bluuebunny/crossref_metadata_2025_split huggingface dataset:
pS421 huntingtin modulates mitochondrial phenotypes and confers neuroprotection in an HD hiPSC model
Authors: Xu Xiaohong , Ng Bryan , Sim Bernice , Radulescu Carola I. , Yusof Nur Amirah Binte Mohammad , Goh Wah Ing , Lin Shuping , Lim John Soon Yew , Cha Yoonjeong , Kusko Rebecca , Kay Chris , Ratovitski Tamara , Ross Christopher , Hayden Michael R. , Wright Graham , Pouladi Mahmoud A. 
Published: September 2020

AbstractHuntington disease (HD) is a hereditary neurodegenerative disorder caused by mutant huntingtin (mHTT). Phosphorylation at serine-421 (pS421) of mHTT has been shown to be neuroprotective in cellular and rodent models. However, the genetic context of these models differs from that of HD patients. Here we employed human pluripotent stem cells (hiPSCs), which express endogenous full-length mHTT. Using genome editing, we generated isogenic hiPSC lines in which the S421 site in mHTT has been mutated into a phospho-mimetic aspartic acid (S421D) or phospho-resistant alanine (S421A). We observed that S421D, rather than S421A, confers neuroprotection in hiPSC-derived neural cells. Although we observed no effect of S421D on mHTT clearance or axonal transport, two aspects previously reported to be impacted by phosphorylation of mHTT at S421, our analysis revealed modulation of several aspects of mitochondrial form and function. These include mitochondrial surface area, volume, and counts, as well as improved mitochondrial membrane potential and oxidative phosphorylation. Our study validates the protective role of pS421 on mHTT and highlights a facet of the relationship between mHTT and mitochondrial changes in the context of human physiology with potential relevance to the pathogenesis of HD.
A trimeric CrRLK1L-LLG1 complex genetically modulates SUMM2-mediated autoimmunity
Authors: Huang Yanyan , Yin Chuanchun , Liu Jun , Feng Baomin , Ge Dongdong , Kong Liang , Ortiz-Morea Fausto Andres , Richter Julia , Hauser Marie-Theres , Wang Wen-Ming , Shan Libo , He Ping 
Published: September 2020

AbstractCell death is intrinsically linked with immunity. Disruption of an immune-activated MAPK cascade, consisting of MEKK1, MKK1/2, and MPK4, triggers cell death and autoimmunity through the nucleotide-binding leucine-rich repeat (NLR) protein SUMM2 and the MAPK kinase kinase MEKK2. In this study, we identify a Catharanthus roseus receptor-like kinase 1-like (CrRLK1L), named LETUM2/MEDOS1 (LET2/MDS1), and the glycosylphosphatidylinositol (GPI)-anchored protein LLG1 as regulators of mekk1-mkk1/2-mpk4 cell death. LET2/MDS1 functions additively with LET1, another CrRLK1L, and acts genetically downstream of MEKK2 in regulating SUMM2 activation. LET2/MDS1 complexes with LET1 and promotes LET1 phosphorylation, revealing an intertwined regulation between different CrRLK1Ls. LLG1 interacts with the ectodomain of LET1/2 and mediates LET1/2 transport to the plasma membrane, corroborating its function as a co-receptor of LET1/2 in the mekk1-mkk1/2-mpk4 cell death pathway. Thus, our data suggest that a trimeric complex consisting of two CrRLK1Ls LET1, LET2/MDS1, and a GPI-anchored protein LLG1 that regulates the activation of NLR SUMM2 for initiating cell death and autoimmunity.
Molecular correlates of cisplatin-based chemotherapy response in muscle invasive bladder cancer by integrated multi-omics analysis
Authors: Taber Ann , Christensen Emil , Lamy Philippe , Nordentoft Iver , Prip Frederik , Lindskrog Sia Viborg , Birkenkamp-Demtröder Karin , Okholm Trine Line Hauge , Knudsen Michael , Pedersen Jakob Skou , Steiniche Torben , Agerbæk Mads , Jensen Jørgen Bjerggaard , Dyrskjøt Lars 
Published: September 2020

AbstractOvertreatment with cisplatin-based chemotherapy is a major issue in the management of muscle-invasive bladder cancer (MIBC), and currently none of the reported biomarkers for predicting response have been implemented in the clinic. Here we perform a comprehensive multi-omics analysis (genomics, transcriptomics, epigenomics and proteomics) of 300 MIBC patients treated with chemotherapy (neoadjuvant or first-line) to identify molecular changes associated with treatment response. DNA-based associations with response converge on genomic instability driven by a high number of chromosomal alterations, indels, signature 5 mutations and/orBRCA2mutations. Expression data identifies the basal/squamous gene expression subtype to be associated with poor response. Immune cell infiltration and high PD-1 protein expression are associated with treatment response. Through integration of genomic and transcriptomic data, we demonstrate patient stratification to groups of low and high likelihood of cisplatin-based response. This could pave the way for future patient selection following validation in prospective clinical trials.
Emergent solidity of amorphous materials as a consequence of mechanical self-organisation
Authors: Tong Hua , Sengupta Shiladitya , Tanaka Hajime 
Published: September 2020

AbstractAmorphous solids have peculiar properties distinct from crystals. One of the most fundamental mysteries is the emergence of solidity in such nonequilibrium, disordered state without the protection by long-range translational order. A jammed system at zero temperature, although marginally stable, has solidity stemming from the space-spanning force network, which gives rise to the long-range stress correlation. Here, we show that such nonlocal correlation already appears at the nonequilibrium glass transition upon cooling. This is surprising since we also find that the system suffers from giant anharmonic fluctuations originated from the fractal-like potential energy landscape. We reveal that it is the percolation of the force-bearing network that allows long-range stress transmission even under such circumstance. Thus, the emergent solidity of amorphous materials is a consequence of nontrivial self-organisation of the disordered mechanical architecture. Our findings point to the significance of understanding amorphous solids and nonequilibrium glass transition from a mechanical perspective.
Engineering domain-inlaid SaCas9 adenine base editors with reduced RNA off-targets and increased on-target DNA editing
Authors: Nguyen Tran Minh Thuan , Mohd Khalid Mohd Khairul Nizam , Wang Qi , Walker Jacqueline K. R. , Lidgerwood Grace E. , Dilworth Kimberley L. , Lisowski Leszek , Pébay Alice , Hewitt Alex W. 
Published: September 2020

AbstractPrecision genome engineering has dramatically advanced with the development of CRISPR/Cas base editing systems that include cytosine base editors and adenine base editors (ABEs). Herein, we compare the editing profile of circularly permuted and domain-inlaid Cas9 base editors, and find that on-target editing is largely maintained following their intradomain insertion, but that structural permutation of the ABE can affect differing RNA off-target events. With this insight, structure-guided design was used to engineer an SaCas9 ABE variant (microABE I744) that has dramatically improved on-target editing efficiency and a reduced RNA-off target footprint compared to current N-terminal linked SaCas9 ABE variants. This represents one of the smallest AAV-deliverable Cas9-ABEs available, which has been optimized for robust on-target activity and RNA-fidelity based upon its stereochemistry.
ARe we there yet? Understanding androgen receptor signaling in breast cancer
Authors: Michmerhuizen Anna R. , Spratt Daniel E. , Pierce Lori J. , Speers Corey W. 
Published: September 2020

AbstractThe role of androgen receptor (AR) activation and expression is well understood in prostate cancer. In breast cancer, expression and activation of AR is increasingly recognized for its role in cancer development and its importance in promoting cell growth in the presence or absence of estrogen. As both prostate and breast cancers often share a reliance on nuclear hormone signaling, there is increasing appreciation of the overlap between activated cellular pathways in these cancers in response to androgen signaling. Targeting of the androgen receptor as a monotherapy or in combination with other conventional therapies has proven to be an effective clinical strategy for the treatment of patients with prostate cancer, and these therapeutic strategies are increasingly being investigated in breast cancer. This overlap suggests that targeting androgens and AR signaling in other cancer types may also be effective. This manuscript will review the role of AR in various cellular processes that promote tumorigenesis and metastasis, first in prostate cancer and then in breast cancer, as well as discuss ongoing efforts to target AR for the more effective treatment and prevention of cancer, especially breast cancer.
Hydrogen peroxide diffusion and scavenging shapes mitochondrial network instability and failure by sensitizing ROS-induced ROS release
Authors: Millare Brent , O’Rourke Brian , Trayanova Natalia 
Published: September 2020

AbstractThe mitochondrial network of cardiac cells is finely tuned for ATP delivery to sites of energy demand; however, emergent phenomena, such as mitochondrial transmembrane potential oscillations or propagating waves of depolarization have been observed under metabolic stress. While regenerative signaling by reactive oxygen species (ROS)-induced ROS release (RIRR) has been suggested as a potential trigger, it is unknown how it could lead to widespread responses. Here, we present a novel computational model of RIRR transmission that explains the mechanisms of this phenomenon. The results reveal that superoxide mediates neighbor-neighbor activation of energy-dissipating ion channels, while hydrogen peroxide distributes oxidative stress to sensitize the network to mitochondrial criticality. The findings demonstrate the feasibility of RIRR as a synchronizing factor across the dimensions of the adult heart cell and illustrate how a cascade of failures at the organellar level can scale to impact cell and organ level functions of the heart.
Efficient chemical fixation and defixation cycle of carbon dioxide under ambient conditions
Authors: Hajra Saumen , Biswas Anurag 
Published: September 2020

AbstractChemical fixation of CO2 as a C1 feedstock for producing value-added products is an important post-combustion technology reducing the CO2 emission. As it is an irreversible process, not considered for the CO2 capture and release. Overall, these chemical transformations also do not help to mitigate global warming, as the energy consumed in different forms is much higher than the amount of CO2 fixed by chemical reactions. Here we describe the development of re-generable chemical fixation of CO2 by spiroaziridine oxindole, where CO2 is captured (chemical fixation) under catalyst-free condition at room temperature both in aqueous and non-aqueous medium even directly from the slow stream of flue gas producing regioselectively spirooxazolidinyl oxindoles, a potential drug. The CO2-adduct is reversed back to the spiroaziridine releasing CO2 under mild conditions. Further both the fixation-defixation of CO2 can be repeated under near ambient conditions for several cycles in a single loop using a recyclable reagent.
Polar functional group-containing glycolipid CD1d ligands modulate cytokine-biasing responses and prevent experimental colitis
Authors: Inuki Shinsuke , Hirata Natsumi , Kashiwabara Emi , Kishi Junichiro , Aiba Toshihiko , Teratani Toshiaki , Nakamura Wataru , Kojima Yoshimi , Maruyama Toru , Kanai Takanori , Fujimoto Yukari 
Published: September 2020

AbstractThe MHC class I-like molecule CD1d is a nonpolymorphic antigen-presenting glycoprotein, and its ligands include glycolipids, such as α-GalCer. The complexes between CD1d and ligands activate natural killer T cells by T cell receptor recognition, leading to the secretion of various cytokines (IFN-γ, IL-4, IL-17A, etc.). Herein, we report structure–activity relationship studies of α-GalCer derivatives containing various functional groups in their lipid acyl chains. Several derivatives have been identified as potent CD1d ligands displaying higher cytokine induction levels and/or unique cytokine polarization. The studies also indicated that flexibility of the lipid moiety can affect the binding affinity, the total cytokine production level and/or cytokine biasing. Based on our immunological evaluation and investigation of physicochemical properties, we chose bisamide- and Bz amide-containing derivatives 2 and 3, and evaluated their in vivo efficacy in a DSS-induced model of ulcerative colitis. The derivative 3 that exhibits Th2- and Th17-biasing responses, demonstrated significant protective effects against intestinal inflammation in the DSS-induced model, after a single intraperitoneal injection.
Laterality of specific binding ratios on DAT-SPECT for differential diagnosis of degenerative parkinsonian syndromes
Authors: Shigekiyo Taro , Arawaka Shigeki 
Published: September 2020

AbstractMotor symptoms of Parkinson’s disease (PD) occur unilaterally and progress with asymmetry, while progressive supranuclear palsy (PSP) and multiple system atrophy of the parkinsonism subtype (MSA-P) lack this tendency. We assessed the laterality of specific binding ratios (SBRs) on dopamine transporter single-photon emission computed tomography (DAT-SPECT) for the differential diagnosis of these diseases in 311 PD, 33 PSP, 20 MSA-P, and 137 control patients. The average SBR in PD was higher than that in PSP (P = 0.035). Compared with Hoehn–Yahr (HY) stages, the average SBR in PD with HY stage I was only higher than that in PSP (P < 0.001). SBR laterality in PD with HY stage I was significantly higher than that in PSP (P = 0.001). This difference was not observed in PD with HY stage II. The average and laterality of SBRs in MSA-P were similar to those in PD and PSP. The asymmetry indices were similar among PD, PSP, and MSA-P. These data suggest that PSP shows a pattern of SBRs different from that in PD, attributed to HY stage I in PD. The limited usefulness of DAT-SPECT may be explained by the low discrimination between PD with bilateral motor symptoms and PSP.
Landing mosquitoes bounce when engaging a substrate
Authors: Smith Nicholas M. , Balsalobre Jasmine B. , Doshi Mona , Willenberg Bradley J. , Dickerson Andrew K. 
Published: September 2020

AbstractIn this experimental study we film the landings ofAedes aegyptimosquitoes to characterize landing behaviors and kinetics, limitations, and the passive physiological mechanics they employ to land on a vertical surface. A typical landing involves 1–2 bounces, reducing inbound momentum by more than half before the mosquito firmly attaches to a surface. Mosquitoes initially approach landing surfaces at 0.1–0.6 m/s, decelerating to zero velocity in approximately 5 ms at accelerations as high as 5.5 gravities. Unlike Dipteran relatives, mosquitoes do not visibly prepare for landing with leg adjustments or body pitching. Instead mosquitoes rely on damping by deforming two forelimbs and buckling of the proboscis, which also serves to distribute the impact force, lessening the potential of detection by a mammalian host. The rebound response of a landing mosquito is well-characterized by a passive mass-spring-damper model which permits the calculation of force across impact velocity. The landing force of the average mosquito in our study is approximately 40$$\upmu$$μN corresponding to an impact velocity of 0.24 m/s. The substrate contact velocity which produces a force perceptible to humans, 0.42 m/s, is above 85% of experimentally observed landing speeds.
Rab13 regulates sEV secretion in mutant KRAS colorectal cancer cells
Authors: Hinger Scott A. , Abner Jessica J. , Franklin Jeffrey L. , Jeppesen Dennis K. , Coffey Robert J. , Patton James G. 
Published: September 2020

AbstractSmall extracellular vesicles (sEVs), 50–150 nm in diameter, have been proposed to mediate cell–cell communication with important implications in tumor microenvironment interactions, tumor growth, and metastasis. We previously showed that mutant KRAS colorectal cancer (CRC) cells release sEVs containing Rab13 protein and mRNA. Previous work had shown that disruption of intracellular Rab13 trafficking inhibits epithelial cell proliferation and invasiveness. Here, we show that Rab13 additionally regulates the secretion of sEVs corresponding to both traditional exosomes and a novel subset of vesicles containing both β1-integrin and Rab13. We find that exposure of recipient cells to sEVs from KRAS mutant donor cells increases proliferation and tumorigenesis and that knockdown of Rab13 blocks these effects. Thus, Rab13 serves as both a cargo protein and as a regulator of sEV secretion. Our data support a model whereby Rab13 can mediate its effects on cell proliferation and invasiveness via autocrine and paracrine signaling.
There is a cycle to cycle variation in ovarian response and pre-hCG serum progesterone level: an analysis of 244 consecutive IVF cycles
Authors: Yildiz Sule , Yakin Kayhan , Ata Baris , Oktem Ozgur 
Published: September 2020

AbstractWe aimed to answer one key question, that was not previously addressed as to whether serum progesterone (P4-hCG day) and its co-variates (estradiol (E2-hCG day) and the number of retrieved oocytes) of a given cycle can be predictive of the subsequent cycle when both cycles are consecutive and comparable for the stimulation protocol, gonadotropin dose and duration of stimulation. We analyzed such 244 consecutive (< 6 months) IVF cycles in 122 patients with GnRH agonist long protocol and found that P4, E2 and the number of retrieved oocytes significantly vary between the two cycles. Although P4 increased (ranging from 4.7 to 266.7%) in the 2nd cycle in 61 patients, E2 and the number of retrieved oocytes, which are normally positively correlated with P4 paradoxically decreased in the 41% and 37.7% respectively, of these same 61 patients. When a similar analysis was done in the 54 out of 122 patients (44.3%) in whom serum P4 was decreased in the 2nd cycle, the mean decrease in P4 was − 34.1 ± 23.3% ranging from − 5.26 to − 90.1%. E2 and the number of retrieved oocytes paradoxically increased in the 42.3% and 40.7% of these 54 patients respectively. P4 remained the same only in the 7 (5.7%) of these 122 patients. These findings indicate that late follicular phase serum P4 may change unpredictably in the subsequent IVF cycle. The changes are not always necessarily proportional with ovarian response of previous cycle suggesting that growth characteristics and steroidogenic activities of antral cohorts may exhibit considerable cycle to cycle variations.
Charge transport mechanism in dielectrics: drift and diffusion of trapped charge carriers
Authors: Pil’nik Andrey A. , Chernov Andrey A. , Islamov Damir R. 
Published: September 2020

AbstractIn this study, we developed a continuum theory of the charge transport in dielectrics by trapped electrons and holes, which takes into account two separate contributions of the current of trapped charge carriers: the drift part and the diffusion one. It was shown that drift current is mostly dominant in the bulk, while the diffusion one reaches significant values near contacts. A comparison with other theoretical models and experiments shows a good agreement. The model can be extended to two- and three-dimensional systems. The developed model, formulated in partial differential equations, can be numerically implemented in the finite element method code.
Community detection with node attributes in multilayer networks
Authors: Contisciani Martina , Power Eleanor A. , De Bacco Caterina 
Published: September 2020

AbstractCommunity detection in networks is commonly performed using information about interactions between nodes. Recent advances have been made to incorporate multiple types of interactions, thus generalizing standard methods to multilayer networks. Often, though, one can access additional information regarding individual nodes, attributes, or covariates. A relevant question is thus how to properly incorporate this extra information in such frameworks. Here we develop a method that incorporates both the topology of interactions and node attributes to extract communities in multilayer networks. We propose a principled probabilistic method that does not assume any a priori correlation structure between attributes and communities but rather infers this from data. This leads to an efficient algorithmic implementation that exploits the sparsity of the dataset and can be used to perform several inference tasks; we provide an open-source implementation of the code online. We demonstrate our method on both synthetic and real-world data and compare performance with methods that do not use any attribute information. We find that including node information helps in predicting missing links or attributes. It also leads to more interpretable community structures and allows the quantification of the impact of the node attributes given in input.
Comparative analysis of chloroplast genomes in Vasconcellea pubescens A.DC. and Carica papaya L.
Authors: Lin Zhicong , Zhou Ping , Ma Xinyi , Deng Youjin , Liao Zhenyang , Li Ruoyu , Ming Ray 
Published: September 2020

AbstractThe chloroplast genome is an integral part of plant genomes in a species along with nuclear and mitochondrial genomes, contributing to adaptation, diversification, and evolution of plant lineages. In the family Caricaceae, only the Carica papaya chloroplast genome and its nuclear and mitochondrial genomes were sequenced, and no chloroplast genome-wide comparison across genera was conducted. Here, we sequenced and assembled the chloroplast genome of Vasconcellea pubescens A.DC. using Oxford Nanopore Technology. The size of the genome is 158,712 bp, smaller than 160,100 bp of the C. papaya chloroplast genome. And two structural haplotypes, LSC_IRa_SSCrc_IRb and LSC_IRa_SSC_IRb, were identified in both V. pubescens and C. papaya chloroplast genomes. The insertion-deletion mutations may play an important role in Ycf1 gene evolution in family Caricaceae. Ycf2 is the only one gene positively selected in the V. pubescens chloroplast genome. In the C. papaya chloroplast genome, there are 46 RNA editing loci with an average RNA editing efficiency of 63%. These findings will improve our understanding of the genomes of these two crops in the family Caricaceae and will contribute to crop improvement.
New marine data and age accuracy of the Romualdo Formation, Araripe Basin, Brazil
Authors: Melo Robbyson Mendes , Guzmán Juliana , Almeida-Lima Débora , Piovesan Enelise Katia , Neumann Virgínio Henrique de Miranda Lopes , Sousa Ariany de Jesus e 
Published: September 2020

AbstractA combined biostratigraphic and palaeoecological study of foraminifera, ostracodes and microfacies was carried out on the Aptian in the Sítio Sobradinho section of the Araripe Basin, northeast Brazil. The analysed section represents a deepening-upward sequence with mid-ramp shoal and outer ramp to basin facies associations on a mixed siliciclastic-carbonate marine ramp. The analysed rocks are dominated by Early Cretaceous planktic foraminifera (Hedbergella aptiana, H. praelippa, H. sigali,Blesfucuianacf.cumulus, Microhedbergella miniglobularis, Gorbachikellacf.kugleri, Pseudoguembelitria blakenosensis, Globigerinelloides clavatus,Globigerinelloidesaff.aptiensis,Gubkinellasp. andLoeblichellasp.). Ostracoda fauna is composed mainly ofPattersoncypris crepataandPattersoncypris micropapillosa. The occurrence ofP.crepataassociated with the Aptian planktic foraminifera demonstrates the potential of this ostracode species to date this interval. The planktic foraminifera from the upper Aptian (Microhedbergella miniglobularisZone) of the Araripe Basin show characteristical Tethyan affinities.