bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural and functional analysis of the role of the chaperonin CCT in mTOR complex assembly
Authors: Cuéllar Jorge , Ludlam W. Grant , Tensmeyer Nicole C. , Aoba Takuma , Dhavale Madhura , Santiago César , Bueno-Carrasco M. Teresa , Mann Michael J. , Plimpton Rebecca L. , Makaju Aman , Franklin Sarah , Willardson Barry M. , Valpuesta José M. 
Published: June 2019

AbstractThe mechanistic target of rapamycin (mTOR) kinase forms two multi-protein signaling complexes, mTORC1 and mTORC2, which are master regulators of cell growth, metabolism, survival and autophagy. Two of the subunits of these complexes are mLST8 and Raptor, β-propeller proteins that stabilize the mTOR kinase and recruit substrates, respectively. Here we report that the eukaryotic chaperonin CCT plays a key role in mTORC assembly and signaling by folding both mLST8 and Raptor. A high resolution (4.0 Å) cryo-EM structure of the human mLST8-CCT intermediate isolated directly from cells shows mLST8 in a near-native state bound to CCT deep within the folding chamber between the two CCT rings, and interacting mainly with the disordered N- and C-termini of specific CCT subunits of both rings. These findings describe a unique function of CCT in mTORC assembly and a distinct binding site in CCT for mLST8, far from those found for similar β-propeller proteins.
On the origin of the extremely different solubilities of polyethers in water
Authors: Ensing Bernd , Tiwari Ambuj , Tros Martijn , Hunger Johannes , Domingos Sérgio R. , Pérez Cristóbal , Smits Gertien , Bonn Mischa , Bonn Daniel , Woutersen Sander 
Published: June 2019

AbstractThe solubilities of polyethers are surprisingly counter-intuitive. The best-known example is the difference between polyethylene glycol ([–CH2–CH2–O–]n) which is infinitely soluble, and polyoxymethylene ([–CH2–O–]n) which is completely insoluble in water, exactly the opposite of what one expects from the C/O ratios of these molecules. Similar anomalies exist for oligomeric and cyclic polyethers. To solve this apparent mystery, we use femtosecond vibrational and GHz dielectric spectroscopy with complementary ab initio calculations and molecular dynamics simulations. We find that the dynamics of water molecules solvating polyethers is fundamentally different depending on their C/O composition. The ab initio calculations and simulations show that this is not because of steric effects (as is commonly believed), but because the partial charge on the O atoms depends on the number of C atoms by which they are separated. Our results thus show that inductive effects can have a major impact on aqueous solubilities.
Selective self-assembly of 2,3-diaminophenazine molecules on MoSe2 mirror twin boundaries
Authors: He Xiaoyue , Zhang Lei , Chua Rebekah , Wong Ping Kwan Johnny , Arramel Arramel , Feng Yuan Ping , Wang Shi Jie , Chi Dongzhi , Yang Ming , Huang Yu Li , Wee Andrew Thye Shen 
Published: June 2019

AbstractThe control of the density and type of line defects on two-dimensional (2D) materials enable the development of new methods to tailor their physical and chemical properties. In particular, mirror twin boundaries (MTBs) on transition metal dichacogenides have attracted much interest due to their metallic state with charge density wave transition and spin-charge separation property. In this work, we demonstrate the self-assembly of 2,3-diaminophenazine (DAP) molecule porous structure with alternate L-type and T-type aggregated configurations on the MoSe2 hexagonal wagon-wheel pattern surface. This site-specific molecular self-assembly is attributed to the more chemically reactive metallic MTBs compared to the pristine semiconducting MoSe2 domains. First-principles calculations reveal that the active MTBs couple with amino groups in the DAP molecules facilitating the DAP assembly. Our results demonstrate the site-dependent electronic and chemical properties of MoSe2 monolayers, which can be exploited as a natural template to create ordered nanostructures.
NIR-light-mediated spatially selective triggering of anti-tumor immunity via upconversion nanoparticle-based immunodevices
Authors: Chu Hongqian , Zhao Jian , Mi Yongsheng , Di Zhenghan , Li Lele 
Published: June 2019

AbstractImmunomodulatory therapies are becoming a paradigm-shifting treatment modality for cancer. Despite promising clinical results, cancer immunotherapy is accompanied with off-tumor toxicity and autoimmune adverse effects. Thus, the development of smarter systems to regulate immune responses with superior spatiotemporal precision and enhanced safety is urgently needed. Here we report an activatable engineered immunodevice that enables remote control over the antitumor immunity in vitro and in vivo with near-infrared (NIR) light. The immunodevice is composed of a rationally designed UV light-activatable immunostimulatory agent and upconversion nanoparticle, which acts as a transducer to shift the light sensitivity of the device to the NIR window. The controlled immune regulation allows the generation of effective immune response within tumor without disturbing immunity elsewhere in the body, thereby maintaining the antitumor efficacy while mitigating systemic toxicity. The present work illustrates the potential of the remote-controlled immunodevice for triggering of immunoactivity at the right time and site.
High efficiency perovskite quantum dot solar cells with charge separating heterostructure
Authors: Zhao Qian , Hazarika Abhijit , Chen Xihan , Harvey Steve P. , Larson Bryon W. , Teeter Glenn R. , Liu Jun , Song Tao , Xiao Chuanxiao , Shaw Liam , Zhang Minghui , Li Guoran , Beard Matthew C. , Luther Joseph M. 
Published: June 2019

AbstractMetal halide perovskite semiconductors possess outstanding characteristics for optoelectronic applications including but not limited to photovoltaics. Low-dimensional and nanostructured motifs impart added functionality which can be exploited further. Moreover, wider cation composition tunability and tunable surface ligand properties of colloidal quantum dot (QD) perovskites now enable unprecedented device architectures which differ from thin-film perovskites fabricated from solvated molecular precursors. Here, using layer-by-layer deposition of perovskite QDs, we demonstrate solar cells with abrupt compositional changes throughout the perovskite film. We utilize this ability to abruptly control composition to create an internal heterojunction that facilitates charge separation at the internal interface leading to improved photocarrier harvesting. We show how the photovoltaic performance depends upon the heterojunction position, as well as the composition of each component, and we describe an architecture that greatly improves the performance of perovskite QD photovoltaics.
A high-throughput screening and computation platform for identifying synthetic promoters with enhanced cell-state specificity (SPECS)
Authors: Wu Ming-Ru , Nissim Lior , Stupp Doron , Pery Erez , Binder-Nissim Adina , Weisinger Karen , Enghuus Casper , Palacios Sebastian R. , Humphrey Melissa , Zhang Zhizhuo , Maria Novoa Eva , Kellis Manolis , Weiss Ron , Rabkin Samuel D. , Tabach Yuval , Lu Timothy K. 
Published: June 2019

AbstractCell state-specific promoters constitute essential tools for basic research and biotechnology because they activate gene expression only under certain biological conditions. Synthetic Promoters with Enhanced Cell-State Specificity (SPECS) can be superior to native ones, but the design of such promoters is challenging and frequently requires gene regulation or transcriptome knowledge that is not readily available. Here, to overcome this challenge, we use a next-generation sequencing approach combined with machine learning to screen a synthetic promoter library with 6107 designs for high-performance SPECS for potentially any cell state. We demonstrate the identification of multiple SPECS that exhibit distinct spatiotemporal activity during the programmed differentiation of induced pluripotent stem cells (iPSCs), as well as SPECS for breast cancer and glioblastoma stem-like cells. We anticipate that this approach could be used to create SPECS for gene therapies that are activated in specific cell states, as well as to study natural transcriptional regulatory networks.
Intensified East Asian winter monsoon during the last geomagnetic reversal transition
Authors: Ueno Yusuke , Hyodo Masayuki , Yang Tianshui , Katoh Shigehiro 
Published: June 2019

AbstractThe strength of Earth’s magnetic dipole field controls galactic cosmic ray (GCR) flux, and GCR-induced cloud formation can affect climate. Here, we provide the first evidence of the GCR-induced cloud effect on the East-Asian monsoon during the last geomagnetic reversal transition. Bicentennial-resolution monsoon records from the Chinese Loess Plateau revealed that the summer monsoon (SM) was affected by millennial-scale climate events that occurred before and after the reversal, and that the winter monsoon (WM) intensified independently of SM variations; dust accumulation rates increased, coinciding with a cooling event in Osaka Bay. The WM intensification event lasted about 5000 years across an SM peak, during which the Earth’s magnetic dipole field weakened to <25% of its present strength and the GCR flux increased by more than 50%. Thus, the WM intensification likely resulted from the increased land–ocean temperature gradient originating with the strong Siberian High that resulted from the umbrella effect of increased low-cloud cover through an increase in GCR flux.
Label propagation defines signaling networks associated with recurrently mutated cancer genes
Authors: Cakir Merve , Mukherjee Sayan , Wood Kris C. 
Published: June 2019

AbstractHuman tumors have distinct profiles of genomic alterations, and each of these alterations has the potential to cause unique changes to cellular homeostasis. Detailed analyses of these changes could reveal downstream effects of genomic alterations, contributing to our understanding of their roles in tumor development and progression. Across a range of tumor types, including bladder, lung, and endometrial carcinoma, we determined genes that are frequently altered in The Cancer Genome Atlas patient populations, then examined the effects of these alterations on signaling and regulatory pathways. To achieve this, we used a label propagation-based methodology to generate networks from gene expression signatures associated with defined mutations. Individual networks offered a large-scale view of signaling changes represented by gene signatures, which in turn reflected the scope of molecular events that are perturbed in the presence of a given genomic alteration. Comparing different networks to one another revealed common biological pathways impacted by distinct genomic alterations, highlighting the concept that tumors can dysregulate key pathways through multiple, seemingly unrelated mechanisms. Finally, altered genes inducing common changes to the signaling network were used to search for genomic markers of drug response, connecting shared perturbations to differential drug sensitivity.
Optimal composition and position of histidine-containing tags improves biodistribution of 99mTc-labeled DARPin G3
Authors: Vorobyeva Anzhelika , Schulga Alexey , Konovalova Elena , Güler Rezan , Löfblom John , Sandström Mattias , Garousi Javad , Chernov Vladimir , Bragina Olga , Orlova Anna , Tolmachev Vladimir , Deyev Sergey M. 
Published: June 2019

AbstractRadionuclide molecular imaging of HER2 expression in disseminated cancer enables stratification of patients for HER2-targeted therapies. DARPin G3, a small (14 kDa) engineered scaffold protein, is a promising probe for imaging of HER2. We hypothesized that position (C- or N-terminus) and composition (hexahistidine or (HE)3) of histidine-containing tags would influence the biodistribution of [99mTc]Tc(CO)3-labeled DARPin G3. To test the hypothesis, G3 variants containing tags at N-terminus (H6-G3 and (HE)3-G3) or at C-terminus (G3-H6 and G3-(HE)3) were labeled with [99mTc]Tc(CO)3. Labeling yield, label stability, specificity and affinity of the binding to HER2, biodistribution and tumor targeting properties of these variants were compared side-by-side. There was no substantial influence of position and composition of the tags on binding of [99mTc]Tc(CO)3-labeled variants to HER2. The specificity of HER2 targeting in vivo was confirmed. The tumor uptake in BALB/c nu/nu mice bearing SKOV3 xenografts was similar for all variants. On the opposite, there was a strong influence of the tags on uptake in normal tissues. The tumor-to-liver ratio for [99mTc]Tc(CO)3-(HE)3-G3 was three-fold higher compared to the hexahistidine-tag containing variants. Overall, [99mTc]Tc(CO)3-(HE)3-G3 variant provided the highest tumor-to-lung, tumor-to-liver, tumor-to-bone and tumor-to-muscle ratios, which should improve sensitivity of HER2 imaging in these common metastatic sites.
lncRNA-PCAT1 rs2632159 polymorphism could be a biomarker for colorectal cancer susceptibility
Authors: Yang Ming-li , Huang Zhe , Wu Li-na , Wu Rong , Ding Han-xi , Wang Ben-gang 
Published: June 2019

Abstract
Background: Single-nucleotide polymorphisms (SNPs) in lncRNAs could be biomarkers for susceptibility to colorectal cancer (CRC), but the association of PCAT1 polymorphisms and CRC susceptibility is yet to be studied. Methods: Five tagSNPs covering the PCAT1 gene were detected through Kompetitive Allele-Specific PCR among 436 CRC patients and 510 controls. An expression quantitative trait locus (eQTL) bioinformatic analysis was then performed. Results: In the present study, PCAT1 rs2632159 polymorphism increased CRC risk by 1.37-fold and 2.19-fold in the dominant and recessive models, respectively (P=0.040 and 0.041). When the CRC cases were divided into colon cancer and rectal cancer, we found that this polymorphism affected colon cancer risk under the dominant model (P=0.022, OR = 1.51) and affected rectal cancer susceptibility under the recessive model (P=0.009, OR = 3.03). A more pronounced effect was observed in the male subgroup in that PCAT1 rs2632159 SNP increased rectal cancer risk by 3.97-fold (P=0.017). When PCAT1 rs2632159 was present, epistatic effects were observed with rs1902432 and rs785005 (P=0.011 and 0.008, respectively). eQTL analysis showed that rs2632159 could influence binding with the transcription factors EBF, LUN-1, and TCF12. Conclusion:PCAT1 rs2632159 SNP could be a biomarker for CRC risk. And the rs1902432 SNP might only have potential to be a biomarker for colon cancer risk.
Effects of Age at Cochlear Implantation on Learning and Cognition: A Critical Assessment
Authors: Marschark Marc , Duchesne Louise , Pisoni David 
Published: June 2019

Purpose
Age at cochlear implantation frequently is assumed to be a key predictor of pediatric implantation benefits, but outcomes related to learning and cognition appear inconsistent. This critical assessment examines relevant literature in an effort to evaluate the impact of age at implantation in those domains for individuals who received their devices as children.

Method
We examined 44 peer-reviewed articles from 2003 to 2018 considering age at implantation and conducted statistical analyses regarding its impact on several domains, including literacy, academic achievement, memory, and theory of mind.

Results
Across 167 assessments in various experiments and conditions, only 21% of the analyses related to age at implantation yielded evidence in favor of earlier implantation, providing greater benefits to academic achievement, learning, or cognition compared to implantation later in childhood. Among studies that considered cognitive processing (e.g., executive function, memory, visual–spatial functioning), over twice as many analyses indicated significant benefits of earlier implantation when it was considered as a discrete rather than a continuous variable.

Conclusion
Findings raise methodological, practical, and theoretical questions concerning how “early” is defined in studies concerning early cochlear implantation, the impact of confounding factors, and the use of nonstandard outcome measures. The present results and convergent findings from other studies are discussed in terms of the larger range of variables that need to be considered in evaluating the benefits of cochlear implantation and question the utility of considering age at implantation as a “gold standard” with regard to evaluating long-term outcomes of the procedure as a medical treatment/intervention for hearing loss.

Supplemental Material

https://doi.org/10.23641/asha.8323625
Longitudinal Change in Speech Rate and Intelligibility Between 5 and 7 Years in Children With Cerebral Palsy
Authors: Braza Meredith D. , Sakash Ashley , Natzke Phoebe , Hustad Katherine C. 
Published: June 2019

PurposeWe examined growth between 5 and 7 years in speech intelligibility, speech rate, and intelligible words per minute (IWPM) in 3 groups of children: those who were typically developing (TD), those with cerebral palsy (CP) and clinical speech motor impairment (SMI), and those with CP and no SMI (NSMI).MethodTwenty-six children with CP, 16 with SMI, and 10 with NSMI were each seen at 5, 6, and 7 years of age. A cross-sectional group of 30 age-matched TD children, 10 in each age group, were included as controls. All children produced a corpus of utterances of 2–7 words.ResultsAll groups of children showed increases in intelligibility and IWPM between 5 and 7 years. Only children with SMI showed increases in speech rate over time. Patterns of change were similar for children in the TD and NSMI groups but different for children in the SMI group.ConclusionsThe window of time between 5 and 7 years is an important period of growth for the production of connected speech where nearly all children, regardless of group, made significant changes in speech intelligibility and IWPM. Interventions focusing specifically on enhancing intelligibility in this age range may help facilitate even further growth in children with SMI, who still had marked intelligibility reductions at 7 years of age.
Effects of Written, Auditory, and Combined Modalities on Comprehension by People With Aphasia
Authors: Knollman-Porter Kelly , Wallace Sarah E. , Brown Jessica A. , Hux Karen , Hoagland Brielle L. , Ruff Darbi R. 
Published: June 2019

Background
People with aphasia experience reading challenges affecting participation in daily activities. Researchers have found combined auditory and written presentation modalities help people with aphasia comprehend contrived sentences and narratives, but less is known about the effects of combined modalities on functional, expository text comprehension.

Aims
This study's purpose was to examine comprehension accuracy, reviewing time, and modality preference of people with aphasia when presented with edited newspaper articles in written only, auditory only, and combined written and auditory modalities.

Method and Procedure
Twenty-eight adults with chronic aphasia read and/or listened to 36 passages. Following each passage, participants answered comprehension questions. Then, they ranked the modalities in accordance with preference and provided a rationale for their ranking.

Outcomes and Results
Comprehension accuracy was significantly better in the combined than auditory-only condition and in the written-only than auditory-only condition; the difference between combined and written-only conditions was not significant. Reviewing time differed significantly among conditions with the written-only condition taking longest and the auditory-only condition taking shortest. Most participants preferred the combined condition.

Conclusions
Access to combined modalities helps people with aphasia comprehend expository passages such as those found in newspapers better than auditory-only presentation. Furthermore, combined presentation decreases reviewing time from that needed for unsupported reading without compromising comprehension accuracy. Given that most participants preferred combined modality presentation, providing simultaneous auditory and written access to content through text-to-speech technology is a viable strategy when aphasia results in persistent reading challenges.
Semantic Category Convergence in Spanish–English Bilingual Children With and Without Developmental Language Disorder
Authors: Shivabasappa Prarthana , Peña Elizabeth D. , Bedore Lisa M. 
Published: June 2019

Purpose
The study examines the extent of convergence of semantic category members in Spanish–English bilingual children with reference to adults using a semantic fluency task.

Method
Thirty-seven children with developmental language disorder (DLD), matched pairwise with 37 typically developing (TD) children in the age range of 7;0–9;11 (years;months), produced items in 7 semantic categories (3 taxonomic and 4 slot-filler) in both Spanish and English. The 10 most frequently produced items for each category by 20 Spanish–English bilingual adults were identified as the most prototypical responses. The top 10 items generated by TD children and children with DLD, in their order of production, were analyzed for the amount of convergence with adults' responses.

Results
The top 5 items produced by children with DLD showed similar convergence scores as those produced by their TD peers. However, their responses in the 6th to 10th positions showed lower convergence scores than their TD peers. Children's convergence scores were higher for the slot-filler condition compared to taxonomic in both English and Spanish. The convergence scores also significantly differed across the semantic categories.

Conclusion
The children with DLD show greater convergence on the typical items generated earlier in their word lists than the items generated later. This pattern of convergence and divergence highlights their strengths and weaknesses in the representation of lexical–semantic knowledge for typical versus less typical items.

Supplemental Material

https://doi.org/10.23641/asha.8323613
Language Training Leads to Global Cognitive Improvement in Older Adults: A Preliminary Study
Authors: Wong Patrick C. M. , Ou Jinghua , Pang Celestina W. Y. , Zhang Ling , Tse Chi Shing , Lam Linda C. W. , Antoniou Mark 
Published: June 2019

Purpose
We report a preliminary study that prospectively tests the potential cognitive enhancing effect of foreign language (FL) learning in older adults with no clear signs of cognitive decline beyond what is age typical. Because language learning engages a large brain network that overlaps with the network of cognitive aging, we hypothesized that learning a new language later in life would be beneficial.

Method
Older adults were randomly assigned to 3 training groups: FL, games, and music appreciation. All were trained predominately by a computer-based program for 6 months, and their cognitive abilities were tested before, immediately after, and 3 months after training.

Results
FL and games, but not music appreciation, improved overall cognitive abilities that were maintained at 3 months after training.

Conclusion
This is the 1st randomized control study providing preliminary support for the cognitive benefits of FL learning.