bluuebunny/crossref_metadata_2025 huggingface dataset:
Suicide Ideation in Adolescents Following Inpatient Hospitalization: Examination of Intensity and Lability Over 6 Months
Authors: Peters Jessica R. , Mereish Ethan H. , Solomon Joel B. , Spirito Anthony S. , Yen Shirley
Published: March 2018

Understanding suicide ideation (SI) in adolescents, especially during the high‐risk time following hospitalization for a suicidal event, is a crucial component of improving risk assessment. Most studies rely on single assessments of SI, despite the potential for SI to vary considerably over time. This study examined how indices of SI intensity (mean values) and lability (mean squared successive difference values) over a 6‐month period predict suicide attempts (SAs) and self‐harm, as well as how they relate to psychosocial risk factors and affective functioning, in a sample of 103 adolescents hospitalized for a SA or significant SI. Across the sample, SI intensity, but not lability, was associated with SAs and nonsuicidal self‐injury at 6‐month follow‐up. SI intensity performed similarly to single time point SI assessments, and its relations were not moderated by SI lability. SI intensity was also associated with borderline personality disorder criteria and a history of sexual abuse. In contrast, SI lability was associated with greater negative affect intensity and lability. These findings suggest that intensity of SI may confer more risk posthospitalization, and provide support for using these statistical methods to capture two distinct parameters of SI.
Psychological Impairment as a Predictor of Suicide Ideation in Individuals with Anorexia Nervosa
Authors: Bodell Lindsay P. , Cheng Yu , Wildes Jennifer E.
Published: March 2018

Anorexia nervosa (AN) is an eating disorder characterized by severe food restriction resulting in low body weight and an intense fear of gaining weight. This disorder has one of the highest suicide rates of any psychiatric illness; however, few studies have investigated prospective predictors of suicide ideation (SI) in this population. Quality‐of‐life impairment may be particularly relevant for understanding suicide risk in AN, given associations with SI in other psychiatric disorders and associations with chronicity and severity in AN. This study explored associations between eating disorder‐related impairment and SI in individuals with AN (n = 113) who completed assessments at treatment discharge and 3, 6, and 12 months after discharge. Greater psychological impairment predicted future occurrence of SI controlling for age, depression, history of SI, and eating disorder variables. Associations were specific to psychological impairment as other domains of impairment did not predict SI over time. Findings highlight the potential importance of targeting interpersonal–psychological consequences of AN to decrease future suicide risk.
The similarity of European pension systems in terms of OMC objectives: A cross‐country study
Authors: Chybalski Filip , Gumola Małgorzata
Published: March 2018

For several decades, pension systems across the world have been undergoing reforms. The main reasons for this are demographic changes and increasing life expectancy. To make these reforms more effective and ensure that they are based on the best benchmarks, the European Union (EU) has introduced the Open Method of Coordination (OMC) in the field of pensions. This study investigates whether European pension systems have become more similar and convergent in terms of the three main objectives of the OMC: adequacy, sustainability, and modernization of pensions. Our methodology is based on multivariate statistical analysis, and employs synthetic indicators as well as agglomerative hierarchical clustering. We analyze 27 countries in the years 2005, 2010, and 2015. The article contributes to the existing literature on pension reforms through investigation of the convergence of EU pension systems in terms of the three OMC objectives, in order to evaluate the effectiveness of this public policy concept. Our approach differs from that generally found in the literature, especially in terms of the methodology employed. The results support the view that the OMC is not an effective means of making European pension systems more convergent and better in terms of adequacy, efficiency, and modernization. Any improvement in OMC performance in the field of pensions, even if observed, is not as significant as expected.
Amenity Decomposition: The Role Played by Firms and Workers in Explaining Spatial Wage Differences in Chile
Authors: Iturra Victor
Published: March 2018

It is well established in the literature that amenities are important in affecting regional patterns by influencing both workers' and firms' location decisions. Using the seminal contribution made by Beeson and Eberts, this study performs a wage change decomposition into amenity (workers) and productivity (firms) components. The results reveal that firms are more significant when explaining high average wage regions in Chile, since they derive more benefits from agglomeration economies and natural resources. Finally, the results also confirm how important agglomeration economies are in developing countries.
Artistic Practices and the Redistribution of the Sensible in Largo do Chiado: Attention, Corporeal Isles, Visceral Politics
Authors: Paiva Daniel , Cachinho Herculano
Published: March 2018

The objective of this paper is to explore how different artistic practices work to alter the distribution of the senses, and consequently, the disposition, processes and practices of the situated surplus of urban places. While it has been acknowledged that artistic performances in public space generate specific appropriations of the urban environment, the role that specific sensorial channels play in these events is still underexplored. Drawing upon fieldwork conducted between 2012 and 2016 in Chiado, our study highlights how dance, music and architecture stimulate, invoke and highlight specific senses while rendering others unnoticed. This causes shifts in bodily rhythms, mood and attention to details in urban space. As certain corporeal isles are enacted through contemplation, the experience and appropriation of urban space is subject to change. A central tension in this matter is the fluctuation between visual and sonic spatialities.
Decomposing Multi‐Level Ethnic Segregation in Auckland, New Zealand, 2001–2013: Segregation Intensity for Multiple Groups at Multiple Scales
Authors: Manley David , Johnston Ron , Jones Kelvyn
Published: March 2018

There has been a growing appreciation that the processes generating urban residential segregation operate at multiple scales, stimulating innovations into the measurement of their outcomes. This paper applies a multi‐level modelling approach to that issue to the situation in Auckland, where multiple migration streams from both Pacific Island and Asian origins have created a complex multi‐ethnic city. We identify two distinct trends. For the larger ethnic groups segregation remained static despite rapid growth over a recent twelve‐year period. For the smaller groups growth has been combined with considerable change; they initially clustered in a few localities and areas within them but then experienced considerable reduction in the intensity of that segregation. By spatially decomposing the segregation levels, this paper extends our appreciation of its underpinning processes when they apply to migration streams that differ in their nature from those on which traditional residential location‐decision theory has been based.
Evaluation of the analytical variability of dipstick protein pads in canine urine
Authors: Giraldi Marco , Paltrinieri Saverio , Zatelli Andrea
Published: March 2018

Background

The dipstick is a first‐line and inexpensive test that can exclude the presence of proteinuria in dogs. However, no information is available about the analytical variability of canine urine dipstick analysis.

Objectives

The aim of this study was to assess the analytical variability in 2 dipsticks and the inter‐operator variability in dipstick interpretation.

Methods

Canine urine supernatants (n = 174) were analyzed with 2 commercially available dipsticks. Two observers evaluated each result blinded to the other observer and to the results of the other dipstick. Intra‐ and inter‐assay variability was assessed in 5 samples (corresponding to the 5 different semi‐quantitative results) tested 10 consecutive times over 5 consecutive days. The agreement between observers and between dipsticks was evaluated with Cohen's k test.

Results

Intra‐assay repeatability was good (≤3/10 errors), whereas inter‐assay variability was higher (from 1/5 to 4/5 discordant results). The concordance between the operators (k = 0.68 and 0.79 for the 2 dipsticks) and that of the dipsticks (k = 0.66 and 0.74 for the 2 operators) was good. However, 1 observer and 1 dipstick overestimated the results compared with the second observer or dipstick. In any case, discordant results accounted for a single unit of the semi‐quantitative scale.

Conclusions

As for any other method, analytic variability may affect the semi‐quantitation of urinary proteins when using the dipstick method. Subjective interpretation of the pad and, to a lesser extent, intrinsic staining properties of the pads could affect the results. Further studies are warranted to evaluate the effect of this variability on clinical decisions.
First insights into Puumala orthohantavirus circulation in a rodent population in Alsace, France
Authors: Monchatre‐Leroy E. , Murri S. , Castel G. , Calavas D. , Boué F. , Hénaux V. , Marianneau P.
Published: March 2018

In‐depth knowledge on the mechanisms that maintain infection by a zoonotic pathogen in an animal reservoir is the key to predicting and preventing transmission to humans. The Puumala orthohantavirus (PUUV), the most prevalent orthohantavirus in Western Europe, causes a mild form of haemorrhagic fever with renal syndrome (HFRS) in humans. In France, this endemic illness affects the north‐eastern part of the country. We conducted a 4‐year capture–mark–recapture study in a bank vole population, combined with molecular analyses, to explore the epidemiological situation of PUUV in Alsace, a French region where human cases have occurred, but for which no studies have been conducted on this reservoir host. PUUV‐infected bank voles were detected in the 2 years that showed high bank vole density with a prevalence of 4%. The individual PUUV sequences identified in this study were similar from year to year and similar to other French sequences. On a very small spatial scale, the distribution of seropositive bank voles was very heterogeneous in time and space. The short distances travelled on average by bank voles resulted in spatial clusters of seropositive rodents, which spread only very gradually throughout the year.
Molecular epidemiology of Shiga toxin‐producing O113:H21 isolates from cattle and meat
Authors: Sanso A. M. , Bustamante A. V. , Krüger A. , Cadona J. S. , Alfaro R. , Cáceres M. E. , Fernández D. , Lucchesi P. M. A. , Padola N. L.
Published: March 2018

The serotype O113:H21 is considered one of the relevant non‐O157 STEC serotypes associated with severe human infections. Due to the increased detection of O113 strains and their relationship with clinical cases, which emphasizes the importance of this serogroup as an emerging pathogen, our aim was to determine the characteristics of STEC O113:H21 strains circulating in bovine cattle and retail meat from Argentina. For this purpose, we determined the presence and combinations of various virulence genes (and their variants) related to adhesion and toxicity in a collection of 34 isolates. Their genetic relatedness using multiple‐locus variable‐number tandem repeat analysis (MLVA) was also studied. Subtyping of stx genes indicated that O113:H21 strains circulating in Argentina mainly present stx2a alone or together with stx2c or, less frequent, with stx2d, all of which are subtypes associated with human disease. We found plasmid markers, such as saa, ehxA and subA, in a higher proportion than previous studies, and five variants of saa, two of which were novel ones. In relation to MLVA subtyping, we detected a limited diversity among the isolates considering that several loci were not discriminative and, that in some farms, the same clone seemed to remain circulating throughout the year. The O113:H21 strains studied harbour several toxin and adhesion genes (saa, espP, fimCD, ehaA, iha, hcpA, elfA, lpfO113, ecpA, subA, cdt‐V) and Stx subtypes associated with human disease. Results also highlighted that subtyping of stx and saa is useful to discriminate O113:H21 strains that share virulence genes. In conclusion, this study shows that a number of O113:H21 strains that occur in foods and bovines could be pathogenic for humans. This situation calls for further attention in the prevention and control of foodborne disease caused by these strains.
Cross‐sectional study to estimate the prevalence of enterohaemorrhagic Escherichia coli on hides of market beef cows at harvest
Authors: Schneider L. G. , Stromberg Z. R. , Lewis G. L. , Moxley R. A. , Smith D. R.
Published: March 2018

Cattle hides are an important source of enterohaemorrhagic Escherichia coli (EHEC) carcass contamination at slaughter. Seven EHEC serogroups are adulterants in raw, non‐intact beef: EHEC O26, O45, O103, O111, O121, O145 and O157. The objective of this study was to estimate the probability for hide contamination with EHEC among US market beef cows at slaughter and to test the effects of season and geographic region on prevalence of hide contamination. Hides (n = 800) of market cows were swabbed at slaughter immediately after exsanguination, prior to hide removal. Cows were sampled from two geographically distinct beef packing plants during four seasons of 2015. Cattle source was categorized by northern or southern region. Samples were tested for EHEC by a molecular screening assay. The effects of region, season and their interaction on the probability of hide contamination by each EHEC serogroup were tested in separate multilevel multivariable logistic regression models, accounting for the random effect of clustering by plant. Statistical significance was set α = .05. Of 800 total samples, at least one EHEC was detected on 630 (79%) hides. Enterohaemorrhagic E. coli O26 was detected on 129 (16%) of all hides sampled, EHEC O45 on 437 (55%), EHEC O103 on 289 (36%), EHEC O111 on 189 (24%), EHEC O121 on 140 (18%), EHEC O145 on 171 (21%) and EHEC O157 on 89 (11%). Detection of EHEC O26 and EHEC O121 was associated with season. Season and region were associated with detecting EHEC O45 and EHEC O157. Season‐by‐region interactions were associated with the outcome of detecting EHEC O103, EHEC O111 and EHEC O145. Season, region of origin and the interaction of these factors affect hide contamination of market beef cattle at slaughter by EHEC, and each serogroup responds to these factors uniquely.
Gamma and infra‐slow oscillations shape neuronal firing in the rat subcortical visual system
Authors: Chrobok Lukasz , Palus‐Chramiec Katarzyna , Jeczmien‐Lazur Jagoda Stanislawa , Blasiak Tomasz , Lewandowski Marian Henryk
Published: March 2018

Key points

Neuronal oscillations observed in sensory systems are physiological carriers of information about stimulus features.

Rhythm in the infra‐slow range, originating from the retina, was previously found in the firing of subcortical visual system nuclei involved in both image and non‐image forming functions.

The present study shows that the firing of neurons in the lateral geniculate nucleus is also governed by gamma oscillation (∼35 Hz) time‐locked to high phase of infra‐slow rhythm that codes the intensity of transient light stimulation.

We show that both physiological rhythms are synchronized within and between ipsilateral nuclei of the subcortical visual system and are dependent on retinal activity.

The present study shows that neurophysiological oscillations characterized by various frequencies not only coexist in the subcortical visual system, but also are subjected to complex interference and synchronization processes.

The physiological function of rhythmic firing in the neuronal networks of sensory systems has been linked with information coding. Also, neuronal oscillations in different frequency bands often change as a signature of brain state or sensory processing. Infra‐slow oscillation (ISO) in the neuronal firing dependent on the retinal network has been described previously in the structures of the subcortical visual system. In the present study, we show for the first time that firing of ISO neurons in the lateral geniculate nucleus is also characterized by a harmonic discharge pattern (i.e. action potentials are separated by the intervals governed by fundamental frequency in the gamma range: ∼35 Hz). A similar phenomenon was recently described in the suprachiasmatic nuclei of the hypothalamus: the master biological clock. We found that both gamma and ISO rhythms were synchronized within and between ipsilateral nuclei of the subcortical visual system and were dependent on the retinal activity of the contralateral eye. These oscillatory patterns were differentially influenced by transient and prolonged light stimulation with respect to both frequency change direction and sustainability. The results of the present study show that the firing pattern of neurons in the subcortical visual system is shaped by oscillations from infra‐slow and gamma frequency bands that are plausibly generated by the retinal network. Additionally, the results demonstrate that both rhythms are not a distinctive feature of image or non‐image forming visual systems but, instead, they comprise two channels carrying distinctive properties of photic information.
Aberrant cortical excitability reflects the loss of hand dexterity in musician's dystonia
Authors: Furuya Shinichi , Uehara Kazumasa , Sakamoto Takashi , Hanakawa Takashi
Published: March 2018

Key points

Dystonia is a movement disorder characterized by abnormalities at multifaceted aspects of motor dexterity and neural functions.

Evidence bridging between pathophysiology and movement abnormalities is limited.

A novel finding was that in focal task‐specific dystonia (FTSD), an aberrantly reduced inhibition at the motor cortex was related to the temporal imprecision of the dexterous finger movements, whereas an elevated facilitation was associated with an abnormally sluggish transition of finger movements from flexion to extension.

We newly identified two sets of behavioural–physiological covariations as hallmarks of hand FTSD, which is clinically significant because these findings provide novel evidence connecting distinct types of malfunctions within the motor cortex at rest with distinct aspects of motor dexterity degradation in FTSD patients.

Focal task‐specific dystonia (FTSD) compromises dexterous movements. A proposed pathophysiological mechanism of FTSD involves malfunction of the motor cortex (M1). However, no evidence is yet available regarding whether and how malfunctions of M1 are responsible for the loss of motor dexterity. Here, we addressed this issue by assessing both M1 excitability and detailed movement parameters, as well as their relationships. Transcranial magnetic stimulation was applied over M1 in 20 pianists with FTSD, 20 healthy pianists and 20 non‐musicians. The patients demonstrated both reduced short‐interval intracortical inhibition (SICI) and elevated intracortical facilitation (ICF) compared with the healthy controls. This indicates that the abnormal cortical excitability reflects pathophysiology but not current skills. Hand motor dexterity was evaluated by position sensors during piano playing at two tempi. The patients showed delayed transition from finger flexion to extension at the fastest tempo and greater timing variability of the finger movements. Furthermore, multivariate analyses identified distinct sets of covariation between cortical excitability and dexterity measures. Namely, the SICI measure and ICF measure were associated with the temporal variability of the movements and the quickness of the transition from flexion to extension, respectively. Specifically, the reduced inhibition and elevated facilitation at M1 in pianists was related to the temporal imprecision and impairment of quick transitions in the sequential finger movements. The present study provides novel evidence associating M1 malfunctions with dexterity loss.
Two new species of the genus Galumna (Acari: Oribatida: Galumnidae) from China
Authors: Liang Wenqin , Yang Maofa , Ren Guoru
Published: March 2018

Two new species of Galumna Heyden, 1826, Galumna (Galumna) wuzhishanensis sp. nov. and Galumna (Galumna) longisensilla sp. nov., are described from soil and leaf litter samples in Hainan and Guizhou Provinces, China. Adults of Galumna (Galumna) wuzhishanensis sp. nov., is morphologically most similar to Galumna (Galumna) acutirostrum Ermilov, 2010, however it differs from the latter by the body length and pattern of surface, length of interlamellar setae, location of im and the absence of median pore and postanal porose area. Adults of Galumna (Galumna) longisensilla sp. nov., is morphologically most similar to Galumna (Galumna) calva Starý, 1997, but differs by the shape of Aa and location of gla, size of A3 and the presence of postanal porose area.
Measuring vocal difference in bird population pairs
Authors: O'Reilly Colm , Analuddin Kangkuso , Kelly David J. , Harte Naomi
Published: March 2018

Over time, a bird population's acoustic and morphological features can diverge from the parent species. A quantitative measure of difference between two populations of species/subspecies is extremely useful to zoologists. Work in this paper takes a dialect difference system first developed for speech and refines it to automatically measure vocalisation difference between bird populations by extracting pitch contours. The pitch contours are transposed into pitch codes. A variety of codebook schemes are proposed to represent the contour structure, including a vector quantization approach. The measure, called Bird Vocalisation Difference, is applied to bird populations with calls that are considered very similar, very different, and between these two extremes. Initial results are very promising, with the behaviour of the metric consistent with accepted levels of similarity for the populations tested to date. The influence of data size on the measure is investigated by using reduced datasets. Results of species pair classification using Gaussian mixture models with Mel-frequency cepstral coefficients is also given as a baseline indicator of class confusability.
The role of gesture delay in coda /r/ weakening: An articulatory, auditory and acoustic study
Authors: Lawson Eleanor , Stuart-Smith Jane , Scobbie James M.
Published: March 2018

The cross-linguistic tendency of coda consonants to weaken, vocalize, or be deleted is shown to have a phonetic basis, resulting from gesture reduction, or variation in gesture timing. This study investigates the effects of the timing of the anterior tongue gesture for coda /r/ on acoustics and perceived strength of rhoticity, making use of two sociolects of Central Scotland (working- and middle-class) where coda /r/ is weakening and strengthening, respectively. Previous articulatory analysis revealed a strong tendency for these sociolects to use different coda /r/ tongue configurations—working- and middle-class speakers tend to use tip/front raised and bunched variants, respectively; however, this finding does not explain working-class /r/ weakening. A correlational analysis in the current study showed a robust relationship between anterior lingual gesture timing, F3, and percept of rhoticity. A linear mixed effects regression analysis showed that both speaker social class and linguistic factors (word structure and the checked/unchecked status of the prerhotic vowel) had significant effects on tongue gesture timing and formant values. This study provides further evidence that gesture delay can be a phonetic mechanism for coda rhotic weakening and apparent loss, but social class emerges as the dominant factor driving lingual gesture timing variation.
Time domain nearfield acoustical holography with three-dimensional linear deconvolution
Authors: Attendu Jean-Michel , Ross Annie
Published: March 2018

In this paper, a formulation is proposed to improve the time domain reconstruction of non-stationary acoustic fields with nearfield acoustical holography. The formulation involves applying three-dimensional (3D) linear deconvolution using a Green's function sampled in the time and spatial domains. Because linear deconvolution does not assume periodic signals, it more appropriately describes the decaying behavior of sources that begin and end at null amplitude and that radiate over a finite amount of time. The proposed method outperforms standard circular convolution-based nearfield acoustical holography by up to a factor three in relative root-mean-square error, when compared using a transient baffled piston model, and its reconstructions remain accurate over large back-propagation distances. Furthermore, it is shown that truncation errors in linear deconvolution can be reduced by applying a 3D patch extrapolation algorithm; however, convergence depends on the choice of an adequate Tikhonov's regularization parameter. Three methods for predicting the optimal parameter are compared: the L-curve, the generalized cross-validation, and the empirical Bayesian method. It is shown that with the proposed formulation applied to reconstructing the field radiated by a transient baffled piston, the generalized cross-validation gives the overall best prediction for the noise levels and back-propagation distances studied.
Engaging Axiology: Enabling Meaningful Transdisciplinary Collaboration in Adapted Physical Activity
Authors: Peers Danielle
Published: March 2018

In this article, I explore the concept of axiology in the context of adapted physical activity research and analyze its connection to the more commonly discussed paradigmatic assumptions of epistemology and ontology. Following methodological scholars, I argue for an acknowledgment of the pivotal role that axiology already plays in adapted physical activity research and for the potential interdisciplinary and transdisciplinary opportunities that could be enabled by engaging with axiology in more explicit ways. I discuss a number of potential axiological gaps between the field of adapted physical activity and disability communities, arguing that such differences may undermine attempts at doing meaningful transdisciplinary research with such communities. I offer strategies for bridging these axiological gaps, encouraging us to work together in axiologically reflexive ways in order to increase meaningful opportunities for more people with disabilities to be engaged in the movement-based activities and communities of their choice.
Successful Treatment of Persistent Burkholderia cepacia Complex Bacteremia with Ceftazidime-Avibactam
Authors: Tamma Pranita D. , Fan Yunfan , Bergman Yehudit , Sick-Samuels Anna C. , Hsu Alice J. , Timp Winston , Simner Patricia J. , Prokesch Bonnie C. , Greenberg David E.
Published: March 2018

We report our clinical experience treating a 2-month-old infant with congenital diaphragmatic hernia who experienced prolonged bacteremia with
Burkholderia cepacia
complex (Bcc) despite conventional antibiotic therapy and appropriate source control measures. The infection resolved after initiation of ceftazidime-avibactam. Whole-genome sequencing revealed that the isolate most closely resembled
B. contaminans
and identified the mechanism of resistance that likely contributed to clinical cure with this agent. Ceftazidime-avibactam should be considered salvage therapy for Bcc infections if other treatment options have been exhausted.
Molecular Characterization of OXA-198 Carbapenemase-Producing Pseudomonas aeruginosa Clinical Isolates
Authors: Bonnin Rémy A. , Bogaerts Pierre , Girlich Delphine , Huang Te-Din , Dortet Laurent , Glupczynski Youri , Naas Thierry
Published: March 2018

Carbapenemase-producing
Pseudomonadaceae
have increasingly been reported worldwide, with an ever-increasing heterogeneity of carbapenem resistance mechanisms, depending on the bacterial species and the geographical location. OXA-198 is a plasmid-encoded class D β-lactamase involved in carbapenem resistance in one
Pseudomonas aeruginosa
isolate from Belgium. In the setting of a multicenter survey of carbapenem resistance in
P. aeruginosa
strains in Belgian hospitals in 2013, three additional OXA-198-producing
P. aeruginosa
isolates originating from patients hospitalized in one hospital were detected. To reveal the molecular mechanism underlying the reduced susceptibility to carbapenems, MIC determinations, whole-genome sequencing, and PCR analyses to confirm the genetic organization were performed. The plasmid harboring the
bla
OXA-198
gene was characterized, along with the genetic relatedness of the four
P. aeruginosa
isolates. The
bla
OXA-198
gene was harbored on a class 1 integron carried by an ∼49-kb IncP-type plasmid proposed as IncP-11. The same plasmid was present in all four
P. aeruginosa
isolates. Multilocus sequence typing revealed that the isolates all belonged to sequence type 446, and single-nucleotide polymorphism analysis revealed only a few differences between the isolates. This report describes the structure of a 49-kb plasmid harboring the
bla
OXA-198
gene and presents the first description of OXA-198-producing
P. aeruginosa
isolates associated with a hospital-associated cluster episode.
Variation at Extra-epitopic Amino Acid Residues Influences Suppression of Influenza Virus Replication by M1
58-66
Epitope-Specific CD8
+
T Lymphocytes
Authors: van de Sandt Carolien E. , Pronk Mark R. , van Baalen Carel A. , Fouchier Ron A. M. , Rimmelzwaan Guus F.
Published: March 2018

Influenza virus-specific CD8
+
T lymphocytes (CTLs) contribute to clearance of influenza virus infections and reduce disease severity. Variation at amino acid residues located in or outside CTL epitopes has been shown to affect viral recognition by virus-specific CTLs. In the present study, we investigated the effect of naturally occurring variation at residues outside the conserved immunodominant and HLA*0201-restricted M1
58-66
epitope, located in the influenza virus M1 protein, on the extent of virus replication in the presence of CTLs specific for the epitope. To this end, we used isogenic viruses with an M1 gene segment derived from either an avian or a human influenza virus, HLA-transgenic human epithelial cells, human T cell clones specific for the M1
58-66
epitope or a control epitope, and a novel, purposely developed
in vitro
system to coculture influenza virus-infected cells with T cells. We found that the M gene segment of a human influenza A/H3N2 virus afforded the virus the capacity to replicate better in the presence of M1
58-66
-specific CTLs than the M gene segment of avian viruses. These findings are in concordance with previously observed differential CTL activation, caused by variation at extra-epitopic residues, and may reflect an immune adaptation strategy of human influenza viruses that allows them to cope with potent CTL immunity to the M1
58-66
epitope in HLA-A*0201-positive individuals, resulting in increased virus replication and shedding and possibly increasing disease severity.

IMPORTANCE
Influenza viruses are among the leading causes of acute respiratory tract infections. CD8
+
T lymphocytes display a high degree of cross-reactivity with influenza A viruses of various subtypes and are considered an important correlate of protection. Unraveling viral immune evasion strategies and identifying signs of immune adaptation are important for defining the role of CD8
+
T lymphocytes in affording protection more accurately. Improving our insight into the interaction between influenza viruses and virus-specific CD8
+
T lymphocyte immunity may help to advance our understanding of influenza virus epidemiology, aid in risk assessment of potentially pandemic influenza virus strains, and benefit the design of vaccines that induce more broadly protective immunity.
A Highly Conserved Leucine in Mammarenavirus Matrix Z Protein Is Required for Z Interaction with the Virus L Polymerase and Z Stability in Cells Harboring an Active Viral Ribonucleoprotein
Authors: Iwasaki Masaharu , de la Torre Juan C.
Published: March 2018

Mammarenaviruses cause chronic infections in their natural rodent hosts. Infected rodents shed infectious virus into excreta. Humans are infected through mucosal exposure to aerosols or direct contact of abraded skin with fomites, resulting in a wide range of manifestations from asymptomatic or mild febrile illness to severe life-threatening hemorrhagic fever. The mammarenavirus matrix Z protein has been shown to be a main driving force of virus budding and to act as a negative regulator of viral RNA synthesis. To gain a better understanding of how the Z protein exerts its several different functions, we investigated the interaction between Z and viral polymerase L protein using the prototypic mammarenavirus, lymphocytic choriomeningitis virus (LCMV). We found that in the presence of an active viral ribonucleoprotein (vRNP), the Z protein translocated from nonionic detergent-resistant, membrane-rich structures to a subcellular compartment with a different membrane composition susceptible to disruption by nonionic detergents. Alanine (A) substitution of a highly conserved leucine (L) at position 72 in LCMV Z protein abrogated Z-L interaction. The L72A mutation did not affect the stability or budding activity of Z when expressed alone, but in the presence of an active vRNP, mutation L72A promoted rapid degradation of Z via a proteasome- and lysosome-independent pathway. Accordingly, L72A mutation in the Z protein resulted in nonviable LCMV. Our findings have uncovered novel aspects of the dynamics of the Z protein for which a highly conserved L residue was strictly required.

IMPORTANCE
Several mammarenaviruses, chiefly Lassa virus (LASV), cause hemorrhagic fever disease in humans and pose important public health concerns in their regions of endemicity. Moreover, mounting evidence indicates that the worldwide-distributed, prototypic mammarenavirus, lymphocytic choriomeningitis virus (LCMV), is a neglected human pathogen of clinical significance. The mammarenavirus matrix Z protein plays critical roles in different steps of the viral life cycle by interacting with viral and host cellular components. Here we report that alanine substitution of a highly conserved leucine residue, located at position 72 in LCMV Z protein, abrogated Z-L interaction. The L72A mutation did not affect Z budding activity but promoted its rapid degradation in the presence of an active viral ribonucleoprotein (vRNP). Our findings have uncovered novel aspects of the dynamics of the Z protein for which a highly conserved L residue was strictly required.
Mixed Communities of Mucoid and Nonmucoid
Pseudomonas aeruginosa
Exhibit Enhanced Resistance to Host Antimicrobials
Authors: Malhotra Sankalp , Limoli Dominique H. , English Anthony E. , Parsek Matthew R. , Wozniak Daniel J.
Published: March 2018

Pseudomonas aeruginosa
causes chronic pulmonary infections in patients with cystic fibrosis (CF).
P. aeruginosa
mucoid conversion, defined by overproduction of the exopolysaccharide alginate, correlates with accelerated decline in CF patient lung function. Recalcitrance of the mucoid phenotype to clearance by antibiotics and the immune response is well documented. However, despite advantages conferred by mucoidy, mucoid variants often revert to a nonmucoid phenotype both
in vitro
and
in vivo
. Mixed populations of mucoid isolates and nonmucoid revertants are recovered from CF lungs, suggesting a selective benefit for coexistence of these variants. In this study, cocultures of mucoid and nonmucoid variants exhibited enhanced resistance to two host antimicrobials: LL-37, a cationic antimicrobial peptide, and hydrogen peroxide (H
2
O
2
). Alginate production by mucoid isolates protected nonmucoid variants in consortia from LL-37, as addition of alginate exogenously to nonmucoid variants abrogated LL-37 killing. Conversely, nonmucoid revertants shielded mucoid variants from H
2
O
2
stress via catalase (KatA) production, which was transcriptionally repressed by AlgT and AlgR, central regulators of alginate biosynthesis. Furthermore, extracellular release of KatA by nonmucoid revertants was dependent on
lys
, encoding an endolysin implicated in autolysis and extracellular DNA (eDNA) release. Overall, these data provide a rationale to study interactions of
P. aeruginosa
mucoid and nonmucoid variants as contributors to evasion of innate immunity and persistence within the CF lung.

IMPORTANCE
P. aeruginosa
mucoid conversion within lungs of cystic fibrosis (CF) patients is a hallmark of chronic infection and predictive of poor prognosis. The selective benefit of mixed populations of mucoid and nonmucoid variants, often isolated from chronically infected CF patients, has not been explored. Here, we show that mixed-variant communities of
P. aeruginosa
demonstrate advantages in evasion of innate antimicrobials via production of shared goods: alginate and catalase. These data argue for therapeutically targeting multiple constituents (both mucoid and nonmucoid variants) within diversified
P. aeruginosa
communities
in vivo
, as these variants can differentially shield one another from components of the host response.
HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain
Authors: Rawle Daniel J. , Li Dongsheng , Swedberg Joakim E. , Wang Lu , Soares Dinesh C. , Harrich David
Published: March 2018

Once HIV-1 enters a cell, the viral core is uncoated by a poorly understood mechanism and the HIV-1 genomic RNA is reverse transcribed into DNA. Host cell factors are essential for these processes, although very few reverse transcription complex binding host cell factors have been convincingly shown to affect uncoating or reverse transcription. We previously reported that cellular eukaryotic translation elongation factor 1A (eEF1A) interacts tightly and directly with HIV-1 reverse transcriptase (RT) for more efficient reverse transcription. Here we report that the surface-exposed acidic residues in the HIV-1 RT thumb domain alpha-J helix and flanking regions are important for interaction with eEF1A. Mutation of surface-exposed acidic thumb domain residues D250, E297, E298, and E300 to arginine resulted in various levels of impairment of the interaction between RT and eEF1A. This indicates that this negatively charged region in the RT thumb domain is important for interaction with the positively charged eEF1A protein. The impairment of RT and eEF1A interaction by the RT mutations correlated with the efficiency of reverse transcription, uncoating, and infectivity. The best example of this is the strictly conserved E300 residue, where mutation significantly impaired the interaction of RT with eEF1A and virus replication in CD4
+
T cells without affecting
in vitro
RT catalytic activity, RT heterodimerization, or RNase H activity. This study demonstrated that the interaction between surface-exposed acidic residues of the RT thumb domain and eEF1A is important for HIV-1 uncoating, reverse transcription, and replication.

IMPORTANCE
HIV-1, like all viruses, requires host cell proteins for its replication. Understanding the mechanisms behind virus-host interactions can lay the foundation for future novel therapeutic developments. Our lab has identified eEF1A as a key HIV-1 RT binding host protein that is important for the reverse transcription of HIV-1 genomic RNA into DNA. Here we identify the first surface-exposed RT residues that underpin interactions with eEF1A. Mutation of one strictly conserved RT residue (E300R) delayed reverse transcription and viral core uncoating and strongly inhibited HIV-1 replication in CD4
+
T cells. This study advances the structural and mechanistic detail of the key RT-eEF1A interaction in HIV-1 infection and indicates its importance in uncoating for the first time. This provides a further basis for the development of an RT-eEF1A interaction-inhibiting anti-HIV-1 drug and suggests that the surface-exposed acidic patch of the RT thumb domain may be an attractive drug target.
Robust Phagocyte Recruitment Controls the Opportunistic Fungal Pathogen
Mucor circinelloides
in Innate Granulomas
In Vivo
Authors: Inglesfield Sarah , Jasiulewicz Aleksandra , Hopwood Matthew , Tyrrell James , Youlden George , Mazon-Moya Maria , Millington Owain R. , Mostowy Serge , Jabbari Sara , Voelz Kerstin
Published: March 2018

Mucormycosis is an emerging fungal infection with extremely high mortality rates in patients with defects in their innate immune response, specifically in functions mediated through phagocytes. However, we currently have a limited understanding of the molecular and cellular interactions between these innate immune effectors and mucormycete spores during the early immune response. Here, the early events of innate immune recruitment in response to infection by
Mucor circinelloides
spores are modeled by a combined
in silico
modeling approach and real-time
in vivo
microscopy. Phagocytes are rapidly recruited to the site of infection in a zebrafish larval model of mucormycosis. This robust early recruitment protects from disease onset
in vivo
.
In silico
analysis identified that protection is dependent on the number of phagocytes at the infection site, but not the speed of recruitment. The mathematical model highlights the role of proinflammatory signals for phagocyte recruitment and the importance of inhibition of spore germination for protection from active fungal disease. These
in silico
data are supported by an
in vivo
lack of fungal spore killing and lack of reactive oxygen burst, which together result in latent fungal infection. During this latent stage of infection, spores are controlled in innate granulomas
in vivo
. Disease can be reactivated by immunosuppression. Together, these data represent the first
in vivo
real-time analysis of innate granuloma formation during the early stages of a fungal infection. The results highlight a potential latent stage during mucormycosis that should urgently be considered for clinical management of patients.

IMPORTANCE
Mucormycosis is a dramatic fungal infection frequently leading to the death of patients. We know little about the immune response to the fungus causing this infection, although evidence points toward defects in early immune events after infection. Here, we dissect this early immune response to infectious fungal spores. We show that specialized white blood cells (phagocytes) rapidly respond to these spores and accumulate around the fungus. However, we demonstrate that the mechanisms that enable phagocytes to kill the fungus fail, allowing for survival of spores. Instead a cluster of phagocytes resembling an early granuloma is formed around spores to control the latent infection. This study is the first detailed analysis of early granuloma formation during a fungal infection highlighting a latent stage that needs to be considered for clinical management of patients.
Redox Regulation, Rather than Stress-Induced Phosphorylation, of a Hog1 Mitogen-Activated Protein Kinase Modulates Its Nitrosative-Stress-Specific Outputs
Authors: Herrero-de-Dios Carmen , Day Alison M. , Tillmann Anna T. , Kastora Stavroula L. , Stead David , Salgado Paula S. , Quinn Janet , Brown Alistair J. P.
Published: March 2018

In all eukaryotic kingdoms, mitogen-activated protein kinases (MAPKs) play critical roles in cellular responses to environmental cues. These MAPKs are activated by phosphorylation at highly conserved threonine and tyrosine residues in response to specific inputs, leading to their accumulation in the nucleus and the activation of their downstream targets. A specific MAP kinase can regulate different downstream targets depending on the nature of the input signal, thereby raising a key question: what defines the stress-specific outputs of MAP kinases? We find that the Hog1 MAPK contributes to nitrosative-stress resistance in
Candida albicans
even though it displays minimal stress-induced phosphorylation under these conditions. We show that Hog1 becomes oxidized in response to nitrosative stress, accumulates in the nucleus, and regulates the nitrosative stress-induced transcriptome. Mutation of specific cysteine residues revealed that C156 and C161 function together to promote stress resistance, Hog1-mediated nitrosative-stress-induced gene expression, resistance to phagocytic killing, and
C. albicans
virulence. We propose that the oxidation of Hog1, rather than its phosphorylation, contributes to the nitrosative-stress-specific responses of this MAP kinase.

IMPORTANCE
Mitogen-activated protein kinases play key roles in the responses of eukaryotic cells to extracellular signals and are critical for environmental-stress resistance. The widely accepted paradigm is that MAP kinases are activated by phosphorylation, which then triggers their nuclear accumulation and the activation of target proteins and genes that promote cellular adaptation. Our data suggest that alternative forms of posttranslational modification can modulate MAP kinase functionality in
Candida albicans
. We demonstrate that Hog1 is not significantly phosphorylated in response to nitrosative stress, yet it displays nuclear accumulation and contributes to the global transcriptional response to this stress, as well as promoting nitrosative-stress resistance. Instead, nitrosative stress triggers changes in the redox status of Hog1. We also show that specific Hog1 cysteine residues influence its activation of stress genes. Therefore, alternative posttranslational modifications appear to regulate the stress-specific outputs of MAP kinases.
Femoroacetabular impingement surgery allows 74% of athletes to return to the same competitive level of sports participation but their level of performance remains unreported: a systematic review with meta-analysis
Authors: Reiman Michael P , Peters Scott , Sylvain Jonathan , Hagymasi Seth , Mather Richard C , Goode Adam P
Published: March 2018

Background

Femoroacetabular impingement (FAI) syndrome is one source of hip pain that can limit sport participation among athletes.

Objective

To summarise the return to sport (RTS) rate for athletes after surgery for FAI syndrome.

Methods

A computer-assisted search of MEDLINE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and EMBASE databases was performed using keywords related to RTS and RTS at preinjury level (RTSPRE) of competition for FAI syndrome. The risk of bias in the included studies was assessed using the Methodological Index for Non-Randomized Studies scale.

Results

35 studies (1634 athletes/1828 hips) qualified for analysis. Based on evidence of limited to moderate strength (level 3b to 4 studies), athletes return to sport at preinjury level post surgery for FAI syndrome at a rate of only 74% (67%–81%). Only 37% of studies reported RTSPRE. The mean time from surgery to RTS was 7.0±2.6 months. The mean follow-up postsurgery was 28.1±15.5 months. Professional athletes returned to sport (p=0.0002) (although not the preinjury sport level; p=0.63) at a higher rate than collegiate athletes. Only 14% of studies reported on athletic presurgery and postsurgery athletic performance, which means it is impossible to comment on whether athletes return to their previous level of performance or not. No studies reported on the specific criteria used to permit players to return to sport. 20% of studies reported on career longevity, 51% reported surgical complications and 77% reported on surgical failures.

Conclusion

There waslimitedtomoderateevidence that one in four athletes did not return to their previous level of sport participation after surgery for FAI syndrome. Only 37% of the included studies clearly distinguished RTS from RTSPRE. Poor outcome reporting on athletic performance postsurgery makes it difficult to determine to what level of performance these athletes actually perform. Thus, if a player asks a surgeon ‘Will I get back to my previous level of performance?’ there are presently little to no published data from which to base an answer.

PROSPERO registration number

CRD42017072762.