bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of short‐term exposure of antifungal agents on hemolysin activity of oral Candida dubliniensis isolates from Kuwait and Sri Lanka
Authors: Ellepola Arjuna N. B. , Jayathilake J. A. M. Sumedha , Sharma Prem N. , Khan Zia U.
Published: June 2015

Objective

Ability to produce hemolysin by Candida species is an important determinant of its pathogenicity. Candida dubliniensis is implicated in the causation of oral candidosis, which can be treated with polyene, echinocandin, and azole groups of antifungal agents as well as chlorhexidine. After oral application, however, the concentrations of these agents tend to decrease quickly to subtherapeutic levels due to the peculiarity of the oral environment. In this study, we have evaluated the effect of short‐term exposure of sublethal concentrations of these drugs on hemolysin production by oral C. dubliniensis isolates obtained from two different geographical locale.

Materials and methods

Twenty C. dubliniensis oral isolates obtained from Kuwait and Sri Lanka were exposed to sublethal concentrations of nystatin, amphotericin B, caspofungin, ketoconazole, fluconazole, and chlorhexidine for 1 h. Thereafter, the drugs were removed by dilution and the hemolysin production determined by a previously described plate assay.

Results

Hemolysin production of these isolates was significantly suppressed with a percentage reduction of 17.09, 16.45, 17.09, 11.39, 8.23 and 12.03 following exposure to nystatin, amphotericin B, caspofungin, ketoconazole, fluconazole, and chlorhexidine, respectively.

Conclusion

Brief exposure to sublethal concentrations of drugs with antifungal properties appears to reduce the pathogenic potential of C. dubliniensis isolates by suppressing hemolysin production.
Drug‐drug interactions in pharmacologic management of gastroparesis
Authors: Youssef A. S. , Parkman H. P. , Nagar S.
Published: June 2015

Background

Gastroparesis is a disorder characterized by delayed gastric emptying due to chronic abnormal gastric motility. The treatment of the disease often entails the co‐administration of several classes of pharmacological agents. These agents may be metabolized via the same pathway. Inhibition or induction of a shared metabolic pathway leads to change in the systemic levels of prescribed drugs, possibly leading to undesired clinical outcomes.

Purpose

This review discusses different pharmacological treatment for gastroparesis patients and describes the potential for drug‐drug interactions (DDIs) in some of the combinations that are currently used. Prokinetic agents such as metoclopramide and domperidone are the cornerstone in treatment of gastroparesis. Antiemetic agents such as promethazine and ondansetron are frequently administered to gastroparesis patients to reduce nausea and vomiting. Gastroparesis is prevalent in diabetic patients and therefore antidiabetic agents are also prescribed. Many of these co‐administered drugs are metabolized via common drug metabolizing enzymes and this can trigger potential DDIs. The scientific literature was reviewed from the years 1975–2014 for original research articles and reviews that evaluated DDIs in gastroparesis. Many commonly prescribed combinations were predicted to cause potential DDIs in gastroparesis patients. This review will help inform about potential hazardous combinations. This information will hopefully lead to less adverse effects and more successful gastroparesis management.
The N‐glycan on Asn54 affects the atypical N‐glycan composition of plant‐produced interleukin‐22, but does not influence its activity
Authors: Wilbers Ruud H. P. , Westerhof Lotte B. , Reuter Lauri J. , Castilho Alexandra , van Raaij Debbie R. , Nguyen Dieu‐Linh , Lozano‐Torres Jose L. , Smant Geert , Hokke Cornelis H. , Bakker Jaap , Schots Arjen
Published: June 2015

Human interleukin‐22 (IL‐22) is a member of the IL‐10 cytokine family that has recently been shown to have major therapeutic potential. IL‐22 is an unusual cytokine as it does not act directly on immune cells. Instead, IL‐22 controls the differentiation, proliferation and antimicrobial protein expression of epithelial cells, thereby maintaining epithelial barrier function. In this study, we transiently expressed human IL‐22 in Nicotiana benthamiana plants and investigated the role of N‐glycosylation on protein folding and biological activity. Expression levels of IL‐22 were up to 5.4 μg/mg TSP, and N‐glycan analysis revealed the presence of the atypical Lewis A structure. Surprisingly, upon engineering of human‐like N‐glycans on IL‐22 by co‐expressing mouse FUT8 in ΔXT/FT plants a strong reduction in Lewis A was observed. Also, core α1,6‐fucoylation did not improve the biological activity of IL‐22. The combination of site‐directed mutagenesis of Asn54 and in vivo deglycosylation with PNGase F also revealed that N‐glycosylation at this position is not required for proper protein folding. However, we do show that the presence of a N‐glycan on Asn54 contributes to the atypical N‐glycan composition of plant‐produced IL‐22 and influences the N‐glycan composition of N‐glycans on other positions. Altogether, our data demonstrate that plants offer an excellent tool to investigate the role of N‐glycosylation on folding and activity of recombinant glycoproteins, such as IL‐22.
Dermatitis Artefacta in Childhood: A Retrospective Analysis of 44 Patients, 1976–2006
Authors: Alcántara Luna Sara , García Bravo Begoña , Rodríguez Pichardo Antonio , Camacho Martínez Francisco M.
Published: June 2015

Background

Dermatitis artefacta (DA) consists of self‐inflicted skin lesions that the patient denies having produced.

Objectives

To conduct a single‐center retrospective clinical review of children and adolescents diagnosed with DA.

Methods

From 1976 to 2006, data were collected on children diagnosed with DA who were seen in the Department of Dermatology in our hospital. Clinical and epidemiologic features are described. Forty‐four children (mean age 12.9 yrs) were selected, representing 21.9% of the total patients with DA recorded (n = 201) during this period.

Results

The most frequent clinical forms were excoriations (16 [36.4%]) and ulcers (10 [22.7%]), followed by blisters (7 [15.9%]), burns (3 [6.8%]), contact dermatitis (3 [6.8%]), hematomas (2 [4.5%]), panniculitis (1 [2.3%]), cheilitis (1 [2.3%]), and hyperpigmentation (1 [2.3%]). Sixteen were located exclusively on the face and neck, whereas 28 also had other locations (upper limbs, n = 10; lower limbs, n = 9; thorax, n = 5; abdomen, n = 4). Cutaneous lesions were treated with occlusive bandages using zinc paste or a plaster splint when necessary.

Conclusion

To our knowledge, this is the largest reported series of DA in childhood. This complicated psychodermatologic condition requires correct diagnosis, appropriate management, and psychiatric assessment.
Pediatric hematopoietic stem cell transplantation in China: Data and trends during 1998–2012
Authors: Du Hong , Chen Jing , Qin Maoquan , Fang Jianpei , Li Zhiguang , Zhu Yiping , Sun Xin , Huang Dongsheng , Yu Jie , Tang Yongmin , Hu Shaoyan , Li Junhui , Zhang Zhiquan , Luan Zuo
Published: June 2015

The success of treating a wide variety of pediatric diseases with HSCT, hematologic malignancies in particular, has resulted in an increased number of long‐term survivors. This study is the first large‐scale, multicentre report that describes the evolution of pediatric HSCTs in China during the period of 1998–2012. Of all 1052 patients, 266 cases were treated with autologous HSCs and 786 used allogeneic HSCs. The disease indications for HSCTs mainly included leukemias, lymphoma, solid tumors, and non‐malignant disorders. The total number of HSCTs, especially unrelated donor transplants, appeared to be increasing year by year. For patients with neuroblastoma, the therapeutic efficacy seemed to be poor, with a five‐yr OS and DFS rate of 34.5 ± 14.3% and 20.7 ± 9.6%, respectively. In contrast, the survival of patients with SAA was prominently improved, and their five‐yr OS and DFS rates were 82.8 ± 4% and 80.7 ± 4.1%, respectively. Patients who received cord blood transplants had a lower incidence of acute GVHD than that of PB and/or BM transplants from unrelated donors. This report offers us a valuable resource for evaluating the changes in HSCTs in China over the past 14 yr.
Probing the functional role of tick metalloproteases
Authors: Ali Abid , Khan Sardar , Ali Ijaz , Karim Shahid , da Silva Vaz Itabajara , Termignoni Carlos
Published: June 2015

Tick saliva assists feeding through a complex mixture of compounds that disarm the host homeostasis processes, such as platelet aggregation, vasoconstriction and blood clotting, as well as innate and acquired immune responses. Although the various properties of tick salivary glands have sparked great interest as candidate sources for anti‐tick vaccines to prevent tick and tick‐borne diseases, antigens that can be useful to induce an immune response against tick bites or the pathogens transmitted by ticks have not yet been developed. Metalloproteases, which have been found in tick saliva, salivary gland, ovary and midgut, play an important role in inflammation, immunomodulation, fibrinolysis, blood protein digestion, nociception, vitellogenesis, remodelling of extracellular matrix and pathogen transmission. A large proportion of tick metalloproteases belong to the metzincin group, whose members characteristically have a highly conserved zinc‐binding motif integrated into the central α helix at the active site, and a methionine‐containing triad called Met‐turn followed by a cysteine‐rich domain at the C‐terminal site. This review discusses specifically the biological aspects of metalloproteases in tick physiology that have been published to date.
The Love Affair between Philosophy and Poetry: Aristotle's Poetics and Narrative Identity
Authors: Carli Silvia
Published: June 2015

In order to grasp the distinctive character of the object imitated in tragedies, Aristotle's Poetics introduces a new notion of action (praxis), which does not refer to individual ethical deeds as in the Ethics. Rather, it signifies a whole with a beginning, a middle, and an end, whose constitutive components are events (pragmata). This paper argues that the notion of agents undergoes a parallel transformation in the treatise on poetry. It no longer refers exclusively to the authors of ethical deeds, but to the characters who enact the entire dramatic action (prattontes). Their nature can be understood in terms of a potential story whose logos (account, articulation) is a muthos (story, narrative). On this ground, the suggestion is made that the Poetics provides the elements of a narrative conception of human identity.
Entry Threats and Inefficiency in ‘Efficient Bargaining’
Authors: Pal Rupayan , Saha Bibhas
Published: June 2015

We study limit pricing in a model of entry with asymmetric information, where the incumbent firm's wage is endogenously determined through ‘efficient bargaining’ with its union. In the presence of entry threat, the incumbent firm‐union pair may face a conflict between rent sharing and transmitting its cost information. When the wage is not observable to outsiders and employment is the only signalling instrument, over‐employment features in all entry deterring contracts. When the wage is also observable, information transmission becomes easier. Most of the time, then, but not always, the efficient contract deters (induces) entry against the low (high) cost incumbent.
Muscle activation patterns in the Nordic hamstring exercise: Impact of prior strain injury
Authors: Bourne M. N. , Opar D. A. , Williams M. D. , Al Najjar A. , Shield A. J.
Published: June 2015

This study aimed to determine: (a) the spatial patterns of hamstring activation during the Nordic hamstring exercise (NHE); (b) whether previously injured hamstrings display activation deficits during the NHE; and (c) whether previously injured hamstrings exhibit altered cross‐sectional area (CSA). Ten healthy, recreationally active men with a history of unilateral hamstring strain injury underwent functional magnetic resonance imaging of their thighs before and after six sets of 10 repetitions of the NHE. Transverse (T2) relaxation times of all hamstring muscles [biceps femoris long head (BFlh); biceps femoris short head (BFsh); semitendinosus (ST); semimembranosus (SM)] were measured at rest and immediately after the NHE and CSA was measured at rest. For the uninjured limb, the ST's percentage increase in T2 with exercise was 16.8%, 15.8%, and 20.2% greater than the increases exhibited by the BFlh, BFsh, and SM, respectively (P < 0.002 for all). Previously injured hamstring muscles (n = 10) displayed significantly smaller increases in T2 post‐exercise than the homonymous muscles in the uninjured contralateral limb (mean difference −7.2%, P = 0.001). No muscles displayed significant between‐limb differences in CSA. During the NHE, the ST is preferentially activated and previously injured hamstring muscles display chronic activation deficits compared with uninjured contralateral muscles.
Money, Empowerment and Neglect – The Europeanization of Gender Equality Promotion in Greek and Portuguese Employment Policies
Authors: Zartaloudis Sotirios
Published: June 2015

This article examines the impact of the European Employment Strategy (EES) on Greek and Portuguese employment policies (GEP and PEP, respectively) with regard to gender equality promotion during 1995–2009. It focuses on the three main EES goals of gender mainstreaming, reconciliation of work and family, and reducing gender pay gaps, drawing on 44 semi‐structured interviews, official documents and the academic literature. The first part discusses the content of GEP and PEP before the introduction of the EES, arguing that gender equality promotion was absent in both countries. The second part examines the reforms promoting gender equality in GEP and PEP after the introduction of the EES in 1997, arguing that both countries implemented a substantial policy change which can be observed in two areas: first, expanding training and providing start‐up subsidies for women; and, second, expanding care facilities to promote the reconciliation of work and family life. In the third part it is argued that these reforms were linked to the EES and that the Europeanization of GEP occurred through the European Social Fund's conditionality, whereas in the case of PEP, Europeanization occurred through the external empowerment of domestic policy entrepreneurs who used the EES to promote their pro‐gender equality agenda. Overall, in both countries the EU caused a considerable but not transformative change in their welfare states, with the EES constituting the key driver of pro‐gender equality reforms in employment policy.
The assessment of inflammatory activity and toxicity of treated sewage using RAW264.7 cells
Authors: Makene Vedastus W. , Pool Edmund J.
Published: June 2015

Toxicity and inflammatory activity of wastewater samples were evaluated using RAW264.7 cells as a bioassay model. The RAW264.7 cell cultures were exposed to sterile filtered wastewater samples collected from a sewage treatment plant. Cell viability was evaluated using WST‐1 and XTT assays. Inflammatory effects of samples were assessed by determination of nitric oxide (NO) and interleukin 6 (IL‐6). The NO was estimated using the Griess reaction and IL‐6 was measured by enzyme‐linked immunoassay. All samples had no toxicity effects to RAW264.7 cells, however they significantly (P < 0.001) induced NO and IL‐6 production. The highest NO (12.5 ± 0.38 μM) and IL‐6 (25383.84 ± 2327 pg/mL) production was induced by postbiofiltration sample. Final effluent induced the lowest inflammatory response, which indicates effective sewage treatment. In conclusion, wastewater samples can induce inflammatory activities in RAW264.7 cells. The RAW264.7 cells, therefore, can be used as a model for monitoring the quality of treated sewage.
Multiphysics Analysis for Temperature Rise of Electronic Connectors Using a Multiscale Model
Authors: Liao K.-C. , Lu H.-L.
Published: June 2015

Temperature rise could be a crucial issue for some electronic connectors subjected to the relative large electrical current. A nonstatistical multiscale sinusoidal rough surface (MSRS) model is adopted to estimate the contact area between matched metallic terminals as a function of contact load. A fast Fourier transform (FFT) is conducted to characterize the measured surface topology of the terminals. Multiphysics three-dimensional (3D) finite element analysis (FEA) is then carried out to evaluate the temperature rise of mated micro-universal serial bus (USB) connectors. Temperature distributions of the terminal based on the numerical simulations are in good agreement with those based on the measurements using a thermal couple and an infrared thermal camera as well.
Female Sport Fans’ Experiences of Marginalization and Empowerment
Authors: Sveinson Katherine , Hoeber Larena
Published: June 2015

Female sport fan research has been gaining momentum in recent years (e.g., Farrell, Fink, & Fields, 2011; Osborne & Coombs, 2013; Pope, 2011, 2013; Sveinson & Hoeber, 2015). Much of this research focuses on the marginalization that these sport fans experience (e.g., Crawford & Gosling, 2004; Jones, 2008; Sherlock & Elsden, 2000), with little attention given to experiences of empowerment. Therefore, this study sought to explore if female sport fans’ experiences involve marginalization, empowerment, or both and what contributes to these experiences. Multiple individual interviews were conducted with seven highly identified, displaced female sport fans. The data were analyzed through a three-step process involving open, axial, and selective coding (Strauss & Corbin, 1990). The findings demonstrated that the participants experience marginalization based on assumptions that women are inauthentic sport fans. They also felt empowered when they were able to demonstrate legitimacy and authenticity in their fanship.
Spectator Sport and Population Health: A Scoping Study
Authors: Inoue Yuhei , Berg Brennan K. , Chelladurai Packianathan
Published: June 2015

This article examines the current state of research regarding the effect of spectator sport on population health. We conducted a scoping study that involved a comprehensive search of published and gray literature between 1990 and 2014, and identified 135 studies empirically examining the effect of spectator sport on population health. A frequency analysis shows that there is a paucity of studies on this topic published in sport management journals. A thematic analysis further reveals that the reviewed studies can be classified into nine research themes depicting the relationships among certain categories of spectator sport and population health. Based on this scoping study, we develop a framework and identify several gaps in the literature that should be addressed to advance our understanding of the relationship between spectator sport and population health.
HIV family trees reveal viral spread
Authors: Cohen Jon
Published: June 2015

New studies could aid public health efforts.
Tomorrow's table
The End of Plenty The Race to Feed a Crowded World
Joel K. Bourne Jr.
Norton, 2015. 414 pp.
Authors: Steiner Jean L.
Published: June 2015

It's time to talk about the future of food
Visual tracking in the dead of night
Authors: Warrant Eric
Published: June 2015

Even in dim light, hawkmoths can track the motions of wind-tossed flowers

[Also see Report by

Sponberg
et al.

]
Can climate feel the pressure?
Authors: Peppe Daniel J. , Royer Dana L.
Published: June 2015

Changes in atmospheric pressure may be an important long-term climate forcing mechanism

[Also see Report by

Poulsen
et al.

]
Microbial metabolite triggers antimicrobial defense
Authors: Brubaker Sky W. , Monack Denise M.
Published: June 2015

Bacteria can activate innate immune responses by releasing a metabolite that enters host cells

[Also see Report by

Gaudet
et al.

]
Molecular Types of Methicillin-Resistant Staphylococcus aureus and Methicillin-Sensitive S. aureus Strains Causing Skin and Soft Tissue Infections and Nasal Colonization, Identified in Community Health Centers in New York City
Authors: Pardos de la Gandara Maria , Raygoza Garay Juan Antonio , Mwangi Michael , Tobin Jonathan N. , Tsang Amanda , Khalida Chamanara , D'Orazio Brianna , Kost Rhonda G. , Leinberger-Jabari Andrea , Coffran Cameron , Evering Teresa H. , Coller Barry S. , Balachandra Shirish , Urban Tracie , Parola Claude , Salvato Scott , Jenks Nancy , Wu Daren , Burgess Rhonda , Chung Marilyn , de Lencastre Herminia , Tomasz Alexander
Published: June 2015

In November 2011, The Rockefeller University Center for Clinical and Translational Science (CCTS), the Laboratory of Microbiology and Infectious Diseases, and Clinical Directors Network (CDN) launched a research and learning collaborative project with six community health centers in the New York City metropolitan area to determine the nature (clonal type) of community-acquired
Staphylococcus aureus
strains causing skin and soft tissue infections (SSTIs). Between November 2011 and March 2013, wound and nasal samples from 129 patients with active SSTIs suspicious for
S. aureus
were collected and characterized by molecular typing techniques. In 63 of 129 patients, the skin wounds were infected by
S. aureus
: methicillin-resistant
S. aureus
(MRSA) was recovered from 39 wounds and methicillin-sensitive
S. aureus
(MSSA) was recovered from 24. Most—46 of the 63–wound isolates belonged to the CC8/Panton-Valentine leukocidin-positive (PVL
+
) group of
S. aureus
clone USA300: 34 of these strains were MRSA and 12 were MSSA. Of the 63 patients with
S. aureus
infections, 30 were also colonized by
S. aureus
in the nares: 16 of the colonizing isolates were MRSA, and 14 were MSSA, and the majority of the colonizing isolates belonged to the USA300 clonal group. In most cases (70%), the colonizing isolate belonged to the same clonal type as the strain involved with the infection. In three of the patients, the identity of invasive and colonizing MRSA isolates was further documented by whole-genome sequencing.
Antibody and Viral Nucleic Acid Testing of Serum and Cerebrospinal Fluid for Diagnosis of Eastern Equine Encephalitis
Authors: Sherwood James A. , Brittain David C. , Howard John J. , Oliver JoAnne
Published: June 2015

Eastern equine encephalitis diagnostic serum antibody can appear 6 days after the onset of symptoms, and its numbers can increase 4-fold in 4 days, arguing for early and frequent serum testing. In populations where cerebrospinal fluid viral nucleic acid testing sensitivity and specificity remain undetermined, cerebrospinal antibody testing should also be performed.
Comparison of Three Different FDA-Approved Plasma HIV-1 RNA Assay Platforms Confirms the Virologic Failure Endpoint of 200 Copies per Milliliter Despite Improved Assay Sensitivity
Authors: Lalama Christina M. , Jennings Cheryl , Johnson Victoria A. , Coombs Robert W. , McKinnon John E. , Bremer James W. , Cobb Bryan R. , Cloherty Gavin A. , Mellors John W. , Ribaudo Heather J.
Published: June 2015

Discrepancies between HIV-1 RNA results assayed by different FDA-approved platforms have been reported. Plasma samples collected from 332 randomly selected clinical trial participants during the second year of antiretroviral treatment were assayed with three FDA-approved platforms: UltraSensitive Roche Amplicor Monitor, v1.5 (Monitor), the Abbott RealTime HIV-1 test on the m2000 system (Abbott), and the Roche TaqMan HIV-1 test, v2.0 (TaqMan). Samples from 61 additional participants with confirmed HIV-1 RNA levels of >50 copies/ml during trial follow-up were also included. Endpoints were HIV-1 RNA quantification of ≤50 copies/ml versus >50 copies/ml at an individual-sample level (primary) and determination of confirmed virologic failure (VF) from longitudinal samples. A total of 389 participants had results obtained from all assays on at least one sample (median = 6). Proportions of results of >50 copies/ml were 19% (Monitor), 22% (TaqMan), and 25% (Abbott). Despite indication of strong agreement (Cohen's kappa, 0.76 to 0.82), Abbott was more likely to detect HIV-1 RNA levels of >50 copies/ml than Monitor (matched-pair odds ratio [mOR] = 4.2; modified Obuchowski
P
< 0.001) and TaqMan (mOR = 2.1;
P
< 0.001); TaqMan was more likely than Monitor (mOR = 2.6;
P
< 0.001). Despite strong agreement in classifying VF across assay comparisons (kappa, 0.75 to 0.92), at a 50-copies/ml threshold, differences in the probability of VF classification (in the same direction as primary) were apparent (all McNemar's
P
< 0.007). At a 200-copies/ml VF threshold, no differences between assays were apparent (all
P
> 0.13). Despite strong agreement among assays, significant differences were observed with respect to detecting HIV-1 RNA levels of >50 copies/ml and identifying VF at the 50-copies/ml threshold. This has important implications for the definition of VF in clinical trials and clinical practice.
Cytomegalovirus Infection Management in Allogeneic Stem Cell Transplant Recipients: a National Survey in Spain
Authors: Solano Carlos , de la Cámara Rafael , Vázquez Lourdes , López Javier , Giménez Estela , Navarro David
Published: June 2015

This study gathered information about current practices of cytomegalovirus (CMV) infection management in allogeneic stem cell transplant recipients at Spanish centers. A wide variety of preemptive antiviral therapy strategies for CMV infection guided by real-time PCR assays was found, yet the incidence of CMV disease was low (<3%).
Candida quercitrusa Candidemia in a 6-Year-Old Child
Authors: Westblade Lars F. , Rostad Christina A. , Hilinski Joseph A. , Stanley Theresa , Jerris Robert C. , Wilkey Kathy , Pincus David H.
Published: June 2015

We present the first case of candidemia due to
Candida quercitrusa
in a pediatric patient. The identification of the isolate was protracted and ultimately dependent upon sequence analysis of the internal transcribed spacer region. To further define the antifungal susceptibility characteristics of this species, we performed antifungal susceptibility testing of clinical and type strains. In light of the antifungal susceptibility testing results, we caution against the use of fluconazole for treating
C. quercitrusa
infections.
Human Papillomavirus Infectious Entry and Trafficking Is a Rapid Process
Authors: Broniarczyk Justyna , Massimi Paola , Bergant Martina , Banks Lawrence
Published: June 2015

Previous studies have indicated that human papillomavirus (HPV) infectious entry is slow, requiring many hours after initial infection for the virus to gain entry into the nucleus. However, intracellular transport pathways typically are very rapid, and in the context of a natural HPV infection in a wounded epithelium, such slow intracellular transport would seem to be at odds with a normal viral infection. Using synchronized cell populations, we show that HPV trafficking can be a rapid process. In cells that are infected in the late S-early G
2
/M phase of the cell cycle, HPV16 pseudovirion (PsV) reporter DNA gene expression is detectable by 8 h postinfection. Likewise, reporter DNA can be visualized within the nucleus in conjunction with PML nuclear bodies 1 h to 2 h postinfection in cells that are infected with PsVs just prior to mitotic entry. This demonstrates that endosomal trafficking of HPV is rapid, with mitosis being the main restriction on nuclear entry.

IMPORTANCE
HPV infectious entry appears to be slow and requires mitosis to occur before the incoming viral DNA can access the nucleus. In this study, we show that HPV trafficking in the cell actually is very rapid. This demonstrates that in the context of a normal virus infection, the cell cycle state will have a major influence on the time it takes for an incoming virus to enter the nucleus and initiate viral gene expression.
Differential Impact of
In Vivo
CD8
+
T Lymphocyte Depletion in Controller versus Progressor Simian Immunodeficiency Virus-Infected Macaques
Authors: Chowdhury Ankita , Hayes Timothy L. , Bosinger Steven E. , Lawson Benton O. , Vanderford Thomas , Schmitz Joern E. , Paiardini Mirko , Betts Michael , Chahroudi Ann , Estes Jacob D. , Silvestri Guido
Published: June 2015

Numerous studies have demonstrated that CD8
+
T lymphocytes suppress virus replication during human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection. However, the mechanisms underlying this activity of T cells remain incompletely understood. Here, we conducted CD8
+
T lymphocyte depletion in 15 rhesus macaques (RMs) infected intravenously (i.v.) with SIV
mac239
. At day 70 postinfection, the animals (10 progressors with high viremia and 5 controllers with low viremia) were CD8 depleted by i.v. administration of the antibody M-T807R1. As expected, CD8 depletion resulted in increased virus replication, more prominently in controllers than progressors, which correlated inversely with predepletion viremia. Of note, the feature of CD8
+
T lymphocyte predepletion that correlated best with the increase in viremia postdepletion was the level of CD8
+
T-bet
+
lymphocytes. We next found that CD8 depletion resulted in a homogenous increase of SIV RNA in superficial and mesenteric lymph nodes, spleen, and the gastrointestinal tract of both controllers and progressors. Interestingly, the level of SIV DNA increased postdepletion in both CD4
+
central memory T lymphocytes (T
CM
) and CD4
+
effector memory T lymphocytes (T
EM
) in progressor RMs but decreased in the CD4
+
T
CM
of 4 out of 5 controllers. Finally, we found that CD8 depletion is associated with a greater increase in CD4
+
T lymphocyte activation (measured by Ki-67 expression) in controllers than in progressors. Overall, these data reveal a differential impact of CD8
+
T lymphocyte depletion between controller and progressor SIV-infected RMs, emphasizing the complexity of the
in vivo
antiviral role of CD8
+
T lymphocytes.

IMPORTANCE
In this study, we further dissect the impact of CD8
+
T lymphocytes on HIV/SIV replication during SIV infection. CD8
+
T lymphocyte depletion leads to a relatively homogenous increase in viral replication in peripheral blood and tissues. CD8
+
T lymphocyte depletion resulted in a more prominent increase in viral loads and CD4
+
T lymphocyte activation in controllers than in progressors. Interestingly, we found T-bet expression on CD8
+
T lymphocytes to be the best predictor of viral load increase following depletion. The levels of SIV DNA increase postdepletion in both CD4
+
T
CM
and T
EM
in progressor RMs but decrease in the CD4
+
T
CM
of controllers. The findings described in this study provide key insights into the differential functions of CD8
+
T lymphocytes in controller and progressor RMs.
Characterization of Two Human Monoclonal Antibodies Neutralizing Influenza A H7N9 Viruses
Authors: Wang Jianmin , Chen Zhe , Bao Linlin , Zhang Weijia , Xue Ying , Pang XingHuo , Zhang Xi , Qin Chuan , Jin Qi
Published: June 2015

H7N9 was a cause of significant global health concern due to its severe infection and approximately 35% mortality in humans. By screening a Fab antibody phage library derived from patients who recovered from H7N9 infections, we characterized two human monoclonal antibodies (HuMAbs), HNIgGD5 and HNIgGH8. The epitope of these two antibodies was dependent on two residues in the receptor binding site at positions V186 and L226 of the hemagglutinin glycoprotein. Both antibodies possessed high neutralizing activity.
After revision anterior cruciate ligament reconstruction, who returns to sport? A systematic review and meta-analysis
Authors: Grassi Alberto , Zaffagnini Stefano , Marcheggiani Muccioli Giulio Maria , Neri Maria Pia , Della Villa Stefano , Marcacci Maurilio
Published: June 2015

Background

Return to sport and to pre-injury level represents an important outcome after both primary and revision anterior cruciate ligament (ACL) reconstructions.

Purpose

The aim of the present meta-analysis was to determine the return to sport rate after revision ACL reconstruction.

Material and methods

A systematic search was performed of the MEDLINE, Embase and the Cochrane Central Register of Controlled Trials Databases. All the studies that reported return to sport, return to pre-injury sport level and return to high level/competitive sport was considered for the meta-analysis. The overall pooled mean of post-operative knee laxity and pooled rate of positive pivot-shift and objective International Knee Documentation Committee (IKDC) categories was calculated as well.

Results

Overall, 472 abstracts were identified and screened for inclusion and only 16 studies reported the rate of return to any level of sport activity at the final follow-up of 4.7 years (range 1.0–13.2 years), showing a pooled rate of 85.3% (CI 79.7 to 90.2). The return to pre-injury sport level was achieved in 53.4% (CI 37.8 to 68.7) of cases. Normal or quasi-normal objective IKDC, less than 5 mm of side-to-side difference at arthrometric evaluations and grade I-II pivot-shift test were reported in 84%, 88% and 93% patients, respectively.

Conclusions

In spite of almost 8 patients out of 10 returning to sport after revision ACL reconstruction and showing good stability, only half of the patients returned to the same pre-injury sport level.
How do GPs in Switzerland perceive their patients’ satisfaction and expectations? An observational study
Authors: Sebo Paul , Herrmann François R , Haller Dagmar M
Published: June 2015

Objectives

To assess doctors’ perceptions of their patients’ satisfaction and expectations in primary care.

Study design

Cross-sectional study using questionnaires completed by general practitioners (GPs) and their patients.

Setting

Primary care practices in Geneva, Switzerland.

Participants

23 GPs from a random list of 75 GPs practising in the canton of Geneva (participation rate 31%), who each recruited between 50 and 100 consecutive patients coming to the practice for a scheduled medical consultation, leading to a total of 1637 patients (participation rate: 97%, women: 63%, mean age: 54 years). Patient exclusion criteria were: new patients, those consulting in an emergency situation or suffering from disorders affecting their ability to consent, and those who did not speak French.

Main outcome measures

Patients satisfaction with and expectations from the care they received in this practice; GPs perceptions of their patient's satisfaction and expectations.

Results

GPs underestimated all patient satisfaction items (p<0.001 for all items) whereas they overestimated their expectations, except for equipment (laboratory and X-ray) and some accessibility items. In a multivariate analysis to assess which GP factors were associated with correct assessment of their patients’ views, only GPs’ certification status was a significant factor.

Conclusions

GPs tend to underestimate patients’ satisfaction but overestimate their expectations in primary care. These findings may help GPs to understand patients’ views in order to adequately meet their expectations and concerns.
Magnetoencephalography to investigate central perception of exercise-induced breathlessness in people with chronic lung disease: a feasibility pilot
Authors: Johnson Miriam J , Simpson Michael IG , Currow David C , Millman Rebecca E , Hart Simon P , Green Gary
Published: June 2015

Objectives

Neuroimaging in chronic breathlessness is challenging. The study objective was to test the feasibility of magnetoencephalography (MEG) for functional neuroimaging of people with chronic breathlessness.

Design

Feasibility pilot study.

Setting

Respiratory clinic out-patients.

Participants

8 patients (mean age=62; (range 47–83); 4 men) with chronic non-malignant lung disease; modified MRC breathlessness score ≥3 (median mMRC=4), intensity of exercise-induced breathlessness >3/10; no contraindication to MRI scanning.

Methods and measures

4 MEG scans were conducted for each participant: (1) at rest (5 mins), (2) postseated leg exercise-induced breathlessness during recovery (10 mins). Recovery scans (2) were conducted with/without facial airflow in random order; both scans were repeated 1 h later. Participants rated breathlessness intensity (0–10 Numerical Rating Scale (NRS)) at baseline, maximal exertion and every minute during recovery, and rated acceptability of study procedures at the end of the study (0–10 NRS). A structural MRI scan was conducted for MEG coregistration and source-space analyses. Rest data were compared with data from healthy volunteers (N=6; 5 men; mean age=30.7 years±3.9 years).

Results

Exercises and MEG scanning were acceptable to all participants; 7/8 completed the MRI scans. Maximum breathlessness intensity was induced by 5 min’ exercise. The same level was induced for repeat scans (median=8; IQR=7–8). All recovered to baseline by 10 min. Time-frequency profiles of data from the first and last 3 min were analysed in MEG source space based on breathlessness location estimates. Source localisation was performed, but anatomical source inference was limited to the level of the lobe. Differences in areas of activity were seen: during recovery scans; with and without airflow; and between participants/normal volunteers at rest.

Conclusions

MEG is a feasible method to investigate exercise-induced breathlessness in people breathless with chronic lung disease, and able to identify neural activity related to changes in breathlessness.
Convergent polymorphism between stream and lake habitats: the case of brook char
Authors: Samways Kurt M. , Leavitt Peter R. , Magnan Pierre , Rodríguez Marco A. , Peres-Neto Pedro R.
Published: June 2015

Phenotypic variability represents an important factor allowing species to adapt to local environmental conditions, but mechanisms underlying such variation are incompletely understood. This study investigated whether habitat-specific demands on swimming performance or difference in trophic relationships in lakes (pelagic, littoral) and streams (riffle, pool) were significant predictors of phenotypic variation exhibited by brook char (Salvelinus fontinalis), the only fish in the study habitats. Specifically, we hypothesized that pelagic and riffle habitats would impose greater selective pressures associated with swimming, resulting in body morphologies that were dorsoventrally compressed, anterior–posteriorly elongated, and that exhibited a long, narrow caudal peduncle. Geometric morphometrics was applied in a quantitative analysis of body morphology among habitats, whereas stable isotope analysis was used to differentiate between food sources. Analyses revealed that while body morphology differed between lake and stream habitats, there was convergence between the pelagic and riffle habitats, as well as among littoral and riffle and pool environments. The littoral and pool habitats were thought to be more structurally complex, thereby selecting for increased maneuverability but lower sustained swimming and correspondingly deeper bodies with shorter, dorsoventrally expanded caudal peduncles. Carbon source and trophic position did not differ among habitats with a system, suggesting that feeding was not the main influence on morphological plasticity; however, fish in the stream were feeding at a higher trophic position than fish in the lake. These findings suggest that individual species may take advantage of morphological variation to better adapt local surroundings.
Quantitative-profiling of neurotransmitter abnormalities in the disease progression of experimental diabetic encephalopathy rat
Authors: Zhou Xueyan , Zhu Qiuxiang , Han Xiaowen , Chen Renguo , Liu Yaowu , Fan Hongbin , Yin Xiaoxing
Published: June 2015

Diabetic encephalopathy (DE) is one of the most prevalent chronic complications of diabetes mellitus (DM), with neither effective prevention nor proven therapeutic regimen. This study aims to uncover the potential dysregulation pattern of the neurotransmitters in a rat model of streptozotocin (STZ)-induced experimental DE. For that purpose, male Sprague–Dawley (SD) rats were treated with a single intraperitoneal injection of STZ. Cognitive performance was detected with the Morris water maze (MWM) test. Serum, cerebrospinal fluid (CSF), and brain tissues were collected to measure the levels of neurotransmitters. Compared with the control rats, the acetylcholine (ACh) levels in serum, CSF, hippocampus, and cortex were all significantly down-regulated as early as 6 weeks in the STZ treatment group. In contrast, the glutamate (Glu) levels were decreased in CSF and the hippocampus, but unaffected in the serum and cortex of STZ-treated rats. As for γ-aminobutyric acid (GABA), it was down-regulated in serum, but up-regulated in CSF, hippocampus, and the cortex in the STZ-treated group. The mRNA expressions of neurotransmitter-related rate limiting enzymes (including AChE, GAD1, and GAD2) and pro-inflammatory cytokines (including IL-1β and TNF-α) were all increased in the DE rats. Our data suggest that DM induces isoform-dependent and tissue-specific neurotransmitter abnormalities, and that neuroinflammation may underlay the nervous system dysfunction observed in the progression of DE.
Enhanced quantum procedures that resolve difficult problems
Authors: Klauder John R.
Published: June 2015

A careful study of the classical/quantum connection with the aid of coherent states offers new insights into various technical problems. This analysis includes both canonical as well as closely related affine quantization procedures. The new tools are applied to several examples including: (1) A quantum formulation that is invariant under arbitrary classical canonical transformations of coordinates; (2) A toy model that for all positive energy solutions has singularities which are removed at the classical level when the correct quantum corrections are applied; (3) A fairly simple model field theory with non-trivial classical behavior that, when conventionally quantized, becomes trivial, but nevertheless finds a proper solution using the enhanced procedures; (4) A model of scalar field theories with non-trivial classical behavior that, when conventionally quantized, becomes trivial, but nevertheless finds a proper solution using the enhanced procedures; (5) A viable formulation of the kinematics of quantum gravity that respects the strict positivity of the spatial metric in both its classical and quantum versions; and (6) A proposal for a non-trivial quantization of [Formula: see text] that is ripe for study by Monte Carlo computational methods. All of these examples use fairly general arguments that can be understood by a broad audience.
𝒩 = 2 supersymmetric Pais–Uhlenbeck oscillator
Authors: Masterov Ivan
Published: June 2015

We construct an [Formula: see text] supersymmetric extension of the Pais–Uhlenbeck oscillator for distinct frequencies of oscillation. A link to a set of decoupled [Formula: see text] supersymmetric harmonic oscillators with alternating sign in the Hamiltonian is introduced. Symmetries of the model are discussed in detail. The investigation of a quantum counterpart of the constructed model shows that the corresponding Fock space contains negative norm states and the energy spectrum of the system is unbounded from below.
Elaboration of an unexplored substitution site in synthetic bacteriochlorins
Authors: Zhang Nuonuo , Reddy Kanumuri Ramesh , Jiang Jianbing , Taniguchi Masahiko , Sommer Roger D. , Lindsey Jonathan S.
Published: June 2015

The ability to introduce substituents at designated sites about the perimeter of synthetic bacteriochlorins – analogs of bacteriochlorophylls of bacterial photosynthesis – remains a subject of ongoing study. Here, the self-condensation of a dihydrodipyrrin-dioxolane affords a 5-[2-(trimethylsiloxy)ethoxy]bacteriochlorin. Like a 5-methoxybacteriochlorin, the latter undergoes regioselective bromination at the 15-position, directed by the distal 5-alkoxy group. On the other hand, attempted bromination of a bacteriochlorin bearing a 5-(2-hydroxyethoxy) group resulted in intramolecular ether formation with the adjacent β-pyrroline position to give an annulated dioxepine ring (confirmed by single-crystal X-ray structural analysis). The hydroxyethoxy group at the 5-position can be derivatized by acylation. In addition, the installation of auxochromes (methoxycarbonyl, phenylethynyl) at the β-pyrrole rings causes a substantial bathochromic shift of the long-wavelength absorption band (812 nm) and companion fluorescence emission band (821 nm). Taken together, the modification of the 5-substituent complements existing methods for installing a single substituent on the bacteriochlorin macrocycle.
The effect of environmental changes on the evolution and extinction of Late Devonian trilobites from the northern Canning Basin, Western Australia
Authors: McNamara Kenneth J. , Feist Raimund
Published: June 2015

The Frasnian–Famennian Virgin Hills Formation represents fore-reef facies deposited as part of the extensive Late Devonian reef system that fringed the SW Kimberley Block in Western Australia. It contains a rich trilobite fauna dominated primarily by proetids and, to a lesser extent, harpetids, phacopids, scutelluids and odontopleurids. To date, 49 taxa have been described, 40 of these being restricted to the Frasnian. Herein five Frasnian taxa are described, three in open nomenclature, and two the new species
Telopeltis intermedia
and
Otarion fugitivum
. Evolutionary trends in the Virgin Hills trilobites are dominated by a reduction in body size and eye size and, to a lesser extent, a reduction in exoskeletal vaulting. Although recording no sedimentological signature, the fauna was strongly affected by the two globally recognized Kellwasser extinction events. The first, at the end of conodont Zone 12, affected taxa at the species and genus level. The second, within Zone 13b, had a much greater impact on the fauna, causing extinctions at the familial and ordinal levels. Evidence is presented to suggest that evolutionary trends in the trilobites during the late Frasnian reflect selection for forms adapted to low nutrient conditions. The two intensive Kellwasser extinction episodes may reflect periodic massive inputs of nutrients from the terrestrial into the shallow-marine environment.
Cells of renin lineage are adult pluripotent progenitors in experimental glomerular disease
Authors: Pippin Jeffrey W. , Kaverina Natalya V. , Eng Diana G. , Krofft Ronald D. , Glenn Sean T. , Duffield Jeremy S. , Gross Kenneth W. , Shankland Stuart J.
Published: June 2015

Modified vascular smooth muscle cells of the kidney afferent arterioles have recently been shown to serve as progenitors for glomerular epithelial cells in response to glomerular injury. To determine whether such cells of renin lineage (CoRL) serve as progenitors for other cells in kidney disease characterized by both glomerular and tubulointerstitial injury, permanent genetic cell fate mapping of adult CoRL using Ren1cCreER × Rs-tdTomato-R reporter mice was performed. TdTomato-labeled CoRL were almost completely restricted to the juxtaglomerular compartment in healthy kidneys. Following 2 wk of antibody-mediated focal segmental glomerulosclerosis (FSGS) or 16 wk of ⅚ nephrectomy-induced chronic kidney diseases, tdTomato-mapped CoRL were identified in both interstitial and glomerular compartments. In the interstitium, PDGFβ receptor (R)-expressing cells significantly increased, and a portion of these expressed tdTomato. This was accompanied by a decrease in native pericyte number, but an increase in the number of tdTomato cells that coexpressed the pericyte markers PDGFβ-R and NG2. These cells surrounded vessels and coexpressed the pericyte markers CD73 and CD146, but not the endothelial marker ERG. Within glomeruli of reporter mice with the ⅚ nephrectomy model, a subset of labeled CoRL migrated to the glomerular tuft and coexpressed podocin and synaptopodin. By contrast, labeled CoRL were not detected in glomerular or interstitial compartments following uninephrectomy. These observations indicate that in addition to supplying new adult podocytes to glomeruli, CoRL have the capacity to become new adult pericytes in the setting of interstitial disease. We conclude that CoRL have the potential to function as progenitors for multiple adult cell types in kidney disease.