupriavidus necatorNH9 CbnR in complex with RBS are available in the Protein Data Bank under the accession code 5XXP.
Inhibition of UVSSA ubiquitination suppresses transcription‐coupled nucleotide excision repair deficiency caused by dissociation from USP7
Authors: Higa Mitsuru , Tanaka Kiyoji , Saijo Masafumi 
Published: January 2018

Transcription‐coupled nucleotide excision repair (TC‐NER) is a subpathway of nucleotide excision repair that efficiently removes transcription‐blocking DNA damage from the transcribed strands of active genes. UVSSA is a causative gene for UV‐sensitive syndrome (UVSS), which is an autosomal recessive disorder characterized by hypersensitivity to UV light and deficiency in TC‐NER. UV‐stimulated scaffold protein A (UVSSA), the product of UVSSA, forms a complex with ubiquitin‐specific peptidase 7 (USP7) and is stabilized by interaction with USP7. The central region of UVSSA, which contains the tumor necrosis factor receptor‐associated factor (TRAF)‐binding motif, is required for the interaction with the N‐terminal TRAF domain of USP7. Here, we showed that UVSSA is mono‐ubiquitinated in vitro and identified a lysine residue (Lys414) in UVSSA as the target of ubiquitination. The deubiquitination activity of USP7 was inhibited by the ubiquitin‐conjugating enzyme UbcH6. Lys414 was also modified by poly‐ubiquitin chains in vivo. UVSSA deficient in the interaction with USP7 is ubiquitinated and degraded by the proteasome, and the degradation leads to deficiency in TC‐NER. The substitution of Lys414 by Arg of UVSSA inhibited its degradation and thereby suppressed the deficiency in TC‐NER.
The retinamide VNLG‐152 inhibits f‐AR/AR‐V7 and MNK–eIF4E signaling pathways to suppress EMT and castration‐resistant prostate cancer xenograft growth
Authors: Ramamurthy Vidya P. , Ramalingam Senthilmurugan , Gediya Lalji K. , Njar Vincent C. O. 
Published: January 2018

VNLG‐152 is a novel retinamide (NR) shown to suppress growth and progression of genetically diverse prostate cancer cells via inhibition of androgen receptor signaling and eukaryotic initiation factor 4E (eIF4E) translational machinery. Herein, we report therapeutic effects of VNLG‐152 on castration‐resistant prostate cancer (CRPC) growth and metastatic phenotype in a CRPC tumor xenograft model. Administration of VNLG‐152 significantly and dose‐dependently suppressed the growth of aggressive CWR22Rv1 tumors by 63.4% and 76.3% at 10 and 20 mg·kg−1 bw, respectively (P < 0.0001), vs. vehicle with no host toxicity. Strikingly, the expression of full‐length androgen receptor (f‐AR)/androgen receptor splice variant‐7 (AR‐V7), mitogen‐activated protein kinase‐interacting kinases 1 and 2 (MNK1/2), phosphorylated eIF4E and their associated target proteins, including prostate‐specific antigen, cyclin D1 and Bcl‐2, were strongly decreased in VNLG‐152‐treated tumors signifying inhibition of f‐AR/AR‐V7 and MNK–eIF4E signaling in VNLG‐152‐treated CWR22Rv1 tumors as observed in vitro. VNLG‐152 also suppressed the epithelial to mesenchymal transition in CWR22Rv1 tumors as evidenced by repression of N‐cadherin, β‐catenin, claudin, Slug, Snail, Twist, vimentin and matrix metalloproteinases (MMP‐2 and MMP‐9) with upsurge in E‐cadherin. These results highlight the promising use of VNLG‐152 in CRPC therapy and justify its further development towards clinical trials.
Large‐scale disturbance legacies and the climate sensitivity of primary Picea abies forests
Authors: Schurman Jonathan S. , Trotsiuk Volodymyr , Bače Radek , Čada Vojtěch , Fraver Shawn , Janda Pavel , Kulakowski Dominik , Labusova Jana , Mikoláš Martin , Nagel Thomas A. , Seidl Rupert , Synek Michal , Svobodová Kristýna , Chaskovskyy Oleh , Teodosiu Marius , Svoboda Miroslav 
Published: January 2018

AbstractDetermining the drivers of shifting forest disturbance rates remains a pressing global change issue. Large‐scale forest dynamics are commonly assumed to be climate driven, but appropriately scaled disturbance histories are rarely available to assess how disturbance legacies alter subsequent disturbance rates and the climate sensitivity of disturbance. We compiled multiple tree ring‐based disturbance histories from primary Picea abies forest fragments distributed throughout five European landscapes spanning the Bohemian Forest and the Carpathian Mountains. The regional chronology includes 11,595 tree cores, with ring dates spanning the years 1750–2000, collected from 560 inventory plots in 37 stands distributed across a 1,000 km geographic gradient, amounting to the largest disturbance chronology yet constructed in Europe. Decadal disturbance rates varied significantly through time and declined after 1920, resulting in widespread increases in canopy tree age. Approximately 75% of current canopy area recruited prior to 1900. Long‐term disturbance patterns were compared to an historical drought reconstruction, and further linked to spatial variation in stand structure and contemporary disturbance patterns derived from LANDSAT imagery. Historically, decadal Palmer drought severity index minima corresponded to higher rates of canopy removal. The severity of contemporary disturbances increased with each stand's estimated time since last major disturbance, increased with mean diameter, and declined with increasing within‐stand structural variability. Reconstructed spatial patterns suggest that high small‐scale structural variability has historically acted to reduce large‐scale susceptibility and climate sensitivity of disturbance. Reduced disturbance rates since 1920, a potential legacy of high 19th century disturbance rates, have contributed to a recent region‐wide increase in disturbance susceptibility. Increasingly common high‐severity disturbances throughout primary Picea forests of Central Europe should be reinterpreted in light of both legacy effects (resulting in increased susceptibility) and climate change (resulting in increased exposure to extreme events).
Temperature sensitivities of extracellular enzymeVmaxandKmacross thermal environments
Authors: Allison Steven D. , Romero‐Olivares Adriana L. , Lu Ying , Taylor John W. , Treseder Kathleen K. 
Published: January 2018

AbstractThe magnitude and direction of carbon cycle feedbacks under climate warming remain uncertain due to insufficient knowledge about the temperature sensitivities of soil microbial processes. Enzymatic rates could increase at higher temperatures, but this response could change over time if soil microbes adapt to warming. We used the Arrhenius relationship, biochemical transition state theory, and thermal physiology theory to predict the responses of extracellular enzymeVmaxandKmto temperature. Based on these concepts, we hypothesized thatVmaxandKmwould correlate positively with each other and show positive temperature sensitivities. For enzymes from warmer environments, we expected to find lowerVmax,Km, andKmtemperature sensitivity but higherVmaxtemperature sensitivity. We tested these hypotheses with isolates of the filamentous fungusNeurospora discretacollected from around the globe and with decomposing leaf litter from a warming experiment in Alaskan boreal forest. ForNeurosporaextracellular enzymes,VmaxQ10ranged from 1.48 to 2.25, andKmQ10ranged from 0.71 to 2.80. In agreement with theory,VmaxandKmwere positively correlated for some enzymes, andVmaxdeclined under experimental warming in Alaskan litter. However, the temperature sensitivities ofVmaxandKmdid not vary as expected with warming. We also found no relationship between temperature sensitivity ofVmaxorKmand mean annual temperature of the isolation site forNeurosporastrains. DecliningVmaxin the Alaskan warming treatment implies a short‐term negative feedback to climate change, but theNeurosporaresults suggest that climate‐driven changes in plant inputs and soil properties are important controls on enzyme kinetics in the long term. Our empirical data on enzymeVmax,Km, and temperature sensitivities should be useful for parameterizing existing biogeochemical models, but they reveal a need to develop new theory on thermal adaptation mechanisms.
Are North American bird species' geographic ranges mainly determined by climate?
Authors: Rich Johnathan L. , Currie David J. 
Published: January 2018

AbstractAimIt is commonly asserted that climate presents the primary constraint on species’ geographic distributions, and that species’ distributions should therefore shift to track changing climate. However, the evidence is surprisingly mixed about the causal link between species’ distributions and climate. Correlations between distributions and climate may be indirect, reflecting influences of other spatially structured habitat variables (e.g., land cover) and/or population processes (e.g., dispersal). Here, we ask if species’ geographic distributions are more strongly related to climate, or to other spatially structured variables.LocationThe contiguous United States and southern Canada.Time period1990–2000.Major taxa studiedNorth American passerine birds.MethodsWe used the breeding‐season distributions of 19 widespread species of passerine birds whose breeding‐season distributions fall entirely within the area sampled by the North American Breeding Bird Survey. We related these distributions to temperature and precipitation, geographic coordinates, and the degree of occupation of neighboring sites by conspecifics. Two spatial scales were examined: the geographic location of species’ ranges within North America, and site occupancy within species' ranges. We examine these relationships using generalized linear models, structural equation modeling, random forest models and spatial correlograms.ResultsOn average, geographic coordinates and a model of neighborhood occupancy outperform a simple climatic model. After controlling for geographic coordinates, species occupancy is poorly related to climate. Neighborhood occupancy accounts for the majority of variance captured by geographic coordinates within ranges, and more for the continental placement of ranges. On average, species’ distributions are more strongly and more directly related to spatial coordinates, and neighborhood occupancy, than to climate.Main conclusionsOur results are inconsistent with the hypothesis that climate is the primary, direct determinant of species’ geographic distributions. Rather, other spatially structured factors appear to be stronger determinants of both continental range placement and within‐range distributions of this sample of North American birds.
Expression of PD‐L1 correlates with pleomorphic morphology and histological patterns of non‐small‐cell lung carcinomas
Authors: Ng Kee Kwong Francois , Laggner Ute , McKinney Olivia , Croud James , Rice Alexandra , Nicholson Andrew G 
Published: January 2018

AimsAs immunomodulatory therapy is being integrated into treatment regimens for non‐small‐cell lung carcinoma, we aimed to prospectively collect data on the immunohistochemical profile of tumours assessed in our institution and to correlate this with morphological tumour features.Methods and resultsImmunohistochemistry for programmed death‐ligand 1 (PD‐L1) was considered to be adequate when >100 tumour cells were seen microscopically. When adequate, PD‐L1 staining was scored as <1%, ≥1–49% or ≥50% positive membrane staining within tumour cells only. There were 197 assessable cases, of which 87% of those with pleomorphic features (n = 39) showed ≥50% positivity for PD‐L1 expression, as compared with only 33% of cases without pleomorphic features (P < 0.05) (90% versus 25% in resected cases). Further correlation of PD‐L1 expression with architectural patterns within the tumours was performed in 74 adenocarcinoma resections. All invasive mucinous adenocarcinomas scored <1%. All lepidic components in non‐mucinous adenocarcinoma resections scored <1%. Thirty‐five per cent of the acinar/papillary components and 53% of the solid/micropapillary components were positive for PD‐L1 expression.ConclusionsThere are significant differences in PD‐L1 expression in relation to histological patterns, with particularly high levels in those with pleomorphic features and low/undetectable levels in invasive mucinous adenocarcinomas and the lepidic components of non‐mucinous adenocarcinomas. Assessment of PD‐L1 expression in a resected adenocarcinoma with a lepidic component may therefore not be reliable when immumodulatory therapy for recurrent disease is being considered, and either re‐biopsy or limiting assessment to the invasive component may be more appropriate.
MAIT cells: an historical and evolutionary perspective
Authors: Lantz Olivier , Legoux François 
Published: January 2018

AbstractIn humans, MAIT cells represent the most abundant T‐cell subset reacting against bacteria. MAIT cells belong to the evolutionarily conserved family of “preset” T cells that includes also NKT cells. Both subsets are selected by double positive thymocytes leading to common features such as PLZF expression. Preset T cells correspond to subsets prepositioned in specific tissue locations with preprogrammed versatile effector functions such as antimicrobial functions and possibly also metabolic control and tissue repair activity. Herein, we recall how several groups studying human samples discovered MAIT cells as T cells expressing either a restricted T‐cell receptors (TCR) repertoire or homogeneous and singular phenotypic and functional characteristics. We then highlight the main evolutionary features of this subset and its restricting element, MR1 (MHC‐related protein (1) with a striking coevolution of TRAV1 and MR1. We introduce another evolutionarily conserved invariant TCRalpha chain coevolving with another MHC class Ib molecule, called MHX, sharing phylogenetic features with MR1. We finally discuss the relationship between MAIT cells and other subsets reacting to microbial antigens or to compounds presented by MR1 in light of confounding experimental issues.
Restorations in primary teeth: a systematic review on survival and reasons for failures
Authors: Chisini Luiz Alexandre , Collares Kauê , Cademartori Mariana Gonzalez , de Oliveira Luísa Jardim Corrêa , Conde Marcus Cristian Muniz , Demarco Flávio Fernando , Corrêa Marcos Britto 
Published: January 2018

BackgroundSeveral restorative materials with specific indications are used for filling cavities in primary teeth.AimTo systematically review the literature in order to investigate the longevity of primary teeth restorations and the reasons for failure.DesignElectronic databases were screened, and eligible studies were hand‐searched to find longitudinal clinical studies evaluating the survival of restorations (class I, class II, and crown) placed with different materials in primary teeth with at least one year of follow‐up.ResultsThirty‐one studies were included, and a high bias risk was observed. Overall, 12,047 restorations were evaluated with 12.5% of failure rate. A high variation on annual failure rate (AFR) was detected (0–29.9%). Composite resin showed the lowest AFRs (1.7–12.9%). Stainless steel crowns (SSC) had the highest success rate (96.1%). Class I restorations and restorations placed using rubber dam presented better AFR. The main reason for failure observed was secondary caries (36.5%).ConclusionsAn elevated number of failures were observed due to recurrent caries, highlighting the need for professionals to work with a health‐promoting approach. The high variation on failure rate among the materials can be due to children's behavior during the procedure, which demands short dental appointments and a controlled environment.
Ten years of clinical trial registration in a resource‐limited setting: Experience of the Sri Lanka clinical trials registry
Authors: Ranawaka Udaya K. , de Abrew Ashwini , Wimalachandra Manu , Samaranayake Nithushi , Goonaratna Colvin 
Published: January 2018

AbstractAimWe describe our experience of the first 10 years at the Sri Lanka Clinical Trials Registry (SLCTR).MethodsWe analyzed all trial records of the SLCTR over the study period. We collected information regarding trial characteristics and completeness of data entry in the SLCTR data set.ResultsDuring the study period, 210 trials (63% of all applications) were registered with the SLCTR. The number of registered trials showed an increasing trend over the years. All trial registrations had complete entries for all the data fields studied. Only 17.6% of the trials were registered retrospectively. All the registered trials were interventional studies, and the majority (87.6%) were randomized controlled trials. A significant proportion of trials (28.6%) were on noncommunicable diseases, and 12.4% were on pregnancy and its outcomes. Several trials (9.5%) were international collaborative studies. A majority of the Principal Investigators (70.9%) were affiliated to a university. Most of the studies (41.9%) were self‐funded by the investigators. Details of ethics review committee approval were available for 96.7% of registered trials. Over a third of the registered trials (37.1%) had completed recruitment at the time of analysis. A majority of the trials (72.8%) had updated trial data since registration.ConclusionsThere is a steady increase in the number of trials registered at the SLCTR. Complete entries for all the data fields were seen in all trial registrations. The SLCTR has made a positive contribution to the emergence of a healthy clinical research environment in Sri Lanka.
Mediterranean fruit fly subplot hot spots prediction by experts' experience
Authors: Mendelsohn O. , Dayan T. , Aidlin‐Harari S. , Silberstein M. , Orlov V. , Blank L. 
Published: January 2018

AbstractThe Mediterranean fruit fly (medfly), Ceratitis capitata (Wiedemann), is a major pest, infesting hundreds of crop types. Since current field monitoring is mostly manual, understanding the spatiotemporal patterns of pest emergence at the fine scale can optimize precise trap placement and site‐specific treatment activities, also within area wide integrated pest management projects. We carried out a three‐year study in deciduous orchards in Israel, testing for the existence of subplot hot spots in which medfly populations display small‐scale aggregations over consecutive seasons, beyond the expected spatial variability resulting from host type and ripening sequence. medfly population increase in these locations often preceded or was parallel to infestations in surrounding orchards, suggesting that hot spots can provide an important tool for effective prediction and control of pest emergence. We also examined the use of expert knowledge to predict hot spot locations and suggest a methodology for verifying them.
Influence of Prehospital Function and Strength on Outcomes of Critically Ill Older Adults
Authors: Files D. Clark , Neiberg Rebecca , Rushing Julia , Morris Peter E. , Young Michael P. , Ayonayon Hilsa , Harris Tamara , Newman Anne , Rubin Susan , Shiroma Eric , Houston Denise , Miller Michael E. , Kritchevsky Stephen B. 
Published: January 2018

ObjectivesTo understand the influence of prehospital physical function and strength on clinical outcomes of critically ill older adults.DesignSecondary analysis of prospective cohort study.SettingHealth, Aging and Body Composition (Health ABC) Study.ParticipantsOf 3,075 older adult Health ABC participants, we identified 575 (60% white, 61% male, mean age 79) with prehospital function or grip strength measurements within 2 years of an intensive care unit stay.MeasurementsThe primary analysis evaluated the association between prehospital walk speed and mortality, and secondary analyses focused on associations between function or grip strength and mortality or hospital length of stay. Function and grip strength were analyzed as continuous and categorical predictors.ResultsSlower prehospital walk speed was associated with greater risk of 30‐day mortality (for each 0.1 m/s slower, odds ratio = 1.13, 95% confidence interval (CI) = 1.04–1.23, P = .004). Grip strength, chair stands, and balance had weaker, non‐statistically significant associations with 30‐day mortality. Participants with slower prehospital walk speed (hazard ratio (HR) = 0.94, 95% CI = 0.90–0.98, P = .005) and weak grip strength (HR = 0.85, 95% CI = 0.73–0.99, P = .03) were less likely to be discharged from the hospital alive. All function and strength measures were significantly associated with 1‐year mortality.ConclusionSlow prehospital walk speed was strongly associated with greater 30‐day mortality and longer hospital stay in critically ill older adults, and measures of function and strength were associated with 1‐year mortality. These data add to the accumulating evidence on the relationship between physical function and critical care outcomes.