bluuebunny/crossref_metadata_2025 huggingface dataset:
Caveolin-1 promotes trophoblast cell invasion through the focal adhesion kinase (FAK) signalling pathway during early human placental development
Authors: Dai Zhihui , Sheng Fei , Sun Ningxia , Ji Yixuan , Liao Qiuying , Sun Shuhan , Yang Fu , Li Wen
Published: April 2019

Normal implantation and placental development depend on the appropriate differentiation and invasion of trophoblast cells. Inadequate trophoblast cell invasion results in pregnancy-related disorders, which endanger both mother and fetus; however, the mechanism of early placental development has not been fully explained. In this study we conducted gene expression profile analysis using mouse placental tissues at different developmental stages (embryonic day (E)7.5, E14.5 and E19.5) using series tests of cluster (STC) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analyses. Focal adhesion kinase (FAK) signalling pathway-related gene expression levels were verified using quantitative reverse transcription polymerase chain reaction and western blot. The results showed that caveolin-1 (Cav1) was downregulated in the placenta of unexplained spontaneous abortion subjects compared with that of induced abortion. Furthermore, by modulating CAV1 expression levels, CAV1 was shown to promote human trophoblast cell proliferation, migration and invasion by activating the FAK signalling pathway. These results indicate that CAV1 and the FAK signalling pathway are crucial for early placental development, which sheds new light on our understanding of the mechanisms of human trophoblast cell invasion and early development of the placenta.
Epigenetic regulation of progesterone receptors and the onset of labour
Authors: Ilicic Marina , Zakar Tamas , Paul Jonathan W.
Published: April 2019

Progesterone plays a crucial role in maintaining pregnancy by promoting myometrial quiescence. The withdrawal of progesterone action signals the end of pregnancy and, in most mammalian species, this is achieved by a rapid fall in progesterone concentrations. However, in humans circulating progesterone concentrations remain high up to and during labour. Efforts to understand this phenomenon led to the ‘functional progesterone withdrawal’ hypothesis, whereby the pro-gestation actions of progesterone are withdrawn, despite circulating concentrations remaining elevated. The exact mechanism of functional progesterone withdrawal is still unclear and in recent years has been the focus of intense research. Emerging evidence now indicates that epigenetic regulation of progesterone receptor isoform expression may be the crucial mechanism by which functional progesterone withdrawal is achieved, effectively precipitating human labour despite high concentrations of circulating progesterone. This review examines current evidence that epigenetic mechanisms play a role in determining whether the pro-gestation or pro-contractile isoform of the progesterone receptor is expressed in the pregnant human uterus. We explore the mechanism by which these epigenetic modifications are achieved and, importantly, how these underlying epigenetic mechanisms are influenced by known regulators of uterine physiology, such as prostaglandins and oestrogens, in order to phenotypically transform the pregnant uterus and initiate labour.
The dynamics of feral pig (Sus scrofa) populations in response to food supply
Authors: Gentle Matthew , Pople Anthony , Scanlan Joseph C. , Carter John
Published: April 2019

Context
Feral pigs (Sus scrofa) are highly fecund, and populations can increase rapidly under favourable conditions. Population size can also fluctuate widely, driven largely by changes in juvenile mortality in response to food availability, but these relationships have only been explored on a limited number of sites and over short periods.
Aims
The present study aimed to investigate and quantify the numerical response of feral pig populations to changes in their food supply in north-eastern Australia.
Methods
Pig population densities were determined from aerial surveys conducted over a 21-year period on 10 regional blocks (~2000–6000 km2) throughout the Queensland rangelands. Densities were used to calculate annual exponential rates of increase (r), which were then corrected for anthropogenic mortality (baiting and commercial harvesting). Six proxy measures of annual food supply, including rainfall, pasture biomass and pasture growth (using the AussieGRASS model), were calculated for each survey block, and assessed as predictors of corrected r. The rates of increase predicted from the first half of the data series were then applied to initial population densities to estimate successive pig densities during the second period in each bioregion.
Key results
The most parsimonious model of the numerical response had parameters common to three bioregions, with rainfall in the 12 months between surveys being the best predictor variable. Modelled densities for each bioregion were a good fit to actual, observed densities. Relationships between r and each measure of food supply at the individual block level were inconsistent.
Conclusions
Using rainfall as a measure of food supply, the numerical response relationship provides a method for predicting the dynamics of feral pig populations at the bioregional scale. Predicting population dynamics at any one site using this relationship is less precise, suggesting that differences in landscape composition affect utilisation of resources supporting population growth.
Implications
The results from the present study could be used to predict feral pig population changes at the bioregional level, supplementing or reducing the need for more frequent, expensive population surveys. This improved ability to predict fluctuations in regional feral pig populations can help guide future management actions.
Prostaglandin signaling regulates renal multiciliated cell specification and maturation
Authors: Marra Amanda N. , Adeeb Basma D. , Chambers Brooke E. , Drummond Bridgette E. , Ulrich Marisa , Addiego Amanda , Springer Meghan , Poureetezadi Shahram J. , Chambers Joseph M. , Ronshaugen Matthew , Wingert Rebecca A.
Published: April 2019

Significance

Multiciliated cells (MCCs) have core roles in organ formation and function, where they control fluid flow and particle displacement. MCCs direct fluid movement in the brain and spinal cord, clearance of respiratory mucus, and ovum transport from the ovary to the uterus. Deficiencies in MCC functionality lead to hydrocephalus, chronic respiratory infections, and infertility. Prostaglandins are lipids that are used to coordinate cellular functions. Here, we discovered that prostaglandin signaling is required for MCC development in the embryonic zebrafish kidney. Understanding renal MCC genesis can lend insights into the puzzling origins of MCCs in several chronic kidney diseases, where it is unclear whether MCCs are a cause or phenotypic outcome of the condition.
Mechanism mediated by a noncoding RNA, nc886, in the cytotoxicity of a DNA-reactive compound
Authors: Kunkeaw Nawapol , Lee Yeon-Su , Im Wonkyun Ronny , Jang Jiyoung Joan , Song Min-Ji , Yang Bobae , Park Jong-Lyul , Kim Seon-Young , Ku Yongsuk , Kim Yoosik , Kang Sangmin , Jo Hye-ram , Jeong Jae-Hoon , Lee Hyun-Sung , Lee Ju-Seog , Kim Hyoung-Pyo , Johnson Betty H. , Kim In-Hoo , Lee Yong Sun
Published: April 2019

DNA-reactive compounds are harnessed for cancer chemotherapy. Their genotoxic effects are considered to be the main mechanism for the cytotoxicity to date. Because this mechanism preferentially affects actively proliferating cells, it is postulated that the cytotoxicity is specific to cancer cells. Nonetheless, they do harm normal quiescent cells, suggesting that there are other cytotoxic mechanisms to be uncovered. By employing doxorubicin as a representative DNA-reactive compound, we have discovered a cytotoxic mechanism that involves a cellular noncoding RNA (ncRNA) nc886 and protein kinase R (PKR) that is a proapoptotic protein. nc886 is transcribed by RNA polymerase III (Pol III), binds to PKR, and prevents it from aberrant activation in most normal cells. We have shown here that doxorubicin evicts Pol III from DNA and, thereby, shuts down nc886 transcription. Consequently, the instantaneous depletion of nc886 provokes PKR and leads to apoptosis. In a short-pulse treatment of doxorubicin, these events are the main cause of cytotoxicity preceding the DNA damage response in a 3D culture system as well as the monolayer cultures. By identifying nc886 as a molecular signal for PKR to sense doxorubicin, we have provided an explanation for the conundrum why DNA-damaging drugs can be cytotoxic to quiescent cells that have the competent nc886/PKR pathway.
Photocycle-dependent conformational changes in the proteorhodopsin cross-protomer Asp–His–Trp triad revealed by DNP-enhanced MAS-NMR
Authors: Maciejko Jakob , Kaur Jagdeep , Becker-Baldus Johanna , Glaubitz Clemens
Published: April 2019

Significance

Proteorhodopsin (PR) is found in marine bacteria in various ecosystems and is one of the most abundant photoreceptors. It converts light into a transmembrane, electrochemical gradient as a source of energy for the cell. PR, like many microbial rhodopsins, forms functionally unresolved higher oligomers. Here, experimental evidence for functionally relevant cross-protomer interactions within the PR pentamer is presented. An Asp–His–Trp triad is formed across the oligomerization interface, participates in the photocycle, and potentially acts as a pH sensor. These findings provide a potentially paradigm shifting aspect for the mechanism of microbial rhodopsins. Such an insight could only be obtained by combining solid-state NMR spectroscopy with dynamic nuclear polarization and light-induced cryotrapping of photointermediates.
Inhibitors of the
Neisseria meningitidis
PilF ATPase provoke type IV pilus disassembly
Authors: Aubey Flore , Corre Jean-Philippe , Kong Youxin , Xu Ximing , Obino Dorian , Goussard Sylvie , Lapeyrere Catherine , Souphron Judith , Couturier Cedric , Renard Stéphane , Duménil Guillaume
Published: April 2019

Significance

A number of multimeric protein nanomachines such as secretion systems and surface appendages allow bacteria to adapt and survive in a variety of environments. Type IV pili are one of the most common of such machineries. The human pathogen
Neisseria meningitidis
uses type IV pili to colonize blood vessels and cause disease. Here, we identify compounds that trigger the rapid retraction of type IV pili. Furthermore, we identify the target of these small molecules as an ATPase known as PilF among the 20 proteins involved in pilus assembly and function. This study paves the way for an innovative treatment strategy for different pathogens and provides information on the molecular mechanisms driving the assembly and dynamics of bacterial machineries.
PCH1 regulates light, temperature, and circadian signaling as a structural component of phytochrome B-photobodies in
Arabidopsis
Authors: Huang He , McLoughlin Katrice E. , Sorkin Maria L. , Burgie E. Sethe , Bindbeutel Rebecca K. , Vierstra Richard D. , Nusinow Dmitri A.
Published: April 2019

Significance

In
Arabidopsis
, phytochrome B (phyB) perceives light and temperature signals to regulate various fundamental morphogenic processes in plants through its interconversion between its active Pfr and inactive Pr states. On photoconversion from Pr to Pfr, phyB forms subnuclear foci called photobodies, whose compositions and molecular functions are unclear. We show here that the phyB-interacting protein PCH1 is a structural component of phyB photobodies that protects Pfr from thermal reversion back to Pr, thereby helping to maintain phyB signaling. Loss of PCH1 compromises photobody formation, which disrupts a number of downstream events, including photomorphogenesis and thermal perception and signaling into the circadian clock. These results demonstrate that the formation of PCH1-dependent phyB photobodies is an essential step connecting light and temperature to controls on plant morphogenesis.
Oncogenic
PIK3CA
promotes cellular stemness in an allele dose-dependent manner
Authors: Madsen Ralitsa R. , Knox Rachel G. , Pearce Wayne , Lopez Saioa , Mahler-Araujo Betania , McGranahan Nicholas , Vanhaesebroeck Bart , Semple Robert K.
Published: April 2019

The
PIK3CA
gene, which encodes the p110α catalytic subunit of PI3 kinase (PI3K), is mutationally activated in cancer and in overgrowth disorders known as
PIK3CA
-related overgrowth spectrum (PROS). To determine the consequences of genetic
PIK3CA
activation in a developmental context of relevance to both PROS and cancer, we engineered isogenic human induced pluripotent stem cells (iPSCs) with heterozygous or homozygous knockin of
PIK3CA

H1047R

. While heterozygous iPSCs remained largely similar to wild-type cells, homozygosity for
PIK3CA

H1047R

caused widespread, cancer-like transcriptional remodeling, partial loss of epithelial morphology, up-regulation of stemness markers, and impaired differentiation to all three germ layers in vitro and in vivo. Genetic analysis of
PIK3CA
-associated cancers revealed that 64% had multiple oncogenic
PIK3CA
copies (39%) or additional PI3K signaling pathway-activating “hits” (25%). This contrasts with the prevailing view that
PIK3CA
mutations occur heterozygously in cancer. Our findings suggest that a PI3K activity threshold determines pathological consequences of oncogenic
PIK3CA
activation and provide insight into the specific role of this pathway in human pluripotent stem cells.
VSMC-specific EP4 deletion exacerbates angiotensin II-induced aortic dissection by increasing vascular inflammation and blood pressure
Authors: Xu Hu , Du Shengnan , Fang Bingying , Li Chaojie , Jia Xiao , Zheng Senfeng , Wang Sailun , Li Qingwei , Su Wen , Wang Nanping , Zheng Feng , Chen Lihong , Zhang Xiaoyan , Gustafsson Jan-Åke , Guan Youfei
Published: April 2019

Significance

AD is a lethal vascular disease with a high mortality. The present study reports a critical role of prostaglandin E2 receptor EP4 in the pathogenesis of AD. VSMC-specific EP4 deletion (VSMC-EP4
−/−
) significantly increases the incidence and severity of AngII-induced aortic aneurysm and dissection. Compared with WT mice, VSMC-EP4
−/−
mice exhibit increased vascular inflammation, oxidative stress, elastic fiber degradation, and VSMC dedifferentiation following chronic AngII infusion. VSMC-EP4
−/−
mice also have higher blood pressure under basal and AngII-infused conditions. Our findings demonstrate that VSMC-EP4 plays an important role in the maintenance of vascular integrity and blood pressure and may represent a potential therapeutic target for the treatment of AD as well as hypertension.
Nebulin and titin modulate cross-bridge cycling and length-dependent calcium sensitivity
Authors: Mijailovich Srboljub M. , Stojanovic Boban , Nedic Djordje , Svicevic Marina , Geeves Michael A. , Irving Thomas C. , Granzier Henk L.
Published: April 2019

Various mutations in the structural proteins nebulin and titin that are present in human disease are known to affect the contractility of striated muscle. Loss of nebulin is associated with reduced actin filament length and impairment of myosin binding to actin, whereas titin is thought to regulate muscle passive elasticity and is likely involved in length-dependent activation. Here, we sought to assess the modulation of muscle function by these sarcomeric proteins by using the computational platform muscle simulation code (MUSICO) to quantitatively separate the effects of structural changes, kinetics of cross-bridge cycling, and calcium sensitivity of the thin filaments. The simulations show that variation in thin filament length cannot by itself account for experimental observations of the contractility in nebulin-deficient muscle, but instead must be accompanied by a decreased myosin binding rate. Additionally, to match the observed calcium sensitivity, the rate of TnI detachment from actin needed to be increased. Simulations for cardiac muscle provided quantitative estimates of the effects of different titin-based passive elasticities on muscle force and activation in response to changes in sarcomere length and interfilament lattice spacing. Predicted force–pCa relations showed a decrease in both active tension and sensitivity to calcium with a decrease in passive tension and sarcomere length. We conclude that this behavior is caused by partial redistribution of the muscle load between active muscle force and titin-dependent passive force, and also by redistribution of stretch along the thin filament, which together modulate the release of TnI from actin. These data help advance understanding of how nebulin and titin mutations affect muscle function.
EDGE2D-EIRENE simulations of the influence of isotope effects and anomalous transport coefficients on near scrape-off layer radial electric field
Authors: Chankin A V , Corrigan G , Maggi C F
Published: April 2019

EDGE2D-EIRENE (the ‘code’) simulations show that radial electric field, E
r, in the near scrape-off layer (SOL) of tokamaks can have large variations leading to a strong local E × B shear greatly exceeding that in the core region. This was pointed out in simulations of JET plasmas with varying divertor geometry, where the magnetic configuration with larger predicted near SOL E
r was found to have lower H-mode power threshold, suggesting that turbulence suppression in the SOL by local E × B shear can be a player in the L–H transition physics (Delabie et al 2015 42nd EPS Conf. on Plasma Physics (Lisbon, Portugal, 22–26 June 2015) paper O3.113 (http://ocs.ciemat.es/EPS2015PAP/pdf/O3.113.pdf), Chankin et al 2017 Nucl. Mater. Energy
12 273). Further code modeling of JET plasmas by changing hydrogen isotopes (H–D–T) showed that the magnitude of the near SOL E
r is lower in H cases in which the H-mode threshold power is higher (Chankin et al 2017 Plasma Phys. Control. Fusion
59 045012). From the experiment it is also known that hydrogen plasmas have poorer particle and energy confinement than deuterium plasmas, consistent with the code simulation results showing larger particle diffusion coefficients at the plasma edge, including SOL, in hydrogen plasmas (Maggi et al 2018 Plasma Phys. Control. Fusion
60 014045). All these experimental observations and code results support the hypothesis that the near SOL E × B shear can have an impact on the plasma confinement. The present work analyzes neutral ionization patterns of JET plasmas with different hydrogen isotopes in L-mode cases with fixed input power and gas puffing rate, and its impact on target electron temperature, T
e, and SOL E
r. The possibility of a self-feeding mechanism for the increase in the SOL E
r via the interplay between poloidal E × B drift and target T
e is discussed. It is also shown that reducing anomalous turbulent transport coefficients, particle diffusion and electron and ion heat conductivities, leads to higher peak target T
e and larger E
r, suggesting the possibility of a positive feedback loop, under an implicitly made assumption that the E × B shear in the SOL is capable of suppressing turbulence.
A spatio-temporal delineation of trans-boundary ecosystem service flows from Inner Mongolia
Authors: Xie Gaodi , Liu Jingya , Xu Jie , Xiao Yu , Zhen Lin , Zhang Changshun , Wang Yangyang , Qin Keyu , Gan Shuang , Jiang Yuan
Published: April 2019

Ecosystem service (ES) flows across geophysical and administrative boundaries are ubiquitous and are receiving more attention in an increasingly metacoupled world. Omitting trans-boundary ES flows from ES assessments will lead to unilateral conclusions and underestimation of ES contributions over distances. Inner Mongolia is an important ecological security barrier of China and Eurasia, but the trans-boundary effect of this barrier is difficult to be quantitatively evaluated and is rarely assessed. This study assessed the ecological security barrier function of Inner Mongolia from the perspective of trans-boundary ES flows, including wind prevention and sand fixation (WPSF), water provision (WP), carbon sequestration (CS) and livestock product provision (LPP) service flows. The trans-boundary value flows for the WPSF, WP, CS and LPP services in 2010 were 6.20 × 1010 CNY (Chinese currency, yuan), 0.21 × 1010 CNY, 1.29 × 1010 CNY and 1.27 × 1010 CNY, respectively, and 5.89 × 1010 CNY, 0.16 × 1010 CNY, 0.37 × 1010 CNY and 1.33 × 1010 CNY, respectively, in 2015; correspondingly, the percentages of these trans-boundary value flows in terms of the total value flow were 69.12%, 2.34%, 14.38% and 14.16%, respectively, in 2010 and 76.00%, 2.06%, 4.77% and 17.16%, respectively, in 2015. Therefore, WPSF service plays a more important role in the trans-boundary ecological security barrier function of Inner Mongolia. This study can enhance the understanding of trans-boundary telecoupling in an integral socio-ecological system and identify the critical ESs to form a foundation for ecological conservation measures considering sustainable development.
Environmental inequality in Austria: do inhabitants’ socioeconomic characteristics differ depending on their proximity to industrial polluters?
Authors: Glatter-Götz Helene , Mohai Paul , Haas Willi , Plutzar Christoph
Published: April 2019

This is the first study to examine the existence of environmental inequality related to industrial facilities in Austria. Using distance-based methods, socioeconomic characteristics of inhabitants living in 1.0 km buffer zones around the 247 polluters registered in the European Pollutant Release and Transfer Registry are compared with those of inhabitants living elsewhere in Austria. While in Vienna no clear signs of environmental inequality can be found, in the rest of Austria people living in close vicinity to industrial sites are more often unemployed, have lower education levels and most notably, are twice as likely to be immigrants. Moreover, a logistic regression shows that the disparities concerning immigrants cannot solely be explained by other socioeconomic characteristics. The results of this study add to the evidentiary base concerning environmental justice disparities in Europe and suggests how application of distance-based methods can facilitate cross-national comparisons.
Decreased Tenofovir Diphosphate Concentrations in a Transgender Female Cohort: Implications for Human Immunodeficiency Virus Preexposure Prophylaxis
Authors: Cottrell Mackenzie L , Prince Heather M A , Schauer Amanda P , Sykes Craig , Maffuid Kaitlyn , Poliseno Amanda , Chun Tae-Wook , Huiting Erin , Stanczyk Frank Z , Peery Anne F , Dellon Evan S , Adams Jessica L , Gay Cindy , Kashuba Angela D M
Published: April 2019

Feminizing hormone therapy (FHT) may interact with human immunodeficiency virus preexposure prophylaxis (PrEP). We found that transgender women who took FHT exhibited a 7-fold lower rectal tissue ratio of PrEP’s active metabolites vs competing deoxynucleotides compared to cisgender women and men (P = .03) that inversely correlated with estradiol (ρ = –0.79; P < .05). Thus, FHT may negatively impact PrEP efficacy.

Clinical Trials Registration . NCT02983110.
Detection of Influenza and Other Respiratory Viruses in Air Sampled From a University Campus: A Longitudinal Study
Authors: Xie Chenyi , Lau Eric H Y , Yoshida Tomoyo , Yu Han , Wang Xin , Wu Huitao , Wei Jianjian , Cowling Ben , Peiris Malik , Li Yuguo , Yen Hui-Ling
Published: April 2019

Background

Respiratory virus–laden particles are commonly detected in the exhaled breath of symptomatic patients or in air sampled from healthcare settings. However, the temporal relationship of detecting virus-laden particles at nonhealthcare locations vs surveillance data obtained by conventional means has not been fully assessed.

Methods

From October 2016 to June 2018, air was sampled weekly from a university campus in Hong Kong. Viral genomes were detected and quantified by real-time reverse-transcription polymerase chain reaction. Logistic regression models were fitted to examine the adjusted odds ratios (aORs) of ecological and environmental factors associated with the detection of virus-laden airborne particles.

Results

Influenza A (16.9% [117/694]) and influenza B (4.5% [31/694]) viruses were detected at higher frequencies in air than rhinovirus (2.2% [6/270]), respiratory syncytial virus (0.4% [1/270]), or human coronaviruses (0% [0/270]). Multivariate analyses showed that increased crowdedness (aOR, 2.3 [95% confidence interval {CI}, 1.5–3.8]; P < .001) and higher indoor temperature (aOR, 1.2 [95% CI, 1.1–1.3]; P < .001) were associated with detection of influenza airborne particles, but absolute humidity was not (aOR, 0.9 [95% CI, .7–1.1]; P = .213). Higher copies of influenza viral genome were detected from airborne particles >4 μm in spring and <1 μm in autumn. Influenza A(H3N2) and influenza B viruses that caused epidemics during the study period were detected in air prior to observing increased influenza activities in the community.

Conclusions

Air sampling as a surveillance tool for monitoring influenza activity at public locations may provide early detection signals on influenza viruses that circulate in the community.
Very long-term survival and late sudden cardiac death in cardiac resynchronization therapy patients
Authors: Barra Sérgio , Duehmke Rudolf , Providência Rui , Narayanan Kumar , Reitan Christian , Roubicek Tomas , Polasek Rostislav , Chow Antony , Defaye Pascal , Fauchier Laurent , Piot Olivier , Deharo Jean-Claude , Sadoul Nicolas , Klug Didier , Garcia Rodrigue , Dockrill Seth , Virdee Munmohan , Pettit Stephen , Agarwal Sharad , Borgquist Rasmus , Marijon Eloi , Boveda Serge
Published: April 2019

Aims

The very long-term outcome of patients who survive the first few years after receiving cardiac resynchronization therapy (CRT) has not been well described thus far. We aimed to provide long-term outcomes, especially with regard to the occurrence of sudden cardiac death (SCD), in CRT patients without (CRT-P) and with defibrillator (CRT-D).

Methods and results

A total of 1775 patients, with ischaemic or non-ischaemic dilated cardiomyopathy, who were alive 5 years after CRT implantation, were enrolled in this multicentre European observational cohort study. Overall long-term mortality rates and specific causes of death were assessed, with a focus on late SCD. Over a mean follow-up of 30 months (interquartile range 10–42 months) beyond the first 5 years, we observed 473 deaths. The annual age-standardized mortality rates of CRT-D and CRT-P patients were 40.4 [95% confidence interval (CI) 35.3–45.5] and 97.2 (95% CI 85.5–109.9) per 1000 patient-years, respectively. The adjusted hazard ratio (HR) for all-cause mortality was 0.99 (95% CI 0.79–1.22). Twenty-nine patients in total died of late SCD (14 with CRT-P, 15 with CRT-D), corresponding to 6.1% of all causes of death in both device groups. Specific annual SCD rates were 8.5 and 5.8 per 1000 patient-years in CRT-P and CRT-D patients, respectively, with no significant difference between groups (adjusted HR 1.0, 95% CI 0.45–2.44). Death due to progressive heart failure represented the principal cause of death (42.8% in CRT-P patients and 52.6% among CRT-D recipients), whereas approximately one-third of deaths in both device groups were due to non-cardiovascular death.

Conclusion

In this first description of very long-term outcomes among CRT recipients, progressive heart failure death still represented the most frequent cause of death in patients surviving the first 5 years after CRT implant. In contrast, SCD represents a very low proportion of late mortality irrespective of the presence of a defibrillator.
Specific Leisure Activities and Cognitive Functions Among the Oldest-Old: The Chinese Longitudinal Healthy Longevity Survey
Authors: Mao Chen , Li Zhi-Hao , Lv Yue-Bin , Gao Xiang , Kraus Virginia Byers , Zhou Jin-Hui , Wu Xian-Bo , Shi Wan-Ying , Li Fu-Rong , Liu Si-Min , Yin Zhao-Xue , Zeng Yi , Shi Xiao-Ming
Published: April 2019

Background: Little is known about the role of specific leisure activities in affecting cognitive functions. We aim to examine the associations of specific leisure activities with the risk of cognitive impairment among oldest-old people in China. Methods: This community-based prospective cohort study included 10,741 cognitively normal Chinese individuals aged 80 years or older (median age 88 years) from the Chinese Longitudinal Healthy Longevity Survey. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Cox proportional hazards models were utilized to estimate the effects of specific leisure activities on cognitive impairment outcome. Results: During a median follow-up time of 3.4 years (41,760 person-years), 2,894 participants developed cognitive impairment. Compared to those who “never” engaged in watching TV or listening to radio, reading books or newspapers, and playing cards or mah-jong, those who engaged in such activities “almost every day” reduced their risk of cognitive impairment, the fully-adjusted hazard ratios were 0.56 (0.51–0.61), 0.64 (0.53–0.78), and 0.70 (0.56–0.86), respectively. The association between the risk of cognitive impairment and watching TV and listening to the radio, playing cards or mah-jong, and reading books or newspapers were stronger among those who had two or more years of education. Moreover, the association between risk of cognitive impairment and watching TV and listening to radio was stronger in men than in women. Conclusions: In conclusion, a greater frequency of TV watching or radio listening, reading books or newspapers, and playing cards or mah-jong may decrease the risk of cognitive impairment among the oldest-old.
Mutation Analysis Using Multiplex Ligation-Dependent Probe Amplification in Consanguineous Families in South India with a Child with Profound Hearing Impairment
Authors: Arunachalam Ravi Kumar , Koshy Teena , Venkatesan Vettriselvi , Dawson Gladys Prathiba , Franklin Durairaj Paul Solomon , George Pratibha
Published: April 2019

Background

Consanguineous marriage, a common practice in South India, increase the incidence of autosomal recessive diseases such as nonsyndromic hearing loss (NSHL) in offspring. This trend was noted in the children with hearing impairment (HI) who received cochlear implants (CI) at our University hospital in Porur, Chennai, India. To ascertain the genetic etiology of HI in these patients, we performed multiplex ligation-dependent probe amplification (MLPA) analysis.

Methods

A total of 25 families who had a child with NSHL were included in the study. MLPA screening of GJB2, GJB6, and GJB3 was performed for all the recruited individuals.

Results

The pathogenic p.W24X* mutation of GJB2 was detected in 2 patients; both of their parents were heterozygous carriers. Both families had a second-degree consanguineous marriage.

Conclusion

This study has important implications for molecular-diagnosis strategy and genetic counseling for families with HI in South India.
Treatment of Asymptomatic Meningioma With Gamma Knife Radiosurgery: Long-Term Follow-up With Volumetric Assessment and Clinical Outcome
Authors: Gupta Amitabh , Xu Zhiyuan , Cohen-Inbar Or , Snyder M Harrison , Hobbs Landon K , Li Chelsea , Nguyen Quoc-Tuan , Sheehan Jason P
Published: April 2019

BACKGROUND

Some patients are diagnosed with asymptomatic meningioma(s) after undergoing a screening CT and MRI for minor ailments or postresection.

OBJECTIVE

To help clinicians in decision making for treatment of asymptomatic meningiomas.

METHODS

A single center retrospective cohort study of 117 patients with 122 tumors treated with Gamma Knife radiosurgery (GKRS; Elekta AB, Stockholm, Sweden). Patients were followed with longitudinal imaging and clinical evaluations. Tumor volumetry and developments of new signs or symptoms after GKRS were the end points in the study.

RESULTS

Median patient age at GKRS was 60 yr (range 21-86 yr) with a median clinical follow-up of 53 mo (range 20-252 mo). The median pre-GKRS tumor volume was 3.6 ± 3.8 cc (±standard deviation). Tumors were treated with a median margin dose of 14 ± 2 Gy. At last follow-up, median tumor volume was 2.5 ± 3.6 cc. Radiological progression-free survival (PFS) rates were 97% and 94.4% at 5 yr and 10 yr, respectively. Clinical PFS rates were 86% and 70% at 5 yr and 10 yr, respectively. Development of neurological complications was seen in 21 (18%) patients, and 11 (52%) of them had undergone surgical resection prior to GKRS.

CONCLUSION

GKRS is a reasonable treatment strategy for asymptomatic meningiomas and compares favorably to natural history studies in terms of tumor control and neurological preservation. It results in relatively low morbidity in previously untreated meningiomas and serves as an appealing alternative treatment modality for recurrent meningiomas in asymptomatic patients.
A Poetics of Discretion
Authors: Froger Marion
Published: April 2019

Through an analysis drawn from microsociology and attentive to the tiny and subtle trials of the relational experience that the “new generation” of Quebec filmmakers tend to point out, this chapter explores how a poetics of “discretion” contributes to give form to a collective sentiment that does not presuppose a community belonging to be felt. By filming the urban sociality, understood as a fleeting experience of an “invisible binding,” the filmmakers find new forms to express this sense of collectivity, which does not pretend to be a sense of collectivity grounded in group identity but instead tends to blur the very issue of collective identity and its correlate (social imaginary). This blurring notably makes sense in the particular context of “the Printemps Erable” and its casserole concerts, which argues for a significant shift in research on imaginary and community in film studies.
Toronto on Screen
Authors: Robinson Ian
Published: April 2019

This chapter investigates the development of the commercial feature film industry in Toronto from the 1980s. It considers policy frameworks that have supported and regulated film production and the representation of Toronto to argue that the city’s image in film culture can be read as a complex mediation of Toronto’s self-crafted image as a city of film production and culture. The chapter begins by historicizing Toronto’s rise to prominence as a leading center of film production in North America. The second section contemplates how films have rendered, both thematically and aesthetically, the city’s placeless identity. Third, the chapter turns to policies and projects since the 2000s that have sought to redefine Toronto’s cultural policy and reinvigorate its status as a global creative city. The final section considers Toronto’s visibility on screen in a number of post-2000 films and examines how the city’s official image is mediated on screen.
Still Here, Still Queer? Rethinking Queer Canadian Cinemas/Canadian Cinemas Queered
Authors: Waugh Thomas , Massimi Fulvia , Aalders Lisa
Published: April 2019

This chapter pushes for a broad revision of Canadian national cinemas, arguing for queerness as their privileged mode of expression. The prominence of queerness in the Canadian cinematic imaginary is explored throughout four sections that demonstrate the uniqueness of Canadian cinemas over examples of queer cinema elsewhere. First, the roots of queer cinema/cinema queered in Canada are located in the work of pre-Stonewall pioneers such as Claude Jutra, Norman McLaren, and David Secter. Second, queerness is seen informing the institutional and political structures of Canadian cinema through practices of activism around identities, intersectionality, and serostatus. Third, queerness is recentered in the oeuvre of the nonqueer auteurs Atom Egoyan, David Cronenberg, and Denys Arcand, as a synonym for sexual fluidity and a symptom of sexual/national anxiety. Finally, the contributions of Léa Pool, John Greyson, Thirza Cuthand, and Xavier Dolan uncover the intersectional heritage and souls of contemporary queer Canadian cinemas.
The World Navigated
Authors: Mulvogue Jessica
Published: April 2019

This chapter provides an overview of the emergence of interactive documentary (i-doc) in Canada and situates it within the history of the National Film Board’s Challenge for Change program, a participatory documentary experiment envisioned as a means of social change. It outlines various kinds of interactivity using examples from recent Canadian works. Additionally, it considers how the interactive documentary shifts spectator/screen relations and the implications this has on the documentary construction of reality. Focusing on how the spectator is positioned differently to the world on screen—as a navigator instead of as a viewer—this article examines two opposing perspectives on the potential of interactivity to be used as a tool for change.
Movie Envy
Authors: Asselin Olivier
Published: April 2019

“Canadian cinema.” The term may appear self-evident but is problematic. First, one may question the value of national approaches to culture, especially here, in Quebec and Canada, where the debates over the Nation seem interminable, and especially now, in an era of globalization. Next, one may question the value of media-centered approaches to culture, especially when the successive waves of the “digital revolution” have blurred the boundaries between technologies and among artistic practices. Rather than try to survey “important” fiction films for theatres in Quebec or Canada, this essay adopts another point of view to examine the presence of cinema in Montreal museums over the past few years by focusing on three singular exhibitions. It may well be symptomatic of the current state of film in Quebec and Canada—but also, paradoxically, everywhere else—and says much about the relationship between medium and nation, the expansion of cinema beyond the movie theatre, and the internationalization of culture.
Canadian Indigenous Cinema
Authors: Bertrand Karine
Published: April 2019

Indigenous peoples of Canada have long been spectators of their own representation. Now, tools such as cinema and new media (blogs, YouTube channels, social networks, and more) allow a rewriting of history from an insider’s perspective and the decolonization of images that perpetuate stereotypes. Situated at the heart of this process, the remediation of oral tradition can be found across Indigenous cinema’s landscape, thus becoming a unifying factor linking works from different parts of the country. This chapter explores the indigenization of film by First Nations and Inuit filmmakers and by the participants of the Wapikoni Mobile project situated in Quebec. The analysis of a variety of short films from Wapikoni and other Indigenous filmmakers, such as Alanis Obomsawin and Zacharias Kunuk, allows an investigation of the ways in which oral tradition is deployed in Indigenous cinema, whether through the orality of the image itself or through narration techniques.
Cross-Cultural Assessment of Situational Experience
Authors: Gardiner Gwendolyn , Baranski Erica , Buehler Janina Larissa
Published: April 2019

Cross-cultural psychology can benefit from the incorporation of psychological situations and the investigation of how cultural influences are manifested in our daily lives. In this chapter, we review the current literature on cross-cultural assessments of situations under the framework of cues (objective attributes of a situation), characteristics (meaning or interpretation of cues), and classes (groups of situations based on cues or characteristics). Cultural situational cues, such as the weather or population density, vary both in frequency and in interpretation across countries. Characteristics of situations differ in the meaning individuals ascribe to cues, the affective response to situations based on culture socialization, and the amount of agency or autonomy perceived in situations. Lastly, classes of situations (e.g., education settings, the workplace, romantic relationships), provide a useful method of grouping common situations for understanding cultural differences.
Schoenberg as Sound Student: Pierrot’s Klang
Authors: Auner Joseph
Published: April 2019

Schoenberg expended enormous energies on rethinking what sound could be and what it could mean in ways that anticipate and can be illuminated by sound studies. Focusing on Schoenberg’s understanding of the word Klang, this chapter explores the creative process and reception of Pierrot lunaire in the context of his writings on “sound,” one of the many possible translations of the term. Approaching Schoenberg’s music and his writings in Style and Idea and elsewhere from the vantage point of sound studies can attune us to his interests in destabilizing the boundaries not only between timbre, melody, and harmony, but also between music, sound, and noise, and between sound and our lived experience. The wide-ranging ramifications of his conception of Klang are evident in the ways that he engages with many aspects of music and its technologies and media while also going beyond specifically musical contexts to understand sound as a fundamental dimension of our thought and creativity, our experience, and our ways of relating with each other and our world.
A Minimal Demographic History of Israel
Authors: DellaPergola Sergio
Published: April 2019

This chapter surveys the demographic development of Israel/Palestine from antiquity through the present and looking toward the future. Territory and habitability is described regarding changing boundary definitions and internal divisions that have reflected shifting political rule. Population change is examined in the long term, noting the significant historical ups and downs in population size and socioeconomic development. The development of contemporary population in Israel and Palestine reflects large-scale international migration, including mass movement of Jewish and Arab refugees. Variable fertility levels and birth rates have also significantly affected the pace of population growth. Attention is paid to the more recent balance of Jews and Palestinians over the whole territory between the Mediterranean Sea and the Jordan River, and an overview is presented of the distribution of world Jewish and Palestinian diasporas. Finally, population projections for the Jewish people, the state of Israel, and the whole territory of Israel/Palestine are presented.
Dysregulated Protein Synthesis in Major Depressive Disorder
Authors: Heaney Chelcie F. , Raab-Graham Kimberly F.
Published: April 2019

Major depressive disorder is a debilitating disorder with a lifetime prevalence of 17% in the adult population. By reverse engineering how antidepressants work at the cellular level, significant progress has been made within the last decade regarding the underlying etiology of depression. Unexpectedly, dysregulation of protein synthesis pathways is at the core of depression. Activation of one or more mRNA translation, initiation, or elongation pathways (including mammalian target of rapamycin [mTOR] kinase, extracellular regulated kinase, and eukaryotic elongation factor 2) is central to symptomatic relief. In preclinical models of stress and/or depression, co-administration of antidepressants and pharmacological inhibitors of these pathways block hallmark characteristics of antidepressant efficacy, including upregulation of key synaptic proteins, increased dendritic and spine complexity, and antidepressant-like behaviors. In this chapter, we review studies demonstrating altered translational pathways in animal models, treated and untreated patients, with a focus on mTOR-regulated protein synthesis.
Corporal Punishment and the Law in Global Perspective
Authors: Durrant Joan E.
Published: April 2019

Debates over corporal punishment’s effectiveness have come to an end. No study has shown it to have long-term benefits, while many have demonstrated its substantial and wide-ranging risks. Today, the primary focus is on ending it. The increasing recognition of children as rights-bearers is leading an ever-growing number of countries to legally prohibit corporal punishment of children. These laws are intended to foster recognition of children’s rights to protection from all violence, reduce approval and use of corporal punishment, and lower the threshold for tolerance of violence against children. Population-level data from Sweden, Germany, and New Zealand indicate that these changes are taking place. Additional research suggests that a combination of prohibition and large-scale public education is the most effective route to ending the corporal punishment of children.
Disputes over Medical Treatment for Children
Authors: Herring Jonathan
Published: April 2019

This chapter explores the law’s response to conflicts between parents and medical professionals over medical treatment of children. It acknowledges that generally the law gives parents considerable leeway over how to raise children and will only allow intervention in cases where the parents cannot reach agreement over an issue or the parents are causing the child significant harm. The chapter explores why medical treatment might be seen as different from other issues concerning children—in particular because there are authoritative alternative decision-makers (doctors) who can claim to have greater expertise than parents. However, it is claimed that end-of-life cases tend to raise issues that are not solely medical and hence a dialogue between doctors and parents is essential to determine the child’s best interests.
Students with Disabilities and School Choice
Authors: Garda Robert , Hensel Wendy , O’Neill Paul
Published: April 2019

School choice is one of the primary education reforms currently sweeping the United States. School choice systems create unique challenges for students with disabilities and schools of choice in serving such students. While there are a variety of school choice systems, this chapter focuses on three types of school choice models—charter schools, portfolio school districts, and voucher programs—and the unique policy and legal challenges they present for students with disabilities. Specifically, this chapter examines the interplay of these school choice reforms with the United States laws regarding students with disabilities: the Individuals with Education in Disabilities Act (IDEA), Section 504 of the Rehabilitation Act (Section 504), and Title II of the Americans with Disabilities Act (ADA). The challenges, barriers and problems are examined and solutions are proposed that consider both the laws regarding students with disabilities and the structures of the choice programs.
Eighty Years of Students’ Free Speech in Public Schools
Authors: Bowman Kristine L.
Published: April 2019

Free speech is the cornerstone of our democracy, and it is also a right that students exercise in public schools. Students’ rights have not always been as robust they are today, though. In fact, over the past century, the way in which we conceptualize students’ rights has changed dramatically. This chapter traces the development of the law in this area, analyzing the handful of U.S. Supreme Court decisions that have established the special rules for deciding school speech cases and engaging the principles that have animated these decisions. The chapter also presents one way of understanding how these cases fit together, underscores questions about the current coherence of the doctrine, and engages the related—and increasingly important—issue of qualified immunity. Student speech cases are among the most commonly litigated issues under the First Amendment, and for many reasons, controversies about free speech present difficult questions.
Managing Risky Bodies
Authors: Reich Jennifer A.
Published: April 2019

Health risk is increasingly calculable, often with new ways to surveil the body, in hopes of enacting change that might treat, manage, or lower that identifiable risk. Nowhere is this more evident than in pregnancy management and childhood vaccination. This chapter examines how women encounter discourses of risk during pregnancy as well as when they consider childhood vaccination and make decisions for themselves and their children. Using two case examples from a larger qualitative study of perceptions of risk and vaccine refusal, this chapter shows how women’s decisions reflect the ways their pregnancy and parenting decisions are driven by perceptions of risk that are embodied, subjective, and contextual, and that reflect different social locations and processes of management.