bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systems genetics in diversity outbred mice inform BMD GWAS and identify determinants of bone strength
Authors: Al-Barghouthi Basel M. , Mesner Larry D. , Calabrese Gina M. , Brooks Daniel , Tommasini Steven M. , Bouxsein Mary L. , Horowitz Mark C. , Rosen Clifford J. , Nguyen Kevin , Haddox Samuel , Farber Emily A. , Onengut-Gumuscu Suna , Pomp Daniel , Farber Charles R. 
Published: June 2021

AbstractGenome-wide association studies (GWASs) for osteoporotic traits have identified over 1000 associations; however, their impact has been limited by the difficulties of causal gene identification and a strict focus on bone mineral density (BMD). Here, we use Diversity Outbred (DO) mice to directly address these limitations by performing a systems genetics analysis of 55 complex skeletal phenotypes. We apply a network approach to cortical bone RNA-seq data to discover 66 genes likely to be causal for human BMD GWAS associations, including the genesSERTAD4andGLT8D2. We also perform GWAS in the DO for a wide-range of bone traits and identifyQsox1as a gene influencing cortical bone accrual and bone strength. In this work, we advance our understanding of the genetics of osteoporosis and highlight the ability of the mouse to inform human genetics.
Attosecond intra-valence band dynamics and resonant-photoemission delays in W(110)
Authors: Heinrich S. , Saule T. , Högner M. , Cui Y. , Yakovlev V. S. , Pupeza I. , Kleineberg U. 
Published: June 2021

AbstractTime-resolved photoelectron spectroscopy with attosecond precision provides new insights into the photoelectric effect and gives information about the timing of photoemission from different electronic states within the electronic band structure of solids. Electron transport, scattering phenomena and electron-electron correlation effects can be observed on attosecond time scales by timing photoemission from valence band states against that from core states. However, accessing intraband effects was so far particularly challenging due to the simultaneous requirements on energy, momentum and time resolution. Here we report on an experiment utilizing intracavity generated attosecond pulse trains to meet these demands at high flux and high photon energies to measure intraband delays between sp- and d-band states in the valence band photoemission from tungsten and investigate final-state effects in resonant photoemission.
Selection on heritable social network positions is context-dependent in Drosophila melanogaster
Authors: Wice Eric Wesley , Saltz Julia Barbara 
Published: June 2021

AbstractSocial group structure is highly variable and can be important for nearly every aspect of behavior and its fitness consequences. Group structure can be modeled using social network analysis, but we know little about the evolutionary factors shaping and maintaining variation in how individuals are embedded within their networks (i.e., network position). While network position is a pervasive target of selection, it remains unclear whether network position is heritable and can respond to selection. Furthermore, it is unclear how environmental factors interact with genotypic effects on network positions, or how environmental factors shape selection on heritable network structure. Here we show multiple measures of social network position are heritable, using replicate genotypes and replicate social groups of Drosophila melanogaster flies. Our results indicate genotypic differences in network position are largely robust to changes in the environment flies experience, though some measures of network position do vary across environments. We also show selection on multiple network position metrics depends on the environmental context they are expressed in, laying the groundwork for better understanding how spatio-temporal variation in selection contributes to the evolution of variable social group structure.
Unique structure of active platinum-bismuth site for oxidation of carbon monoxide
Authors: Nan Bing , Fu Qiang , Yu Jing , Shu Miao , Zhou Lu-Lu , Li Jinying , Wang Wei-Wei , Jia Chun-Jiang , Ma Chao , Chen Jun-Xiang , Li Lina , Si Rui 
Published: June 2021

AbstractAs the technology development, the future advanced combustion engines must be designed to perform at a low temperature. Thus, it is a great challenge to synthesize high active and stable catalysts to resolve exhaust below 100 °C. Here, we report that bismuth as a dopant is added to form platinum-bismuth cluster on silica for CO oxidation. The highly reducible oxygen species provided by surface metal-oxide (M-O) interface could be activated by CO at low temperature (~50 °C) with a high CO2 production rate of 487 μmolCO2·gPt−1·s−1 at 110 °C. Experiment data combined with density functional calculation (DFT) results demonstrate that Pt cluster with surface Pt−O−Bi structure is the active site for CO oxidation via providing moderate CO adsorption and activating CO molecules with electron transformation between platinum atom and carbon monoxide. These findings provide a unique and general approach towards design of potential excellent performance catalysts for redox reaction.
A new high-voltage calcium intercalation host for ultra-stable and high-power calcium rechargeable batteries
Authors: Xu Zheng-Long , Park Jooha , Wang Jian , Moon Hyunseok , Yoon Gabin , Lim Jongwoo , Ko Yoon-Joo , Cho Sung-Pyo , Lee Sang-Young , Kang Kisuk 
Published: June 2021

AbstractRechargeable calcium batteries have attracted increasing attention as promising multivalent ion battery systems due to the high abundance of calcium. However, the development has been hampered by the lack of suitable cathodes to accommodate the large and divalent Ca2+ ions at a high redox potential with sufficiently fast ionic conduction. Herein, we report a new intercalation host which presents 500 cycles with a capacity retention of 90% and a remarkable power capability at ~3.2 V (vs. Ca/Ca2+) in a calcium battery. The cathode material derived from Na0.5VPO4.8F0.7 is demonstrated to reversibly accommodate a large amount of Ca2+ ions, forming a series of CaxNa0.5VPO4.8F0.7 (0 < x < 0.5) phases without any noticeable structural degradation. The robust framework enables one of the smallest volume changes (1.4%) and the lowest diffusion barriers for Ca2+ among the cathodes reported to date, offering the basis for the outstanding cycle life and power capability.
GATA3 induces mitochondrial biogenesis in primary human CD4+ T cells during DNA damage
Authors: Callender Lauren A. , Schroth Johannes , Carroll Elizabeth C. , Garrod-Ketchley Conor , Romano Lisa E. L. , Hendy Eleanor , Kelly Audrey , Lavender Paul , Akbar Arne N. , Chapple J. Paul , Henson Sian M. 
Published: June 2021

AbstractGATA3 is as a lineage-specific transcription factor that drives the differentiation of CD4+ T helper 2 (Th2) cells, but is also involved in a variety of processes such as immune regulation, proliferation and maintenance in other T cell and non-T cell lineages. Here we show a mechanism utilised by CD4+ T cells to increase mitochondrial mass in response to DNA damage through the actions of GATA3 and AMPK. Activated AMPK increases expression of PPARG coactivator 1 alpha (PPARGC1A or PGC1α protein) at the level of transcription and GATA3 at the level of translation, while DNA damage enhances expression of nuclear factor erythroid 2-related factor 2 (NFE2L2 or NRF2). PGC1α, GATA3 and NRF2 complex together with the ATR to promote mitochondrial biogenesis. These findings extend the pleotropic interactions of GATA3 and highlight the potential for GATA3-targeted cell manipulation for intervention in CD4+ T cell viability and function after DNA damage.
Layered double hydroxide membrane with high hydroxide conductivity and ion selectivity for energy storage device
Authors: Hu Jing , Tang Xiaomin , Dai Qing , Liu Zhiqiang , Zhang Huamin , Zheng Anmin , Yuan Zhizhang , Li Xianfeng 
Published: June 2021

AbstractMembranes with fast and selective ions transport are highly demanded for energy storage devices. Layered double hydroxides (LDHs), bearing uniform interlayer galleries and abundant hydroxyl groups covalently bonded within two-dimensional (2D) host layers, make them superb candidates for high-performance membranes. However, related research on LDHs for ions separation is quite rare, especially the deep-going study on ions transport behavior in LDHs. Here, we report a LDHs-based composite membrane with fast and selective ions transport for flow battery application. The hydroxide ions transport through LDHs via vehicular (standard diffusion) & Grotthuss (proton hopping) mechanisms is uncovered. The LDHs-based membrane enables an alkaline zinc-based flow battery to operate at 200 mA cm−2, along with an energy efficiency of 82.36% for 400 cycles. This study offers an in-depth understanding of ions transport in LDHs and further inspires their applications in other energy-related devices.
TET1-mediated DNA hydroxymethylation regulates adult remyelination in mice
Authors: Moyon Sarah , Frawley Rebecca , Marechal Damien , Huang Dennis , Marshall-Phelps Katy L. H. , Kegel Linde , Bøstrand Sunniva M. K. , Sadowski Boguslawa , Jiang Yong-Hui , Lyons David A. , Möbius Wiebke , Casaccia Patrizia 
Published: June 2021

AbstractThe mechanisms regulating myelin repair in the adult central nervous system (CNS) are unclear. Here, we identify DNA hydroxymethylation, catalyzed by the Ten-Eleven-Translocation (TET) enzyme TET1, as necessary for myelin repair in young adults and defective in old mice. Constitutive and inducible oligodendrocyte lineage-specific ablation of Tet1 (but not of Tet2), recapitulate this age-related decline in repair of demyelinated lesions. DNA hydroxymethylation and transcriptomic analyses identify TET1-target in adult oligodendrocytes, as genes regulating neuro-glial communication, including the solute carrier (Slc) gene family. Among them, we show that the expression levels of the Na+/K+/Cl− transporter, SLC12A2, are higher in Tet1 overexpressing cells and lower in old or Tet1 knockout. Both aged mice and Tet1 mutants also present inefficient myelin repair and axo-myelinic swellings. Zebrafish mutants for slc12a2b also display swellings of CNS myelinated axons. Our findings suggest that TET1 is required for adult myelin repair and regulation of the axon-myelin interface.
Temporal evolution of cellular heterogeneity during the progression to advanced AR-negative prostate cancer
Authors: Brady Nicholas J. , Bagadion Alyssa M. , Singh Richa , Conteduca Vincenza , Van Emmenis Lucie , Arceci Elisa , Pakula Hubert , Carelli Ryan , Khani Francesca , Bakht Martin , Sigouros Michael , Bareja Rohan , Sboner Andrea , Elemento Olivier , Tagawa Scott , Nanus David M. , Loda Massimo , Beltran Himisha , Robinson Brian , Rickman David S. 
Published: June 2021

AbstractDespite advances in the development of highly effective androgen receptor (AR)-directed therapies for the treatment of men with advanced prostate cancer, acquired resistance to such therapies frequently ensues. A significant subset of patients with resistant disease develop AR-negative tumors that lose their luminal identity and display neuroendocrine features (neuroendocrine prostate cancer (NEPC)). The cellular heterogeneity and the molecular evolution during the progression from AR-positive adenocarcinoma to AR-negative NEPC has yet to be characterized. Utilizing a new genetically engineered mouse model, we have characterized the synergy between Rb1 loss and MYCN (encodes N-Myc) overexpression which results in the formation of AR-negative, poorly differentiated tumors with high metastatic potential. Single-cell-based approaches revealed striking temporal changes to the transcriptome and chromatin accessibility which have identified the emergence of distinct cell populations, marked by differential expression of Ascl1 and Pou2f3, during the transition to NEPC. Moreover, global DNA methylation and the N-Myc cistrome are redirected following Rb1 loss. Altogether, our data provide insight into the progression of prostate adenocarcinoma to NEPC.
Feeding diversified protein sources exacerbates hepatic insulin resistance via increased gut microbial branched-chain fatty acids and mTORC1 signaling in obese mice
Authors: Choi Béatrice S.-Y. , Daniel Noëmie , Houde Vanessa P. , Ouellette Adia , Marcotte Bruno , Varin Thibault V. , Vors Cécile , Feutry Perrine , Ilkayeva Olga , Ståhlman Marcus , St-Pierre Philippe , Bäckhed Fredrik , Tremblay Angelo , White Phillip J. , Marette André 
Published: June 2021

AbstractAnimal models of human diseases are classically fed purified diets that contain casein as the unique protein source. We show that provision of a mixed protein source mirroring that found in the western diet exacerbates diet-induced obesity and insulin resistance by potentiating hepatic mTORC1/S6K1 signaling as compared to casein alone. These effects involve alterations in gut microbiota as shown by fecal microbiota transplantation studies. The detrimental impact of the mixed protein source is also linked with early changes in microbial production of branched-chain fatty acids (BCFA) and elevated plasma and hepatic acylcarnitines, indicative of aberrant mitochondrial fatty acid oxidation. We further show that the BCFA, isobutyric and isovaleric acid, increase glucose production and activate mTORC1/S6K1 in hepatocytes. Our findings demonstrate that alteration of dietary protein source exerts a rapid and robust impact on gut microbiota and BCFA with significant consequences for the development of obesity and insulin resistance.
Implications of incidental findings from lung screening for primary care: data from a UK pilot
Authors: Bartlett Emily C. , Belsey Jonathan , Derbyshire Jane , Morris Katie , Chen Michelle , Addis James , Martins Maria , Ridge Carole A. , Desai Sujal R. , Mirsadraee Saeed , Padley Simon , Whiteside Sarah , Vaghani Pritti , Morjaria Jaymin B. , Kemp Samuel V. , Devaraj Anand 
Published: June 2021

AbstractRegional lung cancer screening (LCS) is underway in England, involving a “lung health check” (LHC) and low-dose CT scan for those at high risk of cancer. Incidental findings from LHCs or CTs are usually referred to primary care. We describe the proportion of participants referred from the West London LCS pilot to primary care, the indications for referral, the number of general practitioner (GP) attendances and consequent changes to patient management, and provide an estimated cost-burden analysis for primary care. A small proportion (163/1542, 10.6%) of LHC attendees were referred to primary care, primarily for suspected undiagnosed chronic obstructive pulmonary disease (55/163, 33.7%) or for QRISK® (63/163, 38.7%) assessment. Ninety one of 159 (57.2%) participants consenting to follow-up attended GP appointments; costs incurred by primary care were estimated at £5.69/LHC participant. Patient management changes occurred in only 36/159 (22.6%) referred participants. LHCs result in a small increase to primary care workload provided a strict referral protocol is adhered to. Changes to patient management arising from incidental findings referrals are infrequent.
Nanobodies from camelid mice and llamas neutralize SARS-CoV-2 variants
Authors: Xu Jianliang , Xu Kai , Jung Seolkyoung , Conte Andrea , Lieberman Jenna , Muecksch Frauke , Lorenzi Julio Cesar Cetrulo , Park Solji , Schmidt Fabian , Wang Zijun , Huang Yaoxing , Luo Yang , Nair Manoj S. , Wang Pengfei , Schulz Jonathan E. , Tessarollo Lino , Bylund Tatsiana , Chuang Gwo-Yu , Olia Adam S. , Stephens Tyler , Teng I-Ting , Tsybovsky Yaroslav , Zhou Tongqing , Munster Vincent , Ho David D. , Hatziioannou Theodora , Bieniasz Paul D. , Nussenzweig Michel C. , Kwong Peter D. , Casellas Rafael 
Published: June 2021

AbstractSince the start of the COVID-19 pandemic, SARS-CoV-2 has caused millions of deaths worldwide. Although a number of vaccines have been deployed, the continual evolution of the receptor-binding domain (RBD) of the virus has challenged their efficacy. In particular, the emerging variants B.1.1.7, B.1.351 and P.1 (first detected in the UK, South Africa and Brazil, respectively) have compromised the efficacy of sera from patients who have recovered from COVID-19 and immunotherapies that have received emergency use authorization1–3. One potential alternative to avert viral escape is the use of camelid VHHs (variable heavy chain domains of heavy chain antibody (also known as nanobodies)), which can recognize epitopes that are often inaccessible to conventional antibodies4. Here, we isolate anti-RBD nanobodies from llamas and from mice that we engineered to produce VHHs cloned from alpacas, dromedaries and Bactrian camels. We identified two groups of highly neutralizing nanobodies. Group 1 circumvents antigenic drift by recognizing an RBD region that is highly conserved in coronaviruses but rarely targeted by human antibodies. Group 2 is almost exclusively focused to the RBD–ACE2 interface and does not neutralize SARS-CoV-2 variants that carry E484K or N501Y substitutions. However, nanobodies in group 2 retain full neutralization activity against these variants when expressed as homotrimers, and—to our knowledge—rival the most potent antibodies against SARS-CoV-2 that have been produced to date. These findings suggest that multivalent nanobodies overcome SARS-CoV-2 mutations through two separate mechanisms: enhanced avidity for the ACE2-binding domain and recognition of conserved epitopes that are largely inaccessible to human antibodies. Therefore, although new SARS-CoV-2 mutants will continue to emerge, nanobodies represent promising tools to prevent COVID-19 mortality when vaccines are compromised.
Three-dimensional folding dynamics of the Xenopus tropicalis genome
Authors: Niu Longjian , Shen Wei , Shi Zhaoying , Tan Yongjun , He Na , Wan Jing , Sun Jialei , Zhang Yuedong , Huang Yingzhang , Wang Wenjing , Fang Chao , Li Jiashuo , Zheng Piaopiao , Cheung Edwin , Chen Yonglong , Li Li , Hou Chunhui 
Published: June 2021

AbstractAnimal interphase chromosomes are organized into topologically associating domains (TADs). How TADs are formed is not fully understood. Here, we combined high-throughput chromosome conformation capture and gene silencing to obtain insights into TAD dynamics in Xenopus tropicalis embryos. First, TAD establishment in X. tropicalis is similar to that in mice and flies and does not depend on zygotic genome transcriptional activation. This process is followed by further refinements in active and repressive chromatin compartments and the appearance of loops and stripes. Second, within TADs, higher self-interaction frequencies at one end of the boundary are associated with higher DNA occupancy of the architectural proteins CTCF and Rad21. Third, the chromatin remodeling factor ISWI is required for de novo TAD formation. Finally, TAD structures are variable in different tissues. Our work shows that X. tropicalis is a powerful model for chromosome architecture analysis and suggests that chromatin remodeling plays an essential role in de novo TAD establishment.
Backward spatial perception can be augmented through a novel visual-to-auditory sensory substitution algorithm
Authors: Netzer Ophir , Heimler Benedetta , Shur Amir , Behor Tomer , Amedi Amir 
Published: June 2021

AbstractCan humans extend and augment their natural perceptions during adulthood? Here, we address this fascinating question by investigating the extent to which it is possible to successfully augment visual spatial perception to include the backward spatial field (a region where humans are naturally blind) via other sensory modalities (i.e., audition). We thus developed a sensory-substitution algorithm, the “Topo-Speech” which conveys identity of objects through language, and their exact locations via vocal-sound manipulations, namely two key features of visual spatial perception. Using two different groups of blindfolded sighted participants, we tested the efficacy of this algorithm to successfully convey location of objects in the forward or backward spatial fields following ~ 10 min of training. Results showed that blindfolded sighted adults successfully used the Topo-Speech to locate objects on a 3 × 3 grid either positioned in front of them (forward condition), or behind their back (backward condition). Crucially, performances in the two conditions were entirely comparable. This suggests that novel spatial sensory information conveyed via our existing sensory systems can be successfully encoded to extend/augment human perceptions. The implications of these results are discussed in relation to spatial perception, sensory augmentation and sensory rehabilitation.
Isolated sphenoid sinus opacification is often asymptomatic and is not referred for otolaryngology consultation
Authors: Ashida Naoki , Maeda Yohei , Kitamura Takahiro , Hayama Masaki , Tsuda Takeshi , Nakatani Ayaka , Obata Sho , Takeda Kazuya , Akazawa Hitoshi , Inaba Fumitaka , Hosomi Naohiro , Uno Atsuhiko , Inohara Hidenori 
Published: June 2021

AbstractIsolated sphenoid sinus opacifications (ISSOs) are clinically important because they can lead to serious complications. However, some patients with ISSOs are asymptomatic, and not all patients are properly referred to the otolaryngology department. Because past studies of ISSOs focused only on patients who received treatment, in this study we selected ISSO cases based on radiology reports, then determined whether these patients had symptoms and were appropriately referred for specialty care. We conducted a retrospective analysis of data collected from patients who underwent computed tomography or magnetic resonance imaging from January 2007 to March 2017 at Osaka General Medical Center. We searched for the terms “sphenoid” or “sphenoidal” using F-REPORT to identify patients who had a sphenoid disease. We checked all selected images and diagnosed ISSOs. Examination of 1115 cases revealed 223 cases of ISSOs, of whom 167 (74.9%) were asymptomatic. We categorized patients with ISSOs into four groups: inflammation, mucocele, fungal diseases, and unclassifiable; the final category was used when edges were irregular or complete opacity was encountered. In the unclassifiable group, the majority of cases required otolaryngology consultation, but 37 of 47 unclassifiable patients did not have an otolaryngology visit. ISSOs are often identified by chance on imaging tests performed by non-otolaryngologists. However, our study revealed that many patients with ISSOs who should be treated by otolaryngologists were not referred to the otolaryngology department. Accordingly, it is important to promote awareness of the disease among other types of clinicians.
Variations in photoreceptor throughput to mouse visual cortex and the unique effects on tuning
Authors: Rhim I. , Coello-Reyes G. , Nauhaus I. 
Published: June 2021

AbstractVisual input to primary visual cortex (V1) depends on highly adaptive filtering in the retina. In turn, isolation of V1 computations requires experimental control of retinal adaptation to infer its spatio-temporal-chromatic output. Here, we measure the balance of input to mouse V1, in the anesthetized setup, from the three main photoreceptor opsins—M-opsin, S-opsin, and rhodopsin—as a function of two stimulus dimensions. The first dimension is the level of light adaptation within the mesopic range, which governs the balance of rod and cone inputs to cortex. The second stimulus dimension is retinotopic position, which governs the balance of S- and M-cone opsin input due to the opsin expression gradient in the retina. The fitted model predicts opsin input under arbitrary lighting environments, which provides a much-needed handle on in-vivo studies of the mouse visual system. We use it here to reveal that V1 is rod-mediated in common laboratory settings yet cone-mediated in natural daylight. Next, we compare functional properties of V1 under rod and cone-mediated inputs. The results show that cone-mediated V1 responds to 2.5-fold higher temporal frequencies than rod-mediated V1. Furthermore, cone-mediated V1 has smaller receptive fields, yet similar spatial frequency tuning. V1 responses in rod-deficient (Gnat1−/−) mice confirm that the effects are due to differences in photoreceptor opsin contribution.