bluuebunny/crossref_metadata_2025 huggingface dataset:
Microaggressions towards people affected by mental health problems: a scoping review
Authors: Barber S. , Gronholm P. C. , Ahuja S. , Rüsch N. , Thornicroft G.
Published: December 2019

Aims

This review aims to understand the scope of the literature regarding mental health-related microaggressions towards people affected by mental health problems.

Methods

A scoping review was conducted to explore this question. Four electronic health-oriented databases were searched alongside Google Scholar. As per scoping review principles, the inclusion criteria were developed iteratively. The results of included studies were synthesised using a basic narrative synthesis approach, utilising principles of thematic analysis and thematic synthesis where appropriate.

Results

A total of 1196 records were identified, of which 17 met inclusion criteria. Of these, 12 were peer-reviewed journal articles, three were research degree theses and two were book chapters. Six included empirical studies were qualitative, four were quantitative and two employed a mixed-methods design. Within these, five qualitative studies aimed to describe the nature of mental health microaggressions experienced by people with mental health problems. Themes identified in a thematic synthesis of these five studies included stereotypes about mental illness, invalidating peoples' experience and blaming people with mental illness for their condition. The included publications informed on the perpetration of mental health microaggressions by family, friends, health professionals and social workers. In addition, two studies created scales, which were then used in cross-sectional surveys of the general public and community members to assess characteristics, such as right-wing political views, associated with endorsement of mental health microaggressions. A consensus definition of microaggressions emerged from the included studies: microaggressions are brief, everyday slights, snubs or insults, that may be subtle or ambiguous, but communicate a negative message to a target person based on their membership of a marginalised group, in this case, people affected by mental illness.

Conclusions

The study of mental health microaggressions is an emerging, heterogeneous field, embedded in the wider stigma and discrimination literature. It has been influenced by earlier work on racial microaggressions. Both can be ambiguous and contradictory, which creates difficulty defining the boundaries of the concept, but also underpins the key theoretical basis for the negative impact of microaggressions. Mental illness is a more concealable potential type of identity, so it follows that the reported perpetrators of microaggressions are largely friends, family and professionals. This has implications for intervening to reduce the impact of microaggressions. There are several challenges facing research in this area, and further work is needed to understand the impact of mental health microaggressions on people affected by mental health problems.
High-resolution MEMS inertial sensor combining large-displacement buckling behaviour with integrated capacitive readout
Authors: El Mansouri Brahim , Middelburg Luke M. , Poelma René H. , Zhang Guo Qi , van Zeijl Henk W. , Wei Jia , Jiang Hui , Vogel Johan G. , van Driel Willem D.
Published: December 2019

Commercially available gravimeters and seismometers can be used for measuring Earth’s acceleration at resolution levels in the order of $${\mathrm{ng}}/\sqrt {\mathrm{Hz}}$$

ng
∕

Hz

(where g represents earth’s gravity) but they are typically high-cost and bulky. In this work the design of a bulk micromachined MEMS device exploiting non-linear buckling behaviour is described, aiming for $${\mathrm{ng}}/\sqrt {\mathrm{Hz}}$$

ng
∕

Hz

resolution by maximising mechanical and capacitive sensitivity. High mechanical sensitivity is obtained through low structural stiffness. Near-zero stiffness is achieved through geometric design and large deformation into a region where the mechanism is statically balanced or neutrally stable. Moreover, the device has an integrated capacitive comb transducer and makes use of a high-resolution impedance readout ASIC. The sensitivity from displacement to a change in capacitance was maximised within the design and process boundaries given, by making use of a trench isolation technique and exploiting the large-displacement behaviour of the device. The measurement results demonstrate that the resonance frequency can be tuned from 8.7 Hz–18.7 Hz, depending on the process parameters and the tilt of the device. In this system, which combines an integrated capacitive transducer with a sensitivity of 2.55 aF/nm and an impedance readout chip, the theoretically achievable system resolution equals 17.02 $${\mathrm{ng}}/\sqrt {\mathrm{Hz}}$$

ng
∕

Hz

. The small size of the device and the use of integrated readout electronics allow for a wide range of practical applications for data collection aimed at the internet of things.
Mate pair sequencing outperforms fluorescence in situ hybridization in the genomic characterization of multiple myeloma
Authors: Smadbeck James , Peterson Jess F. , Pearce Kathryn E. , Pitel Beth A. , Figueroa Andrea Lebron , Timm Michael , Jevremovic Dragan , Shi Min , Stewart A. Keith , Braggio Esteban , Riggs Daniel L. , Bergsagel P. Leif , Vasmatzis George , Kearney Hutton M. , Hoppman Nicole L. , Ketterling Rhett P. , Kumar Shaji , Rajkumar S. Vincent , Greipp Patricia T. , Baughn Linda B.
Published: December 2019

Fluorescence in situ hybridization (FISH) is currently the gold-standard assay to detect recurrent genomic abnormalities of prognostic significance in multiple myeloma (MM). Since most translocations in MM involve a position effect with heterogeneous breakpoints, we hypothesize that FISH has the potential to miss translocations involving these regions. We evaluated 70 bone marrow samples from patients with plasma cell dyscrasia by FISH and whole-genome mate-pair sequencing (MPseq). Thirty cases (42.9%) displayed at least one instance of discordance between FISH and MPseq for each primary and secondary abnormality evaluated. Nine cases had abnormalities detected by FISH that went undetected by MPseq including 6 tetraploid clones and three cases with missed copy number abnormalities. In contrast, 19 cases had abnormalities detected by MPseq that went undetected by FISH. Seventeen were MYC rearrangements and two were 17p deletions. MPseq identified 36 MYC abnormalities and 17 (50.0% of MYC abnormal group with FISH results) displayed a false negative FISH result. MPseq identified 10 cases (14.3%) with IgL rearrangements, a recent marker of poor outcome, and 10% with abnormalities in genes associated with lenalidomide response or resistance. In summary, MPseq was superior in the characterization of rearrangement complexity and identification of secondary abnormalities demonstrating increased clinical value compared to FISH.
CircRNA hsa_circ_0074834 promotes the osteogenesis-angiogenesis coupling process in bone mesenchymal stem cells (BMSCs) by acting as a ceRNA for miR-942-5p
Authors: Ouyang Zhengxiao , Tan Tingting , Zhang Xianghong , Wan Jia , Zhou Yanling , Jiang Guangyao , Yang Daishui , Guo Xiaoning , Liu Tang
Published: December 2019

Bone tissue has a strong ability to repair itself. When treated properly, most fractures will heal well. However, some fractures are difficult to heal. When a fracture does not heal, it is called nonunion. Approximately, 5% of all fracture patients have difficulty healing. Because of the continuous movement of the fracture site, bone nonunion is usually accompanied by pain, which greatly reduces the quality of life of patients. Bone marrow mesenchymal stem cells (BMSCs) play an important role in the process of nonunion. Circular RNAs (circRNAs) are a unique kind of noncoding RNA and represent the latest research hotspot in the RNA field. At present, no studies have reported a role of circRNAs in the development of nonunion. After isolation of BMSCs from patients with nonunion, the expression of circRNAs in these cells was detected by using a circRNA microarray. Alkaline phosphatase and Alizarin red staining were used to detect the regulation of osteogenic differentiation of BMSCs by hsa_circ_0074834. The target gene of hsa_circ_0074834 was detected by RNA pull-down and double-luciferase reporter assay. The ability of hsa_circ_0074834 to regulate the osteogenesis of BMSCs in vivo was tested by heterotopic osteogenesis and single cortical bone defect experiments. The results showed that the expression of hsa_circ_0074834 in BMSCs from patients with nonunion was decreased. Hsa_circ_0074834 acts as a ceRNA to regulate the expression of ZEB1 and VEGF through microRNA-942-5p. Hsa_circ_0074834 can promote osteogenic differentiation of BMSCs and the repair of bone defects. These results suggest that circRNAs may be a key target for the treatment of nonunion.
RASSF1A, puppeteer of cellular homeostasis, fights tumorigenesis, and metastasis—an updated review
Authors: Dubois Fatéméh , Bergot Emmanuel , Zalcman Gérard , Levallet Guénaëlle
Published: December 2019

The Ras association domain family protein1 isoform A (RASSF1A) is a well-known tumor-suppressor protein frequently inactivated in various human cancers. Consistent with its function as a molecular scaffold protein, referred to in many studies, RASSF1A prevents initiation of tumorigenesis, growth, and dissemination through different biological functions, including cell cycle arrest, migration/metastasis inhibition, microtubular stabilization, and apoptosis promotion. As a regulator of key cancer pathways, namely Ras/Rho GTPases and Hippo signaling without ignoring strong interaction with microtubules, RASSF1A is indeed one of the guardians of cell homeostasis. To date, as we approach the two decade anniversary of RASSF1A’s discovery, this review will summarize our current knowledge on the RASSF1A key interactions as a tumor suppressor and discuss their impact on cell fate during carcinogenesis. This could facilitate a deeper understanding of tumor development and provide us with new strategies in cancer treatment by targeting the RASSF1A pathway.
Aberrant hypermethylation-mediated downregulation of antisense lncRNA ZNF667-AS1 and its sense gene ZNF667 correlate with progression and prognosis of esophageal squamous cell carcinoma
Authors: Dong Zhiming , Li Shengmian , Wu Xuan , Niu Yunfeng , Liang Xiaoliang , Yang Liu , Guo Yanli , Shen Supeng , Liang Jia , Guo Wei
Published: December 2019

Natural antisense lncRNAs can interfere with their corresponding sense transcript to elicit concordant or discordant regulation. LncRNA ZNF667-AS1 and its sense gene ZNF667 were found to be downregulated in esophageal squamous cell carcinoma (ESCC) tissues by RNA sequencing; however, the exact roles of both genes in ESCC occurrence and development have not been clarified. This study was to investigate the expression patterns, epigenetic inactivation mechanisms, function, and prognostic significance of ZNF667-AS1 and ZNF667 in ESCC tumorigenesis. Frequent downregulation of ZNF667-AS1 and ZNF667 was detected in esophageal cancer cells and ESCC tissues. The expression levels of ZNF667-AS1 and ZNF667 were significantly reversed by treatment with 5-Aza-dC and TSA in esophageal cancer cell lines. The CpG sites hypermethylation within proximal promoter influenced the binding ability of transcription factor E2F1 to the binding sites and then affected the transcription and expression of ZNF667-AS1 and ZNF667. Overexpression of ZNF667-AS1 and ZNF667 suppressed the viability, migration, and invasion of esophageal cancer cells in vitro. Overexpression of ZNF667-AS1 increased mRNA and protein expression level of ZNF667. ZNF667-AS1 interacts with and recruits TET1 to its target gene ZNF667 and E-cadherin to hydrolyze 5′-mc to 5′-hmc and further activates their expression, meanwhile, ZNF667-AS1 also interacts with UTX to decrease histone H3K27 tri-methylation to activate ZNF667 and E-cadherin expression. Furthermore, ZNF667-AS1 or ZNF667 expression and promoter methylation status were correlated with ESCC patients’ survival. Thus, these findings suggest that ZNF667-AS1 and ZNF667 may act as tumor suppressors and may serve as potential targets for antitumor therapy.
An epitranscriptomic mechanism underlies selective mRNA translation remodelling in melanoma persister cells
Authors: Shen Shensi , Faouzi Sara , Bastide Amandine , Martineau Sylvain , Malka-Mahieu Hélène , Fu Yu , Sun Xiaoxiao , Mateus Christine , Routier Emilie , Roy Severine , Desaubry Laurent , André Fabrice , Eggermont Alexander , David Alexandre , Scoazec Jean-Yves , Vagner Stéphan , Robert Caroline
Published: December 2019

Cancer persister cells tolerate anticancer drugs and serve as the founders of acquired resistance and cancer relapse. Here we show that a subpopulation of BRAFV600 mutant melanoma cells that tolerates exposure to BRAF and MEK inhibitors undergoes a reversible remodelling of mRNA translation that evolves in parallel with drug sensitivity. Although this process is associated with a global reduction in protein synthesis, a subset of mRNAs undergoes an increased efficiency in translation. Inhibiting the eIF4A RNA helicase, a component of the eIF4F translation initiation complex, abrogates this selectively increased translation and is lethal to persister cells. Translation remodelling in persister cells coincides with an increased N6-methyladenosine modification in the 5′-untranslated region of some highly translated mRNAs. Combination of eIF4A inhibitor with BRAF and MEK inhibitors effectively inhibits the emergence of persister cells and may represent a new therapeutic strategy to prevent acquired drug resistance.
Classification of mouse B cell types using surfaceome proteotype maps
Authors: van Oostrum Marc , Müller Maik , Klein Fabian , Bruderer Roland , Zhang Hui , Pedrioli Patrick G. A. , Reiter Lukas , Tsapogas Panagiotis , Rolink Antonius , Wollscheid Bernd
Published: December 2019

System-wide quantification of the cell surface proteotype and identification of extracellular glycosylation sites is challenging when samples are limited. Here, we miniaturize and automate the previously described Cell Surface Capture (CSC) technology, increasing sensitivity, reproducibility and throughput. We use this technology, which we call autoCSC, to create population-specific surfaceome maps of developing mouse B cells and use targeted flow cytometry to uncover developmental cell subpopulations.
Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa, Asia and Oceania
Authors:   Malaria Genomic Epidemiology Network, Band Gavin , Le Quang Si , Clarke Geraldine M. , Kivinen Katja , Hubbart Christina , Jeffreys Anna E. , Rowlands Kate , Leffler Ellen M. , Jallow Muminatou , Conway David J. , Sisay-Joof Fatoumatta , Sirugo Giorgio , d’Alessandro Umberto , Toure Ousmane B. , Thera Mahamadou A. , Konate Salimata , Sissoko Sibiri , Mangano Valentina D. , Bougouma Edith C. , Sirima Sodiomon B. , Amenga-Etego Lucas N. , Ghansah Anita K. , Hodgson Abraham V. O. , Wilson Michael D. , Enimil Anthony , Ansong Daniel , Evans Jennifer , Ademola Subulade A. , Apinjoh Tobias O. , Ndila Carolyne M. , Manjurano Alphaxard , Drakeley Chris , Reyburn Hugh , Phu Nguyen Hoan , Quyen Nguyen Thi Ngoc , Thai Cao Quang , Hien Tran Tinh , Teo Yik Ying , Manning Laurens , Laman Moses , Michon Pascal , Karunajeewa Harin , Siba Peter , Allen Steve , Allen Angela , Bahlo Melanie , Davis Timothy M. E. , Simpson Victoria , Shelton Jennifer , Spencer Chris C. A. , Busby George B. J. , Kerasidou Angeliki , Drury Eleanor , Stalker Jim , Dilthey Alexander , Mentzer Alexander J. , McVean Gil , Bojang Kalifa A. , Doumbo Ogobara , Modiano David , Koram Kwadwo A. , Agbenyega Tsiri , Amodu Olukemi K. , Achidi Eric , Williams Thomas N. , Marsh Kevin , Riley Eleanor M. , Molyneux Malcolm , Taylor Terrie , Dunstan Sarah J. , Farrar Jeremy , Mueller Ivo , Rockett Kirk A. , Kwiatkowski Dominic P.
Published: December 2019

The human genetic factors that affect resistance to infectious disease are poorly understood. Here we report a genome-wide association study in 17,000 severe malaria cases and population controls from 11 countries, informed by sequencing of family trios and by direct typing of candidate loci in an additional 15,000 samples. We identify five replicable associations with genome-wide levels of evidence including a newly implicated variant on chromosome 6. Jointly, these variants account for around one-tenth of the heritability of severe malaria, which we estimate as ~23% using genome-wide genotypes. We interrogate available functional data and discover an erythroid-specific transcription start site underlying the known association inATP2B4, but are unable to identify a likely causal mechanism at the chromosome 6 locus.  Previously reported HLA associations do not replicate in these samples. This large dataset will provide a foundation for further research on the genetic determinants of malaria resistance in diverse populations.
Deglacial water-table decline in Southern
California recorded by noble gas isotopes
Authors: Seltzer Alan M. , Ng Jessica , Danskin Wesley R. , Kulongoski Justin T. , Gannon Riley S. , Stute Martin , Severinghaus Jeffrey P.
Published: December 2019

Constraining the magnitude of past hydrological change
may improve understanding and predictions of future shifts in water
availability. Here we demonstrate that water-table depth, a
sensitive indicator of hydroclimate, can be quantitatively
reconstructed using Kr and Xe isotopes in groundwater. We present
the first-ever measurements of these dissolved noble gas isotopes in
groundwater at high precision (≤0.005‰
amu−1; 1σ), which reveal
depth-proportional signals set by gravitational settling in soil air
at the time of recharge. Analyses of California groundwater
successfully reproduce modern groundwater levels and indicate a
17.9 ± 1.3 m (±1 SE) decline in water-table depth in Southern
California during the last deglaciation. This hydroclimatic
transition from the wetter glacial period to more arid Holocene
accompanies a surface warming of 6.2 ± 0.6 °C (±1 SE). This new
hydroclimate proxy builds upon an existing paleo-temperature
application of noble gases and may identify regions prone to future
hydrological change.
Millimetre-long transport of photogenerated carriers in topological insulators
Authors: Hou Yasen , Wang Rui , Xiao Rui , McClintock Luke , Clark Travaglini Henry , Paulus Francia John , Fetsch Harry , Erten Onur , Savrasov Sergey Y. , Wang Baigeng , Rossi Antonio , Vishik Inna , Rotenberg Eli , Yu Dong
Published: December 2019

Excitons are spin integer particles that are predicted to condense into a coherent quantum state at sufficiently low temperature. Here by using photocurrent imaging we report experimental evidence of formation and efficient transport of non-equilibrium excitons in Bi2-xSbxSe3 nanoribbons. The photocurrent distributions are independent of electric field, indicating that photoexcited electrons and holes form excitons. Remarkably, these excitons can transport over hundreds of micrometers along the topological insulator (TI) nanoribbons before recombination at up to 40 K. The macroscopic transport distance, combined with short carrier lifetime obtained from transient photocurrent measurements, indicates an exciton diffusion coefficient at least 36 m2 s−1, which corresponds to a mobility of 6 × 104 m2 V−1 s−1 at 7 K and is four order of magnitude higher than the value reported for free carriers in TIs. The observation of highly dissipationless exciton transport implies the formation of superfluid-like exciton condensate at the surface of TIs.
Japanese encephalitis vaccine-specific envelope protein E138K mutation does not attenuate virulence of West Nile virus
Authors: Kaiser Jaclyn A. , Luo Huanle , Widen Steven G. , Wood Thomas G. , Huang Claire Y-H. , Wang Tian , Barrett Alan D. T.
Published: December 2019

West Nile (WNV) and Japanese encephalitis viruses (JEV) are closely related, mosquito-borne neurotropic flaviviruses. Although there are no licensed human vaccines for WNV, JEV has multiple human vaccines, including the live, attenuated vaccine SA14-14-2. Investigations into determinants of attenuation of JE SA14-14-2 demonstrated that envelope (E) protein mutation E138K was crucial to the attenuation of mouse virulence. As WNV is closely related to JEV, we investigated whether or not the E-E138K mutation would be beneficial to be included in a candidate live attenuated WNV vaccine. Rather than conferring a mouse attenuated phenotype, the WNV E-E138K mutant reverted and retained a wild-type mouse virulence phenotype. Next-generation sequencing analysis demonstrated that, although the consensus sequence of the mutant had the E-E138K mutation, there was increased variation in the E protein, including a single-nucleotide variant (SNV) revertant to the wild-type glutamic acid residue. Modeling of the E protein and analysis of SNVs showed that reversion was likely due to the inability of critical E-protein residues to be compatible electrostatically. Therefore, this mutation may not be reliable for inclusion in candidate live attenuated vaccines in related flaviviruses, such as WNV, and care must be taken in translation of attenuating mutations from one virus to another virus, even if they are closely related.
The heterogeneity and change in the urban structure of metropolitan areas in the United States, 1990–2010
Authors: Leyk Stefan , Balk Deborah , Jones Bryan , Montgomery Mark R. , Engin Hasim
Published: December 2019

While the population of the United States has been predominantly urban for nearly 100 years, periodic transformations of the concepts and measures that define urban places and population have taken place, complicating over-time comparisons. We compare and combine data series of officially-designated urban areas, 1990–2010, at the census block-level within Metropolitan Statistical Areas (MSAs) with a satellite-derived consistent series on built-up area from the Global Human Settlement Layer to create urban classes that characterize urban structure and provide estimates of land and population. We find considerable heterogeneity in urban form across MSAs, even among those of similar population size, indicating the inherent difficulties in urban definitions. Over time, we observe slightly declining population densities and increasing land and population in areas captured only by census definitions or low built-up densities, constrained by the geography of place. Nevertheless, deriving urban proxies from satellite-derived built-up areas is promising for future efforts to create spatio-temporally consistent measures for urban land to guide urban demographic change analysis.
Controls on the Isotopic Composition of Nitrite (δ15N and δ18O) during Denitrification in Freshwater Sediments
Authors: Sebilo Mathieu , Aloisi Giovanni , Mayer Bernhard , Perrin Emilie , Vaury Véronique , Mothet Aurélie , Laverman Anniet M.
Published: December 2019

The microbial reduction of nitrate, via nitrite into gaseous di-nitrogen (denitrification) plays a major role in nitrogen removal from aquatic ecosystems. Natural abundance stable isotope measurements can reveal insights into the dynamics of production and consumption of nitrite during denitrification. In this study, batch experiments with environmental bacterial communities were used to investigate variations of concentrations and isotope compositions of both nitrite and nitrate under anoxic conditions. To this end, denitrification experiments were carried out with nitrite or nitrate as sole electron acceptors at two substrate levels respectively. For experiments with nitrate as substrate, where the intermediate compound nitrite is both substrate and product of denitrification, calculations of the extent of isotope fractionation were conducted using a non-steady state model capable of tracing chemical and isotope kinetics during denitrification. This study showed that nitrogen isotope fractionation was lower during the use of nitrite as substrate (ε = −4.2 and −4.5‰ for both treatments) as compared to experiments where nitrite was produced as an intermediate during nitrate reduction (ε = −10 and −15‰ for both treatments). This discrepancy might be due to isotopic fractionation within the membrane of denitrifiers. Moreover, our results confirmed previously observed rapid biotic oxygen isotope exchange between nitrite and water.
Experimental interference of uncorrelated photons
Authors: Kim Heonoh , Kwon Osung , Moon Han Seb
Published: December 2019

The distinguishing of the multiphoton quantum interference effect from the classical one forms one of the most important issues in modern quantum mechanics and experimental quantum optics. For a long time, the two-photon interference (TPI) of correlated photons has been recognized as a pure quantum effect that cannot be simulated with classical lights. In the meantime, experiments have been carried out to investigate the classical analogues of the TPI. In this study, we conduct TPI experiments with uncorrelated photons with different center frequencies from a luminescent light source, and we compare our results with the previous ones of correlated photons. The observed TPI fringe can be expressed in the form of three phase terms related to the individual single-photon and two-photon states, and the fringe pattern is strongly affected by the two single-photon-interference fringes and also by their visibilities. With the exception of essential differences such as valid and accidental coincidence events within a given resolving time and the two-photon spectral bandwidth, the interference phenomenon itself exhibits the same features for both correlated and uncorrelated photons in the single-photon counting regime.
The CC′ loop of IgV domains of the immune checkpoint receptors, plays a key role in receptor:ligand affinity modulation
Authors: Kundapura Shankar V. , Ramagopal Udupi A.
Published: December 2019

Antibodies targeting negative regulators of immune checkpoints have shown unprecedented and durable response against variety of malignancies. While the concept of blocking the negative regulators of the immune checkpoints using mAbs appears to be an outstanding approach, their limited effect and several drawbacks, calls for the rational design of next generation of therapeutics. Soluble isoforms of the negative regulators of immune checkpoint pathways are expressed naturally and regulate immune responses. This suggests, affinity-modified versions of these self-molecules could be effective lead molecules for immunotherapy. To obtain better insights on the hotspot regions for modification, we have analysed structures of 18 immune receptor:ligand complexes containing the IgV domain. Interestingly, this analysis reveals that the CC′ loop of IgV domain, a loop which is distinct from CDRs of antibodies, plays a pivotal role in affinity modulation, which was previously not highlighted. It is noteworthy that a ~5-residue long CC′ loop in a ~120 residue protein makes significant number of hydrophobic and polar interactions with its cognate ligand. The post-interaction movement of CC′ loop to accommodate the incoming ligands, seems to provide additional affinity to the interactions. In silico replacement of the CC′ loop of TIGIT with that of Nectin-2 and PVR followed by protein docking trials suggests a key role of the CC′ loop in affinity modulation in the TIGIT/Nectin pathway. The CC′ loop appears to be a hotspot for the affinity modification without affecting the specificity to their cognate receptors.
Interrater and intrarater agreement and reliability of ratings made using the Zaidi–Dayal and Richards–Jabbour scales for the shape of the foramen magnum
Authors: Amarin Justin Z. , Alzraikat Sayel H. , Suradi Haya H. , Omari Rand Y. , Ghafel Afnan N. , Badran Darwish H. , Samara Osama A.
Published: December 2019

Anatomists and radiologists use the Zaidi–Dayal and Richards–Jabbour scales to study the shape of the foramen magnum. Our aim is to measure the interrater and intrarater agreement and reliability of ratings made using the two scales. We invited 16 radiology residents to attend two sessions, four weeks apart. During each session, we asked the residents to classify the shape of the foramen magnum in 35 images using both scales. We used Fleiss’ κ to measure interrater reliability and Cohen’s κ to measure intrarater reliability. The interrater reliability of ratings made using the Zaidi–Dayal scale was 0.34 (0.26–0.46) for session one and 0.30 (0.24–0.39) for session two, and the intrarater reliability was 0.39 (0.34–0.44). The interrater reliability of ratings made using the Richards–Jabbour scale was 0.14 (0.10–0.19) for session one and 0.12 (0.09–0.17) for session two, and the intrarater reliability was 0.11 (0.07–0.15). In conclusion, the interrater and intrarater agreement and reliability of ratings made using the Zaidi–Dayal and Richards–Jabbour scales are inadequate. We recommend an objective method by Zdilla et al. to researchers interested in studying the shape of the foramen magnum.
Influence of age and gender on sex steroid receptors in rat masticatory muscles
Authors: Galhardo Alessandra Pucci Mantelli , Mukai Márcio Katsuyoshi , Mori Matsuyoshi , Carvalho Katia Candido , Baracat Maria Cândida Pinheiro , Simões Manuel de Jesus , Soares José Maria , Baracat Edmund Chada
Published: December 2019

The temporomandibular muscle dysfunction is characterized by myofascial pain and is more prevalent in women of reproductive age. Sex steroid hormones are hypothetically involved in the dysfunction, but few are the studies of steroid receptors in masticatory and mastication-related muscles. Our aim was to determine estrogen and testosterone receptor expression in rat masticatory and mastication-related muscles within the context of age and gender. Twelve rats were equally divided into four groups: (a) 10-month-old females; (b) 10-month-old males; (c) 24-month-old females; and (d) 24-month-old males. Euthanasia of the females was performed in the proestrous phase (vaginal smears) and the masticatory and accessory muscles were removed for immunohistochemical analysis. Statistical analysis was performed with ANOVA and the Tukey test. Estrogen receptor expression was similarly low in all muscles and groups. Testosterone receptor expression in the Masseter muscle of the 24-month-old male rats was higher than that in the other groups and significantly superior to its expression in the Posterior Digastric muscle. In short, testosterone receptor expression was highest in old male rats. If we generalize to humans, this fact could indicate age- and sex-related hormonal influence on temporomandibular muscle dysfunction. Further studies, however, are necessary to strengthen this hypothesis.
Low genotypic diversity and long-term ecological decline in a spatially structured seagrass population
Authors: Alotaibi Nahaa M. , Kenyon Emma J. , Cook Kevan J. , Börger Luca , Bull James C.
Published: December 2019

In isolated or declining populations, viability may be compromised further by loss of genetic diversity. Therefore, it is important to understand the relationship between long-term ecological trajectories and population genetic structure. However, opportunities to combine these types of data are rare, especially in natural systems. Using an existing panel of 15 microsatellites, we estimated allelic diversity in seagrass, Zostera marina, at five sites around the Isles of Scilly Special Area of Conservation, UK, in 2010 and compared this to 23 years of annual ecological monitoring (1996–2018). We found low diversity and long-term declines in abundance in this relatively pristine but isolated location. Inclusion of the snapshot of genotypic, but less-so genetic, diversity improved prediction of abundance trajectories; however, this was spatial scale-dependent. Selection of the appropriate level of genetic organization and spatial scale for monitoring is, therefore, important to identify drivers of eco-evolutionary dynamics. This has implications for the use of population genetic information in conservation, management, and spatial planning.
Changes in hemodynamics associated with metabolic syndrome are more pronounced in women than in men
Authors: Kangas Pauliina , Tikkakoski Antti , Kettunen Jarkko , Eräranta Arttu , Huhtala Heini , Kähönen Mika , Sipilä Kalle , Mustonen Jukka , Pörsti Ilkka
Published: December 2019

The increase in cardiovascular risk associated with metabolic syndrome (MS) seems higher in women than in men. We examined hemodynamics during head-up tilt in 252 men and 250 women without atherosclerosis, diabetes, or antihypertensive medication, mean age 48 years, using whole-body impedance cardiography and radial pulse wave analysis. MS was defined according to Alberti et al. 2009. Men and women with MS presented with corresponding elevations of systolic and diastolic blood pressure (10-14%, p ≤ 0.001) versus controls. Supine pulse wave velocity (16–17%, p < 0.001) and systemic vascular resistance (7–9%, p ≤ 0.026), and upright cardiac output (6–11%, p ≤ 0.008) were higher in both MS groups than controls. Elevation of supine aortic characteristic impedance was higher in women than in men with MS (16% vs. 8%, p = 0.026), and in contrast to men, no upright impedance reduction was observed in women. When upright, women but not men with MS showed faster return of reflected pressure wave (p = 0.036), and smaller decrease in left cardiac work (p = 0.035) versus controls. The faster upright return of reflected pressure, lower upright decrease in left cardiac work, and higher elevation of aortic characteristic impedance may contribute to the greater increase in MS-related cardiovascular risk in women than in men.
Chaotic Dynamics Enhance the Sensitivity of Inner Ear Hair Cells
Authors: Faber Justin , Bozovic Dolores
Published: December 2019

Hair cells of the auditory and vestibular systems are capable of detecting sounds that induce sub-nanometer vibrations of the hair bundle, below the stochastic noise levels of the surrounding fluid. Furthermore, the auditory system exhibits a highly rapid response time, in the sub-millisecond regime. We propose that chaotic dynamics enhance the sensitivity and temporal resolution of the hair bundle response, and we provide experimental and theoretical evidence for this effect. We use the Kolmogorov entropy to measure the degree of chaos in the system and the transfer entropy to quantify the amount of stimulus information captured by the detector. By varying the viscosity and ionic composition of the surrounding fluid, we are able to experimentally modulate the degree of chaos observed in the hair bundle dynamics in vitro. We consistently find that the hair bundle is most sensitive to a stimulus of small amplitude when it is poised in the weakly chaotic regime. Further, we show that the response time to a force step decreases with increasing levels of chaos. These results agree well with our numerical simulations of a chaotic Hopf oscillator and suggest that chaos may be responsible for the high sensitivity and rapid temporal response of hair cells.
Proteasome inhibition disrupts the metabolism of fumarate hydratase- deficient tumors by downregulating p62 and c-Myc
Authors: Sourbier Carole , Ricketts Christopher J. , Liao Pei-Jyun , Matsumoto Shingo , Wei Darmood , Lang Martin , Railkar Reema , Yang Youfeng , Wei Ming-Hui , Agarwal Piyush , Krishna Murali , Mitchell James B. , Trepel Jane B. , Neckers Len , Linehan W. Marston
Published: December 2019

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is characterized by germline mutations of the FH gene that encodes for the TCA cycle enzyme, fumarate hydratase. HLRCC patients are at risk for the development of an aggressive form of type 2 papillary renal cell carcinoma. By studying the mechanism of action of marizomib, a proteasome inhibitor able to cross the blood-brain barrier, we found that it modulates the metabolism of HLRCC cells. Marizomib decreased glycolysis in vitro and in vivo by downregulating p62 and c-Myc. C-Myc downregulation decreased the expression of lactate dehydrogenase A, the enzyme catalyzing the conversion of pyruvate to lactate. In addition, proteasomal inhibition lowered the expression of the glutaminases GLS and GLS2, which support glutamine metabolism and the maintenance of the redox balance. Thus, in HLRCC cells, proteasome inhibition disrupts glucose and glutamine metabolism, restricting nutrients and lowering the cells’ anti-oxidant response capacity. Although the cytotoxicity induced by proteasome inhibitors is complex, the understanding of their metabolic effects in HLRCC may lead to the development of effective therapeutic strategies or to the development of markers of efficacy.
Synthesis and Characterization of Zirconium Nitride Nanopowders by Internal Gelation and Carbothermic Nitridation
Authors: Zhao Shijiao , Ma Jingtao , Xu Rui , Lin Xuping , Cheng Xing , Hao Shaochang , Zhao Xingyu , Deng Changsheng , Liu Bing
Published: December 2019

Zirconium compounds has been widely attention over the last decades due to its excellent physical and chemical properties. Zirconium nitride nanopowders were synthesized via a simple direct carbothermic nitridation process of internal gel derived zirconia in the presence of nano-sized carbon black. The effects of reaction temperature, dwell time and molar ratio of carbon black to Zr (C/Zr) on the phase composition, grain size and crystal parameters of products were studied. Based upon the analysis of crystallite phase evolution and microstructure characterization, it was found that zirconium oxynitride is intermediate product and then O atoms in oxynitride were extracted by oxygen getter, carbon black. Anion sites were directly replaced by N atoms to form rock-salt type nitride in carbothermic nitridation process.
Tailored modern GERD therapy – steps towards the development of an aid to guide personalized anti-reflux surgery
Authors: Nikolic Milena , Schwameis Katrin , Paireder Matthias , Kristo Ivan , Semmler Georg , Semmler Lorenz , Steindl Ariane , Mosleh Berta O. , Schoppmann Sebastian F.
Published: December 2019

As the incidence of gastroesophageal reflux disease (GERD) is rising, surgical treatment is continuously advancing in an effort to minimize side effects, whilst maintaining efficacy. From a database of patients that underwent anti-reflux surgery at our institution between 2015 and 2018, the last 25 consecutive patients that underwent electrical stimulation (ES), magnetic sphincter augmentation (MSA) and Nissen fundoplication (NF), following a personalized treatment decision aid, were included in a comparative analysis. After preoperative evaluation each patient was referred for an ES, MSA or NF based on esophageal motility, hiatal hernia (HH) size and the patients’ preferences. Postoperative gastrointestinal symptoms and GERD-Health-related-Quality-of-Life were assessed. Preoperatively the median DCI (299 ES vs. 1523.5 MSA vs. 1132 NF, p = 0.001), HH size (0.5 cm ES vs. 1 cm MSA vs. 2 cm NF, p = 0.001) and presence of GERD-related symptoms differed significantly between the groups. The highest rate of postoperative dysphagia was seen after MSA (24%, p = 0.04), while the median GERD HRQL total score was equally distributed between the groups. The positive short-term postoperative outcome and patient satisfaction indicate that such an aid in treatment indication, based on esophageal motility, HH size and patient preference, represents a feasible tool for an ideal choice of operation and an individualized therapy approach.
Genome-wide human brain eQTLs: In-depth analysis and insights using the UKBEC dataset
Authors: Sng Letitia M. F. , Thomson Peter C. , Trabzuni Daniah
Published: December 2019

Understanding the complexity of the human brain transcriptome architecture is one of the most important human genetics study areas. Previous studies have applied expression quantitative trait loci (eQTL) analysis at the genome-wide level of the brain to understand the underlying mechanisms relating to neurodegenerative diseases, primarily at the transcript level. To increase the resolution of our understanding, the current study investigates multi/single-region, transcript/exon-level andcisversustrans-acting eQTL, across 10 regions of the human brain. Some of the key findings of this study are: (i) only a relatively small proportion of eQTLs will be detected, where the sensitivity is under 5%; (ii) when an eQTL is acting in multiple regions (MR-eQTL), it tends to have very similar effects on gene expression in each of these regions, as well as beingcis-acting; (iii)trans-acting eQTLs tend to have larger effects on expression compared tocis-acting eQTLs and tend to be specific to a single region (SR-eQTL) of the brain; (iv) the cerebellum has a very large number of eQTLs that function exclusively in this region, compared with other regions of the brain; (v) importantly, an interactive visualisation tool (Shiny app) was developed to visualise the MR/SR-eQTL at transcript and exon levels.
Zika virus infection in pregnancy and infant growth, body composition in the first three months of life: a cohort study
Authors: Soares Fernanda , Abranches Andrea D. , Villela Letícia , Lara Sarah , Araújo Daniele , Nehab Sylvia , Silva Leila , Amaral Yasmin , Junior Saint Clair G. , Pone Sheila , Lobkowicz Ludmila , Clemente Nuria Sanchez , Brasil Patricia , Nielsen-Saines Karin , Pone Marcos , Brickley Elizabeth , Moreira Maria Elisabeth
Published: December 2019

The implications of Zika Virus exposure in pregnancy for early infant growth remains poorly described. The main goal of this study is to compare the growth, body composition, and feeding modality of infants in the first three months of life by prenatal Zika Virus exposure status. We selected an analytical cohort of 115 infants born without microcephaly, comprising 56 infants with qRT-PCR confirmed exposure to ZIKV during gestation and 59 infants born to women with presumptively no evidence of ZIKV in pregnancy. Infants were evaluated at birth, 1 and 3 months of age in terms of anthropometrics, body composition All the results were adjusted by maternal age, maternal BMI and gestational age. We observe no differences between anthropometric measurements at birth. Mothers in exposed group showed higher BMI. At 1 month and 3 months of age there were differences in mid arm circumference, arm muscle circumference and fat free mass. Weight and length was less in the ZIKV exposed in pregnancy infants and statistically different at 3 month of age. The findings of this investigation provide new evidence that ZIKV exposure in pregnancy may be associated with differences in body composition.
Perioperative multidisciplinary implementation enhancing recovery after hip arthroplasty in geriatrics with preoperative chronic hypoxaemia
Authors: He Liang , Zhang Ruqiang , Yin Jianwei , Zhang Han , Bu Wuming , Wang Fang , Zhang Furong
Published: December 2019

We investigated risk factors for postoperative serious adverse events (SAEs) in elderly patients with preoperative chronic hypoxaemia undergone total hip arthroplasty (THA) or hemiarthroplasty and performed an implementation to modify and improve clinical outcome. A retrospective medical record review was performed to identify geriatric patients who receiving THA or hemiarthroplasty at a single university teaching hospital, Kunming, Yunnan, China between January 2009 and August 2017. Total of 450 elderly patients were included in the study. Data were collected on baseline characteristics, detailed treatments, and adverse events. Univariate and multivariate logistic regression analysis were used to identify risk factors for SAEs. In multivariate regression analysis, a higher occurrence of general anaesthesia and multiple episodes of hypotension were associated with higher risk of SAEs (general anesthesia: odds ratio [OR] 5.09, 95% confidence interval [CI] 1.96–13.24, P = 0.001; hypotension time: OR 4.29, 95% CI 1.66–11.10, P = 0.003). After the multidisciplinary implementation, the postoperative length of stay was decreased from 15 days to 10 days (P < 0.0001); incidence of SAEs was decreased from 21.1% to 7.0% (P = 0.002), and the all-cause mortality rate within 30 days decreased from 4.6% to 1.0% (P = 0.040). Our observational study demonstrated that an increasing application of general anaesthesia and longer time of hypotension were associated with an increased risk of postoperative SAEs in patients after THA or hemiarthroplasty. Additionally, optimizing stable haemodynamics under higher application of combined-spinal epidural anaesthesia was associated with improved outcome up to 30 days after THA or hemiarthroplasty.
The C-terminal domain of EFA6A interacts directly with F-actin and assembles F-actin bundles
Authors: Macia Eric , Partisani Mariagrazia , Wang Hong , Lacas-Gervais Sandra , Le Clainche Christophe , Luton Frederic , Franco Michel
Published: December 2019

The Arf6-specific exchange factor EFA6 is involved in the endocytic/recycling pathway for different cargos. In addition EFA6 acts as a powerful actin cytoskeleton organizer, a function required for its role in the establishment of the epithelial cell polarity and in neuronal morphogenesis. We previously showed that the C-terminus of EFA6 (EFA6-Ct) is the main domain which contributes to actin reorganization. Here, by in vitro and in vivo experiments, we sought to decipher, at the molecular level, how EFA6 controls the dynamic and structuring of actin filaments. We showed that EFA6-Ct interferes with actin polymerization by interacting with and capping actin filament barbed ends. Further, in the presence of actin mono-filaments, the addition of EFA6-Ct triggered the formation of actin bundles. In cells, when the EFA6-Ct was directed to the plasma membrane, as is the case for the full-length protein, its expression induced the formation of membrane protrusions enriched in actin cables. Collectively our data explain, at least in part, how EFA6 plays an essential role in actin organization by interacting with and bundling F-actin.
Damaging coding variants within kainate receptor channel genes are enriched in individuals with schizophrenia, autism and intellectual disabilities
Authors: Koromina Maria , Flitton Miles , Blockley Alix , Mellor Ian R. , Knight Helen M.
Published: December 2019

Schizophrenia (Scz), autism spectrum disorder (ASD) and intellectual disability are common complex neurodevelopmental disorders. Kainate receptors (KARs) are ionotropic glutamate ion channels involved in synaptic plasticity which are modulated by auxiliary NETO proteins. Using UK10K exome sequencing data, we interrogated the coding regions of KAR and NETO genes in individuals with Scz, ASD or intellectual disability and population controls; performed follow-up genetic replication studies; and, conducted in silico and in vitro functional studies. We found an excess of Loss-of-Function and missense variants in individuals with Scz compared with control individuals (p = 1.8 × 10−10), and identified a significant burden of functional variants for Scz (p < 1.6 × 10−11) and ASD (p = 6.9 × 10−18). Single allele associations for 6 damaging missense variants were significantly replicated (p < 5.0 × 10−15) and confirmed GRIK3 S310A as a protective genetic factor. Functional studies demonstrated that three missense variants located within GluK2 and GluK4, GluK2 (K525E) and GluK4 (Y555N, L825W), affect agonist sensitivity and current decay rates. These findings establish that genetic variation in KAR receptor ion channels confers risk for schizophrenia, autism and intellectual disability and provide new genetic and pharmacogenetic biomarkers for neurodevelopmental disease.