bluuebunny/crossref_metadata_2025 huggingface dataset:
The Arabidopsis homologue of an eIF3 complex subunit associates with the COP9 complex1
Authors: Karniol Baruch , Yahalom Avital , Kwok Shing , Tsuge Tomohiko , Matsui Minami , Deng Xing-Wang , Chamovitz Daniel A
Published: July 2002

The Arabidopsis COP9 complex is a multi‐subunit repressor of photomorphogenesis which is conserved among multicellular organisms. Approximately 12 proteins copurify with the COP9 complex. Seven of these proteins are orthologues of subunits of the recently published mammalian COP9 complex. Four of the proteins show amino acid similarity to various subunits of the COP9 complex, eIF3 complex and 19S cap of the proteasome. We have studied one of these proteins in order to determine if it is a component of the COP9 complex. Arabidopsis p105 is highly similar to the p110 subunit of the human eIF3. The p105 gene is induced during photomorphogenesis, and RNA and protein analysis reveal different tissue accumulation patterns. p105 is found in a large protein complex. p105 interacts in yeast with both COP9 and FUS6, two known components of the COP9 complex. Our results indicate that p105 is not a component of the COP9 core complex, though it may interact with components of the complex.
The product of the mammalian orthologue of the Saccharomyces cerevisiaeHBS1 gene is phylogenetically related to eukaryotic release factor 3 (eRF3) but does not carry eRF3‐like activity
Authors: Wallrapp Christine , Verrier Sidonie-Brigitte , Zhouravleva Galina , Philippe Hervé , Philippe Michel , Gress Thomas M. , Jean-Jean Olivier
Published: July 2002

We describe here the cloning and sequencing of human and mouse cDNAs encoding a putative GTP binding protein. Sequence comparison shows that these cDNAs (named eRFS) are likely to represent the orthologues of the yeast Saccharomyces cerevisiae HBS1 gene and that the C‐terminal domains of the encoded proteins share structural features with eukaryotic elongation factor eEF‐1A and release factor 3 (eRF3) families. The phylogenetic analysis suggests that eRFS proteins and Hbs1p form a cluster of orthologous sequences branching with the eRF3 family. Nevertheless, in yeast, the human eRFS protein and Hbs1p do not complement eRF3/Sup35p thermosensitive mutation and do not interact with eRF1.
Catabolite inactivation of the high‐affinity hexose transporters Hxt6 and Hxt7 of Saccharomyces cerevisiae occurs in the vacuole after internalization by endocytosis1
Authors: Krampe Stefanie , Stamm Olaf , Hollenberg Cornelis P , Boles Eckhard
Published: July 2002

After addition of high concentrations of glucose, rates of high‐affinity glucose uptake in Saccharomyces cerevisiae decrease rapidly. We found that the high‐affinity hexose transporters Hxt6 and Hxt7 are subject to glucose‐induced proteolytic degradation (catabolite inactivation). Degradation occurs in the vacuole, as Hxt6/7 were stabilized in proteinase A‐deficient mutant cells. Degradation was independent of the proteasome. The half‐life of Hxt6 and Hxt7 strongly increased in end4, ren1 and act1 mutant strains, indicating that the proteins are delivered to the vacuole by endocytosis. Moreover, both proteins were also stabilized in mutants defective in ubiquitination. However, the initial signal that triggers catabolite inactivation is not relayed via the glucose sensors Snf3 and Rgt2.
Role of the C‐terminal domain of Bax and Bcl‐xL in their localization and function in yeast cells
Authors: Priault Muriel , Camougrand Nadine , Chaudhuri Bhabatosh , Manon Stéphen
Published: July 2002

It has been suggested that the C‐terminal domain of Bcl‐2 family members may contain a signal anchor sequence that targets these proteins to the mitochondrial outer membrane. We have investigated the consequence of deleting this domain upon cytochrome c release in yeast strains that coexpress truncated forms of Bax (i.e. BaxΔ) and Bcl‐xL (i.e. Bcl‐xLΔ). We find that (i) BaxΔ is as efficient as full‐length Bax in promoting cytochrome c release, but Bcl‐xLΔ has remarkably reduced rescuing ability compared to full‐length Bcl‐xL; (ii) full‐length Bcl‐xL protein acts by relocalizing Bax from the mitochondrial fraction to the soluble cytosolic fraction; (iii) Bax undergoes N‐terminal cleavage when expressed in yeast, which is prevented by coexpression of Bcl‐xL, suggesting that Bcl‐xL may mask the cleavage site of Bax through a direct physical interaction of the two proteins.
Dimerization of profilin II upon binding the (GP5)3peptide from VASP overcomes the inhibition of actin nucleation by profilin II and thymosin β4
Authors: Jonckheere Veronique , Lambrechts Anja , Vandekerckhove Joël , Ampe Christophe
Published: July 2002

Profilin II dimers bind the (GP5)3peptide derived from VASP with an affinity of approximately 0.5 μM. The resulting profilin II‐peptide complex overcomes the combined capacity of thymosin β4 and profilin II to inhibit actin nucleation and restores the extent of filament formation. We do not observe such an effect when barbed filament ends are capped. Neither can profilin I, in the presence of the peptide, promote actin polymerization during its early phase consistent with a lower affinity. Since a Pro17peptide‐profilin II complex only partially restores actin polymerization, the glycine residues in the VASP peptide appear important.
Glycodelin and β‐lactoglobulin, lipocalins with a high structural similarity, differ in ligand binding properties
Authors: Koistinen Hannu , Koistinen Riitta , Seppälä Markku , Burova Tatiana V. , Choiset Yvan , Haertlé Thomas
Published: July 2002

Human glycodelin, a lipocalin with a high amino acid similarity to β‐lactoglobulins, appears as various glycoforms with different biological activities in endometrium (glycodelin‐A) and seminal plasma (glycodelin‐S). We found that the structures of these glycodelins and β‐lactoglobulin are similar. Despite this structural similarity, unlike β‐lactoglobulin, glycodelin‐A binds neither retinoic acid nor retinol. It was impossible to detect any endogenous retinoids or steroids in any of the two purified glycodelins. Both their glycoforms share similar thermodynamic parameters of reversible denaturation suggesting that native folding of glycodelin‐A and glycodelin‐S is not influenced by the differences in glycosylation or by ligand binding.
Adaptive hypoxic tolerance in the subterranean mole rat Spalax ehrenbergi: the role of vascular endothelial growth factor
Authors: Avivi A. , Resnick M.B. , Nevo E. , Joel A. , Levy A.P.
Published: July 2002

Spalax ehrenbergi has evolved adaptations that allow it to survive and carry out normal activities in a highly hypoxic environment. A key component of this adaptation is a higher capillary density in some Spalax tissues resulting in a shorter diffusion distance for oxygen. Vascular endothelial growth factor (VEGF) is an angiogenic factor that is critical for angiogenesis during development and in response to tissue ischemia. We demonstrate here that VEGF expression is markedly increased in those Spalax tissues with a higher capillary density relative to the normal laboratory rat Rattus norvegicus. Upregulation of VEGF thus appears to be an additional mechanism by which Spalax has adapted to its hypoxic environment.
Elafin (elastase‐specific inhibitor) has anti‐microbial activity against Gram‐positive and Gram‐negative respiratory pathogens
Authors: Simpson A.J. , Maxwell A.I. , Govan J.R.W. , Haslett C. , Sallenave J.-M.
Published: July 2002

Elafin (elastase‐specific inhibitor) is a low molecular weight inhibitor of neutrophil elastase which is secreted in the lung. Using synthetic peptides corresponding to full‐length elafin (H2N‐1AVT.....95Q‐OH), the NH2‐terminal domain (H2N‐1AVT.....50K‐OH) and the COOH‐terminal domain (H2N‐51PGS.....95Q‐OH), we demonstrate that elafin's anti‐elastase activity resides exclusively in the COOH‐terminus. Several characteristics of elafin suggest potential anti‐microbial activity. The anti‐microbial activity of elafin, and of its two structural domains, was tested against the respiratory pathogensPseudomonas aeruginosa and Staphylococcus aureus. Elafin killed both bacteria efficiently, with 93% killing of P. aeruginosa by 2.5 μM elafin and 48% killing of S. aureus by 25 μM elafin. For both organisms, full‐length elafin was required to optimise bacterial killing. These findings represent the first demonstration of co‐existent anti‐proteolytic and anti‐microbial functions for elafin.
The combination of polymorphisms within interferon‐γ receptor 1 and receptor 2 associated with the risk of systemic lupus erythematosus
Authors: Nakashima Hitoshi , Inoue Hisako , Akahoshi Mitsuteru , Tanaka Yosuke , Yamaoka Kunihiro , Ogami Eiichi , Nagano Shuuji , Arinobu Yojiro , Niiro Hiroaki , Otsuka Takeshi , Niho Yoshiyuki
Published: July 2002

Genetic factors seem to play a significant role in susceptibility to systemic lupus erythematosus (SLE). We previously described the amino acid polymorphism (Val14Met) within the IFN‐γ receptor 1 (IFN‐γR1), and that the frequency of the Met14 allele in SLE patients was significantly higher than that of the healthy control population [Tanaka et al. (1999) Immunogenetics 49, 266–271]. We also found an amino acid polymorphism (Gln64Arg) within IFN‐γ receptor 2 (IFN‐γR2). Since the IFN‐γ receptor is a complex consisting of IFN‐γR1 and IFN‐γR2, we searched for the particular combination of two kinds of amino acid polymorphisms found within the IFN‐γ receptor which plays a prominent role in susceptibility to SLE. The greatest risk of the development of SLE was detected in the individuals who had the combination of IFNGR1 Met14/Val14 genotype and IFNGR2 Gln64/Gln64 genotype.
The role of chloroplastic NAD(P)H dehydrogenase in photoprotection
Authors: Endo Tsuyoshi , Shikanai Toshiharu , Takabayashi Atsushi , Asada Kozi , Sato Fumihiko
Published: July 2002

After a brief exposure to supra‐saturating light, leaves of a tobacco transformant, in which chloroplastic NAD(P)H dehydrogenase (NDH) was defective, showed more severe photoinhibition than the wild‐type, when judged by the parameter of chlorophyll fluorescence Fv/Fm. Repeated application of supra‐saturating light eventually resulted in chlorosis in the NDH‐defective mutant, while the wild‐type sustained less photodamage and was able to recover from it. The mechanism of the phenomena is discussed with respect to the potential role of NDH in photosynthesis.
Alternative splicing of synaptotagmins involving transmembrane exon skipping
Authors: Craxton Molly , Goedert Michel
Published: July 2002

The synaptotagmin gene family currently includes 12 members. Analysis of the three known genomic synaptotagmin sequences reveals conserved exon‐intron patterns which delineate the synaptotagmin structural domains. We used expressed sequence tag, reverse transcription PCR and RNAse protection assay analysis of synaptotagmin messenger RNAs to demonstrate the occurrence of alternative splicing events involving a number of exons. Exon‐skipped messages where transmembrane sequences have been removed or altered were found to be abundantly expressed by synaptotagmins 1, 4, 6 and 7. Although the expression of most synaptotagmins predominates in neural tissue, we find that by contrast, synaptotagmin 6 is more abundant in thymus.
Interactions between the full complement of human RNA polymerase II subunits
Authors: Schaller Sophie , Grandemange Sylvie , Shpakovski George V. , Golemis Erica A. , Kedinger Claude , Vigneron Marc
Published: July 2002

As an approach to elucidating the rules governing the assembly of human RNA polymerase II (hRPB), interactions between its subunits have been systematically analyzed. Eleven of the 12 expected hRPB subunits have previously been tested for reciprocal interactions (J. Biol. Chem. 272 (1997) 16815–16821). We now report the results obtained for the last subunit (hRPB4; Mol. Cell. Biol. 18 (1998) 1935–1945) and propose an essentially complete picture of the potential interactions occurring within hRPB. Finally, complementation experiments in yeast indicated that hRPB4 expression efficiently cured both heat and cold‐sensitivity of RPB4‐lacking strains, supporting the existence of conserved functional subunit interactions.
Hyperinsulinemia increases the risk of gestational hypertension
Authors: Hamasaki Tetsushi , Yasuhi Ichiro , Hirai Masanao , Masuzaki Hideaki , Ishimaru Tadayuki
Published: July 2002

Objective: To determine whether hyperinsulinemia is related to gestational hypertension. Methods: We measured the arterial blood pressure and the level of immunoreactive insulin (IRI) during a 75 g oral glucose tolerance test in a total of 84 pregnant women. Hyperinsulinemia was defined as a fasting IRI level ≥ 9 IU/1, while gestational hypertension was defined as arterial blood pressure ≥ 140/90 mmHg. Results: The incidence of gestational hypertension was higher in the hyperinsulinemic group (n = 29) than in the control group (n = 55) (24.1% vs. 7.3%, respectively P < 0.05). After controlling for maternal age, parity, pre‐pregnancy body mass index and the gestational age at the time of oral glucose tolerance test (OGTT), using a multiple regression model, the relative risk of developing gestational hypertension for a fasting insulin level was 1.19 (95% C.I., 1.03–1.38). Conclusion: Pregnant women with hyperinsulinemia are at increased risk of developing gestational hypertension.
Abdominal hysterectomy practice patterns in the United States
Authors: Sills E.S. , Saini J. , Steiner C.A. , McGee M. , Gretz H.F.
Published: July 2002

Objective: To describe nationwide practice trends for two principal techniques of abdominal hysterectomy in the United States, numbers and rates of total (TAH) and supracervical (SCH) hysterectomy were reviewed with charges for each operation. Methods: Practice patterns for all inpatient TAH and SCH discharges in the US from 1991 to 1994 were studied using HCUP‐3 NIS, a nationwide hospital discharge database. Hysterectomies performed for malignant disease, vaginally or with laparoscopic assistance were not sampled. For each year studied, the number and rate of TAH and SCH, average length of stay (LOS), and mean institutional charge were evaluated. Results: From 1991 to 1994, the US TAH rate (cases/10 000 females) decreased significantly from 25.7 to 20.5 (P = 0.02). During the same interval the SCH rate increased significantly from 0.16 to 0.41 (P = 0.04). Nevertheless, TAH accounted for >99% of all abdominal hysterectomies for each of the 4 years evaluated. The mean institutional charges for the two operations generally depicted SCH to be more costly than TAH. Conclusion: The national rates of TAH and SCH rates changed significantly in the United States from 1991 to 1994, with TAH declining and SCH increasing. This mix of cases continues to reflect a strong preference for TAH. Although hospital charges for both procedures increased during this study, these data show that SCH is more expensive than TAH. The much lower utilization of SCH renders nominal its impact on national healthcare expenditures, however. Further studies are needed to assess specific causative factors for these changes in US hysterectomy technique.
Corticosteroids alter the differentiated phenotype of articular chondrocytes
Authors: Fubini Susan L. , Todhunter Rory J. , Burton‐Wurster Nancy , Vernier‐Singer Margaret , Macleod James N.
Published: July 2002

Experimental evidence suggests that recommended dosages of some corticosteroids used clinically as antiinflammatory agents for treating arthropathies damage articular cartilage, but low dosages may be chondroprotective. The purpose of this study was to evaluate how different concentrations of methylprednisolone affect chondrocyte function and viability. Articular cartilage and chondrocytes were obtained from young adult horses, 1.5–3.5 years of age. Corticosteroid‐induced changes in collagen expression were studied at the transcriptional level by Northern blot analyses and at the translational level by measuring [3H]‐proline incorporation into [3H]‐hydroxyproline. Fibronectin mRNA splicing patterns were evaluated with ribonuclease protection assays. Cytotoxicity was studied using erythrosin B dye exclusion. Steady‐state levels of type II procollagen mRNA decreased without concurrent changes in type I procollagen expression as the medium methylprednisolone concentrations were increased from 1 × 101to 1 × 108pg/ml, dropping below 10% of control values by 1 × 105pg/ml. Cytotoxicity occurred as methylprednisolone levels were increased further from 1 × 108to 1 × 109pg/ml. Changes in total collagen (protein) synthesis were less pronounced, but also demonstrated significant suppression between 1 × 104and 1 × 108pg/ml. Corticosteroid‐induced changes in fibronectin isoform levels were evaluated in articular cartilage samples without in vitro culture. The cartilage‐specific (V + C)−isoform was suppressed in both normal and inflamed joints by a single intraarticular injection (0.1 mg/kg) of methylprednisolone. Combined, these data indicate that methylprednisolone suppresses matrix protein markers of chondrocytic differentiation. Decreased and altered chondrocyte expression of matrix proteins likely contributes to the pathogenesis of corticosteroid‐induced cartilage degeneration. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Truthiness and law: Nonprobative photos bias perceived credibility in forensic contexts
Authors: Derksen Daniel G. , Giroux Megan E. , Connolly Deborah A. , Newman Eryn J. , Bernstein Daniel M.
Published: June 2020

Nonprobative but related photos can increase the perceived truth value of statements relative to when no photo is presented (truthiness). In two experiments, we tested whether truthiness generalizes to credibility judgments in a forensic context. Participants read short vignettes in which a witness viewed an offence. The vignettes were presented with or without a nonprobative, but related photo. In both experiments, participants gave higher witness credibility ratings to photo‐present vignettes compared to photo‐absent vignettes. In Experiment 2, half the vignettes included additional nonprobative information in the form of text. We replicated the photo presence effect in Experiment 2, but the nonprobative text did not significantly alter witness credibility. The results suggest that nonprobative photos can increase the perceived credibility of witnesses in legal contexts.
Nature‐Inspired Adhesive Catecholamines for Highly Concentrated Colorimetric Signal in Spatial Biomarker Labeling
Authors: Kim Seunghwi , Hong Seonki
Published: June 2020

Colorants have been utilized for precise biomarker detection in rapid and convenient colorimetric bioassays. However, the diffusion of colorants in solution often results in poor sensitivity, which is a major obstacle to the clinical translation of current colorants. To address this issue, in the current study, a unique colorant is developed that possesses adhesiveness for concentration near the target biomarker, avoiding diffusion. In nature, the synergistic interplay between catechol and amine functional groups is thought to be key for the unique mechanism of marine mussel adhesion. In addition, polymerized catecholamines are found in nature as biopigments, that is, in melanin. The dual role of catechol/catecholamine moieties in natural organics inspire to design novel colorimetric bioassays based on an adhesive colorant. Horseradish peroxidase (HRP) is used to initiate in situ polymerization of the catecholic precursors with amine‐containing additive molecules and simultaneously attach them near the HRP‐labeled biomarkers. This novel catecholamine‐based adhesive colorant provides an excellent quantitative (naked‐eye) visible signal and it also generates superb spatial information on the biomarkers on complex surfaces (e.g., cell membranes).
Nanobottles for Controlled Release and Drug Delivery
Authors: Qiu Jichuan , Xu Jianchang , Xia Younan
Published: June 2020

Nanobottles refer to colloidal particles with a hollow interior and a single opening in the wall. These unique features make them ideal carriers for the loading, encapsulation, release, and delivery of various types of theranostic agents in an array of biomedical applications. The hollow interior gives them a high loading capacity while the opening enables quick loading and controlled release of the payload(s). More significantly, on‐demand release can be readily achieved by adding a stimuli‐responsive material as the inner matrix or cork stopper. This progress report begins with an introduction to the general structures and properties of nanobottles, followed by a brief discussion on the methods developed for their fabrication. The use of nanobottles for loading different types of payloads is then showcased, including small‐molecule drugs, biomacromolecules, imaging contrast agents, and functional nanoparticles. The strategies explored for controlling the release by varying the size of the opening and/or integrating with a stimuli‐responsive material are also highlighted. This paper concludes with some perspectives on future directions for this class of nanomaterials in terms of fabrication, functionalization, and application.
Combining Qdot Nanotechnology and DNA Nanotechnology for Sensitive Single‐Cell Imaging
Authors: Zhou Wen , Han Yan , Beliveau Brian J. , Gao Xiaohu
Published: June 2020

Immunohistochemistry (IHC) can provide detailed information about protein expression within the cell microenvironment and is one of the most common techniques in biology and medicine due to the broad availability of highly specific antibodies and well‐established bioconjugation methods for modification of these antibodies with chromogens and fluorophores. Despite recent advances in this field, it remains challenging to simultaneously achieve high multiplexing, sensitivity, and throughput in single‐cell profiling experiments. Here, the combination of two powerful technologies is reported, quantum dot and signal amplification by exchange reaction (QD‐SABER), for sensitive and multiplexed imaging of endogenous proteins. Compared to the conventional IHC process using dye‐labeled secondary antibodies (which already has a built‐in signal amplification mechanism), QD‐SABER provides an additional 7.6‐fold signal amplification. In addition, the DNA hybridization‐based IHC can be rapidly removed to regenerate the sample for subsequent cycles of immunostaining (>10 cycles), greatly expanding the multiplexing capability.
Direct Dehydrogenation for the Synthesis of α,β‐Unsaturated Carbonyl Compounds
Authors: Chen Hong , Liu Long , Huang Tianzeng , Chen Jing , Chen Tieqiao
Published: June 2020

α,β‐Unsaturated carbonyl compounds are among the most fundamentally important functional compounds and are widely applied in synthetic chemistry, medical chemistry and material chemistry. Thus, their synthesis has attracted much attention of chemists. The dehydrogenation of two adjacent sp3C−H bonds can directly construct carbon‐carbon double bonds with high atom efficiency, and has been used for preparing unsaturated compounds as a powerful strategy. Herein, we highlight recent advances in the preparation of the valuable α,β‐unsaturated carbonyl compounds through α,β‐dehydrogenation.

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An Easy, General and Practical Method for the Construction of Alkyl Sulfonyl Fluorides
Authors: Zhang Xu , Fang Wan‐Yin , Lekkala Ravindar , Tang Wenjian , Qin Hua‐Li
Published: June 2020

A visible light‐induced reductive addition of 1°, 2° and 3° alkyl iodides to ethenesulfonyl fluoride, employing Hantzsch ester as a hydrogen source at room temperature was developed. This method featured a wide substrate scope and great functional group compatibility, providing facile and robust process to alkyl sulfonyl fluorides including enzyme inhibitors, natural products and drugs derivatives in up to 99% yield. Further derivatization of resultant aliphatic sulfonyl fluorides was also achieved through sulfur fluoride exchange (SuFEx) reactions to deliver sulfonates and sulfonamides as privileged motifs for medicinal chemistry.

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Proteomic Identification Reveals the Role of Ciliary Extracellular‐Like Vesicle in Cardiovascular Function
Authors: Mohieldin Ashraf M. , Pala Rajasekharreddy , Sherpa Rinzhin T. , Alanazi Madhawi , Alanazi Ashwaq , Shamloo Kiumars , Ahsan Amir , AbouAlaiwi Wissam A. , Moresco James J. , Yates John R. , Nauli Surya M.
Published: June 2020

Primary cilia are shown to have membrane swelling, also known as ciliary bulbs. However, the role of these structures and their physiological relevance remains unknown. Here, it is reported that a ciliary bulb has extracellular vesicle (EV)‐like characteristics. The ciliary extracellular‐like vesicle (cELV) has a unique dynamic movement and can be released by mechanical fluid force. To better identify the cELV, differential multidimensional proteomic analyses are performed on the cELV. A database of 172 cELV proteins is generated, and all that examined are confirmed to be in the cELV. Repressing the expression of these proteins in vitro and in vivo inhibits cELV formation. In addition to the randomized heart looping, hydrocephalus, and cystic kidney in fish, compensated heart contractility is observed in both fish and mouse models. Specifically, low circulation of cELV results in hypotension with compensated heart function, left ventricular hypertrophy, cardiac fibrosis, and arrhythmogenic characteristics, which result in a high mortality rate in mice. Furthermore, the overall ejection fraction, stroke volume, and cardiac output are significantly decreased in mice lacking cELV. It is thus proposed that the cELV as a nanocompartment within a primary cilium plays an important role in cardiovascular functions.
Racially diverse participant registries to facilitate the recruitment of African Americans into presymptomatic Alzheimer's disease studies
Authors: Cocroft Shelytia , Welsh‐Bohmer Kathleen A. , Plassman Brenda L. , Chanti‐Ketterl Marianne , Edmonds Henry , Gwyther Lisa , McCart Michelle , MacDonald Heather , Potter Guy , Burke James R.
Published: June 2020

Introduction

The Alzheimer's Disease Prevention Registry (ADPR) of the Joseph and Kathleen Bryan Alzheimer's Disease Research Center at Duke University has been successful in achieving a racially diverse and “research ready” cohort of cognitively healthy volunteers.

Methods

The ADPR is based on an infrastructure that includes: (1) an administrative leadership team; (2) a coordinating center; (3) an IT management team; (4) a community engagement team; and (5) collaborations with study partners across disciplines.

Results

The ADPR currently has more than 4677 members, 26% of whom are African American. The ADPR has supported 21 studies including 8 biomarker studies, 7 clinical trials, 4 cognitive neuroscience studies, and 2 studies assessing novel computerized measures.

Discussion

We describe our experiences establishing and maintaining a diverse ADPR as well as insights on recruitment strategies to increase the representation of African Americans in Alzheimer's disease studies.
Drug‐Responsive Inhomogeneous Cortical Modulation by Direct Current Stimulation
Authors: Sun Yan , Dhamne Sameer C. , Carretero‐Guillén Alejandro , Salvador Ricardo , Goldenberg Marti C. , Godlewski Brianna R. , Pascual‐Leone Alvaro , Madsen Joseph R. , Stone Scellig S. D. , Ruffini Giulio , Márquez‐Ruiz Javier , Rotenberg Alexander
Published: June 2020

Objective

Cathodal direct current stimulation (cDCS) induces long‐term depression (LTD)‐like reduction of cortical excitability (DCS‐LTD), which has been tested in the treatment of epilepsy with modest effects. In part, this may be due to variable cortical neuron orientation relative to the electric field. We tested, in vivo and in vitro, whether DCS‐LTD occurs throughout the cortical thickness, and if not, then whether drug–DCS pairing can enhance the uniformity of the cortical response and the cDCS antiepileptic effect.

Methods

cDCS‐mediated changes in cortical excitability were measured in vitro in mouse motor cortex (M1) and in human postoperative neocortex, in vivo in mouse somatosensory cortex (S1), and in a mouse kainic acid (KA)‐seizure model. Contributions of N‐methyl‐D‐aspartate–type glutamate receptors (NMDARs) to cDCS‐mediated plasticity were tested with application of NMDAR blockers (memantine/D‐AP5).

Results

cDCS reliably induced DCS‐LTD in superficial cortical layers, and a long‐term potentiation (LTP)‐like enhancement (DCS‐LTP) was recorded in deep cortical layers. Immunostaining confirmed layer‐specific increase of phospho‐S6 ribosomal protein in mouse M1. Similar nonuniform cDCS aftereffects on cortical excitability were also found in human neocortex in vitro and in S1 of alert mice in vivo. Application of memantine/D‐AP5 either produced a more uniform DCS‐LTD throughout the cortical thickness or at least abolished DCS‐LTP. Moreover, a combination of memantine and cDCS suppressed KA‐induced seizures.

Interpretation

cDCS aftereffects are not uniform throughout cortical layers, which may explain the incomplete cDCS clinical efficacy. NMDAR antagonists may augment cDCS efficacy in epilepsy and other disorders where regional depression of cortical excitability is desirable. ANN NEUROL 2020;88:489–502
A General Catalyst Based on Cobalt Core–Shell Nanoparticles for the Hydrogenation of N‐Heteroarenes Including Pyridines
Authors: Murugesan Kathiravan , Chandrashekhar Vishwas G. , Kreyenschulte Carsten , Beller Matthias , Jagadeesh Rajenahally V.
Published: June 2020

Herein, we report the synthesis of specific silica‐supported Co/Co3O4 core–shell based nanoparticles prepared by template synthesis of cobalt‐pyromellitic acid on silica and subsequent pyrolysis. The optimal catalyst material allows for general and selective hydrogenation of pyridines, quinolines, and other heteroarenes including acridine, phenanthroline, naphthyridine, quinoxaline, imidazo[1,2‐a]pyridine, and indole under comparably mild reaction conditions. In addition, recycling of these Co nanoparticles and their ability for dehydrogenation catalysis are showcased.
Thermal‐Gated Polymer Electrolytes for Smart Zinc‐Ion Batteries
Authors: Zhu Jiacai , Yao Minjie , Huang Shuo , Tian Jinlei , Niu Zhiqiang
Published: June 2020

Smart self‐protection is essential for addressing safety issues of energy‐storage devices. However, conventional strategies based on sol‐gel transition electrolytes often suffer from unstable self‐recovery performance. Herein, smart separators based on thermal‐gated poly(N‐isopropylacrylamide) (PNIPAM) hydrogel electrolytes were developed for rechargeable zinc‐ion batteries (ZIBs). Such PNIPAM‐based separators not only display a pore structure evolution from opened to closed states, but also exhibit a surface wettability transition from hydrophilic to hydrophobic behaviors when the temperature rises. This behavior can suppress the migration of electrolyte ions across the separators, realizing the self‐protection of ZIBs at high temperatures. Furthermore, the thermal‐gated behavior is highly reversible, even after multiple heating/cooling cycles, because of the reversibility of temperature‐dependent structural evolution and hydrophilic/hydrophobic transition. This work will pave the way for designing thermal‐responsive energy‐storage devices with safe and controlled energy delivery.
Impact of adolescent obesity on middle‐age health of women given data MAR
Authors: Shin Yongyun , Sun Shumei , Bandyopadhyay Dipankar
Published: June 2020

We analyze adolescent BMI and middle‐age systolic blood pressure (SBP) repeatedly measured on women enrolled in the Fels Longitudinal Study (FLS) between 1929 and 2010 to address three questions: Do adolescent‐specific growth rates in body mass index (BMI) and menarche affect middle‐age SBP? Do they moderate the aging effect on middle‐age SBP? Have the effects changed over historical time? To address the questions, we propose analyzing a growth curve model (GCM) that controls for age, birth‐year cohort, and historical time. However, several complications in the data make the GCM analysis nonstandard. First, the person‐specific adolescent BMI and middle‐age SBP trajectories are unobservable. Second, missing data are substantial on BMI, SBP, and menarche. Finally, modeling the latent trajectories for BMI and SBP, repeatedly measured on two distinct sets of unbalanced time points, are computationally intensive. We adopt a bivariate GCM for BMI and SBP with correlated random coefficients. To efficiently handle missing values of BMI, SBP, and menarche assumed missing at random, we estimate their joint distribution by maximum likelihood via the EM algorithm where the correlated random coefficients and menarche are multivariate normal. The estimated distribution will be transformed to the desired GCM for SBP that includes the random coefficients of BMI and menarche as covariates. We demonstrate unbiased estimation by simulation. We find that adolescent growth rates in BMI and menarche are positively associated with, and moderate, the aging effect on SBP in middle age, controlling for age, cohort, and historical time, but the effect sizes are at most modest. The aging effect is significant on SBP, controlling for cohort and historical time, but not vice versa.
Ki67 expression at Kasai portoenterostomy as a prognostic factor in patients with biliary atresia
Authors: Yoshii D , Inomata Y , Komohara Y , Shimata K , Honda M , Hayashida S , Oya Y , Yamamoto H , Yamamoto H , Sugawara Y , Hibi T
Published: June 2020

Background

Biliary atresia is a rare paediatric biliary obliteration disease with unknown aetiology, and is the most common indication for paediatric liver transplantation (LT). However, no consensus for predicting Kasai portoenterostomy (KP) outcomes using liver histological findings exists. Ki67 is a popular biomarker for measuring and monitoring cellular proliferation.

Methods

Ki67 (clone, MIB-1) liver parenchyma expression was measured by immunohistochemical staining of samples from living donors and patients with biliary atresia to assess its value in predicting outcomes after KP.

Results

Of 35 children with biliary atresia, 13 were native liver survivors (NLS), 17 were non-NLS, and five had primary LT. The median proportion of Ki67 immunostained areas in donors and patients with biliary atresia at KP was 0·06 and 0·99 per cent respectively. Univariable analysis identified a high proportion of Ki67 areas, high Ki67 cell numbers and high Ki67-positive/leucocyte common antigen-positive cell numbers at KP as significant predictors of poor native liver survival after KP (hazard ratio 9·29, 3·37 and 12·17 respectively). The proportion of Ki67 areas in the non-NLS group was significantly higher than that in the NLS group (1·29 versus 0·72 per cent respectively; P = 0·001), and then decreased at LT (0·32 per cent versus 1·29 per cent at KP; P < 0·001).

Conclusion

This study has demonstrated the clinical data and time course of Ki67 expression in patients with biliary atresia. High Ki67 expression at KP may be an important predictor of native liver survival following the procedure.
Application of tail vein serial microsampling for plasma or dried plasma spots in toxicokinetic assessment in rats using acetaminophen as the model compound
Authors: Li Wenkui , Dugyala Ravi , Devine Patrick J. , Jardel Matthew , Doherty John , Kubek Katie , Lapadula Daniel , Flarakos Jimmy
Published: June 2020

In the current study, two groups of rats (five per group) were administered a single oral dose of 500 mg/kg acetaminophen. For toxicokinetic assessment, the Group 1 animals were bled via conventional sparse (two animals/time point) sublingual vein bleeding (~0.5 ml) with anesthesia, while the Group 2 animals were bled via serial tail vein microsampling (~0.075 ml) without anesthesia. All collected blood was processed for plasma. Each Group 2 plasma sample (~30 μl) was divided into ‘wet’ and ‘dried’ (dried plasma spots). All plasma samples were analyzed by LC–MS/MS for acetaminophen and its major metabolites acetaminophen glucuronide and acetaminophen sulfate. In addition, plasma and urine samples were collected for analysis of corticosterone and creatinine to assess stress levels. Comparable plasma exposure to acetaminophen and its two metabolites was observed in the plasma obtained via conventional sparse sublingual vein bleeding and serial tail vein microsampling and between the ‘wet’ and ‘dried’ plasma obtained by the latter. Furthermore, comparable corticosterone levels or corticosterone/creatinine ratios between the two groups suggested that serial microsampling without anesthesia did not increase the levels of stress as compared with conventional sampling with anesthesia, confirming the utility of microsampling for plasma or dried plasma spots in rodent toxicokinetic assessment.
Digital signal processing course on Jupyter–Python Notebook for electronics undergraduates
Authors: Zúñiga‐López Arturo , Avilés‐Cruz Carlos
Published: June 2020

The Jupyter–Python Notebook open source is currently used world‐wide as a programming environment for courses and labs. This paper describes an application of a set of Python computer programs implemented in the form of Jupyter notebooks to learn the course of digital signal processing and also seeks to contribute to the development of innovative teaching methodologies. A set of user‐friendly Jupyter notebooks workflows allows teachers–students to teach and learn theoretical concepts, description of problems, computer code, and simulation results with a graphical output. The proposed environment allows teachers/students to code their simulations in Python or Octave simulating languages. Additionally, a new approach involves student‐centered learning to teach theoretical and lab concepts.
Adjusting to life during a pandemic
Authors: Miles David
Published: June 2020

This article will deal with the pandemic and one university's response. I am sure everyone has their own story, but I am from a town in New Jersey that was called the epicenter of the virus in the early stages of its spread.
Campus climate surveys are a useful, but imperfect, sexual violence barometer
Authors: Sutton Halley
Published: June 2020

Campus climate surveys detailing the prevalence of sexual violence on college campuses are helpful in depicting the realities on campus but not infallible, according to a report by the U.S. Government Accountability Office. The report outlined several problems with the challenges that institutions face in conducting and analyzing the surveys, including the ways that sexual violence is defined on campuses, and the difficulty comparing results across multiple campuses. The writers of the report noted that this is especially problematic, considering that the reports are often used to help prospective college students and their parents determine the relative safety of attending a college campus in comparison to others, but that the lack of uniformity in the reports across institutions makes it difficult to do so.
Study of Protein Adsorption During Sterile Filtration of Protein Formulations by ILC
Authors: Haindl Susanne Maria Hilda , Doppleb Olivia , Förster Lucas , Wraage Sophia , Reiche Annette
Published: June 2020

Protein adsorption is usually regarded as the main reason for filter fouling in sterile filtration of protein formulations. To achieve a better insight into this phenomenon, protein adsorption was studied during filtration of stabilized bovine serum albumin (BSA) and γ‐globulin formulations through 0.2‐µm microfilter membranes by inverse liquid chromatography (ILC). Adsorption processes can be studied with this method by measurement of breakthrough curves. The change of the concentration in the fluid phase is measured with high accuracy by an inline UV‐detector.
Recent Advances in Experimental Techniques for Flow and Mass Transfer Analyses in Thermal Separation Systems
Authors: Hampel Uwe , Schubert Markus , Döß Alexander , Sohr Johanna , Vishwakarma Vineet , Repke Jens‐Uwe , Gerke Sören J. , Leuner Hannes , Rädle Matthias , Kapoustina Viktoria , Schmitt Lucas , Grünewald Marcus , Brinkmann Jost H. , Plate Dominik , Kenig Eugeny Y. , Lutters Nicole , Bolenz Lukas , Buckmann Felix , Toye Dominique , Arlt Wolfgang , Linder Thomas , Hoffmann Rainer , Klein Harald , Rehfeldt Sebastian , Winkler Thomas , Bart Hans‐Jörg , Wirz Dominic , Schulz Jonas , Scholl Stephan , Augustin Wolfgang , Jasch Katharina , Schlüter Florian , Schwerdtfeger Natalie , Jahnke Stefan , Jupke Andreas , Kabatnik Christoph , Braeuer Andreas Siegfried , D'Auria Mirko , Runowski Thomas , Casal Maria Francisco , Becker Karsten , David Anna‐Lena , Górak Andrzej , Skiborowski Mirko , Groß Kai , Qammar Hina
Published: June 2020

Modelling flow and mass transfer of thermal separation equipment constitutes one of the most challenging tasks in fluids process engineering. The difficulty of this task comes from the multiscale multiphase flow phenomena in rather complex geometries. Both analysis of flow and mass transfer on different scales as well as validation of models and simulation results require advanced experimental and measurement techniques. As a follow‐up to intensive discussions during the 2019 Tutzing Symposium “Separation Units 4.0” a wide set of available modern experimental technologies is presented.
The Afirma Xpression Atlas for thyroid nodules and thyroid cancer metastases: Insights to inform clinical decision‐making from a fine‐needle aspiration sample
Authors: Krane Jeffrey F. , Cibas Edmund S. , Endo Mayumi , Marqusee Ellen , Hu Mimi I. , Nasr Christian E. , Waguespack Steven G. , Wirth Lori J. , Kloos Richard T.
Published: June 2020

Recent analytical and clinical validation of the Afirma Xpression Atlas (XA) demonstrates test reliability and the identification of genomic alterations that may inform patient management. The updated Afirma Genomic Sequencing Classifier and XA reports aim to optimize the understanding of these contributions, including decisions about observation versus surgery, the need for disease‐specific preoperative testing, associated neoplasm types, prognostics, the identification of molecular targets for systemic therapy, and the recognition of potential hereditary syndromes.
SA Sketch: A self‐adaption sketch framework for high‐speed network
Authors: Zhu Haiting , Zhang Yuan , Zhang Lu , He Gaofeng , Liu Linfeng , Liu Ning
Published: June 2020

Sketch is a compact data structure used to summarize data streams. It is widely used in the measurement of network traffic, and its accuracy is higher than traditional methods. Currently, there are some typical sketches: Count‐Min Sketch, CU Sketch, and Count Sketch. According to the characteristics of network traffic, we propose a new sketch framework called Self‐Adaption Sketch, which is combined Sketch with Bloom Filter. In the framework, the sketch is created dynamically and the memory space is adjusted timely according to the network traffic by using the concept carrying. Our experiment results showed that the space utilization and accuracy are significantly improved while the throughput of self‐adaption sketch is maintained at a relatively good level.
Lymphocyte Subset Counts in COVID‐19 Patients: A Meta‐Analysis
Authors: Huang Wei , Berube Julie , McNamara Michelle , Saksena Suraj , Hartman Marsha , Arshad Tariq , Bornheimer Scott J. , O'Gorman Maurice
Published: June 2020

A reduced peripheral blood absolute lymphocyte count with an elevated neutrophil count has been a consistent observation in hospitalized coronavirus disease 2019 (COVID‐19) patients. In this brief meta‐analysis, the reduction of lymphocyte subset counts in COVID‐19 patients was investigated across 20 peer‐reviewed studies meeting criteria for reporting lymphocyte subset counts and COVID‐19 disease severity. CD4+ T cell, CD8+ T cell, B cell, NK cell, and total lymphocyte cell counts all showed statistically significant reduction in patients with severe/critical COVID‐19 disease compared to mild/moderate disease. T‐cell subsets showed the largest standardized magnitude of change. In some studies, multivariate analysis has shown that CD4 and/or CD8 T‐cells counts are independently predictive of patient outcomes. © 2020 International Society for Advancement of Cytometry
Help professors direct students to the DS Office
Authors: Hamblet Elizabeth C.
Published: June 2020

Research shows that some students who received accommodations in high school don't register for them in college. Some students might have a learning disability that hasn't been identified but is affecting their performance. Professors can help get students to your office, but you want to make sure they do it effectively.
A high‐throughput method to quantify feeding rates in aquatic organisms: A case study with Daphnia
Authors: Hite Jessica L. , Pfenning‐Butterworth Alaina C. , Vetter Rachel E. , Cressler Clayton E.
Published: June 2020

Food ingestion is one of the most basic features of all organisms. However, obtaining precise—and high‐throughput—estimates of feeding rates remains challenging, particularly for small, aquatic herbivores such as zooplankton, snails, and tadpoles. These animals typically consume low volumes of food that are time‐consuming to accurately measure.

We extend a standard high‐throughput fluorometry technique, which uses a microplate reader and 96‐well plates, as a practical tool for studies in ecology, evolution, and disease biology. We outline technical and methodological details to optimize quantification of individual feeding rates, improve accuracy, and minimize sampling error.

This high‐throughput assay offers several advantages over previous methods, including i) substantially reduced time allotments per sample to facilitate larger, more efficient experiments; ii) technical replicates; and iii) conversion of in vivo measurements to units (mL‐1 hr‐1 ind‐1) which enables broad‐scale comparisons across an array of taxa and studies.

To evaluate the accuracy and feasibility of our approach, we use the zooplankton, Daphnia dentifera, as a case study. Our results indicate that this procedure accurately quantifies feeding rates and highlights differences among seven genotypes.

The method detailed here has broad applicability to a diverse array of aquatic taxa, their resources, environmental contaminants (e.g., plastics), and infectious agents. We discuss simple extensions to quantify epidemiologically relevant traits, such as pathogen exposure and transmission rates, for infectious agents with oral or trophic transmission.
Tolvaptan vs. furosemide‐based diuretic regimens in patients hospitalized for heart failure with hyponatremia (AQUA‐AHF)
Authors: Ng Tien M.H. , Grazette Luanda P. , Fong Michael W. , Yoon Andrew J. , Lou Mimi , Kuo Allen , Upadhyay Rani Y. , Han Emily E. , Mehra Anilkumar , Elkayam Uri
Published: June 2020

Aims

Hyponatremia is associated with poorer outcomes and diuretic response in patients hospitalized for heart failure. This study compared a tolvaptan‐based vs. furosemide‐based diuretic regimen on short‐term clinical responses in hyponatremic acute heart failure.

Methods and results

Prospective, randomized, open‐label, parallel‐group, single‐centre study comparing oral tolvaptan vs. continuous infusion furosemide. Thirty‐three subjects requiring hospitalization for acute congestive heart failure, and a serum sodium < 135 mmol/L, were randomized to tolvaptan 30 mg orally daily or furosemide 5 mg/h intravenously for initial 24 h, after which treatments could be escalated. Median daily dose throughout was tolvaptan 30 mg and furosemide 120 mg, with four subjects in each group requiring dose escalation. Urine output and net fluid balance were not different between groups at 24 h or subsequent time points up to 96 h. Changes in estimated glomerular filtration rate were comparable. Cystatin C improved at 24 h with tolvaptan compared with furosemide (−6.4 ± 11.8 vs. 4.1 ± 17.2% change, P = 0.036), but the effect was transient. No significant between group differences were seen for NT‐proBNP, plasma renin activity, or urinary neutrophil gelatinase‐associated lipocalin:Cr. Serum sodium, as well as copeptin levels, increased with tolvaptan compared with furosemide.

Conclusions

Oral tolvaptan was associated with similar, but not superior, diuresis compared with intravenous furosemide for acute heart failure with concomitant hyponatremia.