bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic changes of serum microRNA‐122‐5p through therapeutic courses indicates amelioration of acute liver injury accompanied by acute cardiac decompensation
Authors: Koyama Satoshi , Kuragaichi Takashi , Sato Yukihito , Kuwabara Yasuhide , Usami Shunsuke , Horie Takahiro , Baba Osamu , Hakuno Daihiko , Nakashima Yasuhiro , Nishino Tomohiro , Nishiga Masataka , Nakao Tetsushi , Arai Hidenori , Kimura Takeshi , Ono Koh
Published: December 2016

Aims

Recent studies have shown that serum microRNA (miR) abundance is informative for the diagnosis or prognosis of heart failure. However, the dynamics and kinetics of miRs in acute heart failure are largely unknown. Serial measurement and analysis of serum miRs changes in individuals along their therapeutic course could reduce inter‐individual variation and should detect potentially important serum miRs related to disease mechanisms. Based on this concept, we profiled serum miR signatures of blood samples that were obtained sequentially on the day of admission and on hospital Day 7.

Methods and results

This prospective, observational study included 42 consecutive acute heart failure patients (74 ± 1 years old, 24 male). From admission to Day 7, most of the patients showed clinical improvement. In such a cohort, we detected several fluctuations of serum miRs by two distinct screening methods (quantitative PCR and high‐throughput sequencing). One of these fluctuating serum miRs, miR‐122‐5p, decreased significantly from Day 1 to Day 7 [median arbitrary unit (1st:3rd quantile value); 4.62 [2.39:12.3] to 3.07 [1.67:5.39], P = 0.007]. This fluctuation was significantly correlated with changes in serum liver function markers (estimated coefficient and 95% confidence interval; vs change in aspartate aminotransferase 1.69, 0.890–2.484, P < 0.001 and r = 0.560, vs change in alanine aminotransferase 1.09, 0.406–1.771, P = 0.007 and r = 0.428).

Conclusions

The serum miR signature of patients with acute heart failure might indicate the severity of the disease or patients' response to therapeutic intervention. Notably, serum miR‐122‐5p levels reflect liver damage in this condition.
Sphaericin, a Lasso Peptide from the Rare Actinomycete Planomonospora sphaerica
Authors: Kodani Shinya , Inoue Yuto , Suzuki Masahiro , Dohra Hideo , Suzuki Tomohiro , Hemmi Hikaru , Ohnishi‐Kameyama Mayumi
Published: December 2016

A lasso peptide named sphaericin was isolated from the ISP2 agar medium culture of the rare actinomycete species Planomonospora sphaerica. The analysis of the amino acid composition of sphaericin gave a total of 15 amino acid units (three units each of Gly, Ile, and Pro; one unit each of Arg, Glu, Leu, Phe, Ser, and Tyr). In addition to these amino acids, NMR spectroscopy experiments indicated the presence of three Trp units. The structure of sphaericin was determined to be a peptide comprising 18 amino acids, and an additional peptide bond between the amino group of Gly‐1 and the γ‐carboxyl group of Glu‐9 forms a macrolactam ring, as demonstrated by analyses of the TOF MS/MS and NMR spectra. The analysis of the solution three‐dimensional structural through NOE experiments revealed that sphaericin possesses a typical lasso structure. From the genome data, the biosynthetic gene cluster of sphaericin was determined to consist of four genes, namely sphA, sphB1, sphB2, and sphC. Sphaericin showed a specific antibacterial activity against Micrococcus luteus at a dosage of 50 µg/disk.
Cu and Ni Nanoparticles Deposited on ITO Electrode for Nonenzymatic Electrochemical Carbohydrates Sensor Applications
Authors: He Yingqiao , Wei Guodong , Lin Junhong , Sun Mingxu , Li Ziheng
Published: December 2016

A novel non‐enzymatic carbohydrates sensor which was an indium tin oxide (ITO) glass electrode modified by nickel and copper nanoparticles (Cu/Ni/ITO) was developed by an electrochemical method. The crystallinity, morphology, electrochemical measurements and amperometric response of the as‐prepared ITO modified electrode were examined by the X‐ray diffraction (XRD), scanning electron microscopic (SEM), cyclic voltammetry (CV) and chronoamperometry, respectively. The Cu/Ni/ITO electrode had better electroactivity for glucose oxidation than that obtained using Cu/ITO, Ni/ITO, and Ni/Cu/ITO. The logistic regression equation, Ipa = (A1 – A2)/[1 + (Cglucose/x0)p] + A2, was used to fit the calibration curves of glucose aqueous solution concentrations and responsive current intensity. In research of other saccharides, such as fructose, lactose, sucrose, and maltose, which were detected by the Cu/Ni/ITO electrode, it was obvious that the Cu/Ni/ITO electrode was more sensitive to monosaccharides than disaccharides. Monosaccharides and disaccharides can be detected because the saccharides themselves had aldehyde group or be isomerized to an isomer having an aldehyde group in alkaline environment, and then aldehyde group produced carboxylic acid in the catalytic oxidation of the electrode, which lead to the change of electrode surface conductivity and the appearance of oxidation peak, and the alkaline environment further promotes the above reaction.
Preoperative surgical simulation and validation of the line of resection in anterolateral craniofacial resection of advanced sinonasal sinus carcinoma
Authors: Nishio Naoki , Fujii Masazumi , Hayashi Yuichiro , Hiramatsu Mariko , Maruo Takashi , Iwami Kenichiro , Kamei Yuzuru , Yagi Shunjiro , Takanari Keisuke , Fujimoto Yasushi
Published: December 2016

Background

The purpose of this study was to assess the usefulness and accuracy of preoperative 3D virtual simulation of anterolateral craniofacial resection in cases of advanced sinonasal sinus carcinoma.

Methods

Seven patients with advanced (T4 classification) sinonasal sinus carcinoma who underwent anterolateral craniofacial resection in our hospital between 2011 and 2013 were included in this study. Postsimulation CT images were fused with postoperative CT images and differences between the planned and actual osteotomy were measured in 3 regions of the skull base.

Results

The differences ranged from 0 mm to 5.8 mm (average, 3.1 mm) at the inferior wall of the cavernous sinus, from 0.8 mm to 8.3 mm (average, 3.5 mm) at the inferior wall of the sphenoid sinus, and from 0 mm to 13.6 mm (average, 2.3 mm) in the palatine bone.

Conclusion

Preoperative 3D virtual surgical simulation and postoperative feedback can contribute to training for surgeons. © 2016 Wiley Periodicals, Inc. Head Neck 39: 512–519, 2017
Mountaintop winds as representatives of low‐level jets and precursors of downstream precipitation over Eastern China
Authors: Yuan Weihua , Zhao Siyao
Published: December 2016

The mountains of Nanyue, Huangshan, and Jiuxianshan in eastern China all have elevations >1200 m and the weather stations on the tops of these mountains directly observe atmospheric conditions in the lower troposphere. This study showed that the low‐level jets derived from a reanalysis dataset (JRA25) were highly consistent with the winds measured at the mountaintop stations in May and June in the time period 2005–2010. The mountain observations were both continuous and hourly, which compensated for the limitations of the reanalysis and sounding datasets in terms of temporal resolution. The zonal and meridional winds and wind speed at Nanyue Mountain were significantly correlated with the downstream rainfall, with the highest correlation several hours before the peak of the region‐average long‐duration rainfall events (lasting >6 h). These results suggest that the winds observed by mountaintop weather stations could be used in rainfall forecasting and confirm the influence of low‐level jets on rainfall downstream.
What is the Flynn Effect, and how does it change our understanding of IQ?
Authors: Shenk David
Published: December 2016

In 1981, psychologist James Flynn noticed that IQ scores had risen streadily over nearly a century a staggering difference of 18 points over two generations. After a careful analysis, he concluded the cause to be culture. Society had become more intelligent—come to grips with bigger, more abstract ideas over time—and had made people smarter. This observation, combined with solid evidence that IQ scores are also not fixed within an individual, neatly dispels the idea of intelligence being an innate and fixed entity. While intelligence clearly has a biological component, it is best defined, as a set of continually developed skills. WIREs Cogn Sci 2017, 8:e1366. doi: 10.1002/wcs.1366

This article is categorized under:

Psychology > Theory and Methods
Development evolving: the origins and meanings of instinct
Authors: Blumberg Mark S.
Published: December 2016

How do migratory birds, herding dogs, and navigating sea turtles do the amazing things that they do? For hundreds of years, scientists and philosophers have struggled over possible explanations. In time, one word came to dominate the discussion: instinct. It became the catch‐all explanation for those adaptive and complex abilities that do not obviously result from learning or experience. Today, various animals are said to possess a survival instinct, migratory instinct, herding instinct, maternal instinct, or language instinct. But a closer look reveals that these and other ‘instincts’ are not satisfactorily described as inborn, pre‐programmed, hardwired, or genetically determined. Rather, research in this area teaches us that species‐typical behaviors develop—and they do so in every individual under the guidance of species‐typical experiences occurring within reliable ecological contexts. WIREs Cogn Sci 2017, 8:e1371. doi: 10.1002/wcs.1371

This article is categorized under:

Cognitive Biology > Genes and Environment

Psychology > Comparative Psychology

Neuroscience > Development
Construction of the human forebrain
Authors: Jernigan Terry L. , Stiles Joan
Published: December 2016

The adult human brain is arguably the most complex of biological systems. It contains 86 billion neurons (the information processing cells of the brain) and many more support cells. The neurons, with the assistance of the support cells, form trillions of connections creating complex, interconnected neural networks that support all human thought, feeling, and action. A challenge for modern neuroscience is to provide a model that accounts for this exquisitely complex and dynamic system. One fundamental part of this model is an account of how the human brain develops. This essay describes two important aspects of this developmental story. The first part of the story focuses on the remarkable and dynamic set of events that unfold during the prenatal period to give rise to cell lineage that form the essential substance of the brain, particularly the structures of the cerebral hemispheres. The second part of the story focuses on the formation of the major brain pathways of the cerebrum, the intricate fiber bundles that connect different populations of neurons to form the information processing systems that support all human thought and action. These two aspects of early brain development provide an essential foundation for understanding how the structure, organization, and functioning of the human brain emerge. WIREs Cogn Sci 2017, 8:e1409. doi: 10.1002/wcs.1409

This article is categorized under:

Neuroscience > Development
Neural plasticity across the lifespan
Authors: Power Jonathan D. , Schlaggar Bradley L.
Published: December 2016

An essential feature of the brain is its capacity to change. Neuroscientists use the term ‘plasticity’ to describe the malleability of neuronal connectivity and circuitry. How does plasticity work? A review of current data suggests that plasticity encompasses many distinct phenomena, some of which operate across most or all of the lifespan, and others that operate exclusively in early development. This essay surveys some of the key concepts related to neural plasticity, beginning with how current patterns of neural activity (e.g., as you read this essay) come to impact future patterns of activity (e.g., your memory of this essay), and then extending this framework backward into more development‐specific mechanisms of plasticity. WIREs Dev Biol 2017, 6:e216. doi: 10.1002/wdev.216

This article is categorized under:

Nervous System Development > Vertebrates: General Principles
Tibial hemimelia: New classification and reconstructive options
Authors: Paley Dror
Published: December 2016

Tibial hemimelia is a rare congenital lower limb deficiency presenting with a wide spectrum of associated congenital anomalies, deficiencies and duplications. Reconstructive options have been limited, and the gold standard for treatment has remained amputation with prosthetic fitting. There is now a better understanding of the genetics, etiology and pathoanatomy of tibial hemimelia. Armed with this knowledge, I present here a new classification to guide treatment and prognosis and then discuss new treatment strategies and techniques for limb reconstruction based on this new classification scheme.
Transitions and oscillatory regimes in two-layer geostrophic hetons and tripoles
Authors: Shteinbuch-Fridman Biana , Makarov Viacheslav , Kizner Ziv
Published: December 2016

We investigate numerically the transitions and oscillatory regimes in two-layer quasigeostrophic hetons and tripoles composed of patches of uniform potential vorticity (PV). The contour-surgery algorithms are employed, in which either some symmetries are preserved, or asymmetric evolution of the vortex structures is allowed, induced by generally asymmetric numerical noise. The fluid layers are assumed equally thick. First, the evolution of hetons is considered. A heton, a steadily translating pair of vortices residing in different layers, is antisymmetric in the sense that the two PV patches are opposite in sign and symmetric in shape about the axis of translation. A feebly stable heton, when exposed to weak antisymmetric perturbations, responds by developing an oscillation, which culminates in a transition to a new, substantially robust oscillating heton. The results obtained reinforce our earlier findings regarding the modon-to-modon transition (Kizner et al., J. Fluid Mech., vol. 468, 2002, pp. 239–270; Kizner, Phys. Fluids, vol. 18 (5), 2006, 056601; Kizner, UTAM Symposium on Hamiltonian Dynamics, Vortex Structures, Turbulence (ed. Borisov et al.), IUTAM Bookseries, vol. 6, 2008, pp. 125–133. Springer) and clarify the transition mechanism. Asymmetric perturbations might cause a heton-to-tripole transition. Next we consider the transitions and oscillations in carousel tripoles exposed to weak, generally asymmetric perturbations. A carousel tripole is a steadily rotating centrally symmetric ensemble of three PV patches, with the central vortex being located in one layer and the two remaining, satellite vortices in the other layer. Depending on the tripoles’ size, hence also on the shape of the satellite vortices, three different types of transition are revealed, the transition to a ringed (shielded) monopole being one of them. Whereas the transition of a ringed monopole into a tripole is a known phenomenon, the reverse transition in baroclinic flows is detected for the first time.
FINITARY REDUCIBILITY ON EQUIVALENCE RELATIONS
Authors: MILLER RUSSELL , NG KENG MENG
Published: December 2016

We introduce the notion of finitary computable reducibility on equivalence relations on the domainω. This is a weakening of the usual notion of computable reducibility, and we show it to be distinct in several ways. In particular, whereas no equivalence relation can be${\rm{\Pi }}_{n + 2}^0$-complete under computable reducibility, we show that, for everyn, there does exist a natural equivalence relation which is${\rm{\Pi }}_{n + 2}^0$-complete under finitary reducibility. We also show that our hierarchy of finitary reducibilities does not collapse, and illustrate how it sharpens certain known results. Along the way, we present several new results which use computable reducibility to establish the complexity of various naturally defined equivalence relations in the arithmetical hierarchy.
THE COMPLEXITY OF INDEX SETS OF CLASSES OF COMPUTABLY ENUMERABLE EQUIVALENCE RELATIONS
Authors: ANDREWS URI , SORBI ANDREA
Published: December 2016

Let$ \le _c $be computable the reducibility on computably enumerable equivalence relations (or ceers). We show that for every ceerRwith infinitely many equivalence classes, the index sets$\left\{ {i:R_i \le _c R} \right\}$(withRnonuniversal),$\left\{ {i:R_i \ge _c R} \right\}$, and$\left\{ {i:R_i \equiv _c R} \right\}$are${\rm{\Sigma }}_3^0$complete, whereas in caseRhas only finitely many equivalence classes, we have that$\left\{ {i:R_i \le _c R} \right\}$is${\rm{\Pi }}_2^0$complete, and$\left\{ {i:R \ge _c R} \right\}$(withRhaving at least two distinct equivalence classes) is${\rm{\Sigma }}_2^0$complete. Next, solving an open problem from [1], we prove that the index set of the effectively inseparable ceers is${\rm{\Pi }}_4^0$complete. Finally, we prove that the 1-reducibility preordering on c.e. sets is a${\rm{\Sigma }}_3^0$complete preordering relation, a fact that is used to show that the preordering relation$ \le _c $on ceers is a${\rm{\Sigma }}_3^0$complete preordering relation.
A REMARK ON THE REGULARITY OF THE DISCRETE MAXIMAL OPERATOR
Authors: LIU FENG
Published: December 2016

We study the regularity properties of several classes of discrete maximal operators acting on $\text{BV}(\mathbb{Z})$ functions or $\ell ^{1}(\mathbb{Z})$ functions. We establish sharp bounds and continuity for the derivative of these discrete maximal functions, in both the centred and uncentred versions. As an immediate consequence, we obtain sharp bounds and continuity for the discrete fractional maximal operators from $\ell ^{1}(\mathbb{Z})$ to $\text{BV}(\mathbb{Z})$.
State Policies Towards Precarious Work: Employment and Unemployment in Contemporary Portugal
Authors: Varela Raquel
Published: December 2016

In the context of the Global Collaboratory on the History of Labour Relations, in this article, we relate the analysis of precarious work in Portugal to the state, in particular, as a direct participant functioning as both employer and mediator. In the second part, we present a short overview of the evolution of casualization in the context of employment and unemployment in contemporary Portugal (1974–2014). In the third section, we discuss state policies on labour relations, particularly in the context of the welfare state. Finally, we compare this present analysis with Swedish research done from the perspective of the state as a direct participant and mediator over the past four decades.
Climate influences assemblages of abomasal nematodes of sheep on steppe pastures in the east of Algeria
Authors: Zouyed I. , Cabaret J. , Bentounsi B.
Published: December 2016

It is a common view that assemblages of parasitic nematodes are influenced by climatic conditions; however, there are only a few articles available regarding those that infect farm animals. We investigated the relationship between climate variables and infection with abomasal trichostrongyles in 335 1-year-old rams grazed on steppe pastures in Eastern Algeria. Abomasa were collected from 12 local slaughterhouses located in four climatic areas (from humid to arid) and the worms extracted, identified and counted. The abundance was low and the fauna composed primarily of Teladorsagia circumcincta, Marshallagia marshalli and Trichostrongylus sp. The high percentage of M. marshalli is typical of steppe areas. Ostertagia ostertagi and Haemonchus contortus were present in low numbers. Rainfall was the most important climatic variable related to the main species. This relationship was not linear for M. marshalli but an optimal rainfall was detected (350–400 mm/year). The more complex climatic indicators used in the study did not demonstrate a more significant correlation than rainfall. The predictive value of rainfall on the abundance or proportion of species in the assemblage was modest but highly significant. The seasonality of assemblages was different between the two main sub-climates (sub-humid and semi-arid).
Cognitive and Behavioral Functioning in Childhood Acquired Demyelinating Syndromes
Authors: Till Christine , Noguera Austin , Verhey Leonard H. , O’Mahony Julia , Yeh E. Ann , Mah Jean K. , Sinopoli Katia J. , Brooks Brian L. , Aubert-Broche Berengere , Collins D. Louis , Narayanan Sridar , Arnold Douglas L. , Banwell Brenda L.
Published: December 2016

Objectives:The aim of this study was to describe cognitive, academic, and psychosocial outcomes after an incident demyelinating event (acquired demyelinating syndromes, ADS) in childhood and to investigate the contribution of brain lesions and confirmed MS diagnosis on outcome.Methods:Thirty-six patients with ADS (mean age=12.2 years,SD=2.7, range: 7–16 years) underwent brain MRI scans at presentation and at 6-months follow-up. T2-weighted lesions on MRI were assessed using a binary classification. At 6-months follow-up, patients underwent neuropsychological evaluation and were compared with 42 healthy controls.Results:Cognitive, academic, and behavioral outcomes did not differ between the patients with ADS and controls. Three of 36 patients (8.3%) were identified with cognitive impairment, as determined by performance falling ≤1.5SDbelow normative values on more than four independent tests in the battery. Poor performance on a visuomotor integration task was most common, observed among 6/32 patients, but this did not differ significantly from controls. Twelve of 36 patients received a diagnosis of MS within 3 years post-ADS. Patients with MS did not differ from children with monophasic ADS in terms of cognitive performance at the 6-months follow-up. Fatigue symptoms were reported in 50% of patients, irrespective of MS diagnosis. Presence of brain lesions at onset and 6 months post-incident demyelinating event did not associate with cognitive outcome.Conclusions:Children with ADS experience a favorable short-term neurocognitive outcome, even those confirmed to have MS. Longitudinal evaluations of children with monophasic ADS and MS are required to determine the possibility of late-emerging sequelae and their time course. (JINS, 2016,22, 1050–1060)
Preimplantation factor is an anti-apoptotic effector in human trophoblasts involving p53 signaling pathway
Authors: Moindjie Hadia , Santos Esther Dos , Gouesse Rita-Josiane , Swierkowski-Blanchard Nelly , Serazin Valérie , Barnea Eytan R , Vialard François , Dieudonné Marie-Noëlle
Published: December 2016

From the earliest stages of gestation, embryonic–maternal interaction has a key role in a successful pregnancy. Various factors present during gestation may significantly influence this type of juxta/paracrine interaction. PreImplantation Factor (PIF) is a recently identified factor with activity at the fetomaternal interface. PIF is secreted by viable embryos and directly controls placental development by increasing the invasive capacity of human extravillous trophoblasts (EVTs). To further specify PIF’s role in the human placenta, we analyzed the genome-wide expression profile of the EVT in the presence of a synthetic PIF analog (sPIF). We found that sPIF exposure altered several pathways related to p53 signaling, survival and the immune response. Functional assays revealed that sPIF acts through the p53 pathway to reduce both early and late trophoblast apoptosis. More precisely, sPIF (i) decreases the phosphorylation of p53 at Ser-15, (ii) enhances the B-cell lymphoma-2 (BCL2) expression and (iii) reduces the BCL2-associated X protein (BAX) and BCL2 homologous antagonist killer (BAK) mRNA expression levels. Furthermore, invalidation experiments of TP53 allowed us to demonstrate that PIF’s effects on placental apoptosis seemed to be essentially mediated by this gene. We have clearly shown that p53 and sPIF pathways could interact in human trophoblast and thus promotes cell survival. Furthermore, sPIF was found to regulate a gene network related to immune tolerance in the EVT, which emphasizes the beneficial effect of this peptide on the human placenta. Finally, the PIF protein levels in placentas from pregnancies affected by preeclampsia or intra-uterine growth restriction were significantly lower than in gestational age-matched control placentas. Taken as a whole, our results suggest that sPIF protects the EVT’s functional status through a variety of mechanisms. Clinical application of sPIF in the treatment of disorders of early pregnancy can be envisioned.
Anti-proliferative activity of the NPM1 interacting natural product avrainvillamide in acute myeloid leukemia
Authors: Andresen Vibeke , Erikstein Bjarte S , Mukherjee Herschel , Sulen André , Popa Mihaela , Sørnes Steinar , Reikvam Håkon , Chan Kok-Ping , Hovland Randi , McCormack Emmet , Bruserud Øystein , Myers Andrew G , Gjertsen Bjørn T
Published: December 2016

Mutated nucleophosmin 1 (NPM1) acts as a proto-oncogene and is present in ~30% of patients with acute myeloid leukemia (AML). Here we examined thein vitroandin vivoanti-leukemic activity of the NPM1 and chromosome region maintenance 1 homolog (CRM1) interacting natural product avrainvillamide (AVA) and a fully syntetic AVA analog. TheNPM1-mutated cell line OCI-AML3 and normal karyotype primary AML cells withNPM1mutations were significantly more sensitive towards AVA than cells expressing wild-type (wt)NPM1. Furthermore, the presence of wt p53 sensitized cells toward AVA. Cells exhibiting fms-like tyrosine kinase 3 (FLT3) internal tandem duplication mutations also displayed a trend toward increased sensitivity to AVA. AVA treatment induced nuclear retention of the NPM1 mutant protein (NPMc+) in OCI-AML3 cells and primary AML cells, caused proteasomal degradation of NPMc+ and the nuclear export factor CRM1 and downregulated wt FLT3 protein. In addition, both AVA and its analog induced differentiation of OCI-AML3 cells together with an increased phagocytotic activity and oxidative burst potential. Finally, the AVA analog displayed anti-proliferative activity against subcutaneous xenografted HCT-116 and OCI-AML3 cells in mice. Our results demonstrate that AVA displays enhanced potency against defined subsets of AML cells, suggesting that therapeutic intervention employing AVA or related compounds may be feasible.
PINK1-dependent phosphorylation of PINK1 and Parkin is essential for mitochondrial quality control
Authors: Zhuang Na , Li Lin , Chen She , Wang Tao
Published: December 2016

Mitochondrial dysfunction has been linked to the pathogenesis of a large number of inherited diseases in humans, including Parkinson’s disease, the second most common neurodegenerative disorder. The Parkinson’s disease genes pink1 and parkin, which encode a mitochondrially targeted protein kinase, and an E3 ubiquitin ligase, respectively, participate in a key mitochondrial quality-control pathway that eliminates damaged mitochondria. In the current study, we established an in vivo PINK1/Parkin-induced photoreceptor neuron degeneration model in Drosophila with the aim of dissecting the PINK1/Parkin pathway in detail. Using LC-MS/MS analysis, we identified Serine 346 as the sole autophosphorylation site of Drosophila PINK1 and found that substitution of Serine 346 to Alanine completely abolished the PINK1 autophosphorylation. Disruption of either PINK1 or Parkin phosphorylation impaired the PINK1/Parkin pathway, and the degeneration phenotype of photoreceptor neurons was obviously alleviated. Phosphorylation of PINK1 is not only required for the PINK1-mediated mitochondrial recruitment of Parkin but also induces its kinase activity toward Parkin. In contrast, phosphorylation of Parkin by PINK1 is dispensable for its translocation but required for its activation. Moreover, substitution with autophosphorylation-deficient PINK1 failed to rescue pink1 null mutant phenotypes. Taken together, our findings suggest that autophosphorylation of PINK1 is essential for the mitochondrial translocation of Parkin and for subsequent phosphorylation and activation of Parkin.
UVR2 ensures transgenerational genome stability under simulated natural UV-B in Arabidopsis t haliana
Authors: Willing Eva-Maria , Piofczyk Thomas , Albert Andreas , Winkler J. Barbro , Schneeberger Korbinian , Pecinka Ales
Published: December 2016

Ground levels of solar UV-B radiation induce DNA damage. Sessile phototrophic organisms such as vascular plants are recurrently exposed to sunlight and require UV-B photoreception, flavonols shielding, direct reversal of pyrimidine dimers and nucleotide excision repair for resistance against UV-B radiation. However, the frequency of UV-B-induced mutations is unknown in plants. Here we quantify the amount and types of mutations in the offspring of Arabidopsis thaliana wild-type and UV-B-hypersensitive mutants exposed to simulated natural UV-B over their entire life cycle. We show that reversal of pyrimidine dimers by UVR2 photolyase is the major mechanism required for sustaining plant genome stability across generations under UV-B. In addition to widespread somatic expression, germline-specific UVR2 activity occurs during late flower development, and is important for ensuring low mutation rates in male and female cell lineages. This allows plants to maintain genome integrity in the germline despite exposure to UV-B.
Echo Chambers: Emotional Contagion and Group Polarization on Facebook
Authors: Del Vicario Michela , Vivaldo Gianna , Bessi Alessandro , Zollo Fabiana , Scala Antonio , Caldarelli Guido , Quattrociocchi Walter
Published: December 2016

Recent findings showed that users on Facebook tend to select information that adhere to their system of beliefs and to form polarized groups – i.e., echo chambers. Such a tendency dominates information cascades and might affect public debates on social relevant issues. In this work we explore the structural evolution of communities of interest by accounting for users emotions and engagement. Focusing on the Facebook pages reporting on scientific and conspiracy content, we characterize the evolution of the size of the two communities by fitting daily resolution data with three growth models – i.e. the Gompertz model, the Logistic model, and the Log-logistic model. Although all the models appropriately describe the data structure, the Logistic one shows the best fit. Then, we explore the interplay between emotional state and engagement of users in the group dynamics. Our findings show that communities’ emotional behavior is affected by the users’ involvement inside the echo chamber. Indeed, to an higher involvement corresponds a more negative approach. Moreover, we observe that, on average, more active users show a faster shift towards the negativity than less active ones.
Infusion with Human Bone Marrow-derived Mesenchymal Stem Cells Improves β-cell Function in Patients and Non-obese Mice with Severe Diabetes
Authors: Li Lirong , Hui Hui , Jia Xiaolei , Zhang Jie , Liu Ying , Xu Qianyue , Zhu Dalong
Published: December 2016

Mesenchymal stem cells (MSCs) transplantation is a promising therapeutic strategy for type 1 diabetes (T1D). However, little is known on whether MSC transplantation can benefit T1D patients with ketoacidosis and its potential actions. Here, we show that infusion with bone marrow MSCs preserves β-cell function in some T1D patients with ketoacidosis by decreasing exogenous insulin requirement and increasing plasma C-peptide levels up to 1–2 years. MSC transplantation increased plasma and islet insulin contents in non-obese diabetic (NOD) mice with severe diabetes. In comparison with severe diabetes controls, MSC infusion reduced insulitis, decreased pancreatic TNF-α, and increased IL-10 and TGF-β1 expression in NOD mice. MSC infusion increased the percentages of splenic Tregs and levels of plasma IL-4, IL-10 and TGF-β1, but reduced the percentages of splenic CD8+ T and levels of plasma IFN-γ, TNF-α and IL-17A in NOD mice. Finally, infused MSCs predominantly accumulated in pancreatic tissues at 28 days post infusion. The effects of MSCs on preserving β-cell function and modulating inflammation tended to be dose-dependent and multiple doses of MSCs held longer effects in NOD mice. Hence, MSC transplantation preserved β-cell function in T1D patients and NOD mice with severe diabetes by enhancing Treg responses.
Surface Protonics Promotes Catalysis
Authors: Manabe R. , Okada S. , Inagaki R. , Oshima K. , Ogo S. , Sekine Y.
Published: December 2016

Catalytic steam reforming of methane for hydrogen production proceeds even at 473 K over 1 wt% Pd/CeO2 catalyst in an electric field, thanks to the surface protonics. Kinetic analyses demonstrated the synergetic effect between catalytic reaction and electric field, revealing strengthened water pressure dependence of the reaction rate when applying an electric field, with one-third the apparent activation energy at the lower reaction temperature range. Operando–IR measurements revealed that proton conduction via adsorbed water on the catalyst surface occurred during electric field application. Methane was activated by proton collision at the Pd–CeO2 interface, based on the inverse kinetic isotope effect. Proton conduction on the catalyst surface plays an important role in methane activation at low temperature. This report is the first describing promotion of the catalytic reaction by surface protonics.
Discovery of piperonal-converting oxidase involved in the metabolism of a botanical aromatic aldehyde
Authors: Doi Shiori , Hashimoto Yoshiteru , Tomita Chiaki , Kumano Takuto , Kobayashi Michihiko
Published: December 2016

Piperonal-catabolizing microorganisms were isolated from soil, the one (strain CT39-3) exhibiting the highest activity being identified as Burkholderia sp. The piperonal-converting enzyme involved in the initial step of piperonal metabolism was purified from strain CT39-3. Gene cloning of the enzyme and a homology search revealed that the enzyme belongs to the xanthine oxidase family, which comprises molybdoenzymes containing a molybdopterin cytosine dinucleotide cofactor. We found that the piperonal-converting enzyme acts on piperonal in the presence of O2, leading to formation of piperonylic acid and H2O2. The growth of strain CT39-3 was inhibited by higher concentrations of piperonal in the culture medium. Together with this finding, the broad substrate specificity of this enzyme for various aldehydes suggests that it would play an important role in the defense mechanism against antimicrobial compounds derived from plant species.
Cellular aspartyl proteases promote the unconventional secretion of biologically active HIV-1 matrix protein p17
Authors: Caccuri Francesca , Iaria Maria Luisa , Campilongo Federica , Varney Kristen , Rossi Alessandro , Mitola Stefania , Schiarea Silvia , Bugatti Antonella , Mazzuca Pietro , Giagulli Cinzia , Fiorentini Simona , Lu Wuyuan , Salmona Mario , Caruso Arnaldo
Published: December 2016

The human immune deficiency virus type 1 (HIV-1) matrix protein p17 (p17), although devoid of a signal sequence, is released by infected cells and detected in blood and in different organs and tissues even in HIV-1-infected patients undergoing successful combined antiretroviral therapy (cART). Extracellularly, p17 deregulates the function of different cells involved in AIDS pathogenesis. The mechanism of p17 secretion, particularly during HIV-1 latency, still remains to be elucidated. A recent study showed that HIV-1-infected cells can produce Gag without spreading infection in a model of viral latency. Here we show that in Gag-expressing cells, secretion of biologically active p17 takes place at the plasma membrane and occurs following its interaction with phosphatidylinositol-(4,5)-bisphosphate and its subsequent cleavage from the precursor Gag (Pr55Gag) operated by cellular aspartyl proteases. These enzymes operate a more complex Gag polypeptide proteolysis than the HIV-1 protease, thus hypothetically generating slightly truncated or elongated p17s in their C-terminus. A 17 C-terminal residues excised p17 was found to be structurally and functionally identical to the full-length p17 demonstrating that the final C-terminal region of p17 is irrelevant for the protein’s biological activity. These findings offer new opportunities to identify treatment strategies for inhibiting p17 release in the extracellular microenvironment.
Targeting intracellular p-aminobenzoic acid production potentiates the anti-tubercular action of antifolates
Authors: Thiede Joshua M. , Kordus Shannon L. , Turman Breanna J. , Buonomo Joseph A. , Aldrich Courtney C. , Minato Yusuke , Baughn Anthony D.
Published: December 2016

The ability to revitalize and re-purpose existing drugs offers a powerful approach for novel treatment options against Mycobacterium tuberculosis and other infectious agents. Antifolates are an underutilized drug class in tuberculosis (TB) therapy, capable of disrupting the biosynthesis of tetrahydrofolate, an essential cellular cofactor. Based on the observation that exogenously supplied p-aminobenzoic acid (PABA) can antagonize the action of antifolates that interact with dihydropteroate synthase (DHPS), such as sulfonamides and p-aminosalicylic acid (PAS), we hypothesized that bacterial PABA biosynthesis contributes to intrinsic antifolate resistance. Herein, we demonstrate that disruption of PABA biosynthesis potentiates the anti-tubercular action of DHPS inhibitors and PAS by up to 1000 fold. Disruption of PABA biosynthesis is also demonstrated to lead to loss of viability over time. Further, we demonstrate that this strategy restores the wild type level of PAS susceptibility in a previously characterized PAS resistant strain of M. tuberculosis. Finally, we demonstrate selective inhibition of PABA biosynthesis in M. tuberculosis using the small molecule MAC173979. This study reveals that the M. tuberculosis PABA biosynthetic pathway is responsible for intrinsic resistance to various antifolates and this pathway is a chemically vulnerable target whose disruption could potentiate the tuberculocidal activity of an underutilized class of antimicrobial agents.
Physical characterization and antioxidant activity of thymol solubilized Tween 80 micelles
Authors: Deng Ling-Li , Taxipalati Maierhaba , Que Fei , Zhang Hui
Published: December 2016

Attempts were made to solubilize thymol in Tween 80 micelle to study the solubilization mechanism of thymol and the effect of solubilization on its antioxidant activity. The maximum solubilized concentration of thymol in a 2.0% (w/v) Tween 80 micelle solution is 0.2 wt%. There was no significant difference in Z-average diameter between the empty micelles and thymol solubilized micelles. 1H NMR spectra indicated that 3-H and 4-H on the benzene ring of thymol interacted with the ester group between the hydrophilic head group and the hydrophobic tail group of Tween 80 by Van der Waals’ force. Ferric reducing antioxidant potential (FRAP) and cupric ion reducing antioxidant capacity (CUPRAC) assays showed that the reducing antioxidant activity of free thymol did not change after solubilized in Tween 80 micelles. Compared to free thymol, the solubilized thymol showed higher activities to scavenge DPPH (2,2-diphenyl-1-picrylhydrazyl) and hydroxyl radicals. The present study suggested a possible preparation of thymol-carrying micelles with enhanced antioxidant activities that could be applied in food beverages.
Test of quantum thermalization in the two-dimensional transverse-field Ising model
Authors: Blaß Benjamin , Rieger Heiko
Published: December 2016

We study the quantum relaxation of the two-dimensional transverse-field Ising model after global quenches with a real-time variational Monte Carlo method and address the question whether this non-integrable, two-dimensional system thermalizes or not. We consider both interaction quenches in the paramagnetic phase and field quenches in the ferromagnetic phase and compare the time-averaged probability distributions of non-conserved quantities like magnetization and correlation functions to the thermal distributions according to the canonical Gibbs ensemble obtained with quantum Monte Carlo simulations at temperatures defined by the excess energy in the system. We find that the occurrence of thermalization crucially depends on the quench parameters: While after the interaction quenches in the paramagnetic phase thermalization can be observed, our results for the field quenches in the ferromagnetic phase show clear deviations from the thermal system. These deviations increase with the quench strength and become especially clear comparing the shape of the thermal and the time-averaged distributions, the latter ones indicating that the system does not completely lose the memory of its initial state even for strong quenches. We discuss our results with respect to a recently formulated theorem on generalized thermalization in quantum systems.
Insights into the Competing Mechanisms and Origin of Enantioselectivity for N-Heterocyclic Carbene-Catalyzed Reaction of Aldehyde with Enamide
Authors: Qiao Yan , Chen Xinhuan , Wei Donghui , Chang Junbiao
Published: December 2016

Hydroacylation reactions and aza-benzoin reactions have attracted considerable attention from experimental chemists. Recently, Wang et al. reported an interesting reaction of N-heterocyclic carbene (NHC)-catalyzed addition of aldehyde to enamide, in which both hydroacylation and aza-benzoin reactions may be involved. Thus, understanding the competing relationship between them is of great interest. Now, density functional theory (DFT) investigation was performed to elucidate this issue. Our results reveal that enamide can tautomerize to its imine isomer with the assistance of HCO3−. The addition of NHC to aldehydes formed Breslow intermediate, which can go through cross-coupling with enamide via hydroacylation reaction or its imine isomer via aza-benzoin reaction. The aza-benzoin reaction requires relatively lower free energy barrier than the hydroacylation reaction. The more polar characteristic of C=N group in the imine isomers, and the more advantageous stereoelectronic effect in the carbon-carbon bond forming transition states in aza-benzoin pathway were identified to determine that the imine isomer can react with the Breslow intermediate more easily. Furthermore, the origin of enantioselectivities for the reaction was explored and reasonably explained by structural analyses on key transition states. The work should provide valuable insights for rational design of switchable NHC-catalyzed hydroacylation and aza-benzoin reactions with high stereoselectivity.
Increased EMR2 expression on neutrophils correlates with disease severity and predicts overall mortality in cirrhotic patients
Authors: Huang Chien-Hao , Jeng Wen-Juei , Ho Yu-Pin , Teng Wei- , Hsieh Yi-Chung , Chen Wei-Ting , Chen Yi-Cheng , Lin Hsi-Hsien , Sheen I-Shyan , Lin Chun-Yen
Published: December 2016

Patients with liver cirrhosis are susceptible to infections with high short-term mortalities. One CD97-related EGF-TM7 molecule, EMR2 (EGF-like molecule containing mucin-like hormone receptor 2), had been shown to regulate human neutrophil function, potentiate systemic inflammation. Nevertheless, EMR2 could also suppress neutrophil survival. Studying the role of EMR2 on neutrophil would be intriguing. 48 healthy volunteers and 100 cirrhotic patients were enrolled. Neutrophils were isolated from peripheral blood and cell surface markers were measured by flow cytometry.EMR2 expression levels correlated with CTP scores and increased further in patients with infections. These EMR2-expressed neutrophils were with activated phenotype, but with deranged functions like increased resting oxidative burst and impaired phagocytosis ability. Ligation of EMR2 could increase the phagoburst capacity but not the phagocytosis ability. Furthermore, neutrophils with higher EMR2 expression were more apoptotic and lost the LPS-induced neutrophil survival. Finally, EMR2 expressions on neutrophils correlated with infections and their levels greater than 25 had an AUC = 0.708 for predicting mortality. In conclusion, EMR2 expression levels correlated with CTP scores and increased further in cirrhotic patients with infections. These high EMR2-expressed neutrophils had activated phenotype but with deranged functions. Higher levels of these EMR2-expressed neutrophils correlated with infectious complications and predict mortality.
Shikonin induces mitochondria-mediated apoptosis and enhances chemotherapeutic sensitivity of gastric cancer through reactive oxygen species
Authors: Liang Wenquan , Cai Aizhen , Chen Guozhu , Xi Hongqing , Wu Xiaosong , Cui Jianxin , Zhang Kecheng , Zhao Xudong , Yu Jiyun , Wei Bo , Chen Lin
Published: December 2016

The prognosis of gastric cancer remains poor due to clinical drug resistance. Novel drugs are urgently needed. Shikonin (SHK), a natural naphthoquinone, has been reported to trigger cell death and overcome drug resistance in anti-tumour therapy. In this study, we investigated the effectiveness and molecular mechanisms of SHK in treatment with gastric cancer. In vitro, SHK suppresses proliferation and triggers cell death of gastric cancer cells but leads minor damage to gastric epithelial cells. SHK induces the generation of intracellular reactive oxygen species (ROS), depolarizes the mitochondrial membrane potential (MMP) and ultimately triggers mitochondria-mediated apoptosis. We confirmed that SHK induces apoptosis of gastric cancer cells not only in a caspase-dependent manner which releases Cytochrome C and triggers the caspase cascade, but also in a caspase-independent manner which mediates the nuclear translocation of apoptosis-inducing factor and Endonuclease G. Furthermore, we demonstrated that SHK enhanced the chemotherapeutic sensitivity of 5-fluorouracil and oxaliplatin in vitro and in vivo. Taken together, our data show that SHK may be a novel therapeutic agent in the clinical treatment of gastric cancer.
A novel ditopic chemosensor for cadmium and fluoride and its possible application as a pH sensor
Authors: Chowdhury Additi Roy , Ghosh Pritam , Paul Suparna , Bhuyan Samuzal , Bose K Jagadeesh C. , Mukhopadhyay Sudit , Banerjee Priyabrata
Published: December 2016

A urea-based molecule behaving as a ditopic sensor for fluoride and cadmium.
A one carbon staple for orthogonal copper-catalyzed azide–alkyne cycloadditions
Authors: Wright Karen , Quinodoz Pierre , Drouillat Bruno , Couty François
Published: December 2016

We describe herein the use of α-hydroxy-β-azidotetrazoles, easily prepared in one step from α,β-epoxynitriles, as new scaffolds for orthogonal CuAAC reactions performed on the same carbon atom.
Unusual cyclic polymerization through Suzuki–Miyaura coupling of polyphenylene bearing diboronate at both ends with excess dibromophenylene
Authors: Sugita Hajime , Nojima Masataka , Ohta Yoshihiro , Yokozawa Tsutomu
Published: December 2016

The Suzuki–Miyaura cyclic polymerization of meta/para- and meta/meta combinations of monomers with the t-Bu3PPd(0) catalyst proceeds when excess dibromophenylene is used.
An unexpected copper-catalyzed carbonylative acetylation of amines
Authors: Li Yahui , Wang Changsheng , Zhu Fengxiang , Wang Zechao , François Soulé Jean , Dixneuf Pierre H. , Wu Xiao-Feng
Published: December 2016

A novel copper-catalyzed carbonylative acetylation of amines has been developed.
Intramolecular cation–π interactions in protonated phenylalanine derivatives
Authors: Fu Weiqiang , Carr Patrick J. J. , Lecours Michael J. , Burt Michael , Marta Rick A. , Steinmetz Vincent , Fillion Eric , McMahon Terrance B. , Hopkins W. Scott
Published: December 2016

The structures and properties of a series of phenylalanine (Phe) derivatives have been investigated in a joint computational and experimental infrared multiple photon dissociation (IRMPD) study.
Hierarchically porous materials: synthesis strategies and structure design
Authors: Yang Xiao-Yu , Chen Li-Hua , Li Yu , Rooke Joanna Claire , Sanchez Clément , Su Bao-Lian
Published: December 2016

This review addresses recent advances in synthesis strategies of hierarchically porous materials and their structural design from micro-, meso- to macro-length scale.