bluuebunny/crossref_metadata_2025 huggingface dataset:
Pseudomonas aeruginosa Outbreak in a Neonatal Intensive Care Unit Attributed to Hospital Tap Water
Authors: Bicking Kinsey Cara , Koirala Samir , Solomon Benjamin , Rosenberg Jon , Robinson Byron F. , Neri Antonio , Laufer Halpin Alison , Arduino Matthew J. , Moulton-Meissner Heather , Noble-Wang Judith , Chea Nora , Gould Carolyn V.
Published: May 2017

OBJECTIVE

To investigate an outbreak of Pseudomonas aeruginosa infections and colonization in a neonatal intensive care unit.

DESIGN

Infection control assessment, environmental evaluation, and case-control study.

SETTING

Newly built community-based hospital, 28-bed neonatal intensive care unit.

PATIENTS

Neonatal intensive care unit patients receiving care between June 1, 2013, and September 30, 2014.

METHODS

Case finding was performed through microbiology record review. Infection control observations, interviews, and environmental assessment were performed. A matched case-control study was conducted to identify risk factors for P. aeruginosa infection. Patient and environmental isolates were collected for pulsed-field gel electrophoresis to determine strain relatedness.

RESULTS

In total, 31 cases were identified. Case clusters were temporally associated with absence of point-of-use filters on faucets in patient rooms. After adjusting for gestational age, case patients were more likely to have been in a room without a point-of-use filter (odds ratio [OR], 37.55; 95% confidence interval [CI], 7.16–∞). Case patients had higher odds of exposure to peripherally inserted central catheters (OR, 7.20; 95% CI, 1.75–37.30) and invasive ventilation (OR, 5.79; 95% CI, 1.39–30.62). Of 42 environmental samples, 28 (67%) grew P. aeruginosa. Isolates from the 2 most recent case patients were indistinguishable by pulsed-field gel electrophoresis from water-related samples obtained from these case-patient rooms.

CONCLUSIONS

This outbreak was attributed to contaminated water. Interruption of the outbreak with point-of-use filters provided a short-term solution; however, eradication of P. aeruginosa in water and fixtures was necessary to protect patients. This outbreak highlights the importance of understanding the risks of stagnant water in healthcare facilities.

Infect Control Hosp Epidemiol 2017;38:801–808
Working Despite Having Influenza-Like Illness: Results of An Anonymous Survey of Healthcare Providers Who Care for Transplant Recipients
Authors: Mossad Sherif B. , Deshpande Abhishek , Schramm Sarah , Liu Xiaobo , Rothberg Michael B.
Published: May 2017

OBJECTIVE

To compare the rates of and reasons for presenteeism associated with influenza-like illness (ILI) among healthcare professionals (HCPs) caring for hospitalized inpatient transplant recipients and internal medicine patients.

DESIGN

We designed a 10-question anonymous survey in which ILI was defined as fever (>37.8°C) and cough and/or sore throat and ILI B was defined as fever (>37.8°C) or cough or sore throat; both definitions were considered in the absence of another known cause.

SETTING

Tertiary-care center.

PARTICIPANTS

Physicians, advanced practice providers (APPs) and nurses.

INTERVENTION

Survey deployed at peak of influenza activity in 2016.

MEASUREMENTS

Rates of ILI, presenteeism, wearing masks, and time away due to ILI.

RESULTS

Of 707 HCPs surveyed, 286 (40%) responded; 15 (5.2%) reported having ILI, and 73 (25.5%) reported having ILI B in the preceding 2 weeks. Presenteeism rates were 92% in both groups of HCPs and were higher among women (adjusted odds ratio [AOR], 2.64; 95% CI, 1.23–5.71;P=.01) and those ≤40 years old (AOR, 1.92; 95% CI, 1.03–3.68;P=.04). Healthcare professionals who cared for transplant recipients and female HCPs were more likely to wear masks (AOR, 2.13; 95% CI, 1.05–3.40;P=.04 for transplant recipients and AOR, 3.96; 95% CI, 1.35–11.63;P=.01 for female HCPs). Nurses were more likely than physicians and APPs to take time off (AOR, 3.33; 95% CI, 1.10–10.09;P=.03.)

CONCLUSIONS

Presenteeism among HCPs with ILI is common, including among those caring for transplant recipients. Nonpunitive systems should encourage HCPs not to work with ILI and to wear masks to prevent spread of infections.

Infect Control Hosp Epidemiol2017;38:966–969
Steps Toward Measurement of 135Cs with AMS at CIAE
Authors: Yin Xinyi , He Ming , Dong Kejun , Pang Yijun , Wu Shaoyong , Jiang Shan
Published: May 2017

135Cs with a half-life of T1/2=2.3×106 yr is an important nuclide in studies of the dispersal of nuclear material in the environment. Preliminary measurements using 133Cs as a proxy for the long-lived 135Cs, with accelerator mass spectrometry (AMS) have been developed at the China Institute of Atomic Energy (CIAE). In order to improve the sensitivity of 135Cs AMS measurement, a new conducting material, Fe powder, was used in the experiment. According to the present results, the background level that can be obtained with blanks was 135Ba/Cs~1.83×10–10 with the CIAE-AMS system. These measurements showed that the Fe was an inferior conducting medium because the interference of 135Ba in Fe powder is 10 times higher than that in Ag powder.
The effect ofTetraneura ulmiL. galling process on the activity of amino acid decarboxylases and the content of biogenic amines in Siberian elm tissues
Authors: Kmieć K. , Sempruch C. , Chrzanowski G. , Czerniewicz P.
Published: May 2017

Tetraneura ulmi(L.), a member of Eriosomatinae subfamily, is one of the gall-forming aphids occurring on elms. Sap-sucking behaviour of founding mothers results in the formation of new plant organs. This study documents the changes in the content of plant biogenic amines (putrescine, cadaverine, spermidine, tryptamine, spermine and histamine) and key enzymes of their biosynthesis: lysine decarboxylase (LDC), tyrosine decarboxylase and ornithine decarboxylase (ODC) in galls and other parts of Siberian elm (Ulmus pumilaL.) leaves during the galling process. The direction and intensity of these changes for particular amines and enzymes were dependent on the stage of gall development and part of the galling leaf. Generally, the amine content tended to increase in gall tissues during the 1st and 2nd period of the galling process and decreased in later phases. LDC and ODC activities were markedly enhanced, especially in gall tissues at the initial stage of the galling process.
Hedge Funds: The Good, the Bad, and the Lucky
Authors: Chen Yong , Cliff Michael , Zhao Haibei
Published: May 2017

We develop an estimation approach based on a modified expectation-maximization (EM) algorithm and a mixture of normal distributions associated with skill groups to assess performance in hedge funds. By allowing luck to affect both skilled and unskilled funds, we estimate the number of skill groups, the fraction of funds from each group, and the mean and variability of skill within each group. For each individual fund, we propose a performance measure combining the fund’s estimated alpha with the cross-sectional distribution of fund skill. In out-of-sample tests, an investment strategy using our performance measure outperforms those using estimated alpha andt-statistic.
Evaluation of benzimidazole resistance status in Ascaridia galli
Authors: TARBIAT B. , JANSSON D. S. , TYDÉN E. , HÖGLUND J.
Published: May 2017

Susceptability of Ascaridia galli to benzimidazole (BZ) was investigated using faecal egg count reduction test (FECRT), in ovo larval development test (LDT) and genetic markers (mutations at codons 167, 198 and 200 of β-tubulin gene). Six flocks (F1−F6) of a commercial laying hen farm with different number of exposure to BZ were recruited. The FECR was calculated by analyzing individual faeces (F1, F2, F4 and F5) before and 10 days after treatment. The LDT was performed on parasite eggs from pooled samples from F1 to F6 and LC50 and LC99 were calculated. DNA was extracted from 120 worms and sequenced for β-tubulin gene. In all flocks, the FECRs were above 95% (lower CI above 90%). No significant difference was observed (p > 0·05) among obtained LC50 (F1/F4 and F2/F5 vs F3/F6) in the LDT. However, LC50 and LC99 were higher than suggested values for declaration of resistance in other nematode species. No variation was observed in codon positions involved in BZ resistance. Overall, our results indicated lack of evidence of resistance to BZ in A. galli. More research is needed to confirm these results and to further optimize the existing tools for detection and monitoring of anthelmintic resistance in A. galli.
The changing epidemiology of spinal tuberculosis: the influence of international immigration in Catalonia, 1993–2014
Authors: PEGHIN M. , RODRIGUEZ-PARDO D. , SANCHEZ-MONTALVA A. , PELLISÉ F. , RIVAS A. , TORTOLA T. , AGUILAR J. , ALMIRANTE B. , PIGRAU C.
Published: May 2017

The overall incidence of spinal tuberculosis (TB) appears to be stable or declining in most European countries, but with an increasing proportion of cases in the foreign-born populations. We performed a retrospective observational study (1993–2014), including all cases of spinal TB diagnosed at a Barcelona hospital to assess the epidemiological changes. Fifty-four episodes (48·1% males, median age 52 years) of spinal TB were diagnosed. The percentage of foreign-born residents with spinal TB increased from 14% to 45·2% in the last 10 years (P = 0·017). Positive Mycobacterium tuberculosis testing in vertebral specimens was 88·2% (15/17) for GeneXpert MTB/RIF. Compared with natives, foreign-born patients were younger (P < 0·01) and required surgery more often (P = 0·003) because of higher percentages of paravertebral abscess (P = 0·038), cord compression (P = 0·05), and persistent neurological sequelae (P = 0·05). In our setting, one-third of spinal TB cases occurred in non-native residents. Compared with natives, foreign-born patients were younger and had greater severity of the disease. The GeneXpert MTB/RIF test may be of value for diagnosing spinal TB.
Migration patterns and seasonal forest use by birds in the Brazilian Pantanal
Authors: DE PINHO JOÃO BATISTA , ARAGONA MÔNICA , HAKAMADA KARLO YOSHIHIRO PIOTO , MARINI MIGUEL ÂNGELO
Published: May 2017

The use of forest habitats and migratory patterns are still unclear for tropical birds. Some are described herein for the Pantanal wetlands of Brazil. Thus, our aim was to describe different patterns of forest habitat use by birds and classify the birds’ migration patterns for the northern Pantanal region, Brazil. From September 1999 to December 2003, we sampled four forest types, during which we collected standardised data with mist-net captures and point counts, with additionalad lib.observations. We recorded 214 bird species: 113 (52.8%) were total habitat generalists; 41 (19.2%) were forest generalists; 19 (8.9%) were flooded habitat specialists; and 28 (13.1%) were not classified due to the low number of records; three other categories of habitat use divide the remaining 6% of records. About half of the species showed some migratory behaviour, these were classified by us according to the season they spent in the area: 121 species (56.5%) asresidents, 28 (13.1%) asrun-off and dry migrants, 11 (5.1%) asrun-off(winter)migrants, eight (3.7%) asdry(breeding)migrants, eight (3.7%) asdry and flooding(summer)migrants, eight (3.7%) asflooding migrants, three (1.4%) asflooding and run-off migrants, and 27 (12.6%) asuncommon. We constructed community occupancy models with six of the eight patterns of migration described; flooding migrants and run-off migrants were not modelled since the few species recorded also had very few detections. As expected, the model confirmed that species from all six tested migration patterns arrive and depart from the Pantanal across the seasons. Contrary to most Neotropical forests, there was a high percentage (43.5%) of non-resident species. The results show the need of investing heavily in preserving different landscape units within the Pantanal, but also in the surrounding Cerrado region, in order to conserve resident and short distance intra-tropical migrants.
How Latina mothers navigate a ‘food swamp’ to feed their children: a photovoice approach
Authors: Colón-Ramos Uriyoán , Monge-Rojas Rafael , Cremm Elena , Rivera Ivonne M , Andrade Elizabeth L , Edberg Mark C
Published: May 2017

Objective

To understand how mothers who recently migrated from Central America to the USA feed their children in a neighbourhood saturated with unhealthful food choices (‘food swamp’) and to formulate a mother-driven plan of action to facilitate their acquisition of foods.

Design/Setting/Subjects

We purposively sampled mothers with children (<10 years old) who were recent immigrants/refugees from Central America and lived in a ‘food swamp’ neighbourhood. We used the photovoice approach to elicit textual data from thirty in-depth interviews, a participatory workshop, and visual data from photographs. Analyses were guided by the Social Ecological Framework and Social Cognitive Theory to identify barriers, facilitators and strategies that support parents in feeding their children.

Results

Mothers valued foods that they considered to be ‘traditional’ and ‘healthful’. They navigated their food retail environment looking for these foods (of good quality and well-priced). Food values were reinforced by pre-migration food customs and culture, health professionals’ advice and, in some cases, by the desire to avoid conflict with their children. The neighbourhood food environment could directly influence children’s food preferences and often created conflict between what the child wanted to eat and the foods that mothers valued. Mothers in this ‘food swamp’ wanted to be engaged in addressing the selection of foods offered in schools and in neighbourhood food venues to reflect their own food values.

Conclusions

These mothers’ feeding choices were influenced directly by their food values, and indirectly by the neighbourhood and school food environments via their children’s preferences.
‘Oh you're a guy, how could you be raped by a woman, that makes no sense’: towards a case for legally recognising and labelling ‘forced-to-penetrate’ cases as rape
Authors: Weare Siobhan
Published: May 2017

The existing legal definition of rape in England and Wales is gendered, only recognising men as offenders. The law also only recognises as victims of rape those who are penetrated by a penis, either vaginally, anally or orally. This therefore excludes the female perpetrator–male victim paradigm, and more specifically those cases where male victims are ‘forced to penetrate’ female perpetrators. This paper argues that consideration needs to be given to legally recognising and thus labelling forced-to-penetrate cases as rape. Applying a methodology that draws upon the lived experiences of male victims, it is argued that there are significant similarities between compelled-penetration cases and those cases legally recognised as rape, not only because they both involve non-consensual penile penetration, but because there are clear similarities in the aggressive strategies used by perpetrators and the subsequent harms experienced by victims.
Das Experten-Novizen-Paradigma und die Vertrauenskrise in der Psychologie
Authors: Furley Philip , Schul Karsten , Memmert Daniel
Published: May 2017

Zusammenfassung. Das Ziel des vorliegenden Beitrages ist es anhand eines vielverwendeten Paradigmas in der Sportwissenschaft – dem Experten-Novizen-Vergleich – zu prüfen, ob die momentane Vertrauenskrise in der Psychologie ebenfalls die Sportpsychologie betreffen könnte. Anhand einer exemplarischen Studie zeigen wir, dass es innerhalb dieses Paradigmas zu kontroversen Befunden kommt, welche durch die vermuteten Ursachen der Vertrauenskrise (Researcher Degrees of Freedom, kleine Stichprobengrößen) erklärt sein könnten. Zusätzlich argumentieren wir, dass weitere Faktoren (Konfundierung, Stichprobengrößen, Rosenthal Effekt, Expertise-Definition) innerhalb dieses Paradigmas die Reproduzierbarkeit von Erkenntnissen in Frage stellen. Wir diskutieren mögliche Maßnahmen, wie die dargestellten Probleme des Experten-Novizen-Paradigmas in zukünftigen Forschungsarbeiten gelöst werden können.
Disulfiram/copper selectively eradicates AML leukemia stem cells in vitro and in vivo by simultaneous induction of ROS-JNK and inhibition of NF-κB and Nrf2
Authors: Xu Bing , Wang Shiyun , Li Rongwei , Chen Kai , He Lingli , Deng Manman , Kannappan Vinodh , Zha Jie , Dong Huijuan , Wang Weiguang
Published: May 2017

Acute myeloid leukemia (AML) is a heterogeneous malignancy. Despite the advances in past decades, the clinical outcomes of AML patients remain poor. Leukemia stem cells (LSCs) is the major cause of the recurrence of AML even after aggressive treatment making, promoting development of LSC-targeted agents is an urgent clinical need. Although the antitumor activity of disulfiram (DS), an approved anti-alcoholism drug, has been demonstrated in multiple types of tumors including hematological malignancies such as AML, it remains unknown whether this agent would also be able to target cancer stem cells like LSCs. Here, we report the in vitro and in vivo activity of DS in combination with copper (Cu) against CD34+/CD38+ leukemia stem-like cells sorted from KG1α and Kasumi-1 AML cell lines, as well as primary CD34+ AML samples. DS plus Cu (DS/Cu) displayed marked inhibition of proliferation, induction of apoptosis, and suppression of colony formation in cultured AML cells while sparing the normal counterparts. DS/Cu also significantly inhibited the growth of human CD34+/CD38+ leukemic cell-derived xenografts in NOD/SCID mice. Mechanistically, DS/Cu-induced cytotoxicity was closely associated with activation of the stress-related ROS-JNK pathway as well as simultaneous inactivation of the pro-survival Nrf2 and nuclear factor-κB pathways. In summary, our findings indicate that DS/Cu selectively targets leukemia stem-like cells both in vitro and in vivo, thus suggesting a promising LSC-targeted activity of this repurposed agent for treatment of relapsed and refractory AML.
CAF-secreted CXCL1 conferred radioresistance by regulating DNA damage response in a ROS-dependent manner in esophageal squamous cell carcinoma
Authors: Zhang Hongfang , Yue Jing , Jiang Zhenzhen , Zhou Rongjing , Xie Ruifei , Xu Yiping , Wu Shixiu
Published: May 2017

Five-year survival rate of esophageal squamous cell carcinoma (ESCC) patients treated with radiotherapy is <20%. Our study aimed to investigate whether cancer-associated fibroblasts (CAFs), one major component of tumor microenvironment, were involved in tumor radioresistance in ESCC. By use of human chemokine/cytokine array, human chemokine CXCL1 was found to be highly expressed in CAFs compared with that in matched normal fibroblasts. Inhibition of CXCL1 expression in CAFs significantly reversed CAF-conferred radioresistance in vitro and in vivo. CAF-secreted CXCL1 inhibited the expression of reactive oxygen species (ROS)-scavenging enzyme superoxide dismutase 1, leading to increased ROS accumulation following radiation, by which DNA damage repair was enhanced and the radioresistance was mediated. CAF-secreted CXCL1 mediated the radioresistance also by activation of Mek/Erk pathway. The cross talk of CAFs and ESCC cells induced CXCL1 expression in an autocrine/paracrine signaling loop, which further enhanced tumor radioresistance. Together, our study highlighted CAF-secreted CXCL1 as an attractive target to reverse tumor radioresistance and can be used as an independent prognostic factor of ESCC patients treated with chemoradiotherapy.
ASIC1 and ASIC3 contribute to acidity-induced EMT of pancreatic cancer through activating Ca2+/RhoA pathway
Authors: Zhu Shuai , Zhou Hai-Yun , Deng Shi-Chang , Deng Shi-Jiang , He Chi , Li Xiang , Chen Jing-Yuan , Jin Yan , Hu Zhuang-Li , Wang Fang , Wang Chun-You , Zhao Gang
Published: May 2017

Extracellular acid can have important effects on cancer cells. Acid-sensing ion channels (ASICs), which emerged as key receptors for extracellular acidic pH, are differently expressed during various diseases and have been implicated in underlying pathogenesis. This study reports that ASIC1 and ASIC3 are mainly expressed on membrane of pancreatic cancer cells and upregulated in pancreatic cancer tissues. ASIC1 and ASIC3 are responsible for an acidity-induced inward current, which is required for elevation of intracellular Ca2+ concentration ([Ca2+]i). Inhibition of ASIC1 and ASIC3 with siRNA or pharmacological inhibitor significantly decreased [Ca2+]i and its downstream RhoA during acidity and, thus, suppressed acidity-induced epithelial–mesenchymal transition (EMT) of pancreatic cancer cells. Meanwhile, downregulating [Ca2+]i with calcium chelating agent BAPTA-AM or knockdown of RhoA with siRNA also significantly repressed acidity-induced EMT of pancreatic cancer cells. Significantly, although without obvious effect on proliferation, knockdown of ASIC1 and ASIC3 in pancreatic cancer cells significantly suppresses liver and lung metastasis in xenograft model. In addition, ASIC1 and ASIC3 are positively correlated with expression of mesenchymal marker vimentin, but inversely correlated with epithelial marker E-cadherin in pancreatic cancer cells. In conclusion, this study indicates that ASICs are master regulator of acidity-induced EMT. In addition, the data demonstrate a functional link between ASICs and [Ca2+]i/RhoA pathway, which contributes to the acidity-induced EMT.
RACK1 depletion in the ribosome induces selective translation for non-canonical autophagy
Authors: Kim Hag Dong , Kong EunBin , Kim YongJoong , Chang Jin-Soo , Kim Joon
Published: May 2017

RACK1, which was first demonstrated as a substrate of PKCβ II, functions as a scaffold protein and associates with the 40S small ribosomal subunit. According to previous reports, ribosomal RACK1 was also suggested to control translation depending on the status in translating ribosome. We here show that RACK1 knockdown induces autophagy independent of upstream canonical factors such as Beclin1, Atg7 and Atg5/12 conjugates. We further report that RACK1 knockdown induces the association of mRNAs of LC3 and Bcl-xL with polysomes, indicating increased translation of these proteins. Therefore, we propose that the RACK1 depletion-induced autophagy is distinct from canonical autophagy. Finally, we confirm that cells expressing mutant RACK1 (RACK1R36D/K38E) defective in ribosome binding showed the same result as RACK1-knockdown cells. Altogether, our data clearly show that the depletion of ribosomal RACK1 alters the capacity of the ribosome to translate specific mRNAs, resulting in selective translation of mRNAs of genes for non-canonical autophagy induction.
The first Japanese case of central precocious puberty with a novel MKRN3 mutation
Authors: Nishioka Junko , Shima Hirohito , Fukami Maki , Yatsuga Shuichi , Matsumoto Takako , Ushijima Kikumi , Kitamura Miyuki , Koga Yasutoshi
Published: May 2017

MKRN3, located on chromosome 15q11.2, encodes makorin ring-finger 3, which is an upstream suppressor of the hypothalamic-pituitary-gonadal axis. Mutation of this gene induces central precocious puberty (CPP). As MKRN3 is maternally imprinted, only the paternal allele is expressed. This is the first report of an 8-year-old Japanese girl with CPP caused by a novel frameshift mutation in MKRN3 (p.Glu229Argfs*3).
Vagal determinants of exercise capacity
Authors: Machhada Asif , Trapp Stefan , Marina Nephtali , Stephens Robert C.M. , Whittle John , Lythgoe Mark F. , Kasparov Sergey , Ackland Gareth L. , Gourine Alexander V.
Published: May 2017

Indirect measures of cardiac vagal activity are strongly associated with exercise capacity, yet a causal relationship has not been established. Here we show that in rats, genetic silencing of the largest population of brainstem vagal preganglionic neurons residing in the brainstem’s dorsal vagal motor nucleus dramatically impairs exercise capacity, while optogenetic recruitment of the same neuronal population enhances cardiac contractility and prolongs exercise endurance. These data provide direct experimental evidence that parasympathetic vagal drive generated by a defined CNS circuit determines the ability to exercise. Decreased activity and/or gradual loss of the identified neuronal cell group provides a neurophysiological basis for the progressive decline of exercise capacity with aging and in diverse disease states.
Equilibrium oxygen storage capacity of ultrathin CeO2-δ depends non-monotonically on large biaxial strain
Authors: Balaji Gopal Chirranjeevi , García-Melchor Max , Lee Sang Chul , Shi Yezhou , Shavorskiy Andrey , Monti Matteo , Guan Zixuan , Sinclair Robert , Bluhm Hendrik , Vojvodic Aleksandra , Chueh William C.
Published: May 2017

Elastic strain is being increasingly employed to enhance the catalytic properties of mixed ion–electron conducting oxides. However, its effect on oxygen storage capacity is not well established. Here, we fabricate ultrathin, coherently strained films of CeO2-δ between 5.6% biaxial compression and 2.1% tension. In situ ambient pressure X-ray photoelectron spectroscopy reveals up to a fourfold enhancement in equilibrium oxygen storage capacity under both compression and tension. This non-monotonic variation with strain departs from the conventional wisdom based on a chemical expansion dominated behaviour. Through depth profiling, film thickness variations and a coupled photoemission–thermodynamic analysis of space-charge effects, we show that the enhanced reducibility is not dominated by interfacial effects. On the basis of ab initio calculations of oxygen vacancy formation incorporating defect interactions and vibrational contributions, we suggest that the non-monotonicity arises from the tetragonal distortion under large biaxial strain. These results may guide the rational engineering of multilayer and core–shell oxide nanomaterials.
Electrostatic melting in a single-molecule field-effect transistor with applications in genomic identification
Authors: Vernick Sefi , Trocchia Scott M. , Warren Steven B. , Young Erik F. , Bouilly Delphine , Gonzalez Ruben L. , Nuckolls Colin , Shepard Kenneth L.
Published: May 2017

The study of biomolecular interactions at the single-molecule level holds great potential for both basic science and biotechnology applications. Single-molecule studies often rely on fluorescence-based reporting, with signal levels limited by photon emission from single optical reporters. The point-functionalized carbon nanotube transistor, known as the single-molecule field-effect transistor, is a bioelectronics alternative based on intrinsic molecular charge that offers significantly higher signal levels for detection. Such devices are effective for characterizing DNA hybridization kinetics and thermodynamics and enabling emerging applications in genomic identification. In this work, we show that hybridization kinetics can be directly controlled by electrostatic bias applied between the device and the surrounding electrolyte. We perform the first single-molecule experiments demonstrating the use of electrostatics to control molecular binding. Using bias as a proxy for temperature, we demonstrate the feasibility of detecting various concentrations of 20-nt target sequences from the Ebolavirus nucleoprotein gene in a constant-temperature environment.
A complete tool set for molecular QTL discovery and analysis
Authors: Delaneau Olivier , Ongen Halit , Brown Andrew A. , Fort Alexandre , Panousis Nikolaos I. , Dermitzakis Emmanouil T.
Published: May 2017

Population scale studies combining genetic information with molecular phenotypes (for example, gene expression) have become a standard to dissect the effects of genetic variants onto organismal phenotypes. These kinds of data sets require powerful, fast and versatile methods able to discover molecular Quantitative Trait Loci (molQTL). Here we propose such a solution, QTLtools, a modular framework that contains multiple new and well-established methods to prepare the data, to discover proximal and distal molQTLs and, finally, to integrate them with GWAS variants and functional annotations of the genome. We demonstrate its utility by performing a complete expression QTL study in a few easy-to-perform steps. QTLtools is open source and available at https://qtltools.github.io/qtltools/.
Ccl2/Ccr2 signalling recruits a distinct fetal microchimeric population that rescues delayed maternal wound healing
Authors: Castela Mathieu , Nassar Dany , Sbeih Maria , Jachiet Marie , Wang Zhe , Aractingi Selim
Published: May 2017

Foetal microchimeric cells (FMCs) traffic into maternal circulation during pregnancy and persist for decades after delivery. Upon maternal injury, FMCs migrate to affected sites where they participate in tissue healing. However, the specific signals regulating the trafficking of FMCs to injury sites had to be identified. Here we report that, in mice, a subset of FMCs implicated in tissue repair displays CD11b+ CD34+ CD31+ phenotype and highly express C-C chemokine receptor 2 (Ccr2). The Ccr2 ligand chemokine ligand 2 (Ccl2) enhances the recruitment of FMCs to maternal wounds where these cells transdifferentiate into endothelial cells and stimulate angiogenesis through Cxcl1 secretion. Ccl2 administration improves delayed maternal wound healing in pregnant and postpartum mice but never in virgin ones. This role of Ccl2/Ccr2 signalling opens new strategies for tissue repair through natural stem cell therapy, a concept that can be later applied to other types of maternal diseases.
Self-folding origami at any energy scale
Authors: Pinson Matthew B. , Stern Menachem , Carruthers Ferrero Alexandra , Witten Thomas A. , Chen Elizabeth , Murugan Arvind
Published: May 2017

Programmable stiff sheets with a single low-energy folding motion have been sought in fields ranging from the ancient art of origami to modern meta-materials research. Despite such attention, only two extreme classes of crease patterns are usually studied; special Miura-Ori-based zero-energy patterns, in which crease folding requires no sheet bending, and random patterns with high-energy folding, in which the sheet bends as much as creases fold. We present a physical approach that allows systematic exploration of the entire space of crease patterns as a function of the folding energy. Consequently, we uncover statistical results in origami, finding the entropy of crease patterns of given folding energy. Notably, we identify three classes of Mountain-Valley choices that have widely varying ‘typical’ folding energies. Our work opens up a wealth of experimentally relevant self-folding origami designs not reliant on Miura-Ori, the Kawasaki condition or any special symmetry in space.
Magnetooptical determination of a topological index
Authors: Assaf Badih A. , Phuphachong Thanyanan , Volobuev Valentine V. , Bauer Günther , Springholz Gunther , de Vaulchier Louis-Anne , Guldner Yves
Published: May 2017

When a Dirac fermion system acquires an energy-gap, it is said to have either trivial (positive energy-gap) or non-trivial (negative energy-gap) topology, depending on the parity ordering of its conduction and valence bands. The non-trivial regime is identified by the presence of topological surface or edge-states dispersing in the energy gap of the bulk and is attributed a non-zero topological index. In this work, we show that such topological indices can be determined experimentally via an accurate measurement of the effective velocity of bulk massive Dirac fermions. We demonstrate this approach analytically starting from the Bernevig-Hughes-Zhang Hamiltonian to show how the topological index depends on this velocity. We then experimentally extract the topological index in Pb
1-x
Sn
x
Se and Pb1-x
Sn
x
Te using infrared magnetooptical Landau level spectroscopy. This approach is argued to be universal to all material classes that can be described by a Bernevig-Hughes-Zhang-like model and that host a topological phase transition.
Bioelectric regulation of innate immune system function in regenerating and intact Xenopus laevis
Authors: Paré Jean-François , Martyniuk Christopher J. , Levin Michael
Published: May 2017

Two key inputs that regulate regeneration are the function of the immune system, and spatial gradients of transmembrane potential (Vmem). Endogenous bioelectric signaling in somatic tissues during regenerative patterning is beginning to be understood, but its role in the context of immune response has never been investigated. Here, we show that Vmem levels modulate innate immunity activity in Xenopus laevis embryos. We developed an assay in which X. laevis embryos are infected with a uropathogenic microorganism, in the presence or absence of reagents that modify Vmem, prior to the ontogenesis of the adaptive immune system. General depolarization of the organism’s Vmem by pharmacological or molecular genetic (ion channel misexpression) methods increased resistance to infection, while hyperpolarization made the embryos more susceptible to death by infection. Hyperpolarized specimens harbored a higher load of infectious microorganisms when compared to controls. We identified two mechanisms by which Vmem mediates immune function: serotonergic signaling involving melanocytes and an increase in the number of primitive myeloid cells. Bioinformatics analysis of genes whose transcription is altered by depolarization revealed a number of immune system targets consistent with mammalian data. Remarkably, amputation of the tail bud potentiates systemic resistance to infection by increasing the number of peripheral myeloid cells, revealing an interplay of regenerative response, innate immunity, and bioelectric regulation. Our study identifies bioelectricity as a new mechanism by which innate immune response can be regulated in the context of infection or regeneration. Vmem modulation using drugs already approved for human use could be exploited to improve resistance to infections in clinical settings.
Secondary metabolite genes encoded by potato rhizosphere microbiomes in the Andean highlands are diverse and vary with sampling site and vegetation stage
Authors: Aleti Gajender , Nikolić Branislav , Brader Günter , Pandey Ram Vinay , Antonielli Livio , Pfeiffer Stefan , Oswald Andreas , Sessitsch Angela
Published: May 2017

Potato (Solanum tuberosum) is an important staple crop worldwide, it has been cultivated in the Andean Altiplano under low-input farming practices at high altitudes and under harsh environment for centuries. We analyzed secondary metabolite (SM) gene diversity encoded in the potato rhizosphere microbiome during plant growth at three distinct sites located in the Andes at high altitudes by 454-pyrosequencing of non-ribosomal peptide and polyketide biosynthetic genes. Phylogenetic analysis indicated that the majority of rhizosphere SM-encoding sequences differed from previously known sequences and may have distinct ancestors. In particular, actinobacterial methyl-malonyl-CoA transferase and acyl carrier protein from Firmicutes, both involved in the synthesis of SMs, showed widespread distribution of clades which were clearly distinct from sequences deposited in public databases, and only 11% of these sequences could be linked to the production of specific classes of SMs. Although the same cultivar was analyzed, SM gene composition radically differed among plant growth stages and across sites, suggesting a distinct repertoire of SM genes that likely encode diverse SM structures. Also, great diversity of non-ribosomal peptide and polyketide biosynthetic pathways in potato-associated microbiomes in the Andean highlands may represent a rich source of novel natural products.
Phylogeography of the Tyrrhenian red deer (Cervus elaphus corsicanus) resolved using ancient DNA of radiocarbon-dated subfossils
Authors: Doan K. , Zachos F. E. , Wilkens B. , Vigne J.-D. , Piotrowska N. , Stanković A. , Jędrzejewska B. , Stefaniak K. , Niedziałkowska M.
Published: May 2017

We present ancient mitochondrial DNA analyses of 31 complete cytochrome b gene sequences from subfossil red deer remains from the Tyrrhenian islands (Corsica and Sardinia) and mainland Italy in a European-wide phylogeographic framework. Tyrrhenian and North African red deer, both going back to human introductions, were previously the only red deer to harbour the mitochondrial B lineage whose origin, however, remained unknown. Our ancient Italian samples from the central part of the peninsula that were radiocarbon-dated to an age of ca. 6300 to 15 600 cal BP all showed B haplotypes, closely related or even identical to those found on Sardinia. Genetic diversity in the mainland population was considerably higher than on the islands. Together with palaeontological evidence our genetic results identify the Italian Peninsula as the ultimate origin of the B lineage and thus the Tyrrhenian and North African red deer. This is in line with previous biogeographic findings that uncovered distinct intraspecific phylogeographic lineages in Italian mammals, underlining Italy’s status as a hotspot of European mammalian diversity.
Atorvastatin Promotes Phagocytosis and Attenuates Pro-Inflammatory Response in Human Retinal Pigment Epithelial Cells
Authors: Tian Bo , Al-Moujahed Ahmad , Bouzika Peggy , Hu Yijun , Notomi Shoji , Tsoka Pavlina , Miller Joan W. , Lin Haijiang , Vavvas Demetrios G.
Published: May 2017

Phagocytosis of daily shed photoreceptor outer segments is an important function of the retinal pigment epithelium (RPE) and it is essential for retinal homeostasis. RPE dysfunction, especially impairment of its phagocytic ability, plays an essential role in the pathogenesis of age-related macular degeneration (AMD). Statins, or HMG CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors, are drugs with multiple properties that have been extensively used to treat hyperlipidemia. However, their effect on RPE cells has not been fully elucidated. Here we report that high dose atorvastatin increased the phagocytic function of ARPE-19 cells, as well as rescue the cells from the phagocytic dysfunction induced by cholesterol crystals and oxidized low-density lipoproteins (ox-LDL), potentially by increasing the cellular membrane fluidity. Similar effects were observed when evaluating two other hydrophobic statins, lovastatin and simvastatin. Furthermore, atorvastatin was able to block the induction of interleukins IL-6 and IL-8 triggered by pathologic stimuli relevant to AMD, such as cholesterol crystals and ox-LDL. Our study shows that statins, a well-tolerated class of drugs with rare serious adverse effects, help preserve the phagocytic function of the RPE while also exhibiting anti-inflammatory properties. Both characteristics make statins a potential effective medication for the prevention and treatment of AMD.
Prostaglandin E2 glyceryl ester is an endogenous agonist of the nucleotide receptor P2Y6
Authors: Brüser Antje , Zimmermann Anne , Crews Brenda C. , Sliwoski Gregory , Meiler Jens , König Gabriele M. , Kostenis Evi , Lede Vera , Marnett Lawrence J. , Schöneberg Torsten
Published: May 2017

Cyclooxygenase-2 catalyses the biosynthesis of prostaglandins from arachidonic acid but also the biosynthesis of prostaglandin glycerol esters (PG-Gs) from 2-arachidonoylglycerol. Previous studies identified PG-Gs as signalling molecules involved in inflammation. Thus, the glyceryl ester of prostaglandin E2, PGE2-G, mobilizes Ca2+ and activates protein kinase C and ERK, suggesting the involvement of a G protein-coupled receptor (GPCR). To identify the endogenous receptor for PGE2-G, we performed a subtractive screening approach where mRNA from PGE2-G response-positive and -negative cell lines was subjected to transcriptome-wide RNA sequencing analysis. We found several GPCRs that are only expressed in the PGE2-G responder cell lines. Using a set of functional readouts in heterologous and endogenous expression systems, we identified the UDP receptor P2Y6 as the specific target of PGE2-G. We show that PGE2-G and UDP are both agonists at P2Y6, but they activate the receptor with extremely different EC50 values of ~1 pM and ~50 nM, respectively. The identification of the PGE2-G/P2Y6 pair uncovers the signalling mode of PG-Gs as previously under-appreciated products of cyclooxygenase-2.
Early-onset mild cognitive impairment in Parkinson’s disease: Altered corticopetal cholinergic network
Authors: Kim Injoong , Shin Na-Young , Yunjin Bak  , Hyu Lee Phil , Lee Seung-Koo , Mee Lim Soo
Published: May 2017

Degeneration of the substantia innominata (SI) is significantly correlated with cognitive performance in Parkinson’s disease (PD). We examined functional and structural patterns of SI degeneration in drug-naïve PD patients according to the duration of parkinsonism before mild cognitive impairment (MCI) diagnosis. Twenty PD patients with a shorter duration (PD-MCI-SD, <1 year), 18 patients with a longer duration (PD-MCI-LD, ≥1 year), and 29 patients with intact cognition (PD-IC) were included. Seed-based resting-state functional connectivity (rsFC) analysis using bilateral SI seed and region-of-interest-based volumetric analysis were performed. Compared to PD-IC, the collapsed PD-MCI group showed altered rsFC in the right frontal and bilateral parietal areas. PD-MCI-SD showed rsFC alteration in broader frontal and parietal areas compared to the other groups. Decreased rsFC in the right frontal area was also significantly correlated with shorter disease duration. No significant SI volume change was found between the groups. Altered rsFC between the SI and the frontal and parietal areas might be relevant to cognitive dysfunction in PD. Decreased rsFC between the SI and frontal area might be associated with early-onset MCI, suggesting that cholinergic deficits in the frontal brain areas might play an important role in the acceleration of cognitive decline in PD.
Effect of excitation power on voltage induced local magnetization dynamics in an ultrathin CoFeB film
Authors: Rana Bivas , Fukuma Yasuhiro , Miura Katsuya , Takahashi Hiromasa , Otani YoshiChika
Published: May 2017

Voltage or electric field induced magnetization dynamics promises low power spintronics devices. For successful operation of some spintronics devices such as magnetic oscillators and magnetization switching devices a clear understanding of nonlinear magnetization dynamics is required. Here, we report a detailed experimental and micromagnetic simulation study about the effect of excitation power on voltage induced local magnetization dynamics in an ultrathin CoFeB film. Experimental results show that the resonance line-width and frequency remains constant, whereas cone angle of the magnetization precession increases linearly with square-root of excitation power below threshold value, known as linear excitation regime. Above threshold power, the dynamics enters into nonlinear regime where resonance line-width monotonically increases and resonance frequency monotonically decreases with increasing excitation power. Simulation results reveal that a strong nonlinear and incoherent magnetization dynamics are observed in our experiment above the threshold power which reduces dynamic magnetic signal by suppressing large cone angle of magnetization precession. Moreover, a significant transfer of spin angular momentum from uniform FMR mode to its degenerate spin waves outside of excitation area further restrict the cone angle of precession within only few degrees in our device. Our results will be very useful to develop all-voltage-controlled spintronics devices.
Fluorescent RNA cytosine analogue – an internal probe for detailed structure and dynamics investigations
Authors: Füchtbauer Anders Foller , Preus Søren , Börjesson Karl , McPhee Scott A. , Lilley David M. J. , Wilhelmsson L. Marcus
Published: May 2017

The bright fluorescent cytosine analogue tCO stands out among fluorescent bases due to its virtually unquenched fluorescence emission in duplex DNA. However, like most reported base analogues, it has not been thoroughly characterized in RNA. We here report on the first synthesis and RNA-incorporation of tCO, and characterize its base-mimicking and fluorescence properties in RNA. As in DNA, we find a high quantum yield inside RNA duplexes (<ΦF> = 0.22) that is virtually unaffected by the neighbouring bases (ΦF = 0.20–0.25), resulting in an average brightness of 1900 M−1 cm−1. The average fluorescence lifetime in RNA duplexes is 4.3 ns and generally two lifetimes are required to fit the exponential decays. Fluorescence properties in ssRNA are defined by a small increase in average quantum yield (<ΦF > = 0.24) compared to dsRNA, with a broader distribution (ΦF = 0.17–0.34) and slightly shorter average lifetimes. Using circular dichroism, we find that the tCO-modified RNA duplexes form regular A-form helices and in UV-melting experiments the stability of the duplexes is only slightly higher than that of the corresponding natural RNA (<ΔTm> = + 2.3 °C). These properties make tCO a highly interesting fluorescent RNA base analogue for detailed FRET-based structural measurements, as a bright internal label in microscopy, and for fluorescence anisotropy measurements of RNA dynamics.
A soluble starch synthase I gene, IbSSI, alters the content, composition, granule size and structure of starch in transgenic sweet potato
Authors: Wang Yannan , Li Yan , Zhang Huan , Zhai Hong , Liu Qingchang , He Shaozhen
Published: May 2017

Soluble starch synthase I (SSI) is a key enzyme in the biosynthesis of plant amylopectin. In this study, the gene named IbSSI, was cloned from sweet potato, an important starch crop. A high expression level of IbSSI was detected in the leaves and storage roots of the sweet potato. Its overexpression significantly increased the content and granule size of starch and the proportion of amylopectin by up-regulating starch biosynthetic genes in the transgenic plants compared with wild-type plants (WT) and RNA interference plants. The frequency of chains with degree of polymerization (DP) 5–8 decreased in the amylopectin fraction of starch, whereas the proportion of chains with DP 9–25 increased in the IbSSI-overexpressing plants compared with WT plants. Further analysis demonstrated that IbSSI was responsible for the synthesis of chains with DP ranging from 9 to 17, which represents a different chain length spectrum in vivo from its counterparts in rice and wheat. These findings suggest that the IbSSI gene plays important roles in determining the content, composition, granule size and structure of starch in sweet potato. This gene may be utilized to improve the content and quality of starch in sweet potato and other plants.
Recalcitrant carbon components in glomalin-related soil protein facilitate soil organic carbon preservation in tropical forests
Authors: Zhang Jing , Tang Xuli , Zhong Siyuan , Yin Guangcai , Gao Yifei , He Xinhua
Published: May 2017

Glomalin-related soil protein (GRSP) is known as an important microbial by-product which is crucial for preserving or accumulating soil organic carbon (SOC). However, the underlying mechanisms are not well understood. In this study, we investigated the chemical structures of GRSP and its relationship with SOC using 13C nuclear magnetic resonance (NMR) in three tropical forests. The three forests, including a planted forest (PF), a secondary forest (MF) and a primary forest (BF), were selected to represent the natural successional process after disturbance in southern China. Results showed that the average concentrations of GRSP were (3.94 ± 1.09) mg cm−3 and accounting for (3.38 ± 1.15)% of the SOC in the top 10 cm soil. NMR analysis indicated rich aromatic C (~30%) and carboxyl C (~40%) in GRSP, and abundant alkyl C (~30%) and O-alkyl C (~50%) in SOC. The recalcitrance indexes (RI), as defined as the ratio of sum of alkyl C and aromatic C over sum of O-alkyl C and carboxyl C, was (98.6 ± 18.9)%, (145.5 ± 10.9)% and (20.7 ± 0.3)% in GRSP higher than that in SOC in the PF, MF and BF, respectively. This study demonstrated that the stubborn structure of GRSP probably regulate the resistance of SOC sequestration in tropical forests, especially in the planted and secondary forests.