bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensory neuropathy in progressive motor neuronopathy (pmn) mice is associated with defects in microtubule polymerization and axonal transport
Authors: Schäfer Michael K. , Bellouze Sarah , Jacquier Arnaud , Schaller Sébastien , Richard Laurence , Mathis Stéphane , Vallat Jean‐Michel , Haase Georg
Published: August 2016

Motor neuron diseases such as amyotrophic lateral sclerosis (ALS) are now recognized as multi‐system disorders also involving various non‐motor neuronal cell types. The precise extent and mechanistic basis of non‐motor neuron damage in human ALS and ALS animal models remain however unclear. To address this, we here studied progressive motor neuronopathy (pmn) mice carrying a missense loss‐of‐function mutation in tubulin binding cofactor E (TBCE). These mice manifest a particularly aggressive form of motor axon dying back and display a microtubule loss, similar to that induced by human ALS‐linked TUBA4A mutations. Using whole nerve confocal imaging of pmn × thy1.2‐YFP16 fluorescent reporter mice and electron microscopy, we demonstrate axonal discontinuities, bead‐like spheroids and ovoids in pmn suralis nerves indicating prominent sensory neuropathy. The axonal alterations qualitatively resemble those in phrenic motor nerves but do not culminate in the loss of myelinated fibers. We further show that the pmn mutation decreases the level of TBCE, impedes microtubule polymerization in dorsal root ganglion (DRG) neurons and causes progressive loss of microtubules in large and small caliber suralis axons. Live imaging of axonal transport using GFP‐tagged tetanus toxin C‐fragment (GFP‐TTC) demonstrates defects in microtubule‐based transport in pmn DRG neurons, providing a potential explanation for the axonal alterations in sensory nerves. This study unravels sensory neuropathy as a pathological feature of mouse pmn, and discusses the potential contribution of cytoskeletal defects to sensory neuropathy in human motor neuron disease.
Versatility of peptide nucleic acids (PNAs): role in chemical biology, drug discovery, and origins of life
Authors: Sharma Chiranjeev , Awasthi Satish Kumar
Published: August 2016

This review briefly discussed nomenclature, synthesis, chemistry, and biophysical properties of a plethora of PNA derivatives reported since the discovery of aegPNA. Different synthetic methods and structural analogs of PNA synthesized till date were also discussed. An insight was gained into various chemical, physical, and biological properties of PNA which make it preferable over all other classes of modified nucleic acid analogs. Thereafter, various approaches with special attention to the practical constraints, characteristics, and inherent drawbacks leading to the delay in the development of PNA as gene therapeutic drug were outlined. An explicit account of the successful application of PNA in different areas of research such as antisense and antigene strategies, diagnostics, molecular probes, and so forth was described along with the current status of PNA as gene therapeutic drug. Further, the plausibility of the existence of PNA and its role in primordial chemistry, that is, origin of life was explored in an endeavor to comprehend the mystery and open up its deepest secrets ever engaging and challenging the human intellect. We finally concluded it with a discussion on the future prospects of PNA technology in the field of therapeutics, diagnostics, and origin of life.
Material hardship and children's social‐emotional development: Testing mitigating effects of Child Development Accounts in a randomized experiment
Authors: Huang J. , Kim Y. , Sherraden M.
Published: August 2016

Background

Research has established a negative association between household material hardship and children's mental health. This study examines whether Child Development Accounts (CDAs), an economic intervention that encourages families to accumulate assets for children's long‐term development, mitigate the association between material hardship and children's social‐emotional development.

Methods

Researchers conducted a randomized experiment of CDAs in Oklahoma, USA, with a probability sample (N = 7328) of all infants born in two 3‐month periods in 2007. After agreeing to participate in the experiment, caregivers of 2704 infants completed a baseline survey and were assigned randomly to the treatment (n = 1358) or control group (n = 1346). The intervention exposed the treatment group to a CDA, which consisted of an Oklahoma 529 College Savings Plan account, financial incentives and financial information.

Results

Material hardship has a negative association with the social‐emotional development of children around the age of 4 years. Estimates from regression analysis indicate that CDAs mitigate about 50% of the negative association between material hardship and children's social‐emotional development.

Conclusions

Although they do not provide direct support for consumption in households experiencing material hardship, CDAs may improve child development by influencing parenting practices and parents' expectations for their children. We discuss the implications of using asset‐building programmes to improve child development.
ECONOMIC FREEDOM & HAPPINESS INEQUALITY: FRIENDS OR FOES?
Authors: Bennett Daniel L. , Nikolaev Boris
Published: August 2016

This article examines the relationship between economic freedom and happiness inequality for a large sample of countries. We find that economic freedom is negatively associated with happiness inequality and robust to several alternative measures of happiness inequality, including the standard deviation, mean absolute difference, coefficient of variation, and Gini coefficient. Among the economic freedom areas, legal system and sound money are negatively correlated with happiness inequality. Drawing on the Engerman‐Sokoloff hypothesis, we use a measure of factor endowments as an instrument for economic freedom to provide a further robustness test, finding a negative association between economic freedom and happiness inequality. (JELD63, I31, P16)
Pleomorphic lobular carcinoma of the breast: a comparison of cytopathological features with other lobular carcinoma variants
Authors: Ohashi R. , Matsubara M. , Watarai Y. , Yanagihara K. , Yamashita K. , Tsuchiya S.‐I. , Takei H. , Naito Z.
Published: August 2016

Objective

Pleomorphic lobular carcinoma (PLC) is a subtype of breast cancer with unique morphological features, but it remains controversial whether PLC should be considered an independent disease entity. The aim of this study was to illustrate cytopathological characteristics of PLC in comparison with other lobular carcinoma variants.

Methods

We investigated clinicopathological features of PLC (n = 11) compared with those of other variants of invasive lobular carcinoma (ILC, non‐PLC) (n = 32). Histological variants of the non‐PLC group consisted of classic (n = 25), solid (n = 2), alveolar (n = 1) and a tubulolobular type (n = 4). A review of cytological reports and fine needle aspiration (FNA) smear samples was performed for the PLC (n = 9) and non‐PLC (n = 27) groups.

Results:

Patients with PLC were older, and had a higher nuclear grade and a higher incidence of axillary lymph node metastasis and triple negative phenotype than non‐PLC patients (P = 0.007, P < 0.001, P = 0.02 and P < 0.001, respectively). Cytological findings in PLC included medium‐ to large‐sized nuclei, prominent nucleoli, a moderate‐to‐severe degree of pleomorphism, apocrine change and background necrosis, none of which were evident in the smears of the non‐PLC group (P < 0.001, P = 0.002, P < 0.001, P < 0.001, and P = 0.03, respectively). Despite these differences, patients with PLC and non‐PLC showed similar clinical outcomes in our follow‐up period.

Conclusions

Based on our results, a cytological diagnosis of PLC should be proposed if there are moderate‐ to large‐sized nuclei, prominent nucleoli, a moderate‐to severe degree of nuclear pleomorphism, apocrine change and necrosis in the background in FNA biopsy samples.
Anti‐ApoA‐1 IgG serum levels predict worse poststroke outcomes
Authors: Carbone Federico , Satta Nathalie , Montecucco Fabrizio , Virzi Julien , Burger Fabienne , Roth Aline , Roversi Gloria , Tamborino Carmine , Casetta Ilaria , Seraceni Silva , Trentini Alessandro , Padroni Marina , Dallegri Franco , Lalive Patrice H. , Mach François , Fainardi Enrico , Vuilleumier Nicolas
Published: August 2016

Background

Autoantibodies to apolipoprotein A‐1 (anti‐ApoA‐1 IgG) were shown to predict major adverse cardiovascular events and promote atherogenesis. However, their potential relationship with clinical disability and ischaemic lesion volume after acute ischaemic stroke (AIS) remains unexplored.

Materials and methods

We included n = 76 patients admitted for AIS and we investigated whether baseline serum anti‐ApoA‐1 IgG levels could predict (i) AIS‐induced clinical disability [assessed by the modified Rankin Scale (mRS)], and (ii) AIS‐related ischaemic lesion volume [assessed by Computed Tomography (CT)]. We also evaluated the possible pro‐apoptotic and pro‐necrotic effects of anti‐ApoA‐1 IgG on human astrocytoma cell line (U251) using flow cytometry.

Results

High levels of anti‐ApoA‐1 IgG were retrieved in 15·8% (12/76) of patients. Increased baseline levels of anti‐ApoA‐1 IgG were independently correlated with worse mRS [β = 0·364; P = 0·002; adjusted odds ratio (OR): 1·05 (95% CI 1·01–1·09); P = 0·017] and CT‐assessed ischaemic lesion volume [β = 0·333; P < 0·001; adjusted OR: 1·06 (95% CI 1·01–1·12); P = 0·048] at 3 months. No difference in baseline clinical, biochemical and radiological characteristics was observed between patients with high vs. low levels of anti‐ApoA‐1 IgG. Incubating human astrocytoma cells with anti‐ApoA‐1 IgG dose dependently induced necrosis and apoptosis of U251 cells in vitro.

Conclusion

Anti‐ApoA‐1 IgG serum levels at AIS onset are associated with poorer clinical recovery and worse brain lesion volume 3 months after AIS. These observations could be partly explained by the deleterious effect of anti‐ApoA‐1 IgG on human brain cell survival in vitro and may have clinical implication in the prediction of poor outcome in AIS.
Carpal arthrodesis using a minimally invasive approach and locking compression plates: Three cases
Authors: Brandenberger O. , Rossignol F. , Bartke S. , Van Bergen T. , Vitte A.
Published: August 2016

Three horses with carpal instability due to comminuted second carpal bone fractures (Cases 1 and 3), fracture of the head of the second metacarpal bone (Case 1) or comminuted fractures of the fourth carpal bone, ulnar and intermediate carpal bones (Case 2) were treated by minimally invasive approach for partial (Cases 1 and 3) or pancarpal (Case 2) joint arthrodesis, using locking compression plates. The joint cartilage was removed by either an arthroscopic approach (middle carpal joint and antebrachiocarpal joint) or a percutaneous drilling technique (carpometacarpal joint). Two or 3 locking compression plates were contoured to the dorsolateral, dorsomedial and dorsoaxial aspects of the carpal joints using a custom‐made tunnelling tool and a minimally invasive tunnelling technique, and the screws were positioned through stab incisions. All cases recovered well, were lame free at the walk, were able to trot and gallop and could be used for leisure and pasture activities (partial carpal arthrodesis) and breeding (pancarpal arthrodesis). Post‐operative x‐rays showed progressive joint fusion after 12 months (Case 1), 5 months (Case 2) and 10 months (Case 3). Case 2 with a pancarpal arthrodesis showed a mechanical lameness at the walk due to the inability to flex the carpus. Carpal flexion after carpometacarpal and middle carpal arthrodesis in Case 1 was calculated to be 42.6° and 44° in Case 3.
Histone deacetylase inhibitors interfere with angiogenesis by decreasing endothelial VEGFR‐2 protein half‐life in part via a VE‐cadherin‐dependent mechanism
Authors: Hrgovic Igor , Doll Monika , Pinter Andreas , Kaufmann Roland , Kippenberger Stefan , Meissner Markus
Published: August 2016

Recent evidence suggests that histone deacetylase inhibitors (HDACi) may mediate part of their antitumor effects by interfering with tumor angiogenesis. As signalling via the vascular endothelial growth factor receptor‐2 (VEGFR‐2) pathway is critical for angiogenic responses during tumor progression, we explored whether established antitumor effects of HDACi are partly mediated through diminished endothelial VEGFR‐2 expression. We therefore examined the potential impact of three different HDACi, trichostatin A (TSA), sodium butyrate (But) and valproic acid (VPA), on VEGFR‐2 protein expression. TSA, VPA and But significantly inhibit VEGFR‐2 protein expression in endothelial cells. Pertinent to these data, VEGFR‐2 protein half‐life is shown to be decreased in response to HDACi. Recently, it could be demonstrated that expression of VE‐cadherin influences VEGFR‐2 protein half‐life. In our experiments, VEGFR‐2 downregulation was accompanied by HDACi‐induced VE‐cadherin suppression. Interestingly, siRNA‐mediated knockdown of VE‐cadherin led to a pronounced loss of VEGFR‐2 expression on the protein as well as on the mRNA level, implicating that VE‐cadherin not only influences VEGFR‐2 protein half‐life but also the transcriptional level. To further distinguish which of the eight different histone deacetylases are responsible for the regulation of VEGFR‐2 expression, specific HDAC genes were silenced by transfecting respective siRNAs. These studies revealed that HDACs 1, 4, 5 and 6 are preferentially involved in VEGFR‐2 expression. Therefore, these results provide an explanation for the anti‐angiogenic action of HDAC inhibitors via a VE‐cadherin, HDAC 1 and HDACs 4–6‐mediated suppression of VEGFR‐2 expression and might be of importance in the development of new anti‐angiogenic drugs.
Interplay between aggression, brain monoamines and fur color mutation in the American mink
Authors: Kulikov A. V. , Bazhenova E. Y. , Kulikova E. A. , Fursenko D. V. , Trapezova L. I. , Terenina E. E. , Mormede P. , Popova N. K. , Trapezov O. V.
Published: August 2016

Domestication of wild animals alters the aggression towards humans, brain monoamines and coat pigmentation. Our aim is the interplay between aggression, brain monoamines and depigmentation. The Hedlund white mutation in the American mink is an extreme case of depigmentation observed in domesticated animals. The aggressive (−2.06 ± 0.03) and tame (+3.5 ± 0.1) populations of wild‐type dark brown color (standard) minks were bred during 17 successive generations for aggressive or tame reaction towards humans, respectively. The Hedlund mutation was transferred to the aggressive and tame backgrounds to generate aggressive (−1.2 ± 0.1) and tame (+3.0 ± 0.2) Hedlund minks. Four groups of 10 males with equal expression of aggressive (−2) or tame (+5) behavior, standard or with the Hedlund mutation, were selected to study biogenic amines in the brain. Decreased levels of noradrenaline in the hypothalamus, but increased concentrations of the serotonin metabolite, 5‐hydroxyindoleacetic acid and dopamine metabolite, homovanillic acid, in the striatum were measured in the tame compared with the aggressive standard minks. The Hedlund mutation increased noradrenaline level in the hypothalamus and substantia nigra, serotonin level in the substantia nigra and striatum and decreased dopamine concentration in the hypothalamus and striatum. Significant interaction effects were found between the Hedlund mutation and aggressive behavior on serotonin metabolism in the substantia nigra (P < 0.001), dopamine level in the midbrain (P < 0.01) and its metabolism in the striatum (P < 0.05). These results provide the first experimental evidence of the interplay between aggression, brain monoamines and the Hedlund mutation in the American minks.
Informing climate models with rapid chamber measurements of forest carbon uptake
Authors: Metcalfe Daniel B. , Ricciuto Daniel , Palmroth Sari , Campbell Catherine , Hurry Vaughan , Mao Jiafu , Keel Sonja G. , Linder Sune , Shi Xiaoying , Näsholm Torgny , Ohlsson Klas E. A. , Blackburn M. , Thornton Peter E. , Oren Ram
Published: August 2016

Models predicting ecosystem carbon dioxide (CO2) exchange under future climate change rely on relatively few real‐world tests of their assumptions and outputs. Here, we demonstrate a rapid and cost‐effective method to estimate CO2 exchange from intact vegetation patches under varying atmospheric CO2 concentrations. We find that net ecosystem CO2 uptake (NEE) in a boreal forest rose linearly by 4.7 ± 0.2% of the current ambient rate for every 10 ppm CO2 increase, with no detectable influence of foliar biomass, season, or nitrogen (N) fertilization. The lack of any clear short‐term NEE response to fertilization in such an N‐limited system is inconsistent with the instantaneous downregulation of photosynthesis formalized in many global models. Incorporating an alternative mechanism with considerable empirical support – diversion of excess carbon to storage compounds – into an existing earth system model brings the model output into closer agreement with our field measurements. A global simulation incorporating this modified model reduces a long‐standing mismatch between the modeled and observed seasonal amplitude of atmospheric CO2. Wider application of this chamber approach would provide critical data needed to further improve modeled projections of biosphere–atmosphere CO2 exchange in a changing climate.
Beyond GRACE: Using Satellite Data for Groundwater Investigations
Authors: Lakshmi Venkat
Published: August 2016

Article impact statement: The use of satellite data along with in‐situ observations and models will help us evaluate groundwater resources.
Cluster headache and other TACs: Pathophysiology and neurostimulation options
Authors: Láinez Miguel JA , Guillamón Edelmira
Published: August 2016

Background

The trigeminal autonomic cephalalgias (TACs) are highly disabling primary headache disorders. There are several issues that remain unresolved in the understanding of the pathophysiology of the TACs, although activation of the trigeminal–autonomic reflex and ipsilateral hypothalamic activation both play a central role. The discovery of the central role of the hypothalamus led to its use as a therapeutic target. After the good results obtained with hypothalamic stimulation, other peripheral neuromodulation targets were tried in the management of refractory cluster headache (CH) and other TACs.

Methods

This review is a summary both of CH pathophysiology and of efficacy of the different neuromodulation techniques.

Results

In chronic cluster headache (CCH) patients, hypothalamic deep brain stimulation (DBS) produced a decrease in attack frequency of more than 50% in 60% of patients. Occipital nerve stimulation (ONS) also elicited favorable outcomes with a reduction of more than 50% of attacks in around 70% of patients with medically intractable CCH. Stimulation of the sphenopalatine ganglion (SPG) with a miniaturized implanted stimulator produced a clinically significant improvement in 68% of patients (acute, preventive, or both). Vagus nerve stimulation (VNS) with a portable device used in conjunction with standard of care in CH patients resulted in a reduction in the number of attacks. DBS and ONS have been used successfully in some cases of other TACs, including hemicrania continua (HC) and short‐lasting unilateral headache attacks (SUNHA).

Conclusions

DBS has good results, but it is a more invasive technique and can generate serious adverse events. ONS has good results, but frequent and not serious adverse events. SPG stimulation (SPGS) is also efficacious in the acute and prophylactic treatment of refractory cluster headache. At this moment, ONS and SPG stimulation techniques are recommended as first line therapy in refractory cluster patients. New recent non‐invasive approaches such as the non‐invasive vagal nerve stimulator (nVNS) have shown efficacy in a few trials and could be an interesting alternative in the management of CH, but require more testing and positive randomized controlled trials.
Correlation study between image features and mechanical properties of Han Chinese facial skin
Authors: Ma L. , Tan Y. , Zheng S. , Li J. , Jiang C. , Chen Z. , Wang X.
Published: August 2016

Objective

Mechanical properties are considered to be vital factors that influence skin physiology during ageing. Wrinkles and skin roughness are the two main features in aged skin. The purpose of this study is to characterize the relationship between facial skin mechanical properties and image features using quantitative methods.

Methods

Two hundred and forty healthy male and female volunteers living in Shanghai, China (aged 20–70 years), were examined in this study. Facial images were photographed by VISIA‐CR. Wrinkle volume of middle forehead and skin roughness of upper cheek were analysed by Skin Surface Analyzer (SSA) software. Mechanical parameters at the middle forehead and upper cheek were measured using Cutometer® MPA 580 and Reviscometer® RVM 600.

Results

Skin wrinkles and roughness increased during ageing, where men have a higher level and earlier manifestation than women. Skin mechanical parameters R2, R5, R7 and RRT were found decreased with age. Moreover, mechanical parameters including R2, R7, RRT and anisotropy showed significant correlations with wrinkle volume and/or skin roughness.

Conclusion

The facial image features including wrinkle volume and skin roughness are significantly correlated with skin elasticity and anisotropy, which could well describe the skin features of Han Chinese.
Skeletal complications in cancer patients with bone metastases
Authors: Tsuzuki Shunsuke , Park Sun Hee , Eber Matthew R , Peters Christopher M , Shiozawa Yusuke
Published: August 2016

As a result of significant improvements in current therapies, the life expectancy of cancer patients with bone metastases has dramatically improved. Unfortunately, these patients often experience skeletal complications that significantly impair their quality of life. The major skeletal complications associated with bone metastases include: cancer‐induced bone pain, hypercalcemia, pathological bone fractures, metastatic epidural spinal cord compression and cancer cachexia. Once cancer cells invade the bone, they perturb the normal physiology of the marrow microenvironment, resulting in bone destruction, which is believed to be a direct cause of skeletal complications. However, full understanding of the mechanisms responsible for these complications remains unknown. In the present review, we discuss the complications associated with bone metastases along with matched conventional therapeutic strategies. A better understanding of this topic is crucial, as targeting skeletal complications can improve both the morbidity and mortality of patients suffering from bone metastases.
A cost‐effectiveness analysis of optimal care for diabetic foot ulcers in Australia
Authors: Cheng Qinglu , Lazzarini Peter A , Gibb Michelle , Derhy Patrick H , Kinnear Ewan M , Burn Edward , Graves Nicholas , Norman Rosana E
Published: August 2016

In addition to affecting quality of life, diabetic foot ulcers (DFUs) impose an economic burden on both patients and the health system. This study developed a Markov model to analyse the cost‐effectiveness of implementing optimal care in comparison with the continuation of usual care for diabetic patients at high risk ofDFUsin the Australian setting. The model results demonstrated overall 5‐year cost savings (AUD9100·11 for those aged 35–54, $9391·60 for those aged 55–74 and $12 394·97 for those aged 75 or older) and improved health benefits measured in quality‐adjusted life years (QALYs) (0·13QALYs, 0·13QALYsand 0·16QALYs, respectively) for high‐risk patients receiving optimal care forDFUscompared with usual care. Total cost savings for Australia were estimated atAUD2·7 billion over 5 years. Probabilistic sensitivity analysis showed that optimal care always had a higher probability of costing less and generating more health benefits. This study provides important evidence to inform Australian policy decisions on the efficient use of health resources and supports the implementation of evidence‐based optimal care in Australia. Furthermore, this information is of great importance for comparable developed countries that could reap similar benefits from investing in these well‐known evidence‐based strategies.
Genetic analyses of herding traits in the Border Collie using sheepdog trial data
Authors: Storteig Horn S. , Steinheim G. , Fjerdingby Olsen H. , Gjerjordet H.F. , Klemetsdal G.
Published: August 2016

The aim of this study was to evaluate the quality of the data provided from sheepdog trials in Norway, estimate heritabilities, repeatabilities and genetic correlations for the traits included in the trial and make recommendations on how sheepdog trials best can be utilized in the breeding of Border Collies in Norway. The analyses were based on test results from sheepdog trials carried out in Norway from 1993 to 2012. A total of 45 732 records from 3841 Border Collies were available, but after quality assurance only a third was left. The results demonstrated little information in the data. Heritabilities varied between 0.010 and 0.056 with standard errors ranging from 0.010 to 0.023, while repeatabilities ranged from 0.041 to 0.286. There is a need to assure the quality of data to improve the information in the test results. We recommend adding new traits based on the Herding Trait Characterization scheme evaluated in Sweden, and on traits from the predatory motor pattern, regarded as common for all dogs. These new traits may be scored across the elements that make up the current trial system, which should be kept in place to stimulate participation in the genetic evaluation scheme.
Long‐Term Results After Single and Multiple Procedures of Ablation of Ventricular Tachycardia
Authors: DONATEO PAOLO , BOTTONI NICOLA , ODDONE DANIELE , QUARTIERI FABIO , IORI MATTEO , MAGGI ROBERTO , BRIGNOLE MICHELE
Published: August 2016

VT Ablation

Introduction

The aim of this study was to assess long‐term results after single and multiple procedures of catheter ablation of ventricular tachycardia (VT). While it is generally accepted that multiple procedures are sometimes necessary in order to achieve long‐term clinical success, the literature on this issue displays wide variability.

Methods

We assessed the outcome of 160 consecutive patients who underwent 214 ablation procedures in the period 2008 to May 2015: 93 had overt structural heart disease (SHD) (previous myocardial infarction in 74 cases) and 67 had no SHD.

Results

After the first procedure, the 1‐year actuarial recurrence rates were 25% in patients with SHD and 5% in those without. However, recurrences increased progressively after the first year, reaching 46% and 35%, respectively, at 5 years. Overall, VT recurred in 35/93 (38%) patients with SHD and 22/67 (33%) patients without. Redo (1 to 4) procedures were performed in 28 (20%) patients with SHD and 18 (27%) patients without. After the last procedure, the 1‐year actuarial recurrence rates were 5% in patients with SHD and 7% in those without, and the corresponding rates at 5 years were 23% and 7%. During follow‐up, 21 patients died (all in the SHD group): no death was related to VT recurrence.

Conclusions

During long‐term follow‐up, VT frequently recurs after the first procedure, both in patients with SHD and in those without; multiple procedures are needed in order to increase the success rate.
Activation of liver X receptor attenuates lysophosphatidylcholine‐induced IL‐8 expression in endothelial cells via the NF‐κB pathway and SUMOylation
Authors: Bi Xukun , Song Jiale , Gao Jing , Zhao Juanjuan , Wang Meihui , Scipione Corey A. , Koschinsky Marlys L. , Wang Zhao V. , Xu Shiming , Fu Guosheng
Published: August 2016

The liver X receptor (LXR) is a cholesterol‐sensing nuclear receptor that has an established function in lipid metabolism; however, its role in inflammation is elusive. In this study, we showed that the LXR agonist GW3965 exhibited potent anti‐inflammatory activity by suppressing the firm adhesion of monocytes to endothelial cells. To further address the mechanisms underlying the inhibition of inflammatory cell infiltration, we evaluated the effects of LXR agonist on interleukin‐8 (IL‐8) secretion and nuclear factor‐kappa B (NF‐κB) activation in human umbilical vein endothelial cells (HUVECs). The LXR agonist significantly inhibited lysophosphatidylcholine (LPC)‐induced IL‐8 production in a dose‐dependent manner without appreciable cytotoxicity. Western blotting and the NF‐κB transcription activity assay showed that the LXR agonist inhibited p65 binding to the IL‐8 promoter in LPC‐stimulated HUVECs. Interestingly, knockdown of the indispensable small ubiquitin‐like modifier (SUMO) ligases Ubc9 and Histone deacetylase 4 (HDAC4) reversed the increase in IL‐8 induced by LPC. Furthermore, the LPC‐induced degradation of inhibitory κBα was delayed under the conditions of deficient SUMOylation or the treatment of LXR agonist. After enhancing SUMOylation by knockdown SUMO‐specific protease Sentrin‐specific protease 1 (SENP1), the inhibition of GW3965 was rescued on LPC‐mediated IL‐8 expression. These findings indicate that LXR‐mediated inflammatory gene repression correlates to the suppression of NF‐κB pathway and SUMOylation. Our results suggest that LXR agonist exerts the anti‐atherosclerotic role by attenuation of the NF‐κB pathway in endothelial cells.
Liver stiffness measurement predicts high‐grade post‐hepatectomy liver failure: A prospective cohort study
Authors: Chong Charing Ching‐Ning , Wong Grace Lai‐Hung , Chan Anthony Wing‐Hung , Wong Vincent Wai‐Sun , Fong Anthony Kwong‐wai , Cheung Yue‐Sun , Wong John , Lee Kit‐Fai , Chan Stephen L , Lai Paul Bo‐San , Chan Henry Lik‐Yuen
Published: August 2016

Background and Aim

Liver stiffness measurement using transient elastography appears to be an excellent tool for detection of liver fibrosis and cirrhosis with high accuracy. The aim of this study is to evaluate the efficacy of preoperative liver stiffness measurement in predicting post‐hepatectomy liver failure.

Methods

A prospective cohort study of all consecutive patients undergoing hepatectomy for hepatocellular carcinoma from February 2010 to August 2014 was studied. All patients received detailed preoperative assessments including liver stiffness measurement. The primary outcome was post‐hepatectomy liver failure according to the International Study Group of Liver Surgery definition.

Results

A total of 255 patients were included. Liver stiffness measurement showed significant correlation with grade B or C post‐hepatectomy liver failure. (P = 0.003) Using the cutoff at 12 kPa, liver stiffness measurement had a sensitivity of 52.4% and specificity of 73.3% in predication of high‐grade (grade B or C) post‐hepatectomy liver failure. Liver stiffness measurement > 12 kPa was also an independent prognostic factor for both high‐grade post‐hepatectomy liver failure and major postoperative complications by multivariate analysis. The diagnostic accuracy was better in patients without right lobe tumor with an area under the receiver operating characteristic of 0.83 compared with an area under the receiver operating characteristic of only 0.62 in patients with right lobe tumor.

Conclusions

Liver stiffness measurement using Fibroscan is good to predict high‐grade post‐hepatectomy liver failure especially in patients without right lobe tumor.
Monitoring Urban Copper Flows in Stockholm, Sweden: Implications of Changes Over Time
Authors: Amneklev Jennie , Augustsson Anna , Sörme Louise , Bergbäck Bo
Published: August 2016

In this study, a substance flow analysis (SFA) for copper (Cu) was conducted, in which the inflow, stock, and outflow (in the form of diffuse emissions to soil and water) for Stockholm were estimated for 2013 and compared with a previous study from 1995, hence allowing a discussion on changes over time. A large number of applications containing Cu were analyzed (including power cables, copper alloys, heavy electrical equipment, tap water systems, roofs, cars, various consumer electronics, wood preservatives, and contact cables for the railroad). The results show that the inflow of Cu to Stockholm has increased between 1995 and 2013, both in total and per person, mainly as the result of an increase in heavy electrical equipment, power cables, and cars. The stock remains relatively unchanged, whereas the outflow has increased. For the outflow, the emission increase from brake linings is of greatest quantitative importance, with an estimated 5.8 tonnes annual emission of Cu to the environment of Stockholm in 2013 compared to 3.9 tonnes in 1995. Given that increasing inflows of limited resources drive the global demand, continuous monitoring of flows through society and management of outflow routes are crucial, including improvement of national legislation and regional environmental plans as well as efforts to increase resource‐use efficiency and recycling.
Isoforms of the Erythropoietin receptor in dopaminergic neurons of the Substantia Nigra
Authors: Marcuzzi Federica , Zucchelli Silvia , Bertuzzi Maria , Santoro Claudio , Tell Gianluca , Carninci Piero , Gustincich Stefano
Published: August 2016

Erythropoietin receptor (EpoR) regulates erythrocytes differentiation in blood. In the brain, EpoR has been shown to protect several neuronal cell types from cell death, including the A9 dopaminergic neurons (DA) of the Substantia Nigra (SN). These cells form the nigrostriatal pathway and are devoted to the control of postural reflexes and voluntary movements. Selective degeneration of A9 DA neurons leads to Parkinson's disease. By the use of nanoCAGE, a technology that allows the identification of Transcription Start Sites (TSSs) at a genome‐wide level, we have described the promoter‐level expression atlas of mouse A9 DA neurons purified with Laser Capture Microdissection (LCM). Here, we identify mRNA variants of the Erythropoietin Receptor (DA‐EpoR) transcribed from alternative TSSs. Experimental validation and full‐length cDNA cloning is integrated with gene expression analysis in the FANTOM5 database. In DA neurons, the EpoR gene encodes for a N‐terminal truncated receptor. Based on STAT5 phosphorylation assays, we show that the new variant of N‐terminally truncated EpoR acts as decoy when co‐expressed with the full‐length form. A similar isoform is also found in human. This work highlights new complexities in the regulation of Erythropoietin (EPO) signaling in the brain.

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Infrequent Rebalancing, Return Autocorrelation, and Seasonality
Authors: BOGOUSSLAVSKY VINCENT
Published: August 2016

A model of infrequent rebalancing can explain specific predictability patterns in the time series and cross‐section of stock returns. First, infrequent rebalancing produces return autocorrelations that are consistent with empirical evidence from intraday returns and new evidence from daily returns. Autocorrelations can switch sign and become positive at the rebalancing horizon. Second, the cross‐sectional variance in expected returns is larger when more traders rebalance. This effect generates seasonality in the cross‐section of stock returns, which can help explain available empirical evidence.
Temperature is better than precipitation as a predictor of plant community assembly across a dryland region
Authors: Butterfield Bradley J. , Munson Seth M.
Published: August 2016

Question

How closely do plant communities track climate? Research suggests that plant species converge toward similar environmental tolerances relative to the environments that they experience. Whether these patterns apply to severe environments or scale up to plant community‐level patterns of relative climatic tolerances is poorly understood. Using estimates of species' climatic tolerances acquired from occurrence records, we determined the contributions of individual species' climatic niche breadths and environmental filtering to the relationships between community‐average climatic tolerances and the local climates experienced by those communities.

Location

Southwestern United States drylands.

Methods

Interspecific variation in niche breadth was assessed as a function of species' climatic optima (median climatic niche value). The relationships between climatic optima and tolerances were used as null expectations for the relationship between abundance‐weighted mean climatic tolerances of communities and the local climate of that community. Deviations from this null expectation indicate that species with greater or lesser climatic tolerances are favoured relative to co‐occurring species. The intensity of environmental filtering was estimated by comparing the range of climatic tolerances within each community to a null distribution generated from a random assembly algorithm.

Results

The temperature niches of species were consistently symmetrical and of similar breadths, regardless of their temperature optima. In contrast, precipitation niches were skewed toward wetter conditions, and niche breadth increased with increasing precipitation optima. At the community level, relationships with climate were much stronger for temperature than for precipitation. Furthermore, cold and heat were stronger assembly filters than drought or precipitation, with the intensity of environmental filtering increasing at both ends of climatic gradients. Community‐average climatic tolerances did deviate significantly from null expectations, indicating that species with higher or lower relative climatic tolerances were favoured under certain conditions.

Conclusions

Despite strong water limitation of plant performance in dryland ecosystems, communities tracked variation in temperature much more closely, intimating strong responses to anticipated temperature increases. Furthermore, abundance distributions were biased toward species with higher or lower relative climatic tolerances under different climatic conditions, but predictably so, indicating the need for assembly models that include processes other than simple environmental filtering.
Morphometric analysis and classification of the three‐dimensional geometry of shatter cones
Authors: Baratoux David , Bouley Sylvain , Reimold Wolf Uwe , Baratoux Lenka
Published: August 2016

Shatter cones are curved fractures decorated with divergent striations that are exclusively associated with impact metamorphism. The terminology “cone” was chosen from the observation of complete or near‐complete, roundish, axisymmetric objects with a well‐defined apex/apical area. It also imprecisely extends to the curved or subplanar fractures decorated with striations commonly observed at impact sites. The geometry of these objects is therefore highly variable but its significance was never addressed due to the lack of appropriate data. Here, we apply two methods to derive shape models of shatter cones. The first one is based on images acquired using a commercial camera and may be applied on large samples in the field. The second one uses an articulated arm equipped with a digital laser scanner and produces high‐resolution and precision shape models of hand‐sized samples. The analysis of 20 shape models of shatter cones from nine different impact sites indicates that the surface of shatter cones may be described by quadric surfaces and are generally consistent with hyperboloids, whereas occurrence of paraboloid objects cannot be ruled out. The surface characteristics are generally not consistent with the mathematical definition of a cone. The value of these shape models to discriminate between the different hypotheses of formation of shatter is still limited, as it remains to be resolved which type of surface pertains to which hypothesis. This requires theoretical developments, and experimental or numerical simulations of the propagation of tensile fractures associated with shock waves.
The provenance, formation, and implications of reduced carbon phases in Martian meteorites
Authors: Steele Andrew , McCubbin Francis M. , Fries Marc D.
Published: August 2016

This review is intended to summarize the current observations of reduced carbon in Martian meteorites, differentiating between terrestrial contamination and carbon that is indigenous to Mars. Indeed, the identification of Martian organic matter is among the highest priority targets for robotic spacecraft missions in the next decade, including the Mars Science Laboratory and Mars 2020. Organic carbon compounds are essential building blocks of terrestrial life, so the occurrence and origin (biotic or abiotic) of organic compounds on Mars is of great significance; however, not all forms of reduced carbon are conducive to biological systems. This paper discusses the significance of reduced organic carbon (including methane) in Martian geological and astrobiological systems. Specifically, it summarizes current thinking on the nature, sources, and sinks of Martian organic carbon, a key component to Martian habitability. Based on this compilation, reduced organic carbon on Mars, including detections of methane in the Martian atmosphere, is best described through a combination of abiotic organic synthesis on Mars and infall of extraterrestrial carbonaceous material. Although conclusive signs of Martian life have yet to be revealed, we have developed a strategy for life detection on Mars that can be utilized in future life‐detection studies.
Microcomputed tomography and shock microdeformation studies on shatter cones
Authors: Zaag Patrice Tristan , Reimold Wolf Uwe , Hipsley Christy Anna
Published: August 2016

One of the aspects of impact cratering that are still not fully understood is the formation of shatter cones and related fracturing phenomena. Yet, shatter cones have been applied as an impact‐diagnostic criterion for decades without the role of shock waves and target rock defects in their formation having been elucidated ever. We have tested the application of the nondestructive microcomputed tomography (μCT) method to visualize the interior of shatter cones in order to possibly resolve links between fracture patterns and shatter cone surface features (striations and intervening “valleys”). Shatter‐coned samples from different impact sites and in different lithologies were investigated for their μCT suitability, with a shatter cone in sandstone from the Serra da Cangalha impact structure (Brazil) remaining as the most promising candidate because of the fracture resolution achieved. To validate the obtained CT data, the scanned specimen was cut into three orthogonal sets of thin sections. Scans with 13 μm resolution were obtained. μCT scans and microscopic analysis unraveled an orientation of subplanar fractures and related fluid inclusion trails, and planar fracture (PF) orientations in the interior of shatter cones. Planar deformation features (PDF) were observed predominantly near the shatter cone surface. Previously undescribed varieties of feather features (FF), in the form of lamellae emanating from curviplanar and curved fractures, as well as an “arrowhead”‐like FF development with microlamellae originating from both sides of a PF, were observed. The timing of shatter cone formation was investigated by establishing temporal relations to the generation of various shock microscopic effects. Shatter cones are, thus, generated post‐ or syn‐formation of PF, FF, subplanar fractures, and PDF. The earliest possible time for shatter cone formation is during the late stage of the compressional phase, that is, shock wave passage, of an impact event.
Brentano's Dual‐Framing Theory of Consciousness
Authors: Kriegel Uriah
Published: August 2016

Brentano's theory of consciousness has garnered a surprising amount of attention in recent philosophy of mind (Thomasson, Caston 2002, Hossack 2002, 2006, Kriegel 2003a, 2003b, 2009, Thomas, Smith, Zahavi 2004, Drummond 2006, Textor 2006,). Here I argue for a novel interpretation of Brentano's theory that casts it as more original than previously appreciated and yet quite plausible upon inspection. According to Brentano's theory, as interpreted here, a conscious experience of a tree is a mental state that can be simultaneously thought of, or framed, equally accurately as (i) an awareness of a tree or (ii) an awareness of an awareness of a tree.
The Will to Make‐Believe: Religious Fictionalism, Religious Beliefs, and the Value of Art
Authors: Sauchelli Andrea
Published: August 2016

I explore some of the reasons why, under specific circumstances, it may be rational to make‐believe or imagine certain religious beliefs. Adopting a jargon familiar to certain contemporary philosophers, my main concern here is to assess what reasons can be given for adopting a fictionalist stance towards some religious beliefs. My understanding of fictionalism does not involve solely a propositional attitude but a broader stance, which may include certain acts of pretence. I also argue that a plausible reason to be fictionalist about a specific set of religious beliefs and practices has to do with the value of some artistic creations; namely, those that require the adoption of a religious point of view for their understanding.
Sulla carnosa modulates root invertase activity in response to the inhibition of long‐distance sucrose transport under magnesium deficiency
Authors: Farhat N. , Smaoui A. , Maurousset L. , Porcheron B. , Lemoine R. , Abdelly C. , Rabhi M.
Published: August 2016

Being the principal product of photosynthesis, sucrose is involved in many metabolic processes in plants. As magnesium (Mg) is phloem mobile, an inverse relationship between Mg shortage and sugar accumulation in leaves is often observed.

Mg deficiency effects on carbohydrate contents and invertase activities were determined in Sulla carnosa Desf. Plants were grown hydroponically at different Mg concentrations (0.00, 0.01, 0.05 and 1.50 mM Mg) for one month.

Mineral analysis showed that Mg contents were drastically diminished in shoots and roots mainly at 0.01 and 0.00 mM Mg. This decline was adversely associated with a significant increase of sucrose, fructose and mainly glucose in shoots of plants exposed to severe deficiency. By contrast, sugar contents were severely reduced in roots of these plants indicating an alteration of carbohydrate partitioning between shoots and roots of Mg‐deficient plants. Cell wall invertase activity was highly enhanced in roots of Mg‐deficient plants, while the vacuolar invertase activity was reduced at 0.00 mM Mg. This decrease of vacuolar invertase activity may indicate the sensibility of roots to Mg starvation resulting from sucrose transport inhibition. 14CO2 labeling experiments were in accordance with these findings showing an inhibition of sucrose transport from source leaves to sink tissues (roots) under Mg depletion.

The obtained results confirm previous findings about Mg involvement in photosynthate loading into phloem and add new insights into mechanisms evolved by S. carnosa to cope with Mg shortage in particular the increase of the activity of cell wall invertase.
Upstream Product Market Regulations, ICT, R&D and Productivity
Authors: Cette Gilbert , Lopez Jimmy , Mairesse Jacques
Published: August 2016

Our study investigates the importance of two main channels through which upstream anti‐competitive sector regulations impact productivity growth: investments in R&D and in ICT, as opposed to alternative channels we cannot explicitly consider for lack of appropriate data such as improvements in skills, management and organization. We specify a three equations model: an extended production function relating total factor productivity to both R&D and ICT capital, and to upstream regulations, and two factor demand functions relating R&D and ICT capital to upstream regulations. We estimate these relations on an unbalanced panel of 15 OECD countries and 13 industries over the period 1987–2007. We find that the total impact of upstream regulations on total factor productivity is sizeable, a large part of which is transmitted through investments in R&D and ICT, mainly the former.