bluuebunny/crossref_metadata_2025_split huggingface dataset:
A common computational principle for vibrotactile pitch perception in mouse and human
Authors: Prsa Mario , Kilicel Deniz , Nourizonoz Ali , Lee Kuo-Sheng , Huber Daniel 
Published: September 2021

AbstractWe live surrounded by vibrations generated by moving objects. These oscillatory stimuli propagate through solid substrates, are sensed by mechanoreceptors in our body and give rise to perceptual attributes such as vibrotactile pitch (i.e. the perception of how high or low a vibration’s frequency is). Here, we establish a mechanistic relationship between vibrotactile pitch perception and the physical properties of vibrations using behavioral tasks, in which vibratory stimuli were delivered to the human fingertip or the mouse forelimb. The resulting perceptual reports were analyzed with a model demonstrating that physically different combinations of vibration frequencies and amplitudes can produce equal pitch perception. We found that the perceptually indistinguishable but physically different stimuli follow a common computational principle in mouse and human. It dictates that vibrotactile pitch perception is shifted with increases in amplitude toward the frequency of highest vibrotactile sensitivity. These findings suggest the existence of a fundamental relationship between the seemingly unrelated concepts of spectral sensitivity and pitch perception.
Oncogenic KRAS is dependent upon an EFR3A-PI4KA signaling axis for potent tumorigenic activity
Authors: Adhikari Hema , Kattan Walaa E. , Kumar Shivesh , Zhou Pei , Hancock John F. , Counter Christopher M. 
Published: September 2021

AbstractThe HRAS, NRAS, and KRAS genes are collectively mutated in a fifth of all human cancers. These mutations render RAS GTP-bound and active, constitutively binding effector proteins to promote signaling conducive to tumorigenic growth. To further elucidate how RAS oncoproteins signal, we mined RAS interactomes for potential vulnerabilities. Here we identify EFR3A, an adapter protein for the phosphatidylinositol kinase PI4KA, to preferentially bind oncogenic KRAS. Disrupting EFR3A or PI4KA reduces phosphatidylinositol-4-phosphate, phosphatidylserine, and KRAS levels at the plasma membrane, as well as oncogenic signaling and tumorigenesis, phenotypes rescued by tethering PI4KA to the plasma membrane. Finally, we show that a selective PI4KA inhibitor augments the antineoplastic activity of the KRASG12C inhibitor sotorasib, suggesting a clinical path to exploit this pathway. In sum, we have discovered a distinct KRAS signaling axis with actionable therapeutic potential for the treatment of KRAS-mutant cancers.
Super liquid repellent surfaces for anti-foaming and froth management
Authors: Wong William S. Y. , Naga Abhinav , Hauer Lukas , Baumli Philipp , Bauer Hoimar , Hegner Katharina I. , D’Acunzi Maria , Kaltbeitzel Anke , Butt Hans-Jürgen , Vollmer Doris 
Published: September 2021

AbstractWet and dry foams are prevalent in many industries, ranging from the food processing and commercial cosmetic sectors to industries such as chemical and oil-refining. Uncontrolled foaming results in product losses, equipment downtime or damage and cleanup costs. To speed up defoaming or enable anti-foaming, liquid oil or hydrophobic particles are usually added. However, such additives may need to be later separated and removed for environmental reasons and product quality. Here, we show that passive defoaming or active anti-foaming is possible simply by the interaction of foam with chemically or morphologically modified surfaces, of which the superamphiphobic variant exhibits superior performance. They significantly improve retraction of highly stable wet foams and prevention of growing dry foams, as quantified for beer and aqueous soap solution as model systems. Microscopic imaging reveals that amphiphobic nano-protrusions directly destabilize contacting foam bubbles, which can favorably vent through air gaps warranted by a Cassie wetting state. This mode of interfacial destabilization offers untapped potential for developing efficient, low-power and sustainable foam and froth management.
Digital immunoassay for biomarker concentration quantification using solid-state nanopores
Authors: He Liqun , Tessier Daniel R. , Briggs Kyle , Tsangaris Matthaios , Charron Martin , McConnell Erin M. , Lomovtsev Dmytro , Tabard-Cossa Vincent 
Published: September 2021

ABSTRACTSingle-molecule counting is the most accurate and precise method for determining the concentration of a biomarker in solution and is leading to the emergence of digital diagnostic platforms enabling precision medicine. In principle, solid-state nanopores—fully electronic sensors with single-molecule sensitivity—are well suited to the task. Here we present a digital immunoassay scheme capable of reliably quantifying the concentration of a target protein in complex biofluids that overcomes specificity, sensitivity, and consistency challenges associated with the use of solid-state nanopores for protein sensing. This is achieved by employing easily-identifiable DNA nanostructures as proxies for the presence (“1”) or absence (“0”) of the target protein captured via a magnetic bead-based sandwich immunoassay. As a proof-of-concept, we demonstrate quantification of the concentration of thyroid-stimulating hormone from human serum samples down to the high femtomolar range. Further optimization to the method will push sensitivity and dynamic range, allowing for development of precision diagnostic tools compatible with point-of-care format.
Unconventional supercurrent phase in Ising superconductor Josephson junction with atomically thin magnetic insulator
Authors: Idzuchi H. , Pientka F. , Huang K.-F. , Harada K. , Gül Ö. , Shin Y. J. , Nguyen L. T. , Jo N. H. , Shindo D. , Cava R. J. , Canfield P. C. , Kim P. 
Published: September 2021

AbstractIn two-dimensional (2D) NbSe2 crystal, which lacks inversion symmetry, strong spin-orbit coupling aligns the spins of Cooper pairs to the orbital valleys, forming Ising Cooper pairs (ICPs). The unusual spin texture of ICPs can be further modulated by introducing magnetic exchange. Here, we report unconventional supercurrent phase in van der Waals heterostructure Josephson junctions (JJs) that couples NbSe2 ICPs across an atomically thin magnetic insulator (MI) Cr2Ge2Te6. By constructing a superconducting quantum interference device (SQUID), we measure the phase of the transferred Cooper pairs in the MI JJ. We demonstrate a doubly degenerate nontrivial JJ phase (ϕ), formed by momentum-conserving tunneling of ICPs across magnetic domains in the barrier. The doubly degenerate ground states in MI JJs provide a two-level quantum system that can be utilized as a new dissipationless component for superconducting quantum devices. Our work boosts the study of various superconducting states with spin-orbit coupling, opening up an avenue to designing new superconducting phase-controlled quantum electronic devices.
TNK1 is a ubiquitin-binding and 14-3-3-regulated kinase that can be targeted to block tumor growth
Authors: Chan Tsz-Yin , Egbert Christina M. , Maxson Julia E. , Siddiqui Adam , Larsen Logan J. , Kohler Kristina , Balasooriya Eranga Roshan , Pennington Katie L. , Tsang Tsz-Ming , Frey Madison , Soderblom Erik J. , Geng Huimin , Müschen Markus , Forostyan Tetyana V. , Free Savannah , Mercenne Gaelle , Banks Courtney J. , Valdoz Jonard , Whatcott Clifford J. , Foulks Jason M. , Bearss David J. , O’Hare Thomas , Huang David C. S. , Christensen Kenneth A. , Moody James , Warner Steven L. , Tyner Jeffrey W. , Andersen Joshua L. 
Published: September 2021

AbstractTNK1 is a non-receptor tyrosine kinase with poorly understood biological function and regulation. Here, we identify TNK1 dependencies in primary human cancers. We also discover a MARK-mediated phosphorylation on TNK1 at S502 that promotes an interaction between TNK1 and 14-3-3, which sequesters TNK1 and inhibits its kinase activity. Conversely, the release of TNK1 from 14-3-3 allows TNK1 to cluster in ubiquitin-rich puncta and become active. Active TNK1 induces growth factor-independent proliferation of lymphoid cells in cell culture and mouse models. One unusual feature of TNK1 is a ubiquitin-association domain (UBA) on its C-terminus. Here, we characterize the TNK1 UBA, which has high affinity for poly-ubiquitin. Point mutations that disrupt ubiquitin binding inhibit TNK1 activity. These data suggest a mechanism in which TNK1 toggles between 14-3-3-bound (inactive) and ubiquitin-bound (active) states. Finally, we identify a TNK1 inhibitor, TP-5801, which shows nanomolar potency against TNK1-transformed cells and suppresses tumor growth in vivo.
Locus specific epigenetic modalities of random allelic expression imbalance
Authors: Marion-Poll Lucile , Forêt Benjamin , Zielinski Dina , Massip Florian , Attia Mikael , Carter Ava C. , Syx Laurène , Chang Howard Y. , Gendrel Anne-Valerie , Heard Edith 
Published: September 2021

AbstractMost autosomal genes are thought to be expressed from both alleles, with some notable exceptions, including imprinted genes and genes showing random monoallelic expression (RME). The extent and nature of RME has been the subject of debate. Here we investigate the expression of several candidate RME genes in F1 hybrid mouse cells before and after differentiation, to define how they become persistently, monoallelically expressed. Clonal monoallelic expression is not present in embryonic stem cells, but we observe high frequencies of monoallelism in neuronal progenitor cells by assessing expression status in more than 200 clones. We uncover unforeseen modes of allelic expression that appear to be gene-specific and epigenetically regulated. This non-canonical allelic regulation has important implications for development and disease, including autosomal dominant disorders and opens up therapeutic perspectives.
DnaJC7 binds natively folded structural elements in tau to inhibit amyloid formation
Authors: Hou Zhiqiang , Wydorski Pawel M. , Perez Valerie A. , Mendoza-Oliva Aydé , Ryder Bryan D. , Mirbaha Hilda , Kashmer Omar , Joachimiak Lukasz A. 
Published: September 2021

AbstractMolecular chaperones, including Hsp70/J-domain protein (JDP) families, play central roles in binding substrates to prevent their aggregation. How JDPs select different conformations of substrates remains poorly understood. Here, we report an interaction between the JDP DnaJC7 and tau that efficiently suppresses tau aggregation in vitro and in cells. DnaJC7 binds preferentially to natively folded wild-type tau, but disease-associated mutants in tau reduce chaperone binding affinity. We identify that DnaJC7 uses a single TPR domain to recognize a β-turn structural element in tau that contains the 275VQIINK280 amyloid motif. Wild-type tau, but not mutant, β-turn structural elements can block full-length tau binding to DnaJC7. These data suggest DnaJC7 preferentially binds and stabilizes natively folded conformations of tau to prevent tau conversion into amyloids. Our work identifies a novel mechanism of tau aggregation regulation that can be exploited as both a diagnostic and a therapeutic intervention.
Coexistence of resistance oscillations and the anomalous metal phase in a lithium intercalated TiSe2 superconductor
Authors: Liao Menghan , Wang Heng , Zhu Yuying , Shang Runan , Rafique Mohsin , Yang Lexian , Zhang Hao , Zhang Ding , Xue Qi-Kun 
Published: September 2021

AbstractSuperconductivity and charge density wave (CDW) appear in the phase diagram of a variety of materials including the high-Tc cuprate family and many transition metal dichalcogenides (TMDs). Their interplay may give rise to exotic quantum phenomena. Here, we show that superconducting arrays can spontaneously form in TiSe2–a TMD with coexisting superconductivity and CDW—after lithium ion intercalation. We induce a superconducting dome in the phase diagram of LixTiSe2 by using the ionic solid-state gating technique. Around optimal doping, we observe magnetoresistance oscillations, indicating the emergence of periodically arranged domains. In the same temperature, magnetic field and carrier density regime where the resistance oscillations occur, we observe signatures for the anomalous metal—a state with a resistance plateau across a wide temperature range below the superconducting transition. Our study not only sheds further insight into the mechanism for the periodic electronic structure, but also reveals the interplay between the anomalous metal and superconducting fluctuations.
A barbed end interference mechanism reveals how capping protein promotes nucleation in branched actin networks
Authors: Funk Johanna , Merino Felipe , Schaks Matthias , Rottner Klemens , Raunser Stefan , Bieling Peter 
Published: September 2021

AbstractHeterodimeric capping protein (CP/CapZ) is an essential factor for the assembly of branched actin networks, which push against cellular membranes to drive a large variety of cellular processes. Aside from terminating filament growth, CP potentiates the nucleation of actin filaments by the Arp2/3 complex in branched actin networks through an unclear mechanism. Here, we combine structural biology with in vitro reconstitution to demonstrate that CP not only terminates filament elongation, but indirectly stimulates the activity of Arp2/3 activating nucleation promoting factors (NPFs) by preventing their association to filament barbed ends. Key to this function is one of CP’s C-terminal “tentacle” extensions, which sterically masks the main interaction site of the terminal actin protomer. Deletion of the β tentacle only modestly impairs capping. However, in the context of a growing branched actin network, its removal potently inhibits nucleation promoting factors by tethering them to capped filament ends. End tethering of NPFs prevents their loading with actin monomers required for activation of the Arp2/3 complex and thus strongly inhibits branched network assembly both in cells and reconstituted motility assays. Our results mechanistically explain how CP couples two opposed processes—capping and nucleation—in branched actin network assembly.
Global increase in tropical cyclone rain rate
Authors: Guzman Oscar , Jiang Haiyan 
Published: September 2021

AbstractTheoretical models of the potential intensity of tropical cyclones (TCs) suggest that TC rainfall rates should increase in a warmer environment but limited observational evidence has been studied to test these hypotheses on a global scale. The present study explores the general trends of TC rainfall rates based on a 19-year (1998–2016) time series of continuous observational data collected by the Tropical Rainfall Measuring Mission and the Global Precipitation Measurement mission. Overall, observations exhibit an increasing trend in the average TC rainfall rate of about 1.3% per year, a fact that is contributed mainly by the combined effect of the reduction in the inner-core rainfall rate with the increase in rainfall rate on the rainband region. We found that the increasing trend is more pronounced in the Northwestern Pacific and North Atlantic than in other global basins, and it is relatively uniform for all TC intensities. Further analysis shows that these trends are associated with increases in sea surface temperature and total precipitable water in the TC environment.
Corneal nerve fiber loss relates to cognitive impairment in patients with Parkinson’s disease
Authors: Che Ning-Ning , Jiang Qiu-Huan , Ding Guan-Xiao , Chen Si-Yuan , Zhao Zhen-Xiang , Li Xue , Malik Rayaz A. , Ma Jian-Jun , Yang Hong-Qi 
Published: September 2021

AbstractCognitive impairment in Parkinson’s disease (PD) adversely influences quality of life. There is currently no available biomarker to predict cognitive decline in PD. Corneal confocal microscopy (CCM) has been used as a non-invasive tool for quantifying small nerve damage in PD. The present study investigated whether corneal nerve measures were associated with cognitive function in PD. Patients with PD were classified into those with normal cognitive function (PD-CN), mild cognitive impairment (PD-MCI), and dementia (PDD). Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL) were quantified with CCM and compared with a control group. Sixty-five PD patients and thirty controls were studied. CNFD was decreased and CNBD was increased in PD patients compared to controls (P < 0.05). CNBD and CNBD/CNFD ratio was higher in PD-CN compared to controls. CNFD was positively correlated with the Montreal cognitive assessment (MoCA) score (r = 0.683, P < 0.001), but negatively associated with unified Parkinson disease rating scale (UPDRS)-part III (r = −0.481, P < 0.001) and total UPDRS scores (r = −0.401, P = 0.001) in PD patients. There was no correlation between CNFD and Levodopa equivalent daily dose (LEDD) (r = 0.176, P = 0.161). CNFD, CNBD, CNFL, and CNBD/CNFD ratio was lower with increasing Hoehn and Yahr stage. PD patients show evidence of corneal nerve loss compared with controls and corneal nerve parameters are associated with the severity of cognitive and motor dysfunction in PD. CCM could serve as an objective in vivo ophthalmic imaging technique to assess neurodegeneration in PD.
Child and caregiver experiences and perceptions of asthma self-management
Authors: Kelada Lauren , Molloy Charlotte J. , Hibbert Peter , Wiles Louise K. , Gardner Claire , Klineberg Emily , Braithwaite Jeffrey , Jaffe Adam 
Published: September 2021

AbstractAsthma is the most common chronic condition of childhood. Self-management is integral to good asthma control. This qualitative paper explores how children with asthma and their parents perceive asthma, their experience with asthma, and how they manage symptoms, preventions and medications within and outside the home. We undertook 15 focus groups with 41 school-aged (6–11 years) children with asthma and 38 parents. Parents and their children attended the same focus groups. We used thematic analysis to analyse the transcripts. Our findings show the impact asthma can have on children’s social and emotional wellbeing and highlight how reliant school-aged children are on their parents to effectively manage their asthma. Parents reported being unsure when their child’s symptoms warranted visiting their doctor or hospital. Schools were identified as a source of difficulty regarding asthma management; families reported that children may be self-conscious about their asthma and using their inhaler at school. School policies and teachers’ lack of asthma knowledge were reported to exacerbate children’s reluctance to use their inhaler at school. Our results have implications for the design and implementation of children’s self-management interventions for their asthma, particularly when they are at school and away from their parents.
Targeting exertional breathlessness to improve physical activity: the role of primary care
Authors: Román-Rodríguez Miguel , Kocks Janwillem W. H. 
Published: September 2021

AbstractPrimary care physicians (PCPs) play a crucial role in the diagnosis and management of chronic obstructive pulmonary disease (COPD). By working together with patients to target exertional breathlessness and increase physical activity, PCPs have an important role to play, early in the disease course, in improving patient outcomes in both the short and long term. In this article, we consider how physical activity affects disease progression from the PCP perspective. We discuss the role of pharmacological therapy, the importance of an holistic approach and the role of PCPs in assessing and promoting physical activity. The complexity and heterogeneity of COPD make it a challenging disease to treat. Patients’ avoidance of activity, and subsequent decline in capacity to perform it, further impacts the management of the disease. Improving patient tolerance of physical activity, increasing participation in daily activities and helping patients to remain active are clear goals of COPD management. These may require an holistic approach to management, including pulmonary rehabilitation and psychological programmes in parallel with bronchodilation therapy, in order to address both physiological and behavioural factors. PCPs have an important role to optimise therapy, set goals and communicate the importance of maintaining physical activity to their patients. In addition, optimal treatment that addresses activity-related breathlessness can help prevent the downward spiral of inactivity and get patients moving again, to improve their overall health and long-term prognosis.
All-optical polarization and amplitude modulation of second-harmonic generation in atomically thin semiconductors
Authors: Klimmer Sebastian , Ghaebi Omid , Gan Ziyang , George Antony , Turchanin Andrey , Cerullo Giulio , Soavi Giancarlo 
Published: September 2021

AbstractSecond-harmonic generation is of paramount importance in several fields of science and technology, including frequency conversion, self-referencing of frequency combs, nonlinear spectroscopy and pulse characterization. Advanced functionalities are enabled by modulation of the harmonic generation efficiency, which can be achieved with electrical or all-optical triggers. Electrical control of the harmonic generation efficiency offers large modulation depth at the cost of low switching speed, by contrast to all-optical nonlinear devices, which provide high speed and low modulation depth. Here we demonstrate all-optical modulation of second-harmonic generation in MoS2 with a modulation depth of close to 100% and speed limited only by the fundamental pulse duration. This result arises from a combination of D3h crystal symmetry and the deep subwavelength thickness of the sample, it can therefore be extended to the whole family of transition metal dichalcogenides to provide great flexibility in the design of advanced nonlinear optical devices such as high-speed integrated frequency converters, broadband autocorrelators for ultrashort pulse characterization, and tunable nanoscale holograms.
The largest and earliest known sample of dental caries in an extinct mammal (Mammalia, Euarchonta, Microsyops latidens) and its ecological implications
Authors: Selig Keegan R. , Silcox Mary T. 
Published: September 2021

AbstractDental cavities or caries is a common disease among modern humans, affecting almost every adult. Caries frequency has been used to study dietary change in humans over time, based on an inferred tie between the incidence of caries and a carbohydrate-rich diet. However, the disease is not unique to our species. Among non-human primates, there is also variation in caries frequency associated with diet, suggesting that this metric may provide a mechanism for studying diet in broader contexts, and across geological time. To date, very few studies have examined caries among fossil mammals, and none have done so among Eocene mammals. Here, we present our analysis of the largest sample to date of fossil caries in a single extinct mammal species,Microsyops latidens, a stem primate from the early Eocene, which is known from over a thousand specimens from the Southern Bighorn Basin of Wyoming (n = 1030). Our results show thatMicrosyops latidensis characterized by a high prevalence of dental caries (7.48% of individuals), with notable variation through time, reaching 17.24% of individuals from a particular interval. This interval is also associated with a change in overall dental form, as quantified by dental topographic analysis, which measures functional aspects of the chewing surface of teeth. These observations suggest that this species experienced a shift in their diet to include more fruit or other sugar rich-foods for a short period. Our analysis, therefore, suggests that the diet ofM. latidensfluctuated over time, as well as providing a framework for assessing caries in other fossil taxa.