bluuebunny/crossref_metadata_2025_split huggingface dataset:
The androgen receptor is a therapeutic target in desmoplastic small round cell sarcoma
Authors: Lamhamedi-Cherradi Salah-Eddine , Maitituoheti Mayinuer , Menegaz Brian A. , Krishnan Sandhya , Vetter Amelia M. , Camacho Pamela , Wu Chia-Chin , Beird Hannah C. , Porter Robert W. , Ingram Davis R. , Ramamoorthy Vandhana , Mohiuddin Sana , McCall David , Truong Danh D. , Cuglievan Branko , Futreal P. Andrew , Velasco Alejandra Ruiz , Anvar Nazanin Esmaeili , Utama Budi , Titus Mark , Lazar Alexander J. , Wang Wei-Lien , Rodriguez-Aguayo Cristian , Ratan Ravin , Livingston J. Andrew , Rai Kunal , MacLeod A. Robert , Daw Najat C. , Hayes-Jordan Andrea , Ludwig Joseph A. 
Published: June 2022

AbstractDesmoplastic small round cell tumor (DSRCT) is an aggressive, usually incurable sarcoma subtype that predominantly occurs in post-pubertal young males. Recent evidence suggests that the androgen receptor (AR) can promote tumor progression in DSRCTs. However, the mechanism of AR-induced oncogenic stimulation remains undetermined. Herein, we demonstrate that enzalutamide and AR-directed antisense oligonucleotides (AR-ASO) block 5α-dihydrotestosterone (DHT)-induced DSRCT cell proliferation and reduce xenograft tumor burden. Gene expression analysis and chromatin immunoprecipitation sequencing (ChIP-seq) were performed to elucidate how AR signaling regulates cellular epigenetic programs. Remarkably, ChIP-seq revealed novel DSRCT-specific AR DNA binding sites adjacent to key oncogenic regulators, including WT1 (the C-terminal partner of the pathognomonic fusion protein) and FOXF1. Additionally, AR occupied enhancer sites that regulate the Wnt pathway, neural differentiation, and embryonic organ development, implicating AR in dysfunctional cell lineage commitment. Our findings have direct clinical implications given the widespread availability of FDA-approved androgen-targeted agents used for prostate cancer.
Jamming a terahertz wireless link
Authors: Shrestha Rabi , Guerboukha Hichem , Fang Zhaoji , Knightly Edward , Mittleman Daniel M. 
Published: June 2022

AbstractAs the demand for bandwidth in wireless communication increases, carrier frequencies will reach the terahertz (THz) regime. One of the common preconceived notions is that, at these high frequencies, signals can radiate with high directivity which inherently provides more secure channels. Here, we describe the first study of the vulnerability of these directional links to jamming, in which we identify several features that are distinct from the usual considerations of jamming at low frequencies. We show that the receiver’s use of an envelope detector provides the jammer with the ability to thwart active attempts to adapt to their attack. In addition, a jammer can exploit the broadband nature of typical receivers to implement a beat jamming attack, which allows them to optimize the efficacy of the interference even if their broadcast is detuned from the frequency of the intended link. Our work quantifies the increasing susceptibility of broadband receivers to jamming, revealing previously unidentified vulnerabilities which must be considered in the development of future wireless systems operating above 100 GHz.
Induction of synapse formation by de novo neurotransmitter synthesis
Authors: Burlingham Scott R. , Wong Nicole F. , Peterkin Lindsay , Lubow Lily , Dos Santos Passos Carolina , Benner Orion , Ghebrial Michael , Cast Thomas P. , Xu-Friedman Matthew A. , Südhof Thomas C. , Chanda Soham 
Published: June 2022

AbstractA vital question in neuroscience is how neurons align their postsynaptic structures with presynaptic release sites. Although synaptic adhesion proteins are known to contribute in this process, the role of neurotransmitters remains unclear. Here we inquire whether de novo biosynthesis and vesicular release of a noncanonical transmitter can facilitate the assembly of its corresponding postsynapses. We demonstrate that, in both stem cell-derived human neurons as well as in vivo mouse neurons of purely glutamatergic identity, ectopic expression of GABA-synthesis enzymes and vesicular transporters is sufficient to both produce GABA from ambient glutamate and transmit it from presynaptic terminals. This enables efficient accumulation and consistent activation of postsynaptic GABAA receptors, and generates fully functional GABAergic synapses that operate in parallel but independently of their glutamatergic counterparts. These findings suggest that presynaptic release of a neurotransmitter itself can signal the organization of relevant postsynaptic apparatus, which could be directly modified to reprogram the synapse identity of neurons.
Robust derivation of transplantable dopamine neurons from human pluripotent stem cells by timed retinoic acid delivery
Authors: Alekseenko Zhanna , Dias José M. , Adler Andrew F. , Kozhevnikova Mariya , van Lunteren Josina Anna , Nolbrant Sara , Jeggari Ashwini , Vasylovska Svitlana , Yoshitake Takashi , Kehr Jan , Carlén Marie , Alexeyenko Andrey , Parmar Malin , Ericson Johan 
Published: June 2022

AbstractStem cell therapies for Parkinson’s disease (PD) have entered first-in-human clinical trials using a set of technically related methods to produce mesencephalic dopamine (mDA) neurons from human pluripotent stem cells (hPSCs). Here, we outline an approach for high-yield derivation of mDA neurons that principally differs from alternative technologies by utilizing retinoic acid (RA) signaling, instead of WNT and FGF8 signaling, to specify mesencephalic fate. Unlike most morphogen signals, where precise concentration determines cell fate, it is the duration of RA exposure that is the key-parameter for mesencephalic specification. This concentration-insensitive patterning approach provides robustness and reduces the need for protocol-adjustments between hPSC-lines. RA-specified progenitors promptly differentiate into functional mDA neurons in vitro, and successfully engraft and relieve motor deficits after transplantation in a rat PD model. Our study provides a potential alternative route for cell therapy and disease modelling that due to its robustness could be particularly expedient when use of autologous- or immunologically matched cells is considered.
Cloning of the broadly effective wheat leaf rust resistance gene Lr42 transferred from Aegilops tauschii
Authors: Lin Guifang , Chen Hui , Tian Bin , Sehgal Sunish K. , Singh Lovepreet , Xie Jingzhong , Rawat Nidhi , Juliana Philomin , Singh Narinder , Shrestha Sandesh , Wilson Duane L. , Shult Hannah , Lee Hyeonju , Schoen Adam William , Tiwari Vijay K. , Singh Ravi P. , Guttieri Mary J. , Trick Harold N. , Poland Jesse , Bowden Robert L. , Bai Guihua , Gill Bikram , Liu Sanzhen 
Published: June 2022

AbstractThe wheat wild relative Aegilops tauschii was previously used to transfer the Lr42 leaf rust resistance gene into bread wheat. Lr42 confers resistance at both seedling and adult stages, and it is broadly effective against all leaf rust races tested to date. Lr42 has been used extensively in the CIMMYT international wheat breeding program with resulting cultivars deployed in several countries. Here, using a bulked segregant RNA-Seq (BSR-Seq) mapping strategy, we identify three candidate genes for Lr42. Overexpression of a nucleotide-binding site leucine-rich repeat (NLR) gene AET1Gv20040300 induces strong resistance to leaf rust in wheat and a mutation of the gene disrupted the resistance. The Lr42 resistance allele is rare in Ae. tauschii and likely arose from ectopic recombination. Cloning of Lr42 provides diagnostic markers and over 1000 CIMMYT wheat lines carrying Lr42 have been developed documenting its widespread use and impact in crop improvement.
Cryo-EM structures of Gid12-bound GID E3 reveal steric blockade as a mechanism inhibiting substrate ubiquitylation
Authors: Qiao Shuai , Lee Chia-Wei , Sherpa Dawafuti , Chrustowicz Jakub , Cheng Jingdong , Duennebacke Maximilian , Steigenberger Barbara , Karayel Ozge , Vu Duc Tung , von Gronau Susanne , Mann Matthias , Wilfling Florian , Schulman Brenda A. 
Published: June 2022

AbstractProtein degradation, a major eukaryotic response to cellular signals, is subject to numerous layers of regulation. In yeast, the evolutionarily conserved GID E3 ligase mediates glucose-induced degradation of fructose-1,6-bisphosphatase (Fbp1), malate dehydrogenase (Mdh2), and other gluconeogenic enzymes. “GID” is a collection of E3 ligase complexes; a core scaffold, RING-type catalytic core, and a supramolecular assembly module together with interchangeable substrate receptors select targets for ubiquitylation. However, knowledge of additional cellular factors directly regulating GID-type E3s remains rudimentary. Here, we structurally and biochemically characterize Gid12 as a modulator of the GID E3 ligase complex. Our collection of cryo-EM reconstructions shows that Gid12 forms an extensive interface sealing the substrate receptor Gid4 onto the scaffold, and remodeling the degron binding site. Gid12 also sterically blocks a recruited Fbp1 or Mdh2 from the ubiquitylation active sites. Our analysis of the role of Gid12 establishes principles that may more generally underlie E3 ligase regulation.
Short chain fatty acids-producing and mucin-degrading intestinal bacteria predict the progression of early Parkinson’s disease
Authors: Nishiwaki Hiroshi , Ito Mikako , Hamaguchi Tomonari , Maeda Tetsuya , Kashihara Kenichi , Tsuboi Yoshio , Ueyama Jun , Yoshida Takumi , Hanada Hiroyuki , Takeuchi Ichiro , Katsuno Masahisa , Hirayama Masaaki , Ohno Kinji 
Published: June 2022

AbstractTo elucidate the relevance of gut dysbiosis in Parkinson’s disease (PD) in disease progression, we made random forest models to predict the progression of PD in two years by gut microbiota in 165 PD patients. The area under the receiver operating characteristic curves (AUROCs) of gut microbiota-based models for Hoehn & Yahr (HY) stages 1 and 2 were 0.799 and 0.705, respectively. Similarly, gut microbiota predicted the progression of Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) III scores in an early stage of PD with AUROC = 0.728. Decreases of short-chain fatty acid-producing genera, Fusicatenibacter, Faecalibacterium, and Blautia, as well as an increase of mucin-degrading genus Akkermansia, predicted accelerated disease progression. The four genera remained unchanged in two years in PD, indicating that the taxonomic changes were not the consequences of disease progression. PD patients with marked gut dysbiosis may thus be destined to progress faster than those without gut dysbiosis.
An oxygen-sensing mechanism for angiosperm adaptation to altitude
Authors: Abbas Mohamad , Sharma Gunjan , Dambire Charlene , Marquez Julietta , Alonso-Blanco Carlos , Proaño Karina , Holdsworth Michael J. 
Published: June 2022

AbstractFlowering plants (angiosperms) can grow at extreme altitudes, and have been observed growing as high as 6,400 metres above sea level1,2; however, the molecular mechanisms that enable plant adaptation specifically to altitude are unknown. One distinguishing feature of increasing altitude is a reduction in the partial pressure of oxygen (pO2). Here we investigated the relationship between altitude and oxygen sensing in relation to chlorophyll biosynthesis—which requires molecular oxygen3—and hypoxia-related gene expression. We show that in etiolated seedlings of angiosperm species, steady-state levels of the phototoxic chlorophyll precursor protochlorophyllide are influenced by sensing of atmospheric oxygen concentration. InArabidopsis thaliana, this is mediated by the PLANT CYSTEINE OXIDASE (PCO) N-degron pathway substrates GROUP VII ETHYLENE RESPONSE FACTOR transcription factors (ERFVIIs). ERFVIIs positively regulate expression ofFLUORESCENT IN BLUE LIGHT(FLU), which represses the first committed step of chlorophyll biosynthesis, forming an inactivation complex with tetrapyrrole synthesis enzymes that are negatively regulated by ERFVIIs, thereby suppressing protochlorophyllide. In natural populations representing diverse angiosperm clades, we find oxygen-dependent altitudinal clines for steady-state levels of protochlorophyllide, expression of inactivation complex components and hypoxia-related genes. Finally,A. thalianaaccessions from contrasting altitudes display altitude-dependent ERFVII activity and accumulation. We thus identify a mechanism for genetic adaptation to absolute altitude through alteration of the sensitivity of the oxygen-sensing system.
Clonal dynamics of haematopoiesis across the human lifespan
Authors: Mitchell Emily , Spencer Chapman Michael , Williams Nicholas , Dawson Kevin J. , Mende Nicole , Calderbank Emily F. , Jung Hyunchul , Mitchell Thomas , Coorens Tim H. H. , Spencer David H. , Machado Heather , Lee-Six Henry , Davies Megan , Hayler Daniel , Fabre Margarete A. , Mahbubani Krishnaa , Abascal Federico , Cagan Alex , Vassiliou George S. , Baxter Joanna , Martincorena Inigo , Stratton Michael R. , Kent David G. , Chatterjee Krishna , Parsy Kourosh Saeb , Green Anthony R. , Nangalia Jyoti , Laurenti Elisa , Campbell Peter J. 
Published: June 2022

AbstractAge-related change in human haematopoiesis causes reduced regenerative capacity1, cytopenias2, immune dysfunction3 and increased risk of blood cancer4–6, but the reason for such abrupt functional decline after 70 years of age remains unclear. Here we sequenced 3,579 genomes from single cell-derived colonies of haematopoietic cells across 10 human subjects from 0 to 81 years of age. Haematopoietic stem cells or multipotent progenitors (HSC/MPPs) accumulated a mean of 17 mutations per year after birth and lost 30 base pairs per year of telomere length. Haematopoiesis in adults less than 65 years of age was massively polyclonal, with high clonal diversity and a stable population of 20,000–200,000 HSC/MPPs contributing evenly to blood production. By contrast, haematopoiesis in individuals aged over 75 showed profoundly decreased clonal diversity. In each of the older subjects, 30–60% of haematopoiesis was accounted for by 12–18 independent clones, each contributing 1–34% of blood production. Most clones had begun their expansion before the subject was 40 years old, but only 22% had known driver mutations. Genome-wide selection analysis estimated that between 1 in 34 and 1 in 12 non-synonymous mutations were drivers, accruing at constant rates throughout life, affecting more genes than identified in blood cancers. Loss of the Y chromosome conferred selective benefits in males. Simulations of haematopoiesis, with constant stem cell population size and constant acquisition of driver mutations conferring moderate fitness benefits, entirely explained the abrupt change in clonal structure in the elderly. Rapidly decreasing clonal diversity is a universal feature of haematopoiesis in aged humans, underpinned by pervasive positive selection acting on many more genes than currently identified.
A multimodal sensor dataset for continuous stress detection of nurses in a hospital
Authors: Hosseini Seyedmajid , Gottumukkala Raju , Katragadda Satya , Bhupatiraju Ravi Teja , Ashkar Ziad , Borst Christoph W. , Cochran Kenneth 
Published: June 2022

AbstractAdvances in wearable technologies provide the opportunity to monitor many physiological variables continuously. Stress detection has gained increased attention in recent years, mainly because early stress detection can help individuals better manage health to minimize the negative impacts of long-term stress exposure. This paper provides a unique stress detection dataset created in a natural working environment in a hospital. This dataset is a collection of biometric data of nurses during the COVID-19 outbreak. Studying stress in a work environment is complex due to many social, cultural, and psychological factors in dealing with stressful conditions. Therefore, we captured both the physiological data and associated context pertaining to the stress events. We monitored specific physiological variables such as electrodermal activity, Heart Rate, and skin temperature of the nurse subjects. A periodic smartphone-administered survey also captured the contributing factors for the detected stress events. A database containing the signals, stress events, and survey responses is publicly available on Dryad.
Lifetime distribution of clusters in binary mixtures involving hydrogen bonding liquids
Authors: Jukić Ivo , Požar Martina , Lovrinčević Bernarda , Perera Aurélien 
Published: June 2022

AbstractHydrogen bonded liquids are associated liquids and tend to exhibit local inhomogeneity in the form of clusters and segregated sub-nano domains. It is an open question as to whether Hbonded clusters in pure water have common features with the water segregated pockets observed in various aqueous binary mixtures, such as water–alcohol mixtures, for example. In the present study, we demonstrate through classical molecular dynamics studies of the lifetime distributions of the hydrogen bonds in different types of binary mixtures, that these lifetimes exhibit the same universal features in the case of the pure liquids, independently of the species concentrations. The same types of three distinct lifetimes are observed, all of them in the sub picosecond regime. The primary lifetime concerns that of Hbonded dimers, and strongly depends on Hbonding criteria such as the bonding distance. The two others are independent of bonding criteria and appear as universal accross many liquids and mixtures. The secondary lifetime ($$\tau _1 \approx 20$$

τ
1

≈
20

fs) concerns Hbonded cluster lifetimes, while the tertiary lifetime ($$\tau _2 \approx 50$$

τ
2

≈
50

fs) concerns the topology of these clusters, such as chains or globules, for example. This surprizing separation in three distinct lifetimes suggests the existence of associated three distinct kinetic mechanisms in the very short sub-picosecond time scales, with, in addition, an appealing connection to the concepts of local energy and entropy.
Ploidy dynamics in aphid host cells harboring bacterial symbionts
Authors: Nozaki Tomonari , Shigenobu Shuji 
Published: June 2022

AbstractAphids have evolved bacteriocytes or symbiotic host cells that harbor the obligate mutualistic bacterium Buchnera aphidicola. Because of the large cell size (approximately 100 μm in diameter) of bacteriocytes and their pivotal role in nutritional symbiosis, researchers have considered that these cells are highly polyploid and assumed that bacteriocyte polyploidy may be essential for the symbiotic relationship between the aphid and the bacterium. However, little is known about the ploidy levels and dynamics of aphid bacteriocytes. Here, we quantitatively analyzed the ploidy levels in the bacteriocytes of the pea-aphid Acyrthosiphon pisum. Image-based fluorometry revealed the hyper polyploidy of the bacteriocytes ranging from 16- to 256-ploidy throughout the lifecycle. Bacteriocytes of adult parthenogenetic viviparous females were ranged between 64 and 128C DNA levels, while those of sexual morphs (oviparous females and males) were comprised of 64C, and 32–64C cells, respectively. During post-embryonic development of viviparous females, the ploidy level of bacteriocytes increased substantially, from 16 to 32C at birth to 128–256C in actively reproducing adults. These results suggest that the ploidy levels are dynamically regulated among phenotypes and during development. Our comprehensive and quantitative data provides a foundation for future studies to understand the functional roles and biological significance of the polyploidy of insect bacteriocytes.
Double-diffusive convection in Jeffery–Hamel flow
Authors: Noureen  , Marwat Dil Nawaz Khan 
Published: June 2022

AbstractIn this paper, double-diffusive convection in flow of viscous fluid is investigated inside a horizontal channel. It has heated, inclined and rectangular plane walls. The upper wall has non-uniform temperature and variable species concentration. Note that the Jeffery–Hamel flow depends upon the radial component of velocity, whereas, the peripheral velocity is taken zero. However, the current simulation has been accomplished in view of new procedures and we dealt with two non-zero components of velocity. The problem has been described in a set of four PDEs and the relevant BCs, whereas, the whole set of BVP is taken in Cartesian Coordinates. A set of proper transformation is formed, which reduces the system of PDEs into a new system of ODEs. The system of ODEs is solved with the help of several methods in order to check the validity of the solution. An approximate analytical solution is provided for small values of inclination parameter. An accurate numerical solution of the modelled equations is also given. Moreover, skin friction, rate of the two diffusions are investigated for all different cases of assisting (opposing) and converging (diverging) flows. Thus, the current modelled problem perfectly describes the physical problems of real world in such special circumstances.
Below ground efficiency of a parasitic wasp for Drosophila suzukii biocontrol in different soil types
Authors: Häussling Benedikt J. M. , Mautner Melinda , Stökl Johannes 
Published: June 2022

AbstractThe parasitoid wasp Trichopria drosophilae is promising as a biocontrol agent for controlling the ubiquitous pest Drosophila suzukii (Matsumura). Crucial for the successful implementation of any biocontrol agent is a high parasitisation rate by the parasitoid. Most studies investigating the parasitisation rate of D. suzukii pupae have focused on parasitisation in the fruit or in a petri dish. However, the predominant pupation site of D. suzukii in the field is the soil. Unfortunately, little is known on how well parasitoid wasps can detect and parasitise pupae of D. suzukii buried in the soil. Therefore, we conducted soil parasitisation experiments of T. drosophilae on D. suzukii pupae using two pupation depths in three different soil types (loamy sand, loam, and clay). In all three soil types, we found generally low D. suzukii pupae parasitisation rate by T. drosophilae, independent of the pupation depth. The pupation behaviour of D. suzukii and the parasitisation behaviour of T. drosophilae are discussed in detail. For pest control in most soil types, our results mean that the number of D. suzukii larvae pupating in the soil should be reduced, e.g., by adding a layer of sandy soil or covering the soil with plastic mulch. This might increase the probability of success when using T. drosophilae as a biocontrol agent.
High-order harmonics generation in the laser-induced lead-free perovskites-containing plasmas
Authors: Kim Vyacheslav V. , Ganeev Rashid A. , Konda Srinivasa Rao , Boltaev Ganjaboy S. , Sapaev Ibrohim B. , Yu Weili , Li Wei 
Published: June 2022

AbstractHigh-order harmonics generation in the laser-induced plasmas produced on the surfaces of lead-free perovskites is studied. We analyze the harmonics generation in (CH3NH3)2CuCl4 and (CH3NH3)2CuBr4 plasmas during their ablation by the femtosecond, picosecond, and nanosecond pulses. The modifications of the high-order harmonics spectra are studied using the -color pump scheme (800 nm and 400 nm, 40 fs pulses). The influence of the variations of laser chirp and pulse duration on the dynamics of high-order harmonics generation is examined. The spectral shift, chirp-related harmonic cutoff scaling, and the role of the pulse duration of converting and heating laser radiation are examined at different conditions of plasma formation and harmonic generation. The dependencies of the pulse duration and the fluence of heating pulses on the harmonic’s blue shift are found. The effect of harmonics broadening and splitting on the two red- and blue-shifted components is demonstrated.