bluuebunny/crossref_metadata_2025_split huggingface dataset:
c-Rel is a critical mediator of NF-κB-dependent TRAIL resistance of pancreatic cancer cells
Authors: Geismann C , Grohmann F , Sebens S , Wirths G , Dreher A , Häsler R , Rosenstiel P , Hauser C , Egberts J-H , Trauzold A , Schneider G , Sipos B , Zeissig S , Schreiber S , Schäfer H , Arlt A 
Published: October 2014

AbstractPancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest malignancies with an overall life expectancy of 6 months despite current therapies. NF-κB signalling has been shown to be critical for this profound cell-autonomous resistance against chemotherapeutic drugs and death receptor-induced apoptosis, but little is known about the role of the c-Rel subunit in solid cancer and PDAC apoptosis control. In the present study, by analysis of genome-wide patterns of c-Rel-dependent gene expression, we were able to establish c-Rel as a critical regulator of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in PDAC. TRAIL-resistant cells exhibited a strong TRAIL-inducible NF-κB activity, whereas TRAIL-sensitive cells displayed only a small increase in NF-κB-binding activity. Transfection with siRNA against c-Rel sensitized the TRAIL-resistant cells in a manner comparable to siRNA targeting the p65/RelA subunit. Gel-shift analysis revealed that c-Rel is part of the TRAIL-inducible NF-κB complex in PDAC. Array analysis identified NFATc2 as a c-Rel target gene among the 12 strongest TRAIL-inducible genes in apoptosis-resistant cells. In line, siRNA targeting c-Rel strongly reduced TRAIL-induced NFATc2 activity in TRAIL-resistant PDAC cells. Furthermore, siRNA targeting NFATc2 sensitized these PDAC cells against TRAIL-induced apoptosis. Finally, TRAIL-induced expression of COX-2 was diminished through siRNA targeting c-Rel or NFATc2 and pharmacologic inhibition of COX-2 with celecoxib or siRNA targeting COX-2, enhanced TRAIL apoptosis. In conclusion, we were able to delineate a novel c-Rel-, NFATc2- and COX-2-dependent antiapoptotic signalling pathway in PDAC with broad clinical implications for pharmaceutical intervention strategies.
Serpina3n accelerates tissue repair in a diabetic mouse model of delayed wound healing
Authors: Hsu I , Parkinson L G , Shen Y , Toro A , Brown T , Zhao H , Bleackley R C , Granville D J 
Published: October 2014

AbstractChronic, non-healing wounds are a major complication of diabetes and are characterized by chronic inflammation and excessive protease activity. Although once thought to function primarily as a pro-apoptotic serine protease, granzyme B (GzmB) can also accumulate in the extracellular matrix (ECM) during chronic inflammation and cleave ECM proteins that are essential for proper wound healing, including fibronectin. We hypothesized that GzmB contributes to the pathogenesis of impaired diabetic wound healing through excessive ECM degradation. In the present study, the murine serine protease inhibitor, serpina3n (SA3N), was administered to excisional wounds created on the dorsum of genetically induced type-II diabetic mice. Wound closure was monitored and skin wound samples were collected for analyses. Wound closure, including both re-epithelialization and contraction, were significantly increased in SA3N-treated wounds. Histological and immunohistochemical analyses of SA3N-treated wounds revealed a more mature, proliferative granulation tissue phenotype as indicated by increased cell proliferation, vascularization, fibroblast maturation and differentiation, and collagen deposition. Skin homogenates from SA3N-treated wounds also exhibited greater levels of full-length intact fibronectin compared with that of vehicle wounds. In addition, GzmB-induced detachment of mouse embryonic fibroblasts correlated with a rounded and clustered phenotype that was prevented by SA3N. In summary, topical administration of SA3N accelerated wound healing. Our findings suggest that GzmB contributes to the pathogenesis of diabetic wound healing through the proteolytic cleavage of fibronectin that is essential for normal wound closure, and that SA3N promotes granulation tissue maturation and collagen deposition.
Global abundance of planktonic heterotrophic protists in the deep ocean
Authors: Pernice Massimo C , Forn Irene , Gomes Ana , Lara Elena , Alonso-Sáez Laura , Arrieta Jesus M , del Carmen Garcia Francisca , Hernando-Morales Victor , MacKenzie Roy , Mestre Mireia , Sintes Eva , Teira Eva , Valencia Joaquin , Varela Marta M , Vaqué Dolors , Duarte Carlos M , Gasol Josep M , Massana Ramon 
Published: October 2014

Abstract
The dark ocean is one of the largest biomes on Earth, with critical roles in organic matter remineralization and global carbon sequestration. Despite its recognized importance, little is known about some key microbial players, such as the community of heterotrophic protists (HP), which are likely the main consumers of prokaryotic biomass. To investigate this microbial component at a global scale, we determined their abundance and biomass in deepwater column samples from the Malaspina 2010 circumnavigation using a combination of epifluorescence microscopy and flow cytometry. HP were ubiquitously found at all depths investigated down to 4000 m. HP abundances decreased with depth, from an average of 72±19 cells ml−1 in mesopelagic waters down to 11±1 cells ml−1 in bathypelagic waters, whereas their total biomass decreased from 280±46 to 50±14 pg C ml−1. The parameters that better explained the variance of HP abundance were depth and prokaryote abundance, and to lesser extent oxygen concentration. The generally good correlation with prokaryotic abundance suggested active grazing of HP on prokaryotes. On a finer scale, the prokaryote:HP abundance ratio varied at a regional scale, and sites with the highest ratios exhibited a larger contribution of fungi molecular signal. Our study is a step forward towards determining the relationship between HP and their environment, unveiling their importance as players in the dark ocean’s microbial food web.
Following movement of domain IV of elongation factor G during ribosomal translocation
Authors: Salsi Enea , Farah Elie , Dann Jillian , Ermolenko Dmitri N. 
Published: October 2014

Significance
The ribosome synthesizes proteins in all living organisms. During the process of protein synthesis, tRNAs and mRNA move through the ribosome, and this movement is catalyzed by the binding of a protein called elongation factor G (EF-G). The mechanism of EF-G–induced translocation of mRNA and tRNAs is not fully understood. In this work, we show that EF-G undergoes structural rearrangements and adopts at least two distinct conformations during translocation. Our work provides new insights into how EF-G promotes tRNA and mRNA translocation.
Gene coexpression measures in large heterogeneous samples using count statistics
Authors: Wang Y. X. Rachel , Waterman Michael S. , Huang Haiyan 
Published: October 2014

Significance
Coexpression analysis is one of the earliest tools for inferring gene associations using expression data but faces new challenges in this “big data” era. In a large heterogeneous dataset, it is likely that gene relationships may change or only exist in a subset of the samples, and they can be nonlinear or nonfunctional. We propose two new robust count statistics to account for local patterns in gene expression profiles. The statistics are generalizable to detect statistical dependence in other application domains. The performance of the statistics is evaluated against a number of popular bivariate dependence measures, showing favorable results. The asymptotic studies of the statistics provide an interesting addition to the combinatorics literature.
Angler‐Caught Piscivore Diets Reflect Fish Community Changes in Lake Huron
Authors: Roseman Edward F. , Schaeffer Jeffrey S. , Bright Ethan , Fielder David G. 
Published: October 2014

AbstractExamination of angler‐caught piscivore stomachs revealed that Lake Trout Salvelinus namaycush, Chinook Salmon Oncorhynchus tshawytscha, and Walleyes Sander vitreus altered their diets in response to unprecedented declines in Lake Huron's main‐basin prey fish community. Diets varied by predator species, season, and location but were nearly always dominated numerically by some combination of Alewife Alosa pseudoharengus, Rainbow Smelt Osmerus mordax, Emerald Shiner Notropis atherinoides, Round Goby Neogobius melanostomus, or terrestrial insects. Rainbow Trout Oncorhynchus mykiss (steelhead), Coho Salmon Oncorhynchus kisutch, and Atlantic Salmon Salmo salar had varied diets that reflected higher contributions of insects. Compared with an earlier (1983–1986) examination of angler‐caught predator fishes from Lake Huron, the contemporary results showed an increase in consumption of nontraditional prey (including conspecifics), use of smaller prey, and an increase in insects in the diet, suggesting that piscivores were faced with chronic prey limitation during this study. The management of all piscivores in Lake Huron will likely require consideration of the pervasive effects of changes in food webs, especially if prey fish remain at low levels.Received December 19, 2013; accepted June 30, 2014
Spatial and Temporal Variation of the Gill Rakers of Gizzard Shad and Silver Carp in Three Midwestern Rivers
Authors: Walleser Liza R. , Sandheinrich Mark B. , Howard David R. , Gaikowski Mark P. , Amberg Jon J. 
Published: October 2014

Abstract
Improved management of invasive Silver Carp Hypophthalmichthys molitrix in the upper Mississippi River basin may be possible by better understanding the feeding abilities of this population. Food collection for filter-feeding fishes, such as Silver Carp, is influenced by the species-specific structure of their gill rakers. To investigate structural variation in gill rakers of Silver Carp, the morphology of gill rakers was quantified and compared with that of a native filter-feeding fish species which may compete with Silver Carp for food resources, Gizzard Shad Dorosoma cepedianum. Intra- and interspecies variation of gill rakers was examined in both species collected from three locations among four months. Interspecies analysis indicated the size of pores in gill rakers of Silver Carp were much larger than the interraker spacings of Gizzard Shad (95% CI ranged from 80.69 to 185.75 μm versus 16.72 to 47.36 μm, respectively). Intraspecies variation of gill rakers from Silver Carp was related to the overall size of fish and occurred only among sites where dissimilar sizes of fish were collected. This suggested the size of particles filtered by Silver Carp may be dependent upon ontogenic development rather than phenotypic plasticity in response to spatial or temporal factors. Intraspecies variation of gill rakers from Gizzard Shad occurred among site and monthly sampling data; however, variation was only attributable to overall size of fish for monthly sampling data. This suggested ontogeny may influence the filter-feeding ability of this species within a habitat. However, variation noted among sites, which was not attributable to size of fish, may indicate gill rakers are phenotypically plastic among Gizzard Shad populations of various river systems of the upper Mississippi River basin.
Received January 16, 2014; accepted April 13, 2014
Effects of Fish Length and Anatomical Placement on Retention of Visible Implant Alpha Tags in Hatchery-Reared Rainbow Trout
Authors: Davis Jacob L. , Barnes Michael E. , Kientz Jeremy L. , Galinat Austin G. 
Published: October 2014

Abstract
We examined the effects of anatomical placement and fish TL on 8-month retention of standard-sized (1.2 × 2.7 mm) visible implant alpha (VIA) tags in 255 Rainbow Trout Oncorhynchus mykiss (128–368 mm TL) at 14-d intervals in a hatchery setting. Anatomical placement was strongly associated with tag retention at each sampling period following day 154, culminating with significantly fewer (P &lt; 0.05) VIA tags retained in anal fin tissue (25%) than in postorbital adipose tissue (55%) on day 224. Logistic regression models suggested that TL was more strongly associated with retention when VIA tags were placed in postorbital adipose tissue than in anal fins. Visible implant alpha tag retention was significantly associated with TL for placement in the postorbital adipose tissue at each 14-d interval. Tag retention in anal fin tissue was associated with TL during the first 6-month period of the study and became less significant after day 182. Overall tag retention rates were lowest for fish &lt; 200 mm TL at 15% and 25% for anal fin and postorbital adipose placement, respectively, but rose to 28% and 63% for fish 200–300 mm TL and 30% and 75% for fish &gt;300 mm TL. Due to the effects of fish size and tagging location on tag retention in Rainbow Trout, we recommend VIA tag use only in fish &gt; 200 mm, with placement in postorbital tissue. Estimates of VIA tag retention should also be considered before or during marking studies involving Rainbow Trout.
Received January 8, 2014; accepted June 4, 2014
Annual Variation of Spawning Cutthroat Trout in a Small Western USA Stream: A Case Study with Implications for the Conservation of Potamodromous Trout Life History Diversity
Authors: Bennett Stephen , Al-Chokhachy Robert , Roper Brett B. , Budy Phaedra 
Published: October 2014

Abstract
Little is known about the variability in the spatial and temporal distribution of spawning potamodromous trout despite decades of research directed at salmonid spawning ecology and the increased awareness that conserving life history diversity should be a focus of management. We monitored a population of fluvial–resident Bonneville Cutthroat Trout Oncorhynchus clarkii utah in a tributary to the Logan River, Utah, from 2006 to 2012 to gain insight into the distribution and timing of spawning and what factors may influence these spawning activities. We monitored Bonneville Cutthroat Trout using redd surveys with multiple observers and georeferenced redd locations. We documented an extended spawning period that lasted from late April to mid-July. The onset, median, and end of spawning was best predicted by the mean maximum water temperature during the first 13 weeks of the year (F = 130. 4, df = 5, R2 = 0.96, P &lt; 0.0001) with spawning beginning and ending earlier in years that had warmer water temperatures prior to spawning. The distribution of redds was clumped each year and the relative density of redds was greater in a reach dominated by dams constructed by beavers Castor canadensis. Both dam failure and construction appeared to be responsible for creating new spawning habitat that was quickly occupied, demonstrating rapid temporal response to local habitat changes. Bonneville Cutthroat Trout appeared to establish and defend a redd for up to 2 d, and spawning most often occurred between similar-sized individuals. Spawning surveys for potamodromous trout are an underutilized tool that could be used to better understand the distribution and timing of spawning as well as determine the size and trends of the reproducing portion of populations of management concern. Without efforts to document the diversity of this important aspect of potamodromous trout life history, prioritization of conservation will be problematic.
A Morphometric Approach for Stocking Walleye Fingerlings in Lakes Invaded by Rainbow Smelt
Authors: Lawson Zach J. , Carpenter Stephen R. 
Published: October 2014

Abstract
Invasive Rainbow Smelt Osmerus mordax have been associated with reductions in Walleye Sander vitreus recruitment, and predation by adult smelt on age-0 Walleyes has been identified as one of the potential mechanisms contributing to recruitment failure. Predation effects could be mitigated by stocking Walleye fingerlings based on smelt and Walleye morphometric relationships. By combining 0.95 quantile regression of smelt gape size on TL and 0.05 quantile regression of Walleye body depth on TL, we constructed a stocking tool to determine the appropriate size to stock Walleye fingerlings in lakes invaded by smelt such that few Walleyes are vulnerable to predation by smelt. In lakes where the largest smelt TL is known, Walleye fingerlings can be stocked according to the model: TLWYE = 0.819(TLRWS) − 23.838. In cases where the smelt population size structure is unknown, Walleyes should be stocked at sizes larger than 142 mm, which would be a sufficient size for Walleye fingerlings to avoid predation by Rainbow Smelt in all lakes in this study.
Received January 16, 2014; accepted June 30, 2014
Laboratory Evaluation of a Bioacoustic Bubble Strobe Light Barrier for Reducing Walleye Escapement
Authors: Flammang Mark K. , Weber Michael J. , Thul Megan D. 
Published: October 2014

Abstract
Fish escapement is a largely overlooked challenge to managing reservoir fisheries. Physical barriers may help retain fish in reservoirs but are often not practical due to high reservoir debris loads and maintenance requirements of these structures. As an alternative, nonphysical barriers may also be successful at increasing fish retention in reservoirs through the use of negative stimuli that divert fish away from targeted locations. However, the effectiveness of nonphysical barriers can vary considerably among barrier stimuli and fish species because the barrier's success is dependent upon on a behavioral response from fish. We conducted a laboratory experiment to evaluate the effectiveness of a bioacoustic bubble–strobe light barrier at reducing Walleye Sander vitreus escapement rates. We hypothesized that increasing the number and frequency of barrier stimuli would result in Walleyes approaching the barrier less frequently, reduced escapement, and increased amount of time before escapement occurred. Walleyes approached the barrier and were successfully deterred most often when lights were off and sound was on. Walleye escapement rates declined from 89.3% with the barrier off to 44.1% with low and medium sound, whereas up to 100% of the fish escaped with the addition of light. Mean time before escapement and time to 50% escapement increased with the use of sound, whereas fish escaped in less time when light was used as a deterrent. Most Walleyes escaped around sunset indicating that fish were most active during the crepuscular period. Despite reductions in escapement associated with sound–bubble barriers, we recommend that alternative nonphysical barriers be evaluated for their potential to further increase retention of Walleyes before installation of sound barrier deterrent systems in reservoirs.
Received December 23, 2013; accepted June 27, 2014
Executive Summary: Clinical Practice Guideline for the Management of Chronic Kidney Disease in Patients Infected With HIV: 2014 Update by the HIV Medicine Association of the Infectious Diseases Society of America
Authors: Lucas Gregory M. , Ross Michael J. , Stock Peter G. , Shlipak Michael G. , Wyatt Christina M. , Gupta Samir K. , Atta Mohamed G. , Wools-Kaloustian Kara K. , Pham Paul A. , Bruggeman Leslie A. , Lennox Jeffrey L. , Ray Patricio E. , Kalayjian Robert C. 
Published: October 2014

Abstract
It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.
From Bad to Worse: Anemia on Admission and Hospital-Acquired Anemia
Authors: Koch Colleen G. , Li Liang , Sun Zhiyuan , Hixson Eric D. , Tang Anne S. , Phillips Shannon C. , Blackstone Eugene H. , Henderson J. Michael 
Published: October 2014

Background
Anemia at hospitalization is often treated as an accompaniment to an underlying illness, without active investigation, despite its association with morbidity. Development of hospital-acquired anemia (HAA) has also been associated with increased risk for poor outcomes. Together, they may further heighten morbidity risk from bad to worse.

Objectives
The aims of this study were to (1) examine mortality, length of stay, and total charges in patients with present-on-admission (POA) anemia and (2) determine whether these are exacerbated by development of HAA.

Design/Setting/Patients
In this cohort investigation, from January 1, 2009, to August 31, 2011, a total of 44,483 patients with POA anemia were admitted to a single health system compared with a reference group of 48,640 without POA anemia or HAA.

Measurements
Data sources included the University HealthSystem Consortium database and electronic medical records. Risk-adjustment methods included logistic and linear regression models for mortality, length of stay, and total charges. Present-on-admission anemia was defined by administrative coding. Hospital-acquired anemia was determined by changes in hemoglobin values from the electronic medical record.

Results
Approximately one-half of the patients experienced worsening of anemia with development of HAA. Risk for death and resource use increased with increasing severity of HAA. Those who developed severe HAA had 2-fold greater odds for death; that is, mild POA anemia with development of severe HAA resulted in greater mortality (odds ratio, 2.57; 95% confidence interval, 2.08–3.18; P < 0.001), increased length of stay (2.23; 2.16–2.31; P < 0.001), and higher charges (2.09; 2.03–2.15; P < 0.001).

Conclusions
Present-on-admission anemia is associated with increased mortality and resource use. This risk is further increased from bad to worse when patients develop HAA. Efforts to address POA anemia and HAA deserve attention.
Skip and bin: pervasive alternative splicing triggers degradation by nuclear RNA surveillance in fission yeast
Authors: Bitton Danny A. , Atkinson Sophie R. , Rallis Charalampos , Smith Graeme C. , Ellis David A. , Jeffares Daniel C. , Chen Yuan Y.C. , Malecki Michal , Codlin Sandra , Lubas Michal , Lemay Jean-François , Bachand François , Cotobal Cristina , Marguerat Samuel , Mata Juan , Heick Jensen Torben , Bähler Jürg 
Published: October 2014

AbstractExon-skipping is considered a principal mechanism by which eukaryotic cells expand their transcriptome and proteome repertoires, creating different slice varaiants with distinct cellular functions. Here we analyze RNA-seq data from 116 transcriptomes in fission yeast (Schizosaccharomyces pombe), covering multiple physiological conditions as well as transcriptional and RNA processing mutants. We applied brute-force algorithms to detect all possible exon-skipping events, which were ubiquitous but rare compared to canonical splicing events. Exon-skipping events increased in cells deficient for the nuclear exosome or the 5’-3’ exonuclease Dhp1, and also at late stages of meiotic differentiation when nuclear-exosome transcripts were down-regulated. The pervasive exon-skipping transcripts were stochastic, did not increase in specific physiological conditions, and were mostly present at below 1 copy per cell, even in the absence of nuclear RNA surveillance and late during meiosis. These exon-skipping transcripts are therefore unlikely to be functional and may reflect splicing errors that are actively removed by nuclear RNA surveillance. The average splicing error-rate was ∼0.24% in wild-type and ∼1.75% in nuclear exonuclease mutants. Using an exhaustive search algorithm, we also uncovered thousands of previously unknown splice sites, indicating pervasive splicing, yet most of these novel splicing events were rare and targeted for nuclear degradation. Analysis of human transcriptomes revealed similar, albeit much weaker trends for pervasive exon-skipping transcripts, some of which being degraded by the nuclear exosome. This study highlights widespread, but low frequency alternative splicing which is targeted by nuclear RNA surveillance.