bluuebunny/crossref_metadata_2025 huggingface dataset:
Dancing to “groovy” music enhances the experience of flow
Authors: Bernardi Nicolò F. , Bellemare‐Pepin Antoine , Peretz Isabelle
Published: May 2018

We investigated whether dancing influences the emotional response to music, compared to when music is listened to in the absence of movement. Forty participants without previous dance training listened to “groovy” and “nongroovy” music excerpts while either dancing or refraining from movement. Participants were also tested while imitating their own dance movements, but in the absence of music as a control condition. Emotion ratings and ratings of flow were collected following each condition. Dance movements were recorded using motion capture. We found that the state of flow was increased specifically during spontaneous dance to groovy excerpts, compared with both still listening and motor imitation. Emotions in the realms of vitality (such as joy and power) and sublimity (such as wonder and nostalgia) were evoked by music in general, whether participants moved or not. Significant correlations were found between the emotional and flow responses to music and whole‐body acceleration profiles. Thus, the results highlight a distinct state of flow when dancing, which may be of use to promote well‐being and to address certain clinical conditions.
A systematic review and meta‐analysis of exercise‐based falls prevention strategies in adults aged 50+ years with visual impairment
Authors: Dillon Lisa , Clemson Lindy , Ramulu Pradeep , Sherrington Catherine , Keay Lisa
Published: May 2018

Purpose

To determine the impact of exercise or physical training on falls or physical function in people aged 50+ years with visual impairment, compared with control (no intervention or usual care).

Methods

An updated systematic review of randomised controlled trials, investigating the effect of exercise or physical activity on falls prevention or physical function in adults aged 50+ with visual impairment. Searches of CINAHL, the Cochrane Register of Controlled Trials (CENTRAL), Embase, and Medline were undertaken. Three trials were identified for the period February 2013 to July 2017 and added to the four in the original review.

Results

New trials evaluated yoga, the Otago Exercise Programme in combination with a home safety programme and the Alexander Technique. Meta‐analysis of data from two trials (n = 163) indicated a non‐statistically significant positive impact of exercise on the Chair Stand Test (WMD −1.85 s, 95% CI −4.65 to 0.96, p = 0.20, I2 22%). In this update, two new trials measured falls so meta‐analysis was possible for three trials (n = 539) and revealed no impact on falls (RR 1.05, 95% CI 0.73 to 1.50, p = 0.81, I2 30%).

Discussion

Although exercise or physical training can improve physical function in older adults with visual impairment, and diverse strategies are being evaluated, there are no proven falls prevention strategies. In the few studies available, falls are not consistently reported and more work is required to investigate falls prevention in older adults with visual impairment.
Tracheobronchial angles in children: Three‐dimensional computed tomography‐based measurements
Authors: Wani Tariq M. , Buchh Basharat , AlGhamdi Faris Saeed , Jan Ravees , Tumin Dmitry , Tobias Joseph D.
Published: May 2018

Background

Studies have shown significant variation in the tracheobronchial angles in pediatric‐aged patients. The current study revisits tracheobronchial angle measurements in children using accurate computed tomography‐based 3‐dimensional images to add clarity to the understanding of tracheobronchial angles. The primary objective of the current study was to measure the right and left bronchial angle take off from the trachea using 3‐dimensional computed tomography‐based images of the air column in the tracheobronchial tree.

Methods

Computed tomography‐based images of 45 children younger than 8 years were reviewed. The children were evaluated during spontaneous ventilation either during natural sleep or with sedation. The right and left bronchial angles were computed between the central axes of the respective main bronchi and a vertical line passing through the central axis of the longitudinal tracheal air column. The right and left bronchial angles were compared using paired t tests, and the age dependence of the right bronchial angle and left bronchial angle difference was evaluated using Pearson's correlation coefficient.

Results

The study cohort included 18 males and 27 females with an average age of 49 ± 25 months. The right bronchial angle ranged from 23° to 56° (mean 42 ± 7°), whereas left bronchial angle varied between 25° and 68° (mean 43 ± 9°). The difference in means of 1 degree was not statistically significant (95% confidence interval of difference: −1°, 4°; P = .282). No association was found between left and right bronchial angle difference and patient age (r = −.019).

Conclusion

According to computed tomography‐based 3‐dimensional imaging, right and left bronchial angles are virtually identical in children up to 8 years of age, and the difference between right and left bronchial angles does not vary with age in this population.
Water relations in silver birch during springtime: How is sap pressurised?
Authors: Hölttä T. , Dominguez Carrasco M. D. R. , Salmon Y. , Aalto J. , Vanhatalo A. , Bäck J. , Lintunen A.
Published: May 2018

Positive sap pressures are produced in the xylem of birch trees in boreal conditions during the time between the thawing of the soil and bud break. During this period, xylem embolisms accumulated during wintertime are refilled with water. The mechanism for xylem sap pressurization and its environmental drivers are not well known.

We measured xylem sap flow, xylem sap pressure, xylem sap osmotic concentration, xylem and whole stem diameter changes, and stem and root non‐structural carbohydrate concentrations, along with meteorological conditions at two sites in Finland during and after the sap pressurisation period.

The diurnal dynamics of xylem sap pressure and sap flow during the sap pressurisation period varied, but were more often opposite to the diurnal pattern after bud burst,i.e. sap pressure increased and sap flow rate mostly decreased when temperature increased. Net conversion of soluble sugars to starch in the stem and roots occurred during the sap pressurisation period. Xylem sap osmotic pressure was small in comparison to total sap pressure, and it did not follow changes in environmental conditions or tree water relations.

Based on these findings, we suggest that xylem sap pressurisation and embolism refilling occur gradually over a few weeks through water transfer from parenchyma cells to xylem vessels during daytime, and then the parenchyma are refilled mostly during nighttime by water uptake from soil. Possible drivers for water transfer from parenchyma cells to vessels are discussed. Also the functioning of thermal dissipation probes in conditions of changing stem water content is discussed.
Party System Change and the Quality of Democracy in East Africa
Authors: Pelizzo Riccardo , Nwokora Zim
Published: May 2018

This article explores in greater detail the nexus between party system change and democratic qualities. In doing so, we do not simply assess whether, how, and to what extent qualities of democracy in East Africa are affected by the instability of the patterns of interparty competition (fluidity of the party system); we also plan to show how the subcomponents of party system fluidity (frequency of change, scope of change, variety of change) influence the democratic qualities. By disaggregating fluidity in its constitutive elements and by testing how each of them affects the qualities of democracy, we find that while the frequency of change has a beneficial impact on the qualities of democracy, the other subcomponents of fluidity—namely, the “scope” and “variety” of system change—have a consistently negative effect on democratic quality.

Related Articles

Nwokora, Zim, and
Riccardo Pelizzo. 2015. “.” Politics & Policy 43 (): 453‐473. http://onlinelibrary.wiley.com/doi/10.1111/polp.12124/full

Pelizzo, Riccardo, and
Zim Nwokora. 2016. “.” Politics & Policy 44 (): 1017‐1052. http://onlinelibrary.wiley.com/doi/10.1111/polp.12188/full

Ikeanyibe, Okechukwu. 2014. “.” Politics & Policy 42 (): 769‐804. http://onlinelibrary.wiley.com/doi/10.1111/polp.12094/full

Related Media

The East African. 2018. “Wachira Maina, Africa's Constitutional Democracies.” March 12. http://www.theeastafrican.co.ke/news/Africa-constitutional-democracies/2558-4338554-15s7ca3z/index.html

BBC Africa. 2016. “Debate: Is Africa Reinventing Democracy?” https://www.youtube.com/watch?v=BJc2b47EiGE

ISS Africa TV. 2016. “The Future of Democracy in Africa.” https://www.youtube.com/watch?v=uQiTtArtupE

Babones, Salvatore. 2018. “Midnight in America with Riccardo Pelizzo.” February 16‐27. https://www.youtube.com/watch?v=advrSqmO96g&t=13s
It is not a panacea! The conditional effect of bricolage in SME opportunity exploitation
Authors: Guo Zisheng , Zhang Jianqi , Gao Linrui
Published: May 2018

Previous literature has recommended that small and medium enterprises (SMEs) use bricolage to exploit opportunities. However, some authors have warned that the abuse of bricolage might extrude standardized resources from a firm's resource portfolio and lower firm performance. Basing itself on resource management, this article suggests that medium‐sized firms benefit less from bricolage because they are more formalized and can afford standardized resources. If they rely too heavily on bricolage, they can fail to adopt the optimal solutions for the exploitation of recognizable opportunities. Data from 336 Chinese SMEs indicates that the moderating effect of bricolage on the relationship between opportunity recognition and SME performance is weaker in medium than in small‐sized firms. This study contributes to the literature by elaborating how bricolage influences firms in distinct resource environments.
Effect of cumulus cells and sperm concentration on fertilization and development of pig oocytes
Authors: Li R , Liu Y , Pedersen HS , Callesen H
Published: May 2018

Contents

Effect of sperm concentrations and cumulus cells (CCs) on porcine IVF was re‐evaluated using current improved IVM and IVC system. Our results showed that both CCs and sperm concentration had significant effect on penetration rate, frequency of polyspermy and embryonic development. The best IVF results were obtained with oocytes with CCs fertilized with 0.5 × 105 sperm/ml. Such an IVP system works on both sow and gilt oocytes.
GLOBAL FINANCIAL CRISIS AND SOUTHEAST ASIAN TRADE PERFORMANCE: EMPIRICAL EVIDENCE
Authors: Kabir Shahriar , Bloch Harry , Salim Ruhul A
Published: May 2018

The literature on the recent Global Financial Crisis (GFC) focuses on the decimation of Western economies; however, the impact of the crisis on Asian economies has remained largely unexplored. Using the classic dependency approach of the “core‐periphery” framework, this paper investigates the trade performance of Association of South East Asian Nation (ASEAN) members during (2008–2009) and after (2010–2012) the GFC and analyses the transmission of shocks to these countries from the Western core. A modified gravity model of trade flows is estimated for a panel of five leading ASEAN economies and their trading partners for the period 2002–2012. The empirical results show a decline in ASEAN trade during the financial crisis that becomes stronger during the post‐crisis period. The decline in trade exceeds that associated with changing gross domestic product at home and abroad, suggesting the crisis and its aftermath have been particularly disadvantageous for ASEAN trade.
Complement system's role in cancer and its therapeutic potential in ovarian cancer
Authors: Bareke H. , Akbuga J.
Published: May 2018

Cancer immunotherapy is a strong candidate for the long‐awaited new edition to standard cancer therapies. For an effective immunotherapy, it is imperative to delineate the players of antitumour immune response. As an important innate immune system effector mechanism, complement is highly likely to play a substantial role in cancer immunity. Studies suggest that there may be two different “states of complement” that show opposing effects on cancer cells; a complement profile that has antitumour effects with low expression of membrane‐bound complement regulator proteins (mCRPs), lytic membrane attack complex (MAC) concentration and moderate C5a concentration, and a complement profile that has protumour effects with high expression of mCRPs, sublytic MAC and high concentrations of C5a. One of the cancers that urgently require innovative therapeutic approaches is ovarian cancer, and complement has a potential to be a good target for this purpose. A combinatorial approach where the complement cascade is fine‐tuned by inhibiting some of its activities while promoting the others can prove to be a fruitful approach. Herein, we will briefly discuss the cancer‐immune system interaction and then present a discussion of complement system's role in tumour immunity and its therapeutic potential for ovarian cancer immunotherapy.
Estimated fetal weight percentile as a tool to predict collection of cord blood units with higher cellular content: implications for prenatal selection of cord blood donors
Authors: Lin Xinxin , Torrabadella Marta , Amat Lluís , Gómez Susana , Azqueta Carmen , Sánchez Mar , Cuadras Daniel , Martínez Lorenzo Maria José , Brull José María , Gayà Antoni , Cemborain Arantxa , Pérez Garcia Cristina , Arroyo JoséLuís , Querol Sergi , Gómez Roig Maria Dolores
Published: May 2018

BACKGROUND

The need for high‐cellular‐content cord blood units (CBUs) for allogenic transplantation is evident to improve clinical outcomes. In our environment and with current donation programs, very few collected units meet suggested clinical thresholds, making collection programs highly inefficient. To increase the clinical conversion rate, we have assessed factors influencing the cellular content of the cord blood collection and established the estimated fetal weight percentile (EFWp) as a tool to predict which deliveries will obtain higher cellular counts.

STUDY DESIGN AND METHODS

We conducted a retrospective analysis of 11,349 collected CBUs. An analysis of diagnostic efficiency (receiver operating characteristic [ROC] curve) was performed to establish the cutoffs of several obstetric and perinatal variables from which we would obtain more than 1500 × 106 total nucleated cells and 4 × 106 CD34 cells. We then calculated the optimal EFWp cutoff to increase efficiency.

RESULTS

In the univariate analysis, factors positively and significantly associated were a greater neonatal and placental weight and longer weeks of gestation. In the multivariate analysis only neonatal and placental weight remain significant (p < 0.001). The ROC curve analysis showed that the optimal EFWp cutoff is 60, which has the maximum area under the curve. Applying this, donations meeting clinical cellular numbers will increase more than 30% with respect to not using any threshold.

CONCLUSION

The EFWp predicts the quality of the collected CBUs and can be used to make a prenatal selection of the donors, therefore increasing the efficiency of umbilical cord blood collection programs.
Inactivation of Ebola virus and Middle East respiratory syndrome coronavirus in platelet concentrates and plasma by ultraviolet C light and methylene blue plus visible light, respectively
Authors: Eickmann Markus , Gravemann Ute , Handke Wiebke , Tolksdorf Frank , Reichenberg Stefan , Müller Thomas H. , Seltsam Axel
Published: May 2018

BACKGROUND

Ebola virus (EBOV) and Middle East respiratory syndrome coronavirus (MERS‐CoV) have been identified as potential threats to blood safety. This study investigated the efficacy of the THERAFLEX UV‐Platelets and THERAFLEX MB‐Plasma pathogen inactivation systems to inactivate EBOV and MERS‐CoV in platelet concentrates (PCs) and plasma, respectively.

STUDY DESIGN AND METHODS

PCs and plasma were spiked with high titers of cell culture–derived EBOV and MERS‐CoV, treated with various light doses of ultraviolet C (UVC; THERAFLEX UV‐Platelets) or methylene blue (MB) plus visible light (MB/light; THERAFLEX MB‐Plasma), and assessed for residual viral infectivity.

RESULTS

UVC reduced EBOV (≥4.5 log) and MERS‐CoV (≥3.7 log) infectivity in PCs to the limit of detection, and MB/light decreased EBOV (≥4.6 log) and MERS‐CoV (≥3.3 log) titers in plasma to nondetectable levels.

CONCLUSIONS

Both THERAFLEX UV‐Platelets (UVC) and THERAFLEX MB‐Plasma (MB/light) effectively reduce EBOV and MERS‐CoV infectivity in platelets and plasma, respectively.
A triangular purchasing power parity hypothesis
Authors: Wang Peijie , Liu Zhiyuan
Published: May 2018

We propose a triangular purchasing power parity (PPP) analytical framework, which is theoretically justified and empirically validated. The mechanisms and channels through which a seemingly mystery relationship emerges are deliberated and examined, which renders significant implications to international monetary economics, finance and business. The de facto peg of the RMB to the US dollar, together with trade activities and arrangements, causes a triangular PPP effect that the dollar euro exchange rate is not a function of the relative prices in the US and Euroland. Instead, it becomes a function of the relative prices in the People's Republic of China (PRC) and Euroland. The results are supportive of triangular PPP in a three‐economy world of the US, Euroland and PRC.
The WTO in Buenos Aires: The outcome and its significance for the future of the multilateral trading system
Authors: Hannah Erin , Scott James , Wilkinson Rorden
Published: May 2018

The conclusion of the World Trade Organization's (WTO) Buenos Aires ministerial conference (10–13 December 2017) was immediately celebrated and derided in equal measure. For its supporters, Buenos Aires opened the way toward negotiations in e‐commerce, investment facilitation for development, and measures designed to help micro, small and medium sized enterprises (MSMEs). For its detractors, the meeting underscored the gridlock that continues to blight the WTO’s negotiating function and underlined the organisation's declining credibility as a mechanism for governing global trade. In this paper we provide one of the first full length critical evaluations of the Buenos Aires conference and its outcome. In so doing, we offer answers to three questions. What accounts for such dramatically different assessments of the meeting's outcome? How should the outcome be interpreted? What is its significance for the future of the WTO and the multilateral trading system? We argue that the meeting's outcome was indeed significant. It has consolidated the process of reconfiguring the WTO‘s negotiating function; and it enables members to tackle more effectively a range of pressing economic and social issues as well as to navigate blockers and blockages in the negotiations. However, it also poses challenges for the WTO‘s poorest constituents.
The comparative efficacy of afoxolaner, spinosad, milbemycin, spinosad plus milbemycin, and nitenpyram for the treatment of canine cutaneous myiasis
Authors: Han Hock Siew , Chen Charles , Schievano Carlo , Noli Chiara
Published: May 2018

Background

Canine screw‐worm myiasis due to Cochliomyia hominivorax or Chrysomya bezziana has traditionally been treated with extra‐label use of ivermectin. The larvicidal activities of nitenpyram and spinosad/milbemycin also have been described, but there have been no reports to describe the efficacy of isoxazolines such as afoxolaner.

Objectives

To evaluate and compare the efficacy of spinosad, spinosad/milbemycin, milbemycin, nitenpyram and afoxolaner for the treatment of canine screw‐worm myiasis.

Animals

Forty client‐owned and naturally infested dogs.

Methods

Cases were randomized into five groups of eight dogs, with each receiving an insecticide at the dose recommended by the manufacturer. Each case was evaluated hourly for 7 h and then again 24 h after treatment. Scores of 0 (no visualized effect), 0.5 (partial eradication) or 1 (complete kill and eradication) were recorded at each observation and compared between groups. Time to complete killing of all larvae was recorded for each dog and compared between treatment groups.

Results

Nitenpyram killed all larvae at 6 h post‐consumption and spinosad/milbemycin at 7 h. In groups receiving afoxolaner or spinosad, all larvae were killed within 24 h. For those receiving milbemycin, two cases were still infested with live larvae at 24 h. Shih tzus and their crosses were most commonly affected.

Conclusion

Spinosad/milbemycin or nitenpyram seem to be effective drugs for the treatment of canine screw‐worm myiasis. Afoxolaner and milbemycin are effective but exhibited slower larvicidal activity. Synergism between spinosad and milbemycin was observed.
Quality of life of living with a transplanted liver :The issue of returning to normalcy
Authors: Wainwright Bethli , Waring Marilyn J , Julich Shirley , Yeung Polly , Green Jenny K
Published: May 2018

INTRODUCTION: Advanced technology in medical and pharmacology has increased surgical survival rates for transplant recipients. Therefore, post-transplant care is critical and tightly connected with key focuses on the recipient’s quality of life (QOL). Post-transplant QOL is multifaceted,  encompassing morbidity and personal, social, familial and environmental support for recipients. Post-liver transplantation recovery extends well beyond returning home.METHOD: Building on Wainwright’s research  (Wainwright, 2011a, 2011b; Wainwright, Jülich, Waring, Yeung, & Green, 2016), herself a liver transplant recipient, this article reports transplant recipients’ perceptions and experiences after the first three years and discusses how they re-established function in everyday life as they adapted to their new normal to achieve QOL. The research employed interpretive description to interview transcripts and field-notes of 17 liver transplant recipients. Data were evaluated according to inductive thematic analysis. Eschewing the health-related QOL measure for its rigidity and lack of qualitative data, this research captured the lived experiences of liver transplant recipients unlike clinically  focused studies.FINDINGS: The results showed that, although transplantation can make positive changes in their lives, recipients continued to be influenced subtly by illness which can alter their re-conceptualisation and re-definition of QOL and normalcy. The success of a liver transplant does not depend only on the physical care given; to the recipients as the spectre of future ill health and transplant failure continue to be perceived as a constant risks. Ongoing support from family, friends, and healthcare professionals are none-the-less fundamental in the post-transplantation journey.
Real-space pseudopotential calculations for simulating noncontact atomic force microscopy images
Authors: Fan Dingxin , Sakai Yuki , Chelikowsky James R.
Published: May 2018

Noncontact atomic force microscopy (nc-AFM) with a CO-functionalized tip yields high resolution images under many situations. However, nc-AFM images are sometimes difficult to interpret when visualizing polycyclic aromatic hydrocarbons. The authors employ real-space pseudopotentials constructed using density functional theory to simulate nc-AFM images of benzene and dibenzo(cd,n)naphtho(3,2,1,8-pqra)perylene molecules with selected probe tips (such as CO, H2, N2, Br, and CH2O). The selected tips provide accurate simulations, save for the tip functionalized with a Br atom. The authors find contrast inversion with CO and N2 tips at small tip heights and image distortion with the CH2O tip.
Dispersive Radon transform
Authors: Xu Kailiang , Laugier Pascal , Minonzio Jean-Gabriel
Published: May 2018

Dispersion results in the spreading and overlapping of the wave-packets, which often limits the capability of signal interpretation; on the other hand, such a phenomenon can also be used for structure or media evaluation. In this study, the authors propose an original dispersive Radon transform (DRT), which is formulated as integration transform along a set of dispersion curves. Multichannel dispersive signals of each individual mode can be concentrated to a well localized region in the DRT domain. The proposed DRT establishes the sparse projection of the dispersive components and provides an efficient solution for mode separation, noise filtering, and missing data reconstruction. Particularly the DRT method allows projecting the temporal signals of dispersive waves on the space of parameters of interest, which can be used to solve the inverse problem for waveguide or media property estimation. The least-square procedure and sparse scheme of the DRT are introduced. A high-resolution DRT is designed based on an iterative reweighting inversion scheme, which resembles the infinite-aperture velocity gather. The proposed method is applied by analyzing ultrasonic guided waves in plate-like structures and in a human radius specimen. The results suggest that the DRT method can significantly enhance the interpretation of dispersive signals.
Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq
Authors: Filbin Mariella G. , Tirosh Itay , Hovestadt Volker , Shaw McKenzie L. , Escalante Leah E. , Mathewson Nathan D. , Neftel Cyril , Frank Nelli , Pelton Kristine , Hebert Christine M. , Haberler Christine , Yizhak Keren , Gojo Johannes , Egervari Kristof , Mount Christopher , van Galen Peter , Bonal Dennis M. , Nguyen Quang-De , Beck Alexander , Sinai Claire , Czech Thomas , Dorfer Christian , Goumnerova Liliana , Lavarino Cinzia , Carcaboso Angel M. , Mora Jaume , Mylvaganam Ravindra , Luo Christina C. , Peyrl Andreas , Popović Mara , Azizi Amedeo , Batchelor Tracy T. , Frosch Matthew P. , Martinez-Lage Maria , Kieran Mark W. , Bandopadhayay Pratiti , Beroukhim Rameen , Fritsch Gerhard , Getz Gad , Rozenblatt-Rosen Orit , Wucherpfennig Kai W. , Louis David N. , Monje Michelle , Slavc Irene , Ligon Keith L. , Golub Todd R. , Regev Aviv , Bernstein Bradley E. , Suvà Mario L.
Published: May 2018

The cellular composition of H3K27M gliomas

Diffuse midline gliomas with histone H3 lysine27-to-methionine mutations (H3K27M-glioma) are an aggressive type of childhood cancer with few options for treatment. Filbin
et al.
used a single-cell sequencing approach to study the oncogenic programs, genetics, and cellular hierarchies of H3K27M-glioma. Tumors were mainly composed of cells resembling oligodendrocyte precursor cells, whereas differentiated malignant cells were a smaller fraction. In comparison with other gliomas, these cancers had distinct oncogenic programs and stem cell–like profiles that contributed to their stable tumor-propagating potential. The analysis also identified a lineage-specific marker that may be useful in developing therapies.

Science
, this issue p.
331
Synaptic transmission from subplate neurons controls radial migration of neocortical neurons
Authors: Ohtaka-Maruyama Chiaki , Okamoto Mayumi , Endo Kentaro , Oshima Minori , Kaneko Noe , Yura Kei , Okado Haruo , Miyata Takaki , Maeda Nobuaki
Published: May 2018

Transient instruction changes migration

The brain neocortex is built by waves of neurons migrating from deep within the brain to the surface layers. Ohtaka-Maruyama
et al.
found that a layer of neurons that multipolar neurons encounter on their travels instructs the migrating neurons to change phenotype and direction (see the Perspective by Schinder and Lanuza). These subplate neurons form transient glutamatergic synapses with the immature migrants. This results in the migrating multipolar neurons becoming bipolar, more directed, and faster in their final migrations.

Science
, this issue p.
313
; see also p.
265
Plant responses to CO
2
are a question of time
Authors: Hovenden Mark , Newton Paul
Published: May 2018

Long-term experiments show unexpected plant responses to elevated CO
2
concentrations
If two deletions don't stop growth, try three
Authors: Walhout Albertha J. M.
Published: May 2018

Triple mutations in yeast reveal broad scope of genetic interactions
Protein Binding of First-Line Antituberculosis Drugs
Authors: Alghamdi Wael A. , Al-Shaer Mohammad H. , Peloquin Charles A.
Published: May 2018

The 4-drug regimen of rifampin, isoniazid, pyrazinamide, and ethambutol is an inexpensive, reliable option for treating patients with drug-susceptible tuberculosis (TB). Its efficacy could be further improved by determining the free drug concentrations in plasma, knowing that only the unbound drug can freely penetrate to the tissues. Using an ultrafiltration technique, we determined the protein binding (PB) extent and variability of the first-line anti-TB drugs when given simultaneously to TB patients, representing a real-life case scenario. We used clinical samples routinely received by our laboratory. Plasma proteins were also measured. A protein-free medium was used to determine the nonspecific binding. Plasma samples from 22 patients were included, of which plasma proteins were measured for 18 patients. The median PB was determined for rifampin (88%; range, 72 to 91%), isoniazid (14%; range, 0 to 34%), pyrazinamide (1%; range, 0 to 7%), and ethambutol (12%; range, 4 to 24%). Plasma proteins were not found to be significant predictors for the PB of first-line anti-TB drugs. Rifampin PB was positively correlated with its plasma concentration (
P
value = 0.0051). Conversely, isoniazid PB was negatively correlated with its plasma concentration (
P
value = 0.0417). Age was found to have a significant effect on isoniazid PB (
P
value = 0.0376). No correlations were observed in pyrazinamide or ethambutol. In conclusion, we have determined variable PB of rifampin, isoniazid, pyrazinamide, and ethambutol in patient plasma samples, with median values of 88, 14, 1, and 12%, respectively. In this small study, PB of rifampin and that of isoniazid are dependent on their plasma concentrations.
Small and Low but Potent: the Complex Regulatory Role of the Small RNA SolB in Solventogenesis in Clostridium acetobutylicum
Authors: Jones Alexander J. , Fast Alan G. , Clupper Michael , Papoutsakis Eleftherios T.
Published: May 2018

The recently revived
Clostridium acetobutylicum
-based acetone-butanol-ethanol (ABE) fermentation is widely celebrated and studied for its impact on industrial biotechnology.
C. acetobutylicum
has been studied and engineered extensively, yet critical areas of the molecular basis for how solvent formation is regulated remain unresolved. The core solventogenic genes (
adhE1/aad
,
ctfA
,
ctfB
, and
adc
) are carried on the sol locus of the pSOL1 megaplasmid, whose loss leads to asporogenous, “degenerate” cells. The sol locus includes a noncoding small RNA (sRNA), SolB, whose role is presumed to be critical for solventogenesis but has eluded resolution. In the present study, SolB overexpression downregulated the sol-locus genes at the transcript level, resulting in attenuated protein expression and a solvent-deficient phenotype, thus suggesting that SolB affects expression of all sol-locus transcripts and seemingly validating its hypothesized role as a repressor. However, deletion of
solB
resulted in a total loss of acetone production and severe attenuation of butanol formation, with complex effects on sol-locus genes and proteins: it had a small impact on
adc
mRNA or its corresponding protein (acetoacetate decarboxylase) expression level, somewhat reduced
adhE1
and
ctfA-ctfB
mRNA levels, and abolished the
ctfA-ctfB
-encoded coenzyme A transferase (CoAT) activity. Computational predictions support a model whereby SolB expressed at low levels enables the stabilization and translation of sol-locus transcripts to facilitate tuning of the production of various solvents depending on the prevailing culture conditions. A key predicted SolB target is the ribosome binding site (RBS) of the
ctfA
transcript, and this was verified by expressing variants of the
ctfA-ctfB
genes to demonstrate the importance of SolB for acetone formation.

IMPORTANCE
Small noncoding RNAs regulate many important metabolic and developmental programs in prokaryotes, but their role in anaerobes has been explored minimally. Regulation of solvent formation in the important industrial organism
C. acetobutylicum
remains incompletely understood. While the genes for solvent formation and their promoters are known, the means by which this organism tunes the ratios of key solvents, notably the butanol/acetone ratio to balance its electron resources, remains unknown. Significantly, the roles of several coding and noncoding genes in the sol locus in tuning the solvent formation ratios have not been explored. Here we show that the small RNA SolB fine-tunes the expression of solvents, with acetone formation being a key target, by regulating the translation of the acetone formation rate-limiting enzyme, the coenzyme A transferase (CoAT). It is notable that SolB expressed at very low levels enables CoAT translation, while at high, nonphysiological expression levels, it leads to degradation of the corresponding transcript.
Proteins Encoded by the
gerP
Operon Are Localized to the Inner Coat in Bacillus cereus Spores and Are Dependent on GerPA and SafA for Assembly
Authors: Ghosh Abhinaba , Manton James D. , Mustafa Amin R. , Gupta Mudit , Ayuso-Garcia Alejandro , Rees Eric J. , Christie Graham
Published: May 2018

The germination of
Bacillus
spores is triggered by certain amino acids and sugar molecules which permeate the outermost layers of the spore to interact with receptor complexes that reside in the inner membrane. Previous studies have shown that mutations in the hexacistronic
gerP
locus reduce the rate of spore germination, with experimental evidence indicating that the defect stems from reduced permeability of the spore coat to germinant molecules. Here, we use the ellipsoid localization microscopy technique to reveal that all six
Bacillus cereus
GerP proteins share proximity with cortex-lytic enzymes within the inner coat. We also reveal that the GerPA protein alone can localize in the absence of all other GerP proteins and that it has an essential role for the localization of all other GerP proteins within the spore. Its essential role is also demonstrated to be dependent on SafA, but not CotE, for localization, which is consistent with an inner coat location. GerP-null spores are shown also to have reduced permeability to fluorescently labeled dextran molecules compared to wild-type spores. Overall, the results support the hypothesis that the GerP proteins have a structural role within the spore associated with coat permeability.

IMPORTANCE
The bacterial spore coat comprises a multilayered proteinaceous structure that influences the distribution, survival, and germination properties of spores in the environment. The results from the current study are significant since they increase our understanding of coat assembly and architecture while adding detail to existing models of germination. We demonstrate also that the ellipsoid localization microscopy (ELM) image analysis technique can be used as a novel tool to provide direct quantitative measurements of spore coat permeability. Progress in all of these areas should ultimately facilitate improved methods of spore control in a range of industrial, health care, and environmental sectors.
A Capsular Polysaccharide-Specific Antibody Alters Streptococcus pneumoniae Gene Expression during Nasopharyngeal Colonization of Mice
Authors: Doyle Christopher R. , Moon Jee-Young , Daily Johanna P. , Wang Tao , Pirofski Liise-anne
Published: May 2018

Pneumococcal conjugate vaccines (PCV) elicit opsonophagocytic (opsonic) antibodies to pneumococcal capsular polysaccharides (PPS) and reduce nasopharyngeal (NP) colonization by vaccine-includedStreptococcus pneumoniaeserotypes. However, nonopsonic antibodies may also be important for protection against pneumococcal disease. For example, 1E2, a mouse IgG1 monoclonal antibody (MAb) to the serotype 3 (ST3) PPS (PPS3), reduced ST3 NP colonization in mice and altered ST3 gene expressionin vitro. Here, we determined whether 1E2 affects ST3 gene expressionin vivoduring colonization of mice by performing RNA sequencing on NP lavage fluid from ST3-infected mice treated with 1E2, a control MAb, or phosphate-buffered saline. Compared to the results for the controls, 1E2 significantly altered the expression of over 50 genes. It increased the expression of thepiuBCDAoperon, which encodes an iron uptake system, and decreased the expression ofdpr, which encodes a protein critical for resistance to oxidative stress. 1E2-mediated effects on ST3in vivorequired divalent binding, as Fab fragments did not reduce NP colonization or alter ST3 gene expression.In vitro, 1E2 induced dose-dependent ST3 growth arrest and alteredpiuBanddprexpression, whereas an opsonic PPS3 MAb, 5F6, did not. 1E2-treated bacteria were more sensitive to hydrogen peroxide and the iron-requiring antibiotic streptonigrin, suggesting that 1E2 may increase iron import and enhance sensitivity to oxidative stress. Finally, 1E2 also induced rapid capsule sheddingin vitro, suggesting that this may initiate 1E2-induced changes in sensitivity to oxidative stress and gene expression. Our data reveal a novel mechanism of direct, antibody-mediated antibacterial activity that could inform new directions in antipneumococcal therapy and vaccine development.
Metabolic Reprogramming of Vibrio cholerae Impaired in Respiratory NADH Oxidation Is Accompanied by Increased Copper Sensitivity
Authors: Toulouse Charlotte , Metesch Kristina , Pfannstiel Jens , Steuber Julia
Published: May 2018

The importance of the central metabolism for bacterial virulence has raised interest in studying catabolic enzymes not present in the host, such as NQR, as putative targets for antibiotics.
Vibrio cholerae
lacking the NQR, which is studied here, is a model to estimate the impact of specific NQR inhibitors on the phenotype of a pathogen. Our comparative proteomic study provides a framework to evaluate the chances of success of compounds directed against NQR with respect to their bacteriostatic or bactericidal action.
Diversity and Dynamics of the Canadian Coastal Vibrio Community: an Emerging Trend Detected in the Temperate Regions
Authors: Banerjee Swapan K. , Rutley Rebecca , Bussey Jeff
Published: May 2018

Proliferation and abundance of the harmful biotypes of
Vibrio
spp. in the estuaries of Canada indicate the possibility of producing contaminated seafood for human consumption. The findings of this surveillance study may lead to awareness which may help efforts to reduce the occurrence of illnesses or outbreaks caused by
Vibrio
spp. in seafood.
Inhibitory Effects of HIV-2 Vpx on Replication of HIV-1
Authors: Mahdi Mohamed , Szojka Zsófia , Mótyán János András , Tőzsér József
Published: May 2018

Human immunodeficiency virus type 1 (HIV-1) and HIV-2 share a striking genomic resemblance; however, variability in the genetic sequence accounts for the presence of unique accessory genes, such as the viral protein X (
vpx
) gene in HIV-2. Dual infection with both viruses has long been described in the literature, yet the molecular mechanism of how dually infected patients tend to do better than those who are monoinfected with HIV-1 has not yet been explored. We hypothesized that in addition to extracellular mechanisms, an HIV-2 accessory gene is the culprit, and interference at the viral accessory/regulatory protein level is perhaps responsible for the attenuated pathogenicity of HIV-1 observed in dually infected patients. Following simulation of dual infection in cell culture experiments, we found that pretransduction of cells with HIV-2 significantly protects against HIV-1 transduction. Importantly, we have found that this dampening of the infectivity of HIV-1 was a result of interviral interference carried out by viral protein X of HIV-2, resulting in a severe hindrance to the replication dynamics of HIV-1, influencing both its early and late phases of the viral life cycle. Our findings shed light on potential intracellular interactions between the two viruses and broaden our understanding of the observed clinical spectrum in dually infected patients, highlighting HIV-2 Vpx as a potential candidate worth exploring in the fight against HIV-1.

IMPORTANCE
Dual infection with human immunodeficiency virus types 1 and 2 is relatively common in areas of endemicity. For as-yet-unclarified reasons, patients who are dually infected were shown to have lower viral loads and generally a lower rate of progression to AIDS than those who are monoinfected. We aimed to explore dual infection in cell culture, to elucidate possible mechanisms by which HIV-2 may be able to exert such an effect. Our results indicate that on the cellular level, pretransduction of cells with HIV-2 significantly protects against HIV-1 transduction, which was found to be a result of interviral interference carried out by viral protein X of HIV-2. These findings broaden our knowledge of interviral interactions on the cellular level and may provide an explanation for the decreased pathogenicity of HIV-1 in dually infected patients, highlighting HIV-2 Vpx as a potential candidate worth exploring in the fight against HIV.
Comparative Population Genomics Analysis of the Mammalian Fungal Pathogen
Pneumocystis
Authors: Cissé Ousmane H. , Ma Liang , Wei Huang Da , Khil Pavel P. , Dekker John P. , Kutty Geetha , Bishop Lisa , Liu Yueqin , Deng Xilong , Hauser Philippe M. , Pagni Marco , Hirsch Vanessa , Lempicki Richard A. , Stajich Jason E. , Cuomo Christina A. , Kovacs Joseph A.
Published: May 2018

Pneumocystis
species are opportunistic mammalian pathogens that cause severe pneumonia in immunocompromised individuals. These fungi are highly host specific and uncultivable
in vitro
. Human
Pneumocystis
infections present major challenges because of a limited therapeutic arsenal and the rise of drug resistance. To investigate the diversity and demographic history of natural populations of
Pneumocystis
infecting humans, rats, and mice, we performed whole-genome and large-scale multilocus sequencing of infected tissues collected in various geographic locations. Here, we detected reduced levels of recombination and variations in historical demography, which shape the global population structures. We report estimates of evolutionary rates, levels of genetic diversity, and population sizes. Molecular clock estimates indicate that
Pneumocystis
species diverged before their hosts, while the asynchronous timing of population declines suggests host shifts. Our results have uncovered complex patterns of genetic variation influenced by multiple factors that shaped the adaptation of
Pneumocystis
populations during their spread across mammals.

IMPORTANCE
Understanding how natural pathogen populations evolve and identifying the determinants of genetic variation are central issues in evolutionary biology.
Pneumocystis
, a fungal pathogen which infects mammals exclusively, provides opportunities to explore these issues. In humans,
Pneumocystis
can cause a life-threatening pneumonia in immunosuppressed individuals. In analysis of different
Pneumocystis
species infecting humans, rats, and mice, we found that there are high infection rates and that natural populations maintain a high level of genetic variation despite low levels of recombination. We found no evidence of population structuring by geography. Our comparisons of the times of divergence of these species to their respective hosts suggest that
Pneumocystis
may have undergone recent host shifts. The results demonstrate that
Pneumocystis
strains are widely disseminated geographically and provide a new understanding of the evolution of these pathogens.
Repurposing Cytarabine for Treating Primary Effusion Lymphoma by Targeting Kaposi’s Sarcoma-Associated Herpesvirus Latent and Lytic Replications
Authors: Gruffaz Marion , Zhou Shenghua , Vasan Karthik , Rushing Teresa , Michael Qing Liu , Lu Chu , Jung Jae U. , Gao Shou-Jiang
Published: May 2018

Oncogenic Kaposi’s sarcoma-associated herpesvirus (KSHV) is etiologically linked to primary effusion lymphoma (PEL), an aggressive and nontreatable malignancy commonly found in AIDS patients. In this study, we performed a high-throughput screening of 3,731 characterized compounds and identified cytarabine, approved by the FDA for treating numerous types of cancer, as a potent inhibitor of KSHV-induced PEL. We showed the high efficacy of cytarabine in the growth inhibition of various PEL cells by inducing cell cycle arrest and apoptosis. Cytarabine inhibited host DNA and RNA syntheses and therefore induced cellular cytotoxicity. Furthermore, cytarabine inhibited viral DNA and RNA syntheses and induced the rapid degradation of KSHV major latent protein LANA (latency-associated nuclear antigen), leading to the suppression of KSHV latent replication. Importantly, cytarabine effectively inhibited active KSHV replication and virion production in PEL cells. Finally, cytarabine treatments not only effectively inhibited the initiation and progression of PEL tumors but also induced regression of grown PEL tumors in a xenograft mouse model. Altogether, our study has identified cytarabine as a novel therapeutic agent for treating PEL as well as eliminating KSHV persistent infection.

IMPORTANCE
Primary effusion lymphoma is an aggressive malignancy caused by Kaposi’s sarcoma-associated herpesvirus. The outcome of primary effusion lymphoma is dismal without specific treatment. Through a high-throughput screening of characterized compounds, we identified an FDA-approved compound, cytarabine, as a potent inhibitor of primary effusion lymphoma. We showed that cytarabine induced regression of PEL tumors in a xenograft mouse model. Cytarabine inhibited host and viral DNA and RNA syntheses, resulting in the induction of cytotoxicity. Of interest, cytarabine induced the degradation of KSHV major latent protein LANA, hence suppressing KSHV latent replication, which is required for PEL cell survival. Furthermore, cytarabine inhibited KSHV lytic replication program, preventing virion production. Our findings identified cytarabine as a novel therapeutic agent for treating PEL as well as for eliminating KSHV persistent infection. Since cytarabine is already approved by the FDA, it might be an ideal candidate for repurposing for PEL therapy and for further evaluation in advanced clinical trials.