bluuebunny/crossref_metadata_2025 huggingface dataset:
Watershed‐Scale Effective Hydraulic Properties of the Continental United States
Authors: Tashie Arik , Pavelsky Tamlin , Band Lawrence , Topp Simon
Published: May 2021

In land surface models (LSMs), the hydraulic properties of the subsurface are commonly estimated according to the texture of soils at the Earth's surface. This approach ignores macropores, fracture flow, heterogeneity, and the effects of variable distribution of water in the subsurface on effective watershed‐scale hydraulic variables. Using hydrograph recession analysis, we empirically constrain estimates of watershed‐scale effective hydraulic conductivities (K) and effective drainable aquifer storages (S) of all reference watersheds in the conterminous United States for which sufficient streamflow data are available (n = 1,561). Then, we use machine learning methods to model these properties across the entire conterminous United States. Model validation results in high confidence for estimates of log(K) (r2 > 0.89; 1% < bias < 9%) and reasonable confidence for S (r2 > 0.83; −70% < bias < −18%). Our estimates of effective K are, on average, two orders of magnitude higher than comparable soil‐texture‐based estimates of average K, confirming the importance of soil structure and preferential flow pathways at the watershed scale. Our estimates of effective S compare favorably with recent global estimates of mobile groundwater and are spatially heterogeneous (5–3,355 mm). Because estimates of S are much lower than the global maximums generally used in LSMs (e.g., 5,000 mm in Noah‐MP), they may serve both to limit model spin‐up time and to constrain model parameters to more realistic values. These results represent the first attempt to constrain estimates of watershed‐scale effective hydraulic variables that are necessary for the implementation of LSMs for the entire conterminous United States.
Paleoseismic Evidence of anMw7 Pre‐Hispanic Earthquake in the Peruvian Forearc
Authors: Benavente Carlos , Wimpenny Sam , Rosell Lorena , Robert Xavier , Palomino Anderson , Audin Laurence , Aguirre Enoch , García Briant
Published: May 2021

We present the results of a paleoseismic survey of the Incapuquio Fault System, a prominent transpressional fault system cutting the forearc of South Perú. High‐resolution Digital Elevation Models, optical satellite imagery, radiocarbon dating, and paleoseismic trenching indicate that at least 2–3 m of net slip occurred on the Incapuquio Fault generating a complex, ∼100‐km long set of segmented fault scarps in the early 15th century (∼1400–1440 CE). We interpret the consistent along‐strike pattern of fault scarp heights, geometries and kinematics to reflect a surface rupture generated by a singleMw7.4–7.7 earthquake, suggesting that brittle failure of the forearc poses a significant, yet mostly overlooked, seismic hazard to the communities in coastal areas of Perú. The timing of this earthquake coincides with the collapse of the Chiribaya civilization in ∼1360–1400 CE, and we present evidence of damaged buildings along the fault trace that may be of Chiribayas age. Our surface faulting observations, when combined with observations of deformation in the forearc from geodesy and seismology, also demonstrate that the forearc in South Perú experiences a complex, time‐varying pattern of permanent strain, with evidence for trench‐parallel shortening, trench‐parallel extension, and trench‐perpendicular shortening all in close proximity but in different periods of the megathrust earthquake cycle. The kinematics of recent slip on the Incapuquio Fault are consistent with the sense of interseismic strain within the forearc measured by GPS, suggesting the fault is loaded toward failure between megathrust earthquakes.
Morphological Response of Channelized, Sinuous Gravel‐Bed Rivers to Sediment Replenishment
Authors: Rachelly C. , Friedl F. , Boes R. M. , Weitbrecht V.
Published: May 2021

Anthropogenic alterations of sediment supply and transport processes may impact the ecological state of riverscapes and threaten infrastructure along the river. Sediment replenishment is one restoration method that is employed in channels impacted by sediment deficit. We performed flume experiments to investigate the channel bed response of a channelized, sinuous gravel‐bed river to periodic and episodic sediment replenishment. The grain size distribution of the replenished material, flow discharge, and sediment supply level were varied in long‐term steady‐state experiments. In addition, the channel routing of a single sediment pulse was investigated. The long‐term channel response included intensified sediment relocation and transversal bed leveling. Sediment supply level and flow discharge thereby exerted the strongest control over channel response, whereas the influence of the grain size distribution of the replenished material was minor. A simple habitat analysis using grayling as example species revealed that replenished sediment retained within the channel and thus providing episodically renewed clean gravel patches may increase spawning habitat availability. However, the general shortage of shallow habitats for grayling fry and juveniles in channelized rivers persisted regardless of sediment replenishment. Overall, the experiments illustrate that sediment replenishment may provide valuable habitats within a channelized river. Accompanying measures such as channel widening and the careful consideration of other remaining stressors are strongly recommended to increase restoration benefits further.
A Well-Balanced Ecosystem Uses Water Most Efficiently
Authors: Thompson Elizabeth
Published: May 2021

Excess of a single nutrient, such as nitrogen, may boost plant productivity, but the imbalance leads to less efficient water use as plants scramble for the nutrients they lack.
The Changing Face of Winter: Lessons and Questions From the Laurentian Great Lakes
Authors: Ozersky Ted , Bramburger Andrew J. , Elgin Ashley K. , Vanderploeg Henry A. , Wang Jia , Austin Jay A. , Carrick Hunter J. , Chavarie Louise , Depew David C. , Fisk Aaron T. , Hampton Stephanie E. , Hinchey Elizabeth K. , North Rebecca L. , Wells Mathew G. , Xenopoulos Marguerite A. , Coleman Maureen L. , Duhaime Melissa B. , Fujisaki‐Manome Ayumi , McKay R. Michael , Meadows Guy A. , Rowe Mark D. , Sharma Sapna , Twiss Michael R. , Zastepa Arthur
Published: May 2021

Among its many impacts, climate warming is leading to increasing winter air temperatures, decreasing ice cover extent, and changing winter precipitation patterns over the Laurentian Great Lakes and their watershed. Understanding and predicting the consequences of these changes is impeded by a shortage of winter‐period studies on most aspects of Great Lake limnology. In this review, we summarize what is known about the Great Lakes during their 3–6 months of winter and identify key open questions about the physics, chemistry, and biology of the Laurentian Great Lakes and other large, seasonally frozen lakes. Existing studies show that winter conditions have important effects on physical, biogeochemical, and biological processes, not only during winter but in subsequent seasons as well. Ice cover, the extent of which fluctuates dramatically among years and the five lakes, emerges as a key variable that controls many aspects of the functioning of the Great Lakes ecosystem. Studies on the properties and formation of Great Lakes ice, its effect on vertical and horizontal mixing, light conditions, and biota, along with winter measurements of fundamental state and rate parameters in the lakes and their watersheds are needed to close the winter knowledge gap. Overcoming the formidable logistical challenges of winter research on these large and dynamic ecosystems may require investment in new, specialized research infrastructure. Perhaps more importantly, it will demand broader recognition of the value of such work and collaboration between physicists, geochemists, and biologists working on the world's seasonally freezing lakes and seas.
Alternative regulatory mechanism for the maintenance of bone homeostasis via STAT5-mediated regulation of the differentiation of BMSCs into adipocytes
Authors: Seong Semun , Kim Jung Ha , Kim Kabsun , Kim Inyoung , Koh Jeong-Tae , Kim Nacksung
Published: May 2021

STAT5 is a transcription factor that is activated by various cytokines, hormones, and growth factors. Activated STAT5 is then translocated to the nucleus and regulates the transcription of target genes, affecting several biological processes. Several studies have investigated the role of STAT5 in adipogenesis, but unfortunately, its role in adipogenesis remains controversial. In the present study, we generated adipocyte-specific Stat5 conditional knockout (cKO) (Stat5fl/fl;Apn-cre) mice to investigate the role of STAT5 in the adipogenesis of bone marrow mesenchymal stem cells (BMSCs). BMSC adipogenesis was significantly inhibited upon overexpression of constitutively active STAT5A, while it was enhanced in the absence of Stat5 in vitro. In vivo adipose staining and histological analyses revealed increased adipose volume in the bone marrow of Stat5 cKO mice. ATF3 is the target of STAT5 during STAT5-mediated inhibition of adipogenesis, and its transcription is regulated by the binding of STAT5 to the Atf3 promoter. ATF3 overexpression was sufficient to suppress the enhanced adipogenesis of Stat5-deficient adipocytes, and Atf3 silencing abolished the STAT5-mediated inhibition of adipogenesis. Stat5 cKO mice exhibited reduced bone volume due to an increase in the osteoclast number, and coculture of bone marrow-derived macrophages with Stat5 cKO adipocytes resulted in enhanced osteoclastogenesis, suggesting that an increase in the adipocyte number may contribute to bone loss. In summary, this study shows that STAT5 is a negative regulator of BMSC adipogenesis and contributes to bone homeostasis via direct and indirect regulation of osteoclast differentiation; therefore, it may be a leading target for the treatment of both obesity and bone loss-related diseases.
Dynamical evolution of anisotropic response of type-II Weyl semimetal TaIrTe4 under ultrafast photoexcitation
Authors: Zhuo Xiao , Lai Jiawei , Yu Peng , Yu Ze , Ma Junchao , Lu Wei , Liu Miao , Liu Zheng , Sun Dong
Published: May 2021

Layered type-II Weyl semimetals, such as WTe2, MoTe2, and TaIrTe4 have been demonstrated as a supreme photodetection material with topologically enhanced responsivity and specific sensitivity to the orbital angular momentum of light. Toward future device applications with high performance and ultrafast response, it is necessary to understand the dynamical processes of hot carriers and transient electronic properties of these materials under photoexcitation. In this work, mid-infrared ultrafast spectroscopy is performed to study the dynamical evolution of the anisotropic response of TaIrTe4. The dynamical relaxation of photoexcited carriers exhibits three exponential decay components relating to optical/acoustic phonon cooling and subsequent heat transfer to the substrate. The ultrafast transient dynamics imply that TaIrTe4 is an ideal material candidate for ultrafast optoelectronic applications, especially in the long-wavelength region. The angle-resolved measurement of transient reflection reveals that the reflectivity becomes less anisotropic in the quasi-equilibrium state, indicating a reduction in the anisotropy of dynamical conductivity in presence of photoexcited hot carriers. The results are indispensable in material engineering for polarization-sensitive optoelectronics and high field electronics.
Role of adult hippocampal neurogenesis in the antidepressant actions of lactate
Authors: Carrard Anthony , Cassé Frédéric , Carron Charline , Burlet-Godinot Sophie , Toni Nicolas , Magistretti Pierre J. , Martin Jean-Luc
Published: May 2021

In addition to its role as a neuronal energy substrate and signaling molecule involved in synaptic plasticity and memory consolidation, recent evidence shows that lactate produces antidepressant effects in animal models. However, the mechanisms underpinning lactate’s antidepressant actions remain largely unknown. In this study, we report that lactate reverses the effects of corticosterone on depressive-like behavior, as well as on the inhibition of both the survival and proliferation of new neurons in the adult hippocampus. Furthermore, the inhibition of adult hippocampal neurogenesis prevents the antidepressant-like effects of lactate. Pyruvate, the oxidized form of lactate, did not mimic the effects of lactate on adult hippocampal neurogenesis and depression-like behavior. Finally, our data suggest that conversion of lactate to pyruvate with the concomitant production of NADH is necessary for the neurogenic and antidepressant effects of lactate.
LMW cyclin E and its novel catalytic partner CDK5 are therapeutic targets and prognostic biomarkers in salivary gland cancers
Authors: Lulla Amriti R. , Akli Said , Karakas Cansu , Ha Min Jin , Fowlkes Natalie W. , Mitani Yoshitsugu , Bui Tuyen , Wang Jing , Rao Xiayu , Hunt Kelly K. , Meijer Laurent , El-Naggar Adel K. , Keyomarsi Khandan
Published: May 2021

Salivary gland cancers (SGCs) are rare yet aggressive malignancies with significant histological heterogeneity, which has made prediction of prognosis and development of targeted therapies challenging. In majority of patients, local recurrence and/or distant metastasis are common and systemic treatments have minimal impact on survival. Therefore, identification of novel targets for treatment that can also be used as predictors of recurrence for multiple histological subtypes of SGCs is an area of unmet need. In this study, we developed a novel transgenic mouse model of SGC, efficiently recapitulating the major histological subtype (adenocarcinomas of the parotid gland) of human SGC. CDK2 knock out (KO) mice crossed with MMTV-low molecular weight forms of cyclin E (LMW-E) mice generated the transgenic mouse models of SGC, which arise in the parotid region of the salivary gland, similar to the common site of origin seen in human SGCs. To identify the CDK2 independent catalytic partner(s) of LMW-E, we used LMW-E expressing cell lines in mass spectrometric analysis and subsequent biochemical validation in pull down assays. These studies revealed that in the absence of CDK2, LMW-E preferentially binds to CDK5. Molecular targeting of CDK5, using siRNA, resulted in inhibition of cell proliferation of human SGCs overexpressing LMW-E. We also provide clinical evidence of significant association of LMW-E/CDK5 co-expression and decreased recurrence free survival in human SGC. Immunohistochemical analysis of LMW-E and CDK5 in 424 patients representing each of the four major histological subtypes of human salivary cancers (Aci, AdCC, MEC, and SDC) revealed that LMW-E and CDK5 are concordantly (positive/positive or negative/negative) expressed in 70% of these patients. The co-expression of LMW-E/CDK5 (both positive) robustly predicts the likelihood of recurrence, regardless of the histological classification of these tumors. Collectively, our results suggest that CDK5 is a novel and targetable biomarker for the treatment of patients with SGC presenting with LMW-E overexpressing tumors.
Damage-free transfer mechanics of 2-dimensional materials: competition between adhesion instability and tensile strain
Authors: Kim Chan , Yoon Min-Ah , Jang Bongkyun , Kim Hyeon-Don , Kim Jae-Hyun , Hoang Anh Tuan , Ahn Jong-Hyun , Jung Hyun-June , Lee Hak-Joo , Kim Kwang-Seop
Published: May 2021

The transfer of two-dimensional (2D) materials is crucial to the realization of 2D material-based devices for practical applications. The thinness of 2D materials renders them prone to mechanical damage during the transfer process and to degradation of their superior electrical and mechanical properties. Herein, the mechanisms involved in the damage of chemical vapor deposition-grown graphene (Gr) and MoS2 are investigated during a roll-based transfer process. We identify two different damage mechanisms, i.e., instability-induced damage and tensile strain-induced damage. The two mechanisms compete, depending on the thickness of the transfer medium, and induce dissimilar damage. By minimizing these two mechanisms, we realize and demonstrate the damage-free transfer of 2D materials. The sheet resistance and mobility of transferred Gr are 235 ± 29 Ω sq–1 and 2250 cm2 V–1 s–1, respectively, with no microscopic cracks or tear-out damage. We observe instability-induced damage to be ubiquitous in monolayer MoS2, thin metals, and thin oxide films. By understanding the instability-induced damage mechanism, a broad range of 2D materials and thin films can be transferred without mechanical damage. Damage-free transfer will contribute to the high-yield fabrication of 2D material-based electronic devices.
A novel COL4A1 variant associated with recurrent epistaxis and glioblastoma
Authors: Muto Kohei , Miyamoto Ryosuke , Terasawa Yuka , Shimatani Yoshimitsu , Hara Keijiro , Kakimoto Takumi , Fukumoto Tatsuya , Osaki Yusuke , Fujita Koji , Harada Masafumi , Uehara Hisanori , Takagi Yasushi , Izumi Yuishin
Published: May 2021

COL4A1-related disorders are characterized by a higher incidence of cerebral hemorrhage than other hereditary cerebral small vessel diseases. Accumulating data have shown broad phenotypic variations, and extracerebral hemorrhages have been linked to these disorders. Moreover, the coexistence of neural tumors has been described. Here, we report a Japanese family with a novel COL4A1 variant, including a patient with recurrent epistaxis and glioblastoma.
Submarine landslide megablocks show half of Anak Krakatau island failed on December 22nd, 2018
Authors: Hunt J. E. , Tappin D. R. , Watt S. F. L. , Susilohadi S. , Novellino A. , Ebmeier S. K. , Cassidy M. , Engwell S. L. , Grilli S. T. , Hanif M. , Priyanto W. S. , Clare M. A. , Abdurrachman M. , Udrekh U.
Published: May 2021

As demonstrated at Anak Krakatau on December 22nd, 2018, tsunamis generated by volcanic flank collapse are incompletely understood and can be devastating. Here, we present the first high-resolution characterisation of both subaerial and submarine components of the collapse. Combined Synthetic Aperture Radar data and aerial photographs reveal an extensive subaerial failure that bounds pre-event deformation and volcanic products. To the southwest of the volcano, bathymetric and seismic reflection data reveal a blocky landslide deposit (0.214 ± 0.036 km3) emplaced over 1.5 km into the adjacent basin. Our findings are consistent with en-masse lateral collapse with a volume ≥0.175 km3, resolving several ambiguities in previous reconstructions. Post-collapse eruptions produced an additional ~0.3 km3 of tephra, burying the scar and landslide deposit. The event provides a model for lateral collapse scenarios at other arc-volcanic islands showing that rapid island growth can lead to large-scale failure and that even faster rebuilding can obscure pre-existing collapse.
Engineering T cells to enhance 3D migration through structurally and mechanically complex tumor microenvironments
Authors: Tabdanov Erdem D. , Rodríguez-Merced Nelson J. , Cartagena-Rivera Alexander X. , Puram Vikram V. , Callaway Mackenzie K. , Ensminger Ethan A. , Pomeroy Emily J. , Yamamoto Kenta , Lahr Walker S. , Webber Beau R. , Moriarity Branden S. , Zhovmer Alexander S. , Provenzano Paolo P.
Published: May 2021

Defining the principles of T cell migration in structurally and mechanically complex tumor microenvironments is critical to understanding escape from antitumor immunity and optimizing T cell-related therapeutic strategies. Here, we engineered nanotextured elastic platforms to study and enhance T cell migration through complex microenvironments and define how the balance between contractility localization-dependent T cell phenotypes influences migration in response to tumor-mimetic structural and mechanical cues. Using these platforms, we characterize a mechanical optimum for migration that can be perturbed by manipulating an axis between microtubule stability and force generation. In 3D environments and live tumors, we demonstrate that microtubule instability, leading to increased Rho pathway-dependent cortical contractility, promotes migration whereas clinically used microtubule-stabilizing chemotherapies profoundly decrease effective migration. We show that rational manipulation of the microtubule-contractility axis, either pharmacologically or through genome engineering, results in engineered T cells that more effectively move through and interrogate 3D matrix and tumor volumes. Thus, engineering cells to better navigate through 3D microenvironments could be part of an effective strategy to enhance efficacy of immune therapeutics.
Mitochondrial ATP fuels ABC transporter-mediated drug efflux in cancer chemoresistance
Authors: Giddings Emily L. , Champagne Devin P. , Wu Meng-Han , Laffin Joshua M. , Thornton Tina M. , Valenca-Pereira Felipe , Culp-Hill Rachel , Fortner Karen A. , Romero Natalia , East James , Cao Phoebe , Arias-Pulido Hugo , Sidhu Karatatiwant S. , Silverstrim Brian , Kam Yoonseok , Kelley Shana , Pereira Mark , Bates Susan E. , Bunn Janice Y. , Fiering Steven N. , Matthews Dwight E. , Robey Robert W. , Stich Domink , D’Alessandro Angelo , Rincon Mercedes
Published: May 2021

Chemotherapy remains the standard of care for most cancers worldwide, however development of chemoresistance due to the presence of the drug-effluxing ATP binding cassette (ABC) transporters remains a significant problem. The development of safe and effective means to overcome chemoresistance is critical for achieving durable remissions in many cancer patients. We have investigated the energetic demands of ABC transporters in the context of the metabolic adaptations of chemoresistant cancer cells. Here we show that ABC transporters use mitochondrial-derived ATP as a source of energy to efflux drugs out of cancer cells. We further demonstrate that the loss of methylation-controlled J protein (MCJ) (also named DnaJC15), an endogenous negative regulator of mitochondrial respiration, in chemoresistant cancer cells boosts their ability to produce ATP from mitochondria and fuel ABC transporters. We have developed MCJ mimetics that can attenuate mitochondrial respiration and safely overcome chemoresistance in vitro and in vivo. Administration of MCJ mimetics in combination with standard chemotherapeutic drugs could therefore become an alternative strategy for treatment of multiple cancers.
Printable homocomposite hydrogels with synergistically reinforced molecular-colloidal networks
Authors: Williams Austin H. , Roh Sangchul , Jacob Alan R. , Stoyanov Simeon D. , Hsiao Lilian , Velev Orlin D.
Published: May 2021

The design of hydrogels where multiple interpenetrating networks enable enhanced mechanical properties can broaden their field of application in biomedical materials, 3D printing, and soft robotics. We report a class of self-reinforced homocomposite hydrogels (HHGs) comprised of interpenetrating networks of multiscale hierarchy. A molecular alginate gel is reinforced by a colloidal network of hierarchically branched alginate soft dendritic colloids (SDCs). The reinforcement of the molecular gel with the nanofibrillar SDC network of the same biopolymer results in a remarkable increase of the HHG’s mechanical properties. The viscoelastic HHGs show >3× larger storage modulus and >4× larger Young’s modulus than either constitutive network at the same concentration. Such synergistically enforced colloidal-molecular HHGs open up numerous opportunities for formulation of biocompatible gels with robust structure-property relationships. Balance of the ratio of their precursors facilitates precise control of the yield stress and rate of self-reinforcement, enabling efficient extrusion 3D printing of HHGs.
Alkali-deficiency driven charged out-of-phase boundaries for giant electromechanical response
Authors: Wu Haijun , Ning Shoucong , Waqar Moaz , Liu Huajun , Zhang Yang , Wu Hong-Hui , Li Ning , Wu Yuan , Yao Kui , Lookman Turab , Ding Xiangdong , Sun Jun , Wang John , Pennycook Stephen J.
Published: May 2021

Traditional strategies for improving piezoelectric properties have focused on phase boundary engineering through complex chemical alloying and phase control. Although they have been successfully employed in bulk materials, they have not been effective in thin films due to the severe deterioration in epitaxy, which is critical to film properties. Contending with the opposing effects of alloying and epitaxy in thin films has been a long-standing issue. Herein we demonstrate a new strategy in alkali niobate epitaxial films, utilizing alkali vacancies without alloying to form nanopillars enclosed with out-of-phase boundaries that can give rise to a giant electromechanical response. Both atomically resolved polarization mapping and phase field simulations show that the boundaries are strained and charged, manifesting as head-head and tail-tail polarization bound charges. Such charged boundaries produce a giant local depolarization field, which facilitates a steady polarization rotation between the matrix and nanopillars. The local elastic strain and charge manipulation at out-of-phase boundaries, demonstrated here, can be used as an effective pathway to obtain large electromechanical response with good temperature stability in similar perovskite oxides.
Tunable high-temperature itinerant antiferromagnetism in a van der Waals magnet
Authors: Seo Junho , An Eun Su , Park Taesu , Hwang Soo-Yoon , Kim Gi-Yeop , Song Kyung , Noh Woo-suk , Kim J. Y. , Choi Gyu Seung , Choi Minhyuk , Oh Eunseok , Watanabe Kenji , Taniguchi Takashi , Park J. -H. , Jo Youn Jung , Yeom Han Woong , Choi Si-Young , Shim Ji Hoon , Kim Jun Sung
Published: May 2021

Discovery of two dimensional (2D) magnets, showing intrinsic ferromagnetic (FM) or antiferromagnetic (AFM) orders, has accelerated development of novel 2D spintronics, in which all the key components are made of van der Waals (vdW) materials and their heterostructures. High-performing and energy-efficient spin functionalities have been proposed, often relying on current-driven manipulation and detection of the spin states. In this regard, metallic vdW magnets are expected to have several advantages over the widely-studied insulating counterparts, but have not been much explored due to the lack of suitable materials. Here, we report tunable itinerant ferro- and antiferromagnetism in Co-doped Fe4GeTe2 utilizing the vdW interlayer coupling, extremely sensitive to the material composition. This leads to high TN antiferromagnetism of TN ~ 226 K in a bulk and ~210 K in 8 nm-thick nanoflakes, together with tunable magnetic anisotropy. The resulting spin configurations and orientations are sensitively controlled by doping, magnetic field, and thickness, which are effectively read out by electrical conduction. These findings manifest strong merits of metallic vdW magnets as an active component of vdW spintronic applications.
Total genetic contribution assessment across the human genome
Authors: Li Ting , Ning Zheng , Yang Zhijian , Zhai Ranran , Zheng Chenqing , Xu Wenzheng , Wang Yipeng , Ying Kejun , Chen Yiwen , Shen Xia
Published: May 2021

Quantifying the overall magnitude of every single locus’ genetic effect on the widely measured human phenome is of great challenge. We introduce a unified modelling technique that can consistently provide a total genetic contribution assessment (TGCA) of a gene or genetic variant without thresholding genetic association signals. Genome-wide TGCA in five UK Biobank phenotype domains highlights loci such as the HLA locus for medical conditions, the bone mineral density locus WNT16 for physical measures, and the skin tanning locus MC1R and smoking behaviour locus CHRNA3 for lifestyle. Tissue-specificity investigation reveals several tissues associated with total genetic contributions, including the brain tissues for mental health. Such associations are driven by tissue-specific gene expressions, which share genetic basis with the total genetic contributions. TGCA can provide a genome-wide atlas for the overall genetic contributions in each particular domain of human complex traits.
Cryo-EM structures of an insecticidal Bt toxin reveal its mechanism of action on the membrane
Authors: Byrne Matthew J. , Iadanza Matthew G. , Perez Marcos Arribas , Maskell Daniel P. , George Rachel M. , Hesketh Emma L. , Beales Paul A. , Zack Marc D. , Berry Colin , Thompson Rebecca F.
Published: May 2021

Insect pests are a major cause of crop losses worldwide, with an estimated economic cost of $470 billion annually. Biotechnological tools have been introduced to control such insects without the need for chemical pesticides; for instance, the development of transgenic plants harbouring genes encoding insecticidal proteins. The Vip3 (vegetative insecticidal protein 3) family proteins from Bacillus thuringiensis convey toxicity to species within the Lepidoptera, and have wide potential applications in commercial agriculture. Vip3 proteins are proposed to exert their insecticidal activity through pore formation, though to date there is no mechanistic description of how this occurs on the membrane. Here we present cryo-EM structures of a Vip3 family toxin in both inactive and activated forms in conjunction with structural and functional data on toxin–membrane interactions. Together these data demonstrate that activated Vip3Bc1 complex is able to insert into membranes in a highly efficient manner, indicating that receptor binding is the likely driver of Vip3 specificity.
Andreev reflection of fractional quantum Hall quasiparticles
Authors: Hashisaka M. , Jonckheere T. , Akiho T. , Sasaki S. , Rech J. , Martin T. , Muraki K.
Published: May 2021

Electron correlation in a quantum many-body state appears as peculiar scattering behaviour at its boundary, symbolic of which is Andreev reflection at a metal-superconductor interface. Despite being fundamental in nature, dictated by the charge conservation law, however, the process has had no analogues outside the realm of superconductivity so far. Here, we report the observation of an Andreev-like process originating from a topological quantum many-body effect instead of superconductivity. A narrow junction between fractional and integer quantum Hall states shows a two-terminal conductance exceeding that of the constituent fractional state. This remarkable behaviour, while theoretically predicted more than two decades ago but not detected to date, can be interpreted as Andreev reflection of fractionally charged quasiparticles. The observed fractional quantum Hall Andreev reflection provides a fundamental picture that captures microscopic charge dynamics at the boundaries of topological quantum many-body states.
Real-time monitoring of ruminal microbiota reveals their roles in dairy goats during subacute ruminal acidosis
Authors: Chen Xiaodong , Su Xiaodong , Li Jilong , Yang Yuntian , Wang Peiyue , Yan Fang , Yao Junhu , Wu Shengru
Published: May 2021

Ruminal microbiota changes frequently with high grain diets and the occurrence of subacute ruminal acidosis (SARA). A grain-induced goat model of SARA, with durations of a significant decrease in the rumen pH value to less than 5.6 and an increase in the rumen lipopolysaccharides concentration, is constructed for real-time monitoring of bacteria alteration. Using 16 S rRNA gene sequencing, significant bacterial differences between goats from the SARA and healthy groups are identified at every hour for six continuous hours after feeding. Moreover, 29 common differential genera between two groups over 6 h after feeding are all related to the altered pH and lipopolysaccharides. Transplanting the microbiota from donor goats with SARA could induce colonic inflammation in antibiotic-pretreated mice. Overall, significant differences in the bacterial community and rumen fermentation pattern between the healthy and SARA dairy goats are real-time monitored, and then tested using ruminal microbe transplantation to antibiotic-treated mice.
Biodegradation of chlorpyrifos using isolates from contaminated agricultural soil, its kinetic studies
Authors: Farhan Muhammad , Ahmad Maqsood , Kanwal Amina , Butt Zahid Ali , Khan Qaiser Farid , Raza Syed Ali , Qayyum Haleema , Wahid Abdul
Published: May 2021

Extensive pesticides use is negatively disturbing the environment and humans. Pesticide bioremediation with eco-friendly techniques bears prime importance. This study evaluates the bioremediation of chlorpyrifos in soil using indigenous Bacillus cereus Ct3, isolated from cotton growing soils. Strains were identified through ribotyping (16s rRNA) by Macrogen (Macrogen Inc. Geumchen-gu, South Korea). Bacillus cereus Ct3 was resistant up to 125 mg L−1 of chlorpyrifos and successfully degraded 88% of chlorpyfifos in 8 days at pH 8. Bacillus cereus Ct3 tolerated about 30–40 °C of temperature, this is a good sign for in situ bioremediation. Green compost, farmyard manure and rice husk were tested, where ANOVA (P < 0.05) and Plackett–Burman design, results indicated that the farm yard manure has significant impact on degradation. It reduced the lag phase and brought maximum degradation up to 88%. Inoculum size is a statistically significant (P < 0.05) factor and below 106 (CFU g−1) show lag phase of 4–6 days. Michaelis–Menten model results were as follows; R2 = 0.9919, Vmax = 18.8, Ks = 121.4 and Vmax/Ks = 0.1546. GC–MS study revealed that chlorpyrifos first converted into diethylthiophosphoric acid and 3,5,6-trichloro-2-pyridinol (TCP). Later, TCP ring was broken and it was completely mineralized without any toxic byproduct. Plackett–Burman design was employed to investigate the effect of five factors. The correlation coefficient (R2) between experimental and predicted value is 0.94. Central composite design (CBD) was employed with design matrix of thirty one predicted and experimental values of chlorpyrifos degradation, having “lack of fit P value” of “0.00”. The regression coefficient obtained was R2 = 0.93 which indicate that the experimental vales and the predicted values are closely fitted. The most significant factors highlighted in CBD/ANOVA and surface response plots were chlorpyrifor concentration and inoculum size. Bacillus cereus Ct3 effectively degraded chlorpyrifos and can successfully be used for bioremediation of chlorpyrifos contaminated soils.
trans-Fatty acids promote p53-dependent apoptosis triggered by cisplatin-induced DNA interstrand crosslinks via the Nox-RIP1-ASK1-MAPK pathway
Authors: Hirata Yusuke , Takahashi Miki , Yamada Yuto , Matsui Ryosuke , Inoue Aya , Ashida Ryo , Noguchi Takuya , Matsuzawa Atsushi
Published: May 2021

trans-Fatty acids (TFAs) are food-derived fatty acids associated with various diseases including cardiovascular diseases. However, the underlying etiology is poorly understood. Here, we show a pro-apoptotic mechanism of TFAs such as elaidic acid (EA), in response to DNA interstrand crosslinks (ICLs) induced by cisplatin (CDDP). We previously reported that TFAs promote apoptosis induced by doxorubicin (Dox), a double strand break (DSB)-inducing agent, via a non-canonical apoptotic pathway independent of tumor suppressor p53 and apoptosis signal-regulating kinase (ASK1), a reactive oxygen species (ROS)-responsive kinase. However, here we found that in the case of CDDP-induced apoptosis, EA-mediated pro-apoptotic action was reversed by knockout of either p53 or ASK1, despite no increase in p53 apoptotic activity. Upon CDDP treatment, EA predominantly enhanced ROS generation, ASK1-p38/c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathway activation, and ultimately cell death, all of which were suppressed either by co-treatment of the NADPH oxidase (Nox) inhibitor Apocynin, or by knocking out its regulatory protein, receptor-interacting protein 1 (RIP1). These results demonstrate that in response to CDDP ICLs, TFAs promote p53-dependent apoptosis through the enhancement of the Nox-RIP1-ASK1-MAPK pathway activation, providing insight into the diverse pathogenetic mechanisms of TFAs according to the types of DNA damage.
The influence of body position on bioelectrical impedance spectroscopy measurements in young children
Authors: Lyons-Reid Jaz , Ward Leigh C. , Tint Mya-Thway , Kenealy Timothy , Godfrey Keith M. , Chan Shiao-Yng , Cutfield Wayne S.
Published: May 2021

Bioelectrical impedance techniques are easy to use and portable tools for assessing body composition. While measurements vary according to standing vs supine position in adults, and fasting and bladder voiding have been proposed as additional important influences, these have not been assessed in young children. Therefore, the influence of position, fasting, and voiding on bioimpedance measurements was examined in children. Bioimpedance measurements (ImpediMed SFB7) were made in 50 children (3.38 years). Measurements were made when supine and twice when standing (immediately on standing and after four minutes). Impedance and body composition were compared between positions, and the effect of fasting and voiding was assessed. Impedance varied between positions, but body composition parameters other than fat mass (total body water, intra- and extra-cellular water, fat-free mass) differed by less than 5%. There were no differences according to time of last meal or void. Equations were developed to allow standing measurements of fat mass to be combined with supine measurements. In early childhood, it can be difficult to meet requirements for fasting, voiding, and lying supine prior to measurement. This study provides evidence to enable standing and supine bioimpedance measurements to be combined in cohorts of young children.
Identification and Classification of Rare Variants in NPC1 and NPC2 in Quebec
Authors: Touma Lahoud , Labrecque Marjorie , Tetreault Martine , Duquette Antoine
Published: May 2021

Niemann–Pick disease type C (NPC) is a treatable autosomal recessive neurodegenerative condition which leads to a variety of progressive manifestations. Despite most cases being diagnosed at a young age, disease prevalence may be underestimated, especially in adults, and interpretation of NPC1 and NPC2 variants can be difficult. This study aims to identify potential pathogenic variants in a large cohort of healthy individuals and classify their risk of pathogenicity to assist with future interpretation of variants. The CARTaGENE (CaG) cohort was used to identify possible variants of NPC1 and NPC2. Nine-hundred and eleven RNA samples and 198 exome sequencing were screened for genetic variants through a bio-informatic pipeline performing alignment and variant calling. The identified variants were analyzed using annotations for allelic frequency, pathogenicity and conservation scores. The ACMG guidelines were used to classify the variants. These were then compared to existing databases and previous studies of NPC prevalence, including the Tübingen NPC database. Thirty-two distinct variants were identified after running the samples in the RNA-sequencing pipeline, two of which were classified as pathogenic and 21 of which were not published previously. Furthermore, 46 variants were both identified in our population and with the Tübingen database, the majority of which were of uncertain significance. Ten additional variants were found in our exome-sequencing sample. This study of a sample from a population living in Quebec demonstrates a variety of rare variants, some of which were already described in the literature as well as some novel variants. Classifying these variants is arduous given the scarcity of available literature, even so in a population of healthy individuals. Yet using this data, we were able to identify two pathogenic variants within our population and several new variants not previously identified.
Aggrecan: a new biomarker for acute type A aortic dissection
Authors: König Karl C. , Lahm Harald , Dreßen Martina , Doppler Stefanie A. , Eichhorn Stefan , Beck Nicole , Kraehschuetz Kathrin , Doll Sophia , Holdenrieder Stefan , Kastrati Adnan , Lange Rüdiger , Krane Markus
Published: May 2021

Acute type A aortic dissection (ATAAD) constitutes a life-threatening aortic pathology with significant morbidity and mortality. Without surgical intervention the usual mortality rate averages between 1 and 2% per hour. Thus, an early diagnosis of ATAAD is of pivotal importance to direct the affected patients to the appropriate treatment. Preceding tests to find an appropriate biomarker showed among others an increased aggrecan (ACAN) mRNA expression in aortic tissue of ATAAD patients. As a consequence, we investigated whether ACAN is a potential biomarker for diagnosing ATAAD. Mean ACAN protein concentration showed a significantly higher plasma concentration in ATAAD patients (38.59 ng/mL, n = 33) compared to plasma of patients with thoracic aortic aneurysms (4.45 ng/mL, n = 13), patients with myocardial infarction (11.77 ng/mL, n = 18) and healthy volunteers (8.05 ng/mL, n = 12). Cardiac enzymes like creatine kinase MB and cardiac troponin T showed no correlation with ACAN levels in ATAAD patients. Receiver-operator characteristics (ROC) curve analysis for ATAAD patients versus control subjects an optimum discrimination limit of ACAN plasma levels at 14.3 ng/mL with a corresponding sensitivity of 97% and specificity of 81%. According to our findings ACAN is a reliable potential biomarker in plasma samples to detect ATAAD with high sensitivity and specificity.
Differential features of chronic cough according to etiology and the simple decision tree for predicting causes
Authors: Koo Hyeon-Kyoung , Bae Won , Moon Ji-Yong , Lee Hyun , Kim Jin Woo , Jang Seung Hun , Yoon Hyoung Kyu , Kim Deog Kyeom
Published: May 2021

Finding etiology of chronic cough is an essential part of treatment. Although guidelines include many laboratory tests for diagnosis, these are not possible in many primary care centers. We aimed to identify the characteristics and the differences associated with its cause to develop a clinical prediction model. Adult subjects with chronic cough who completed both Korean version of the Leicester Cough Questionnaire (K-LCQ) and COugh Assessment Test (COAT) were enrolled. Clinical characteristics of each etiology were compared using features included in questionnaires. Decision tree models were built to classify the causes. A total of 246 subjects were included for analysis. Subjects with asthma including cough variant asthma (CVA) suffered from more severe cough in physical and psychological domains. Subjects with eosinophilic bronchitis (EB) presented less severe cough in physical domain. Those with gastro-esophageal reflux disease (GERD) displayed less severe cough in all 3 domains. In logistic regression, voice hoarseness was an independent feature of upper airway cough syndrome (UACS), whereas female sex, tiredness, and hypersensitivity to irritants were predictors of asthma/CVA; less hoarseness was a significant feature of EB, and feeling fed-up and hoarseness were less common characteristics of GERD. The decision tree was built to classify the causes and the accuracy was relatively high for both K-LCQ and COAT, except for UACS. Voice hoarseness, degree of tiredness, hypersensitivity to irritants and feeling fed-up are important features in determining the etiologies. The decision tree may further assists classifying the causes of chronic cough.
Oil palm cultivation critically affects sociality in a threatened Malaysian primate
Authors: Holzner Anna , Balasubramaniam Krishna N. , Weiß Brigitte M. , Ruppert Nadine , Widdig Anja
Published: May 2021

Human-induced habitat alterations globally threaten animal populations, often evoking complex behavioural responses in wildlife. This may be particularly dramatic when negatively affecting social behaviour, which fundamentally determines individual fitness and offspring survival in group-living animals. Here, we provide first evidence for significant behavioural modifications in sociality of southern pig-tailed macaques visiting Malaysian oil palm plantations in search of food despite elevated predation risk. Specifically, we found critical reductions of key positive social interactions but higher rates of aggression in the plantation interior compared to the plantation edge (i.e. plantation areas bordering the forest) and the forest. At the plantation edge, affiliation even increased compared to the forest, while central positions in the macaques' social network structure shifted from high-ranking adult females and immatures to low-ranking individuals. Further, plantations also affected mother–infant relationships, with macaque mothers being more protective in the open plantation environment. We suggest that although primates can temporarily persist in human-altered habitats, their ability to permanently adapt requires the presence of close-by forest and comes with a trade-off in sociality, potentially hampering individual fitness and infant survival. Studies like ours remain critical for understanding species’ adaptability to anthropogenic landscapes, which may ultimately contribute to facilitating their coexistence with humans and preserving biodiversity.
Kaolin based protective barrier in municipal landfills against adverse chemo-mechanical loadings
Authors: Das Partha , Bharat Tadikonda Venkata
Published: May 2021

In this work, we assess the self-sealing and swelling ability of the compacted granular bentonite (GB) under an inorganic salt environment and induced overburden stresses from the landfill waste. The laboratory permeation tests with high ionic strength salt solutions reveal that the GB fails to seal and exhibits a significant mechanical collapse under different applied stresses. The applicability of GB in the form of geosynthetic clay liners as the bottom liner facilities in landfills that produce high ionic strength salt leachates, therefore, remains a serious concern. We propose an additional barrier system based on kaolin, for the first time, to address this problem. The proposed kaolin-GB layered system performs satisfactorily in terms of its sealing and swelling ability even in adverse saline conditions and low overburden stresses. The kaolin improves the osmotic efficiency of the self and also helps the underlying GB layer to seal the inter-granular voids. The estimated design parameters by through-diffusion test suggest that the kaolin-GB layered system effectively attenuates the permeant flux and suitable as a landfill liner.