bluuebunny/crossref_metadata_2025 huggingface dataset:
Only in Africa
Authors: Owen-Smith Norman
Published: September 2021

That humans originated from Africa is well-known. However, this is widely regarded as a chance outcome, dependant simply on where our common ancestor shared the land with where the great apes lived. This volume builds on from the 'Out of Africa' theory, and takes the view that it is only in Africa that the evolutionary transitions from a forest-inhabiting frugivore to savanna-dwelling meat-eater could have occurred. This book argues that the ecological circumstances that shaped these transitions are exclusive to Africa. It describes distinctive features of the ecology of Africa, with emphasis on savanna grasslands, and relates them to the evolutionary transitions linking early ape-men to modern humans. It shows how physical features of the continent, especially those derived from plate tectonics, set the foundations. This volume adequately conveys that we are here because of the distinctive features of the ecology of Africa.
If you've earned it, you deserve it: ultimatums, with Lego
Authors: Oliver Adam
Published: September 2021

The ultimatum and dictator games were developed to help identify the fundamental motivators of human behavior, typically by asking participants to share windfall endowments with other persons. In the ultimatum game, a common observation is that proposers offer, and responders refuse to accept, a much larger share of the endowment than is predicted by rational choice theory. However, in the real world, windfalls are rare: money is usually earned. I report here a small study aimed at testing how participants react to an ultimatum game after they have earned their endowments by either building a Lego model or spending some time sorting out screws by their length. I find that the shares that proposers offer and responders accept are significantly lower than that typically observed with windfall money, an observation that is intensified when the task undertaken to earn the endowment is generally less enjoyable and thus perhaps more effortful (i.e., screw sorting compared to Lego building). I suggest, therefore, that considerations of effort-based desert are often important drivers behind individual decision-making, and that laboratory experiments, if intended to inform public policy design and implementation, ought to mirror the broad characteristics of the realities that people face.
Willingness to Work amongst Australian Frontline Healthcare Workers during Australia’s First Wave of Covid-19 Community Transmission: Results of an Online Survey
Authors: Hill Michella , Smith Erin , Mills Brennen
Published: September 2021

Objectives:

The majority of research investigating healthcare workers’ (HCWs) willingness to work during public health emergencies, asks participants to forecast their perceptions based on hypothetical emergencies, rather than in response to the actual public health emergencies they have experienced. This research explored frontline HCWs willingness to work during Australia’s first wave of the COVID-19 pandemic among frontline HCWs.

Methods:

Participants (n = 580) completed an online questionnaire regarding their willingness to work during the pandemic.

Results:

A total of 42% of participants reported being less willing to work during the pandemic compared to before. Availability of personal protective equipment (PPE), concern expressed by family members, and viral exposure were significant barriers. A third of participants disagreed that some level of occupational risk for exposure to infectious disease was acceptable while a quarter of participants had received communications from their workplace concerning obligations to work during COVID-19.

Conclusions:

The COVID-19 pandemic has impacted Australian frontline HCWs’ willingness to work. Scarcity of PPE and exposure to the virus were the most cited reasons impacting on willingness to work. Appropriate policies and practices should be implemented and communicated efficiently to frontline HCW’s. This research provides insight into the lived experiences of Australian healthcare professionals’ willingness to work during a pandemic.
Strongly aperiodic subshifts of finite type on hyperbolic groups
Authors: COHEN DAVID B. , GOODMAN-STRAUSS CHAIM , RIECK YO’AV
Published: September 2021

We prove that a hyperbolic group admits a strongly aperiodic subshift of finite type if and only if it has at most one end.
Wood and bark lignin contents of trees from deciduous forests of eastern India
Authors: Deb Debal , Roy Priyabrata
Published: September 2021

Lignin is a polyphenolic compound found in plant tissues, especially wood and bark. The lignin content determines the quality of wood biochar in agroecological uses, and is used in the production of synthetic resins and adhesives. Despite its importance in plant physiology and its agricultural and industrial utility, there exists a wide gap of knowledge of lignin contents of tropical hardwood trees of South Asia, except for a few species. We present here the first estimation of lignin content in wood and bark of 48 species from tropical deciduous forests of India. We show that some species are characterized by greater wood lignin (WL) compared with bark lignin (BL) content, contrary to the generalization held for hardwood trees, and suggest a plausible correspondence between the WL to BL ratio and timber quality.
Hanan v. Germany (Eur. Ct. H.R.)
Authors: Mehta Kalika
Published: September 2021

In February 2021, the Grand Chamber of the European Court of Human Rights (ECtHR) ruled in favor of Germany in the case Hanan v. Germany, concerning a 2009 NATO airstrike in Kunduz (Afghanistan) resulting in the deaths of many civilians.
A NOTE ON CIRIS 118
Authors: Olszaniec Włodzimierz
Published: September 2021

This note offers a new emendation in the Ciris. The author suggests that the text of line 118 should read: deicere et indomita Minoa retundere mente.
RETIRE WITH THANKS: RETHINKING LUCRETIUS 3.962
Authors: Takeshita Tetsufumi
Published: September 2021

This article aims at proposing a solution to one of the well-known textual cruces in Lucretius’ De rerum natura. After a brief survey of the suggested emendations, the author will shed some fresh light on Manning's gratus, which recent editors have curiously neglected. The idea that the old man should retire from life with thanks is not uncommon among classical writers. In addition, parallel expressions are also found in Epicurus’ own words. This article concludes that gratus is what we would expect in the last line of Nature's admonition in De rerum natura and, therefore, the most probable emendation.
The Río Grío–Pancrudo Fault Zone (central Iberian Chain, Spain): recent extensional activity revealed by drainage reversal
Authors: Peiro Alba , Simón José L.
Published: September 2021

The NNW–SSE-trending extensional Río Grío–Pancrudo Fault Zone is a large-scale structure that obliquely cuts the Neogene NW–SE Calatayud Basin. Its negative inversion during the Neogene–Quaternary extension gave rise to structural and geomorphological rearrangement of the basin margin. Geological mapping has allowed two right-relayed fault segments to be distinguished, whose recent extensional activity has been mainly characterized using a deformed planation surface (Fundamental Erosion Surface (FES) 3; 3.5 Ma) as a geomorphic marker. Normal slip along the Río Grío–Lanzuela Fault Segment has induced hanging-wall tilting, subsequent drainage reversal at the Güeimil valley after the Pliocene–Pleistocene transition, as well as morphological scarps and surficial ruptures in Pleistocene materials. In this sector, an offset of FES3 indicates a total throw ofc. 240 m, resulting in a slip rate of 0.07 mm a–1, while retrodeformation of hanging-wall tilting affecting a younger piedmont surface allows the calculation of a minimum throw in the range of 140–220 m after the Pliocene–Pleistocene transition, with a minimum slip rate of 0.07–0.11 mm a–1. For the late Pleistocene period, vertical displacement ofc. 20 m of a sedimentary level dated to 66.6 ± 6.5 ka yields a slip rate approaching 0.30–0.36 mm a–1. At the Cucalón–Pancrudo Fault Segment, the offset of FES3 allows the calculation of a maximum vertical slip of 300 m for the last 3.5 Ma, and hence a net slip rate close to 0.09 mm a–1. Totallingc. 88 km in length, the Río Grío–Pancrudo Fault Zone could be the largest recent macrostructure in the Iberian Chain, probably active, with the corresponding undeniable seismogenic potential.
Converbs in heritage Turkish: A contrastive approach
Authors: Iefremenko Kateryna , Schroeder Christoph , Kornfilt Jaklin
Published: September 2021

Turkish expresses adverbial subordination predominantly by means of converb clauses. These are headed by nonfinite verbs, i.e. converbs, which have a converb suffix attached to the stem. The different converbs express different aspectual relations between the subordinate and the superordinate clause, and they can be modifying or non-modifying. We analyse data from speakers of Turkish as a heritage language in Germany and the U.S. as well as monolingual speakers of Turkish in Turkey. The data come from two age groups: adults and adolescents. We show that unlike in canonical Turkish, converbs in heritage Turkish can be multifunctional, meaning that they can express both simultaneity and causality, for example. Furthermore, we show that converbs in heritage Turkish can be both modifying and non-modifying. As possible factors which might be responsible for such variation, we discuss language contact, sociolinguistic differences between the speaker communities (Germany vs. the U.S.) and age of the speakers.
Role of saliva use during masturbation in the transmission of Chlamydia trachomatis in men who have sex with men
Authors: Xu Xianglong , Chow Eric P.F. , Regan David , Ong Jason J. , Gray Richard T. , Zhou Pingyu , Fairley Christopher K. , Zhang Lei
Published: September 2021

Masturbation is a common sexual practice in men, and saliva is often used as a lubricant during masturbation by men who have sex with men. However, the role of saliva use during masturbation in the transmission of chlamydia is still unclear. We developed population-level, susceptible-infected-susceptible compartmental models to explore the role of saliva use during masturbation on the transmission of chlamydia at multiple anatomical sites. In this study, we simulated both solo masturbation and mutual masturbation. Our baseline model did not include masturbation but included transmission routes (anal sex, oral-penile sex, rimming, kissing and sequential sexual practices) we have previously validated (model 1). We added masturbation to model 1 to develop the second model (model 2). We calibrated the model to five clinical datasets separately to assess the effects of masturbation on the prevalence of site-specific infection. The inclusion of masturbation (model 2) significantly worsened the ability of the models to replicate the prevalence of C. trachomatis. Using model 2 and the five data sets, we estimated that saliva use during masturbation was responsible for between 3.9% [95% confidence interval (CI) 2.0–6.8] and 6.2% (95% CI 3.8–10.5) of incident chlamydia cases at all sites. Our models suggest that saliva use during masturbation is unlikely to play a major role in chlamydia transmission between men, and even if it does have a role, about one in seven cases of urethral chlamydia might arise from masturbation.
Truncal valve leaflet reconstruction with autologous pericardium in a neonate
Authors: Ishidou Motonori , Ikai Akio , Sakamoto Kisaburo
Published: September 2021

A boy diagnosed with persistent truncus arteriosus and severe truncal valve regurgitation had uncontrollable heart failure. Thus, truncal valve repair, ventricular septal defect closure, and right ventricular outflow tract reconstruction were performed on the second day of life. We report about a neonate with severe truncal valve regurgitation who was successfully treated with autologous pericardial truncal valve leaflet reconstruction.
‘An Amazing Want of Christianity’: Bishop Samuel Wilberforce and John Henry Newman’s Tense Relationship
Authors: Grosclaude Jérôme
Published: September 2021

This paper will examine the relationship between Samuel Wilberforce and John Henry Newman. The two priests had a common cause in their wish to see the Church of England rediscover its Catholic identity – which led them to work alongside one another at the beginning of the Oxford Movement – but quickly drifted apart because of their strong divergences on the nature of the Church and the place of Tradition, as well as Samuel Wilberforce’s strong hostility to Rome. The paper also examines the place of Samuel Wilberforce’s young brother in this relationship.
The People of God, Discipleship and Ministry in the Anglican Church Today and Tomorrow
Authors: Littleton John
Published: September 2021

People of God is a well-known biblical term used to describe and understand the inclusive, holistic and serving nature of the Christian Church. Currently, members of the worldwide Anglican Communion are discussing discipleship and ministry. This paper explores the deep connection between describing the church as the People of God and the practice of discipleship and ministry. That exploration occurs through an examination of the considerable literature on the topic, and by discussing discipleship and ministry in light of understanding the church as the People of God. Discoveries made from the journey may surprise. Suggestions for church practice emerged with implications for: ecclesial language; parish ministry and mission; the processes of Anglican Diocesan Synods; and potential outcomes for the 2022 Lambeth Conference.
On the morphospace of eurypterine sea scorpions
Authors: BICKNELL Russell D. C. , AMATI Lisa
Published: September 2021

Eurypterids (sea scorpions) are a group of extinct, marine euchelicerates that have an extensive Palaeozoic record. Despite lacking a biomineralised exoskeleton, eurypterids are abundantly preserved within select deposits. These collections make statistical analyses comparing the morphology of different genera possible. However, eurypterid shape has not yet been documented with modern geometric morphometric tools. Here, we summarise the previous statistical assessments of eurypterid morphology and expand this research by presenting landmark and semi-landmark analyses of 115 eurypterid specimens within the suborder Eurypterina. We illustrate that lateral compound eye morphology and position drives specimen placement in morphospace and separates proposed apex predators from more generalist forms. Additionally, evidence for size clusters inEurypterusthat may reflect ontogeny is uncovered. We highlight the use of geometric morphometric analyses in supporting the naming of new taxa and demonstrate that these shape data represent a novel means of understanding inter-generic ontogenetic trajectories and uncovering developmental changes within the diverse euarthropod group.
Two-Eyed Seeing and developmental origins of health and disease studies with indigenous partners
Authors: Liberda Eric N. , Zuk Aleksandra M. , Davey Roger , Edwards-Wheesk Ruby , Tsuji Leonard J. S.
Published: September 2021

Globally, mortality of Indigenous persons is greater than that of their non-Indigenous counterparts, which has been shown to be disproportionately attributable to non-communicable diseases. The historically subordinate position that Indigenous Knowledge (IK) held in comparison to Western science has shifted over the last several decades, with the credibility and importance of IK now being internationally recognized. Herein, we examine how Marsahall’s (2014) Two-Eyed Seeing can foster collaborative and culturally relevant Developmental Origins of Health and Disease (DOHaD) studies for health and well-being by using ‘..the best in Indigenous ways of knowing…[and] the best in Western (or mainstream) ways of knowing…and learn to use both these eyes for the benefit of all.’ At its core, Two-Eyed Seeing also includes the principles of ownership, control, access and possession, and Community-Based Participatory Research, which further reinforces the critical role of Indigenous peoples taking active roles in DOHaD research. Additionally, we also present a partnership model for working with Indigenous communities that includes the principles of respect, equity and empowerment. As researchers begin to fill the gap in Indigenous health, we outline how Two-Eyed Seeing should form the basis of DOHaD studies involving Indigenous communities. This model can be used to develop and guide projects that result in robust and meaningful participatory partnerships that have impactful uptake of research findings.
Optimizing chloroacetamide application timing in dicamba-resistant cotton production systems for control of glyphosate-resistant Palmer amaranth (Amaranthus palmeri)
Authors: Buol John T. , Franca Lucas X. , Dodds Darrin M. , Mills J. Anthony , DuBien Janice L. , Brown-Johnson Ashli E. , Shaw David R. , Reynolds Daniel B.
Published: September 2021

A chloroacetamide herbicide by application timing factorial experiment was conducted in 2017 and 2018 in Mississippi to investigate chloroacetamide use in a dicamba-based Palmer amaranth management program in cotton production. Herbicides used were S-metolachlor or acetochlor, and application timings were preemergence, preemergence followed by (fb) early postemergence, preemergence fb late postemergence, early postemergence alone, late postemergence alone, and early postemergence fb late postemergence. Dicamba was included in all preemergence applications, and dicamba plus glyphosate was included with all postemergence applications. Differences in cotton and weed response due to chloroacetamide type were minimal, and cotton injury at 14 d after late postemergence application was less than 10% for all application timings. Late-season weed control was reduced up to 30% and 53% if chloroacetamide application occurred preemergence or late postemergence only, respectively. Late-season weed densities were minimized if multiple applications were used instead of a single application. Cotton height was reduced by up to 23% if a single application was made late postemergence relative to other application timings. Chloroacetamide application at any timing except preemergence alone minimized late-season weed biomass. Yield was maximized by any treatment involving multiple applications or early postemergence alone, whereas applications preemergence or late postemergence alone resulted in up to 56% and 27% yield losses, respectively. While no yield loss was reported by delaying the first of sequential applications until early postemergence, forgoing a preemergence application is not advisable given the multiple factors that may delay timely postemergence applications such as inclement weather.
Response of broadleaf and grass cover crop species to soil residues of glyphosate and aminomethylphosphonic acid (AMPA)
Authors: Ganie Zahoor A. , Jhala Amit J.
Published: September 2021

Glyphosate is the most widely used herbicide in the United States; however, concern is escalating about increasing residues of glyphosate and its metabolite aminomethylphosphonic acid (AMPA) in soil. There is a lack of scientific literature examining the response of cover crops to soil residues of glyphosate or AMPA. The objectives of this study were to evaluate the impact of glyphosate or AMPA residues in silty clay loam soil on emergence, growth, and biomass of cover crops, including cereal rye, crimson clover, field pea, hairy vetch, and winter wheat, as well as their germination in a 0.07% (0.7 g L–1) solution of AMPA or glyphosate. Greenhouse studies were conducted at the University of Nebraska–Lincoln to determine the dose response of broadleaf and grass cover crops to soil-applied glyphosate or AMPA. The results indicated that soil treated with glyphosate or AMPA up to 105 mg ae kg–1 of soil had no effect on the emergence, growth, above-ground biomass, and root biomass of any of the cover crop species tested. To evaluate the impact of AMPA or glyphosate on the seed germination of cover crop species, seeds were soaked in Petri plates filled with a 0.7 g L–1 solution of AMPA or glyphosate. There was no effect of AMPA on seed germination of any of the cover crop species tested. Seed germination of crimson clover and field pea in a 0.7 g L–1 solution of glyphosate was comparable to the nontreated control; however, the germination of cereal rye, hairy vetch, and winter wheat was reduced by 48%, 75%, and 66%, respectively, compared to the nontreated control. The results suggested that glyphosate or AMPA up to 105 mg ae kg–1 in silt clay loam soil is unlikely to cause any negative effect on the evaluated cover crop species.
The Microbiology of Metal Mine Waste: Bioremediation Applications and Implications for Planetary Health
Authors: Newsome Laura , Falagán Carmen
Published: September 2021

Mine wastes pollute the environment with metals and metalloids in toxic concentrations, causing problems for humans and wildlife. Microorganisms colonize and inhabit mine wastes, and can influence the environmental mobility of metals through metabolic activity, biogeochemical cycling and detoxification mechanisms. In this article we review the microbiology of the metals and metalloids most commonly associated with mine wastes: arsenic, cadmium, chromium, copper, lead, mercury, nickel and zinc. We discuss the molecular mechanisms by which bacteria, archaea, and fungi interact with contaminant metals and the consequences for metal fate in the environment, focusing on long‐term field studies of metal‐impacted mine wastes where possible. Metal contamination can decrease the efficiency of soil functioning and essential element cycling due to the need for microbes to expend energy to maintain and repair cells. However, microbial communities are able to tolerate and adapt to metal contamination, particularly when the contaminant metals are essential elements that are subject to homeostasis or have a close biochemical analog. Stimulating the development of microbially reducing conditions, for example in constructed wetlands, is beneficial for remediating many metals associated with mine wastes. It has been shown to be effective at low pH, circumneutral and high pH conditions in the laboratory and at pilot field‐scale. Further demonstration of this technology at full field‐scale is required, as is more research to optimize bioremediation and to investigate combined remediation strategies. Microbial activity has the potential to mitigate the impacts of metal mine wastes, and therefore lessen the impact of this pollution on planetary health.
Estimating Dispersion Coefficient in Flow Through Heterogeneous Porous Media by a Deep Convolutional Neural Network
Authors: Kamrava Serveh , Im Jinwoo , de Barros Felipe P. J. , Sahimi Muhammad
Published: September 2021

Estimating the longitudinal dispersion coefficient in flow through heterogeneous porous media is paramount to many problems in geological formations. Moreover, although it is well‐known that is sensitive to the morphology of such formations, it has been very difficult to establish a firm link between the two. We describe a novel deep convolutional neural network (DCNN) for estimating . The inputs for training of the network are a large and diverse set of data consisting of three‐dimensional images of porous media, as well as their porosity, and the associated values computed by random‐walk particle‐tracking (RWPT) simulations. The trained network predicts very rapidly, and its predictions are in excellent agreement with the data not used in the training. Thus, a combination of the DCNN and RWPT simulation provides a powerful tool for studying many flow‐related phenomena in geological formations, and estimating their properties.
Intron retention-induced neoantigen load correlates with unfavorable prognosis in multiple myeloma
Authors: Dong Chuanpeng , Cesarano Annamaria , Bombaci Giuseppe , Reiter Jill L. , Yu Christina Y. , Wang Yue , Jiang Zhaoyang , Zaid Mohammad Abu , Huang Kun , Lu Xiongbin , Walker Brian A. , Perna Fabiana , Liu Yunlong
Published: September 2021

Neoantigen peptides arising from genetic alterations may serve as targets for personalized cancer vaccines and as positive predictors of response to immune checkpoint therapy. Mutations in genes regulating RNA splicing are common in hematological malignancies leading to dysregulated splicing and intron retention (IR). In this study, we investigated IR as a potential source of tumor neoantigens in multiple myeloma (MM) patients and the relationship of IR-induced neoantigens (IR-neoAg) with clinical outcomes. MM-specific IR events were identified in RNA-sequencing data from the Multiple Myeloma Research Foundation CoMMpass study after removing IR events that also occurred in normal plasma cells. We quantified the IR-neoAg load by assessing IR-induced novel peptides that were predicted to bind to major histocompatibility complex (MHC) molecules. We found that high IR-neoAg load was associated with poor overall survival in both newly diagnosed and relapsed MM patients. Further analyses revealed that poor outcome in MM patients with high IR-neoAg load was associated with high expression levels of T-cell co-inhibitory molecules and elevated interferon signaling activity. We also found that MM cells exhibiting high IR levels had lower MHC-II protein abundance and treatment of MM cells with a spliceosome inhibitor resulted in increased MHC-I protein abundance. Our findings suggest that IR-neoAg may represent a novel biomarker of MM patient clinical outcome and further that targeting RNA splicing may serve as a potential therapeutic strategy to prevent MM immune escape and promote response to checkpoint blockade.
CloneSig can jointly infer intra-tumor heterogeneity and mutational signature activity in bulk tumor sequencing data
Authors: Abécassis Judith , Reyal Fabien , Vert Jean-Philippe
Published: September 2021

Systematic DNA sequencing of cancer samples has highlighted the importance of two aspects of cancer genomics: intra-tumor heterogeneity (ITH) and mutational processes. These two aspects may not always be independent, as different mutational processes could be involved in different stages or regions of the tumor, but existing computational approaches to study them largely ignore this potential dependency. Here, we present CloneSig, a computational method to jointly infer ITH and mutational processes in a tumor from bulk-sequencing data. Extensive simulations show that CloneSig outperforms current methods for ITH inference and detection of mutational processes when the distribution of mutational signatures changes between clones. Applied to a large cohort of 8,951 tumors with whole-exome sequencing data from The Cancer Genome Atlas, and on a pan-cancer dataset of 2,632 whole-genome sequencing tumor samples from the Pan-Cancer Analysis of Whole Genomes initiative, CloneSig obtains results overall coherent with previous studies.
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

We 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

The 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

Wet 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

Single-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

In 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

TNK1 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

Most 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

Molecular 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

Superconductivity 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

Heterodimeric 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

Theoretical 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

Cognitive 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

Asthma 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

Primary 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.