bluuebunny/crossref_metadata_2025 huggingface dataset:
On culture, ethics, and hierarchy: How cultural variations in hierarchical relations are manifested in the code of ethics of British and Korean organizations
Authors: Moon Chanki , Uskul Ayse K. , Weick Mario
Published: November 2017

The present research examined if cultural differences in the extent to which hierarchical relations dictate individuals' behaviors are embedded in objective institutional regulations. Using quantitative and qualitative analysis, we examined codes of ethics of Korean and British organizations in relation to working relationships and corruptive behaviors. We found that, unlike British organizations, Korean organizations endorsed codes of ethics that place greater emphasis on hierarchical relations and contained prescriptions for individuals occupying senior or junior ranks. Ethical codes also appeared to be geared more towards preventing the abuse of power in Korean organizations compared with British organizations. Finally, unlike British organizations, Korean organizations often permitted top‐down exchanges (not bottom‐up exchanges), suggesting that in upper echelons benevolence may be more normative in Korean organizations than in British organizations.
Biological false‐positive venereal disease research laboratory test in cerebrospinal fluid in the diagnosis of neurosyphilis – a case‐control study
Authors: Zheng S. , Lin R.J. , Chan Y.H. , Ngan C.C.L.
Published: November 2017

Background

There is no clear consensus on the diagnosis of neurosyphilis. The Venereal Disease Research Laboratory (VDRL) test from cerebrospinal fluid (CSF) has traditionally been considered the gold standard for diagnosing neurosyphilis but is widely known to be insensitive.

Objective

In this study, we compared the clinical and laboratory characteristics of true‐positive VDRL‐CSF cases with biological false‐positive VDRL‐CSF cases.

Methods

We retrospectively identified cases of true and false‐positive VDRL‐CSF across a 3‐year period received by the Immunology and Serology Laboratory, Singapore General Hospital. A biological false‐positive VDRL‐CSF is defined as a reactive VDRL‐CSF with a non‐reactive Treponema pallidum particle agglutination (TPPA)‐CSF and/or negative Line Immuno Assay (LIA)‐CSF IgG. A true‐positive VDRL‐CSF is a reactive VDRL‐CSF with a concordant reactive TPPA‐CSF and/or positive LIA‐CSF IgG.

Results

During the study period, a total of 1254 specimens underwent VDRL‐CSF examination. Amongst these, 60 specimens from 53 patients tested positive for VDRL‐CSF. Of the 53 patients, 42 (79.2%) were true‐positive cases and 11 (20.8%) were false‐positive cases. In our setting, a positive non‐treponemal serology has 97.6% sensitivity, 100% specificity, 100% positive predictive value and 91.7% negative predictive value for a true‐positive VDRL‐CSF based on our laboratory definition. HIV seropositivity was an independent predictor of a true‐positive VDRL‐CSF.

Conclusion

Biological false‐positive VDRL‐CSF is common in a setting where patients are tested without first establishing a serological diagnosis of syphilis. Serological testing should be performed prior to CSF evaluation for neurosyphilis.
Testing hypotheses for maternal effects inDaphnia magna
Authors: Coakley C. M. , Nestoros E. , Little T. J.
Published: November 2017

Maternal effects are widely observed, but their adaptive nature remains difficult to describe and interpret. We investigated adaptive maternal effects in a clone of the crustaceanDaphnia magna,experimentally varying both maternal age and maternal food and subsequently varying food available to offspring. We had two main predictions: that offspring in a food environment matched to their mothers should fare better than offspring in unmatched environments, and that offspring of older mothers would fare better in low food environments. We detected numerous maternal effects, for example offspring of poorly fed mothers were large, whereas offspring of older mothers were both large and showed an earlier age at first reproduction. However, these maternal effects did not clearly translate into the predicted differences in reproduction. Thus, our predictions about adaptive maternal effects in response to food variation were not met in this genotype of Daphnia magna.
Probing the effect of polymer molecular weight on penetration into the wood cell wall using polyethylenimine (PEI) as a model compound
Authors: DORVEL BRIAN , BOOPALACHANDRAN PRAVEENKUMAR , CHEN IDA , BOWLING ANDREW , WILLIAMS KERRY , KING STEVE
Published: November 2017

Decking is one of the largest applications for the treated wood market. The most challenging property to obtain for treated wood is dimensional stability, which can be achieved, in part, by cell wall bulking, cell wall polymer crosslinking and removal of hygroscopic components in the cell wall. A commonly accepted key requirement is for the actives to infuse through the cell wall, which has a microporosity of ∼5–13 nm. Equally as challenging is being able to measure and quantify the cell wall penetration. Branched polyethylenimine (PEI) was studied as a model polymer for penetration due to its water solubility, polarity, variable molecular weight ranges, and ability to form a chelation complex with preservative metals to treat lumbers. Two different molecular weight polyethylenimines (PEI), one with a weight average molecular weight (Mw) equal to 800 Da and the other 750 000 Da, were investigated for penetration by microscopy and spectroscopy techniques. Analytical methods were developed to both create smooth interfaces and for relative quantitation and visualisation of PEI penetration into the wood. The results showed both PEI with Mw of 800 Da and PEI with Mw of 750 000 Da coated the lumens in high density. However, only the PEI with Mw of 800 appeared to penetrate the cell walls in sufficient levels. Literature has shown the hydrodynamic radii of PEI 750 000 is near 29 nm, whereas a smaller PEI at 25 K showed 4.5 nm. Most importantly the results, based on methods developed, show how molecular weight and tertiary structure of the polymer can affect its penetration, with the microporosity of the wood being the main barrier.
Nursing Gender Pay Differentials in the New Millennium
Authors: Wilson Barbara L. , Butler Matthew J. , Butler Richard J. , Johnson William G.
Published: November 2017

Background

The gender pay gap in the United States is an ongoing issue, affecting women in nearly all occupations. Jobs traditionally associated with men tend to pay better than traditionally female‐dominated jobs, and there is evidence to suggest within‐occupation gender pay differences as well.

Purpose

We compared and contrasted gender wage disparities for registered nurses (RNs), relative to gender wage disparities for another female‐dominated occupation, teachers, while controlling for sociodemographic factors.

Methods

Using data in the American Community Survey, we analyzed the largest U.S. random representative sample of self‐identified RNs and primary or secondary school teachers from 2000 to 2013 using fixed‐effects regression analysis.

Results

There is greater disparity between nurse pay by gender than in teacher pay by gender. In addition, the net return in wages for additional education is higher for school teachers (21.7%) than for RNs (4.7%).

Conclusions

Findings support preferential wages for men in nursing, more so than for men in teaching.

Clinical Relevance

The substantial gender disparities are an indirect measure of the misallocation of resources in effective patient care.
Panama disease and contract farming in the Philippines: Towards a political ecology of risk
Authors: de la Cruz Jaye , Jansen Kees
Published: November 2017

Despite the vast research on contract farming by agrarian scholars, little is known about interactions between biological risks and the social–political effects of contracts. This study analysed contract farming arrangements in the export banana industry in the Philippines amidst an expanding epidemic of Panama disease. We developed a political ecology of risk approach to investigate how ideas about technological and biological risks are influenced by contractual arrangements, and we borrowed from Cultural Theory the insight that risk and blame are connected concepts, always political, and disadvantage marginalized groups through disproportionate risk burdens. Data collection involved the study of contracts, interviews with decision‐makers, and focus group discussions with agrarian cooperatives. The views of both large corporations as well as organized smallholders were recorded. We found that the former contractually compel the latter to bear the burden of the disease, while blaming them for its spread. Risk decisions were embedded in the dynamics of agrarian social relationships, and economic and political arrangements between actors influenced possibilities and limitations for disease control. We argue that the contractual stipulations, in concert with blaming processes, create a discursive environment that both allow inequitable relations to remain unquestioned, and constrain possibilities for control of Panama disease.
Cause‐Related Marketing Persuasion Knowledge: Measuring Consumers' Knowledge and Ability to Interpret CrM Promotions
Authors: Hamby Anne , Brinberg David
Published: November 2017

Cause‐related marketing (CrM), a partnership between a for‐profit and not‐for‐profit company, is an increasingly common promotional approach. Consumers range in awareness of and knowledge about CrM, and vary in their ability to identify and evaluate critical elements of a CrM promotion. The authors describe this knowledge and ability as “CrM persuasion knowledge (CrM‐pk),” which guides consumer response, and can inform how firms use CrM promotions to communicate with consumers. In the current work, the authors define, develop, and evaluate an instrument to measure CrM‐pk, and examine how it moderates the influence of promotional features on consumer attitudes.
The ratification and implementation of the Marrakesh Treaty for visually impaired persons in the Arab Gulf States
Authors: Olwan Rami
Published: November 2017

Visually impaired persons (VIP) have asked the international community to help end the “book famine” they face and increase the number of books available in accessible formats. After 30 years of negotiations, meetings and consultation between member states delegates, negotiators and non‐profit organizations, the World Intellectual Property Organization (WIPO) adopted the VIP Treaty on 27 June 2013 in Marrakesh, Morocco, which entered into force on 30 September 2016. Until today, it is mostly developing countries that have ratified the Treaty and only the United Arab Emirates (UAE) embraced its principles among the Gulf States. This article studies the copyright system in the Arab Gulf States and examines the state's readiness for the adoption of the Treaty. It argues that without considering the cultural and legal implications that influence disability and visual impairment in these states ratifying the Marrakesh Treaty and amending copyright laws in the Gulf States will not alleviate the “book famine” for VIPs in these countries. This article proposes legal and policy recommendations to promote and facilitate accessibility to published works for VIPs that can be adopted in the Arab Gulf States and other developing countries.
Text messaging approach improves weight loss in patients with nonalcoholic fatty liver disease: A randomized study
Authors: Axley Page , Kodali Sudha , Kuo Yong‐Fang , Ravi Sujan , Seay Toni , Parikh Nina M. , Singal Ashwani K.
Published: November 2017

Background & Aims

Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease. The only effective treatment is 7%‐10% weight loss. Mobile technology is increasingly used in weight management. This study was performed to evaluate the effects of text messaging intervention on weight loss in patients with NAFLD.

Methods

Thirty well‐defined NAFLD patients (mean age 52 years, 67% females, mean BMI 38) were randomized 1:1 to control group: counselling on healthy diet and exercise, or intervention group: text messages in addition to healthy life style counselling. NAFLD text messaging program sent weekly messages for 22 weeks on healthy life style education. Primary outcome was change in weight. Secondary outcomes were changes in liver enzymes and lipid profile.

Results

Intervention group lost an average of 6.9 lbs. (P = .03) compared to gain of 1.8 lbs. in the control group (P = .45). Intervention group also showed a decrease in ALT level (−12.5 IU/L, P = .035) and improvement in serum triglycerides (−28 mg/dL, P = .048). There were no changes in the control group on serum ALT level (−6.1 IU/L, P = .46) and on serum triglycerides (−20.3 mg/dL P = .27). Using one‐way analysis of variance, change in outcomes in intervention group compared to control group was significant for weight (P = .02) and BMI (P = .02).

Conclusions

Text messaging on healthy life style is associated with reduction in weight in NAFLD patients. Larger studies are suggested to examine benefits on liver histology, and assess long‐term impact of this approach in patients with NAFLD.
Living quarters of a living fossil—Uncovering the current distribution pattern of the rediscovered Hula painted frog (Latonia nigriventer) using environmental DNA
Authors: Renan Sharon , Gafny Sarig , Perl R. G. Bina , Roll Uri , Malka Yoram , Vences Miguel , Geffen Eli
Published: November 2017

One of the greatest challenges of effective conservation measures is the correct identification of sites where rare and elusive organisms reside. The recently rediscovered Hula painted frog (Latonia nigriventer) has not been seen for many decades and was therefore categorized extinct. Since its rediscovery in 2011, individuals from the critically endangered species have been found, with great effort, only in four restricted sites. We applied the environmental DNA (eDNA) approach to search for new populations of the Hula painted frog in suitable aquatic habitats. We further used the eDNA data to classify the landscape factors associated with the species distribution and to predict its suitable habitats. We sampled 52 aquatic sites in the Hula Valley during the spring of 2015 and 2016 and amplified the samples with a species‐specific qPCR assay. DNA of the Hula painted frog was detected in 22 of the sites, all of which clustered within three main areas. A boosting classification model showed that soil type, vegetation cover and the current and former habitats are all key predictors of the frog's current distribution. Intriguingly, the habitat suitability models reveal a high affinity of the species to its long‐lost habitat of the historical wetlands. Our findings encourage a series of informed searches for new populations of this threatened frog and provide guidance for future conservation management programmes. In the era of global conservation crisis of amphibians, developing the eDNA approach, a reliable detection method for many critically endangered and elusive amphibians, is of particular importance.
Expanding the paradigm for the outer membrane: Acinetobacter baumannii in the absence of endotoxin
Authors: Powers Matthew Joseph , Trent M. Stephen
Published: November 2017

Asymmetry in the outer membrane has long defined the cell envelope of Gram‐negative bacteria. This asymmetry, with lipopolysaccharide (LPS) or lipooligosaccharide (LOS) exclusively in the outer leaflet of the membrane, establishes an impermeable barrier that protects the cell from a number of stressors in the environment. Work done over the past 5 years has shown that Acinetobacter baumannii has the remarkable capability to survive with inactivated production of lipid A biosynthesis and the absence of LOS in its outer membrane. The implications of LOS‐deficient A. baumannii are far‐reaching – from impacts on cell envelope biogenesis and maintenance, bacterial physiology, antibiotic resistance and virulence. This review examines recent work that has contributed to our understanding of LOS‐deficiency and compares it to studies done on Neisseria meningitidis and Moraxella catarrhalis; the two other organisms with this capability.
Using Authentic Materials to Teach Varieties of German: Reflections on a Pedagogical Experiment
Authors: Abrams Zsuzsanna , Schiestl Simone Berchtold
Published: November 2017

German is a language with multiple standard and non‐standard varieties (Fagan, ). Yet L2 textbooks still favor one standard form, offering little information about other varieties of the language. In particular, Austrian and Swiss Standard German are underrepresented, and even when present, the language is often in a mixture of dialect and standard varieties. This is an important limitation, since students who embark on study abroad programs will inevitably be confronted by different standard forms and dialects in spoken language (Lam & O'Brien, ). In order to help learners develop an awareness of varieties of German so that they can succeed in L2 environments, it is essential to supplement textbook materials with other resources. This article describes a ten‐week pedagogical experiment whose objective was to raise learners’ awareness of several spoken varieties of German (standards and dialects) through the use of authentic materials. An attitude survey revealed that the 18 participants viewed learning about German as a multi‐variable language positively. A critical review suggests, however, that not all teaching materials were equally effective in achieving the learning objectives.
Reading Johanna Spyri's Heidi in the Beginning German Language Classroom
Authors: Baumgartner Karin
Published: November 2017

The article explores the benefits of extensive reading in the beginning German language classroom. Employing a simplified version of Johanna Spyri's novel Heidi, the article brings together research on extensive reading and cultural literacy in a unit dedicated to the incorporation of Switzerland into the German language curriculum. The novel is used as a companion piece to the introductory textbooks common at the beginning level and helps develop linguistic skills at that level. Assigning Heidi as part of the German literary canon allows instructors to explore universal themes that align well with the AP curriculum, introduce beginning students to linguistic diversity in the German‐speaking areas of Europe, teach literary analysis, and provide students with a pleasurable extended reading experience.
Survivability of low pathogenic (H9N2) avian influenza virus in water in the presence ofAtyopsis moluccensis(Bamboo shrimp)
Authors: Pathak A. P. , Murugkar H. V. , Nagarajan S. , Sood R. , Tosh C. , Kumar M. , Athira C. K. , Praveen A.
Published: November 2017

Low pathogenic avian influenza virus (LPAIV) exhibits an ecological climax with the aquatic ecosystem. The most widely prevalent subtype ofLPAIVis H9N2. Wild aquatic birds being the natural reservoirs and ducks, the “Trojan horses” for Avian Influenza Virus (AIV), can contaminate the natural water bodies inhabited by them. The virus can persist in the contaminated water from days to years depending upon the environmental conditions. Various aquatic species other than ducks can promote the persistence and transmission ofAIV; however, studies on the role of aquatic fauna in persistence and transmission of avian influenza virus are scarce. This experiment was designed to evaluate the survivability of H9N2LPAIVin water with and withoutAtyopsis moluccensis(bamboo shrimp) for a period of 12 days. The infectivity and amount of virus in water were calculated and were found to be significantly higher in water withA. moluccensisthan in water withoutA. moluccensis. The study also showed thatA. moluccensiscan accumulate the virus mechanically which can infect chicken eggs up to 11 days. The virus transmission potential ofA. moluccensisrequires further studies.
Nihat Keklik's Views of the Theory of Wisdom Building
Authors: Yıldırım Kazım
Published: November 2017

At the entrance of the thesis, Keklik's short life, Turkish Islamic Philosophy organization and his thoughts about Turkish Islamic Philosophy were discussed. In addition, the Wisdom Building (Hikmet Binası) Theory was handled by Keklik. This work, which we have prepared by benefiting from his own works (including lecture notes in undergraduate, graduate and doctoral courses), is composed of the information obtained based on the source scanning.
Virginia Satir’s Family Education and Therapy Model
Authors: Yıldırım Neşide
Published: November 2017

Satir’s model (1916-1988) is not theoretical; it is a practical model; she has developed it by applying herself. It does not include stereotyped shapes in human relationships, but dynamic, variable applications. According to Satir, “the form is not the method itself”, the method is motion; this is a dynamic phenomenon. It constantly changes and tries to remove certain bans that have examined itself and prevented it from changing. A person who grows in a constantly restricted, prohibited environment since childhood cannot fully demonstrate his capacity without being aware of his potential. Such a result is manifested only in a limited environment where development is hindered. The change will take place after the problem is recognized. The goal is to increase self-confidence in the family, to nurture or support better choices, to increase responsibility, and to improve compliance within the family or between people.This study was carried out by using the copy of Satir’s book, which was originally called “The Conjoint Family Therapy” and translated into Turkish by Selim Ali Yeniçeri as “Basic Family Therapy” and published in Istanbul by Beyaz Yayınları in 2016.
Age‐related microvascular dysfunction: novel insight from near‐infrared spectroscopy
Authors: Rosenberry Ryan , Munson Madison , Chung Susie , Samuel T. Jake , Patik Jordan , Tucker Wesley J. , Haykowsky Mark J. , Nelson Michael D.
Published: November 2017

New Findings

What is the central question of this study?

Can near‐infrared spectroscopy (NIRS)‐derived post‐occlusion tissue oxygen saturation recovery kinetics be used to study age‐related impairments in microvascular function?

What is the main finding and its importance?

Using a previously established 5 min cuff occlusion protocol, we found that NIRS‐derived indices of microvascular function were markedly reduced in elderly compared with young participants. However, when we controlled for the absolute level of vasodilatory stimulus and matched the tissue desaturation level between groups, we found similar responses in young and elderly participants. Overall, these data highlight the important role NIRS can serve in clinical vascular biology, but also establish the need for assessing tissue ischaemia during cuff occlusion protocols.

Near‐infrared spectroscopy (NIRS) has emerged as a promising tool to evaluate vascular reactivity in vivo. Whether this approach can be used to assess age‐related impairments in microvascular function has not been tested. Tissue oxygen saturation () post‐occlusion recovery kinetics were measured in two distinct age groups (<35 and >65 years of age) using NIRS placed over the flexor digitorum profundus. Key end‐points included the following: (i) the desaturation rate during cuff occlusion; (ii) the lowest value obtained during ischaemia (); (iii)  reperfusion rate; (iv) the highest value reached after cuff release (); and (v) the reactive hyperaemia area under the curve (AUC). At first, using a conventional 5 min cuff occlusion protocol, the elderly participants achieved a much slower rate of oxygen recovery (1.5 ± 0.2 versus 2.5 ± 0.2% s−1), lower (85.2 ± 2.9 versus 92.3 ± 1.5%) and lower reactive hyperaemia AUC (2651.8 ± 307.0 versus 4940.0 ± 375.8% s−1). However, owing to a lower skeletal muscle resting metabolic rate, was also significantly attenuated in the elderly participants compared with the young control subjects (55.7 ± 3.5 versus 41.0 ± 3.4%), resulting in a much lower ischaemic stimulus. To account for this important difference between groups, we then matched the level of tissue ischaemia in a subset of young healthy participants by reducing the cuff occlusion protocol to 3 min. Remarkably, when we controlled for tissue ischaemia, we observed no differences in any of the hyperaemic end‐points between the young and elderly participants. These data highlight the important role NIRS can serve in vascular biology, but also establish the need for assessing tissue ischaemia during cuff occlusion protocols.
A New Method of Porous Space Reconstruction Using Multipoint Histogram Technology
Authors: Zhang Na , Sun Qian , Fadlelmula Mohamed , Rahman Aziz , Wang Yuhe
Published: November 2017

Pore-scale modeling is becoming a hot topic in overall reservoir characterization process. It is an important approach for revealing the flow behaviors in porous media and exploring unknown flow patterns at pore scale. Over the past few decades, many reconstruction methods have been proposed, and among them the simulated annealing method (SAM) is extensively tested and easier to program. However, SAM is usually based on the two-point probability function or linear-path function, which fails to capture much more information on the multipoint connectivity of various shapes. For this reason, a new reconstruction method is proposed to reproduce the characteristics of a two-dimensional (2D) thin section based on the multipoint histogram. First, the two-point correlation coefficient matrix will be introduced to determine an optimal unit configuration of a multipoint histogram. Second, five different types of seven-point unit configurations will be used to test the unit configuration selection algorithm. Third, the multipoint histogram technology is used for generating the porous space reconstruction based on the prior unit configuration with a different calculation of the objective function. Finally, the spatial connectivity, patterns reproduction, the local percolation theory (LPT), and hydraulic connectivity are used to compare with those of the reference models. The results show that the multipoint histogram technology can produce better multipoint connectivity information than SAM. The reconstructed system matches the training image very well, which reveals that the reconstruction captures the geometry and topology information of the training image, for instance, the shape and distribution of pore space. The seven-point unit configuration is enough to get the spatial characters of the training image. The quality of pattern reproduction of the reconstruction is assessed by computing the multipoint histogram, and the similarity is around 97.3%. Based on the LPT analysis, the multipoint histogram can describe the anticipated patterns of geological heterogeneities and reproduce the connectivity of pore media with a high degree of accuracy. The two-point correlation coefficient matrix and a new construction theory are proposed. The new construction theory provides a stable theory and technology guidance for the study of pore space development and multiphase fluid flow rule in the digital rock.
Low Temperature Cu–Cu Bonding Technology in Three-Dimensional Integration: An Extensive Review
Authors: Panigrahy Asisa Kumar , Chen Kuan-Neng
Published: November 2017

Arguably, the integrated circuit (IC) industry has received robust scientific and technological attention due to the ultra-small and extremely fast transistors since past four decades that consents to Moore's law. The introduction of new interconnect materials as well as innovative architectures has aided for large-scale miniaturization of devices, but their contributions were limited. Thus, the focus has shifted toward the development of new integration approaches that reduce the interconnect delays which has been achieved successfully by three-dimensional integrated circuit (3D IC). At this juncture, semiconductor industries utilize Cu–Cu bonding as a key technique for 3D IC integration. This review paper focuses on the key role of low temperature Cu–Cu bonding, renaissance of the low temperature bonding, and current research trends to achieve low temperature Cu–Cu bonding for 3D IC and heterogeneous integration applications.
Topical valsartan increases the healing pressure on wounds
Authors: Lev-Tov Hadar
Published: November 2017

Topical valsartan may help heal wounds in people with diabetes.
Stress CRasHes into fertility command center
Authors: Michopoulos Vasiliki
Published: November 2017

Corticotropin-releasing hormone alters activity of gonadotropin-releasing hormone neurons in an estradiol-dependent manner.
lytA
Quantitative PCR on Sputum and Nasopharyngeal Swab Samples for Detection of Pneumococcal Pneumonia among the Elderly
Authors: Saukkoriipi Annika , Palmu Arto A. , Pascal Thierry , Verlant Vincent , Hausdorff William P. , Jokinen Jukka
Published: November 2017

Real-time quantitative PCR (qPCR) assay of sputum or nasopharyngeal specimens has shown promising results in the detection of pneumococcal community-acquired pneumonia (PncCAP). We applied qPCR for the autolysin gene (
lytA
) and compared sputum and nasopharyngeal swab (NPS) pneumococcal loads in elderly patients with community-acquired pneumonia (CAP), and specifically in patients with PncCAP, to those in patient groups with other respiratory diseases. We studied patients aged ≥65 years with radiologically confirmed CAP, clinical CAP not retrospectively radiologically confirmed, other acute respiratory infections, or stable chronic lung disease. Pneumococcal etiology of CAP was ascertained by using a combination of multiple diagnostic methods. We analyzed sputum and NPS specimens by
lytA
qPCR with 10
4
pneumococcal genome equivalents (GE)/ml as a cutoff for positivity. Among PncCAP patients,
lytA
qPCR detected pneumococci in 94% of the sputum samples and in large quantities (mean, 6.82 ± 1.02 log
10
GE/ml) but less frequently in NPS (44%) and in smaller quantities (5.55 ± 0.92 log
10
GE/ml). In all other patient groups, ≤10% of the sputum samples and <5% of the NPS samples were
lytA
qPCR positive; but when they were positive, the sputum pneumococcal loads were similar to those in the PncCAP patients, suggesting a pneumococcal etiology in these patients. This was supported by other pneumococcal assay results. Overall, sputum
lytA
qPCR positivity was more common in PncCAP patients than in the other patient groups, but the quantitative results were mainly similar. NPS
lytA
qPCR was less sensitive than sputum
lytA
qPCR in detecting PncCAP.
HIV-1 R5 Macrophage-Tropic Envelope Glycoprotein Trimers Bind CD4 with High Affinity, while the CD4 Binding Site on Non-macrophage-tropic, T-Tropic R5 Envelopes Is Occluded
Authors: Quitadamo Briana , Peters Paul J. , Repik Alexander , O'Connell Olivia , Mou Zhongming , Koch Matthew , Somasundaran Mohan , Brody Robin , Luzuriaga Katherine , Wallace Aaron , Wang Shixia , Lu Shan , McCauley Sean , Luban Jeremy , Duenas-Decamp Maria , Gonzalez-Perez Maria Paz , Clapham Paul R.
Published: November 2017

HIV-1 R5 variants exploit CCR5 as a coreceptor to infect both T cells and macrophages. R5 viruses that are transmitted or derived from immune tissue and peripheral blood are mainly inefficient at mediating infection of macrophages. In contrast, highly macrophage-tropic (mac-tropic) R5 viruses predominate in brain tissue and can be detected in cerebrospinal fluid but are infrequent in immune tissue or blood even in late disease. These mac-tropic R5 variants carry envelope glycoproteins (Envs) adapted to exploit low levels of CD4 on macrophages to induce infection. However, it is unclear whether this adaptation is conferred by an increased affinity of the Env trimer for CD4 or is mediated by postbinding structural rearrangements in the trimer that enhance the exposure of the coreceptor binding site and facilitate events leading to fusion and virus entry. In this study, we investigated CD4 binding to mac-tropic and non-mac-tropic Env trimers and showed that CD4-IgG binds efficiently to mac-tropic R5 Env trimers, while binding to non-mac-tropic trimers was undetectable. Our data indicated that the CD4 binding site (CD4bs) is highly occluded on Env trimers of non-mac-tropic R5 viruses. Such viruses may therefore infect T cells via viral synapses where Env and CD4 become highly concentrated. This environment will enable high-avidity interactions that overcome extremely low Env-CD4 affinities.

IMPORTANCE
HIV R5 variants bind to CD4 and CCR5 receptors on T cells and macrophages to initiate infection. Transmitted HIV variants infect T cells but not macrophages, and these viral strains persist in immune tissue even in late disease. Here we show that the binding site for CD4 present on HIV's envelope protein is occluded on viruses replicating in immune tissue. This occlusion likely prevents antibody binding to this site and neutralization of the virus, but it makes it difficult for virus-CD4 interactions to occur. Such viruses probably pass from T cell to T cell via cell contacts where CD4 is highly concentrated and allows infection via inefficient envelope-CD4 binding. Our data are highly relevant for vaccines that aim to induce antibodies targeting the CD4 binding site on the envelope protein.
N-Myc Downstream-Regulated Gene 1 Restricts Hepatitis C Virus Propagation by Regulating Lipid Droplet Biogenesis and Viral Assembly
Authors: Schweitzer Cameron J. , Zhang Fang , Boyer Audrey , Valdez Kristin , Cam Maggie , Liang T. Jake
Published: November 2017

Host cells harbor various intrinsic mechanisms to restrict viral infections as a first line of antiviral defense. Viruses have evolved various countermeasures against these antiviral mechanisms. Here we show that N-Myc downstream-regulated gene 1 (
NDRG1
) limits productive hepatitis C virus (HCV) infection by inhibiting viral assembly. Interestingly, HCV infection downregulates NDRG1 protein and mRNA expression. The loss of NDRG1 increases the size and number of lipid droplets, which are the sites of HCV assembly. HCV suppresses NDRG1 expression by upregulating MYC, which directly inhibits the transcription of
NDRG1
. The upregulation of MYC also leads to the reduced expression of the NDRG1-specific kinase serum/glucocorticoid-regulated kinase 1 (SGK1), resulting in a markedly diminished phosphorylation of NDRG1. The knockdown of MYC during HCV infection rescues NDRG1 expression and phosphorylation, suggesting that MYC regulates NDRG1 at both the transcriptional and posttranslational levels. Overall, our results suggest that NDRG1 restricts HCV assembly by limiting lipid droplet formation. HCV counteracts this intrinsic antiviral mechanism by downregulating NDRG1 via a MYC-dependent mechanism.

IMPORTANCE
Hepatitis C virus (HCV) is an enveloped single-stranded RNA virus that targets hepatocytes in the liver. HCV is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma, and estimates suggest a global prevalence of 2.35%. Up to 80% of acutely infected individuals will develop chronic infection, and as many as 5% eventually progress to liver cancer. An understanding of the mechanisms behind virus-host interactions and viral carcinogenesis is still lacking. The significance of our research is that it identifies a previously unknown relationship between HCV and a known tumor-associated gene. Furthermore, our data point to a new role for this gene in the liver and in lipid metabolism. Thus, HCV infection serves as a great biological model to advance our knowledge of liver functions and the development of liver cancer.
c-Myc Represses Transcription of Epstein-Barr Virus Latent Membrane Protein 1 Early after Primary B Cell Infection
Authors: Price Alexander M. , Messinger Joshua E. , Luftig Micah A.
Published: November 2017

Recent evidence has shown that the Epstein-Barr virus (EBV) oncogene LMP1 is not expressed at high levels early after EBV infection of primary B cells, despite its being essential for the long-term outgrowth of immortalized lymphoblastoid cell lines (LCLs). In this study, we found that expression of LMP1 increased 50-fold between 7 days postinfection and the LCL state. Metabolic labeling of nascent transcribed mRNA indicated that this was primarily a transcription-mediated event. EBNA2, the key viral transcription factor regulating LMP1, and CTCF, an important chromatin insulator, were recruited to the LMP1 locus similarly early and late after infection. However, the activating histone H3K9Ac mark was enriched at the LMP1 promoter in LCLs relative to that in infected B cells early after infection. We found that high c-Myc activity in EBV-infected lymphoma cells as well as overexpression of c-Myc in an LCL model system repressed LMP1 transcription. Finally, we found that chemical inhibition of c-Myc both in LCLs and early after primary B cell infection increased LMP1 expression. These data support a model in which high levels of endogenous c-Myc activity induced early after primary B cell infection directly repress LMP1 transcription.

IMPORTANCE
EBV is a highly successful pathogen that latently infects more than 90% of adults worldwide and is also causally associated with a number of B cell malignancies. During the latent life cycle, EBV expresses a set of viral oncoproteins and noncoding RNAs with the potential to promote cancer. Critical among these is the viral latent membrane protein LMP1. Prior work suggests that LMP1 is essential for EBV to immortalize B cells, but our recent work indicates that LMP1 is not produced at high levels during the first few weeks after infection. Here we show that transcription of the LMP1 gene can be negatively regulated by a host transcription factor, c-Myc. Ultimately, understanding the regulation of EBV oncogenes will allow us to better treat cancers that rely on these viral products for survival.
Peripheral Blood Biomarkers of Disease Outcome in a Monkey Model of Rift Valley Fever Encephalitis
Authors: Wonderlich Elizabeth R. , Caroline Amy L. , McMillen Cynthia M. , Walters Aaron W. , Reed Douglas S. , Barratt-Boyes Simon M. , Hartman Amy L.
Published: November 2017

Rift Valley Fever (RVF) is an emerging arboviral disease of livestock and humans. Although the disease is caused by a mosquito-borne virus, humans are infected through contact with, or inhalation of, virus-laden particles from contaminated animal carcasses. Some individuals infected with RVF virus (RVFV) develop meningoencephalitis, resulting in morbidity and mortality. Little is known about the pathogenic mechanisms that lead to neurologic sequelae, and thus, animal models that represent human disease are needed. African green monkeys (AGM) exposed to aerosols containing RVFV develop a reproducibly lethal neurological disease that resembles human illness. To understand the disease process and identify biomarkers of lethality, two groups of 5 AGM were infected by inhalation with either a lethal or a sublethal dose of RVFV. Divergence between lethal and sublethal infections occurred as early as 2 days postinfection (dpi), at which point CD8
+
T cells from lethally infected AGM expressed activated caspase-3 and simultaneously failed to increase levels of major histocompatibility complex (MHC) class II molecules, in contrast to surviving animals. At 4 dpi, lethally infected animals failed to demonstrate proliferation of total CD4
+
and CD8
+
T cells, in contrast to survivors. These marked changes in peripheral blood cells occur much earlier than more-established indicators of severe RVF disease, such as granulocytosis and fever. In addition, an early proinflammatory (gamma interferon [IFN-γ], interleukin 6 [IL-6], IL-8, monocyte chemoattractant protein 1 [MCP-1]) and antiviral (IFN-α) response was seen in survivors, while very late cytokine expression was found in animals with lethal infections. By characterizing immunological markers of lethal disease, this study furthers our understanding of RVF pathogenesis and will allow the testing of therapeutics and vaccines in the AGM model.

IMPORTANCE
Rift Valley Fever (RVF) is an important emerging viral disease for which we lack both an effective human vaccine and treatment. Encephalitis and neurological disease resulting from RVF lead to death or significant long-term disability for infected people. African green monkeys (AGM) develop lethal neurological disease when infected with RVF virus by inhalation. Here we report the similarities in disease course between infected AGM and humans. For the first time, we examine the peripheral immune response during the course of infection in AGM and show that there are very early differences in the immune response between animals that survive infection and those that succumb. We conclude that AGM are a novel and suitable monkey model for studying the neuropathogenesis of RVF and for testing vaccines and therapeutics against this emerging viral pathogen.
HupB Is a Bacterial Nucleoid-Associated Protein with an Indispensable Eukaryotic-Like Tail
Authors: Hołówka Joanna , Trojanowski Damian , Ginda Katarzyna , Wojtaś Bartosz , Gielniewski Bartłomiej , Jakimowicz Dagmara , Zakrzewska-Czerwińska Jolanta
Published: November 2017

In bacteria, chromosomal DNA must be efficiently compacted to fit inside the small cell compartment while remaining available for the proteins involved in replication, segregation, and transcription. Among the nucleoid-associated proteins (NAPs) responsible for maintaining this highly organized and yet dynamic chromosome structure, the HU protein is one of the most conserved and highly abundant. HupB, a homologue of HU, was recently identified in mycobacteria. This intriguing mycobacterial NAP is composed of two domains: an N-terminal domain that resembles bacterial HU, and a long and distinctive C-terminal domain that contains several PAKK/KAAK motifs, which are characteristic of the H1/H5 family of eukaryotic histones. In this study, we analyzed the
in vivo
binding of HupB on the chromosome scale. By using PALM (photoactivated localization microscopy) and ChIP-Seq (chromatin immunoprecipitation followed by deep sequencing), we observed that the C-terminal domain is indispensable for the association of HupB with the nucleoid. Strikingly, the
in vivo
binding of HupB displayed a bias from the origin (
oriC
) to the terminus (
ter
) of the mycobacterial chromosome (numbers of binding sites decreased toward
ter
). We hypothesized that this binding mode reflects a role for HupB in organizing newly replicated
oriC
regions. Thus, HupB may be involved in coordinating replication with chromosome segregation.

IMPORTANCE
We currently know little about the organization of the mycobacterial chromosome and its dynamics during the cell cycle. Among the mycobacterial nucleoid-associated proteins (NAPs) responsible for chromosome organization and dynamics, HupB is one of the most intriguing. It contains a long and distinctive C-terminal domain that harbors several PAKK/KAAK motifs, which are characteristic of the eukaryotic histone H1/H5 proteins. The HupB protein is also known to be crucial for the survival of tubercle bacilli during infection. Here, we provide
in vivo
experimental evidence showing that the C-terminal domain of HupB is crucial for its DNA binding. Our results suggest that HupB may be involved in organizing newly replicated regions and could help coordinate chromosome replication with segregation. Given that tuberculosis (TB) remains a serious worldwide health problem (10.4 million new TB cases were diagnosed in 2015, according to WHO) and new multidrug-resistant
Mycobacterium tuberculosis
strains are continually emerging, further studies of the biological function of HupB are needed to determine if this protein could be a prospect for novel antimicrobial drug development.
The NOX Family of Proteins Is Also Present in Bacteria
Authors: Hajjar Christine , Cherrier Mickaël V. , Dias Mirandela Gaëtan , Petit-Hartlein Isabelle , Stasia Marie José , Fontecilla-Camps Juan C. , Fieschi Franck , Dupuy Jérôme
Published: November 2017

Transmembrane NADPH oxidase (NOX) enzymes have been so far only characterized in eukaryotes. In most of these organisms, they reduce molecular oxygen to superoxide and, depending on the presence of additional domains, are called NOX or dual oxidases (DUOX). Reactive oxygen species (ROS), including superoxide, have been traditionally considered accidental toxic by-products of aerobic metabolism. However, during the last decade it has become evident that both O
2
•−
and H
2
O
2
are key players in complex signaling networks and defense. A well-studied example is the production of O
2
•−
during the bactericidal respiratory burst of phagocytes; this production is catalyzed by NOX2. Here, we devised and applied a novel algorithm to search for additional
NOX
genes in genomic databases. This procedure allowed us to discover approximately 23% new sequences from bacteria (in relation to the number of NOX-related sequences identified by the authors) that we have added to the existing eukaryotic NOX family and have used to build an expanded phylogenetic tree. We cloned and overexpressed the identified
nox
gene from
Streptococcus pneumoniae
and confirmed that it codes for an NADPH oxidase. The membrane of the
S. pneumoniae
NOX protein (SpNOX) shares many properties with its eukaryotic counterparts, such as affinity for NADPH and flavin adenine dinucleotide, superoxide dismutase and diphenylene iodonium inhibition, cyanide resistance, oxygen consumption, and superoxide production. Traditionally, NOX enzymes in eukaryotes are related to functions linked to multicellularity. Thus, the discovery of a large family of NOX-related enzymes in the bacterial world brings up fascinating questions regarding their role in this new biological context.

IMPORTANCE
NADPH oxidase (NOX) enzymes have not yet been reported in bacteria. Here, we carried out computational and experimental studies to provide the first characterization of a prokaryotic NOX. Out of 996 prokaryotic proteins showing NOX signatures, we initially selected, cloned, and overexpressed four of them. Subsequently, and based on preliminary testing, we concentrated our efforts on
Streptococcus
SpNOX, which shares many biochemical characteristics with NOX2, the referent model of NOX enzymes. Our work makes possible, for the first time, the study of pure forms of this important family of enzymes, allowing for biophysical and molecular characterization in an unprecedented way. Similar advances regarding other membrane protein families have led to new structures, further mechanistic studies, and the improvement of inhibitors. In addition, biological functions of these newly described bacterial enzymes will be certainly discovered in the near future.