bluuebunny/crossref_metadata_2025 huggingface dataset:
VGF and striatal cell damage in in vitro and in vivo models of Huntington's disease
Authors: Noda Yasuhiro , Shimazawa Masamitsu , Tanaka Hirotaka , Tamura Shigeki , Inoue Teruyoshi , Tsuruma Kazuhiro , Hara Hideaki
Published: June 2015

Huntington's disease (HD) is an inherited genetic disorder, characterized by cognitive dysfunction and abnormal body movements, and at present there is no effective treatment for HD. Therapeutic options for HD are limited to symptomatic treatment approaches and there is no cure for this devastating disease. Here, we examined whether SUN N8075, (2S)‐1‐(4‐amino‐2,3,5‐trimethylphenoxy)‐3‐{4‐[4‐(4‐fluorobenzyl)phenyl]‐1‐piperazinyl}‐2‐propanol dimethanesulfonate, which exerts neuroprotective effects by antioxidant effects and induction of VGF nerve growth factor inducible (VGF), has beneficial effects in STHdh cells derived from striatum of knock‐in HD mice and R6/2 HD mice. In an in vitro study, SUN N8075 inhibited the cell death caused by mutant huntingtin (mHtt) and upregulated the VGF mRNA level via the phosphorylation of extracellular signal‐regulated kinase 1/2 (ERK1/2). Furthermore, 30 amino acid of VGF C‐terminal peptide, AQEE‐30 inhibited the cell death and the aggregation of mHtt. In an in vivo study, SUN N8075 improved the survival and the clasping response in the R6/2 mice. Furthermore, SUN N8075 increased the number of surviving neurons in the striatum of the R6/2 mice. These findings suggest that SUN N8075 may be an effective candidate for HD treatments.
Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation
Authors: Lenarczyk Marek , Su Jidong , Haworth Steven T. , Komorowski Richard , Fish Brian L. , Migrino Raymond Q. , Harmann Leanne , Hopewell John W. , Kronenberg Amy , Patel Shailendra , Moulder John E. , Baker John E.
Published: June 2015

The ability of simvastatin to mitigate the increases in risk factors for and the occurrence of cardiac disease after 10 Gy total body irradiation (TBI) was determined. This radiation dose is relevant to conditioning for stem cell transplantation and threats from radiological terrorism. Male rats received single dose TBI of 10 Gy. Age‐matched, sham‐irradiated rats served as controls. Lipid profile, heart and liver morphology and cardiac mechanical function were determined for up to 120 days after irradiation. TBI resulted in a sustained increase in total‐ and LDL‐cholesterol (low‐density lipoprotein‐cholesterol), and triglycerides. Simvastatin (10 mg/kg body weight/day) administered continuously from 9 days after irradiation mitigated TBI‐induced increases in total‐ and LDL‐cholesterol and triglycerides, as well as liver injury. TBI resulted in cellular peri‐arterial fibrosis, whereas control hearts had less collagen and fibrosis. Simvastatin mitigated these morphological injuries. TBI resulted in cardiac mechanical dysfunction. Simvastatin mitigated cardiac mechanical dysfunction 20–120 days following TBI. To determine whether simvastatin affects the ability of the heart to withstand stress after TBI, injury from myocardial ischemia/reperfusion was determined in vitro. TBI increased the severity of an induced myocardial infarction at 20 and 80 days after irradiation. Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI. It is concluded simvastatin mitigated the increases in risk factors for cardiac disease and the extent of cardiac disease following TBI. This statin may be developed as a medical countermeasure for the mitigation of radiation‐induced cardiac disease.
Bilateral Pheochromocytomas in MEN2A Syndrome: A Two‐Institution Experience
Authors: Lang Brian Hung‐Hin , Yu Hyeong Won , Lo Chung‐Yau , Lee Kyu Eun , Garcia‐Barcelo Maria‐Mercedes , Woo Yu Cho , Lee Paul C. H. , Wong Kai Pun , Tam Paul K. H. , Lam Karen S. L.
Published: June 2015

Background

Bilateral pheochromocytoma (PHEO) is more frequently found in patients with multiple endocrine neoplasia 2A carrying a RET germline mutation located in codon 634 (C634). However, it is unclear whether different amino acid substitutions within C634 cause differences in bilateral PHEOs expression. We aimed to answer this by pooling data from two Asian institutions.

Methods

Sixty‐seven patients had confirmed C634 germline mutation. Age‐dependent penetrance of bilateral PHEO was calculated from date of birth to the date when bilateral PHEO was first diagnosed or when the contralateral gland became a PHEO (if the patient already had one adrenal gland removed). Age‐dependent penetrance was estimated by the Kaplan–Meier method and compared by log‐rank test.

Results

The 4 different amino acid substitutions included C634R (arginine) (n = 19, 28.4 %), C634Y (tyrosine) (n = 36, 38.8 %), C634G (glycine) (n = 4, 6.0 %), and C634W (tryptophan) (n = 8, 11.9 %). The age‐related penetrance of PHEO was similar between C634R, C634Y, C634G, and C634W (by age 40, 69.8, 55.2, 25.0, and 56.2 %, respectively) (p = 0.529). However, the age‐related penetrance of bilateral PHEO in C634R was significantly higher than C634Y (by age of 40, 59.3 % vs. 25.2 %, p = 0.046) or C634Y, C634G, and C634W combined (59.3 % vs. 21.5 %, p = 0.024). Nevertheless, the accumulative risk of bilateral PHEOs across all four C634 mutations almost approached 100 % over time.

Conclusion

The accumulative risk of bilateral PHEOs almost reached 100 % but its onset was significantly earlier in C634R mutation. These findings implied that those with C634R mutation might benefit from earlier screening of contralateral PHEO than other C634 mutations after an unilateral adrenalectomy.
A case of inappropriate implantable cardioverter defibrillator therapy induced by T‐wave oversensing due to hyperkalemia
Authors: Aoki Kosuke , Okajima Katsunori , Kiuchi Kunihiko , Yokoi Kiminobu , Teranishi Jin , Shimane Akira
Published: June 2015

There have been reports of hyperkalemia‐induced T‐wave oversensing in patients with implantable cardioverter defibrillators (ICDs). However, a comparison of T‐wave amplitudes and morphologies between the surface 12‐lead electrocardiogram (ECG) and ICD electrogram has not been reported. We present the case of a 70‐year‐old man who received inappropriate ICD shocks due to hyperkalemia‐induced T‐wave oversensing. The T‐wave amplitudes on both the ICD electrogram and 12‐lead ECG corresponded and normalized after normalization of the potassium level.
WAS THE WAGE BURDEN TOO HEAVY? SETTLER FARMING, PROFITABILITY, AND WAGE SHARES OF SETTLER AGRICULTURE IN NYASALAND, c. 1900–60
Authors: BOLT JUTTA , GREEN ERIK
Published: June 2015

The historical role of European farming in Southern and Central Africa has received a great deal of attention among scholars over the years. A striking consensus exists in the Scholarly literature, namely that the success or failure of European farming in Southern Africa was to a large extent dependent upon the colonizers' access to and control over cheap labour, which they in turn could only access through strong support of the colonial state. Yet, these propositions have so far not been systematically and empirically tested. This article is a first attempt to do that by analysing the ‘wage-burden’ European settler farmers faced. The wage-burden is identified by measuring wage shares (total amount paid in the form of wages as a share of total profits) on European farms in colonial Africa. Based on archival documents, we construct time-series for value of output, transportation costs, investments in agriculture, and wages paid for the European tobacco and tea sector in colonial Malawi. Our results contradict both previous research on settler colonialism in Africa and the historiography of Nyasaland. Our estimates show that settler farming did not collapse in the 1930s as commonly assumed. On the contrary, the value of production on both tobacco and tea farms increased significantly. And so did the settler farmers' capacity to capture the profits, which was manifested in a declining wage share over time. In contrast with previous research, we argue that the declining wage share cannot be explained by domestic colonial policies but rather through changes in regional migration patterns, and global commodity markets. Migration patterns had a significant impact on the supply of farm labour and global commodity markets influenced value of production. Market forces rather than colonial policies shaped the development trajectory of settler farming in Nyasaland.
The Responsibility to Protect Turns Ten
Authors: Bellamy Alex J.
Published: June 2015

Ten years since its adoption by the UN General Assembly, the Responsibility to Protect (RtoP) has become an established international norm associated with positive changes to the way that international society responds to genocide and mass atrocities. In its first decade, RtoP has moved from being a controversial and indeterminate concept seldom utilized by international society to a norm utilized almost habitually. This is an assessment that stands in contrast to the widespread view that RtoP is associated with “growing controversy,” but is one that rests on evidence of state practice.
The Idea of Universality in the Sustainable Development Goals
Authors: Long Graham
Published: June 2015

A new set of “Sustainable Development Goals” (SDGs) are currently being negotiated at the United Nations, and there is a widespread consensus that these goals must be “universal.” This article analyses what universality might mean in this context, and its normative significance as a guiding principle for the goals. After briefly introducing the Sustainable Development Goals as found in the current stage of the negotiations, thearticle proceeds in three sections that consider three different senses of universality. In the first, I outline the most intuitive or straightforward sense of universality as a claim about the scope of the goals, with limited import for the content. In the second section, I expand on this idea by noting a widespread understanding of the content of the goals which might also be thought universal and which reflects a moral cosmopolitan constraint on the ambition of each goal. Universality is paired with, and contrasted against, the need fordifferentiation. In the final section, I examine this idea of differentiation, asking how and how far, the goals should allow for country context. From this discussion arises a third account of universality which incorporates a demand for fair burden-sharing. I consider, and ultimately caution against, this account of universality, even though the demand forfairness is crucial in its own right.
Human Rights Law Without Natural Moral Rights
Authors: Cruft Rowan
Published: June 2015

In this latest work by one of our leading political and legal philosophers, Allen Buchanan outlines a novel framework for assessing the system of international human rights law—the system that he takes to be the heart of modern human rights practice. Buchanan does not offer a full justification for the current system, but rather aims “to make a strong prima facie case that the existing system as a whole has what it takes to warrant our support of it on moral grounds, even if some aspects of it are defective and should be the object of serious efforts at improvement” (p. 173).
Raynauds phenomenon - assessment and differential diagnoses
Authors: Linnemann Birgit , Erbe Matthias
Published: June 2015

Raynauds phenomenon (RP) is characterised by paroxysmal reversible episodes of vasospasm, usually involving peripheral small vessels of the fingers or toes and resulting in a triple-colour change starting with pallor and followed by cyanosis and erythema. Attacks are typically triggered by cold or emotional stress. The diagnosis of RP can be made on the basis of the patients clinical symptoms. Primary RP occurs without underlying disease and is considered a benign condition. A normal erythrocyte sedimentation rate, negative testing for antinuclear antibodies, normal nailfold capillaries and the absence of structural micro- or macrovascular damage and other diseases lead to the diagnosis of primary RP. Digital photoplethysmography and pulse contour analysis can be used as an additional tool to exclude structural macro- or microvascular disease. In contrast, secondary RP is associated with other diseases, mainly connective tissue diseases such as systemic sclerosis. If there is a suspicion of secondary RP, a thorough laboratory and vascular assessment is required to make the diagnosis of underlying disease. Acrocyanosis and erythromelalgia are additional functional vascular disorders that can be easily distinguished when patients are carefully assessed for their history and clinical symptoms.
Positive correlation between neovascularization degree of carotid atherosclerosis determined by contrast-enhanced ultrasound and level of serum C-reactive protein
Authors: Chang Xiaoni , Feng Jun , Ruan Litao , Shang Jing , Yang Yanqiu , Sun Jian , Dang Ying , Song Yan
Published: June 2015

Background: Neovascularization is one of the most important risk factors for unstable plaque. This study was designed to correlate plaque thickness, artery stenosis and levels of serum C-reactive protein with the degree of intraplaque enhancement determined by contrast-enhanced ultrasound. Patients and methods: Contrast-enhanced ultrasound was performed on 72 carotid atherosclerotic plaques in 48 patients. Contrast enhancement within the plaque was categorized as grade 1, 2 or 3. Maximum plaque thickness was measured in short-axis view. Carotid artery stenosis was categorized as mild, moderate or severe. Results: Plaque contrast enhancement was not associated with the degree of artery stenosis or with plaque thickness. Serum C-reactive protein levels were positively correlated with the number of new vessels in the plaque. C-reactive protein levels increased in the three groups(Grade 1: 3.72±1.79mg/L; Grade 2: 7.88±4.24 mg/L; Grade 3: 11.02±3.52 mg/L), with significant differences among them (F=10.14, P<0.01), and significant differences between each two groups (P<0.05). Spearmans rank correlation analysis showed that serum C-reactive protein levels were positively correlated with the degree of carotid plaque enhancement (Rs =0.69, P<0.01). Conclusions: The combination of C-reactive protein levels and intraplaque neovascularization detected by contrast-enhanced ultrasound may allow more accurate evaluation of plaque stability.
Comparison of one-year prognosis of patients classified as chronic critical lower limb ischaemia according to TASC II or European consensus definition in the COPART cohort
Authors: Vircoulon Marion , Boulon Carine , Desormais Ileana , Lacroix Philippe , Aboyans Victor , Bura-Riviere Alessandra , Cambou Jean-Pierre , Becker François , Constans Joel
Published: June 2015

Background: We compared one-year amputation and survival rates in patients fulfilling 1991 European consensus critical limb ischaemia (CLI) definition to those clas, sified as CLI by TASC II but not European consensus (EC) definition. Patients and methods: Patients were selected from the COPART cohort of hospitalized patients with peripheral occlusive arterial disease suffering from lower extremity rest pain or ulcer and who completed one-year follow-up. Ankle and toe systolic pressures and transcutaneous oxygen pressure were measured. The patients were classified into two groups: those who could benefit from revascularization and those who could not (medical group). Within these groups, patients were separated into those who had CLI according to the European consensus definition (EC + TASC II: group A if revascularization, group C if medical treatment) and those who had no CLI by the European definition but who had CLI according to the TASC II definition (TASC: group B if revascularization and D if medical treatment). Results: 471 patients were included in the study (236 in the surgical group, 235 in the medical group). There was no difference according to the CLI definition for survival or cardiovascular event-free survival. However, major amputations were more frequent in group A than in group B (25 vs 12 %, p = 0.046) and in group C than in group D (38 vs 20 %, p = 0.004). Conclusions: Major amputation is twice as frequent in patients with CLI according to the historical European consensus definition than in those classified to the TASC II definition but not the EC. Caution is required when comparing results of recent series to historical controls. The TASC II definition of CLI is too wide to compare patients from clinical trials so we suggest separating these patients into two different stages: permanent (TASC II but not EC definition) and critical ischaemia (TASC II and EC definition).
Kardiologische Abklärung und Behandlung vor chirurgischen Eingriffen
Authors: Schwarz Stefanie , Bernheim Alain M.
Published: June 2015

Bei der präoperativen kardialen Risikostratifizierung werden Patienten-bezogene Risikofaktoren, die Umstände, die zur Operation führen und das Operationsrisiko berücksichtigt. Während eine Notfalloperation ohne präoperative Abklärungen durchgeführt werden soll, haben instabile kardiale Situationen Behandlungspriorität gegenüber einer elektiven Operation. Bei stabilen Patienten sind prophylaktische Koronareingriffe zur Verhinderung perioperativer Komplikationen sehr selten indiziert. Ein präoperativer kardialer Stresstest oder eine Koronarangiografie wird daher nur in wenigen Fällen veranlasst. Die Durchführung eines Stresstests wird nur für Patienten mit schlechter Leistungsfähigkeit und hohem kardiovaskulärem Risiko vor einer Hochrisiko-Operation explizit empfohlen. Der Nutzen einer perioperativen prophylaktischen Gabe von Betablockern und Aspirin ist gemäss neueren Daten umstritten. Die präoperative Unterbrechung einer dualen Plättchenaggregationshemmung innert sechs Monaten nach Implantation beschichteter Koronarstents sollte dagegen nach Möglichkeit vermieden werden.
Take the Student Travel Grant Challenge
Authors: Borchardt Jeff
Published: June 2015

The founder of AGU's Student Travel Grant program challenges AGU donors to make a record-breaking impact in 2015. Learn how you can help.
Small-molecule activation of SERCA2a SUMOylation for the treatment of heart failure
Authors: Kho Changwon , Lee Ahyoung , Jeong Dongtak , Oh Jae Gyun , Gorski Przemek A. , Fish Kenneth , Sanchez Roberto , DeVita Robert J. , Christensen Geir , Dahl Russell , Hajjar Roger J.
Published: June 2015

Decreased activity and expression of the cardiac sarcoplasmic reticulum calcium ATPase (SERCA2a), a critical pump regulating calcium cycling in cardiomyocyte, are hallmarks of heart failure. We have previously described a role for the small ubiquitin-like modifier type 1 (SUMO-1) as a regulator of SERCA2a and have shown that gene transfer of SUMO-1 in rodents and large animal models of heart failure restores cardiac function. Here, we identify and characterize a small molecule, N106, which increases SUMOylation of SERCA2a. This compound directly activates the SUMO-activating enzyme, E1 ligase, and triggers intrinsic SUMOylation of SERCA2a. We identify a pocket on SUMO E1 likely to be responsible for N106’s effect. N106 treatment increases contractile properties of cultured rat cardiomyocytes and significantly improves ventricular function in mice with heart failure. This first-in-class small-molecule activator targeting SERCA2a SUMOylation may serve as a potential therapeutic strategy for treatment of heart failure.
Synthesis of three-dimensionally interconnected sulfur-rich polymers for cathode materials of high-rate lithium–sulfur batteries
Authors: Kim Hoon , Lee Joungphil , Ahn Hyungmin , Kim Onnuri , Park Moon Jeong
Published: June 2015

Elemental sulfur is one of the most attractive cathode active materials in lithium batteries because of its high theoretical specific capacity. Despite the positive aspect, lithium–sulfur batteries have suffered from severe capacity fading and limited rate capability. Here we report facile large-scale synthesis of a class of organosulfur compounds that could open a new chapter in designing cathode materials to advance lithium–sulfur battery technologies. Porous trithiocyanuric acid crystals are synthesized for use as a soft template, where the ring-opening polymerization of elemental sulfur takes place along the thiol surfaces to create three-dimensionally interconnected sulfur-rich phases. Our lithium–sulfur cells display discharge capacity of 945 mAh g−1 after 100 cycles at 0.2 C with high-capacity retention of 92%, as well as lifetimes of 450 cycles. Particularly, the organized amine groups in the crystals increase Li+-ion transfer rate, affording a rate performance of 1210, mAh g−1 at 0.1 C and 730 mAh g−1 at 5 C.
Proximity-dependent initiation of hybridization chain reaction
Authors: Koos Björn , Cane Gaëlle , Grannas Karin , Löf Liza , Arngården Linda , Heldin Johan , Clausson Carl-Magnus , Klaesson Axel , Hirvonen M. Karoliina , de Oliveira Felipe M. S. , Talibov Vladimir O. , Pham Nhan T. , Auer Manfred , Danielson U. Helena , Haybaeck Johannes , Kamali-Moghaddam Masood , Söderberg Ola
Published: June 2015

Sensitive detection of protein interactions and post-translational modifications of native proteins is a challenge for research and diagnostic purposes. A method for this, which could be used in point-of-care devices and high-throughput screening, should be reliable, cost effective and robust. To achieve this, here we design a method (proxHCR) that combines the need for proximal binding with hybridization chain reaction (HCR) for signal amplification. When two oligonucleotide hairpins conjugated to antibodies bind in close proximity, they can be activated to reveal an initiator sequence. This starts a chain reaction of hybridization events between a pair of fluorophore-labelled oligonucleotide hairpins, generating a fluorescent product. In conclusion, we show the applicability of the proxHCR method for the detection of protein interactions and posttranslational modifications in microscopy and flow cytometry. As no enzymes are needed, proxHCR may be an inexpensive and robust alternative to proximity ligation assays.
Structural basis of asymmetric DNA methylation and ATP-triggered long-range diffusion by EcoP15I
Authors: Gupta Yogesh K. , Chan Siu-Hong , Xu Shuang-yong , Aggarwal Aneel K.
Published: June 2015

Type III R–M enzymes were identified >40 years ago and yet there is no structural information on these multisubunit enzymes. Here we report the structure of a Type III R–M system, consisting of the entire EcoP15I complex (Mod2Res1) bound to DNA. The structure suggests how ATP hydrolysis is coupled to long-range diffusion of a helicase on DNA, and how a dimeric methyltransferase functions to methylate only one of the two DNA strands. We show that the EcoP15I motor domains are specifically adapted to bind double-stranded DNA and to facilitate DNA sliding via a novel ‘Pin’ domain. We also uncover unexpected ‘division of labour’, where one Mod subunit recognizes DNA, while the other Mod subunit methylates the target adenine—a mechanism that may extend to adenine N6 RNA methylation in mammalian cells. Together the structure sheds new light on the mechanisms of both helicases and methyltransferases in DNA and RNA metabolism.
Host-virus interaction: the antiviral defense function of small interfering RNAs can be enhanced by host microRNA-7 in vitro
Authors: Zhang Xiaoying , Liu Dongyun , Zhang Sheng , Wei Xiujuan , Song Jie , Zhang Yupei , Jin Min , Shen Zhiqiang , Wang Xinwei , Feng Zhichun , Li Junwen
Published: June 2015

Small interfering RNAs (siRNAs) directed against poliovirus (PV) and other viruses effectively inhibit viral replication and have been developed as antiviral agents. Here, we demonstrate that a specific siRNA targeting the region between nucleotides 100–125 (siRNA-100) from the 5′-untranslated region (5′-UTR) of PV plays a critical role in inhibiting PV replication. Our data demonstrate that siRNA-100 treatment can greatly reduce PV titers, resulting in up-regulation of host microRNA-7 (miR-7), which in turn, leads to enhance inhibition of PV infection further. Moreover, our results suggest that siRNA-100 can also impair the spread of PV to uninfected cells by increasing host resistance to PV, resulting in decreasing necrosis and cytopathic effects (CPE) levels, as well as prolonging the survival of infected cells. Indeed, the active antiviral effect of siRNA-100 was potentially supplemented by the activity of miR-7 and both of them can serve as stabilizing factors for maintenance of cellular homeostasis. Results of this study identify a molecular mechanism of RNAi for antiviral defense and extend our knowledge of the complex interplay between host and PV, which will provide a basis for the development of effective RNAi-based therapies designed to inhibit PV replication and protect host cells.
Oxygen Vacancy Induced Flat Phonon Mode at FeSe /SrTiO3 interface
Authors: Xie Yun , Cao Hai-Yuan , Zhou Yang , Chen Shiyou , Xiang Hongjun , Gong Xin-Gao
Published: June 2015

A high-frequency optical phonon mode of SrTiO3 (STO) was found to assist the high-temperature superconductivity observed recently at the interface between monolayer FeSe and STO substrate. However, the origin of this mode is not clear. Through first-principles calculations, we find that there is a novel polar phonon mode on the surface layers of the STO substrate, which does not exist in the STO crystals. The oxygen vacancies near the FeSe/STO interface drives the dispersion of this phonon mode to be flat and lowers its energy, whereas the charge transfer between STO substrate and FeSe monolayer further reduces its energy to 81 meV. This energy is in good agreement with the experimental value fitted by Lee et al. for the phonon mode responsible for the observed replica band separations and the increased superconducting gap. The oxygen-vacancy-induced flat and polar phonon mode provides clues for understanding the origin of high Tc superconductivity at the FeSe/STO interface.
Variation in the bovine FABP4 gene affects milk yield and milk protein content in dairy cows
Authors: Zhou H. , Cheng L. , Azimu W. , Hodge S. , Edwards G. R. , Hickford J. G. H.
Published: June 2015

Fatty acid binding proteins (FABPs) bind long-chain fatty acids and are involved in their intracellular transport. Of the known bovine FABP genes,FABP4has been mapped to a region on chromosome 14 that contains quantitative trait loci for milk traits. This study investigated the association ofFABP4haplotypes with milk production traits in 719 Holstein-Friesian × Jersey cows. Polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis of a variable region of the gene revealed three haplotypes (A,BandC). Five single nucleotide polymorphisms (SNPs) were identified: two in exon 3 and three in intron 3.Awas associated (P = 0.032) with increased milk protein percentage (present: 4.00 ± 0.02%; absent: 3.95 ± 0.02%) andBwas associated (P = 0.009) with increased milk yield (present: 23.81 ± 0.23 kg/d; absent: 23.06 ± 0.21 kg/d), but tended to be associated with a decrease in protein percentage and an increase in protein yield. Cows with genotypesAA,ABandACproduced less milk, but with a higher protein percentage thanBCcows. This suggest thatFABP4affects milk yield and milk protein content, both economically important traits and that further study of this gene is warranted.
Rational design of binder-free noble metal/metal oxide arrays with nanocauliflower structure for wide linear range nonenzymatic glucose detection
Authors: Li Zhenzhen , Xin Yanmei , Zhang Zhonghai , Wu Hongjun , Wang Peng
Published: June 2015

One-dimensional nanocomposites of metal-oxide and noble metal were expected to present superior performance for nonenzymatic glucose detection due to its good conductivity and high catalytic activity inherited from noble metal and metal oxide respectively. As a proof of concept, we synthesized gold and copper oxide (Au/CuO) composite with unique one-dimensional nanocauliflowers structure. Due to the nature of the synthesis method, no any foreign binder was needed in keeping either Au or CuO in place. To the best of our knowledge, this is the first attempt in combining metal oxide and noble metal in a binder-free style for fabricating nonenzymatic glucose sensor. The Au/CuO nanocauliflowers with large electrochemical active surface and high electrolyte contact area would promise a wide linear range and high sensitive detection of glucose with good stability and reproducibility due to its good electrical conductivity of Au and high electrocatalytic activity of CuO.
Researchers’ perspectives on scientific and ethical issues with transcranial direct current stimulation: An international survey
Authors: Riggall Kate , Forlini Cynthia , Carter Adrian , Hall Wayne , Weier Megan , Partridge Brad , Meinzer Marcus
Published: June 2015

In the last decade, an increasing number of studies have suggested that transcranial direct current stimulation (tDCS) may enhance brain function in healthy individuals and ameliorate cognitive and other symptoms in patients suffering from various medical conditions. This, along with its presumed safety, simplicity and affordability, has generated great enthusiasm amongst researchers, clinicians, patient populations and the public (including a growing “do-it-yourself” community). However, discussion about the effectiveness and ethics of tDCS thus far has been confined to small groups of tDCS researchers and bioethicists. We conducted an international online survey targeting the opinions of researchers using tDCS who were asked to rate the technique’s efficacy in different contexts. We also surveyed opinions about ethical concerns, self-enhancement and public availability. 265 complete responses were received and analyzed statistically and thematically. Our results emphasize the potential uses of tDCS in clinical and research contexts, but also highlight a number of emerging methodological and safety concerns, ethical challenges and the need for improved communication between researchers and bioethicists with regard to regulation of the device. Neither the media reputation of tDCS as a “miracle device” nor concerns expressed in recent neuroethical publications were entirely borne out in expert opinion.
Transition to turbulence in Taylor-Couette ferrofluidic flow
Authors: Altmeyer Sebastian , Do Younghae , Lai Ying-Cheng
Published: June 2015

It is known that in classical fluids turbulence typically occurs at high Reynolds numbers. But can turbulence occur at low Reynolds numbers? Here we investigate the transition to turbulence in the classic Taylor-Couette system in which the rotating fluids are manufactured ferrofluids with magnetized nanoparticles embedded in liquid carriers. We find that, in the presence of a magnetic field transverse to the symmetry axis of the system, turbulence can occur at Reynolds numbers that are at least one order of magnitude smaller than those in conventional fluids. This is established by extensive computational ferrohydrodynamics through a detailed investigation of transitions in the flow structure and characterization of behaviors of physical quantities such as the energy, the wave number and the angular momentum through the bifurcations. A finding is that, as the magnetic field is increased, onset of turbulence can be determined accurately and reliably. Our results imply that experimental investigation of turbulence may be feasible by using ferrofluids. Our study of transition to and evolution of turbulence in the Taylor-Couette ferrofluidic flow system provides insights into the challenging problem of turbulence control.
Generation of pure lymphatic endothelial cells from human pluripotent stem cells and their therapeutic effects on wound repair
Authors: Lee Shin-Jeong , Park Changwon , Lee Ji Yoon , Kim Sangsung , Kwon Pil Jae , Kim Woansang , Jeon Yong Heui , Lee Eugine , Yoon Young-sup
Published: June 2015

Human pluripotent stem cells (hPSCs) have emerged as an important source for cell therapy. However, to date, no studies demonstrated generation of purified hPSC-derived lymphatic endothelial cells (LECs) and tested their therapeutic potential in disease models. Here we sought to differentiate hPSCs into the LEC lineage, purify them with LEC markers and evaluate their therapeutic effects. We found that an OP9-assisted culture system reinforced by addition of VEGF-A, VEGF-C and EGF most efficiently generated LECs, which were then isolated via FACS-sorting with LYVE-1 and PODOPLANIN. These hPSC-derived LYVE-1+PODOPLANIN+cells showed a pure committed LEC phenotype, formed new lymphatic vessels and expressed lymphangiogenic factors at high levels. These hPSC-derived LECs enhanced wound healing through lymphangiogenesis and lymphvasculogenesis. Here we report, for the first time, that LECs can be selectively isolated from differentiating hPSCs and that these cells are potent for lymphatic vessel formation in vivo and wound healing. This system and the purified hPSC-derived LECs can serve as a new platform for studying LEC development as well as for cell therapy.
Electrical Switchability and Dry-Wash Durability of Conductive Textiles
Authors: Wu Bangting , Zhang Bowu , Wu Jingxia , Wang Ziqiang , Ma Hongjuan , Yu Ming , Li Linfan , Li Jingye
Published: June 2015

There is growing interest in the area of conductive textiles in the scientific and industrial community. Herein, we successfully prepared a conductive textile via covalently grafting polyaniline (PANI) onto cotton by a multi-step treatment process. The conductivity of the resultant fabric could be tuned by immersing in water having different pH values. The conductive and insulating properties of the textile could be conveniently switched by alternately immersing in acidic and alkaline bath solutions. Most importantly, the resultant conductive fabrics were able to withstand 40 simulated dry-wash cycles, with almost no decay in the electrical conductivity, indicating their excellent dry-wash durability. The present strategy for fabricating conductive fabrics with excellent switchability of electrical properties and dry-wash durability is expected to provide inspiration for the production of multifunctional conductive textiles for use in hash or sensitive conditions.
Chitosan grafted methoxy poly(ethylene glycol)-poly(ε-caprolactone) nanosuspension for ocular delivery of hydrophobic diclofenac
Authors: Shi Shuai , Zhang Zhaoliang , Luo Zichao , Yu Jing , Liang Renlong , Li Xingyi , Chen Hao
Published: June 2015

This study aimed to develop a cationic nanosuspension of chitosan (CS) and methoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) for ocular delivery of diclofenac (DIC). MPEG-PCL-CS block polymer was synthesized by covalent coupling of MPEG-PCL with CS. The critical micelle concentration of the MPEG-PCL-CS block polymer was 0.000692 g/L. DIC/MPEG-PCL-CS nanosuspension (mean particle size = 105 nm, zeta potential = 8 mV) was prepared and characterized by Fourier transform infrared spectroscopy, X-ray diffraction and differential scanning calorimetry. The nanosuspension was very stable without apparent physical property changes after storage at 4 °C or 25 °C for 20 days, but it was unstable in the aqueous humor solution after 24 h incubation. Sustained release of the encapsulated DIC from the nanosuspension occurred over 8 h. Neither a blank MPEG-PCL-CS nanosuspension nor a 0.1% (mass fraction) DIC/MPEG-PCL-CS nanosuspension caused ocular irritation after 24 h of instillation. Enhanced penetration and retention in corneal tissue was achieved with a Nile red/MPEG-PCL-CS nanosuspension compared with a Nile red aqueous solution. In vivo pharmacokinetics studies showed enhanced pre-corneal retention and penetration of the DIC/MPEG-PCL-CS nanosuspension, which resulted in a higher concentration of DIC (Cmax) in the aqueous humor and better bioavailability compared with commercial DIC eye drops (P < 0.01).
Frequency-resolved optical gating technique for retrieving the amplitude of a vibrational wavepacket
Authors: Nabekawa Yasuo , Furukawa Yusuke , Okino Tomoya , Amani Eilanlou A. , Takahashi Eiji J. , Yamanouchi Kaoru , Midorikawa Katsumi
Published: June 2015

We propose a novel method to determine the complex amplitude of each eigenfunction composing a vibrational wavepacket of "Equation missing"/"Equation missing" molecular ions evolving with a ~10 fs time scale. We find that the two-dimensional spectrogram of the kinetic energy release (KER) of H+/D+ fragments plotted against the time delay of the probe pulse is equivalent to the spectrogram used in the frequency-resolved optical gating (FROG) technique to retrieve the complex amplitude of an ultrashort optical pulse. By adapting the FROG algorithm to the delay-KER spectrogram of the vibrational wavepacket, we have successfully reconstructed the complex amplitude. The deterioration in retrieval accuracy caused by the bandpass filter required to process actual experimental data is also discussed.
Schottky barrier formation and band bending revealed by first- principles calculations
Authors: Jiao Yang , Hellman Anders , Fang Yurui , Gao Shiwu , Käll Mikael
Published: June 2015

The formation of a Schottky barrier at the metal-semiconductor interface is widely utilised in semiconductor devices. With the emerging of novel Schottky barrier based nanoelectronics, a further microscopic understanding of this interface is in high demand. Here we provide an atomistic insight into potential barrier formation and band bending by ab initio simulations and model analysis of a prototype Schottky diode, i.e., niobium doped rutile titania in contact with gold (Au/Nb:TiO2). The local Schottky barrier height is found to vary between 0 and 1.26 eV depending on the position of the dopant. The band bending is caused by a dopant induced dipole field between the interface and the dopant site, whereas the pristine Au/TiO2 interface does not show any band bending. These findings open the possibility for atomic scale optimisation of the Schottky barrier and light harvesting in metal-semiconductor nanostructures.
The significance of membrane fluidity of feeder cell-derived substrates for maintenance of iPS cell stemness
Authors: Zhou Yue , Mao Hongli , Joddar Binata , Umeki Nobuhisa , Sako Yasushi , Wada Ken-Ichi , Nishioka Chieko , Takahashi Eiki , Wang Yi , Ito Yoshihiro
Published: June 2015

The biological activity of cell-derived substrates to maintain undifferentiated murine-induced pluripotent stem (iPS) cells was correlated to membrane fluidity as a new parameter of cell culture substrates. Murine embryonic fibroblasts (MEFs) were employed as feeder cells and their membrane fluidity was tuned by chemical fixation using formaldehyde (FA). Membrane fluidity was evaluated by real-time single-molecule observations of green fluorescent protein-labeled epidermal growth factor receptors on chemically fixed MEFs. Biological activity was monitored by colony formation of iPS cells. Treatment with a low concentration of FA sustained the membrane fluidity and biological activity, which were comparable to those of mitomycin C-treated MEFs. The biological activity was further confirmed by sustained expression of alkaline phosphatase, SSEA-1 and other pluripotency markers in iPS cells after 3–5 days of culture on FA-fixed MEFs. Chemical fixation of feeder cells has several advantages such as providing ready-to-use culture substrates without contamination by proliferating feeder cells. Therefore, our results provide an important basis for the development of chemically fixed culture substrates for pluripotent stem cell culture as an alternative to conventional treatment by mitomycin C or x-ray irradiation.
On the formation of current ripples
Authors: Bartholdy J. , Ernstsen V. B. , Flemming B. W. , Winter C. , Bartholomä A. , Kroon A.
Published: June 2015

For grain sizes finer than coarse sand, the first flow-transverse bedforms to develop are current ripples. Although numerous studies have analysed different aspects of bedform morphodynamics, to date no comprehensive physical explanation for the formation of ripples has been given. We offer such an explanation based on a virtual boundary layer concept and present a model predicting ripple height on the basis of grain size, current velocity and water depth. The model contradicts the conventional view of current ripples as bedforms not scaling with flow depth. Furthermore, it confirms the dependence of ripple dimensions on grain size and their relative insensitivity to flow strength.
Barriers to Adopting Green Chemistry in Drug Discovery
Authors: Sneddon Helen F.
Published: June 2015

In drug discovery, the barriers to adopting green chemistry can be broadly classified as economic, technical, and cultural, with cultural barriers posing by far the greatest challenge. Economic and technical barriers pertaining to solvents, reagents, time, and technologies are briefly covered, with some suggestions as to how some of these may be addressed. The cultural barriers mainly result from a lack of awareness of green chemistry both within the industry and in the wider chemistry community, including academia, and the perception that incorporation of green chemistry could slow down the pace of research. Specific concerns arising from each of the 12 principles of green chemistry are considered, as is the possibility of confusion over communication, especially over how reagents, solvents, or processes are labelled as “green” or which metrics should be used. Some recommendations for overcoming these barriers and embedding a green chemistry culture are discussed.
Green Chemistry and High Throughput Screening
Authors: Richardson Paul
Published: June 2015

This chapter describes the implementation and value that high throughput reaction screening can provide within a drug discovery environment. In addition, particular focus is placed on its utility in making rapid and more informed decisions based on environmental aspects of the chemistry. Examples are drawn from our internal projects in order to provide full details of background, learning, and concepts derived from each of these.
Recycling and Reuse in the Laboratory
Authors: Richter Daniel T.
Published: June 2015

In a discovery laboratory setting there are a multitude of opportunities to reduce, reuse, or recycle many of the items that are used every day. In this chapter, the focus will be on several areas of high impact that are common to all discovery laboratories where waste can be reduced through reuse or recycling of materials: solvents, precious metal catalysts, glass, chromatography columns, and cardboard or plastic. These areas of frequent use can yield the greatest returns in the goal of minimizing waste and environmental footprint in a drug discovery setting. Furthermore, an explanation of the practical limitations and issues with these options will be included as various factors may impact feasibility due to scale, cost, or safety and regulatory concerns.
Toxicology for Chemical Safety and Sustainability
Authors: Anastas Nicholas D.
Published: June 2015

Toxicology has assumed a more prominent role in the design and discovery of new products, including pharmaceuticals, in part because of the advancements made in computational chemistry coupled with an increased understanding of the mechanisms of toxicity. Twenty-first century toxicology allows scientists to describe adverse outcome pathways at the molecular level as well as to predict toxicity based on a comprehensive suite of modern techniques including in silico methods, in vivo bioassays, and mechanistic in vitro screening methods. Integrating the information generated from these tools by holistically trained scientists will allow for the articulation of design rules that are necessary tools for synthetic chemists to design safer, healthier, and sustainable chemistries.
Emerging translational research on magnetic nanoparticles for regenerative medicine
Authors: Gao Yu , Lim Jing , Teoh Swee-Hin , Xu Chenjie
Published: June 2015

This review summarizes current advances, challenges, and future opportunities of magnetic nanoparticles for regenerative medicine.
ATR-FTIR spectroscopy coupled with chemometric analysis discriminates normal, borderline and malignant ovarian tissue: classifying subtypes of human cancer
Authors: Theophilou Georgios , Lima Kássio M. G. , Martin-Hirsch Pierre L. , Stringfellow Helen F. , Martin Francis L.
Published: June 2015

Spectrochemical discrimination of ovarian cancer.
Spectral data quality assessment based on variability analysis: application to noninvasive hemoglobin measurement by dynamic spectrum
Authors: He Wenqin , Li Xiaoxia , Wang Mengjun , Li Gang , Lin Ling
Published: June 2015

It could be applied not only to the noninvasive hemoglobin measurement but also to other related fields such as signal processing.
Cut-off on demand: adjustment of the threshold level of an immunochromatographic assay for chloramphenicol
Authors: Zvereva Elena A. , Byzova Nadezhda A. , Sveshnikov Peter G. , Zherdev Anatoly V. , Dzantiev Boris B.
Published: June 2015

In this study, adjusting the threshold level was investigated for an immunochromatographic assay for chloramphenicol, which is a veterinary drug of concern in the food industry because of its toxic effects.
Modulation of neuronal network activity using magnetic nanoparticle-based astrocytic network integration
Authors: Saito Atsushi , Nakashima Yutaro , Shimba Kenta , Takayama Yuzo , Kotani Kiyoshi , Jimbo Yasuhiko
Published: June 2015

Magnetic nanoparticle-based novel co-culture method to investigate direct and rapid interaction between neuronal and astrocytic network activity.
A new designed hydrazine group-containing ruthenium complex used for catalytic hydrogenation of esters
Authors: Tan Xuefeng , Wang Qingli , Liu Yuanhua , Wang Fangyuan , Lv Hui , Zhang Xumu
Published: June 2015

Hydrazine group-containing nitrogen–phosphine ruthenium complexes were synthesized and used for hydrogenation of esters, and excellent performance was observed (TON up to 17 200).
A doubly responsive probe for the detection of Cys4-tagged proteins
Authors: Kotera N. , Dubost E. , Milanole G. , Doris E. , Gravel E. , Arhel N. , Brotin T. , Dutasta J.-P. , Cochrane J. , Mari E. , Boutin C. , Léonce E. , Berthault P. , Rousseau B.
Published: June 2015

A biosensor for bimodal detection of recombinant Cys-tagged proteins via fluorescence and hyperpolarized 129Xe NMR is presented. Interaction with a peptide containing the motif Cys–Cys–X–X–Cys–Cys activates both fluorescence and NMR responses.
Inverted planar NH2CHNH2PbI3 perovskite solar cells with 13.56% efficiency via low temperature processing
Authors: Yuan Da-Xing , Gorka Adam , Xu Mei-Feng , Wang Zhao-Kui , Liao Liang-Sheng
Published: June 2015

High efficiency inverted planar NH2CHNH2PbI3 perovskite solar cells fabricated by a low-temperature solution-process.
Anisotropically branched metal nanostructures
Authors: Ye Enyi , Regulacio Michelle D. , Zhang Shuang-Yuan , Loh Xian Jun , Han Ming-Yong
Published: June 2015

This tutorial review provides an essential introduction to colloidally prepared branched metal nanostructures and their utility in plasmonics, catalysis and biomedicine.
Insights into the effects of steam on propane dehydrogenation over a Pt/Al2O3 catalyst
Authors: Shan Yu-Ling , Zhu Yi-An , Sui Zhi-Jun , Chen De , Zhou Xing-Gui
Published: June 2015

Steam and its dissociated species can be involved in the elementary steps of propane dehydrogenation through two mechanisms.
Synthesis of highly dispersed Pd nanoparticles supported on multi-walled carbon nanotubes and their excellent catalytic performance for oxidation of benzyl alcohol
Authors: Shinde Vijay M. , Skupien Emmanuel , Makkee Michiel
Published: June 2015

A simple approach to synthesize highly dispersed Pd nanoparticles on CNTs without a capping agent is presented which exhibits high activity and selectivity for selective oxidation of benzyl alcohol.
Correction: New knowledge on the antiglycoxidative mechanism of chlorogenic acid
Authors: Fernandez-Gomez Beatriz , Ullate Monica , Picariello Gianluca , Ferranti Pasquale , Dolores Mesa Maria , Dolores del Castillo Maria
Published: June 2015

Correction for ‘New knowledge on the antiglycoxidative mechanism of chlorogenic acid’ by Beatriz Fernandez-Gomez et al., Food Funct., 2015, DOI: 10.1039/c5fo00194c.