bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developmental bias in the evolution of phalanges
Authors: Kavanagh Kathryn D. , Shoval Oren , Winslow Benjamin B. , Alon Uri , Leary Brian P. , Kan Akinori , Tabin Clifford J. 
Published: October 2013

SignificanceIt has long been proposed that rules stemming from the mechanisms used during development can constrain the range of evolvable variations in a given form, but few empirical examples are known. We have focused on developmental processes determining proportions of phalanx size along individual digits (fingers/toes) of vertebrates. We find that phalangeal variation seen in nature is indeed constrained by an ancestral developmental program, limiting morphologies to a continuum from nearly equal-sized phalanges to a large-to-small gradient of relative sizes. Nonetheless, later innovations in distal regulation expanded variational possibilities for groups that needed greater grasping ability. These data provide a better understanding of how properties of developmental systems work in combination with natural selection to guide evolution of skeletal proportions.
On a one-dimensional 𝛼-patch model with nonlocal drift and fractional dissipation
Authors: Dong Hongjie , Li Dong 
Published: October 2013

We consider a one-dimensional nonlocal nonlinear equation of the form

∂
t

u
=
(

Λ

−
α

u
)

∂
x

u
−
ν

Λ

β

u

\partial _t u = (\Lambda ^{-\alpha } u)\partial _x u - \nu \Lambda ^{\beta }u

, where

Λ
=
(
−

∂

x
x

)

1
2

\Lambda =(-\partial _{xx})^{\frac 12}

is the fractional Laplacian and

ν
≥
0

\nu \ge 0

is the viscosity coefficient. We primarily consider the regime

0
>
α
>
1

0>\alpha >1

and

0
≤
β
≤
2

0\le \beta \le 2

for which the model has nonlocal drift, fractional dissipation, and captures essential features of the 2D

α
\alpha

-patch models. In the critical and subcritical range

1
−
α
≤
β
≤
2

1-\alpha \le \beta \le 2

, we prove global wellposedness for arbitrarily large initial data in Sobolev spaces. In the full supercritical range

0
≤
β
>
1
−
α

0 \le \beta >1-\alpha

, we prove formation of singularities in finite time for a class of smooth initial data. Our proof is based on a novel nonlocal weighted inequality which can be of independent interest.
SeqPig: simple and scalable scripting for large sequencing data sets in Hadoop
Authors: Schumacher André , Pireddu Luca , Niemenmaa Matti , Kallio Aleksi , Korpelainen Eija , Zanetti Gianluigi , Heljanko Keijo 
Published: October 2013

Abstract
Summary: Hadoop MapReduce-based approaches have become increasingly popular due to their scalability in processing large sequencing datasets. However, as these methods typically require in-depth expertise in Hadoop and Java, they are still out of reach of many bioinformaticians. To solve this problem, we have created SeqPig, a library and a collection of tools to manipulate, analyze and query sequencing datasets in a scalable and simple manner. SeqPigscripts use the Hadoop-based distributed scripting engine Apache Pig, which automatically parallelizes and distributes data processing tasks. We demonstrate SeqPig’s scalability over many computing nodes and illustrate its use with example scripts.
Availability and Implementation: Available under the open source MIT license at http://sourceforge.net/projects/seqpig/
Contact: andre.schumacher@yahoo.com
Supplementary information: Supplementary data are available at Bioinformatics online.
Cascleave 2.0, a new approach for predicting caspase and granzyme cleavage targets
Authors: Wang Mingjun , Zhao Xing-Ming , Tan Hao , Akutsu Tatsuya , Whisstock James C. , Song Jiangning 
Published: October 2013

Abstract
Motivation: Caspases and granzyme B (GrB) are important proteases involved in fundamental cellular processes and play essential roles in programmed cell death, necrosis and inflammation. Although a number of substrates for both types have been experimentally identified, the complete repertoire of caspases and granzyme B substrates remained to be fully characterized. Accordingly, systematic bioinformatics studies of known cleavage sites may provide important insights into their substrate specificity and facilitate the discovery of novel substrates.
Results: We develop a new bioinformatics tool, termed Cascleave 2.0, which builds on previous success of the Cascleave tool for predicting generic caspase cleavage sites. It can be efficiently used to predict potential caspase-specific cleavage sites for the human caspase-1, 3, 6, 7, 8 and GrB. In particular, we integrate heterogeneous sequence and protein functional information from various sources to improve the prediction accuracy of Cascleave 2.0. During classification, we use both maximum relevance minimum redundancy and forward feature selection techniques to quantify the relative contribution of each feature to prediction and thus remove redundant as well as irrelevant features. A systematic evaluation of Cascleave 2.0 using the benchmark data and comparison with other state-of-the-art tools using independent test data indicate that Cascleave 2.0 outperforms other tools on protease-specific cleavage site prediction of caspase-1, 3, 6, 7 and GrB. Cascleave 2.0 is anticipated to be used as a powerful tool for identifying novel substrates and cleavage sites of caspases and GrB and help understand the functional roles of these important proteases in human proteolytic cascades.
Availability and implementation: http://www.structbioinfor.org/cascleave2/.
Contact: Jiangning.Song@monash.edu or James.Whisstock@monash.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Early pathological alterations of lower lumbar cords detected by ultrahigh-field MRI in a mouse multiple sclerosis model
Authors: Mori Yuki , Murakami Masaaki , Arima Yasunobu , Zhu Dasong , Terayama Yasuo , Komai Yutaka , Nakatsuji Yuji , Kamimura Daisuke , Yoshioka Yoshichika 
Published: October 2013

Abstract
Magnetic resonance imaging (MRI) is widely employed for the diagnosis of multiple sclerosis (MS). However, sometimes, the lesions found by MRI do not correlate with the neurological impairments observed in MS patients. We recently showed autoreactive T cells accumulate in the fifth lumbar cord (L5) to pass the blood–brain barrier and cause inflammation in the central nervous system of experimental autoimmune encephalomyelitis (EAE) mice, an MS model. We here investigated this early event using ultrahigh-field MRI. T2-weighted image signals, which conform to the water content, increased in L4 and L5 during the development of EAE. At the same time, the sizes of L4 and L5 changed. Moreover, angiographic images of MRI showed branch positions of the blood vessels in the lower lumbar cords were significantly altered. Interestingly, EAE mice showed occluded and thickened vessels, particularly during the peak phase, followed by reperfusion in the remission phase. Additionally, demyelination regions of some MS patients had increased lactic acid content, suggesting the presence of ischemic events. These results suggest that inflammation-mediated alterations in the lower lumbar cord change the homeostasis of the spinal cord and demonstrate that ultrahigh-field MRI enables the detection of previously invisible pathological alterations in EAE.
Hypoxia-induced and A2A adenosine receptor-independent T-cell suppression is short lived and easily reversible
Authors: Ohta Akio , Madasu Manasa , Subramanian Meenakshi , Kini Radhika , Jones Graham , Choukèr Alexander , Ohta Akiko , Sitkovsky Michail 
Published: October 2013

Abstract
Tissue hypoxia plays a key role in establishing an immunosuppressive environment in vivo by, among other effects, increasing the level of extracellular adenosine, which then signals through A2A adenosine receptor (A2AR) to elicit its immunosuppressive effect. Although the important role of the adenosine–A2AR interaction in limiting inflammation has been established, the current study revisited this issue by asking whether hypoxia can also exert its T-cell inhibitory effects even without A2AR. A similar degree of hypoxia-triggered inhibition was observed in wild-type and A2AR-deficient T cells both in vitro and, after exposure of mice to a hypoxic atmosphere, in vivo. This A2AR-independent hypoxic T-cell suppression was qualitatively and mechanistically different from immunosuppression by A2AR stimulation. The A2AR-independent hypoxic immunosuppression strongly reduced T-cell proliferation, while IFN-γ-producing activity was more susceptible to the A2AR-dependent inhibition. In contrast to the sustained functional impairment after A2AR-mediated T-cell inhibition, the A2AR-independent inhibition under hypoxia was short lived, as evidenced by the quick recovery of IFN-γ-producing activity upon re-stimulation. These data support the view that T-cell inhibition by hypoxia can be mediated by multiple mechanisms and that both A2AR and key molecules in the A2AR-independent T-cell inhibition should be targeted to overcome the hypoxia-related immunosuppression in infected tissues and tumors.
Th2-type inflammation instructs inflammatory dendritic cells to induce airway hyperreactivity
Authors: Iwata Arifumi , Kawashima Saki , Kobayashi Midori , Okubo Ayako , Kawashima Hirotoshi , Suto Akira , Hirose Koichi , Nakayama Toshinori , Nakajima Hiroshi 
Published: October 2013

Abstract
Dendritic cells (DCs) play critical roles in determining the fate of CD4+ T cells. Among DC sub-populations, monocyte-derived inflammatory DCs (iDCs) have been shown to play an important role in the induction of adaptive immune responses under inflammatory conditions. Although previous studies have shown that DCs have an indispensable role in the induction of allergic airway inflammation and airway hyperreactivity (AHR) in murine asthma models, the precise roles of iDCs in the asthmatic responses remain largely unknown. We show here that Th2 cell-mediated inflammation in murine asthma models induces the expression of some markers of alternatively activated macrophage such as arginase 1 and resistin-like molecule-α in iDCs by a mechanism depending on the intrinsic expression of STAT6. In contrast, Th1 cell-mediated inflammation induces iDCs to express TNF-α and inducible nitric oxide synthase (iNOS), markers of TNF-α- and iNOS-producing DCs. Moreover, we show that iDCs under a Th2 environment play an important role in the induction of AHR, independently of allergic airway inflammation. Our results thus indicate the importance of iDCs in the induction of AHR as downstream effector cells in Th2 cell-mediated asthmatic responses.
The double PHD finger domain of MOZ/MYST3 induces α-helical structure of the histone H3 tail to facilitate acetylation and methylation sampling and modification
Authors: Dreveny Ingrid , Deeves Sian E. , Fulton Joel , Yue Baigong , Messmer Marie , Bhattacharya Amit , Collins Hilary M. , Heery David M. 
Published: October 2013

Abstract
Histone tail modifications control many nuclear processes by dictating the dynamic exchange of regulatory proteins on chromatin. Here we report novel insights into histone H3 tail structure in complex with the double PHD finger (DPF) of the lysine acetyltransferase MOZ/MYST3/KAT6A. In addition to sampling H3 and H4 modification status, we show that the DPF cooperates with the MYST domain to promote H3K9 and H3K14 acetylation, although not if H3K4 is trimethylated. Four crystal structures of an extended DPF alone and in complex with unmodified or acetylated forms of the H3 tail reveal the molecular basis of crosstalk between H3K4me3 and H3K14ac. We show for the first time that MOZ DPF induces α-helical conformation of H3K4-T11, revealing a unique mode of H3 recognition. The helical structure facilitates sampling of H3K4 methylation status, and proffers H3K9 and other residues for modification. Additionally, we show that a conserved double glycine hinge flanking the H3 tail helix is required for a conformational change enabling docking of H3K14ac with the DPF. In summary, our data provide the first observations of extensive helical structure in a histone tail, revealing the inherent ability of the H3 tail to adopt alternate conformations in complex with chromatin regulators.
Intrathecal Substance P-Saporin in the Dog
Authors: Brown Dorothy Cimino , Agnello Kimberly 
Published: October 2013

Abstract

Background:
Substance P-saporin (SP-SAP), a chemical conjugate of substance P and a recombinant version of the ribosome-inactivating protein, saporin, when administered intrathecally, acts as a targeted neurotoxin producing selective destruction of superficial neurokinin-1 receptor–bearing cells in the spinal dorsal horn. The goal of this study was to provide proof-of-concept data that a single intrathecal injection of SP-SAP could safely provide effective pain relief in spontaneous bone cancer pain in companion (pet) dogs.

Methods:
In a single-blind, controlled study, 70 companion dogs with bone cancer pain were randomized to standard-of-care analgesic therapy alone (control, n = 35) or intrathecal SP-SAP (20–60 µg) in addition to standard-of-care analgesic therapy (n = 35). Activity, pain scores, and videography data were collected at baseline, 2 weeks postrandomization, and then monthly until death.

Results:
Although the efficacy results at the 2-week postrandomization point were equivocal, the outcomes evaluated beyond 2 weeks revealed a positive effect of SP-SAP on chronic pain management. Significantly, more dogs in the control group (74%) required unblinding and adjustment in analgesic protocol or euthanasia within 6 weeks of randomization than dogs that were treated with SP-SAP (24%; P < 0.001); and overall, dogs in the control group required unblinding significantly sooner than dogs that had been treated with SP-SAP (P < 0.01).

Conclusion:
Intrathecal administration of SP-SAP in dogs with bone cancer produces a time-dependent antinociceptive effect with no evidence of development of deafferentation pain syndrome which can be seen with neurolytic therapies.
Geochemical, metagenomic and metaproteomic insights into trace metal utilization by methane‐oxidizing microbial consortia in sulphidic marine sediments
Authors: Glass Jennifer B. , Yu Hang , Steele Joshua A. , Dawson Katherine S. , Sun Shulei , Chourey Karuna , Pan Chongle , Hettich Robert L. , Orphan Victoria J. 
Published: October 2013

SummaryMicrobes have obligate requirements for trace metals in metalloenzymes that catalyse important biogeochemical reactions. In anoxic methane‐ and sulphide‐rich environments, microbes may have unique adaptations for metal acquisition and utilization because of decreased bioavailability as a result of metal sulphide precipitation. However, micronutrient cycling is largely unexplored in cold (≤ 10°C) and sulphidic (> 1 mM ΣH2S) deep‐sea methane seep ecosystems. We investigated trace metal geochemistry and microbial metal utilization in methane seeps offshore Oregon and California, USA, and report dissolved concentrations of nickel (0.5–270 nM), cobalt (0.5–6 nM), molybdenum (10–5600 nM) and tungsten (0.3–8 nM) in Hydrate Ridge sediment porewaters. Despite low levels of cobalt and tungsten, metagenomic and metaproteomic data suggest that microbial consortia catalysing anaerobic oxidation of methane (AOM) utilize both scarce micronutrients in addition to nickel and molybdenum. Genetic machinery for cobalt‐containing vitamin B12 biosynthesis was present in both anaerobic methanotrophic archaea (ANME) and sulphate‐reducing bacteria. Proteins affiliated with the tungsten‐containing form of formylmethanofuran dehydrogenase were expressed in ANME from two seep ecosystems, the first evidence for expression of a tungstoenzyme in psychrophilic microorganisms. Overall, our data suggest that AOM consortia use specialized biochemical strategies to overcome the challenges of metal availability in sulphidic environments.
Consumption of atmospheric hydrogen during the life cycle of soil‐dwelling actinobacteria
Authors: Meredith Laura K. , Rao Deepa , Bosak Tanja , Klepac‐Ceraj Vanja , Tada Kendall R. , Hansel Colleen M. , Ono Shuhei , Prinn Ronald G. 
Published: October 2013

SummaryMicrobe‐mediated soil uptake is the largest and most uncertain variable in the budget of atmospheric hydrogen (H2). The diversity and ecophysiological role of soil microorganisms that can consume low atmospheric abundances ofH2with high‐affinity [NiFe]‐hydrogenases is unknown. We expanded the library of atmosphericH2‐consuming strains to include four soilHarvardForestIsolate (HFI)Streptomycesspp.,Streptomyces cattleyaandRhodococcus equiby assaying for high‐affinity hydrogenase (hhyL) genes and quantifyingH2uptake rates. We find that aerial structures (hyphae and spores) are important forStreptomyces H2consumption; uptake was not observed inS. griseoflavus Tu4000 (deficient in aerial structures) and was reduced by physical disruption ofStreptomycessp.HFI8 aerial structures.H2consumption depended on the life cycle stage in developmentally distinct actinobacteria:Streptomycessp.HFI8 (sporulating) andR. equi(non‐sporulating, non‐filamentous). StrainHFI8 took upH2only after forming aerial hyphae and sporulating, whileR. equionly consumedH2in the late exponential and stationary phase. These observations suggest that conditions favouringH2uptake by actinobacteria are associated with energy and nutrient limitation. Thus,H2may be an important energy source for soil microorganisms inhabiting systems in which nutrients are frequently limited.
Computed Tomographic Anatomy of the Equine Foot
Authors: Claerhoudt S. , Bergman E. H. J. , Saunders J. H. 
Published: October 2013

SummaryThis study describes a detailed computed tomographic reference of the normal equine foot. Ten forefeet of five adult cadavers, without evidence of orthopaedic disease, were used. Computed tomography (CT) was performed on all feet. Two‐millimetre thick transverse slices were obtained, and sagittal and dorsal planes were reformatted. The CT images were matched with the corresponding anatomic slices. The phalanges and the distal sesamoid bone showed excellent detail. The extensor and flexor tendons (including their attachments) could be clearly evaluated. The collateral (sesamoidean) ligaments could be readily located, but were difficult to delineate at their proximal attachment. The distal digital annular ligament could only be distinguished from the deep digital flexor tendon proximal to the distal sesamoid bone, and its proximal attachment could be identified, but not its distal insertion. Small ligaments (impar ligament, chondrosesamoidean, chondrocoronal and chondrocompedal ligaments, axial and abaxial palmar ligaments of the proximal inter‐phalangeal joint) were seen with difficulty and not at all slices. The joint capsules could not be delineated from the surrounding soft tissue structures. The lateral and medial proprius palmar digital artery and vein could be visualized occasionally on some slices. The ungular cartilages, corium and hoof wall layering were seen. The nerves, the articular and fibrocartilage of the distal sesamoid bone and the chondroungular ligament could not be assessed. Computed tomography of the equine foot can be of great value when results of radiography and ultrasonography are inconclusive. Images obtained in this study may serve as reference for CT of the equine foot.
Resting ST Amplitude: Prognosis and Normal Values in an Ambulatory Clinical Population
Authors: Zarafshar Shirin , Wong Myo , Singh Nikhil , Aggarwal Sonya , Adhikarla Chandana , Froelicher V.F. 
Published: October 2013

BackgroundThere is limited data describing ST segment amplitude in apparently healthy, asymptomatic populations. We analyzed ST amplitude in the standard resting electrocardiogram (ECG) in a large, multiethnic, stable, clinical population.MethodsWe evaluated computerized ST amplitude measurements from the resting ECGs of 29,281 ambulatory outpatients collected between 1987 and 1999 at the Palo Alto, VA. With the PR interval as the isoelectric line, both elevation criteria (≥0.1 mV, ≥0.15 mV, and ≥0.2 mV) and depression criteria (≤–0.05 mV or ≤–0.1 mV), were applied. Cox–Hazard survival analysis techniques were used to demonstrate in which leads ST amplitude displacement was associated with cardiovascular (CV) death. To create a cohort without ECG patterns clearly associated with disease, we excluded ECGs with inverted T waves, wide QRS, or diagnostic Q waves and coded the remaining “normal” ECGs for ST elevation and depression to determine a normal range.ResultsThe only ST amplitudes that were significantly and independently associated with time to CV death when adjusted for age, gender, and ethnicity were ST depression in all of the lateral leads (I, V4–V6). When isolated to the inferior leads, (II and AVF), no ST amplitude criteria were associated with CV death. Among the “normal ECG” subgroup the precordial leads exhibited the greatest median ST amplitudes and the most significant differences between the leads, genders and ethnicities.ConclusionsSignificant differences in ST amplitude were present in the precordial leads according to gender and ethnicity. This was particularly apparent when amplitude threshold were set for comparisons. Our findings provide the normal range for ST amplitude that when exceeded, should raise clinical concern.
Single‐incision laparoscopic partial gastrectomy for gastric submucosal tumors without compromising transumbilical stapling
Authors: Takata Akihiro , Nakajima Kiyokazu , Kurokawa Yukinori , Takahashi Tsuyoshi , Yamasaki Makoto , Miyata Hiroshi , Takiguchi Shuji , Mori Masaki , Doki Yuichiro 
Published: October 2013

AbstractIntroductionAlthough SILS has become an increasingly popular type of surgery, its application for gastric submucosal tumors (SMT) has been only sporadically reported. We herein describe 12 recent cases with gastric SMT located in the greater curvature or anterior wall. The aim is to validate technical feasibility and safety of single‐incision laparoscopic partial gastrectomy. Thus far, this is one of the largest series of patients with gastric SMT who underwent SILS.MethodsFrom July 2009 to April 2013, single‐incision laparoscopic partial gastrectomy was attempted in 12 consecutive patients with gastric SMT. Three trocars were assembled in the umbilical incision, and the lesion was mobilized and staple‐resected with endoscopic stapling devices.ResultsSILS surgery was successfully completed without any additional trocars. The median operating time was 96.5 min, and median blood loss was 7.5 mL. The median tumor size was 30 mm, with histopathologic diagnosis of gastrointestinal stromal tumor (10) and schwannoma (2). There was no immediate postoperative morbidity. During a median follow‐up of 12 months, all patients were on full regular diet without any gastrointestinal symptoms.ConclusionSILS with transumbilical gastric stapling is a safe and practical alternative to conventional multiport laparoscopy in patients with gastric SMT, except for cases originating in the lesser curvature and close to the cardia/ pylorus.