bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating dose to thyroid gland in women with breast cancer during radiotherapy with different radiation energies at supraclavicular fossa region
Authors: Mirsadraei Marjaneh , Seilanian Toosi Mehdi , Mohebbi Shokoufeh , Khalili-Hezarjaribi Hojjat
Published: July 2018

Background and aim

During the treatment of breast cancer, radiotherapy to the supraclavicular fossa region results in absorption of radiation by the thyroid gland and consequently leads to hypothyroidism in 40% of patients. The aim of this study was to compare thyroid gland radiation absorption during radiotherapy with different anterioposterior beam radiation of 6–15 and 15–15 MV photon beam energies.

Materials and methods

In total, 29 patients with breast cancer were recruited to this study. Adjuvant radiotherapy with a total dose of 50 Gy was performed for each participant. Thyroid gland dosimetric measurements were evaluated including, mean dose, minimum and maximum dose, and V20, V30, V40 and V50 (percentage of thyroid volume receiving ≥20, ≥30, ≥40 and ≥50 Gy, respectively). The irradiation delivered doses were measured using Prowess Panther treatment planning system (Version 5.5). All data were evaluated using SPSS software.

Results

In total, 29 subjects with mean age of 53·4±9·4 were studied. According to the obtained results, at 15–15 MV energies, a significantly lower dose was absorbed by the thyroid gland, was observed in contrast to their counterparts who were treated with 6–15 MV photon beam energies.

Findings

Using 15–15 MV photon beam energies field can significantly reduce the absorbed dose to the thyroid gland and consequently can reduce the risk of developing hypothyroidism in breast cancer patients treated with radiotherapy.
Treatment-seeking differences for mental health problems in male- and non-male-dominated occupations: evidence from the HILDA cohort
Authors: Milner A. , Scovelle A. J. , King T.
Published: July 2018

Background

There is a well-established gender divide among people who do and do not seek professional help from mental health professionals. Females are typically more likely to report, and seek help for, mental health problems. The current paper sought to examine the role of employment context on help-seeking for mental health issues. We hypothesised that men and women in male-dominated occupations would be less likely to seek help than those in non-male-dominated occupations.

Methods

Data from the Household, Income and Labour Dynamics in Australia survey were used. Help-seeking, measured in 2013, was defined as whether a person reported attending a mental health professional in the 12 months prior to the survey. The exposure, male- and non-male-dominated occupations (measured in 2012), was defined using census data based on self-reported occupation. Analyses were stratified by gender and controlled for relevant confounders (measured in 2012), including mental health and prior help-seeking. We conducted multivariate logistic and propensity score analyses to improve exchangeability of those exposed and unexposed.

Results

For males, being in a male-dominated occupation was independently associated with reduced likelihood of help-seeking (OR 0.66, 95% CI 0.46–0.95) in the adjusted model, although this result fell just out of significance in the propensity score analysis. There was no independent effect of being in a male-/non-male-dominated occupation for help-seeking among women.

Conclusions

Results suggest that male-dominated occupations may negatively influence help-seeking among males. There is a need for more research to understand this relationship and for workplace-based prevention initiatives.
Continuous Use of Tribenuron-Methyl Selected for Cross-Resistance to Acetolactate Synthase–inhibiting Herbicides in Wild Mustard (Sinapis arvensis)
Authors: Gherekhloo Javid , Hatami Zahra M. , Alcántara-de la Cruz Ricardo , Sadeghipour Hamid R. , De Prado Rafael
Published: July 2018

Wild mustard (Sinapis arvensis L.) is a weed that frequently infests winter wheat (Triticum aestivum L.) fields in Golestan province, Iran. Tribenuron-methyl (TM) has been used recurrently to control this species, thus selecting for resistant S. arvensis populations. The objectives were: (1) to determine the resistance level to TM of 14 putatively resistant (PR) S. arvensis populations, collected from winter wheat fields in Golestan province, Iran, in comparison to one susceptible (S) population; and (2) to characterize the resistance mechanisms and the potential evolution of cross-resistance to other classes of acetolactate synthase (ALS)-inhibiting herbicides in three populations (AL-3, G-5, and Ag-Sr) confirmed as being resistant (R) to TM. The TM doses required to reduce the dry weight of the PR populations by 50% were between 2.2 and 16.8 times higher than those needed for S plants. The ALS enzyme activity assays revealed that the AL-3, G-5, and Ag-Sr populations evolved cross-resistance to the candidate ALS-inhibiting herbicides from the sulfonylureas (SU), triazolopyrimidines (TP), pyrimidinyl-thiobenzoates (PTB), sulfonyl-aminocarbonyl-triazolinone (SCT), and imidazolinones (IMI) classes. No differences in absorption, translocation, or metabolism of [14C]TM between R and S plants were observed, suggesting that these non-target mechanisms were not responsible for the resistance. The ALS gene of the R populations contained the Trp-574-Leu mutation, conferring cross-resistance to the SU, SCT, PTB, TP, and IMI classes. The Trp-574-Leu mutation in the ALS gene conferred cross-resistance to ALS-inhibiting herbicides in S. arvensis from winter wheat fields in Golestan province. This is the first TM resistance case confirmed in this species in Iran.
KSTP 94, an Open-pollinated Maize Variety Has Postattachment Resistance to Purple Witchweed (Striga hermonthica)
Authors: Mutinda Sylvia Mbula , Masanga Joel , Mutuku J. Musembi , Runo Steven , Alakonya Amos
Published: July 2018

Striga spp. are obligate root hemiparasites that constrain cereal production in sub-Saharan Africa. Although purple witchweed [Striga hermonthica (Delile) Benth.] and Asiatic witchweed [Striga asiatica (L.) Kuntze] infect all cereal crops, maize (Zea mays L.) is particularly vulnerable to their infestations. A sustainable control strategy for Striga would be to breed crops with host-based resistance as part of an integrated management plan. In maize, the open-pollinated variety Kakamega Striga-tolerant population of the year 1994 (‘KSTP 94’) has been popularized as a Striga-tolerant/resistant variety. This resistance was earlier reported to result from production of low amounts of sorgomol, a less potent strigolactone. To determine whether KSTP 94 harbors postattachment resistance, we used a soil-free assay based on observation chambers called rhizotrons. We found that the size of Striga seedlings attached to ‘CML 144’ (a susceptible maize inbred line) were 2.5-fold longer than those on KSTP 94. In addition, KSTP 94 had significantly fewer Striga attachments, which corresponded to significantly lower biomass (2.6-fold) compared with CML 144. Histological analysis revealed that the low Striga growth and development while infecting KSTP 94 was due the parasite’s inability to penetrate the host’s endodermis and make effective xylem–xylem connections. We therefore conclude that in addition to preattachment resistance, KSTP 94 exhibits postattachment resistance to S. hermonthica and could therefore be a good genetic source for postattachment resistance breeding.
Thermodynamic Constraints on the Size Distributions of Tropical Clouds
Authors: Garrett Timothy J. , Glenn Ian B. , Krueger Steven K.
Published: July 2018

Tropical convective clouds evolve over a wide range of temporal and spatial scales, which makes them difficult to simulate numerically. Here we propose that cloud statistical properties can be derived within a simplified time‐independent coordinate system of cloud numbern, saturated static energyh⋆, and cloud perimeterλ. Under the constraint that circulations around cloud edge compete with each other for total buoyant energy and air, we show that the product of cloud number and cloud perimeternλis invariant withλand that cloud number follows a negative exponential with respect to cloud‐edge deviations ofh⋆with respect to the mean. Overall, the summed perimeter of all clouds scales as the square root of the atmospheric static stability. These theoretical results suggest that the complexity of cloud field structures can be viewed statistically as an emergent property of atmospheric bulk thermodynamics. Comparison with a detailed tropical cloud field simulation shows general agreement to within ≤13%. For the sake of developing hypotheses about cloud temporal evolution that are testable in high resolution simulations, the shapes of tropical cloud perimeter distributions are predicted to be invariant as climate warms, although with a modest increase in total cloud amount.
Framework for Competencies for U.S. Psychologists Engaging Internationally
Authors: Morgan-Consoli Melissa L. , Inman Arpana G. , Bullock Merry , Nolan Susan A.
Published: July 2018

Despite some general guidelines, tips, and calls for international engagement, there are no explicit descriptions of competencies for U.S. psychologists engaged in professional work outside of their own country. This article outlines the rationale for developing such competencies needed to engage effectively outside one’s country and proposes broad descriptions of core competencies and specific competencies for teaching, practice, research, and consultation and policy work. This article’s authors are U.S. psychologists and cannot speak from the perspective of psychologists working in other countries; thus, although competencies for engaging internationally may be helpful for psychologists in all countries, this article is explicitly written through the lens of U.S. psychologists and is focused on outlining and describing competencies applicable to U.S. psychologists working internationally ( Altmaier & Hall, 2008 ). Psychologists from other countries may use the framework developed in this article to gauge the extent to which psychology-specific competencies and examples are generalizable to their specific context.
Loss of DDHD2, whose mutation causes spastic paraplegia, promotes reactive oxygen species generation and apoptosis
Authors: Maruyama Tomohiro , Baba Takashi , Maemoto Yuki , Hara-Miyauchi Chikako , Hasegawa-Ogawa Minami , Okano Hirotaka James , Enda Yuki , Matsumoto Kei , Arimitsu Nagisa , Nakao Kazuki , Hamamoto Hiroshi , Sekimizu Kazuhisa , Ohto-Nakanishi Takayo , Nakanishi Hiroki , Tokuyama Takeshi , Yanagi Shigeru , Tagaya Mitsuo , Tani Katsuko
Published: July 2018

DDHD2/KIAA0725p is a mammalian intracellular phospholipase A1 that exhibits phospholipase and lipase activities. Mutation of the DDHD2 gene causes hereditary spastic paraplegia (SPG54), an inherited neurological disorder characterized by lower limb spasticity and weakness. Although previous studies demonstrated lipid droplet accumulation in the brains of SPG54 patients and DDHD2 knockout mice, the cause of SPG54 remains elusive. Here, we show that ablation of DDHD2 in mice induces age-dependent apoptosis of motor neurons in the spinal cord. In vitro, motor neurons and embryonic fibroblasts from DDHD2 knockout mice fail to survive and are susceptible to apoptotic stimuli. Chemical and probe-based analysis revealed a substantial decrease in cardiolipin content and an increase in reactive oxygen species generation in DDHD2 knockout cells. Reactive oxygen species production in DDHD2 knockout cells was reversed by the expression of wild-type DDHD2, but not by an active-site DDHD2 mutant, DDHD2 mutants related to hereditary spastic paraplegia, or DDHD1, another member of the intracellular phospholipase A1 family whose mutation also causes spastic paraplegia (SPG28). Our results demonstrate the protective role of DDHD2 for mitochondrial integrity and provide a clue to the pathogenic mechanism of SPG54.
Long noncoding RNA Sox2ot and transcription factor YY1 co-regulate the differentiation of cortical neural progenitors by repressing Sox2
Authors: Knauss Jennifer L. , Miao Nan , Kim Seung-Nam , Nie Yanzhen , Shi Yuelin , Wu Tao , Pinto Hugo Borges , Donohoe Mary E. , Sun Tao
Published: July 2018

Long noncoding RNAs (lncRNAs) are emerging as key regulators of crucial cellular processes. However, the molecular mechanisms of many lncRNA functions remain uncharacterized. Sox2ot is an evolutionarily conserved lncRNA that transcriptionally overlaps the pluripotency gene Sox2, which maintains the stemness of embryonic stem cells and tissue-specific stem cells. Here, we show that Sox2ot is expressed in the developing mouse cerebral cortex, where it represses neural progenitor (NP) proliferation and promotes neuronal differentiation. Sox2ot negatively regulates self-renewal of neural stem cells, and is predominately expressed in the nucleus and inhibits Sox2 levels. Sox2ot forms a physical interaction with a multifunctional transcriptional regulator YY1, which binds several CpG islands in the Sox2 locus in a Sox2ot-dependent manner. Similar to Sox2ot, YY1 represses NP expansion in vivo. These results demonstrate a regulatory role of Sox2ot in promoting cortical neurogenesis, possibly by repressing Sox2 expression in NPs, through interacting with YY1.
METTL3 regulates WTAP protein homeostasis
Authors: Sorci Melissa , Ianniello Zaira , Cruciani Sonia , Larivera Simone , Ginistrelli Lavinia Ceci , Capuano Ernestina , Marchioni Marcella , Fazi Francesco , Fatica Alessandro
Published: July 2018

The Wilms tumor 1 (WT1)-associated protein (WTAP) is upregulated in many tumors, including, acute myeloid leukemia (AML), where it plays an oncogenic role by interacting with different proteins involved in RNA processing and cell proliferation. In addition, WTAP is also a regulator of the nuclear complex required for the deposition of N6-methyladenosine (m6A) into mRNAs, containing the METTL3 methyltransferase. However, it is not clear if WTAP may have m6A-independent regulatory functions that might contribute to its oncogenic role. Here, we show that both knockdown and overexpression of METTL3 protein results in WTAP protein upregulation, indicating that METTL3 levels are critical for WTAP protein homeostasis. However, we show that WTAP upregulation is not sufficient to promote cell proliferation in the absence of a functional METTL3. Therein, these data indicate that the reported oncogenic function of WTAP is strictly connected to a functional m6A methylation complex.
Correction: Multiscale analysis of a regenerative therapy for treatment of volumetric muscle loss injury
Authors: Aguilar Carlos A. , Greising Sarah M. , Watts Alain , Goldman Stephen M. , Peragallo Chelsea , Zook Christina , Larouche Jacqueline , Corona Benjamin T.
Published: July 2018

Correction to:Cell Death and Discovery (2018) 4, 33; https://doi.org/10.1038/s41420-018-0027-8; published online 20 February 2018.
Mitochondrial dynamics regulates Drosophila intestinal stem cell differentiation
Authors: Deng Hansong , Takashima Shigeo , Paul Manash , Guo Ming , Hartenstein Volker
Published: July 2018

Differentiation of stem/progenitor cells is associated with a substantial increase in mitochondrial mass and complexity. Mitochondrial dynamics, including the processes of fusion and fission, plays an important role for somatic cell reprogramming and pluripotency maintenance in induced pluripotent cells (iPSCs). However, the role of mitochondrial dynamics during stem/progenitor cell differentiation in vivo remains elusive. Here we found differentiation of Drosophila intestinal stem cell is accompanied with continuous mitochondrial fusion. Mitochondrial fusion defective(opa1RNAi) ISCs contain less mitochondrial membrane potential, reduced ATP, and increased ROS level. Surprisingly, suppressing fusion also resulted in the failure of progenitor cells to differentiate. Cells did not switch on the expression of differentiation markers, and instead continued to show characteristics of progenitor cells. Meanwhile, proliferation or apoptosis was unaffected. The differentiation defect could be rescued by concomitant inhibition of Drp1, a mitochondrial fission molecule. Moreover, ROS scavenger also partially rescues opa1RNAi-associated differentiation defects via down-regulating JNK activity. We propose that mitochondrial fusion plays a pivotal role in controlling the developmental switch of stem cell fate.
Chemically specific termination control of oxide interfaces via layer-by-layer mean inner potential engineering
Authors: Sun H. Y. , Mao Z. W. , Zhang T. W. , Han L. , Zhang T. T. , Cai X. B. , Guo X. , Li Y. F. , Zang Y. P. , Guo W. , Song J. H. , Ji D. X. , Gu C. Y. , Tang C. , Gu Z. B. , Wang N. , Zhu Y. , Schlom D. G. , Nie Y. F. , Pan X. Q.
Published: July 2018

Creating oxide interfaces with precise chemical specificity at the atomic layer level is desired for the engineering of quantum phases and electronic applications, but highly challenging, owing partially to the lack of in situ tools to monitor the chemical composition and completeness of the surface layer during growth. Here we report the in situ observation of atomic layer-by-layer inner potential variations by analysing the Kikuchi lines during epitaxial growth of strontium titanate, providing a powerful real-time technique to monitor and control the chemical composition during growth. A model combining the effects of mean inner potential and step edge density (roughness) reveals the underlying mechanism of the complex and previously not well-understood reflection high-energy electron diffraction oscillations observed in the shuttered growth of oxide films. General rules are proposed to guide the synthesis of atomically and chemically sharp oxide interfaces, opening up vast opportunities for the exploration of intriguing quantum phenomena at oxide interfaces.
Persistent CO2 emissions and hydrothermal unrest following the 2015 earthquake in Nepal
Authors: Girault Frédéric , Adhikari Lok Bijaya , France-Lanord Christian , Agrinier Pierre , Koirala Bharat P. , Bhattarai Mukunda , Mahat Sudhan S. , Groppo Chiara , Rolfo Franco , Bollinger Laurent , Perrier Frédéric
Published: July 2018

Fluid–earthquake interplay, as evidenced by aftershock distributions or earthquake-induced effects on near-surface aquifers, has suggested that earthquakes dynamically affect permeability of the Earth’s crust. The connection between the mid-crust and the surface was further supported by instances of carbon dioxide (CO2) emissions associated with seismic activity, so far only observed in magmatic context. Here we report spectacular non-volcanic CO2 emissions and hydrothermal disturbances at the front of the Nepal Himalayas following the deadly 25 April 2015 Gorkha earthquake (moment magnitude Mw = 7.8). The data show unambiguously the appearance, after the earthquake, sometimes with a delay of several months, of CO2 emissions at several sites separated by > 10 kilometres, associated with persistent changes in hydrothermal discharges, including a complete cessation. These observations reveal that Himalayan hydrothermal systems are sensitive to co- and post- seismic deformation, leading to non-stationary release of metamorphic CO2 from active orogens. Possible pre-seismic effects need further confirmation.
A framework for enhancing ethical genomic research with Indigenous communities
Authors: Claw Katrina G. , Anderson Matthew Z. , Begay Rene L. , Tsosie Krystal S. , Fox Keolu , Garrison Nanibaa’ A. ,   Summer internship for INdigenous peoples in Genomics (SING) Consortium, Bader Alyssa C. , Bardill Jessica , Bolnick Deborah A. , Brooks Jada , Cordova Anna , Malhi Ripan S. , Nakatsuka Nathan , Neller Angela , Raff Jennifer A. , Singson Jamie , TallBear Kim , Vargas Tada , Yracheta Joseph M.
Published: July 2018

Integration of genomic technology into healthcare settings establishes new capabilities to predict disease susceptibility and optimize treatment regimes. Yet, Indigenous peoples remain starkly underrepresented in genetic and clinical health research and are unlikely to benefit from such efforts. To foster collaboration with Indigenous communities, we propose six principles for ethical engagement in genomic research: understand existing regulations, foster collaboration, build cultural competency, improve research transparency, support capacity building, and disseminate research findings. Inclusion of underrepresented communities in genomic research has the potential to expand our understanding of genomic influences on health and improve clinical approaches for all populations.
The influence of Arctic amplification on mid-latitude summer circulation
Authors: Coumou D. , Di Capua G. , Vavrus S. , Wang L. , Wang S.
Published: July 2018

Accelerated warming in the Arctic, as compared to the rest of the globe, might have profound impacts on mid-latitude weather. Most studies analyzing Arctic links to mid-latitude weather focused on winter, yet recent summers have seen strong reductions in sea-ice extent and snow cover, a weakened equator-to-pole thermal gradient and associated weakening of the mid-latitude circulation. We review the scientific evidence behind three leading hypotheses on the influence of Arctic changes on mid-latitude summer weather: Weakened storm tracks, shifted jet streams, and amplified quasi-stationary waves. We show that interactions between Arctic teleconnections and other remote and regional feedback processes could lead to more persistent hot-dry extremes in the mid-latitudes. The exact nature of these non-linear interactions is not well quantified but they provide potential high-impact risks for society.
Exploiting a cognitive bias promotes cooperation in social dilemma experiments
Authors: Wang Zhen , Jusup Marko , Shi Lei , Lee Joung-Hun , Iwasa Yoh , Boccaletti Stefano
Published: July 2018

The decoy effect is a cognitive bias documented in behavioural economics by which the presence of a third, (partly) inferior choice causes a significant shift in people’s preference for other items. Here, we performed an experiment with human volunteers who played a variant of the repeated prisoner’s dilemma game in which the standard options of “cooperate” and “defect” are supplemented with a new, decoy option, “reward”. We show that although volunteers rarely chose the decoy option, its availability sparks a significant increase in overall cooperativeness and improves the likelihood of success for cooperative individuals in this game. The presence of the decoy increased willingness of volunteers to cooperate in the first step of each game, leading to subsequent propagation of such willingness by (noisy) tit-for-tat. Our study thus points to decoys as a means to elicit voluntary prosocial action across a spectrum of collective endeavours.
Horse Y chromosome assembly displays unique evolutionary features and putative stallion fertility genes
Authors: Janečka Jan E. , Davis Brian W. , Ghosh Sharmila , Paria Nandina , Das Pranab J. , Orlando Ludovic , Schubert Mikkel , Nielsen Martin K. , Stout Tom A. E. , Brashear Wesley , Li Gang , Johnson Charles D. , Metz Richard P. , Zadjali Al Muatasim Al , Love Charles C. , Varner Dickson D. , Bellott Daniel W. , Murphy William J. , Chowdhary Bhanu P. , Raudsepp Terje
Published: July 2018

Dynamic evolutionary processes and complex structure make the Y chromosome among the most diverse and least understood regions in mammalian genomes. Here, we present an annotated assembly of the male specific region of the horse Y chromosome (eMSY), representing the first comprehensive Y assembly in odd-toed ungulates. The eMSY comprises single-copy, equine specific multi-copy, PAR transposed, and novel ampliconic sequence classes. The eMSY gene density approaches that of autosomes with the highest number of retained X–Y gametologs recorded in eutherians, in addition to novel Y-born and transposed genes. Horse, donkey and mule testis RNAseq reveals several candidate genes for stallion fertility. A novel testis-expressed XY ampliconic sequence class, ETSTY7, is shared with the parasite Parascaris genome, providing evidence for eukaryotic horizontal transfer and inter-chromosomal mobility. Our study highlights the dynamic nature of the Y and provides a reference sequence for improved understanding of equine male development and fertility.
A facile strategy for realizing room temperature phosphorescence and single molecule white light emission
Authors: Wang Jianguo , Gu Xinggui , Ma Huili , Peng Qian , Huang Xiaobo , Zheng Xiaoyan , Sung Simon H. P. , Shan Guogang , Lam Jacky W. Y. , Shuai Zhigang , Tang Ben Zhong
Published: July 2018

Research on materials with pure organic room temperature phosphorescence (RTP) and their application as organic single-molecule white light emitters is a hot area and relies on the design of highly efficient pure organic RTP luminogens. Herein, a facile strategy of heavy-atom-participated anion–π+ interactions is proposed to construct RTP-active organic salt compounds (1,2,3,4-tetraphenyloxazoliums with different counterions). Those compounds with heavy-atom counterions (bromide and iodide ions) exhibit outstanding RTP due to the external heavy atom effect via anion–π+ interactions, evidently supported by the single-crystal X-ray diffraction analysis and theoretical calculation. Their single-molecule white light emission is realized by tuning the degree of crystallization. Such white light emission also performs well in polymer matrices and their use in 3D printing is demonstrated by white light lampshades.
Designing with living systems in the synthetic yeast project
Authors: Szymanski Erika , Calvert Jane
Published: July 2018

Synthetic biology is challenged by the complexity and the unpredictability of living systems. While one response to this complexity involves simplifying cells to create more fully specified systems, another approach utilizes directed evolution, releasing some control and using unpredictable change to achieve design goals. Here we discuss SCRaMbLE, employed in the synthetic yeast project, as an example of synthetic biology design through working with living systems. SCRaMbLE is a designed tool without being a design tool, harnessing the activities of the yeast rather than relying entirely on scientists’ deliberate choices. We suggest that directed evolution at the level of the whole organism allows scientists and microorganisms to “collaborate” to achieve design goals, suggesting new directions for synthetic biology.
Spindle tubulin and MTOC asymmetries may explain meiotic drive in oocytes
Authors: Wu Tianyu , Lane Simon I. R. , Morgan Stephanie L. , Jones Keith T.
Published: July 2018

In the first meiotic division (MI) of oocytes, the cortically positioned spindle causes bivalent segregation in which only the centre-facing homologue pairs are retained. ‘Selfish’ chromosomes are known to exist, which bias their spindle orientation and hence retention in the egg, a process known as ‘meiotic drive’. Here we report on this phenomenon in oocytes from F1 hybrid mice, where parental strain differences in centromere size allows distinction of the two homologue pairs of a bivalent. Bivalents with centromere and kinetochore asymmetry show meiotic drive by rotating during prometaphase, in a process dependent on aurora kinase activity. Cortically positioned homologue pairs appear to be under greater stretch than their centre-facing partners. Additionally the cortex spindle-half contain a greater density of tubulin and microtubule organising centres. A model is presented in which meiotic drive is explained by the impact of microtubule force asymmetry on chromosomes with different sized centromeres and kinetochores.
Macrophages are exploited from an innate wound healing response to facilitate cancer metastasis
Authors: Muliaditan Tamara , Caron Jonathan , Okesola Mary , Opzoomer James W. , Kosti Paris , Georgouli Mirella , Gordon Peter , Lall Sharanpreet , Kuzeva Desislava M. , Pedro Luisa , Shields Jacqueline D. , Gillett Cheryl E. , Diebold Sandra S. , Sanz-Moreno Victoria , Ng Tony , Hoste Esther , Arnold James N.
Published: July 2018

Tumour-associated macrophages (TAMs) play an important role in tumour progression, which is facilitated by their ability to respond to environmental cues. Here we report, using murine models of breast cancer, that TAMs expressing fibroblast activation protein alpha (FAP) and haem oxygenase-1 (HO-1), which are also found in human breast cancer, represent a macrophage phenotype similar to that observed during the wound healing response. Importantly, the expression of a wound-like cytokine response within the tumour is clinically associated with poor prognosis in a variety of cancers. We show that co-expression of FAP and HO-1 in macrophages results from an innate early regenerative response driven by IL-6, which both directly regulates HO-1 expression and licenses FAP expression in a skin-like collagen-rich environment. We show that tumours can exploit this response to facilitate transendothelial migration and metastatic spread of the disease, which can be pharmacologically targeted using a clinically relevant HO-1 inhibitor.
Predicting treatment benefit in multiple myeloma through simulation of alternative treatment effects
Authors: Ubels Joske , Sonneveld Pieter , van Beers Erik H. , Broijl Annemiek , van Vliet Martin H. , de Ridder Jeroen
Published: July 2018

Many cancer treatments are associated with serious side effects, while they often only benefit a subset of the patients. Therefore, there is an urgent clinical need for tools that can aid in selecting the right treatment at diagnosis. Here we introduce simulated treatment learning (STL), which enables prediction of a patient’s treatment benefit. STL uses the idea that patients who received different treatments, but have similar genetic tumor profiles, can be used to model their response to the alternative treatment. We apply STL to two multiple myeloma gene expression datasets, containing different treatments (bortezomib and lenalidomide). We find that STL can predict treatment benefit for both; a twofold progression free survival (PFS) benefit is observed for bortezomib for 19.8% and a threefold PFS benefit for lenalidomide for 31.1% of the patients. This demonstrates that STL can derive clinically actionable gene expression signatures that enable a more personalized approach to treatment.
Real-space imaging with pattern recognition of a ligand-protected Ag374 nanocluster at sub-molecular resolution
Authors: Zhou Qin , Kaappa Sami , Malola Sami , Lu Hui , Guan Dawei , Li Yajuan , Wang Haochen , Xie Zhaoxiong , Ma Zhibo , Häkkinen Hannu , Zheng Nanfeng , Yang Xueming , Zheng Lansun
Published: July 2018

High-resolution real-space imaging of nanoparticle surfaces is desirable for better understanding of surface composition and morphology, molecular interactions at the surface, and nanoparticle chemical functionality in its environment. However, achieving molecular or sub-molecular resolution has proven to be very challenging, due to highly curved nanoparticle surfaces and often insufficient knowledge of the monolayer composition. Here, we demonstrate sub-molecular resolution in scanning tunneling microscopy imaging of thiol monolayer of a 5 nm nanoparticle Ag374 protected by tert-butyl benzene thiol. The experimental data is confirmed by comparisons through a pattern recognition algorithm to simulated topography images from density functional theory using the known total structure of the Ag374 nanocluster. Our work demonstrates a working methodology for investigations of structure and composition of organic monolayers on curved nanoparticle surfaces, which helps designing functionalities for nanoparticle-based applications.
Scutoids are a geometrical solution to three-dimensional packing of epithelia
Authors: Gómez-Gálvez Pedro , Vicente-Munuera Pablo , Tagua Antonio , Forja Cristina , Castro Ana M. , Letrán Marta , Valencia-Expósito Andrea , Grima Clara , Bermúdez-Gallardo Marina , Serrano-Pérez-Higueras Óscar , Cavodeassi Florencia , Sotillos Sol , Martín-Bermudo María D. , Márquez Alberto , Buceta Javier , Escudero Luis M.
Published: July 2018

As animals develop, tissue bending contributes to shape the organs into complex three-dimensional structures. However, the architecture and packing of curved epithelia remains largely unknown. Here we show by means of mathematical modelling that cells in bent epithelia can undergo intercalations along the apico-basal axis. This phenomenon forces cells to have different neighbours in their basal and apical surfaces. As a consequence, epithelial cells adopt a novel shape that we term “scutoid”. The detailed analysis of diverse tissues confirms that generation of apico-basal intercalations between cells is a common feature during morphogenesis. Using biophysical arguments, we propose that scutoids make possible the minimization of the tissue energy and stabilize three-dimensional packing. Hence, we conclude that scutoids are one of nature's solutions to achieve epithelial bending. Our findings pave the way to understand the three-dimensional organization of epithelial organs.
Contact inhibition controls cell survival and proliferation via YAP/TAZ-autophagy axis
Authors: Pavel Mariana , Renna Maurizio , Park So Jung , Menzies Fiona M. , Ricketts Thomas , Füllgrabe Jens , Ashkenazi Avraham , Frake Rebecca A. , Lombarte Alejandro Carnicer , Bento Carla F. , Franze Kristian , Rubinsztein David C.
Published: July 2018

Contact inhibition enables noncancerous cells to cease proliferation and growth when they contact each other. This characteristic is lost when cells undergo malignant transformation, leading to uncontrolled proliferation and solid tumor formation. Here we report that autophagy is compromised in contact-inhibited cells in 2D or 3D-soft extracellular matrix cultures. In such cells, YAP/TAZ fail to co-transcriptionally regulate the expression of myosin-II genes, resulting in the loss of F-actin stress fibers, which impairs autophagosome formation. The decreased proliferation resulting from contact inhibition is partly autophagy-dependent, as is their increased sensitivity to hypoxia and glucose starvation. These findings define how mechanically repressed YAP/TAZ activity impacts autophagy to contribute to core phenotypes resulting from high cell confluence that are lost in various cancers.
Pairwise library screen systematically interrogates Staphylococcus aureus Cas9 specificity in human cells
Authors: Tycko Josh , Barrera Luis A. , Huston Nicholas C. , Friedland Ari E. , Wu Xuebing , Gootenberg Jonathan S. , Abudayyeh Omar O. , Myer Vic E. , Wilson Christopher J. , Hsu Patrick D.
Published: July 2018

Therapeutic genome editing with Staphylococcus aureus Cas9 (SaCas9) requires a rigorous understanding of its potential off-target activity in the human genome. Here we report a high-throughput screening approach to measure SaCas9 genome editing variation in human cells across a large repertoire of 88,692 single guide RNAs (sgRNAs) paired with matched or mismatched target sites in a synthetic cassette. We incorporate randomized barcodes that enable whitelisting of correctly synthesized molecules for further downstream analysis, in order to circumvent the limitation of oligonucleotide synthesis errors. We find SaCas9 sgRNAs with 21-mer or 22-mer spacer sequences are generally more active, although high efficiency 20-mer spacers are markedly less tolerant of mismatches. Using this dataset, we developed an SaCas9 specificity model that performs robustly in ranking off-target sites. The barcoded pairwise library screen enabled high-fidelity recovery of guide-target relationships, providing a scalable framework for the investigation of CRISPR enzyme properties and general nucleic acid interactions.
Lighting up silicon nanoparticles with Mie resonances
Authors: Zhang Chengyun , Xu Yi , Liu Jin , Li Juntao , Xiang Jin , Li Hui , Li Jinxiang , Dai Qiaofeng , Lan Sheng , Miroshnichenko Andrey E.
Published: July 2018

As one of the most important semiconductors, silicon has been used to fabricate electronic devices, waveguides, detectors, solar cells, etc. However, the indirect bandgap and low quantum efficiency (10−7) hinder the use of silicon for making good emitters. For integrated photonic circuits, silicon-based emitters with sizes in the range of 100−300 nm are highly desirable. Here, we show the use of the electric and magnetic resonances in silicon nanoparticles to enhance the quantum efficiency and demonstrate the white-light emission from silicon nanoparticles with feature sizes of ~200 nm. The magnetic and electric dipole resonances are employed to dramatically increase the relaxation time of hot carriers, while the magnetic and electric quadrupole resonances are utilized to reduce the radiative recombination lifetime of hot carriers. This strategy leads to an enhancement in the quantum efficiency of silicon nanoparticles by nearly five orders of magnitude as compared with bulk silicon, taking the three-photon-induced absorption into account.
Two-dimensional multibit optoelectronic memory with broadband spectrum distinction
Authors: Xiang Du , Liu Tao , Xu Jilian , Tan Jun Y. , Hu Zehua , Lei Bo , Zheng Yue , Wu Jing , Neto A. H. Castro , Liu Lei , Chen Wei
Published: July 2018

Optoelectronic memory plays a vital role in modern semiconductor industry. The fast emerging requirements for device miniaturization and structural flexibility have diverted research interest to two-dimensional thin layered materials. Here, we report a multibit nonvolatile optoelectronic memory based on a heterostructure of monolayer tungsten diselenide and few-layer hexagonal boron nitride. The tungsten diselenide/boron nitride memory exhibits a memory switching ratio approximately 1.1 × 106, which ensures over 128 (7 bit) distinct storage states. The memory demonstrates robustness with retention time over 4.5 × 104 s. Moreover, the ability of broadband spectrum distinction enables its application in filter-free color image sensor. This concept is further validated through the realization of integrated tungsten diselenide/boron nitride pixel matrix which captured a specific image recording the three primary colors (red, green, and blue). The heterostructure architecture is also applicable to other two-dimensional materials, which is confirmed by the realization of black phosphorus/boron nitride optoelectronic memory.
How do our cells build their protein interactome?
Authors: Coulombe Benoit , Cloutier Philippe , Gauthier Marie-Soleil
Published: July 2018

Chaperones are cellular factors that help in the folding of newly synthesized polypeptides (or clients) and, in some cases, ensure their integration within larger complexes. They often require non-client proteins, or co-chaperones, to help drive specificity to particular target polypeptides or facilitate the nucleotide hydrolysis cycle of some chaperones. The latest findings on the characterization of the PAQosome (Particle for Arrangement of Quaternary structure; formerly known as R2TP/PFDL complex) published recently in Nature Communications help to explain how this particular co-chaperone plays a central role in organizing our proteome into protein complexes and networks. The exploitation by the cell of alternative PAQosomes formed through the differential integration of homologous subunits, in conjunction with the use of several adaptors (specificity factors), provide the conceptual basis for interaction of multiple clients in a structure that is favorable to their simultaneous binding en route to protein complex and network assembly/maturation.
Author Correction: NSAIDs Use and Reduced Metastasis in Cancer Patients: results from a meta-analysis
Authors: Zhao Xiaoping , Xu Zhi , Li Haoseng
Published: July 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
miRNAs regulate acute transcriptional changes in broiler embryos in response to modification of incubation temperature
Authors: Naraballobh Watcharapong , Trakooljul Nares , Murani Eduard , Krischek Carsten , Janisch Sabine , Wicke Michael , Ponsuksili Siriluck , Wimmers Klaus
Published: July 2018

MicroRNAs are post-transcriptional regulators that play critical roles in diverse biological processes. We hypothesize that miRNAs may be involved in regulating transcriptome responses to changes in embryonic incubation temperature in chickens affecting differentiation and proliferation processes during tissue development. Therefore, we conducted comparative transcriptome profiling of miRNAs to examine altered expression in breast and hind muscle of embryos and day 35 chickens experiencing high (38.8 °C), control (37.8 °C), or low (36.8 °C) embryonic incubation temperature during embryonic day (ED) 7–10 or ED10–13. The results revealed differential expression of miRNAs due to modification of embryonic incubation temperature in a muscle type-specific and a developmental stage-specific manner. The immediate effects of thermal change observed in embryos were substantial compared to the subtle long-term effects in chickens at day 35 post-hatch. Upregulation of miR-133 in breast muscle and downregulation of miR-199a-5p, miR-1915, and miR-638 in hind muscle post ED7–10 high-temperature treatment are functionally associated with myogenesis and body size. ED10–13 low-temperature treatment led to downregulation of let-7, miR-93, and miR-130c that are related to proliferation and differentiation. The results provide insight into the dynamics of miRNA expression at variable embryonic incubation temperatures during developmental processes and indicate a major regulatory role of miRNAs in acute responses to modified environmental conditions that affect remodelling of cells and tissues.
Linking mixing processes and climate variability to the heat content distribution of the Eastern Mediterranean abyss
Authors: Artale Vincenzo , Falcini Federico , Marullo Salvatore , Bensi Manuel , Kokoszka Florian , Iudicone Daniele , Rubino Angelo
Published: July 2018

The heat contained in the ocean (OHC) dominates the Earth’s energy budget and hence represents a fundamental parameter for understanding climate changes. However, paucity of observational data hampers our knowledge on OHC variability, particularly in abyssal areas. Here, we analyze water characteristics, observed during the last three decades in the abyssal Ionian Sea (Eastern Mediterranean), where two competing convective sources of bottom water exist. We find a heat storage of ~1.6 W/m2 – twice that assessed globally in the same period – exceptionally well-spread throughout the local abyssal layers. Such an OHC accumulation stems from progressive warming and salinification of the Eastern Mediterranean, producing warmer near-bottom waters. We analyze a new process that involves convectively-generated waters reaching the abyss as well as the triggering of a diapycnal mixing due to rough bathymetry, which brings to a warming and thickening of the bottom layer, also influencing water-column potential vorticity. This may affect the prevailing circulation, altering the local cyclonic/anticyclonic long-term variability and hence precondition future water-masses formation and the redistribution of heat along the entire water-column.
Cotton rat lung transcriptome reveals host immune response to Respiratory Syncytial Virus infection
Authors: Rajagopala Seesandra V. , Singh Harinder , Patel Mira C. , Wang Wei , Tan Yi , Shilts Meghan H. , Hartert Tina V. , Boukhvalova Marina S. , Blanco Jorge C. G. , Das Suman R.
Published: July 2018

Acute respiratory infection (ARI) with respiratory syncytial virus (RSV) is the most common cause of both hospitalizations and mortality in young infants worldwide. Repeat infections with RSV are common throughout life in both pediatric and elderly populations. Thus far, cotton rats (Sigmodon hispidus) are found to be the best animal model to study RSV infection. However, the lack of a cotton rat reference genome limits genome-wide host gene expression studies. We constructed the first lung tissue de novo transcriptome for the cotton rat. Cotton rat lung tissue transcripts were assigned to 12,211 unique UniProt genes, which were then utilized to profile the host immune response after RSV infection. Differential expression analysis showed up-regulation of host genes involved in cellular functions including defense responses to viral infection and immune system processes. A number of transcripts were downregulated during the later stage of infection. A set of transcripts unique to RSV-infected cotton rats was identified. To validate RNA-Seq data of three such transcripts (TR453762, TR529629, and TR5333), their expression was confirmed by quantitative real-time polymerase chain reaction.
Formation of unique nanocrystalline Cu-In-Se bulk pn homojunctions for opto-electronic devices
Authors: Menezes Shalini , Samantilleke Anura
Published: July 2018

Semiconductor pn junctions, integrated in optoelectronic devices require high quality crystals, made by expensive, technically difficult processes. Bulk heterojunction (BHJ) structures offer practical alternatives to circumvent the cost, flexibility and scale-up challenges of crystalline planar pn junctions. Fabrication methods for the current organic or inorganic BHJ structures invariably create interface mismatch and low doping issues. To overcome such issues, we devised an innovative approach, founded on novel inorganic material system that ensued from single-step electrodeposited copper-indium-selenide compounds. Surface analytical microscopies and spectroscopies reveal unusual phenomena, electro-optical properties and quantum effects. They support the formation of highly-ordered, sharp, abrupt 3-dimensional nanoscale pn BHJs that facilitate efficient charge carrier separation and transport, and essentially perform the same functions as crystalline planar pn junctions. This approach offers a low-cost processing platform to create nanocrystalline films, with the attributes necessary for efficient BHJ operation. It allows roll-to-roll processing of flexible devices in simple thin-film form factor.
Histone deacetylase 8 protects human proximal tubular epithelial cells from hypoxia-mimetic cobalt- and hypoxia/reoxygenation-induced mitochondrial fission and cytotoxicity
Authors: Ha Soon-Duck , Solomon Ori , Akbari Masoud , Sener Alp , Kim Sung Ouk
Published: July 2018

Cell death by hypoxia followed by reoxygenation (H/R) is responsible for tissue injury in multiple pathological conditions. Recent studies found that epigenetic reprogramming mediated by histone deacetylases (HDACs) is implicated in H/R-induced cell death. However, among 18 different isoforms comprising 4 classes (I-IV), the role of each HDAC in cell death is largely unknown. This study examined the role of HDAC8, which is the most distinct isoform of class I, in the hypoxia mimetic cobalt- and H/R-induced cytotoxicity of human proximal tubular HK-2 cells. Using the HDAC8-specific activator TM-2-51 (TM) and inhibitor PCI34051, we found that HDAC8 played a protective role in cytotoxicity. TM or overexpression of wild-type HDAC8, but not a deacetylase-defective HDAC8 mutant, prevented mitochondrial fission, loss of mitochondrial transmembrane potential and release of cytochrome C into the cytoplasm. TM suppressed expression of dynamin-related protein 1 (DRP1) which is a key factor required for mitochondrial fission. Suppression of DRP1 by HDAC8 was likely mediated by decreasing the level of acetylated histone H3 lysine 27 (a hallmark of active promoters) at the DRP1 promoter. Collectively, this study shows that HDAC8 inhibits cytotoxicity induced by cobalt and H/R, in part, through suppressing DRP1 expression and mitochondrial fission.