bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic Compensation of Fitness Costs Is a General Outcome for Antibiotic-Resistant
Pseudomonas aeruginosa
Mutants Overexpressing Efflux Pumps
Authors: Olivares Pacheco Jorge , Alvarez-Ortega Carolina , Alcalde Rico Manuel , Martínez José Luis 
Published: July 2017

ABSTRACT

It is generally assumed that the acquisition of antibiotic resistance is associated with a fitness cost. We have shown that overexpression of the MexEF-OprN efflux pump does not decrease the fitness of a resistant
Pseudomonas aeruginosa
strain compared to its wild-type counterpart. This lack of fitness cost was associated with a metabolic rewiring that includes increased expression of the anaerobic nitrate respiratory chain when cells are growing under fully aerobic conditions. It was not clear whether this metabolic compensation was exclusive to strains overexpressing MexEF-OprN or if it extended to other resistant strains that overexpress similar systems. To answer this question, we studied a set of
P. aeruginosa
mutants that independently overexpress the MexAB-OprM, MexCD-OprJ, or MexXY efflux pumps. We observed increased expression of the anaerobic nitrate respiratory chain in all cases, with a concomitant increase in NO
3
consumption and NO production. These efflux pumps are proton/substrate antiporters, and their overexpression may lead to intracellular H
+
accumulation, which may in turn offset the pH homeostasis. Indeed, all studied mutants showed a decrease in intracellular pH under anaerobic conditions. The fastest way to eliminate the excess of protons is by increasing oxygen consumption, a feature also displayed by all analyzed mutants. Taken together, our results support metabolic rewiring as a general mechanism to avoid the fitness costs derived from overexpression of
P. aeruginosa
multidrug efflux pumps. The development of drugs that block this metabolic “reaccommodation” might help in reducing the persistence and spread of antibiotic resistance elements among bacterial populations.

IMPORTANCE
It is widely accepted that the acquisition of resistance confers a fitness cost in such a way that in the absence of antibiotics, resistant populations will be outcompeted by susceptible ones. Based on this assumption, antibiotic cycling regimes have been proposed in the belief that they will reduce the persistence and spread of resistance among bacterial pathogens. Unfortunately, trials testing this possibility have frequently failed, indicating that resistant microorganisms are not always outcompeted by susceptible ones. Indeed, some mutations do not result in a fitness cost, and in case they do, the cost may be compensated for by a secondary mutation. Here we describe an alternative nonmutational mechanism for compensating for fitness costs, which consists of the metabolic rewiring of resistant mutants. Deciphering the mechanisms involved in the compensation of fitness costs of antibiotic-resistant mutants may help in the development of drugs that will reduce the persistence of resistance by increasing said costs.
Galectin-3 Inhibits Galectin-8/Parkin-Mediated Ubiquitination of Group A Streptococcus
Authors: Cheng Yi-Lin , Wu Yan-Wei , Kuo Chih-Feng , Lu Shiou-Ling , Liu Fu-Tong , Anderson Robert , Lin Chiou-Feng , Liu Yi-Ling , Wang Wan-Yu , Chen Ying-Da , Zheng Po-Xing , Wu Jiunn-Jong , Lin Yee-Shin 
Published: July 2017

ABSTRACT
Group A streptococcus (GAS) is an important human pathogen that causes a wide variety of cutaneous and systemic infections. Although originally thought to be an extracellular bacterium, numerous studies have demonstrated that GAS can trigger internalization into nonimmune cells to escape from immune surveillance or antibiotic-mediated killing. Epithelial cells possess a defense mechanism involving autophagy-mediated targeting and killing of GAS within lysosome-fused autophagosomes. In endothelial cells, in contrast, we previously showed that autophagy is not sufficient for GAS killing. In the present study, we showed higher galectin-3 (Gal-3) expression and lower Gal-8 expression in endothelial cells than in epithelial cells. The recruitment of Gal-3 to GAS is higher and the recruitment of Gal-8 to GAS is lower in endothelial cells than in epithelial cells. We further showed that Gal-3 promotes GAS replication and diminishes the recruitment of Gal-8 and ubiquitin, the latter of which is a critical protein for autophagy sequestration. After knockdown of Gal-3 in endothelial cells, the colocalization of Gal-8, parkin, and ubiquitin-decorated GAS is significantly increased, as is the interaction of Gal-8 and parkin, an E3 ligase. Furthermore, inhibition of Gal-8 in epithelial cells attenuates recruitment of parkin; both Gal-8 and parkin contribute to ubiquitin recruitment and GAS elimination. Animal studies confirmed that Gal-3-knockout mice develop less-severe skin damage and that GAS replication can be detected only in the air pouch and not in organs and endothelial cells. These results demonstrate that Gal-3 inhibits ubiquitin recruitment by blocking Gal-8 and parkin recruitment, resulting in GAS replication in endothelial cells.

IMPORTANCE
In epithelial cells, GAS can be efficiently killed within the lysosome-fused autophaosome compartment. However, we previously showed that, in spite of LC-3 recruitment, the autophagic machinery is not sufficient for GAS killing in endothelial cells. In this report, we provide the first evidence that Gal-3, highly expressed in endothelial cells, blocks the tagging of ubiquitin to GAS by inhibiting recruitment of Gal-8 and parkin, leading to an enhancement of GAS replication. We also provide the first demonstration that Gal-8 can interact with parkin, the critical E3 ligase, for resistance to intracellular bacteria by facilitating the decoration of bacteria with ubiquitin chains. Our findings reveal that differential levels of Gal-3 and Gal-8 expression and recruitment to GAS between epithelial cells and endothelial cells may contribute to the different outcomes of GAS elimination or survival and growth of GAS in these two types of cells.
Penile Anaerobic Dysbiosis as a Risk Factor for HIV Infection
Authors: Liu Cindy M. , Prodger Jessica L. , Tobian Aaron A. R. , Abraham Alison G. , Kigozi Godfrey , Hungate Bruce A. , Aziz Maliha , Nalugoda Fred , Sariya Sanjeev , Serwadda David , Kaul Rupert , Gray Ronald H. , Price Lance B. 
Published: July 2017

ABSTRACTSexual transmission of HIV requires exposure to the virus and infection of activated mucosal immune cells, specifically CD4+T cells or dendritic cells. The foreskin is a major site of viral entry in heterosexual transmission of HIV. Although the probability of acquiring HIV from a sexual encounter is low, the risk varies even after adjusting for known HIV risk factors. The genital microbiome may account for some of the variability in risk by interacting with the host immune system to trigger inflammatory responses that mediate the infection of mucosal immune cells. We conducted a case-control study of uncircumcised participants nested within a randomized-controlled trial of male circumcision in Rakai, Uganda. Using penile (coronal sulcus) swabs collected by study personnel at trial enrollment, we characterized the penile microbiome by sequencing and real-time PCR and cytokine levels by electrochemiluminescence assays. The absolute abundances of penile anaerobes at enrollment were associated with later risk of HIV seroconversion, with a 10-fold increase inPrevotella,Dialister,Finegoldia, andPeptoniphilusincreasing the odds of HIV acquisition by 54 to 63%, after controlling for other known HIV risk factors. Increased abundances of anaerobic bacteria were also correlated with increased cytokines, including interleukin-8, which can trigger an inflammatory response that recruits susceptible immune cells, suggesting a mechanism underlying the increased risk. These same anaerobic genera can be shared between heterosexual partners and are associated with increased HIV acquisition in women, pointing to anaerobic dysbiosis in the genital microbiome and an accompanying inflammatory response as a novel, independent, and transmissible risk factor for HIV infection.IMPORTANCEWe found that uncircumcised men who became infected by HIV during a 2-year clinical trial had higher levels of penile anaerobes than uncircumcised men who remained HIV negative. We also found that having higher levels of penile anaerobes was also associated with higher production of immune factors that recruit HIV target cells to the foreskin, suggesting that anaerobes may modify HIV risk by triggering inflammation. These anaerobes are known to be shared by heterosexual partners and are associated with HIV risk in women. Therefore, penile anaerobes may be a sexually transmissible risk factor for HIV, and modifying the penile microbiome could potentially reduce HIV acquisition in both men and women.
The third-stimulus temporal discrimination threshold: focusing on the temporal processing of sensory input within primary somatosensory cortex
Authors: Leodori Giorgio , Formica Alessandra , Zhu Xiaoying , Conte Antonella , Belvisi Daniele , Cruccu Giorgio , Hallett Mark , Berardelli Alfredo 
Published: July 2017

The somatosensory temporal discrimination threshold (STDT) has been used in recent years to investigate time processing of sensory information, but little is known about the physiological correlates of somatosensory temporal discrimination. The objective of this study was to investigate whether the time interval required to discriminate between two stimuli varies according to the number of stimuli in the task. We used the third-stimulus temporal discrimination threshold (ThirdDT), defined as the shortest time interval at which an individual distinguishes a third stimulus following a pair of stimuli delivered at the STDT. The STDT and ThirdDT were assessed in 31 healthy subjects. In a subgroup of 10 subjects, we evaluated the effects of the stimuli intensity on the ThirdDT. In a subgroup of 16 subjects, we evaluated the effects of S1 continuous theta-burst stimulation (S1-cTBS) on the STDT and ThirdDT. Results show that ThirdDT is shorter than STDT. We found a positive correlation between STDT and ThirdDT values. As long as the stimulus intensity was within the perceivable and painless range, it did not affect ThirdDT values. S1-cTBS significantly affected both STDT and ThirdDT, although the latter was affected to a greater extent and for a longer period of time. We conclude that the interval needed to discriminate between time-separated tactile stimuli is related to the number of stimuli used in the task. STDT and ThirdDT are encoded in S1, probably by a shared tactile temporal encoding mechanism whose performance rapidly changes during the perception process. ThirdDT is a new method to measure somatosensory temporal discrimination. NEW & NOTEWORTHY To investigate whether the time interval required to discriminate between stimuli varies according to changes in the stimulation pattern, we used the third-stimulus temporal discrimination threshold (ThirdDT). We found that the somatosensory temporal discrimination acuity varies according to the number of stimuli in the task. The ThirdDT is a new method to measure somatosensory temporal discrimination and a possible index of inhibitory activity at the S1 level.
<b>Measuring Indian Blackbuck <I>Antilope cervicapra</I> (Mammalia: Cetartiodactyla: Bovidae) abundance at Basur Amruth Mahal Kaval Conservation Reserve, Chikkamagaluru, southern India</b>
Authors: Sagar H.S. Sathya Chandra , Antoney P. U. 
Published: July 2017

Grasslands are among the most critically endangered ecosystems in the tropics, but they are often treated as wastelands and conservation efforts are seldom directed towards these landscapes. The Blackbuck Antilope cervicapra is a large wild herbivore found in most grassland ecosystems across India. Despite their critical role in their trophic web, there are no reliable estimates of Blackbuck populations from their geographic range that takes detection probability into consideration. In this study, we conducted field surveys to estimate Blackbuck density in Basur Amruth Mahal Kaval Conservation (BAMKCR) with an area of 7.36km2 in southern India. We surveyed Blackbucks for a week in July 2014 along straight line transects between 09:00–12:00 hr and used the distance sampling approach to address the imperfect detection. A total of three transect lines of lengths 3.01km, 2.4km and 1.2km were sampled for seven temporal replicates. With an effort of 46.27km, 56 sightings of Blackbucks were recorded that was analyzed using the program DISTANCE. With a detection probability of 0.58 (0.053 SD) the estimated density of Blackbuck was 26.23 (6 SD) individuals/km2. The derived abundance estimate was 193 (c. 148–238) individuals in the study area. Our results show implications of a statistically robust design that accounts for imperfect detection. It provides an insight into a resident population of Blackbucks in a dynamic and fragile habitat. Blackbuck density estimate from this study sets the background for periodic monitoring of their populations, examination of the impacts of habitat modifications and gauge long-term viability of the grassland habitat in BAMKCR.
<b>Influence of seasonal and edaphic factors on the diversity of scolopendromorph centipedes (Chilopoda: Scolopendromorpha) and general observations on their ecology from Kerala, India</b>
Authors: Balan Dhanya , Sureshan P. M. 
Published: July 2017

Scolopendromorph centipedes (Chilopoda: Scolopendromorpha) are a diverse group of invertebrate communities, which play significant, but often poorly acknowledged or understood roles in the delivery of soil ecosystem services. In the present paper we analyze the impact of seasonal and edaphic factors on the species diversity of scolopendromorph centipedes based on the field studies conducted in three selected sites. The study sites included a protected forest ecosystem, an undisturbed isolated hillock and a residential plot at Kozhikode District, Kerala, India. The study was performed from April 2011 to November 2012. Overall 486 individuals belonging to 18 species under the families Cryptopidae and Scolopendridae were collected. The range of Shannon-Wiener diversity was 0.89–2.58 and Simpson diversity was 1.91–13.69. Species diversity is also influenced by variations in seasons and various physico–chemical properties of soil in the study area. General observations on parental care, moulting, hibernation and ectoparasitism were also included.
<b>Records of the Indian Sand Snake <I>Psammophis condanarus</I> (Merrem, 1820) (Reptilia: Lamprophiidae) in southern India</b>
Authors: Ganesh S. R. , Sharma Vivek , Guptha M. Bubesh 
Published: July 2017

We present new records of the Indian Sand Snake Psammophis condanarus from southern India, where its existence has remained doubtful till date. Our records are based on both live and preserved voucher specimens that are illustrated and described here. We furnish distribution records of this species from two sites belonging to two different ecoregions in southern India—Tirupati in the Eastern Ghats and Hospete in the Deccan plateau. Our work highlights the obscurity of certain, large-growing, diurnal land snakes that have as yet managed to evade the attention of field biologists largely due to a lack of field surveys in certain ecoregions.
Multiscale Dynamical Processes Underlying the Wintertime Atlantic Blockings
Authors: Ma Jiwang , San Liang X. 
Published: July 2017

Abstract
The wintertime atmospheric blocking over the Atlantic is investigated using a newly developed methodology—namely, localized multiscale energy and vorticity analysis (MS-EVA)—and the theory of canonical energy transfer. Through a multiscale window transform (MWT), the atmospheric fields from the ERA-40 data are reconstructed on three-scale ranges or scale windows: basic-flow window, blocking window, and synoptic window. The blocking event is obtained by compositing the wintertime blocking episodes, and a clear westward-retrograding signal is identified on the blocking window. Likewise, the local multiscale energetics following the signal are composited. It is found that a life cycle of the blocking-scale kinetic energy (KE) may be divided into three phases: onset phase, amplification phase, and decay phase. Different phases have different mechanisms in play. In general, pressure work and the canonical transfer from the synoptic eddies initiate the generation of the blocking, while the latter contributes to its amplification. The blocking decays as the system transports the KE away and as it converts the KE into available potential energy (APE) through buoyancy conversion. For the APE on the blocking window, its evolution experiences two maxima and, correspondingly, two phases can be distinguished. In the first maximum phase, the dominating mechanism is baroclinic instability; in the second, buoyancy conversion takes place. These are also the mechanisms that cause the warm core of the blocking in the troposphere.
Evaluation of Parkinson’s disease by neuromelanin-sensitive magnetic resonance imaging and 123I-FP-CIT SPECT
Authors: Kuya Keita , Ogawa Toshihide , Shinohara Yuki , Ishibashi Mana , Fujii Shinya , Mukuda Naoko , Tanabe Yoshio 
Published: July 2017

Background Both neuromelanin-sensitive magnetic resonance imaging (NmMRI) and 123I-FP-CIT single photon emission computed tomography (SPECT) (DaTSCAN) assist the diagnosis of Parkinson’s disease (PD). However, there have been few studies investigating a correlation between them. Purpose To correlate the utility of NmMRI and DaTSCAN and to evaluate the relationship between both imaging findings and the Unified PD rating scale part III (UPDRS III) score for the diagnosis and management of PD. Material and Methods Seventeen patients with PD who underwent both NmMRI and DaTSCAN were included. We measured the volume of the neuromelanin-positive substantia nigra pars compacta (SNc volume) on NmMRI and measured the specific binding ratio (SBR) on DaTSCAN. The asymmetry index (AI) of the SNc volume and SBR were also calculated. We evaluated the relationship between the UPDRS III score and the SNc volume and SBR, respectively. Results The SNc volume showed a significant correlation with the SBR. The AIs of them also showed a significant correlation. Both the mean of the bilateral SBR and the mean of the bilateral SNc volume showed significant negative correlations with the UPDRS III score. However, the correlation between the SBR and the UPDRS III score was stronger than that between the SNc volume and the UPDRS III score. Conclusion Both NmMRI and DaTSCAN are helpful for PD diagnosis. However, we conclude that DaTSCAN is more suitable for the evaluation of the clinical motor severity and would be more useful for the management of PD patients than NmMRI.
A 20-Year Follow-up After First-Generation Autologous Chondrocyte Implantation
Authors: Ogura Takahiro , Mosier Brian A. , Bryant Tim , Minas Tom 
Published: July 2017

Background:Treating articular cartilage defects is a demanding problem. Although several studies have reported durable and improved clinical outcomes after autologous chondrocyte implantation (ACI) over a long-term period, there is no report with over 20 years’ follow-up.Purpose:To evaluate clinical outcomes after first-generation ACI for the treatment of knees with disabling, large single and multiple cartilage defects for which patients wished to avoid prosthetic arthroplasty, with a minimum of 20 years’ follow-up.Study Design:Case series; Level of evidence, 4.Methods:The authors reviewed prospectively collected data from 23 patients (24 knees; mean age, 35.4 years [range, 13-52 years]) undergoing ACI for the treatment of symptomatic, full-thickness articular cartilage lesions. A mean of 2.1 lesions per knee were treated over a mean total surface area of 11.8 cm2(range, 2.4-30.5 cm2) per knee. Kaplan-Meier survival analysis and functional outcome scores, including the modified Cincinnati Knee Rating System, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Short Form–36 (SF-36), were used. Patients also self-reported an improvement in pain with a visual analog scale and a satisfaction survey.Results:The 20-year survival rate was 63% (95% CI, 40%-78%). The evaluation of the 15 knees with retained grafts demonstrated that all clinical scores except the WOMAC subscore for stiffness and SF-36 mental component summary score improved significantly and were sustained to 20 years postoperatively. Ninety-three percent of these patients rated knee-specific outcomes as good or excellent. The outcomes for 9 of 24 knees were considered failures, including 5 undergoing revision ACI and 4 being converted to arthroplasty at a mean of 1.7 and 5.9 years, respectively. Only 1 of 5 knees that underwent revision ACI was converted to arthroplasty at 1.9 years after the index surgery, and the other 4 patients were able to maintain their biological knee. Overall, 20 years later, 79% of patients maintained their native knee, for which they initially sought treatment, and were satisfied when evaluated.Conclusion:First-generation ACI provided satisfactory survival rates and significant clinical improvements over a 20-year follow-up, which offers an important standard for comparison with newer-generation ACI technologies of the future.
Age discrimination in healthcare institutions perceived by seniors and students
Authors: Dobrowolska Beata , Jędrzejkiewicz Bernadeta , Pilewska-Kozak Anna , Zarzycka Danuta , Ślusarska Barbara , Deluga Alina , Kościołek Aneta , Palese Alvisa 
Published: July 2017

Background: Old age–based discrimination is observed as the most tolerated prejudice in society and has also been witnessed in healthcare institutions. Aims: The aim of this study is to explore age-based discrimination in healthcare institutions as perceived by seniors and students of Medicine and Nursing. Research design: A multi-method study design, by involving a triangulation design. Participants and research context: A purposeful sample of individuals aged 65+ (n = 80) and medical and nursing students (n = 100) in the eastern region of Poland. Ethical considerations: Ethical approval of the research protocol was received from the Ethics Committee at the Medical University of Lublin. Findings: ‘Old age’ was perceived by groups of participants based on three themes: (a) positive, (b) negative and (c) neutral connotations. The negative connotations predominated. The beginning of old age was defined by the metric of age and described by showing the complexity of the ageing process involving subjective, objective and societal aspects. Experience of age discrimination in healthcare institutions was reported by 24 (30%) seniors and witnessed by 47 (47%) students surveyed and for both groups occurred mainly at the hospital level and by physicians. Only 48 students (48%) declared a willingness to work with the older people in the future, and barriers were reported at the personal and professional levels, and also in some visions of older people. Conclusion: The conceptualization of old age as reported by seniors and students mainly carried negative connotations, reflecting the profoundly based stereotypes within society regarding the older people. Seniors have reported being exposed to ageism and have witnessed ageism episodes in HCIs; also, students have faced ageism episodes during their clinical education. There is a need for ethical education within medical and nursing courses to shape positive attitudes towards the older people. A positive vision of ageing should be promoted not only among young people but also among adults and older people to avoid self-stereotyping of older people and seeing old age from negative perspective.