bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of genetic differences between psychiatric disorders: exploring pathways and cell types/tissues involved and ability to differentiate the disorders by polygenic scores
Authors: Rao Shitao , Yin Liangying , Xiang Yong , So Hon-Cheong
Published: August 2021

Although displaying genetic correlations, psychiatric disorders are clinically defined as categorical entities as they each have distinguishing clinical features and may involve different treatments. Identifying differential genetic variations between these disorders may reveal how the disorders differ biologically and help to guide more personalized treatment. Here we presented a statistical framework and comprehensive analysis to identify genetic markers differentially associated with various psychiatric disorders/traits based on GWAS summary statistics, covering 18 psychiatric traits/disorders and 26 comparisons. We also conducted comprehensive analysis to unravel the genes, pathways and SNP functional categories involved, and the cell types and tissues implicated. We also assessed how well one could distinguish between psychiatric disorders by polygenic risk scores (PRS). SNP-based heritabilities (h2snp) were significantly larger than zero for most comparisons. Based on current GWAS data, PRS have mostly modest power to distinguish between psychiatric disorders. For example, we estimated that AUC for distinguishing schizophrenia from major depressive disorder (MDD), bipolar disorder (BPD) from MDD and schizophrenia from BPD were 0.694, 0.602 and 0.618, respectively, while the maximum AUC (based on h2snp) were 0.763, 0.749 and 0.726, respectively. We also uncovered differences in each pair of studied traits in terms of their differences in genetic correlation with comorbid traits. For example, clinically defined MDD appeared to more strongly genetically correlated with other psychiatric disorders and heart disease, when compared to non-clinically defined depression in UK Biobank. Our findings highlight genetic differences between psychiatric disorders and the mechanisms involved. PRS may help differential diagnosis of selected psychiatric disorders in the future with larger GWAS samples.
Investigating the inequalities in route to diagnosis amongst patients with diffuse large B-cell or follicular lymphoma in England
Authors: Smith Matthew J. , Fernandez Miguel Angel Luque , Belot Aurélien , Quartagno Matteo , Bonaventure Audrey , Majano Sara Benitez , Rachet Bernard , Njagi Edmund Njeru
Published: August 2021

Introduction

Diagnostic delay is associated with lower chances of cancer survival. Underlying comorbidities are known to affect the timely diagnosis of cancer. Diffuse large B-cell (DLBCL) and follicular lymphomas (FL) are primarily diagnosed amongst older patients, who are more likely to have comorbidities. Characteristics of clinical commissioning groups (CCG) are also known to impact diagnostic delay. We assess the association between comorbidities and diagnostic delay amongst patients with DLBCL or FL in England during 2005–2013.

Methods

Multivariable generalised linear mixed-effect models were used to assess the main association. Empirical Bayes estimates of the random effects were used to explore between-cluster variation. The latent normal joint modelling multiple imputation approach was used to account for partially observed variables.

Results

We included 30,078 and 15,551 patients diagnosed with DLBCL or FL, respectively. Amongst patients from the same CCG, having multimorbidity was strongly associated with the emergency route to diagnosis (DLBCL: odds ratio 1.56, CI 1.40–1.73; FL: odds ratio 1.80, CI 1.45–2.23). Amongst DLBCL patients, the diagnostic delay was possibly correlated with CCGs that had higher population densities.

Conclusions

Underlying comorbidity is associated with diagnostic delay amongst patients with DLBCL or FL. Results suggest a possible correlation between CCGs with higher population densities and diagnostic delay of aggressive lymphomas.
Monolithic polymeric porous superhydrophobic material with pneumatic plastron stabilization for functionally durable drag reduction in blood-contacting biomedical applications
Authors: Marlena Jennifer , Tan Justin Kok Soon , Lin Zenggan , Li David Xinzheyang , Zhao Boxin , Leo Hwa Liang , Kim Sangho , Yap Choon Hwai
Published: August 2021

Superhydrophobic (SHP) surfaces can provide substantial reductions in flow drag forces and reduce blood damage in cardiovascular medical devices. However, strategies for functional durability are necessary, as many SHP surfaces have low durability under abrasion or strong fluid jetting or eventually lose their air plastron and slip-flow capabilities due to plastron gas dissolution, high fluid pressure, or fouling. Here, we present a functional material that extends the functional durability of superhydrophobic slip flow. Facile modification of a porous superhydrophobic polytetrafluoroethylene (PTFE, Teflon) foam produced suitable surface structures to enable fluid slip flow and resist protein fouling. Its monolithic nature offered abrasion durability, while its porosity allowed pressurized air to be supplied to resist fluid impalement and to replenish the air plastron lost to the fluid through dissolution. Active pore pressure control could resist high fluid pressures and turbulent flow conditions across a wide range of applied pressures. The pneumatically stabilized material yielded large drag reductions (up to 50%) even with protein fouling, as demonstrated from high-speed water jetting and closed loop pressure drop tests. Coupled with its high hemocompatibility and impaired protein adsorption, this easily fabricated material can be viable for incorporation into blood-contacting medical devices.
Structures of tmRNA and SmpB as they transit through the ribosome
Authors: Guyomar Charlotte , D’Urso Gaetano , Chat Sophie , Giudice Emmanuel , Gillet Reynald
Published: August 2021

In bacteria, trans-translation is the main rescue system, freeing ribosomes stalled on defective messenger RNAs. This mechanism is driven by small protein B (SmpB) and transfer-messenger RNA (tmRNA), a hybrid RNA known to have both a tRNA-like and an mRNA-like domain. Here we present four cryo-EM structures of the ribosome during trans-translation at resolutions from 3.0 to 3.4 Å. These include the high-resolution structure of the whole pre-accommodated state, as well as structures of the accommodated state, the translocated state, and a translocation intermediate. Together, they shed light on the movements of the tmRNA-SmpB complex in the ribosome, from its delivery by the elongation factor EF-Tu to its passage through the ribosomal A and P sites after the opening of the B1 bridges. Additionally, we describe the interactions between the tmRNA-SmpB complex and the ribosome. These explain why the process does not interfere with canonical translation.
A direct interareal feedback-to-feedforward circuit in primate visual cortex
Authors: Siu Caitlin , Balsor Justin , Merlin Sam , Federer Frederick , Angelucci Alessandra
Published: August 2021

The mammalian sensory neocortex consists of hierarchically organized areas reciprocally connected via feedforward (FF) and feedback (FB) circuits. Several theories of hierarchical computation ascribe the bulk of the computational work of the cortex to looped FF-FB circuits between pairs of cortical areas. However, whether such corticocortical loops exist remains unclear. In higher mammals, individual FF-projection neurons send afferents almost exclusively to a single higher-level area. However, it is unclear whether FB-projection neurons show similar area-specificity, and whether they influence FF-projection neurons directly or indirectly. Using viral-mediated monosynaptic circuit tracing in macaque primary visual cortex (V1), we show that V1 neurons sending FF projections to area V2 receive monosynaptic FB inputs from V2, but not other V1-projecting areas. We also find monosynaptic FB-to-FB neuron contacts as a second motif of FB connectivity. Our results support the existence of FF-FB loops in primate cortex, and suggest that FB can rapidly and selectively influence the activity of incoming FF signals.
Nuclear export and translation of circular repeat-containing intronic RNA in C9ORF72-ALS/FTD
Authors: Wang Shaopeng , Latallo Malgorzata J. , Zhang Zhe , Huang Bo , Bobrovnikov Dmitriy G. , Dong Daoyuan , Livingston Nathan M. , Tjoeng Wilson , Hayes Lindsey R. , Rothstein Jeffrey D. , Ostrow Lyle W. , Wu Bin , Sun Shuying
Published: August 2021

C9ORF72 hexanucleotide GGGGCC repeat expansion is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Repeat-containing RNA mediates toxicity through nuclear granules and dipeptide repeat (DPR) proteins produced by repeat-associated non-AUG translation. However, it remains unclear how the intron-localized repeats are exported and translated in the cytoplasm. We use single molecule imaging approach to examine the molecular identity and spatiotemporal dynamics of the repeat RNA. We demonstrate that the spliced intron with G-rich repeats is stabilized in a circular form due to defective lariat debranching. The spliced circular intron, instead of pre-mRNA, serves as the translation template. The NXF1-NXT1 pathway plays an important role in the nuclear export of the circular intron and modulates toxic DPR production. This study reveals an uncharacterized disease-causing RNA species mediated by repeat expansion and demonstrates the importance of RNA spatial localization to understand disease etiology.
Wide range continuously tunable and fast thermal switching based on compressible graphene composite foams
Authors: Du Tingting , Xiong Zixin , Delgado Luis , Liao Weizhi , Peoples Joseph , Kantharaj Rajath , Chowdhury Prabudhya Roy , Marconnet Amy , Ruan Xiulin
Published: August 2021

Thermal switches have gained intense interest recently for enabling dynamic thermal management of electronic devices and batteries that need to function at dramatically varied ambient or operating conditions. However, current approaches have limitations such as the lack of continuous tunability, low switching ratio, low speed, and not being scalable. Here, a continuously tunable, wide-range, and fast thermal switching approach is proposed and demonstrated using compressible graphene composite foams. Large (~8x) continuous tuning of the thermal resistance is achieved from the uncompressed to the fully compressed state. Environmental chamber experiments show that our variable thermal resistor can precisely stabilize the operating temperature of a heat generating device while the ambient temperature varies continuously by ~10 °C or the heat generation rate varies by a factor of 2.7. This thermal device is promising for dynamic control of operating temperatures in battery thermal management, space conditioning, vehicle thermal comfort, and thermal energy storage.
Retention and deformation of the blue phases in liquid crystalline elastomers
Authors: Schlafmann Kyle R. , White Timothy J.
Published: August 2021

The blue phases are observed in highly chiral liquid crystalline compositions that nascently organize into a three-dimensional, crystalline nanostructure. The periodicity of the unit cell lattice spacing is on the order of the wavelength of visible light and accordingly, the blue phases exhibit a selective reflection as a photonic crystal. Here, we detail the synthesis of liquid crystalline elastomers that retain blue phase I, blue phase II, and blue phase III. The mechanical properties and optical reconfiguration via deformation of retained blue phases are contrasted to the cholesteric phase in fully solid elastomers with glass transition temperatures below room temperature. Mechanical deformation and chemical swelling of the lightly crosslinked polymer networks induces lattice asymmetry in the blue phase evident in the tuning of the selective reflection. The lattice periodicity of the blue phase elastomer is minimally affected by temperature. The oblique lattice planes of the blue phase tilt and red-shift in response to mechanical deformation. The retention of the blue phases in fully solid, elastomeric films could enable functional implementations in photonics, sensing, and energy applications.
RSPO3 is important for trabecular bone and fracture risk in mice and humans
Authors: Nilsson Karin H. , Henning Petra , El Shahawy Maha , Nethander Maria , Andersen Thomas Levin , Ejersted Charlotte , Wu Jianyao , Gustafsson Karin L. , Koskela Antti , Tuukkanen Juha , Souza Pedro P. C. , Tuckermann Jan , Lorentzon Mattias , Ruud Linda Engström , Lehtimäki Terho , Tobias Jon H. , Zhou Sirui , Lerner Ulf H. , Richards J. Brent , Movérare-Skrtic Sofia , Ohlsson Claes
Published: August 2021

With increasing age of the population, countries across the globe are facing a substantial increase in osteoporotic fractures. Genetic association signals for fractures have been reported at the RSPO3 locus, but the causal gene and the underlying mechanism are unknown. Here we show that the fracture reducing allele at the RSPO3 locus associate with increased RSPO3 expression both at the mRNA and protein levels, increased trabecular bone mineral density and reduced risk mainly of distal forearm fractures in humans. We also demonstrate that RSPO3 is expressed in osteoprogenitor cells and osteoblasts and that osteoblast-derived RSPO3 is the principal source of RSPO3 in bone and an important regulator of vertebral trabecular bone mass and bone strength in adult mice. Mechanistic studies revealed that RSPO3 in a cell-autonomous manner increases osteoblast proliferation and differentiation. In conclusion, RSPO3 regulates vertebral trabecular bone mass and bone strength in mice and fracture risk in humans.
Frustrated self-assembly of non-Euclidean crystals of nanoparticles
Authors: Serafin Francesco , Lu Jun , Kotov Nicholas , Sun Kai , Mao Xiaoming
Published: August 2021

Self-organized complex structures in nature, e.g., viral capsids, hierarchical biopolymers, and bacterial flagella, offer efficiency, adaptability, robustness, and multi-functionality. Can we program the self-assembly of three-dimensional (3D) complex structures using simple building blocks, and reach similar or higher level of sophistication in engineered materials? Here we present an analytic theory for the self-assembly of polyhedral nanoparticles (NPs) based on their crystal structures in non-Euclidean space. We show that the unavoidable geometrical frustration of these particle shapes, combined with competing attractive and repulsive interparticle interactions, lead to controllable self-assembly of structures of complex order. Applying this theory to tetrahedral NPs, we find high-yield and enantiopure self-assembly of helicoidal ribbons, exhibiting qualitative agreement with experimental observations. We expect that this theory will offer a general framework for the self-assembly of simple polyhedral building blocks into rich complex morphologies with new material capabilities such as tunable optical activity, essential for multiple emerging technologies.
The Hippo kinase LATS2 impairs pancreatic β-cell survival in diabetes through the mTORC1-autophagy axis
Authors: Yuan Ting , Annamalai Karthika , Naik Shruti , Lupse Blaz , Geravandi Shirin , Pal Anasua , Dobrowolski Aleksandra , Ghawali Jaee , Ruhlandt Marina , Gorrepati Kanaka Durga Devi , Azizi Zahra , Lim Dae-Sik , Maedler Kathrin , Ardestani Amin
Published: August 2021

Diabetes results from a decline in functional pancreatic β-cells, but the molecular mechanisms underlying the pathological β-cell failure are poorly understood. Here we report that large-tumor suppressor 2 (LATS2), a core component of the Hippo signaling pathway, is activated under diabetic conditions and induces β-cell apoptosis and impaired function. LATS2 deficiency in β-cells and primary isolated human islets as well as β-cell specific LATS2 ablation in mice improves β-cell viability, insulin secretion and β-cell mass and ameliorates diabetes development. LATS2 activates mechanistic target of rapamycin complex 1 (mTORC1), a physiological suppressor of autophagy, in β-cells and genetic and pharmacological inhibition of mTORC1 counteracts the pro-apoptotic action of activated LATS2. We further show a direct interplay between Hippo and autophagy, in which LATS2 is an autophagy substrate. On the other hand, LATS2 regulates β-cell apoptosis triggered by impaired autophagy suggesting an existence of a stress-sensitive multicomponent cellular loop coordinating β-cell compensation and survival. Our data reveal an important role for LATS2 in pancreatic β-cell turnover and suggest LATS2 as a potential therapeutic target to improve pancreatic β-cell survival and function in diabetes.
Interacting evolutionary pressures drive mutation dynamics and health outcomes in aging blood
Authors: Skead Kimberly , Ang Houle Armande , Abelson Sagi , Agbessi Mawusse , Bruat Vanessa , Lin Boxi , Soave David , Shlush Liran , Wright Stephen , Dick John , Morris Quaid , Awadalla Philip
Published: August 2021

Age-related clonal hematopoiesis (ARCH) is characterized by age-associated accumulation of somatic mutations in hematopoietic stem cells (HSCs) or their pluripotent descendants. HSCs harboring driver mutations will be positively selected and cells carrying these mutations will rise in frequency. While ARCH is a known risk factor for blood malignancies, such as Acute Myeloid Leukemia (AML), why some people who harbor ARCH driver mutations do not progress to AML remains unclear. Here, we model the interaction of positive and negative selection in deeply sequenced blood samples from individuals who subsequently progressed to AML, compared to healthy controls, using deep learning and population genetics. Our modeling allows us to discriminate amongst evolutionary classes with high accuracy and captures signatures of purifying selection in most individuals. Purifying selection, acting on benign or mildly damaging passenger mutations, appears to play a critical role in preventing disease-predisposing clones from rising to dominance and is associated with longer disease-free survival. Through exploring a range of evolutionary models, we show how different classes of selection shape clonal dynamics and health outcomes thus enabling us to better identify individuals at a high risk of malignancy.
The pathogenesis of mesothelioma is driven by a dysregulated translatome
Authors: Grosso Stefano , Marini Alberto , Gyuraszova Katarina , Voorde Johan Vande , Sfakianos Aristeidis , Garland Gavin D. , Tenor Angela Rubio , Mordue Ryan , Chernova Tanya , Morone Nobu , Sereno Marco , Smith Claire P. , Officer Leah , Farahmand Pooyeh , Rooney Claire , Sumpton David , Das Madhumita , Teodósio Ana , Ficken Catherine , Martin Maria Guerra , Spriggs Ruth V. , Sun Xiao-Ming , Bushell Martin , Sansom Owen J. , Murphy Daniel , MacFarlane Marion , Le Quesne John P. C. , Willis Anne E.
Published: August 2021

Malignant mesothelioma (MpM) is an aggressive, invariably fatal tumour that is causally linked with asbestos exposure. The disease primarily results from loss of tumour suppressor gene function and there are no ‘druggable’ driver oncogenes associated with MpM. To identify opportunities for management of this disease we have carried out polysome profiling to define the MpM translatome. We show that in MpM there is a selective increase in the translation of mRNAs encoding proteins required for ribosome assembly and mitochondrial biogenesis. This results in an enhanced rate of mRNA translation, abnormal mitochondrial morphology and oxygen consumption, and a reprogramming of metabolic outputs. These alterations delimit the cellular capacity for protein biosynthesis, accelerate growth and drive disease progression. Importantly, we show that inhibition of mRNA translation, particularly through combined pharmacological targeting of mTORC1 and 2, reverses these changes and inhibits malignant cell growth in vitro and in ex-vivo tumour tissue from patients with end-stage disease. Critically, we show that these pharmacological interventions prolong survival in animal models of asbestos-induced mesothelioma, providing the basis for a targeted, viable therapeutic option for patients with this incurable disease.
CRISPR-Cas9 globin editing can induce megabase-scale copy-neutral losses of heterozygosity in hematopoietic cells
Authors: Boutin J. , Rosier J. , Cappellen D. , Prat F. , Toutain J. , Pennamen P. , Bouron J. , Rooryck C. , Merlio J. P. , Lamrissi-Garcia I. , Cullot G. , Amintas S. , Guyonnet-Duperat V. , Ged C. , Blouin J. M. , Richard E. , Dabernat S. , Moreau-Gaudry F. , Bedel A.
Published: August 2021

CRISPR-Cas9 is a promising technology for gene therapy. However, the ON-target genotoxicity of CRISPR-Cas9 nuclease due to DNA double-strand breaks has received little attention and is probably underestimated. Here we report that genome editing targeting globin genes induces megabase-scale losses of heterozygosity (LOH) from the globin CRISPR-Cas9 cut-site to the telomere (5.2 Mb). In established lines, CRISPR-Cas9 nuclease induces frequent terminal chromosome 11p truncations and rare copy-neutral LOH. In primary hematopoietic progenitor/stem cells, we detect 1.1% of clones (7/648) with acquired megabase LOH induced by CRISPR-Cas9. In-depth analysis by SNP-array reveals the presence of copy-neutral LOH. This leads to 11p15.5 partial uniparental disomy, comprising two Chr11p15.5 imprinting centers (H19/IGF2:IG-DMR/IC1 and KCNQ1OT1:TSS-DMR/IC2) and impacting H19 and IGF2 expression. While this genotoxicity is a safety concern for CRISPR clinical trials, it is also an opportunity to model copy-neutral-LOH for genetic diseases and cancers.
Nucleolar release of rDNA repeats for repair involves SUMO-mediated untethering by the Cdc48/p97 segregase
Authors: Capella Matías , Mandemaker Imke K. , Martín Caballero Lucía , den Brave Fabian , Pfander Boris , Ladurner Andreas G. , Jentsch Stefan , Braun Sigurd
Published: August 2021

Ribosomal RNA genes (rDNA) are highly unstable and susceptible to rearrangement due to their repetitive nature and active transcriptional status. Sequestration of rDNA in the nucleolus suppresses uncontrolled recombination. However, broken repeats must be first released to the nucleoplasm to allow repair by homologous recombination. Nucleolar release of broken rDNA repeats is conserved from yeast to humans, but the underlying molecular mechanisms are currently unknown. Here we show that DNA damage induces phosphorylation of the CLIP-cohibin complex, releasing membrane-tethered rDNA from the nucleolus in Saccharomyces cerevisiae. Downstream of phosphorylation, SUMOylation of CLIP-cohibin is recognized by Ufd1 via its SUMO-interacting motif, which targets the complex for disassembly through the Cdc48/p97 chaperone. Consistent with a conserved mechanism, UFD1L depletion in human cells impairs rDNA release. The dynamic and regulated assembly and disassembly of the rDNA-tethering complex is therefore a key determinant of nucleolar rDNA release and genome integrity.
Macroscopic weavable fibers of carbon nanotubes with giant thermoelectric power factor
Authors: Komatsu Natsumi , Ichinose Yota , Dewey Oliver S. , Taylor Lauren W. , Trafford Mitchell A. , Yomogida Yohei , Wehmeyer Geoff , Pasquali Matteo , Yanagi Kazuhiro , Kono Junichiro
Published: August 2021

Low-dimensional materials have recently attracted much interest as thermoelectric materials because of their charge carrier confinement leading to thermoelectric performance enhancement. Carbon nanotubes are promising candidates because of their one-dimensionality in addition to their unique advantages such as flexibility and light weight. However, preserving the large power factor of individual carbon nanotubes in macroscopic assemblies has been challenging, primarily due to poor sample morphology and a lack of proper Fermi energy tuning. Here, we report an ultrahigh value of power factor (14 ± 5 mW m−1 K−2) for macroscopic weavable fibers of aligned carbon nanotubes with ultrahigh electrical and thermal conductivity. The observed giant power factor originates from the ultrahigh electrical conductivity achieved through excellent sample morphology, combined with an enhanced Seebeck coefficient through Fermi energy tuning. We fabricate a textile thermoelectric generator based on these carbon nanotube fibers, which demonstrates high thermoelectric performance, weavability, and scalability. The giant power factor we observe make these fibers strong candidates for the emerging field of thermoelectric active cooling, which requires a large thermoelectric power factor and a large thermal conductivity at the same time.
The missing linker between SUN5 and PMFBP1 in sperm head-tail coupling apparatus
Authors: Zhang Ying , Liu Chao , Wu Bingbing , Li Liansheng , Li Wei , Yuan Li
Published: August 2021

The sperm head-to-tail coupling apparatus (HTCA) ensures sperm head-tail integrity while defective HTCA causes acephalic spermatozoa, rendering males infertile. Here, we show that CENTLEIN is indispensable for HTCA integrity and function, and that inactivation of CENTLEIN in mice leads to sperm decapitation and male sterility. We demonstrate that CENTLEIN directly interacts with both SUN5 and PMFBP1, two proteins localized in the HTCA and related with acephalic spermatozoa syndrome. We find that the absence of Centlein sets SUN5 and PMFBP1 apart, the former close to the sperm head and the latter in the decapitated tail. We show that lack of Sun5 results in CENTLEIN and PMFBP1 left in the decapitated tail, while disruption of Pmfbp1 results in SUN5 and CENTLEIN left on the detached sperm head. These results demonstrate that CENTLEIN cooperating with SUN5 and PMFBP1 participates in the HTCA assembly and integration of sperm head to the tail, indicating that impairments of CENTLEIN might be associated with acephalic spermatozoa syndrome in humans.
Tuning the performance of a micrometer-sized Stirling engine through reservoir engineering
Authors: Roy Niloyendu , Leroux Nathan , Sood A. K. , Ganapathy Rajesh
Published: August 2021

Colloidal heat engines are paradigmatic models to understand the conversion of heat into work in a noisy environment - a domain where biological and synthetic nano/micro machines function. While the operation of these engines across thermal baths is well-understood, how they function across baths with noise statistics that is non-Gaussian and also lacks memory, the simplest departure from the thermal case, remains unclear. Here we quantified the performance of a colloidal Stirling engine operating between an engineered memoryless non-Gaussian bath and a Gaussian one. In the quasistatic limit, the non-Gaussian engine functioned like a thermal one as predicted by theory. On increasing the operating speed, due to the nature of noise statistics, the onset of irreversibility for the non-Gaussian engine preceded its thermal counterpart and thus shifted the operating speed at which power is maximum. The performance of nano/micro machines can be tuned by altering only the nature of reservoir noise statistics.
Episodic construction of the early Andean Cordillera unravelled by zircon petrochronology
Authors: Jara José Joaquín , Barra Fernando , Reich Martin , Leisen Mathieu , Romero Rurik , Morata Diego
Published: August 2021

The subduction of oceanic plates beneath continental lithosphere is responsible for continental growth and recycling of oceanic crust, promoting the formation of Cordilleran arcs. However, the processes that control the evolution of these Cordilleran orogenic belts, particularly during their early stages of formation, have not been fully investigated. Here we use a multi-proxy geochemical approach, based on zircon petrochronology and whole-rock analyses, to assess the early evolution of the Andes, one of the most remarkable continental arcs in the world. Our results show that magmatism in the early Andean Cordillera occurred over a period of ~120 million years with six distinct plutonic episodes between 215 and 94 Ma. Each episode is the result of a complex interplay between mantle, crust, slab and sediment contributions that can be traced using zircon chemistry. Overall, the magmatism evolved in response to changes in the tectonic configuration, from transtensional/extensional conditions (215–145 Ma) to a transtensional regime (138–94 Ma). We conclude that an external (tectonic) forcing model with mantle-derived inputs is responsible for the episodic plutonism in this extensional continental arc. This study highlights the use of zircon petrochronology in assessing the multimillion-year crustal scale evolution of Cordilleran arcs.
Soft robotic constrictor for in vitro modeling of dynamic tissue compression
Authors: Paek Jungwook , Song Joseph W. , Ban Ehsan , Morimitsu Yuma , Osuji Chinedum O. , Shenoy Vivek B. , Huh Dan Dongeun
Published: August 2021

Here we present a microengineered soft-robotic in vitro platform developed by integrating a pneumatically regulated novel elastomeric actuator with primary culture of human cells. This system is capable of generating dynamic bending motion akin to the constriction of tubular organs that can exert controlled compressive forces on cultured living cells. Using this platform, we demonstrate cyclic compression of primary human endothelial cells, fibroblasts, and smooth muscle cells to show physiological changes in their morphology due to applied forces. Moreover, we present mechanically actuatable organotypic models to examine the effects of compressive forces on three-dimensional multicellular constructs designed to emulate complex tissues such as solid tumors and vascular networks. Our work provides a preliminary demonstration of how soft-robotics technology can be leveraged for in vitro modeling of complex physiological tissue microenvironment, and may enable the development of new research tools for mechanobiology and related areas.
Patient-specific computational simulation of coronary artery bifurcation stenting
Authors: Zhao Shijia , Wu Wei , Samant Saurabhi , Khan Behram , Kassab Ghassan S. , Watanabe Yusuke , Murasato Yoshinobu , Sharzehee Mohammadali , Makadia Janaki , Zolty Daniel , Panagopoulos Anastasios , Burzotta Francesco , Migliavacca Francesco , Johnson Thomas W. , Lefevre Thierry , Lassen Jens Flensted , Brilakis Emmanouil S. , Bhatt Deepak L. , Dangas George , Chiastra Claudio , Stankovic Goran , Louvard Yves , Chatzizisis Yiannis S.
Published: August 2021

Patient-specific and lesion-specific computational simulation of bifurcation stenting is an attractive approach to achieve individualized pre-procedural planning that could improve outcomes. The objectives of this work were to describe and validate a novel platform for fully computational patient-specific coronary bifurcation stenting. Our computational stent simulation platform was trained using n = 4 patient-specific bench bifurcation models (n = 17 simulations), and n = 5 clinical bifurcation cases (training group, n = 23 simulations). The platform was blindly tested in n = 5 clinical bifurcation cases (testing group, n = 29 simulations). A variety of stent platforms and stent techniques with 1- or 2-stents was used. Post-stenting imaging with micro-computed tomography (μCT) for bench group and optical coherence tomography (OCT) for clinical groups were used as reference for the training and testing of computational coronary bifurcation stenting. There was a very high agreement for mean lumen diameter (MLD) between stent simulations and post-stenting μCT in bench cases yielding an overall bias of 0.03 (− 0.28 to 0.34) mm. Similarly, there was a high agreement for MLD between stent simulation and OCT in clinical training group [bias 0.08 (− 0.24 to 0.41) mm], and clinical testing group [bias 0.08 (− 0.29 to 0.46) mm]. Quantitatively and qualitatively stent size and shape in computational stenting was in high agreement with clinical cases, yielding an overall bias of < 0.15 mm. Patient-specific computational stenting of coronary bifurcations is a feasible and accurate approach. Future clinical studies are warranted to investigate the ability of computational stenting simulations to guide decision-making in the cardiac catheterization laboratory and improve clinical outcomes.
Underlying SUSY in a generalized Jaynes–Cummings model
Authors: Maldonado-Villamizar F. H. , González-Gutiérrez C. A. , Villanueva-Vergara L. , Rodríguez-Lara B. M.
Published: August 2021

We present a general qubit-boson interaction Hamiltonian that describes the Jaynes–Cummings model and its extensions as a single Hamiltonian class. Our model includes non-linear processes for both the free qubit and boson field as well as non-linear, multi-boson excitation exchange between them. It shows an underlying algebra with supersymmetric quantum mechanics features allowing an operator based diagonalization that simplifies the calculations of observables. As a practical example, we show the evolution of the population inversion and the boson quadratures for an initial state consisting of the qubit in the ground state interacting with a coherent field for a selection of cases covering the standard Jaynes–Cummings model and some of its extensions including Stark shift, Kerr-like, intensity dependent coupling, multi-boson exchange and algebraic deformations.
Morphological variation of the deciduous second molars in the Baka Pygmies
Authors: Šimková Petra G. , Weber Gerhard W. , Ramirez Rozzi Fernando V. , Slimani Lotfi , Sadoine Jérémy , Fornai Cinzia
Published: August 2021

The Baka Pygmies are known for their short stature resulting from a reduced growth rate during infancy. They are peculiar also for their teeth erupt earlier than in any other African population, and their posterior dentition is larger than in non-Pygmy populations. However, the Baka’s dental morphology, like several other aspects of their biology, is still understudied. Here, we explore the variation of the Baka’s deciduous upper and lower second molars (dm2s) in comparison to a geographically heterogeneous human sample by means of 3D geometric morphometrics and analysis of dental traits. Our results show that the different populations largely overlap based on the shape of their dm2s, especially the lower ones. Their distal region and the height of the dentinal crown differ the most, with the Baka showing the most extreme range of variation. Upper and lower dm2s covary to a great extent (RV = 0.82). The Baka’s and South Americans’ dm2s were confirmed among the largest in our sample. Despite the Baka’s unique growth pattern, long-lasting isolation, and extreme dental variation, it is not possible to distinguish them from other populations based on their dm2s’ morphology only.
Diagnostic and prognostic implications of 2018 guideline for the diagnosis of idiopathic pulmonary fibrosis in clinical practice
Authors: Choe Jooae , Kwon Byoung Soo , Do Kyung-Hyun , Hwang Hee Sang , Song Jin Woo , Chae Eun Jin
Published: August 2021

The purpose of this study was to evaluate the implications of the 2018 updated guideline for the diagnosis of idiopathic pulmonary fibrosis (IPF) in clinical practice compared to 2011 guideline. This study involved 535 patients including 339 IPF and 196 non-IPF, and we retrospectively evaluated CT classifications of usual interstitial pneumonia (UIP) by two guidelines. Interobserver agreement of 2018 criteria showed moderate reliability (κ = 0.53) comparable to 2011 (κ = 0.56) but interobserver agreement for probable UIP was fair (κ = 0.40). CT pattern of indeterminate for UIP was associated with better prognosis compared with the other groups (adjusted hazard ratio [HR] = 0.36, p < 0.001). Compared to possible UIP, probable UIP demonstrated a lower positive predictive value (PPV, 62.9% vs 65.8%). In analysis of patients with CT patterns of non-definite UIP, diagnosing IPF when CT pattern showed probable UIP with lymphocyte count ≤ 15% in BAL fluid, and either male sex or age ≥ 60 years showed a high specificity of 90.6% and a PPV of 80.8% in the validation cohort. The 2018 criteria provide better prognostic stratification than the 2011 in patients with possible UIP. BAL fluid analysis can improve the diagnostic certainty for IPF diagnosis in patients with probable UIP CT pattern.
Autonomous navigation of a magnetic colonoscope using force sensing and a heuristic search algorithm
Authors: Huang Hao-En , Yen Sheng-Yang , Chu Chia-Feng , Suk Fat-Moon , Lien Gi-Shih , Liu Chih-Wen
Published: August 2021

This paper presents an autonomous navigation system for cost-effective magnetic-assisted colonoscopy, employing force-based sensors, an actuator, a proportional–integrator controller and a real-time heuristic searching method. The force sensing system uses load cells installed between the robotic arm and external permanent magnets to derive attractive force data as the basis for real-time surgical safety monitoring and tracking information to navigate the disposable magnetic colonoscope. The average tracking accuracy on magnetic field navigator (MFN) platform in x-axis and y-axis are 1.14 ± 0.59 mm and 1.61 ± 0.45 mm, respectively, presented in mean error ± standard deviation. The average detectable radius of the tracking system is 15 cm. Three simulations of path planning algorithms are presented and the learning real-time A* (LRTA*) algorithm with our proposed directional heuristic evaluation design has the best performance. It takes 75 steps to complete the traveling in unknown synthetic colon map. By integrating the force-based sensing technology and LRTA* path planning algorithm, the average time required to complete autonomous navigation of a highly realistic colonoscopy training model on the MFN platform is 15 min 38 s and the intubation rate is 83.33%. All autonomous navigation experiments are completed without intervention by the operator.
Comparison of gene expression in the red imported fire ant (Solenopsis invicta) under different temperature conditions
Authors: Vatanparast Mohammad , Puckett Robert T. , Choi Deuk-Soo , Park Youngjin
Published: August 2021

The red imported fire ant (RIFA), Solenopsis invicta Buren is native to South America and is known as a global problematic invasive species. This study focused on the molecular response of RIFA by comparing gene expression profiles after exposing ants to low (10 °C) and high (40 °C) temperature stress and comparing them to untreated controls (30 °C). A total of 99,085 unigenes (the clustered non-redundant transcripts that are filtered from the longest assembled contigs) were obtained, of which 19,154 were annotated with gene descriptions, gene ontology terms, and metabolic pathways. 86 gene ontology (GO) functional sub-groups and 23 EggNOG terms resulted. Differentially expressed genes (DEGs) with log2FC ≥ 10 were screened and were compared at different temperatures. We found 203, 48, and 66 specific DEGs co-regulated at 10, 20, and 40 °C. Comparing transcriptome profiles for differential gene expression resulted in various DE genes, including cytochrome P450, NADH dehydrogenase subunit 1, cuticle protein and heat shock protein (HSP), which have previously been reported to be involved in cold and high temperature resistance. GO analysis revealed that antioxidant activity is up-regulated under high temperature stress. We verified the RNA-seq data by qPCR on 20 up- and down-regulated DEGs. These findings provide a basis for future understanding of the adaptation mechanisms of RIFA and the molecular mechanisms underlying the response to low and high temperatures.
The ERAP1 active site cannot productively access the N-terminus of antigenic peptide precursors stably bound onto MHC class I
Authors: Mavridis George , Mpakali Anastasia , Zoidakis Jerome , Makridakis Manousos , Vlahou Antonia , Kaloumenou Eleni , Ziotopoulou Angeliki , Georgiadis Dimitris , Papakyriakou Athanasios , Stratikos Efstratios
Published: August 2021

Processing of N-terminally elongated antigenic peptide precursors by Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) is a key step in antigen presentation and the adaptive immune response. Although ERAP1 can efficiently process long peptides in solution, it has been proposed that it can also process peptides bound onto Major Histocompatibility Complex I molecules (MHCI). In a previous study, we suggested that the occasionally observed “ontο MHCI” trimming by ERAP1 is likely due to fast peptide dissociation followed by solution trimming, rather than direct action of ERAP1 onto the MHCI complex. However, other groups have proposed that ERAP1 can trim peptides covalently bound onto MHCI, which would preclude peptide dissociation. To explore this interaction, we constructed disulfide-linked MHCI-peptide complexes using HLA-B*08 and a 12mer kinetically labile peptide, or a 16mer carrying a phosphinic transition-state analogue N-terminus with high-affinity for ERAP1. Kinetic and biochemical analyses suggested that while both peptides could access the ERAP1 active site when free in solution, they were unable to do so when tethered in the MHCI binding groove. Our results suggest that MHCI binding protects, rather than promotes, antigenic peptide precursor trimming by ERAP1 and thus solution trimming is the more likely model of antigenic peptide processing.
Galerkin finite element analysis of magneto two-phase nanofluid flowing in double wavy enclosure comprehending an adiabatic rotating cylinder
Authors: Al-Kouz Wael , Bendrer Bilal Abdel-Illah , Aissa Abderrahmane , Almuhtady Ahmad , Jamshed Wasim , Nisar Kottakkaran Sooppy , Mourad Abed , Alshehri Nawal A. , Zakarya Mohammed
Published: August 2021

In this work, the finite element method is employed to simulate heat transfer and irreversibilities in a mixed convection two-phase flow through a wavy enclosure filled with water–alumina nanoliquid and contains a rotating solid cylinder in the presence of a uniform magnetic field. Impact of the variations of undulations number (0 ≤ N ≤ 5), Ra (103 ≤ Ra ≤ 106), Ha (0 ≤ Ha ≤ 100), and angular rotational velocity (− 500 ≤ Ω ≤ 500) were presented. Isotherms distribution, streamlines and isentropic lines are displayed. The governing equations are verified by using the Galerkin Finite Element Method (GFEM). The Nusselt numbers are calculated and displayed graphically for several parametric studies. The computational calculations were carried out using Buongiorno's non-homogeneous model. To illustrate the studied problem, a thorough discussion of the findings was conducted. The results show the enhacement of the maximum value of the flow function and the heat transfer process by increasing the value of Rayleigh number. Furthermore the irreversibility is primarily governed by the heat transfer component and the increment of the waviness of the active surfaces or the cylinder rotational velocity or hartmann number will suppress the fluid motion and hinders the heat transfer process.
Tokorhabditis n. gen. (Rhabditida, Rhabditidae), a comparative nematode model for extremophilic living
Authors: Kanzaki Natsumi , Yamashita Tatsuya , Lee James Siho , Shih Pei-Yin , Ragsdale Erik J. , Shinya Ryoji
Published: August 2021

Life in extreme environments is typically studied as a physiological problem, although the existence of extremophilic animals suggests that developmental and behavioral traits might also be adaptive in such environments. Here, we describe a new species of nematode, Tokorhabditistufae, n. gen., n. sp., which was discovered from the alkaline, hypersaline, and arsenic-rich locale of Mono Lake, California. The new species, which offers a tractable model for studying animal-specific adaptations to extremophilic life, shows a combination of unusual reproductive and developmental traits. Like the recently described sister group Auanema, the species has a trioecious mating system comprising males, females, and self-fertilizing hermaphrodites. Our description of the new genus thus reveals that the origin of this uncommon reproductive mode is even more ancient than previously assumed, and it presents a new comparator for the study of mating-system transitions. However, unlike Auanema and almost all other known rhabditid nematodes, the new species is obligately live-bearing, with embryos that grow in utero, suggesting maternal provisioning during development. Finally, our isolation of two additional, molecularly distinct strains of the new genus—specifically from non-extreme locales—establishes a comparative system for the study of extremophilic traits in this model.
Development of a groundwater quality index: GWQI, for the aquifers of the state of Bahia, Brazil using multivariable analyses
Authors: Barbosa Filho José , de Oliveira Iara Brandão
Published: August 2021

This work elaborated a groundwater quality index—GWQI, for the aquifers of the state of Bahia, Brazil, using multivariable analyses. Data from 600 wells located in the four hydrogeological domains: sedimentary, crystalline, karstic, and metasedimentary, were subjected to exploratory statistical analysis, and 22 out of 26 parameters were subjected to multivariable analysis using Statistica (Version 7.0). From the PCA, 5 factors were sufficient to participate in the index, due to sufficient explanation of the cumulative variance. The matrix of factorial loads (for 1–5 factors) indicated 9 parameters related to water quality and 4 hydrological, with factor loads above ± 0.50, to be part of the hierarchical cluster analysis. The dendrogram allowed to choose the 5 parameters related to groundwater quality, to participate in the GWQI (hardness, total residue, sulphate, fluoride and iron). From the multivariable analyses, three parameters from a previous index—NGWQI, were not selected for the GWQI: chloride (belongs to the hardness hierarchical group); pH (insignificant factor load); and nitrate (significant factor load only for 6 factors), also, not a regionalized variable. From the set of communality values (5 factors), the degree of relevance of each parameter was extracted. Based on these values, were determined the relative weights (wi) for the parameters. Using similar WQI-NSF formulation, a product of quality grades raised to a power, which is the weight of importance of each variable, the GWQI values were calculated. Spatialization of 1369 GWQI values, with the respective colors, on the map of the state of Bahia, revealed good correlation between the groundwater quality and the index quality classification. According to the literature on water quality indexing, the GWQI developed here, using emerging technologies, is a mathematical tool developed as specific index, as it was derived using limits for drinking water. This new index was tailored to represent the quality of the groundwater of the four hydrogeological domains of the state of Bahia. Although it has a regionalized application, its development, using, factor analysis, principal component analysis, and hierarchical cluster analysis, participates of the new trend for WQI development, which uses rational, rather than subjective assessment. The GWQI is a successful index due to its ability to represent the groundwater quality of the state of Bahia, using a single mathematical formulation, the same five parameters, and unique weight for each parameter.