bluuebunny/crossref_metadata_2025 huggingface dataset:
Nocardia
Authors: Chazen Geoffrey
Published: August 2016

In 1888, Nocard isolated the microorganism responsible for a disease in cattle known as farcy. Eppinger, in 1890, isolated the same pathogen from man. With time, this aerobic gram-positive, partially acid-fast, branching rod became known asNocardia. WhetherNocardiais a bacterium or fungus was debated for some years.Nocardiahas now been classified according to Bergey's system as a bacterium in group 17, order 1: Actinomycetales, family VI: Nocardiaceae.
Diffusion and Adoption of CDC Guidelines for the Prevention and Control of Nosocomial Infections in US Hospitals
Authors: Celentano David D. , Morlock Laura L. , Malitz Faye E.
Published: August 2016

Since 1981, the Centers for Disease Control (CDC) has been publishing Guidelines for the Prevention and Control of Nosocomial Infections as a useful reference tool in infection control. The extent to which practices recommended by CDC to reduce hospital-acquired infections have been successfully diffused and adopted were evaluated in a stratified random sample of 445 US hospitals that were sent a questionnaire in 1985. The data suggest that over 84% of infection control practitioner respondents (78% response rate) are aware of each guideline, although small hospitals (<50 beds) are least likely to be aware of the guidelines or to have reviewed them thoroughly. Adoption of the recommendations remains far from universal, ranging from 23% to 75% for 16 specific recommendations investigated. Smaller hospitals were significantly less likely than large hospitals to have adopted each suggested policy. Recommendations that carried Category I rankings were more likely to be adopted, as were those procedures that had cost-savings implications.
The Detection of Blood on Nonporous Environmental Surfaces: An Approach for Assessing Factors Contributing to the Risk of Occupational Exposure to Blood in the Autopsy Suite
Authors: Beaumont Lorraine R.
Published: August 2016

A simple and inexpensive method to assess the contamination of environmental surfaces and the associated potential risk of exposure of autopsy room personnel to potentially hazardous materials is described. Blood was selected as a marker of contamination and HEMASTIX® reagent strips were used to determine its presence on selected surfaces. The surfaces selected for examination typically do not come into direct contact with cadavers or tissues during a routine postmortem examination and thus are not included in routine cleanup. We documented the presence of blood on a variety of environmental surfaces in the autopsy suite and suggest that the contamination resulted from a breakdown in good work practices, most probably the indiscriminate handling or touching of materials and equipment with contaminated gloves. The risk of exposure to blood by the indirect route was deemed significant. The results of this study underscore the importance of establishing and consistently following good work practices and cleanup procedures to minimize the risk of exposure to blood before, during, and after postmortem examinations.
Acyclovir
Authors: Zabrosky Cynthia Ann , Milkovich Gary
Published: August 2016

In recent years there have been great advances made in antiviral therapy. One of the most promising of the new agents to be introduced is acyclovir. This antiviral, which selectively inhibits the replication of particular DNA viruses, is being used clinically in the treatment and prevention of viral infections caused by several of the herpes viruses. Though not a cure, acyclovir can be effective for the management of symptoms associated with these infections. Since acyclovir acts only on replicating viral DNA, the drug has no effect on the latent virus which establishes itself in neural tissue. This makes eradication of the virus very difficult.
Nosocomial Infection in an Intensive-Care Unit Identification of Risk Factors
Authors: Fernandez-Crehuet Rafael , Diaz-Molina Carmen , de Irala Jokin , Martinez-Concha Diego , Salcedo-Leal Inmaculada , Masa-Calles Josefa
Published: August 2016

Objective:

To identify risk factors predictive of nosocomial infection in an intensive-care unit (ICU) and to identify patients with a higher risk of nosocomial infection using a predictive model of nosocomial infection in our ICU.

Design:

Prospective study; daily concurrent surveillance of intensive-care-unit patients.

Setting/Patients:

All patients admitted for at least 24 hours to the ICU of a tertiary-level hospital from February to November 1994 were followed daily.

Methods:

Variables measuring extrinsic and intrinsic risk factors for nosocomial infection were collected on each patient during their ICU stay, and the Cox Proportional Hazards multivariable technique was used to identify the variables significantly associated with infection.

Results:

The population studied consisted of 944 patients. The main risk factors identified were intrinsic; the significant extrinsic risk ofactors identified were head of the bed in a horizontal (<30°) position (this variable presented the highest increase of the infection hazard ratio) and the use of sedative medication. Patients presenting the highest risk scores using the predictive model are those with the highest risk of nosocomial infection.

Conclusion:

The important preventive measures derived from our results are that underlying conditions suffered by the patient at the ICU admission should be corrected promptly, the depression of the patient's level of consciousness with sedatives should be monitored carefully, and the horizontal position of the head of the bed should be avoided totally. Patients with a high risk of infection can be the target of special preventive measures.
Strategies to Prevent Central Line-Associated Bloodstream Infections in Acute Care Hospitals: 2014 Update
Authors: Marschall Jonas , Mermel Leonard A. , Fakih Mohamad , Hadaway Lynn , Kallen Alexander , O’Grady Naomi P. , Pettis Ann Marie , Rupp Mark E. , Sandora Thomas , Maragakis Lisa L. , Yokoe Deborah S.
Published: August 2016

Previously published guidelines are available that provide comprehensive recommendations for detecting and preventing healthcare-associated infections (HAIs). The intent of this document is to highlight practical recommendations in a concise format designed to assist acute care hospitals in implementing and prioritizing their central line-associated bloodstream infection (CLABSI) prevention efforts. This document updates “Strategies to Prevent Central Line-Associated Bloodstream Infections in Acute Care Hospitals,” published in 2008. This expert guidance document is sponsored by the Society for Healthcare Epidemiology of America (SHEA) and is the product of a collaborative effort led by SHEA, the Infectious Diseases Society of America (IDSA), the American Hospital Association (AHA), the Association for Professionals in Infection Control and Epidemiology (APIC), and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise. The list of endorsing and supporting organizations is presented in the introduction to the 2014 updates.
Outcomes of Patients with Healthcare-Associated Pneumonia: Worse Disease or Sicker Patients?
Authors: Rothberg Michael B. , Haessler Sarah , Lagu Tara , Lindenauer Peter K. , Pekow Penelope S. , Priya Aruna , Skiest Daniel , Zilberberg Marya D.
Published: August 2016

Background.

Healthcare-associated pneumonia (HCAP) is an entity distinct from community-acquired pneumonia (CAP). HCAP has a higher case-fatality rate, due either to HCAP organisms or to the health status of HCAP patients. The contribution of HCAP criteria to case-fatality rate is unknown.

Methods.

We conducted a retrospective review of adult patients admitted with a diagnosis of pneumonia from July 2007 through November 2011 to 491 US hospitals. HCAP was defined as having at least 1 of the following: prior hospitalization within 90 days, hemodialysis, admission from a skilled nursing facility, or immune suppression. We compared characteristics of patients with CAP and patients with HCAP and explored the contribution of HCAP criteria to case-fatality rate in a hierarchical generalized linear model.

Results.

Of 436,483 patients hospitalized with pneumonia, 149,963 (34.4%) had HCAP. Compared to CAP patients, HCAP patients were older, had more comorbidities, and were more likely to require intensive care unit (ICU) care. In-hospital case-fatality rate was higher among patients with HCAP, compared to those with CAP (11.1% vs 5.1%, P < .001). After adjustment for demographics, comorbidities, presence of other infections, early ICU admission, chronic and acute medications, early tests and therapies, and length of stay, HCAP remained associated with increased case-fatality rate (odds ratio [OR], 1.35 [95% confidence interval (CI), 1.32-1.39]); odds of death increased for each additional HCAP criterion (OR [95% CI]: 1 criterion, 1.27 [1.23-1.31], 2 criteria, 1.55 [1.49-1.62], and 3 or more criteria, 1.88 [1.72-2.06]).

Conclusions.

After adjustment for differences in patient characteristics, HCAP was associated with greater case-fatality rate than CAP. This difference may be due to HCAP organisms or to HCAP criteria themselves.
Detection of core–periphery structure in networks using spectral methods and geodesic paths
Authors: CUCURINGU MIHAI , ROMBACH PUCK , LEE SANG HOON , PORTER MASON A.
Published: August 2016

We introduce several novel and computationally efficient methods for detecting “core–periphery structure” in networks. Core–periphery structure is a type of mesoscale structure that consists of densely connected core vertices and sparsely connected peripheral vertices. Core vertices tend to be well-connected both among themselves and to peripheral vertices, which tend not to be well-connected to other vertices. Our first method, which is based on transportation in networks, aggregates information from many geodesic paths in a network and yields a score for each vertex that reflects the likelihood that that vertex is a core vertex. Our second method is based on a low-rank approximation of a network's adjacency matrix, which we express as a perturbation of a tensor-product matrix. Our third approach uses the bottom eigenvector of the random-walk Laplacian to infer a coreness score and a classification into core and peripheral vertices. We also design an objective function to (1) help classify vertices into core or peripheral vertices and (2) provide a goodness-of-fit criterion for classifications into core versus peripheral vertices. To examine the performance of our methods, we apply our algorithms to both synthetically generated networks and a variety of networks constructed from real-world data sets.
Hazardous Beginnings
Authors: Saunders Kay , Spearritt Katie
Published: August 2016

Europeans living in the northern half of the Australian continent during the nineteenth century were united, and spurred on by, a dominant ideology of material progress, combined with a strong fear of being engulfed, both numerically and culturally, by foreign invaders. These bulwarks of Eurocentricism gave voice to strongly pro-natalist policies, coupled with intense immigration drives. The image of vast, uninhabited stretches of country waiting to be tamed by resolute, hard-working Britons added to the momentum for increased population. Progress, conceived in the masculinist framework of aggressive expansion, ruthless destruction of the Aboriginal people, economic development and environmental exploitation, needed not only capital, brawn and sheer determination to succeed but, also, healthy young citizens. Demographers graphs, however, fuelled anxiety that this dream might be undermined - for infant and maternal mortality rates in the tropics and sub-tropics were high compared with the rest of Australia and Britain. Masculinist attributes alone could not build the new society. Childbirth was potentially a hazardous and lethal undertaking which threatened to deprive the nascent colony of many fertile women and, in their demise, future generations.
Relative Poverty, British Social Policy Writing and Public Experience
Authors: Dunn Andrew
Published: August 2016

Relative poverty, a concept developed by left-wing social scientists, categorises as ‘poor’ those who fall seriously behind normal nationwide material standards. This article argues that the widespread view that the word ‘poverty’ means ‘relative poverty’, which in left-dominated social policy academia often extends to implying that those who do not define poverty this way are necessarily misguided, has led to an incomplete portrayal of poorer British people's lived experience. The article examines published empirical work, before presenting findings from British Social Attitudes surveys and interviews with forty unemployed Jobseeker's Allowance claimants and thirty employed people. Both the existing and new findings exposed aspects of public attitudes and experience which resonate with unanswered academic criticisms of defining poverty as relative poverty. These public contributions have tended to be glossed over or treated dismissively by social policy authors, despite them attaching importance to Left-friendly aspects of poorer people's experience and attitudes.
Intrapair Comparison of Life-Course Appetite and Physical Activity in Elderly Danish Twins: Reliability and Association With Subsequent Survival
Authors: Løkkegaard Laura E. , Larsen Lisbeth A. , Christensen Kaare
Published: August 2016

Avoiding overeating and being physically active is associated with healthy aging, but methodological issues challenge the quantification of the association. Intrapair comparison of twins is a study design that attempts to minimize social norm-driven biased self-reporting of lifestyle factors. We aimed to investigate the association between self-reported lifestyle factors and subsequent survival in 347 Danish twin pairs aged 70 years and older and, additionally, to investigate the reliability of these self-reports. The twins were interviewed in 2003 and followed for mortality until 2015. They were asked to compare their appetite and physical activity to that of their co-twins in different stages of life. On an individual level, we found a positive association between current self-reported physical activity and late-life survival for elderly twins. This was supported by the intrapair analyses, which revealed a positive association between midlife and current physical activity and late-life survival. A positive association between lower appetite and late-life survival was found generally over the life course in the individual level analyses but not in the intrapair analyses. Kappa values for the inter-twin agreement on who ate the most were 0.16 to 0.34 in different life stages, and for physical activity 0.19 to 0.26, corresponding to a slight-to-fair agreement. Approximately, 50% of the twin pairs were not in agreement regarding physical activity, and of these twins 75% (95% CI: 67–82%) considered themselves the most active twin. These findings indicate a still-existing tendency of answering according to social norms, even in a twin study designed to minimize this.
Whole-animal genome-wide RNAi screen identifies networks regulating male germline stem cells in Drosophila
Authors: Liu Ying , Ge Qinglan , Chan Brian , Liu Hanhan , Singh Shree Ram , Manley Jacob , Lee Jae , Weideman Ann Marie , Hou Gerald , Hou Steven X.
Published: August 2016

Stem cells are regulated both intrinsically and externally, including by signals from the local environment and distant organs. To identify genes and pathways that regulate stem-cell fates in the whole organism, we perform a genome-wide transgenic RNAi screen through ubiquitous gene knockdowns, focusing on regulators of adultDrosophilatestis germline stem cells (GSCs). Here we identify 530 genes that regulate GSC maintenance and differentiation. Of these, we further knock down 113 selected genes using cell-type-specific Gal4s and find that more than half were external regulators, that is, from the local microenvironment or more distal sources. Some genes, for example,versatile(vers), encoding a heterochromatin protein, regulates GSC fates differentially in different cell types and through multiple pathways. We also find that mitosis/cytokinesis proteins are especially important for male GSC maintenance. Our findings provide valuable insights and resources for studying stem cell regulation at the organismal level.
Multivariate analysis of ultrasound-recorded dorsal strain sequences: Investigation of dynamic neck extensions in women with chronic whiplash associated disorders
Authors: Peolsson Anneli , Peterson Gunnel , Trygg Johan , Nilsson David
Published: August 2016

Whiplash Associated Disorders (WAD) refers to the multifaceted and chronic burden that is common after a whiplash injury. Tools to assist in the diagnosis of WAD and an increased understanding of neck muscle behaviour are needed. We examined the multilayer dorsal neck muscle behaviour in nine women with chronic WAD versus healthy controls during the entire sequence of a dynamic low-loaded neck extension exercise, which was recorded using real-time ultrasound movies with high frame rates. Principal component analysis and orthogonal partial least squares were used to analyse mechanical muscle strain (deformation in elongation and shortening). The WAD group showed more shortening during the neck extension phase in the trapezius muscle and during both the neck extension and the return to neutral phase in the multifidus muscle. For the first time, a novel non-invasive method is presented that is capable of detecting altered dorsal muscle strain in women with WAD during an entire exercise sequence. This method may be a breakthrough for the future diagnosis and treatment of WAD.
Optogenetic and chemogenetic strategies for sustained inhibition of pain
Authors: Iyer Shrivats M. , Vesuna Sam , Ramakrishnan Charu , Huynh Karen , Young Stephanie , Berndt Andre , Lee Soo Yeun , Gorini Christopher J. , Deisseroth Karl , Delp Scott L.
Published: August 2016

Spatially targeted, genetically-specific strategies for sustained inhibition of nociceptors may help transform pain science and clinical management. Previous optogenetic strategies to inhibit pain have required constant illumination and chemogenetic approaches in the periphery have not been shown to inhibit pain. Here, we show that the step-function inhibitory channelrhodopsin, SwiChR, can be used to persistently inhibit pain for long periods of time through infrequent transdermally delivered light pulses, reducing required light exposure by >98% and resolving a long-standing limitation in optogenetic inhibition. We demonstrate that the viral expression of the hM4D receptor in small-diameter primary afferent nociceptor enables chemogenetic inhibition of mechanical and thermal nociception thresholds. Finally, we develop optoPAIN, an optogenetic platform to non-invasively assess changes in pain sensitivity and use this technique to examine pharmacological and chemogenetic inhibition of pain.
The sense of body ownership relaxes temporal constraints for multisensory integration
Authors: Maselli Antonella , Kilteni Konstantina , López-Moliner Joan , Slater Mel
Published: August 2016

Experimental work on body ownership illusions showed how simple multisensory manipulation can generate the illusory experience of an artificial limb as being part of the own-body. This work highlighted how own-body perception relies on a plastic brain representation emerging from multisensory integration. The flexibility of this representation is reflected in the short-term modulations of physiological states and perceptual processing observed during these illusions. Here, we explore the impact of ownership illusions on the temporal dimension of multisensory integration. We show that, during the illusion, the temporal window for integrating touch on the physical body with touch seen on a virtual body representation, increases with respect to integration with visual events seen close but separated from the virtual body. We show that this effect is mediated by the ownership illusion. Crucially, the temporal window for visuotactile integration was positively correlated with participants’ scores rating the illusory experience of owning the virtual body and touching the object seen in contact with it. Our results corroborate the recently proposed causal inference mechanism for illusory body ownership. As a novelty, they show that the ensuing illusory causal binding between stimuli from the real and fake body relaxes constraints for the integration of bodily signals.
Secreted Isoform of Human Lynx1 (SLURP-2): Spatial Structure and Pharmacology of Interactions with Different Types of Acetylcholine Receptors
Authors: Lyukmanova E. N. , Shulepko M. A. , Shenkarev Z. O. , Bychkov M. L. , Paramonov A. S. , Chugunov A. O. , Kulbatskii D. S. , Arvaniti M. , Dolejsi Eva , Schaer T. , Arseniev A. S. , Efremov R. G. , Thomsen M. S. , Dolezal V. , Bertrand D. , Dolgikh D. A. , Kirpichnikov M. P.
Published: August 2016

Human-secreted Ly-6/uPAR-related protein-2 (SLURP-2) regulates the growth and differentiation of epithelial cells. Previously, the auto/paracrine activity of SLURP-2 was considered to be mediated via its interaction with the α3β2 subtype of the nicotinic acetylcholine receptors (nAChRs). Here, we describe the structure and pharmacology of a recombinant analogue of SLURP-2. Nuclear magnetic resonance spectroscopy revealed a ‘three-finger’ fold of SLURP-2 with a conserved β-structural core and three protruding loops. Affinity purification using cortical extracts revealed that SLURP-2 could interact with the α3, α4, α5, α7, β2, and β4 nAChR subunits, revealing its broader pharmacological profile. SLURP-2 inhibits acetylcholine-evoked currents at α4β2 and α3β2-nAChRs (IC50 ~0.17 and >3 μM, respectively) expressed in Xenopus oocytes. In contrast, at α7-nAChRs, SLURP-2 significantly enhances acetylcholine-evoked currents at concentrations <1 μM but induces inhibition at higher concentrations. SLURP-2 allosterically interacts with human M1 and M3 muscarinic acetylcholine receptors (mAChRs) that are overexpressed in CHO cells. SLURP-2 was found to promote the proliferation of human oral keratinocytes via interactions with α3β2-nAChRs, while it inhibited cell growth via α7-nAChRs. SLURP-2/mAChRs interactions are also probably involved in the control of keratinocyte growth. Computer modeling revealed possible SLURP-2 binding to the ‘classical’ orthosteric agonist/antagonist binding sites at α7 and α3β2-nAChRs.
Incubation of food craving is independent of macronutrient composition
Authors: Darling Rebecca A. , Dingess Paige M. , Schlidt Kevin C. , Smith Erin M. , Brown Travis E.
Published: August 2016

Cues previously paired with rewarding stimuli induce a time-dependent increase in the motivational craving state (incubation of craving). Whether there is an increase in craving for high-fat (HF) food over time, which may contribute to overeating and obesity, has not been determined. We hypothesized that cues paired with HF pellets would elicit a greater incubation of craving effect than those paired with standard chow (SC) pellets. Rats exposed to cues associated with either HF or SC pellets demonstrated equivalent levels of craving over an abstinence period of 30 days. Diet preference tests between SC pellets and LabDiet revealed that SC pellets were preferred over LabDiet. Rats reared on SC pellets exclusively, did not display incubation of craving for SC pellets, suggesting that prior history with the food plays an important role in cue-induced seeking behavior. Results identified cues previously associated with food undergo a comparable magnitude of incubation of craving. When ingestive behavior was measured after 30 days of abstinence, rats significantly increased their consumption of HF pellets. Our results indicate that food cues gain importance over time, trigger increased approach behaviors and increased consumption of HF food following abstinence. This may contribute to overeating and the development of obesity.
Manipulating the Biosynthesis of Bioactive Compound Alkaloids for Next-Generation Metabolic Engineering in Opium Poppy Using CRISPR-Cas 9 Genome Editing Technology
Authors: Alagoz Yagiz , Gurkok Tugba , Zhang Baohong , Unver Turgay
Published: August 2016

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated9 (Cas9) endonuclease system is a powerful RNA-guided genome editing tool. CRISPR/Cas9 has been well studied in model plant species for targeted genome editing. However, few studies have been reported on plant species without whole genome sequence information. Currently, no study has been performed to manipulate metabolic pathways using CRISPR/Cas9. In this study, the type II CRISPR/SpCas9 system was used to knock out, via nonhomologous end-joining genome repair, the 4′OMT2 in opium poppy (Papaver somniferum L.), a gene which regulates the biosythesis of benzylisoquinoline alkaloids (BIAs). For sgRNA transcription, viral-based TRV and synthetic binary plasmids were designed and delivered into plant cells with a Cas9 encoding-synthetic vector by Agrobacterium-mediated transformation. InDels formed by CRISPR/Cas9 were detected by sequence analysis. Our results showed that the biosynthesis of BIAs (e.g. morphine, thebaine) was significantly reduced in the transgenic plants suggesting that 4′OMT2 was efficiently knocked-out by our CRISPR-Cas9 genome editing approach. In addition, a novel uncharacterized alkaloid was observed only in CRISPR/Cas9 edited plants. Thus, the applicabilitiy of the CRISPR/Cas9 system was demonstrated for the first time for medicinal aromatic plants by sgRNAs transcribed from both synthetic and viral vectors to regulate BIA metabolism and biosynthesis.
MicroRNA-491 regulates the proliferation and apoptosis of CD8+ T cells
Authors: Yu Ting , Zuo Qian-Fei , Gong Li , Wang Li-Na , Zou Quan-Ming , Xiao Bin
Published: August 2016

T lymphocyte-mediated immune responses are critical for antitumour immunity; however, T cell function is impaired in the tumour environment. MicroRNAs are involved in regulation of the immune system. While little is known about the function of intrinsic microRNAs in CD8+ T cells in the tumour microenvironment. Here, we found that miR-491 was upregulated in CD8+ T cells from mice with colorectal cancer. Retroviral overexpression of miR-491 in CD8+ and CD4+ T cells inhibited cell proliferation and promoted cell apoptosis and decreased the production of interferon-γ in CD8+ T cells. We found that miR-491 directly targeted cyclin-dependent kinase 4, the transcription factor T cell factor 1 and the anti-apoptotic protein B-cell lymphoma 2-like 1 in CD8+ T cells. Furthermore, tumour-derived TGF-β induced miR-491 expression in CD8+ T cells. Taken together, our results suggest that miR-491 can act as a negative regulator of T lymphocytes, especially CD8+ T cells, in the tumour environment; thus, this study provides a novel insight on dysfunctional CD8+ T cells during tumourigenesis and cancer progression. In conclusion, miR-491 may be a new target for antitumour immunotherapy.
Non-monotonic temperature dependence of radiation defect dynamics in silicon carbide
Authors: Bayu Aji L. B. , Wallace J. B. , Shao L. , Kucheyev S. O.
Published: August 2016

Understanding response of solids to particle irradiation remains a major materials physics challenge. This applies even to SiC, which is a prototypical nuclear ceramic and wide-band-gap semiconductor material. The lack of predictability is largely related to the complex, dynamic nature of radiation defect formation. Here, we use a novel pulsed-ion-beam method to study dynamic annealing in 4H-SiC ion-bombarded in the temperature range of 25–250 °C. We find that, while the defect recombination efficiency shows an expected monotonic increase with increasing temperature, the defect lifetime exhibits a non-monotonic temperature dependence with a maximum at ~100 °C. This finding indicates a change in the dominant defect interaction mechanism at ~100 °C. The understanding of radiation defect dynamics may suggest new paths to designing radiation-resistant materials.
Efficient Suppression of Hepatitis C Virus Replication by Combination Treatment with miR-122 Antagonism and Direct-acting Antivirals in Cell Culture Systems
Authors: Liu Fanwei , Shimakami Tetsuro , Murai Kazuhisa , Shirasaki Takayoshi , Funaki Masaya , Honda Masao , Murakami Seishi , Yi Minkyung , Tang Hong , Kaneko Shuichi
Published: August 2016

Direct-acting antivirals (DAAs) against Hepatitis C virus (HCV) show effective antiviral activity with few side effects. However, the selection of DAA-resistance mutants is a growing problem that needs to be resolved. In contrast, miR-122 antagonism shows extensive antiviral effects among all HCV genotypes and a high barrier to drug resistance. In the present study, we evaluated three DAAs (simeprevir, daclatasvir and sofosbuvir) in combination with anti-miR-122 treatment against HCV genotype 1a in cell cultures. We found that combination treatments with anti-miR-122 and a DAA had additive or synergistic antiviral effects. The EC50 values of simeprevir in simeprevir-resistant mutants were significantly decreased by combining simeprevir with anti-miR-122. A similar reduction in EC50 in daclatasvir-resistant mutants was achieved by combining daclatasvir with anti-miR-122. Combination treatment in HCV-replicating cells with DAA and anti-miR-122 sharply reduced HCV RNA amounts. Conversely, DAA single treatment with simeprevir or daclatasvir reduced HCV RNA levels initially, but the levels later rebounded. DAA-resistant mutants were less frequently observed in combination treatments than in DAA single treatments. In summary, the addition of miR-122 antagonism to DAA single treatments had additive or synergistic antiviral effects and helped to efficiently suppress HCV replication and the emergence of DAA-resistant mutants.
Fiberless multicolor neural optoelectrode for in vivo circuit analysis
Authors: Kampasi Komal , Stark Eran , Seymour John , Na Kyounghwan , Winful Herbert G. , Buzsáki György , Wise Kensall D. , Yoon Euisik
Published: August 2016

Maximizing the potential of optogenetic approaches in deep brain structures of intact animals requires optical manipulation of neurons at high spatial and temporal resolutions, while simultaneously recording electrical data from those neurons. Here, we present the first fiber-less optoelectrode with a monolithically integrated optical waveguide mixer that can deliver multicolor light at a common waveguide port to achieve multicolor modulation of the same neuronal population in vivo. We demonstrate successful device implementation by achieving efficient coupling between a side-emitting injection laser diode (ILD) and a dielectric optical waveguide mixer via a gradient-index (GRIN) lens. The use of GRIN lenses attains several design features, including high optical coupling and thermal isolation between ILDs and waveguides. We validated the packaged devices in the intact brain of anesthetized mice co-expressing Channelrhodopsin-2 and Archaerhodopsin in pyramidal cells in the hippocampal CA1 region, achieving high quality recording, activation and silencing of the exact same neurons in a given local region. This fully-integrated approach demonstrates the spatial precision and scalability needed to enable independent activation and silencing of the same or different groups of neurons in dense brain regions while simultaneously recording from them, thus considerably advancing the capabilities of currently available optogenetic toolsets.
Genome-wide association study of aggressive behaviour in chicken
Authors: Li Zhenhui , Zheng Ming , Abdalla Bahareldin Ali , Zhang Zhe , Xu Zhenqiang , Ye Qiao , Xu Haiping , Luo Wei , Nie Qinghua , Zhang Xiquan
Published: August 2016

In the poultry industry, aggressive behaviour is a large animal welfare issue all over the world. To date, little is known about the underlying genetics of the aggressive behaviour. Here, we performed a genome-wide association study (GWAS) to explore the genetic mechanism associated with aggressive behaviour in chickens. The GWAS results showed that a total of 33 SNPs were associated with aggressive behaviour traits (P < 4.6E-6). rs312463697 on chromosome 4 was significantly associated with aggression (P = 2.10905E-07) and it was in the intron region of the sortilin-related VPS10 domain containing receptor 2 (SORCS2) gene. In addition, biological function analysis of the nearest 26 genes around the significant SNPs was performed with Ingenuity Pathway Analysis. An interaction network contained 17 genes was obtained and SORCS2 was involved in this network, interacted with nerve growth factor (NGF), nerve growth factor receptor (NGFR), dopa decarboxylase (L-dopa) and dopamine. After knockdown of SORCS2, the mRNA levels of NGF, L-dopa and dopamine receptor genes DRD1, DRD2, DRD3 and DRD4 were significantly decreased (P < 0.05). In summary, our data indicated that SORCS2 might play an important role in chicken aggressive behaviour through the regulation of dopaminergic pathways and NGF.
1H NMR metabolomic study of auxotrophic starvation in yeast using Multivariate Curve Resolution-Alternating Least Squares for Pathway Analysis
Authors: Puig-Castellví Francesc , Alfonso Ignacio , Piña Benjamin , Tauler Romà
Published: August 2016

Disruption of specific metabolic pathways constitutes the mode of action of many known toxicants and it is responsible for the adverse phenotypes associated to human genetic defects. Conversely, many industrial applications rely on metabolic alterations of diverse microorganisms, whereas many therapeutic drugs aim to selectively disrupt pathogens’ metabolism. In this work we analyzed metabolic changes induced by auxotrophic starvation conditions in yeast in a non-targeted approach, using one-dimensional proton Nuclear Magnetic Resonance spectroscopy (1H NMR) and chemometric analyses. Analysis of the raw spectral datasets showed specific changes linked to the different stages during unrestricted yeast growth, as well as specific changes linked to each of the four tested starvation conditions (L-methionine, L-histidine, L-leucine and uracil). Analysis of changes in concentrations of more than 40 metabolites by Multivariate Curve Resolution – Alternating Least Squares (MCR-ALS) showed the normal progression of key metabolites during lag, exponential and stationary unrestricted growth phases, while reflecting the metabolic blockage induced by the starvation conditions. In this case, different metabolic intermediates accumulated over time, allowing identification of the different metabolic pathways specifically affected by each gene disruption. This synergy between NMR metabolomics and molecular biology may have clear implications for both genetic diagnostics and drug development.
ZnCr2S4: Highly effective photocatalyst converting nitrate into N2 without over-reduction under both UV and pure visible light
Authors: Yue Mufei , Wang Rong , Cheng Nana , Cong Rihong , Gao Wenliang , Yang Tao
Published: August 2016

We propose several superiorities of applying some particular metal sulfides to the photocatalytic nitrate reduction in aqueous solution, including the high density of photogenerated excitons, high N2 selectivity (without over-reduction to ammonia). Indeed, ZnCr2S4 behaved as a highly efficient photocatalyst and with the assistance of 1 wt% cocatalysts (RuOx, Ag, Au, Pd, or Pt), the efficiency was greatly improved. The simultaneous loading of Pt and Pd led to a synergistic effect. It offered the highest nitrate conversion rate of ~45 mg N/h together with the N2 selectivity of ~89%. Such a high activity remained steady after 5 cycles. The optimal apparent quantum yield at 380 nm was 15.46%. More importantly, with the assistance of the surface plasma resonance effect of Au, the visible light activity achieved 1.352 mg N/h under full arc Xe-lamp and 0.452 mg N/h under pure visible light (λ > 400 nm). Comparing to the previous achievements in photocatalytic nitrate removal, our work on ZnCr2S4 eliminates the over-reduction problem and possesses an extremely high and steady activity under UV-light, as well as a decent conversion rate under pure visible light.
Dynamics Correlation Network for Allosteric Switching of PreQ1 Riboswitch
Authors: Wang Wei , Jiang Cheng , Zhang Jinmai , Ye Wei , Luo Ray , Chen Hai-Feng
Published: August 2016

Riboswitches are a class of metabolism control elements mostly found in bacteria. Due to their fundamental importance in bacteria gene regulation, riboswitches have been proposed as antibacterial drug targets. Prequeuosine (preQ1) is the last free precursor in the biosynthetic pathway of queuosine that is crucial for translation efficiency and fidelity. However, the regulation mechanism for the preQ1riboswitch remains unclear. Here we constructed fluctuation correlation network based on all-atom molecular dynamics simulations to reveal the regulation mechanism. The results suggest that the correlation network in the bound riboswitch is distinctly different from that in the apo riboswitch. The community network indicates that the information freely transfers from the binding site of preQ1to the expression platform of the P3 helix in the bound riboswitch and the P3 helix is a bottleneck in the apo riboswitch. Thus, a hypothesis of “preQ1-binding induced allosteric switching” is proposed to link riboswitch and translation regulation. The community networks of mutants support this hypothesis. Finally, a possible allosteric pathway of A50-A51-A52-U10-A11-G12-G56 was also identified based on the shortest path algorithm and confirmed by mutations and network perturbation. The novel fluctuation network analysis method can be used as a general strategy in studies of riboswitch structure-function relationship.
Synaptic Basis for the Generation of Response Variation in Auditory Cortex
Authors: Tao Can , Zhang Guangwei , Zhou Chang , Wang Lijuan , Yan Sumei , Zhang Li I. , Zhou Yi , Xiong Ying
Published: August 2016

Cortical neurons can exhibit significant variation in their responses to the same sensory stimuli, as reflected by the reliability and temporal precision of spikes. However the synaptic mechanism underlying response variation still remains unclear. Here, in vivo whole-cell patch-clamp recording of excitatory neurons revealed variation in the amplitudes as well as the temporal profiles of excitatory and inhibitory synaptic inputs evoked by the same sound stimuli in layer 4 of the rat primary auditory cortex. Synaptic inputs were reliably induced by repetitive stimulation, although with large variation in amplitude. The variation in the amplitude of excitation was much higher than that of inhibition. In addition, the temporal jitter of the synaptic onset latency was much smaller than the jitter of spike response. We further demonstrated that the amplitude variation of excitatory inputs can largely account for the spike variation, while the jitter in spike timing can be primarily attributed to the temporal variation of excitatory inputs. Furthermore, the spike reliability of excitatory but not inhibitory neurons is dependent on tone frequency. Our results thus revealed an inherent cortical synaptic contribution for the generation of variation in the spike responses of auditory cortical neurons.
Advanced Mitigation Process (AMP) for Improving Laser Damage Threshold of Fused Silica Optics
Authors: Ye Xin , Huang Jin , Liu Hongjie , Geng Feng , Sun Laixi , Jiang Xiaodong , Wu Weidong , Qiao Liang , Zu Xiaotao , Zheng Wanguo
Published: August 2016

The laser damage precursors in subsurface of fused silica (e.g. photosensitive impurities, scratches and redeposited silica compounds) were mitigated by mineral acid leaching and HF etching with multi-frequency ultrasonic agitation, respectively. The comparison of scratches morphology after static etching and high-frequency ultrasonic agitation etching was devoted in our case. And comparison of laser induce damage resistance of scratched and non-scratched fused silica surfaces after HF etching with high-frequency ultrasonic agitation were also investigated in this study. The global laser induce damage resistance was increased significantly after the laser damage precursors were mitigated in this case. The redeposition of reaction produce was avoided by involving multi-frequency ultrasonic and chemical leaching process. These methods made the increase of laser damage threshold more stable. In addition, there is no scratch related damage initiations found on the samples which were treated by Advanced Mitigation Process.
A CRISPR-Cas9 sex-ratio distortion system for genetic control
Authors: Galizi Roberto , Hammond Andrew , Kyrou Kyros , Taxiarchi Chrysanthi , Bernardini Federica , O’Loughlin Samantha M. , Papathanos Philippos-Aris , Nolan Tony , Windbichler Nikolai , Crisanti Andrea
Published: August 2016

Genetic control aims to reduce the ability of insect pest populations to cause harm via the release of modified insects. One strategy is to bias the reproductive sex ratio towards males so that a population decreases in size or is eliminated altogether due to a lack of females. We have shown previously that sex ratio distortion can be generated synthetically in the main human malaria vector Anopheles gambiae, by selectively destroying the X-chromosome during spermatogenesis, through the activity of a naturally-occurring endonuclease that targets a repetitive rDNA sequence highly-conserved in a wide range of organisms. Here we describe a CRISPR-Cas9 sex distortion system that targets ribosomal sequences restricted to the member species of the Anopheles gambiae complex. Expression of Cas9 during spermatogenesis resulted in RNA-guided shredding of the X-chromosome during male meiosis and produced extreme male bias among progeny in the absence of any significant reduction in fertility. The flexibility of CRISPR-Cas9 combined with the availability of genomic data for a range of insects renders this strategy broadly applicable for the species-specific control of any pest or vector species with an XY sex-determination system by targeting sequences exclusive to the female sex chromosome.
Divergent Annexin A1 expression in periphery and gut is associated with systemic immune activation and impaired gut immune response during SIV infection
Authors: Sena Angela A. S. , Glavan Tiffany , Jiang Guochun , Sankaran-Walters Sumathi , Grishina Irina , Dandekar Satya , Goulart Luiz R.
Published: August 2016

HIV-1 disease progression is paradoxically characterized by systemic chronic immune activation and gut mucosal immune dysfunction, which is not fully defined. Annexin A1 (ANXA1), an inflammation modulator, is a potential link between systemic inflammation and gut immune dysfunction during the simian immunodeficiency virus (SIV) infection. Gene expression of ANXA1 and cytokines were assessed in therapy-naïve rhesus macaques during early and chronic stages of SIV infection and compared with SIV-negative controls. ANXA1 expression was suppressed in the gut but systemically increased during early infection. Conversely, ANXA1 expression increased in both compartments during chronic infection. ANXA1 expression in peripheral blood was positively correlated with HLA-DR+CD4+ and CD8+ T-cell frequencies and negatively associated with the expression of pro-inflammatory cytokines and CCR5. In contrast, the gut mucosa presented an anergic cytokine profile in relation to ANXA1 expression. In vitro stimulations with ANXA1 peptide resulted in decreased inflammatory response in PBMC but increased activation of gut lymphocytes. Our findings suggest that ANXA1 signaling is dysfunctional in SIV infection and may contribute to chronic inflammation in periphery and with immune dysfunction in the gut mucosa. Thus, ANXA1 signaling may be a novel therapeutic target for the resolution of immune dysfunction in HIV infection.
Magnetic field effects of photocarrier generation in bulk heterojunctions at low temperature
Authors: Tajima H. , Nishioka Y. , Sato S. , Suzuki T. , Kimata M.
Published: August 2016

We report an experimental investigation of the magnetic field effect (MFE) in polymer bulk heterojunction devices at temperatures below 10 K using photocarrier extraction by linearly increasing voltages.
Hypolipidemic and cardioprotective benefits of a novel fireberry hawthorn fruit extract in the JCR:LA-cp rodent model of dyslipidemia and cardiac dysfunction
Authors: Diane Abdoulaye , Borthwick Faye , Wu Sheng , Lee Jeanette , Brown Paula N. , Dickinson Timothy A. , Croft Kevin D. , Vine Donna F. , Proctor Spencer D.
Published: August 2016

Hawthorn is a widely used herbal alternative medicine for the treatment of various cardiovascular diseases.
Effects of protein species and surface physicochemical features on the deposition of nanoparticles onto protein-coated planar surfaces
Authors: Ikuma Kaoru , Shi Zhiwei , Walker Amy V. , Lau Boris L. T.
Published: August 2016

Proteins are often an important component of many bulk surfaces in biological and environmental systems that are coated with complex organic compounds that may also interact with nanoparticles.
Comparison of antidiabetic potential of (+) and (−)-hopeaphenol, a pair of enantiomers isolated from Ampelocissus indica (L.) and Vateria indica Linn., with respect to inhibition of digestive enzymes and induction of glucose uptake in L6 myotubes
Authors: Sasikumar P. , Prabha B. , Reshmitha T. R. , Veluthoor Sheeba , Pradeep A. K. , Rohit K. R. , Dhanya B. P. , Sivan V. V. , Jithin M. M. , Kumar N. Anil , Shibi I. G. , Nisha P. , Radhakrishnan K. V.
Published: August 2016

The remarkable α-glucosidase inhibition exhibited by the acetone extract of the rhizome ofAmpelocissus indica(L.) and stem bark ofVateria indicaLinn. (IC5023.2 and 1.47 μg mL−1) encouraged us to isolate the phytochemicals from these plants.
Polyaminoacid–doxorubicin prodrug micelles as highly selective therapeutics for targeted cancer therapy
Authors: Mauro N. , Campora S. , Adamo G. , Scialabba C. , Ghersi G. , Giammona G.
Published: August 2016

An amphiphilic copolymer carrying high-dose doxorubicin (21% on a weight basis), PHEA–EDA–P,C–Doxo, was prepared by coupling doxorubicin with a biocompatible polyaminoacid through a pH-sensitive spacer.
Ecological insights into low-level antibiotics interfered biofilms of Synechococcus elongatus
Authors: Tan Lin-Rui , Xia Peng-Fei , Sun Xue-Fei , Guo Ning , Song Chao , Li Qian , Wang Shu-Guang
Published: August 2016

The ecological impacts of low-level kanamycin onS. elongatushave been investigated through combined biofilm formation and transcriptional analysis.
Discovery of a new class of 16-membered (2Z,11Z)-3,11-di(aryl/naphthyl)-1,13-dioxa-5,9-dithia-2,12-diazacyclohexadeca-2,11-dienes as anti-tumor agents
Authors: Bodireddy Mohan Reddy , Mahla Ranjeet Singh , Khaja Mohinuddin P. Md. , Reddy G. Trivikram , Raghava Prasad D. Vijaya , Kumar Himanshu , Reddy N. C. Gangi
Published: August 2016

A series of new 16-membered macrocyclic compounds were synthesized and evaluation of in vitro anti-tumor activities on MDAMB-231 cell lines reveal that the macrocycles,1a,1f,1g,1iand1kare promising anti-tumor agents.
Temperature dependent Raman spectroscopy of electrochemically exfoliated few layer black phosphorus nanosheets
Authors: Pawbake Amit S. , Erande Manisha B. , Jadkar Sandesh R. , Late Dattatray J.
Published: August 2016

The present investigation deals with temperature dependant Raman spectroscopy of electrochemically exfoliated few layer black phosphorus nanosheets.
Magnetic properties and giant reversible magnetocaloric effect in GdCoC2
Authors: Meng Lingjian , Xu Chi , Yuan Ye , Qi Yang , Zhou Shengqiang , Li Lingwei
Published: August 2016

The crystal structure, magnetic properties and magnetocaloric effect (MCE) of GdCoC2 have been studied.
Efficient hydroarylation and hydroalkenylation of vinylarenes by Brønsted acid catalysis
Authors: Liu Muwen , Zhang Jinlong , Zhou Hui , Yang Huameng , Xia Chungu , Jiang Gaoxi
Published: August 2016

Brønsted acid Tf2NH-catalyzed hydroarylation and hydroalkenylation of 4 vinylarenes under mild reaction conditions is herein shown to provide access to 1,1-diarylalkane scaffolds and trans-1,3-diaryl-1-butenes in high yields and with excellent regioselectivity.