bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial Quality Control via the PGC1α-TFEB Signaling Pathway Is Compromised by Parkin Q311X Mutation But Independently Restored by Rapamycin
Authors: Siddiqui Almas , Bhaumik Dipa , Chinta Shankar J. , Rane Anand , Rajagopalan Subramanian , Lieu Christopher A. , Lithgow Gordon J. , Andersen Julie K. 
Published: September 2015

Following its activation by PINK1, parkin is recruited to depolarized mitochondria where it ubiquitinates outer mitochondrial membrane proteins, initiating lysosomal-mediated degradation of these organelles. Mutations in the gene encoding parkin, PARK2, result in both familial and sporadic forms of Parkinson's disease (PD) in conjunction with reductions in removal of damaged mitochondria. In contrast to what has been reported for other PARK2 mutations, expression of the Q311X mutationin vivoin mice appears to involve a downstream step in the autophagic pathway at the level of lysosomal function. This coincides with increased PARIS expression and reduced expression of a reciprocal signaling pathway involving the master mitochondrial regulator peroxisome proliferator-activated receptor-gamma coactivator (PGC1α) and the lysosomal regulator transcription factor EB (TFEB). Treatment with rapamycin was found to independently restore PGC1α-TFEB signaling in a manner not requiring parkin activity and to abrogate impairment of mitochondrial quality control and neurodegenerative features associated with thisin vivomodel. Losses in PGC1α-TFEB signaling in cultured rat DAergic cells expressing the Q311X mutation associated with reduced mitochondrial function and cell viability were found to be PARIS-dependent and to be independently restored by rapamycin in a manner requiring TFEB. Studies in human iPSC-derived neurons demonstrate that TFEB induction can restore mitochondrial function and cell viability in a mitochondrially compromised human cell model. Based on these data, we propose that the parkin Q311X mutation impacts on mitochondrial quality control via PARIS-mediated regulation of PGC1α-TFEB signaling and that this can be independently restored via upregulation of TFEB function.SIGNIFICANCE STATEMENTMutations in PARK2 are generally associated with loss in ability to interact with PINK1, impacting on autophagic initiation. Our data suggest that, in the case of at least one parkin mutation, Q311X, detrimental effects are due to inhibition at the level of downstream lysosomal function. Mechanistically, this involves elevations in PARIS protein levels and subsequent effects on PGC1α-TFEB signaling that normally regulates mitochondrial quality control. Treatment with rapamycin independently restores PGC1α-TFEB signaling in a manner not requiring parkin activity and abrogates subsequent mitochondrial impairment and neuronal cell loss. Taken in total, our data suggest that the parkin Q311X mutation impacts on mitochondrial quality control via PARIS-mediated regulation of PGC1α-TFEB signaling and that this can be independently restored via rapamycin.
A Neural Basis for Developmental Topographic Disorientation
Authors: Kim Jiye G. , Aminoff Elissa M. , Kastner Sabine , Behrmann Marlene 
Published: September 2015

Developmental topographic disorientation (DTD) is a life-long condition in which affected individuals are severely impaired in navigating around their environment. Individuals with DTD have no apparent structural brain damage on conventional imaging and the neural mechanisms underlying DTD are currently unknown. Using functional and diffusion tensor imaging, we present a comprehensive neuroimaging study of an individual, J.N., with well defined DTD. J.N. has intact scene-selective responses in the parahippocampal place area (PPA), transverse occipital sulcus, and retrosplenial cortex (RSC), key regions associated with scene perception and navigation. However, detailed fMRI studies probing selective tuning properties of these regions, as well as functional connectivity, suggest that J.N.'s RSC has an atypical response profile and an atypical functional coupling to PPA compared with human controls. This deviant functional profile of RSC is not due to compromised structural connectivity. This comprehensive examination suggests that the RSC may play a key role in navigation-related processing and that an alteration of the RSC's functional properties may serve as the neural basis for DTD.SIGNIFICANCE STATEMENTIndividuals with developmental topographic disorientation (DTD) have a life-long impairment in spatial navigation in the absence of brain damage, neurological conditions, or basic perceptual or memory deficits. Although progress has been made in identifying brain regions that subserve normal navigation, the neural basis of DTD is unknown. Using functional and structural neuroimaging and detailed statistical analyses, we investigated the brain regions typically involved in navigation and scene processing in a representative DTD individual, J.N. Although scene-selective regions were identified, closer scrutiny indicated that these areas, specifically the retrosplenial cortex (RSC), were functionally disrupted in J.N. This comprehensive examination of a representative DTD individual provides insight into the neural basis of DTD and the role of the RSC in navigation-related processing.
“Well, we must be for ourselves in the long run”
Authors: Joudrey Thomas J. 
Published: September 2015

Thomas J. Joudrey, “‘Well, we must be for ourselves in the long run’: Selfishness and Sociality in Wuthering Heights” (pp. 165–193)
This essay traces a problem that has long dogged criticism of Emily Brontë’s Wuthering Heights (1847): why is a novel concerned with passionate love for others populated by characters who are radically selfish? Brontë, drawing on the Byronic tradition and eschewing contemporary exhortations to self-renunciation, validates selfish desire even at the expense of communal responsibility. In so doing, she is forced to contend with the possibility that selfishness risks disabling sociality and marooning the self in shame, isolation, or solipsism. Brontë shows, however, that selfishness and sociality are symbiotically implicated, in that selfishness acts as a precondition of robust sociality. After a series of failures—represented in Lockwood’s shame-saturated retreat into childish sociality, Heathcliff and Catherine’s self-destroying soul fusion, and Linton Heathcliff’s masturbatory selfishness—Brontë ultimately locates a brokered compromise between selfishness and sociality in the relationship of Cathy and Hareton. By maintaining their respective boundaries of self and yet making them selectively permeable, the two demonstrate that susceptibility to interpersonal exchange proves vital to fostering their autonomy as discrete selves. Wuthering Heights wages battle on two fronts, excoriating the temptation to enclose the self behind impenetrable barriers, but simultaneously denouncing the other extreme that would eradicate all difference through metaphysical soul-fusion. Brontë posits instead that mature selfhood can only be yielded by a posture of openness to external influences, even as the coherence of the self must be fortified against appropriation by those influences.
Selection Against Maternal microRNA Target Sites in Maternal Transcripts
Authors: Marco Antonio 
Published: September 2015

AbstractIn animals, before the zygotic genome is expressed, the egg already contains gene products deposited by the mother. These maternal products are crucial during the initial steps of development. In Drosophila melanogaster, a large number of maternal products are found in the oocyte, some of which are indispensable. Many of these products are RNA molecules, such as gene transcripts and ribosomal RNAs. Recently, microRNAs (small RNA gene regulators) have been detected early during development and are important in these initial steps. The presence of some microRNAs in unfertilized eggs has been reported, but whether they have a functional impact in the egg or early embryo has not being explored. I have extracted and sequenced small RNAs from Drosophila unfertilized eggs. The unfertilized egg is rich in small RNAs and contains multiple microRNA products. Maternal microRNAs often are encoded within the intron of maternal genes, suggesting that many maternal microRNAs are the product of transcriptional hitchhiking. Comparative genomics analyses suggest that maternal transcripts tend to avoid target sites for maternal microRNAs. I also developed a microRNA target mutation model to study the functional impact of polymorphisms at microRNA target sites. The analysis of Drosophila populations suggests that there is selection against maternal microRNA target sites in maternal transcripts. A potential role of the maternal microRNA mir-9c in maternal-to-zygotic transition is also discussed. In conclusion, maternal microRNAs in Drosophila have a functional impact in maternal protein−coding transcripts.
The Genetic Architecture of Hearing Impairment in Mice: Evidence for Frequency-Specific Genetic Determinants
Authors: Crow Amanda L , Ohmen Jeffrey , Wang Juemei , Lavinsky Joel , Hartiala Jaana , Li Qingzhong , Li Xin , Salehide Pezhman , Eskin Eleazar , Pan Calvin , Lusis Aldons J , Allayee Hooman , Friedman Rick A 
Published: September 2015

Abstract
Genome-wide association studies (GWAS) have been successfully applied in humans for the study of many complex phenotypes. However, identification of the genetic determinants of hearing in adults has been hampered, in part, by the relative inability to control for environmental factors that might affect hearing throughout the lifetime, as well as a large degree of phenotypic heterogeneity. These and other factors have limited the number of large-scale studies performed in humans that have identified candidate genes that contribute to the etiology of this complex trait. To address these limitations, we performed a GWAS analysis using a set of inbred mouse strains from the Hybrid Mouse Diversity Panel. Among 99 strains characterized, we observed approximately two-fold to five-fold variation in hearing at six different frequencies, which are differentiated biologically from each other by the location in the cochlea where each frequency is registered. Among all frequencies tested, we identified a total of nine significant loci, several of which contained promising candidate genes for follow-up study. Taken together, our results indicate the existence of both genes that affect global cochlear function, as well as anatomical- and frequency-specific genes, and further demonstrate the complex nature of mammalian hearing variation.
Persistent Activation of the Innate Immune Response in AdultDrosophilaFollowing Radiation Exposure During Larval Development
Authors: Sudmeier Lisa J , Samudrala Sai-Suma , Howard Steven P , Ganetzky Barry 
Published: September 2015

AbstractCranial radiation therapy (CRT) is an effective treatment for pediatric central nervous system malignancies, but survivors often suffer from neurological and neurocognitive side effects that occur many years after radiation exposure. Although the biological mechanisms underlying these deleterious side effects are incompletely understood, radiation exposure triggers an acute inflammatory response that may evolve into chronic inflammation, offering one avenue of investigation. Recently, we developed a Drosophila model of the neurotoxic side effects of radiation exposure. Here we use this model to investigate the role of the innate immune system in response to radiation exposure. We show that the innate immune response and NF-ĸB target gene expression is activated in the adult Drosophila brain following radiation exposure during larval development, and that this response is sustained in adult flies weeks after radiation exposure. We also present preliminary data suggesting that innate immunity is radioprotective during Drosophila development. Together our data suggest that activation of the innate immune response may be beneficial initially for survival following radiation exposure but result in long-term deleterious consequences, with chronic inflammation leading to impaired neuronal function and viability at later stages. This work lays the foundation for future studies of how the innate immune response is triggered by radiation exposure and its role in mediating the biological responses to radiation. These studies may facilitate the development of strategies to reduce the deleterious side effects of CRT.
'INIAP-Palmira 2014': a new drought-resistance barley variety
Authors: Falconí Esteban , Garófalo Javier , Ponce Luis , Coronel Jorge , Abad Segundo , Rivadeneira Miguel 
Published: September 2015

Barley (Hordeum vulgare L.) is produced in the Ecuadorian highlands ( > 3,000 m a.s.l.) primarily for self-consumption and small-scale commercialization. Not many crop species are adapted to this altitude; therefore, barley is one of a few crop species that can be grown at these locations. Severe environmental conditions can be found in the Ecuadorian highlands since the region is characterized by poor soils and water deficiency (< 300 mm yr-1). The Instituto Nacional de Investigaciones Agropecuarias (INIAP) has developed 'INIAP-Palmira 2014', a hulled two-row barley variety adapted to Ecuadorian agricultural conditions in the highlands. 'INIAP-Palmira 2014' showed acceptable yield performance as compared with the most popular improved barley cultivars in different production areas located in Ecuador. However, this new barley variety showed superior performance under water stress conditions in the highlands highlands (>3,000 m a.s.l.). Additionally, 'INIAP-Palmira 2014' showed disease resistance, mainly to yellow rust, in all of the locations where the new variety was evaluated.
A Qualitative Inquiry About Pruno, an Illicit Alcoholic Beverage Linked to Botulism Outbreaks in United States Prisons
Authors: Walters Maroya Spalding , Sreenivasan Nandini , Person Bobbie , Shew Mark , Wheeler Daniel , Hall Julia , Bogdanow Linda , Leniek Karyn , Rao Agam 
Published: September 2015

Objectives. Since 2011, 3 outbreaks of botulism in US prisons have been attributed to pruno, which is an alcoholic beverage made by inmates. Following 1 outbreak, we conducted a qualitative inquiry to understand pruno brewing and its social context to inform outbreak prevention measures. Methods. We interviewed staff, inmates, and parolees from 1 prison about pruno production methods, the social aspects of pruno, and strategies for communicating the association between botulism and pruno. Results. Twenty-seven inmates and parolees and 13 staff completed interviews. Pruno is fermented from water, fruit, sugar, and miscellaneous ingredients. Knowledge of pruno making was widespread among inmates; staff were familiar with only the most common ingredients and supplies inmates described. Staff and inmates described inconsistent consequences for pruno possession and suggested using graphic health messages from organizations external to the prison to communicate the risk of botulism from pruno. Conclusions. Pruno making was frequent in this prison. Improved staff recognition of pruno ingredients and supplies might improve detection of brewing activities in this and other prisons. Consistent consequences and clear messages about the association between pruno and botulism might prevent outbreaks.
Extended Spectrum Beta-Lactamase Production in Uropathogens Isolated from Hospitalized Patients with Chronic Pyelonephritis
Authors: Chub Olga I , Bilchenko Aleksandr V , Khalin Igor 
Published: September 2015

Background :Increased multidrug resistance of extended-spectrum beta-lactamases (ESBLs) compromises the efficacy of treatment of urinary tract infections.Objective :The objective of this study is to determine the prevalence of ESBL-producing uropathogens from hospitalized patients with chronic pyelonephritis and to identify the presence of genes involved in the resistance.Methods :A cross-sectional study of 105 patients with chronic pyelonephritis, treated in Kharkiv City Clinical Emergency Hospital, Ukraine was carried. Bacterial isolates were collected, antimicrobial susceptibility of isolates was determined by the Kirby Bauer disk diffusion method and screening for the presence of blaSHV, blaTEM, blaCTX-M ESBL genes was performed by polymerase chain reaction.Results :84 (80%) patients had positive urine cultures.Eschеrichia coliwаs the most common microorganism isolated. Among them, 29 (25.2%) were found to be ESBL producers. Out of 53E. coliisolates, 10 (18.9%), 4 (7.5%) and 6 (11.3%) were identified to carry bla(TEM), bla(SHV) and bla(CTX-M) beta-lactamase genes, respectively. The highest resistance was observed against ampicillin (75.9%), ciprofloxacin (48.3%), levofloxacin (41.4%) and gentamicin (41.4%). Beside this, only meropenem (96.6% susceptibility), nitroxolinum (86.2%) and fosfomycin (72.4%) exhibited a good enough activity against ESBLs-producing urinary strains.Conclusion :Isоlation and detеction of ESBL-prоducing strаins are еssential fоr the sеlection оf the mоst effеctive antibiоtic for the empiric trеatment.
Ten-Year Results of Primary and Revision Condylar-Constrained Total Knee Arthroplasty in Patients with Severe Coronal Plane Instability
Authors: Camera Andrea , Biggi Stefano , Cattaneo Gabriele , Brusaferri Giovanni 
Published: September 2015

Objective :
To retrospectively review the results at minimum ten years after surgery of a consecutive series of total knee arthroplasties (TKAs) performed using a constrained condylar implant in patients with severe coronal plane instability.

Materials and Methods :
The series comprised of 44 patients (45 knees) who received primary (19 knees) or revision (26 knees) TKA with a constrained condylar implant between 2001 and 2003 at a single institution.

Results :
There were no revisions or any other surgery related complications at a mean implantation time of 11.0 years. In 38 patients (15 knees in the primary group and 24 knees in the revision group) who were available for clinico-radiographic follow-up at a minimum of ten years, there was no sign of radiographic loosening. Two patients showed cortical hypertrophy at the extension stem tip but none complained of pain around the stem tip.
According to the TLKSS score grading, 73% of the patients in the primary group had results categorized as good or excellent, while 54% of the patients in the revision group had fair results. Four patients (one (7%) in the primary group and three (13%) in the revision group) had poor results. The median WOMAC Index was 80.2% (interquartile range: 74.0% - 81.2%) and 74.0% (interquartile range: 72.1% - 75.8%) in the primary and in the revision groups, respectively (p=0.010).

Conclusion :
This study showed satisfactory clinical outcomes with no re-operations at minimum ten years after implantation in patients who had undergone primary or revision TKA with a condylar constrained implant.
Increased Mortality Amongst Patients Sustaining Neck of Femur Fractures as In-Patients in a Trauma Centre
Authors: Mohamed Mohamed , Patel Dhawal , Zhao Sizheng , Ballal Moeez S , Scott Simon 
Published: September 2015

Purpose: Neck of Femur (NOF) fracture is a common injury with high mortality that all orthopaedic departments must contend with [1]. The aim of this study was to report incidence and mortality of NOF fractures occurring while patients were being admitted to hospital for other conditions.

Methods:
A retrospective review was performed of all NOF fracture admissions between 1st of Jan 2010 to 31st of Dec 2012 at a University Hospital trauma centre. Fractures were divided according to the location where the fracture occurred, either in the community (acute NOF) or in-hospital (in-hospital NOF).

Results:
In-hospital mortality, 30-day, 90-day and 1 year mortality were recorded. There were 1086 patients in the acute NOF fracture group (93.9%) and 70 patients in the in-hospital group (6.1%) over three years. The odds of inpatient death was 2.25 times higher for inpatient NOFs (p=0.012). 86% of all in-hospital NOF fractures occurred on medical and rehabilitation wards. NOF fractures result in increased mortality and morbidity.

Conclusion:
All patients in hospital should be assessed to identify those at high risk of falls and implemented measures should be taken to reduce this.
High Rates of Postoperative Wound Infection Following Elective Implant Removal
Authors: Backes M , Schep N.W.L , Luitse J.S.K , Goslings J.C , Schepers T 
Published: September 2015

Introduction :Metal implants placed during fracture surgery are often removed for various reasons (i.e. pain, prominent material, patients request). The removal of implants is considered a ‘clean’ procedure and as low risk surgery. The incidence of wound infections following implant removal has received little attention in the literature. The aim of the current study was to assess the incidence and risk factors of postoperative wound infections (POWIs) following implant removal.Material and Methods :All consecutive adult patients in a Level 1 and Level 2 Trauma Center who had their implants removed during a 6.5 years period were included. Exclusion criteria were removal of implants because of an ongoing infection or fistula and removal followed by placement of new implants. Primary outcome measure was a POWI as defined by the US Centers for Disease Control and Prevention. Patient characteristics and peri-operative characteristics were collected from the medical charts.Results :A total of 452 patients were included (512 procedures). The overall POWI rate was 11.6% (10% superficial, 1.6% deep). A total of 403 procedures (78.7%) comprised of implant removal below the knee joint with a 12.2% POWI rate. A POWI following initial fracture treatment was associated with a higher rate of POWI following implant removal (p=0.012). A POWI occurred more often in younger patients (median age 36versus43 years; p=0.004).Conclusion :The overall incidence of postoperative wound infection was 11.6% with 10% superficial and 1.6% of deep infections in patients with elective implant removal. A risk factor for POWI following implant removal was a previous wound infection.