bluuebunny/crossref_metadata_2025 huggingface dataset:
SPARCL1 suppresses metastasis in prostate cancer
Authors: Xiang Yuzhu , Qiu Qingchao , Jiang Ming , Jin Renjie , Lehmann Brian D. , Strand Douglas W. , Jovanovic Bojana , DeGraff David J. , Zheng Yi , Yousif Dina A. , Simmons Christine Q. , Case Thomas C. , Yi Jia , Cates Justin M. , Virostko John , He Xiusheng , Jin Xunbo , Hayward Simon W. , Matusik Robert J. , George Alfred L. , Yi Yajun
Published: July 2013

Purpose

Metastasis, the main cause of death from cancer, remains poorly understood at the molecular level.

Experimental design

Based on a pattern of reduced expression in human prostate cancer tissues and tumor cell lines, a candidate suppressor gene (SPARCL1) was identified. We used in vitro approaches to determine whether overexpression of SPARCL1 affects cell growth, migration, and invasiveness. We then employed xenograft mouse models to analyze the impact of SPARCL1 on prostate cancer cell growth and metastasis in vivo.

Results

SPARCL1 expression did not inhibit tumor cell proliferation in vitro. By contrast, SPARCL1 did suppress tumor cell migration and invasiveness in vitro and tumor metastatic growth in vivo, conferring improved survival in xenograft mouse models.

Conclusions

We present the first in vivo data suggesting that SPARCL1 suppresses metastasis of prostate cancer.
Nelfinavir and bortezomib inhibit mTOR activity via ATF4‐mediated sestrin‐2 regulation
Authors: Brüning Ansgar , Rahmeh Martina , Friese Klaus
Published: July 2013

Endoplasmic reticulum (ER) stress and autophagy are two basic cell survival mechanisms often occurring in concert. Extensive ER stress in cancer cells deliberately induced by chemotherapeutic drugs may lead to growth arrest and cell death. However, the link between ER stress and autophagy is not well understood. In this study, the treatment of cancer cells with ER stress‐inducing drug nelfinavir resulted in the expression of endogenous mTOR inhibitor sestrin‐2 (SESN2). Upregulation of SESN2 expression was associated with expression of ER stress markers ATF4, ATF3, and CHOP. SESN2 upregulation also occurred in cells treated with the proteasome inhibitor bortezomib. Ectopic expression of ATF4, but not of ATF3 or CHOP, caused transcriptional upregulation of SESN2 expression, indicating expressional regulation of SESN2 by ATF4. Transient overexpression of ectopic SESN2 resulted in mTOR inhibition and autophagy, confirming a link between ER stress, SESN2 upregulation, and mTOR inhibition. Accordingly, cancer cells treated with the ER stress‐inducing agent nelfinavir showed reduced mTOR activity and associated increases in the expression levels of ATF4 and SESN2. These results show that ATF4‐regulated SESN2 expression presents a new link between ER stress and mTOR inhibition and autophagy. mTOR inhibition by nelfinavir, which is currently in clinical trials for cancer patients, may also explain its observed ability to induce autophagy, growth arrest, and radiosensitization in cancer cells.
Phantom Limb Pain From Spinal Sarcoma: A Case Report
Authors: Cruz Ernesto , Dangaria Harsh T.
Published: July 2013

Phantom limb pain is a frequent sequela of amputation. A high prevalence of residual limb pain and back pain also exists among amputees. We present a case of a new‐onset severe phantom limb pain resulting from a metastatic spinal mass in an 81‐year‐old patient with a history of malignant sarcoma and an old hip disarticulation amputation. The metastatic lesion, upon imaging, was found to involve the L3 vertebra and caused moderate compression of the thecal sac on the right and severe right lateral recess stenosis. After the mass was resected, the patient's phantom limb pain resolved. Our case report demonstrates that spinal metastatic pathologies may be a cause of phantom limb pain and should be included in the differential diagnosis of new‐onset phantom limb pain or a change in phantom limb pain.
Analytical Review: Focus on Fall Screening Assessments
Authors: Lee Jacob , Geller Andrew I. , Strasser Dale C.
Published: July 2013

Background

Falls and their associated injuries profoundly impact health outcomes, functional independence, and health care expenses, particularly for the ever‐increasing elderly population. This systematic search and review assessed the current evidence for the role of fall screening assessments.

Objective

To review the current evidence for fall risk screening assessments in community‐dwelling (outpatient), inpatient medical and surgical wards, inpatient rehabilitation centers, and postrehabilitation outpatient settings.

Data Sources

MEDLINE and Embase (January 1980 to December 2012).

Study Selection

Prospective validation studies of acute medical or surgical inpatients, acute rehabilitation inpatients, outpatients who completed acute inpatient rehabilitation, or community‐dwelling elderly.

Data Extraction

Sensitivity, specificity, positive predictive value, negative predictive value, receiver operating characteristics with area under the curve.

Results

We summarized key findings from 6 literature reviews. We then identified 31 articles: 12 studies in community setting, 13 in the acute medical inpatient or surgical inpatient setting, and 6 studies in the rehabilitation setting. Twenty‐two studies not previously reviewed were included, and 9 studies previously reviewed were considered relevant and were included to allow comparison with data from the studies not previously reviewed.

Conclusion

We recommend consideration of 7 assessment tools to be used in conjunction with overall clinical evaluation to assess falls risk: the Timed Up and Go Test with a cutoff of >12.34 seconds and Functional Gait Assessment among community‐dwelling elderly; St Thomas Risk Assessment Tool in medical inpatients <65 years old and surgical inpatients; Hendrich fall risk model II in medical inpatients; 10‐Minute Walk Test in patients in poststroke rehabilitation; and Berg Balance Scale or the Step Test in patients in poststroke rehabilitation who had fallen during their inpatient stay.
Compliance and non-compliance as sources of recognition: Slovakia and NATO
Authors: Bátora Jozef
Published: July 2013

This article argues that there is a difference in what constitutes the sources of recognition prior to countries’ membership in the Euro-Atlantic community represented by NATO and after countries become its members. While prior to membership, countries are recognized for their compliance with NATO standards and policies, upon membership countries get the opportunity to promote specific interests legitimately and may seek recognition via non-compliance with NATO mainstream.

The paper explores this dynamic of recognition on the issue of Kosovo independence where Slovakia went from supporting NATO in its effort to protect civilians in Kosovo in the late 1990s to non-recognition of Kosovo in defiance of the majority of NATO member states less than a decade later. The crucial point proposed here is that there was a shift in how recognition by NATO worked prior to Slovakia’s membership and upon membership in these frameworks. While prior to membership recognition was achieved by compliance and identification with NATO standpoints, policies and actions, upon membership, recognition is achieved by differentiation from these patterns. More generally, the study shows that NATO membership is a powerful source of conditionality in relation to future members and a powerful source of legitimacy in relation to current members’ actions. While this has been discussed in the literature, the point here is that recognition in its various forms is an important driving force in these conditionality processes.
Overmilking causes deterioration in teat-end condition of dairy cows in late lactation
Authors: Edwards J Paul , O'Brien Bernadette , Lopez-Villalobos Nicolas , Jago Jenny G
Published: July 2013

The objective of the study was to determine the effect of varying degrees of overmilking on teat-end hyperkeratosis, milk production variables and indicators of udder health during late lactation. This was examined by assessing the effect of four end-of-milking criteria on 181 spring-calving, mixed-age Holstein-Friesian cows, at an average 217±24 d in milk, over a six-week period. The four treatments were: remove cluster once milk flow rate fell to 0·2 kg/min plus 5 s (Ovr0), plus 120 s (Ovr2), plus 300 s (Ovr5), and plus 540 s (Ovr9). Daily measurements included individual cow milk yield, milking duration, overmilking duration, maximum milk flow rate, milk flow rate at cluster removal and the number of cluster re-attachments. Individual cow bulk milk samples were collected weekly at AM and PM milkings to determine composition (fat, protein and lactose) and somatic cell count (SCC; AM only). Teat-end hyperkeratosis score was assessed at weeks 0, 3, 5 and 6. At week 6 mean teat-end hyperkeratosis score of the Ovr2 treatment was not greater than Ovr0, whilst Ovr5 was greater than Ovr2 and Ovr9 was greater than Ovr5 and Ovr2. Milk production, milking characteristics and SCC were not different between treatments, except milking duration and milk flow rate at cluster removal. However, higher teat-end hyperkeratosis scores may have a longer-term impact on indicators of udder health if teat-end condition reaches severe levels. Results indicate that to minimise changes in teat-end condition overmilking should be limited to 2 min, which has implications for milking management in large parlours not fitted with automatic cluster removers.
Pre-adjustment of adult attachment style to extrinsic risk levels via early attachment style is neither specific, nor reliable, nor effective, and is thus not an adaptation
Authors: Hönekopp Johannes
Published: July 2013

The mechanism proposed by Del Giudice by which adult attachment style is adapted to the extrinsic risk in the local environment via attachment style during the early years does not fulfill important criteria of an adaptation. The proposed mechanism is neither specific, nor developmentally reliable, nor effective. Therefore, it should not be considered an adaptation.
Is the second-step conditionalization unnecessary?
Authors: Liu In-mao
Published: July 2013

Because the addition of the conditional premise tends to increase modus ponens (MP) inferences, Oaksford & Chater argue that the additional knowledge is assimilated to world knowledge before the Ramsey test is carried out to evaluate P(q|p), so that the process of applying the Ramsey test could become indistinguishable from the process of applying the second-step conditionalization.
Uncertain premises and Jeffrey's rule
Authors: Over David E. , Hadjichristidis Constantinos
Published: July 2013

Oaksford & Chater (O&C) begin in the halfway Bayesian house of assuming that minor premises in conditional inferences are certain. We demonstrate that this assumption is a serious limitation. They additionally suggest that appealing to Jeffrey's rule could make their approach more general. We present evidence that this rule is not limited enough to account for actual probability judgements.
Exposure to Suicide and Identification as Survivor
Authors: Cerel Julie , Maple Myfanwy , Aldrich Rosalie , van de Venne Judy
Published: July 2013

Background: There is little empirical evidence regarding lifetime exposure to suicide or identification of those impacted by suicide deaths. Studies previously conducted used only convenience samples. Aims: To determine the prevalence of suicide exposure in the community and those affected by suicide deaths. Methods: A random digit dial sample of 302 adults. Results: 64% of the sample knew someone who had attempted or died by suicide, and 40% knew someone who died by suicide. No demographic variables differentiated exposed versus unexposed, indicating that exposure to suicide cuts across demographics. Almost 20% said they were a “survivor” and had been significantly affected by a suicide death. Demographic variables did not differentiate groups. The relationship to the decedent was not related to self-identified survivor status; what did differentiate those individuals impacted by the death from those who did not was their perception of their relationship with the decedent. Conclusions: Kinship proximity and relationship category to the deceased appeared to be unrelated to survivor status, but perceived psychological closeness to the deceased showed a robust association with self-identified survivor status. We need an expanded definition of “suicide survivor” to account for the profound impact of suicide in the community.
Responses to a Self-Presented Suicide Attempt in Social Media
Authors: Fu King-wa , Cheng Qijin , Wong Paul W. C. , Yip Paul S. F.
Published: July 2013

Background: The self-presentation of suicidal acts in social media has become a public health concern. Aims: This article centers on a Chinese microblogger who posted a wrist-cutting picture that was widely circulated in Chinese social media in 2011. This exploratory study examines written reactions of a group of Chinese microbloggers exposed to the post containing a self-harming message and photo. In addition, we investigate the pattern of information diffusion via a social network. Methods: We systematically collected and analyzed 5,971 generated microblogs and the network of information diffusion. Results: We found that a significant portion of written responses (36.6%) could help vulnerable netizens by providing peer-support and calls for help. These responses were reposted and diffused via an online social network with markedly more clusters of users – and at a faster pace – than a set of randomly generated networks. Conclusions: We conclude that social media can be a double-edged sword: While it may contagiously affect others by spreading suicidal thoughts and acts, it may also play a positive role by assisting people at risk for suicide, providing rescue or support. More research is needed to learn how suicidally vulnerable people interact with online suicide information, and how we can effectively intervene.
Seasonal Variation of Suicide in the City of São Paulo, Brazil, 1996–2010
Authors: Bando Daniel Hideki , Volpe Fernando Madalena
Published: July 2013

Background: In light of the few reports from intertropical latitudes and their conflicting results, we aimed to replicate and update the investigation of seasonal patterns of suicide occurrences in the city of São Paulo, Brazil. Methods: Data relating to male and female suicides were extracted from the Mortality Information Enhancement Program (PRO-AIM), the official health statistics of the municipality of São Paulo. Seasonality was assessed by studying distribution of suicides over time using cosinor analyses. Results: There were 6,916 registered suicides (76.7% men), with an average of 39.0 ± 7.0 observed suicides per month. For the total sample and for both sexes, cosinor analysis estimated a significant seasonal pattern. For the total sample and for males suicide peaked in November (late spring) with a trough in May–June (late autumn). For females, the estimated peak occurred in January, and the trough in June–July. Conclusions: A seasonal pattern of suicides was found for both males and females, peaking in spring/summer and dipping in fall/winter. The scarcity of reports from intertropical latitudes warrants promoting more studies in this area.
An experimental investigation on fluidic behaviors in a two-dimensional nanoenvironment
Authors: Li Hui , Xu Xiang , Qiao Yu
Published: July 2013

Behaviors of liquids in two-dimensional (2D), lyophobic nanoenvironment were investigated experimentally by using a surface-modified, graphene-based nanoslit composite (GBNC). Different from previous reports on one-dimensional (1D) nanofludic behaviors, the infiltration pressure of 2D nanofluid is not dependent on the infiltration volume, leading to a flat infiltration plateau in the sorption isotherm curve. This unique phenomenon implies that, compared with a 1D nanoenvironment, more energetically favorable molecular configurations may be formed in a 2D nanoslit, probably due to the relaxation of the lateral confinement.
Three-dimensional anti-Brownian electrokinetic trapping of a single nanoparticle in solution
Authors: King Jason K. , Canfield Brian K. , Davis Lloyd M.
Published: July 2013

A microfluidic device with four electrodes in a tetrahedral arrangement is used to demonstrate three-dimensional (3D) trapping of an individual 40 nm fluorescent nanoparticle in solution. Astigmatic imaging is used to determine the particle position in 3D for real-time control of the electrode potentials, which regulate the magnitude and direction of the electric field and the resulting electrokinetic motion of the particle so as to counteract Brownian diffusion. Trapping within a radius of 5 μm for extended periods (>1 min) is exhibited for particles with diffusivity 5.2 μm2/s and could be improved by increasing the imaging rate of 30 Hz.
Dynamic switching mechanism of conduction/set process in Cu/a-Si/Si memristive device
Authors: Gao Ligang , Lee Shin Buhm , Hoskins Brian , Yoo Hyang Keun , Kang Bo Soo
Published: July 2013

The conduction/set processes of resistive switching have been systemically investigated for Cu/a-Si/Si electrochemical memristive devices. Experimental results indicate that the set process was driven by two different mechanisms, depending on the programming pulse amplitude: a purely electrical dielectric breakdown and a thermally assisted dielectric breakdown. For the latter process, we observe that the set time decreased exponentially with the increase in the programming pulse amplitude, whereas the former process shows amplitude independence. Through the temperature-dependent set transition characteristics, we argue that the filament growth in set process could be dominated by cation transport in the dielectric film. The thermal activation energy of Cu hopping in a-Si is extracted to be 0.16 eV.
Structural insights into the proton pumping by unusual proteorhodopsin from nonmarine bacteria
Authors: Gushchin Ivan , Chervakov Pavel , Kuzmichev Pavel , Popov Alexander N. , Round Ekaterina , Borshchevskiy Valentin , Ishchenko Andrii , Petrovskaya Lada , Chupin Vladimir , Dolgikh Dmitry A. , Arseniev Alexander S. , Kirpichnikov Mikhail , Gordeliy Valentin
Published: July 2013

Light-driven proton pumps are present in many organisms. Here, we present a high-resolution structure of a proteorhodopsin from a permafrost bacterium,
Exiguobacterium sibiricum
rhodopsin (ESR). Contrary to the proton pumps of known structure, ESR possesses three unique features. First, ESR's proton donor is a lysine side chain that is situated very close to the bulk solvent. Second, the α-helical structure in the middle of the helix F is replaced by 3
10
- and π-helix–like elements that are stabilized by the Trp-154 and Asn-224 side chains. This feature is characteristic for the proteorhodopsin family of proteins. Third, the proton release region is connected to the bulk solvent by a chain of water molecules already in the ground state. Despite these peculiarities, the positions of water molecule and amino acid side chains in the immediate Schiff base vicinity are very well conserved. These features make ESR a very unusual proton pump. The presented structure sheds light on the large family of proteorhodopsins, for which structural information was not available previously.
Integrated biophysical approach to fragment screening and validation for fragment-based lead discovery
Authors: Silvestre Hernani Leonardo , Blundell Thomas L. , Abell Chris , Ciulli Alessio
Published: July 2013

In fragment-based drug discovery, the weak affinities exhibited by fragments pose significant challenges for screening. Biophysical techniques are used to address this challenge, but there is no clear consensus on which cascade of methods is best suited to identify fragment hits that ultimately translate into bound X-ray structures and provide bona fide starting points for synthesis. We have benchmarked an integrated biophysical approach for fragment screening and validation against
Mycobacterium tuberculosis
pantothenate synthetase. A primary screen of 1,250 fragments library was performed by thermal shift, followed by secondary screen using one-dimensional NMR spectroscopy (water ligand observed gradient spectroscopy and saturation transfer difference binding experiments) and ultimate hit validation by isothermal titration calorimetry and X-ray crystallography. Our multibiophysical approach identified three distinct binding sites for fragments and laid a solid foundation for successful structure-based elaboration into potent inhibitors.
Reactivity landscape of pyruvate under simulated hydrothermal vent conditions
Authors: Novikov Yehor , Copley Shelley D.
Published: July 2013

Pyruvate is an important “hub” metabolite that is a precursor for amino acids, sugars, cofactors, and lipids in extant metabolic networks. Pyruvate has been produced under simulated hydrothermal vent conditions from alkyl thiols and carbon monoxide in the presence of transition metal sulfides at 250 °C [Cody GD et al. (2000)
Science
289(5483):1337–1340], so it is plausible that pyruvate was formed in hydrothermal systems on the early earth. We report here that pyruvate reacts readily in the presence of transition metal sulfide minerals under simulated hydrothermal vent fluids at more moderate temperatures (25–110 °C) that are more conducive to survival of biogenic molecules. We found that pyruvate partitions among five reaction pathways at rates that depend upon the nature of the mineral present; the concentrations of H
2
S, H
2
, and NH
4
Cl; and the temperature. In most cases, high yields of one or two primary products are found due to preferential acceleration of certain pathways. Reactions observed include reduction of ketones to alcohols and aldol condensation, both reactions that are common in extant metabolic networks. We also observed reductive amination to form alanine and reduction to form propionic acid. Amino acids and fatty acids formed by analogous processes may have been important components of a protometabolic network that allowed the emergence of life.
Targeting H3K4 trimethylation in Huntington disease
Authors: Vashishtha Malini , Ng Christopher W. , Yildirim Ferah , Gipson Theresa A. , Kratter Ian H. , Bodai Laszlo , Song Wan , Lau Alice , Labadorf Adam , Vogel-Ciernia Annie , Troncosco Juan , Ross Christopher A. , Bates Gillian P. , Krainc Dimitri , Sadri-Vakili Ghazaleh , Finkbeiner Steven , Marsh J. Lawrence , Housman David E. , Fraenkel Ernest , Thompson Leslie M.
Published: July 2013

Significance

Transcriptional dysregulation is an early and reproducible feature of Huntington disease (HD); however, mechanisms underlying this dysregulation are unclear. This article describes a unique pattern of the chromatin mark H3K4me3 at transcriptionally repressed promoters in HD mouse and human brain identified by genome-wide analysis. Reducing the levels of the demethylase
SMCX/Jarid1c
in primary neurons reversed down-regulation of key neuronal genes caused by mutant Huntingtin expression and was neuroprotective in a
Drosophila
HD model. These results suggest that targeting epigenetic signatures may be an effective strategy to ameliorate the consequences of HD and other neurodegenerative diseases.
Testing for presence of known and unknown molecules in imaging mass spectrometry
Authors: Alexandrov Theodore , Bartels Andreas
Published: July 2013

Motivation: Imaging mass spectrometry has emerged in the past decade as a label-free, spatially resolved and multi-purpose bioanalytical technique for direct analysis of biological samples. However, solving two everyday data analysis problems still requires expert judgment: (i) the detection of unknown molecules and (ii) the testing for presence of known molecules.

Results: We developed a measure of spatial chaos of a molecular image corresponding to a mass-to-charge value, which is a proxy for the molecular presence, and developed methods solving considered problems. The statistical evaluation was performed on a dataset from a rat brain section with test sets of molecular images selected by an expert. The measure of spatial chaos has shown high agreement with expert judges. The method for detection of unknown molecules allowed us to find structured molecular images corresponding to spectral peaks of any low intensity. The test for presence applied to a list of endogenous peptides ranked them according to the proposed measure of their presence in the sample.

Availability: The source code and test sets of mass-to-charge images are available at http://www.math.uni-bremen.de/∼theodore.

Supplementary information:  Supplementary materials are available at Bioinformatics online.

Contact:  theodore@uni-bremen.de
Combining quantitative and qualitative models to identify functional groups for monitoring changes in the Bay of Biscay continental shelf exploited foodweb
Authors: Lassalle Géraldine , Nelva Pasqual Jean-Sébastien , Boët Philippe , Rochet Marie-Joëlle , Trenkel Verena M. , Niquil Nathalie
Published: July 2013

Lassalle, G., Nelva Pasqual, J-S., Boët, P., Rochet, M-J., Trenkel, V. M., and Niquil, N. Combining quantitative and qualitative models to identify functional groups for monitoring changes in the Bay of Biscay continental shelf exploited foodweb. – ICES Journal of Marine Science, 71: . To develop and implement ecosystem-based management, it is critical to monitor foodweb components or functional groups which are robust to uncertainty in ecosystem structure and functioning yet sensitive to changes. To select such functional groups for the Bay of Biscay continental shelf, both quantitative and qualitative foodweb models were developed. First, functional groups for which predictions of directions of change following an increase in primary productivity, prey or predators, or in fishing activities were identical across alternative qualitative model structures were identified. Second, the robustness to model type was assessed by comparing qualitative predictions with quantitative Ecopath model results. The demersal fish community was identified as a sensitive and robust indicator for monitoring foodweb ecological status in the Bay of Biscay. The present study also suggested the potential antagonistic effects of alternative management measures on small pelagic fish and highlighted the need for the joint management of all pressures.
Coelacanth genomes reveal signatures for evolutionary transition from water to land
Authors: Nikaido Masato , Noguchi Hideki , Nishihara Hidenori , Toyoda Atsushi , Suzuki Yutaka , Kajitani Rei , Suzuki Hikoyu , Okuno Miki , Aibara Mitsuto , Ngatunga Benjamin P. , Mzighani Semvua I. , Kalombo Hassan W.J. , Masengi Kawilarang W.A. , Tuda Josef , Nogami Sadao , Maeda Ryuichiro , Iwata Masamitsu , Abe Yoshitaka , Fujimura Koji , Okabe Masataka , Amano Takanori , Maeno Akiteru , Shiroishi Toshihiko , Itoh Takehiko , Sugano Sumio , Kohara Yuji , Fujiyama Asao , Okada Norihiro
Published: July 2013

Coelacanths are known as “living fossils,” as they show remarkable morphological resemblance to the fossil record and belong to the most primitive lineage of living Sarcopterygii (lobe-finned fishes and tetrapods). Coelacanths may be key to elucidating the tempo and mode of evolution from fish to tetrapods. Here, we report the genome sequences of five coelacanths, including four Latimeria chalumnae individuals (three specimens from Tanzania and one from Comoros) and one L. menadoensis individual from Indonesia. These sequences cover two African breeding populations and two known extant coelacanth species. The genome is ∼2.74 Gbp and contains a high proportion (∼60%) of repetitive elements. The genetic diversity among the individuals was extremely low, suggesting a small population size and/or a slow rate of evolution. We found a substantial number of genes that encode olfactory and pheromone receptors with features characteristic of tetrapod receptors for the detection of airborne ligands. We also found that limb enhancers of bmp7 and gli3, both of which are essential for limb formation, are conserved between coelacanth and tetrapods, but not ray-finned fishes. We expect that some tetrapod-like genes may have existed early in the evolution of primitive Sarcopterygii and were later co-opted to adapt to terrestrial environments. These coelacanth genomes will provide a cornerstone for studies to elucidate how ancestral aquatic vertebrates evolved into terrestrial animals.
Distinct Detoxification Mechanisms Confer Resistance to Mesotrione and Atrazine in a Population of Waterhemp
Authors: Ma Rong , Kaundun Shiv S. , Tranel Patrick J. , Riggins Chance W. , McGinness Daniel L. , Hager Aaron G. , Hawkes Tim , McIndoe Eddie , Riechers Dean E.
Published: July 2013

Previous research reported the first case of resistance to mesotrione and other 4-hydroxyphenylpyruvate dioxygenase (HPPD) herbicides in a waterhemp (Amaranthus tuberculatus) population designated MCR (for McLean County mesotrione- and atrazine-resistant). Herein, experiments were conducted to determine if target site or nontarget site mechanisms confer mesotrione resistance in MCR. Additionally, the basis for atrazine resistance was investigated in MCR and an atrazine-resistant but mesotrione-sensitive population (ACR for Adams County mesotrione-sensitive but atrazine-resistant). A standard sensitive population (WCS for Wayne County herbicide-sensitive) was also used for comparison. Mesotrione resistance was not due to an alteration in HPPD sequence, HPPD expression, or reduced herbicide absorption. Metabolism studies using whole plants and excised leaves revealed that the time for 50% of absorbed mesotrione to degrade in MCR was significantly shorter than in ACR and WCS, which correlated with previous phenotypic responses to mesotrione and the quantity of the metabolite 4-hydroxy-mesotrione in excised leaves. The cytochrome P450 monooxygenase inhibitors malathion and tetcyclacis significantly reduced mesotrione metabolism in MCR and corn (Zea mays) excised leaves but not in ACR. Furthermore, malathion increased mesotrione activity in MCR seedlings in greenhouse studies. These results indicate that enhanced oxidative metabolism contributes significantly to mesotrione resistance in MCR. Sequence analysis of atrazine-resistant (MCR and ACR) and atrazine-sensitive (WCS) waterhemp populations detected no differences in the psbA gene. The times for 50% of absorbed atrazine to degrade in corn, MCR, and ACR leaves were shorter than in WCS, and a polar metabolite of atrazine was detected in corn, MCR, and ACR that cochromatographed with a synthetic atrazine-glutathione conjugate. Thus, elevated rates of metabolism via distinct detoxification mechanisms contribute to mesotrione and atrazine resistance within the MCR population.
Remifentanil as analgesia for labour pain
Authors: TVEIT TOR O.
Published: July 2013

Background

To collect updated information about pharmacological labour analgesia in Norway, especially systemic opioids and epidural. Evaluation of efficacy and safety with remifentanil intravenous patient‐controlled analgesia (IVPCA) for pain relief during labour. To compare remifentanil IVPCA with epidural analgesia (EDA) regarding efficacy and safety during labour.

Methods

In paper I, two national surveys identified Norwegian labour analgesia methods and changes during the study period (2005–2008). Paper II is a prospective, observational study of analgesic efficacy and safety with remifentanil IVPCA. Paper III is a prospective, randomized controlled trial comparing remifentanil IVPCA with EDA regarding analgesic efficacy and safety.

Results

The surveys in paper I found the frequency of EDA in Norwegian hospitals to be increasing, but still low (25.9%) compared with other western countries. Nitrous oxide and traditional systemic opioids, like pethidine, were frequently used. In paper II, remifentanil IVPCA was found to give satisfactory labour analgesia in more than 90% of the parturients with an average maximal pain reduction of 60%. Maternal oxygen desaturation and sedation were acceptable, and neonatal data reassuring. In paper III, a randomized controlled trial found remifentanil IVPCA and EDA to be comparable both regarding analgesic efficacy (pain reduction; Fig. ) and maternal satisfaction. Remifentanil IVPCA produced more maternal sedation and oxygen desaturation; neonatal outcome was reassuring in both groups.

Reduction in pain score [visual analogue scale (VAS)] during labour analgesia with patient‐controlled intravenous remifentanil and continuous epidural infusion with ropivacaine and fentanyl.

figure

Conclusion

The frequency of epidural labour analgesia in Norway has increased, but is still relatively low. Nitrous oxide and traditional systemic opioids are frequently used. The clinical practice seems conservative; newer short‐acting opioids are seldom used for systemic labour analgesia. The studies on remifentanil IVPCA revealed adequate pain relief, high maternal satisfaction, and no serious neonatal side effects. There were no differences in analgesic efficacy, maternal satisfaction, and neonatal outcome when comparing remifentanil IVPCA with EDA. However, remifentanil caused maternal sedation and oxygen desaturation. We recommend the use of IVPCA remifentanil as labour analgesia instead of traditional opioids as pethidine and morphine when EDA is not an option. The presence of skilled personnel and close monitoring is mandatory.
Chemokine receptor CXCR2 is transactivated by p53 and induces p38‐mediated cellular senescence in response to DNA damage
Authors: Guo Haiyang , Liu Zhaojian , Xu Bing , Hu Huili , Wei Zhao , Liu Qiao , Zhang Xiyu , Ding Xuebin , Wang Yu , Zhao Minnan , Gong Yaoqin , Shao Changshun
Published: July 2013

Mammalian cells may undergo permanent growth arrest/senescence when they incur excessive DNA damage. As a key player during DNA damage response (DDR), p53 transactivates an array of target genes that are involved in various cellular processes including the induction of cellular senescence. Chemokine receptor CXCR2 was previously reported to mediate replicative and oncogene‐induced senescence in a DDR and p53‐dependent manner. Here, we report that CXCR2 is upregulated in various types of cells in response to genotoxic or oxidative stress. Unexpectedly, we found that the upregulation of CXCR2 depends on the function of p53. Like other p53 target genes such as p21, CXCR2 is transactivated by p53. We identified a p53‐binding site in the CXCR2 promoter that responds to changes in p53 functional status. Thus, CXCR2 may act downstream of p53. While the senescence‐associated secretory phenotype (SASP) exhibits a kinetics that is distinct from that of CXCR2 expression and does not require p53, it reinforces senescence. We further showed that the cellular senescence caused by CXCR2 upregulation is mediated by p38 activation. Our results thus demonstrate CXCR2 as a critical mediator of cellular senescence downstream of p53 in response to DNA damage.
Respiratory muscle force and lung volume changes in a population of children with sickle cell disease
Authors: Ong Bruce A. , Caboot Jason , Jawad Abbas , McDonough Joseph , Jackson Tannoa , Arens Raanan , Marcus Carole L. , Smith‐Whitley Kim , Mason Thornton B. A. , Ohene‐Frempong Kwaku , Allen Julian L.
Published: July 2013

Sickle cell disease (SCD) is a disorder known to impact the respiratory system. We sought to identify respiratory muscle force and lung volume relationships in a paediatric SCD population. Thirty‐four SCD‐SS subjects underwent pulmonary function testing. Height, weight, age, and gender‐adjusted percent predicted maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) values were compared to spirometry and lung volumes. Statistical analyses were performed using Pearson's correlation coefficient and paired two‐tailed t‐test. The mean ± standard deviation (SD) MIP and MEP was 69·6 ± 31·6 cm H2O and 66·9 ± 22·9 cm H2O, respectively, and mean ± SD percent predicted MIP (101·3 ± 45·9) exceeded MEP (72·1 ± 26·0) (P = 0·002). MIP correlated with forced vital capacity (FVC; r = 0·51, P = 0·001) and TLC (r = 0·54, P < 0·0001). MEP also correlated with FVC (r = 0·43, P = 0·011) and total lung capacity (TLC; r = 0·42, P = 0·013). Pearson's correlation coefficient testing yielded relationships between MIP and MEP (r = 0·64, P < 0·0001). SCD‐SS patients showed correlations between respiratory muscle force and lung volume, and reduced percent predicted expiratory muscle force compared to inspiratory muscle force. Respiratory muscle strength may affect lung volumes in these patients, and expiratory muscles may be more susceptible than the diaphragm to SCD‐induced vaso‐occlusive damage.
The recruitment of p47phox and Rac2G12V at the phagosome is transient and phosphatidylserine dependent
Authors: Faure Marie Cécile , Sulpice Jean‐Claude , Delattre Maud , Lavielle Marc , Prigent Magali , Cuif Marie‐Hélène , Melchior Chantal , Tschirhart Eric , Nüße Oliver , Dupré‐Crochet Sophie
Published: July 2013

Background information

During phagocytosis, neutrophils internalise pathogens in a phagosome and produce reactive oxygen species (ROS) by the NADPH oxidase to kill the pathogen. The cytosolic NADPH oxidase subunits p40phox, p47phox, p67phox and Rac2 translocate to the phagosomal membrane to participate in enzyme activation. The kinetics of this recruitment and the underlying signalling pathways are only partially understood. Anionic phospholipids, phosphatidylserine (PS) and phosphoinositides (PPI) provide an important attachment site for numerous proteins, including several oxidase subunits.

Results

We investigated the kinetics of p47phox and Rac2 phagosomal membrane recruitment. Both subunits are known to interact with anionic phospholipids; we therefore addressed the role of PS in this recruitment. Phagosomal accumulation of p47phox and Rac2 tagged with fluorescent proteins was analysed by videomicroscopy. We used the C2 domain of lactadherin (lactC2) that interacts strongly and specifically with PS to monitor intracellular PS localisation and to decrease PS accessibility. During phagocytosis of opsonised zymosan, p47phox and constitutively active Rac2G12V briefly translocated to the phagosomal membrane, whereas ROS production continued for a longer period. However, in the presence of lactC2, Rac2G12V recruitment was inhibited and the kinetics of p47phox recruitment and detachment were delayed. A reduced phagosomal ROS production was also observed during the first 7 min following the phagosome closure.

Conclusions

These results suggest that p47phox and Rac2 accumulate only transiently at the phagosome at the onset of NADPH activity and detach from the phagosome before the end of ROS production. Furthermore, lactC2, by masking PS, interfered with the phagosomal recruitment of p47phox and Rac2 and disturbed NADPH oxidase activity. Thus, PS appears as a modulator of NADPH oxidase activation.
Psychometrics of the Neonatal Oral Motor Assessment Scale
Authors: Zarem Cori , Kidokoro Hiroyuki , Neil Jeffrey , Wallendorf Michael , Inder Terrie , Pineda Roberta
Published: July 2013

Aim

To establish the psychometrics of the Neonatal Oral Motor Assessment Scale (NOMAS).

Method

In this prospective cohort study of 75 preterm infants (39 females, 36 males) born at or before 30 weeks gestation (mean gestational age 26.56wks, SD 1.90, range 23–30wks; mean birthweight 967.33g, SD 288.54, range 480–2240), oral feeding was videotaped before discharge from the neonatal intensive care unit (NICU). The NOMAS was used to classify feeding as normal, disorganized, or dysfunctional. Neurobehavior was assessed at term equivalent, and infants underwent magnetic resonance imaging. Children returned for developmental testing at 2 years corrected age. Associations between NOMAS scores and (1) neurobehavior; (2) cerebral injury and metrics; and (3) developmental outcome were investigated using χ2‐analyses, t‐tests, and linear regression. For reliability, six certified NOMAS evaluators rated five randomly selected NOMAS recordings and re‐scored them 2 weeks later in a second randomized order. Reliability was calculated with Cohen's kappa statistics.

Results

Dysfunctional NOMAS scores were associated with lower Dubowitz scores [t=−2.14; mean difference −2.32 (95% confidence interval [CI] −0.157 to −4.49); p=0.036], higher stress on the NICU Network Neurobehavioral Scale (t=2.61; mean difference 0.073 [95% CI 0.017–0.129]; p=0.0110), and decreased transcerebellar diameter (t=−2.22; mean difference −2.04 [CI=−3.89 to −0.203]; p=0.03). No significant associations were found between NOMAS scores and 2‐year outcome.

Interpretation

Some concurrent validity was established with associations between NOMAS scores and measures of infant behavior and cerebral structure. The NOMAS did not show predictive validity in this study of preterm infants at high risk of developmental delay. Reliability was variable and suboptimal.
The use of technology to promote physical activity in Type 2 diabetes management: a systematic review
Authors: Connelly J. , Kirk A. , Masthoff J. , MacRury S.
Published: July 2013

Introduction

With increasing evidence available on the importance of physical activity in the management of Type 2 diabetes, there has been an increase in technology‐based interventions. This review provides a systematic and descriptive assessment of the effectiveness of technology to promote physical activity in people with Type 2 diabetes. For this review, technology included mobile phones and text messages, websites, CD‐ROMs and computer‐learning‐based technology, and excluded telephone calls.

Methods

A systematic literature search was conducted to retrieve articles from January 2001 to March 2013 using the following databases: the Cochrane Library, EMBASE, MEDLINE, PsycINFO and PubMed. Articles had to describe an intervention that used technology to promote physical activity in people with Type 2 diabetes. A methodological quality assessment of the studies was conducted and data synthesis was performed.

Results

In total, 15 articles were eligible for review: web‐based (9), mobile phone (3), CD‐ROM (2) and computer based (1). All studies found an increase in physical activity but only nine were significant. The use of a personal coach, logbooks and reinforcement strategies such as phone calls and email counselling were found to be effective components for behaviour change. No studies were ranked as low in terms of methodological quality.

Conclusions

Technology‐based interventions to promote physical activity are effective; using further methods to promote participant adherence is associated with greater benefit. Further research should look into strategies to enhance adherence and sustainability in order to increase the effectiveness of technology‐based physical activity intervention in diabetes care.
Heat freezes niche evolution
Authors: Araújo Miguel B. , Ferri‐Yáñez Francisco , Bozinovic Francisco , Marquet Pablo A. , Valladares Fernando , Chown Steven L.
Published: July 2013

Climate change is altering phenology and distributions of many species and further changes are projected. Can species physiologically adapt to climate warming? We analyse thermal tolerances of a large number of terrestrial ectotherm (n = 697), endotherm (n = 227) and plant (n = 1816) species worldwide, and show that tolerance to heat is largely conserved across lineages, while tolerance to cold varies between and within species. This pattern, previously documented for ectotherms, is apparent for this group and for endotherms and plants, challenging the longstanding view that physiological tolerances of species change continuously across climatic gradients. An alternative view is proposed in which the thermal component of climatic niches would overlap across species more than expected. We argue that hard physiological boundaries exist that constrain evolution of tolerances of terrestrial organisms to high temperatures. In contrast, evolution of tolerances to cold should be more frequent. One consequence of conservatism of upper thermal tolerances is that estimated niches for cold‐adapted species will tend to underestimate their upper thermal limits, thereby potentially inflating assessments of risk from climate change. In contrast, species whose climatic preferences are close to their upper thermal limits will unlikely evolve physiological tolerances to increased heat, thereby being predictably more affected by warming.
Migraine with aura and silent brain infarcts lack of mediation of patent foramen ovale
Authors: Calviere L. , Tall P. , Massabuau P. , Bonneville F. , Larrue V.
Published: July 2013

Background and purpose

Population‐based studies have shown a heightened prevalence of clinically silent brain infarcts in subjects who have migraine with aura (MA). We sought to determine whether this association could be confirmed in young patients with cryptogenic ischemic stroke, and explored the role of patent foramen ovale (PFO) as a potential underlying mechanism.

Methods

Patients were selected from a registry of young patients consecutively treated for ischemic stroke in a tertiary university hospital among those without definite cause of stroke. Patients with PFO were matched for age and gender with patients with normal atrial septum. Migraine and MA were evaluated after patient selection and matching. Silent brain infarcts were independently evaluated on MRI.

Results

We included 100 patients [60 men; mean age (SD), 44.8 years (8.3)], 50 patients with PFO. We found silent brain infarcts in 36 patients and MA in 13 patients. MA was more frequent in patients with silent brain infarcts than in patients without silent brain infarcts (25.0% vs. 6.3%; OR, 5; 95% CI, 1.4–17.6; P = 0.01). Traditional cardiovascular risk factors were not associated with silent brain infarcts. PFO was neither associated with MA (OR, 1.7; 95% CI, 0.5–5.3) nor silent brain infarcts (OR, 0.7; 95% CI, 0.3–1.5). The association of MA with silent brain infarcts was not altered after adjustment for PFO.

Conclusion

Findings suggest that silent brain infarcts in young patients with cryptogenic stroke is associated with MA. We found no evidence for a mediating effect of PFO on this association.
A study of the endodontic workforce in Australia in 2010
Authors: Motearefi P. , Abbott P. V.
Published: July 2013

Aims

To investigate the current workforce situation for specialist Endodontists in Australia to help plan for the future of the specialty.

Methodology

An online questionnaire was sent via email to all registered Endodontists that were identified from the Australian and New Zealand Academy of Endodontists database and the Australian Dental Association Directory. The questionnaire comprised questions on demographic characteristics, practice type, teaching and research activities, busyness and expected retirement time. All results were transferred to a statistical software program (SPSS v.19) for analysis.

Results

The response rate was 50%. The majority of respondents (84%) were male. The most common (64.5%) type of practice was single location private practice. The majority (93%) of Endodontists are located in state capital cities. Many respondents (61%) did some teaching. A minority of respondents (16%) were currently involved in research. The next available nonemergency appointment was more than 1 week away for 84% of respondents. More than half the respondents (52%) do not have allocated time for emergency patients. Only 18% of respondents plan to retire in the next 5 years and another 15% within 5–10 years. Although 58% of practice owners indicated that they have sufficient space and facilities to employ another Endodontist, only 33% would consider to employ or have an associate join their practice.

Conclusion

Most Endodontists in Australia are male private practitioners who work in a single state capital city location. Many teach but few carry out research. They are fully booked with routine patients and have no spare scheduled appointments for emergencies; these have to be seen at the end of the day, or between scheduled patients. There will be a steady rate of retirement in the future and only just enough newly qualified Endodontists are being trained to maintain the specialty workforce at current levels.