bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacterial microcompartments: widespread prokaryotic organelles for isolation and optimization of metabolic pathways
Authors: Bobik Thomas A. , Lehman Brent P. , Yeates Todd O.
Published: July 2015

Prokaryotes use subcellular compartments for a variety of purposes. An intriguing example is a family of complex subcellular organelles known as bacterial microcompartments (MCPs). MCPs are widely distributed among bacteria and impact processes ranging from global carbon fixation to enteric pathogenesis. Overall, MCPs consist of metabolic enzymes encased within a protein shell, and their function is to optimize biochemical pathways by confining toxic or volatile metabolic intermediates. MCPs are fundamentally different from other organelles in having a complex protein shell rather than a lipid‐based membrane as an outer barrier. This unusual feature raises basic questions about organelle assembly, protein targeting and metabolite transport. In this review, we discuss the three best‐studied MCPs highlighting atomic‐level models for shell assembly, targeting sequences that direct enzyme encapsulation, multivalent proteins that organize the lumen enzymes, the principles of metabolite movement across the shell, internal cofactor recycling, a potential system of allosteric regulation of metabolite transport and the mechanism and rationale behind the functional diversification of the proteins that form the shell. We also touch on some potential biotechnology applications of an unusual compartment designed by nature to optimize metabolic processes within a cellular context.
Epidemiology and outcomes of patients with invasive mould infections: a retrospective observational study from a single centre (2005–2009)
Authors: Klingspor Lena , Saaedi Baharak , Ljungman Per , Szakos Attila
Published: July 2015

Invasive mould infection (IMI) is an important cause of morbidity and mortality in immunocompromised patients. However, Swedish epidemiology data are lacking. The aim of this study was to investigate the epidemiology and outcome of IMI. Cases of proven/probable IMI at Karolinska University Hospital, Stockholm, from 2005 to 2009, were included. A total of 100 patients with 104 episodes of IMI were enrolled. Identified isolates included 101 mould isolates. The majority of the isolates were Aspergillus spp. (74.3%), followed by Mucorales spp. (13.9%), Fusarium spp. (4.9%) and other mould spp. (6.9%). In 13% of the episodes, more than one mould caused the IMI. The lung was most often affected (88.5%). The most frequent underlying disease was haematological malignancies (70%). Following diagnosis, 83.7% initially received antifungal monotherapy, 9.6% received combination therapy and 6.7% no treatment. The overall 90‐day and 1‐year overall survival was 49% and 46% respectively. Survival at 90 days post diagnosis was 71.4% in the solid tumour cohort, 62.5% in patients with solid organ transplants, 43.5% in haematological malignancy (HMs) and 37% in those undergoing allogeneic haematopoietic stem cell transplantation (HSCT). Overall survival was poor in the studied cohort, but is variable among different host categories, with particular opportunities for improvement in patients with underlying HMs and allogeneic HSCT.
Human sporotrichosis beyond the epidemic front reveals classical transmission types in Espírito Santo, Brazil
Authors: de Araujo Mariceli L. , Rodrigues Anderson M. , Fernandes Geisa F. , de Camargo Zoilo P. , de Hoog G. Sybren
Published: July 2015

Sporotrichosis has emerged as the main subcutaneous mycosis of humans and animals around the world. With particular differences in frequency, the major species includes Sporothrix brasiliensis, S. schenckii, S. globosa and S. luriei. In Brazil, the main aspect of this epidemic is based on the zoonotic transmission through the scratches and bites of diseased cats contaminated with S. brasiliensis. Areas free of feline sporotrichosis are poorly characterised in Brazil. We investigated by molecular tools the epidemiology of human sporotrichosis in the Espírito Santo (ES) state, an area adjacent to Rio de Janeiro where is the epicentre of the long‐lasting outbreak of cat‐transmitted sporotrichosis. The human cases in the ES state reveal the prevalence of classical transmission types where subjects are mainly infected by accidental traumatic inoculation during manipulation of contaminated plant material. In agreement with an environmental source, Sporothrix schenckii was the major aetiological agent in the classical transmission. Unlike Rio de Janeiro, this study shows that cat‐transmitted epidemic in Espírito Santo is still scanty, although the geographic proximity and similar climatic features. Sporothrix brasiliensis was the agent in the feline‐transmitted cases. Sporothrix globosa was isolated from a patient with fixed cutaneous lesions that did not report any contact with diseased animals. In conclusion, beyond the borders of Rio de Janeiro epidemic, agents of sporotrichosis in Espírito Santo show a scattered occurrence with high species diversity.
Epidemiology of candidaemia in a tertiary care university hospital: 10‐year experience with 381 candidaemia episodes between 2001 and 2010
Authors: Alp Sehnaz , Arikan‐Akdagli Sevtap , Gulmez Dolunay , Ascioglu Sibel , Uzun Omrum , Akova Murat
Published: July 2015

Defining the epidemiology of and risk factors for candidaemia is necessary to guide empirical treatment. The objectives of this study were to determine the ranking of Candida among positive blood cultures, to define the epidemiology of candidaemia and to investigate patient characteristics and their relationship with C. albicans vs. non‐albicans Candida (NAC) candidaemia. Candidaemia episodes between January 2001 and December 2010 were evaluated retrospectively. Patient characteristics were compared across Candida species. Candida ranked as the fifth most frequently isolated pathogen. Among 381 candidaemia episodes, 58.3% were due to C. albicans, followed by C. parapsilosis (15.2%), C. tropicalis (13.4%) and C. glabrata (6.8%). No statistically significant difference was observed in the distribution of C. albicans vs. NAC (P = 0.432). Patients with NAC had significantly higher rates of haematological disorders (P < 0.001) and neutropenia (P = 0.003), and were older (P = 0.024) than patients with C. albicans, whereas patients with urinary catheters had higher rates of C. albicans (P = 0.007). On species basis, C. tropicalis was more frequently isolated from patients with haematological disorders (P < 0.001) and neutropenia (P = 0.008). Patients with urinary catheters were less likely to have C. parapsilosis (P = 0.043). C. glabrata was most prevalent among patients with solid organ tumours (P = 0.038), but not evident in patients with haematological disorders. Local epidemiological features and risk factors may have important implications for the management of candidaemia.
Evaluation of improvement of onychomycosis in HIV‐infected patients after initiation of combined antiretroviral therapy without antifungal treatment
Authors: Ruíz‐López Patricia , Moreno‐Coutiño Gabriela , Fernández‐Martínez Ramón , Espinoza‐Hernández Jessica , Rodríguez‐Zulueta Patricia , Reyes‐Terán Gustavo
Published: July 2015

Onychomycosis in HIV‐infected patients has a prevalence of 20–44% and is more frequently seen with CD4+ T cell counts ≤450 cel μl−1. There are case reports of improvement in onychomycosis after initiation of combined antiretroviral therapy (cART), but there are no prospective studies that prove the existence and frequency of this phenomenon. The aim of this study was to evaluate if HIV‐infected patients with onychomycosis who begin cART improve and/or cure without antifungal treatment. We included HIV‐infected patients with onychomycosis who had not started cART and nor received antifungal therapy during 6 months prior to the study. We evaluated affected the nails with the Onychomycosis Severity Index (OSI); nail scrapings were collected and direct microscopy with potassium hydroxide (KOH) as well as mycological culture were performed. We repeated these procedures at 3 and 6 months to assess changes. CD4 T cell counts and HIV viral load were obtained. A total of 16 patients were included, with male gender predominance (68.7%); distal and lateral subungual onychomycosis (DLSO) was the most common form (31.3%). Trichophyton rubrum was the most frequently isolated microorganism. OSI decreased 21.5% at 3 months and 40% at 6 months after initiation of antiretrovirals (P = 0.05). We found a non‐significant tendency towards improvement with higher CD4+ T cell counts and with viral loads <100 000 copies ml−1. This could be due to the increase in CD4+ T cells, decreased percentage of Treg (CD4+CD25+) among CD4+ Tcells and/or a decreased viral load; further studies are necessary to prove these hypothesis.
Nutritional status and immune response in murine experimental Jorge Lobo's disease
Authors: Barbosa Adriana Sierra Assencio Almeida , Diório Suzana Madeira , Pedrini Silvia Cristina Barboza , Silva Sônia Maria Uso Ruiz , Sartori Beatriz Gomes Carreira , Calvi Sueli Aparecida , Pereira Paulo Câmara Marques , Vilani‐Moreno Fátima Regina
Published: July 2015

There are no studies investigating the role of nutritional status and immunity associated with Jorge Lobo's disease. The objective of this study was to evaluate the effects of protein‐calorie malnutrition on the immune response of BALB/c mice inoculated with Lacazia loboi. In this study,the animals were divided into four groups: G1: inoculated with restricted diet, G2: not inoculated with restricted diet, G3: inoculated with regular diet, G4: not inoculated with regular diet. The animals of groups G1 and G2 were submitted to malnutrition for 20 days and once installed the animals were inoculated intradermally into the footpad. After 4 months, they were euthanised for the isolation of peritoneal lavage cells and removal of the footpad. The production of IL‐2, IL‐4, IL‐10, IL‐12, IFN‐γ, TNF‐α, H2O2 and nitric oxide (NO) was evaluated in the peritoneal lavage cells. The footpad was evaluated regarding the size of macroscopic lesions, number of fungi and viability index. The results showed that the infection did not exert great influence on the body weight of the mice and previous malnutrition was an unfavourable factor for viability index, number of fungi, macroscopic lesion size in the footpad and production of H2O2, NO, IL‐12, IL‐10 and IFN‐γ, suggesting that malnutrition significantly altered fungal activity and peritoneal cells. The results suggest considerable interaction between nutrition and immunity in Jorge Lobo's disease.
Age‐related aspects of human IgM+ B cell heterogeneity
Authors: Martin Victoria , Wu Yu‐Chang , Kipling David , Dunn‐Walters Deborah K.
Published: July 2015

The CD27+IgD+ B cell population, known as IgM memory, reduces with age. It is thought that this population is responsible for pneumococcal polysaccharide T‐independent responses, and that the age‐related reduction might be partially responsible for the increased susceptibility of older people to bacterial pathogens. There are other IgM+ B cell populations that do not express IgD. We compared the different IgM populations using high‐throughput sequencing of the immunoglobulin (Ig) gene repertoire and multidimensional cell phenotyping and found that the different populations of IgM cells, defined by CD27 and IgD expression, have repertoire differences. Some of these differences are likely indicative of different selection pressures in an immune response, although the older individuals were found to have a changed repertoire in naive B cells, which may contribute to some of the changes seen in memory cells. In addition, even within the CD27+IgD+ IgM memory population there are multiple cell types. We show that the level of IgM expression varies substantially and hypothesize that this distinguishes between T‐dependent and T‐independent types of IgM memory cells. Significant age‐related changes in the relative proportions of these populations may exacerbate the reduction in T‐independent responders in old age.
Change of function of the wheat stress‐responsive transcriptional repressor TaRAP2.1L by repressor motif modification
Authors: Amalraj Amritha , Luang Sukanya , Kumar Manoj Yadav , Sornaraj Pradeep , Eini Omid , Kovalchuk Nataliya , Bazanova Natalia , Li Yuan , Yang Nannan , Eliby Serik , Langridge Peter , Hrmova Maria , Lopato Sergiy
Published: July 2015

Plants respond to abiotic stresses by changes in gene regulation, including stress‐inducible expression of transcriptional activators and repressors. One of the best characterized families of drought‐related transcription factors are dehydration‐responsive element binding (DREB) proteins, known as C‐repeat binding factors (CBF). The wheat DREB/CBF gene TaRAP2.1L was isolated from drought‐affected tissues using a dehydration‐responsive element (DRE) as bait in a yeast one‐hybrid screen. TaRAP2.1L is induced by elevated abscisic acid, drought and cold. A C‐terminal ethylene responsive factor‐associated amphiphilic repression (EAR) motif, known to be responsible for active repression of target genes, was identified in the TaRAP2.1L protein. It was found that TaRAP2.1L has a unique selectivity of DNA‐binding, which differs from that of DREB activators. This binding selectivity remains unchanged in a TaRAP2.1L variant with an inactivated EAR motif (TaRAP2.1Lmut). To study the role of the TaRAP2.1L repressor activity associated with the EAR motif in planta, transgenic wheat overexpressing native or mutated TaRAP2.1L was generated. Overexpression of TaRAP2.1L under constitutive and stress‐inducible promoters in transgenic wheat and barley led to dwarfism and decreased frost tolerance. By contrast, constitutive overexpression of the TaRAP2.1Lmut gene had little or no negative influence on wheat development or grain yield. Transgenic lines with the TaRAP2.1Lmut transgene had an enhanced ability to survive frost and drought. The improved stress tolerance is attributed to up‐regulation of several stress‐related genes known to be downstream genes of DREB/CBF activators.
Subungual Congenital Nevus with Recurrent Nevus Phenomenon
Authors: El‐Khayat Rami H. , Rashid Abid , Walsh Maureen Y. , McKenna Kevin E.
Published: July 2015

Melanonychia is uncommon. We report the first case of histopathologic recurrence of a completely excised subungual congenital nevus that presented as congenital melanonychia
Proteomic analysis of Arabidopsis thaliana (L.) Heynh responses to a generalist sucking pest (Myzus persicae Sulzer)
Authors: Truong D.‐H. , Bauwens J. , Delaplace P. , Mazzucchelli G. , Lognay G. , Francis F.
Published: July 2015

Herbivorous insects can cause severe cellular changes to plant foliage following infestations, depending on feeding behaviour. Here, a proteomic study was conducted to investigate the influence of green peach aphid (Myzus persicae Sulzer) as a polyphagous pest on the defence response of Arabidopsis thaliana (L.) Heynh after aphid colony establishment on the host plant (3 days). Analysis of about 574 protein spots on 2‐DE gels revealed 31 differentially expressed protein spots. Twenty out of these 31 differential proteins were selected for analysis by mass spectrometry. In 12 of the 20 analysed spots, we identified seven and nine proteins using MALDI‐TOF‐MS and LC‐ESI‐MS/MS, respectively. Of the analysed spots, 25% contain two proteins. Different metabolic pathways were modulated in Arabidopsis leaves according to aphid feeding: most corresponded to carbohydrate, amino acid and energy metabolism, photosynthesis, defence response and translation. This paper has established a survey of early alterations induced in the proteome of Arabidopsis by M. persicae aphids. It provides valuable insights into the complex responses of plants to biological stress, particularly for herbivorous insects with sucking feeding behaviour.
A Case‐Crossover Study of Temperature and Infant Mortality in California
Authors: Basu Rupa , Pearson Dharshani , Sie Lillian , Broadwin Rachel
Published: July 2015

Background

While most research on temperature and mortality has focused on the elderly, little has concentrated on infants, who may also lack thermoregulatory responses to heat exposure.

Methods

We examined mean daily apparent temperature, a combination of temperature and humidity, and infant deaths in California during the warm season of May through October 1999 to 2011. Deaths from all causes and specifically from congenital malformations, sudden infant death syndrome, abnormal gestation duration, respiratory causes, and circulatory causes were considered in a time‐stratified case‐crossover analysis of 12 356 infant deaths.

Results

For all‐cause mortality, excess risk was 4.4% (95% confidence interval −0.3, 9.2) per 5.6°C increase for average of same day and previous 3 days apparent temperature (lag 03). The associations for apparent temperature and both all‐cause mortality and deaths caused by gestation duration were highest for Black infants (13.3%, 95% CI 0.6, 27.6 and 23.7%, 95% CI −3.3, 58.2, respectively), while White infants had elevated risk for deaths from respiratory causes (44.6%; −0.7, 110.5). We further observed differential effects for neonates (infants aged 28 days and under) and post‐neonates (infants above 28 days and under 1 year), and coastal and non‐coastal regions. These associations remained even after considering criteria air pollutants.

Conclusions

This study suggests that infants are a vulnerable subgroup to heat exposure. Further studies should be conducted with a sufficient number of cases of infant deaths in other locales.
Randomization Inference for Treatment Effect Variation
Authors: Ding Peng , Feller Avi , Miratrix Luke
Published: July 2015

Applied researchers are increasingly interested in whether and how treatment effects vary in randomized evaluations, especially variation that is not explained by observed covariates. We propose a model-free approach for testing for the presence of such unexplained variation. To use this randomization-based approach, we must address the fact that the average treatment effect, which is generally the object of interest in randomized experiments, actually acts as a nuisance parameter in this setting. We explore potential solutions and advocate for a method that guarantees valid tests in finite samples despite this nuisance. We also show how this method readily extends to testing for heterogeneity beyond a given model, which can be useful for assessing the sufficiency of a given scientific theory. We finally apply our method to the National Head Start impact study, which is a large-scale randomized evaluation of a Federal preschool programme, finding that there is indeed significant unexplained treatment effect variation.
Effortful Control Mediates Relations Between Children's Attachment Security and their Regard for Rules of Conduct
Authors: Nordling J. K. , Boldt Lea J. , O'Bleness Jessica , Kochanska Grazyna
Published: July 2015

Although attachment security has been associated with children's rule‐compatible conduct, the mechanism through which attachment influences early regard for rules is not well established. We hypothesized that effortful control would mediate the link between security and indicators of children's emerging regard for rules (discomfort following rule violations, internalization of parents’ and experimenter's rules, few externalizing behaviors). In a longitudinal study, the Attachment Q‐Set was completed by parents, effortful control was observed, and Regard for Rules was observed and rated by parents. The proposed model fit the data well: Children's security to mothers predicted their effortful control, which in turn had a direct link to a greater Regard for Rules. Children's security with fathers did not predict effortful control. The mother‐child relationship appears particularly important for positive developmental cascades of self‐regulation and socialization.
Sex Differences in Preadolescents’ Attachment Strategies: Products of Harsh Environments or of Gender Identity?
Authors: Pauletti Rachel E. , Cooper Patrick J. , Aults Christopher D. , Hodges Ernest V. E. , Perry David G.
Published: July 2015

We evaluated two hypotheses proposed to account for sex differences in preadolescents’ insecure attachment strategies (more avoidant for boys, more preoccupied for girls). The first hypothesis, rooted in life history theory, is that the sex differences develop among children who experience adverse environmental conditions (e.g., harsh parenting). The second hypothesis, grounded in gender self‐socialization theory, is that the sex differences develop among children who identify confidently with their gender collective. Data from an ethnically/racially diverse sample (443 girls, 420 boys; M age = 11.1 years) supported the second hypothesis: Sex differences were evident mainly among children who felt gender‐typical, were content with their gender, or felt pressure to avoid cross‐sex behavior. Further, sex differences were generally smaller rather than larger among children experiencing adverse environments.
HLA genetic diversity in Hungarians and Hungarian Gypsies: complementary differentiation patterns and demographic signals revealed by HLA‐A, ‐B and ‐DRB1 in Central Europe
Authors: Inotai D. , Szilvasi A. , Benko S. , Boros‐Major A. , Illes Z. , Bors A. , Kiss K. P. , Rajczy K. , Gelle‐Hossó A. , Buhler S. , Nunes J. M. , Sanchez‐Mazas A. , Tordai A.
Published: July 2015

Systematic analyses of human leukocyte antigen (HLA) profiles in different populations may increase the efficiency of bone marrow donor selection and help reconstructing human peopling history. We typed HLA‐A, ‐B, and ‐DRB1 allele groups in two bone marrow donor cohorts of 2402 Hungarians and 186 Hungarian Gypsies and compared them with several Central‐European, Spanish Gypsy, and Indian populations. Our results indicate that different European Gypsy populations share a common origin but diverged genetically as a consequence of founder effect and rapid genetic drift, whereas other European populations are related genetically in relation to geography. This study also suggests that while HLA‐A accurately depicts the effects of genetic drift, HLA‐B, and ‐DRB1 conserve more signatures of ancient population relationships, as a result of balancing selection.
Selecting registration schemes in case of interstitial lung disease follow‐up in CT
Authors: Vlachopoulos Georgios , Korfiatis Panayiotis , Skiadopoulos Spyros , Kazantzi Alexandra , Kalogeropoulou Christina , Pratikakis Ioannis , Costaridou Lena
Published: July 2015

Purpose:

Primary goal of this study is to select optimal registration schemes in the framework of interstitial lung disease (ILD) follow‐up analysis in CT.

Methods:

A set of 128 multiresolution schemes composed of multiresolution nonrigid and combinations of rigid and nonrigid registration schemes are evaluated, utilizing ten artificially warped ILD follow‐up volumes, originating from ten clinical volumetric CT scans of ILD affected patients, to select candidate optimal schemes. Specifically, all combinations of four transformation models (three rigid: rigid, similarity, affine and one nonrigid: third order B‐spline), four cost functions (sum‐of‐square distances, normalized correlation coefficient, mutual information, and normalized mutual information), four gradient descent optimizers (standard, regular step, adaptive stochastic, and finite difference), and two types of pyramids (recursive and Gaussian‐smoothing) were considered. The selection process involves two stages. The first stage involves identification of schemes with deformation field singularities, according to the determinant of the Jacobian matrix. In the second stage, evaluation methodology is based on distance between corresponding landmark points in both normal lung parenchyma (NLP) and ILD affected regions. Statistical analysis was performed in order to select near optimal registration schemes per evaluation metric. Performance of the candidate registration schemes was verified on a case sample of ten clinical follow‐up CT scans to obtain the selected registration schemes.

Results:

By considering near optimal schemes common to all ranking lists, 16 out of 128 registration schemes were initially selected. These schemes obtained submillimeter registration accuracies in terms of average distance errors 0.18 ± 0.01 mm for NLP and 0.20 ± 0.01 mm for ILD, in case of artificially generated follow‐up data. Registration accuracy in terms of average distance error in clinical follow‐up data was in the range of 1.985–2.156 mm and 1.966–2.234 mm, for NLP and ILD affected regions, respectively, excluding schemes with statistically significant lower performance (Wilcoxon signed‐ranks test, p < 0.05), resulting in 13 finally selected registration schemes.

Conclusions:

Selected registration schemes in case of ILD CT follow‐up analysis indicate the significance of adaptive stochastic gradient descent optimizer, as well as the importance of combined rigid and nonrigid schemes providing high accuracy and time efficiency. The selected optimal deformable registration schemes are equivalent in terms of their accuracy and thus compatible in terms of their clinical outcome.
Optical delay encoding for fast timing and detector signal multiplexing in PET
Authors: Grant Alexander M. , Levin Craig S.
Published: July 2015

Purpose:

The large number of detector channels in modern positron emission tomography (PET) scanners poses a challenge in terms of readout electronics complexity. Multiplexing schemes are typically implemented to reduce the number of physical readout channels, but often result in performance degradation. Novel methods of multiplexing in PET must be developed to avoid this data degradation. The preservation of fast timing information is especially important for time‐of‐flight PET.

Methods:

A new multiplexing scheme based on encoding detector interaction events with a series of extremely fast overlapping optical pulses with precise delays is demonstrated in this work. Encoding events in this way potentially allows many detector channels to be simultaneously encoded onto a single optical fiber that is then read out by a single digitizer. A two channel silicon photomultiplier‐based prototype utilizing this optical delay encoding technique along with dual threshold time‐over‐threshold is demonstrated.

Results:

The optical encoding and multiplexing prototype achieves a coincidence time resolution of 160 ps full width at half maximum (FWHM) and an energy resolution of 13.1% FWHM at 511 keV with 3 × 3 × 5 mm3 LYSO crystals. All interaction information for both detectors, including timing, energy, and channel identification, is encoded onto a single optical fiber with little degradation.

Conclusions:

Optical delay encoding and multiplexing technology could lead to time‐of‐flight PET scanners with fewer readout channels and simplified data acquisition systems.
Analysis of an impulse response measured at the basilar membrane of the chinchilla
Authors: Wit Hero P. , Bell Andrew
Published: July 2015

In a recent paper [J. Acoust. Soc. Am. 133, 2224–2239 (2013)], Shera and Cooper report on the impulse response of the basilar membrane (BM) of a chinchilla, a waveform which shows repetitive bursts. They explain the bursts in terms of repeated coherent reflection at BM discontinuities and partial reflection at the stapes (“coherent reflection filtering”). Here the same waveform is examined in detail, highlighting features which indicate that the coherent reflection model, with calls for the same repetitive process to act on each successive burst, does not fully account for the shape of the measured impulse response.
To Run or Not to Run? A Community in Crisis
Authors: Marks Whitney W. , Martin Tiesha R. , Warner Stacy
Published: July 2015

This case addresses the events leading up to the cancellation of the 2012 New York City Marathon in the aftermath of Superstorm Sandy. The case highlights the importance of making fair and timely decisions. The case is assembled based on newspaper accounts of the circumstances that led to New York City’s Mayor Bloomberg declaring the 2012 marathon would be held and then two days later canceling the event. The facts that were available to Mayor Bloomberg are presented in such a way that students can consider and analyze what they would have done and when, and how this may or may not differ from what actually occurred. Most importantly, the case highlights the decision-making process that many sport and event managers will encounter in the field when a weather-related event occurs in the midst of a planned athletic event. Consequently, the case provides students with an opportunity to critically examine the following: 1) how a sport organization should respond to a crisis; 2) the impact of decision-making on various event stakeholders; 3) the ethics involved in decision-making; and 4) how sport and event managers should respond to public criticism. The case is intended for use in classes focused on event management, sport ethics, and public relations.
Getting Clipped: An Evaluation of Crisis Management and the NBA’s Response to the Actions of Donald Sterling
Authors: Shreffler Megan Beth , Presley Gin , Schmidt Samuel
Published: July 2015

In 1981, Donald Sterling became the owner of the San Diego Clippers, an ownership that would prove troublesome for the National Basketball Association (NBA). During his 33 years as an owner of the Clippers, Sterling had four major lawsuits for racial discrimination filed against him and was accused of running the organization with the vision of a “southern plantation-type structure.” On April 25, 2014, the allegations of racist behavior were taken to a new level when Sterling was recorded by his girlfriend, V. Stiviano, proclaiming racist statements toward minorities. The audio recording was put online for the world to hear (mere hours after the conversation) leading to extensive public backlash. Sterling’s comments ultimately led to his demise in the NBA, as NBA Commissioner Adam Silver announced, 4 days after the incident, that Sterling received a $2.5 million fine and was banned from the Clippers organization and the NBA for life. Given the immediacy of the spreading of information on the incident, the NBA and Commissioner Silver knew they had to manage the crisis as swiftly as possible. This case examines Sterling’s involvement with the NBA, his history with racism, and the NBA’s responses to the leaked recording. Multiple models for crisis management and decision making are discussed to help readers develop their own plan for working through organizational crises.
A pro-memory prion protein
Authors: Ferrarelli Leslie K.
Published: July 2015

Neuronal activity stimulates the deSUMOylation and aggregation of CPEB3, which promotes memory formation and maintenance.
Sleep cyclin
Authors: VanHook Annalisa M.
Published: July 2015

The transcriptional cofactor Taranis promotes sleep by decreasing the abundance of CycA and inhibiting Cdk1.
Constraining regulatory T cells
Authors: Foley John F.
Published: July 2015

A receptor for the lipid lysophosphatidylserine reduces regulatory T cell function during inflammation to promote immune responses.
SR-2P Vaginal Microbicide Gel Provides Protection against Herpes Simplex Virus 2 When Administered as a Combined Prophylactic and Postexposure Therapeutic
Authors: Fields Scott A. , Bhatia Gaurav , Fong Julie M. , Liu Mingtao , Shankar Gita N.
Published: July 2015

Previously, we demonstrated that a single prophylactic dose of SR-2P, a novel dual-component microbicide gel comprising acyclovir and tenofovir, led to a modest increase in mouse survival following a lethal challenge of herpes simplex virus 2 (HSV-2). Here, we show that a dose of SR-2P administered 24 h prior to infection provides some protection against the virus, but to a lesser degree than SR-2P administered either once a day for 2 days or 1 h prior to infection. None of the prophylactic doses blocked infection by the virus, and all resulted in 80 to 100% lethality. However, given that a prophylactic dose still provided a significant reduction in overall clinical score, reduced rate of body weight loss, and increased median survival of the mice, we examined whether a repetitive dose regimen (postinfection) in addition to the prophylactic dose could prevent death and reduce the levels of virus in mice. Nearly all (9 of 10 in each group) of the mice that received SR-2P for 2 days prior to infection or that received SR-2P 1 h prior to infection and were administered SR-2P once a day for 10 days after infection showed no clinical symptoms of infection and no viral loads in vaginal swabs and survived for 28 days postinfection. Conversely, mice receiving no treatment or an identical vehicle treatment demonstrated advanced clinical signs and did not survive past day 9 postinfection. We conclude that SR-2P is an effective anti-HSV-2 agent in mice.
Effective Sequestration of Clostridium difficile Protein Toxins by Calcium Aluminosilicate
Authors: Sturino Joseph M. , Pokusaeva Karina , Carpenter Robert
Published: July 2015

Clostridium difficile
is a leading cause of antibiotic-associated diarrhea and the etiologic agent responsible for
C. difficile
infection. Toxin A (TcdA) and toxin B (TcdB) are nearly indispensable virulence factors for
Clostridium difficile
pathogenesis. Given the toxin-centric mechanism by which
C. difficile
pathogenesis occurs, the selective sequestration with neutralization of TcdA and TcdB by nonantibiotic agents represents a novel mode of action to prevent or treat
C. difficile-
associated disease. In this preclinical study, we used quantitative enzyme immunoassays to determine the extent by which a novel drug, calcium aluminosilicate uniform particle size nonswelling M-1 (CAS UPSN M-1), is capable of sequestering TcdA and TcdB
in vitro
. The following major findings were derived from the present study. First, we show that CAS UPSN M-1 efficiently sequestered both TcdA and TcdB to undetectable levels. Second, we show that CAS UPSN M-1's affinity for TcdA is greater than its affinity for TcdB. Last, we show that CAS UPSN M-1 exhibited limited binding affinity for nontarget proteins. Taken together, these results suggest that ingestion of calcium aluminosilicate might protect gastrointestinal tissues from antibiotic- or chemotherapy-induced
C. difficile
infection by neutralizing the cytotoxic and proinflammatory effects of luminal TcdA and TcdB.
Improving the Thermostability and Activity of a Thermophilic Subtilase by Incorporating Structural Elements of Its Psychrophilic Counterpart
Authors: Xu Bi-Lin , Dai Meihong , Chen Yuanhao , Meng Dongheng , Wang Yasi , Fang Nan , Tang Xiao-Feng , Tang Bing
Published: July 2015

The incorporation of the structural elements of thermostable enzymes into their less stable counterparts is generally used to improve enzyme thermostability. However, the process of engineering enzymes with both high thermostability and high activity remains an important challenge. Here, we report that the thermostability and activity of a thermophilic subtilase were simultaneously improved by incorporating structural elements of a psychrophilic subtilase. There were 64 variable regions/residues (VRs) in the alignment of the thermophilic WF146 protease, mesophilic sphericase, and psychrophilic S41. The WF146 protease was subjected to systematic mutagenesis, in which each of its VRs was replaced with those from S41 and sphericase. After successive rounds of combination and screening, we constructed the variant PBL5X with eight amino acid residues from S41. The half-life of PBL5X at 85°C (57.1 min) was approximately 9-fold longer than that of the wild-type (WT) WF146 protease (6.3 min). The substitutions also led to an increase in the apparent thermal denaturation midpoint temperature (

T
m

) of the enzyme by 5.5°C, as determined by differential scanning calorimetry. Compared to the WT, PBL5X exhibited high caseinolytic activity (25 to 95°C) and high values of

K
m

and
k
cat
(25 to 80°C). Our study may provide a rational basis for developing highly stable and active enzymes, which are highly desired in industrial applications.
Arsenophonus and Sodalis Symbionts in Louse Flies: an Analogy to the Wigglesworthia and Sodalis System in Tsetse Flies
Authors: Nováková Eva , Husník Filip , Šochová Eva , Hypša Václav
Published: July 2015

Symbiosis between insects and bacteria result in a variety of arrangements, genomic modifications, and metabolic interconnections. Here, we present genomic, phylogenetic, and morphological characteristics of a symbiotic system associated with
Melophagus ovinus
, a member of the blood-feeding family Hippoboscidae. The system comprises four unrelated bacteria representing different stages in symbiosis evolution, from typical obligate mutualists inhabiting bacteriomes to freely associated commensals and parasites. Interestingly, the whole system provides a remarkable analogy to the association between
Glossina
and its symbiotic bacteria. In both, the symbiotic systems are composed of an obligate symbiont and two facultative intracellular associates,
Sodalis
and
Wolbachia
. In addition, extracellular
Bartonella
resides in the gut of
Melophagus
. However, the phylogenetic origins of the two obligate mutualist symbionts differ. In
Glossina
, the mutualistic
Wigglesworthia
appears to be a relatively isolated symbiotic lineage, whereas in
Melophagus
, the obligate symbiont originated within the widely distributed
Arsenophonus
cluster. Although phylogenetically distant, the two obligate symbionts display several remarkably similar traits (e.g., transmission via the host's “milk glands” or similar pattern of genome reduction). To obtain better insight into the biology and possible role of the
M. ovinus
obligate symbiont, “
Candidatus
Arsenophonus melophagi,” we performed several comparisons of its gene content based on assignments of the Cluster of Orthologous Genes (COG). Using this criterion, we show that within a set of 44 primary and secondary symbionts, “
Ca
. Arsenophonus melophagi” is most similar to
Wigglesworthia
. On the other hand, these two bacteria also display interesting differences, such as absence of flagellar genes in
Arsenophonus
and their presence in
Wigglesworthia
. This finding implies that a flagellum is not essential for bacterial transmission via milk glands.
Copper Reduction and Contact Killing of Bacteria by Iron Surfaces
Authors: Mathews Salima , Kumar Ranjeet , Solioz Marc
Published: July 2015

The well-established killing of bacteria by copper surfaces, also called contact killing, is currently believed to be a combined effect of bacterial contact with the copper surface and the dissolution of copper, resulting in lethal bacterial damage. Iron can similarly be released in ionic form from iron surfaces and would thus be expected to also exhibit contact killing, although essentially no contact killing is observed by iron surfaces. However, we show here that the exposure of bacteria to iron surfaces in the presence of copper ions results in efficient contact killing. The process involves reduction of Cu
2+
to Cu
+
by iron; Cu
+
has been shown to be considerably more toxic to cells than Cu
2+
. The specific Cu
+
chelator, bicinchoninic acid, suppresses contact killing by chelating the Cu
+
ions. These findings underline the importance of Cu
+
ions in the contact killing process and infer that iron-based alloys containing copper could provide novel antimicrobial materials.
Uterine Microbiota Progression from Calving until Establishment of Metritis in Dairy Cows
Authors: Jeon Soo Jin , Vieira-Neto Achilles , Gobikrushanth Mohanathas , Daetz Rodolfo , Mingoti Rodolfo D. , Parize Ana Carolina Brigolin , de Freitas Sabrina Lucas , da Costa Antonio Nelson Lima , Bicalho Rodrigo C. , Lima Svetlana , Jeong K. Casey , Galvão Klibs N.
Published: July 2015

The objective of this study was to evaluate the progression of the uterine microbiota from calving until establishment of metritis. Uterine swabs (
n
= 72) collected at 0, 2, and 6 ± 2 days postpartum (dpp) from 12 metritic and 12 healthy cows were used for metagenomic sequencing of the 16S rRNA gene on the Illumina MiSeq platform. A heat map showed that uterine microbiota was established at calving. The microbiota changed rapidly from 0 to 6 ± 2 dpp, with a decrease in the abundance of
Proteobacteria
and an increase in the abundance of
Bacteroidetes
and
Fusobacteria
, which were dominant in metritic cows. Uterine microbiota composition was shared; however, metritic and healthy cows could be discriminated using relative abundance of bacterial genera at 0, 2, and 6 ± 2 dpp.
Bacteroides
was the main genus associated with metritis because it was the only genus that showed significantly greater abundance in cows with metritis. As the abundance of
Bacteroides
organisms increased, the uterine discharge score, a measure of uterine health, worsened.
Fusobacterium
was also an important genus associated with metritis because
Fusobacterium
abundance increased as
Bacteroides
abundance increased and the uterine discharge score worsened as the abundance increased. The correlation with uterine discharge score and the correlation with
Bacteroides
or
Fusobacterium
showed that other bacteria, such as
Helcoccocus
,
Filifactor
, and
Porphyromonas
, were also associated with metritis. There were also bacteria associated with uterine health, such as “
Candidatus
Blochmannia,”
Escherichia
,
Sneathia
, and
Pedobacter
.
Ineffective Phosphorylation of Mitogen-Activated Protein Kinase Hog1p in Response to High Osmotic Stress in the Yeast Kluyveromyces lactis
Authors: Velázquez-Zavala Nancy , Rodríguez-González Miriam , Navarro-Olmos Rocío , Ongay-Larios Laura , Kawasaki Laura , Torres-Quiroz Francisco , Coria Roberto
Published: July 2015

When treated with a hyperosmotic stimulus,
Kluyveromyces lactis
cells respond by activating the mitogen-activated protein kinase (MAPK)
K. lactis
Hog1 (KlHog1) protein via two conserved branches, SLN1 and SHO1. Mutants affected in only one branch can cope with external hyperosmolarity by activating KlHog1p by phosphorylation, except for single Δ
Klste11
and Δ
Klste50
mutants, which showed high sensitivity to osmotic stress, even though the other branch (SLN1) was intact. Inactivation of both branches by deletion of
KlSHO1
and
KlSSK2
also produced sensitivity to high salt. Interestingly, we have observed that in Δ
Klste11
and Δ
Klsho1
Δ
Klssk2
mutants, which exhibit sensitivity to hyperosmotic stress, and contrary to what would be expected, KlHog1p becomes phosphorylated. Additionally, in mutants lacking both MAPK kinase kinases (MAPKKKs) present in
K. lactis
(KlSte11p and KlSsk2p), the hyperosmotic stress induced the phosphorylation and nuclear internalization of KlHog1p, but it failed to induce the transcriptional expression of
KlSTL1
and the cell was unable to grow in high-osmolarity medium. KlHog1p phosphorylation via the canonical HOG pathway or in mutants where the SHO1 and SLN1 branches have been inactivated requires not only the presence of KlPbs2p but also its kinase activity. This indicates that when the SHO1 and SLN1 branches are inactivated, high-osmotic-stress conditions activate an independent input that yields active KlPbs2p, which, in turn, renders KlHog1p phosphorylation ineffective. Finally, we found that KlSte11p can alleviate the sensitivity to hyperosmotic stress displayed by a Δ
Klsho1
Δ
Klssk2
mutant when it is anchored to the plasma membrane by adding the KlSho1p transmembrane segments, indicating that this chimeric protein can substitute for KlSho1p and KlSsk2p.
A Cyclic GMP-Dependent K
+
Channel in the Blastocladiomycete Fungus Blastocladiella emersonii
Authors: Avelar Gabriela Mól , Glaser Talita , Leonard Guy , Richards Thomas A. , Ulrich Henning , Gomes Suely L.
Published: July 2015

Phototaxis in flagellated zoospores of the aquatic fungus
Blastocladiella emersonii
depends on a novel photosensor,
Blastocladiella emersonii
GC1 (BeGC1), comprising a type I (microbial) rhodopsin fused to a guanylyl cyclase catalytic domain, that produces the conserved second messenger cyclic GMP (cGMP). The rapid and transient increase in cGMP levels during the exposure of zoospores to green light was shown to be necessary for phototaxis and dependent on both rhodopsin function and guanylyl cyclase activity. It is noteworthy that BeGC1 was localized to the zoospore eyespot apparatus, in agreement with its role in the phototactic response. A putative cyclic nucleotide-gated channel (BeCNG1) was also identified in the genome of the fungus and was implicated in flagellar beating via the action of a specific inhibitor (
l
-
cis
-diltiazem) that compromised zoospore motility. Here we show that
B. emersonii
expresses a K
+
channel that is activated by cGMP. The use of specific channel inhibitors confirmed the activation of the channel by cGMP and its K
+
selectivity. These characteristics are consistent with the function of an ion channel encoded by the
BeCNG1
gene. Other blastocladiomycete fungi, such as
Allomyces macrogynus
and
Catenaria anguillulae
, possess genes encoding a similar K
+
channel and the rhodopsin–guanylyl cyclase fusion protein, while the genes encoding both these proteins are absent in nonflagellated fungi. The presence of these genes as a pair seems to be an exclusive feature of blastocladiomycete fungi. Taken together, these data demonstrate that the
B. emersonii
cGMP-activated K
+
channel is involved in the control of zoospore motility, most probably participating in the cGMP-signaling pathway for the phototactic response of the fungus.
Conserved Mode of Interaction between Yeast Bro1 Family V Domains and YP(X)
n
L Motif-Containing Target Proteins
Authors: Kimura Yoko , Tanigawa Mirai , Kawawaki Junko , Takagi Kenji , Mizushima Tsunehiro , Maeda Tatsuya , Tanaka Keiji
Published: July 2015

Yeast Bro1 and Rim20 belong to a family of proteins which possess a common architecture of Bro1 and V domains. Alix and His domain protein tyrosine phosphatase (HD-PTP), mammalian Bro1 family proteins, bind YP(X)
n
L (
n
= 1 to 3) motifs in their target proteins through their V domains. In Alix, the Phe residue, which is located in the hydrophobic groove of the V domain, is critical for binding to the YP(X)
n
L motif. Although the overall sequences are not highly conserved between mammalian and yeast V domains, we show that the conserved Phe residue in the yeast Bro1 V domain is important for binding to its YP(X)
n
L-containing target protein, Rfu1. Furthermore, we show that Rim20 binds to its target protein Rim101 through the interaction between the V domain of Rim20 and the YPIKL motif of Rim101. The mutation of either the critical Phe residue in the Rim20 V domain or the YPIKL motif of Rim101 affected the Rim20-mediated processing of Rim101. These results suggest that the interactions between V domains and YP(X)
n
L motif-containing proteins are conserved from yeast to mammalian cells. Moreover, the specificities of each V domain to their target protein suggest that unidentified elements determine the binding specificity.