bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction of heparin with annexin V
Authors: Capila Ishan , VanderNoot Victoria A , Mealy Tanya R , Seaton Barbara A , Linhardt Robert J
Published: July 2002

The energetics and kinetics of the interaction of heparin with the Ca+2 and phospholipid binding protein annexin V, was examined and the minimum oligosaccharide sequence within heparin that binds annexin V was identified. Affinity chromatography studies confirmed the Ca+2 dependence of this binding interaction. Analysis of the data obtained from surface plasmon resonance afforded a K
d of ∼21 nM for the interaction of annexin V with end‐chain immobilized heparin and a K
d of ∼49 nM for the interaction with end‐chain immobilized heparan sulfate. Isothermal titration calorimetry showed the minimum annexin V binding oligosaccharide sequence within heparin corresponds to an octasaccharide sequence. The K
d of a heparin octasaccharide binding to annexin V was ∼1 μM with a binding stoichiometry of 1:1.
Formation of adenosine 5′‐tetraphosphate from the acyl phosphate intermediate: a difference between the MurC and MurD synthetases of Escherichia coli
Authors: Bouhss Ahmed , Dementin Sébastien , van Heijenoort Jean , Parquet Claudine , Blanot Didier
Published: July 2002

The mechanism of the Mur synthetases of peptidoglycan biosynthesis is thought to involve in each case the successive formation of an acyl phosphate and a tetrahedral intermediate. The existence of the acyl phosphates for the MurC and MurD enzymes from Escherichia coli was firmly established by their in situ reduction by sodium borohydride followed by acid hydrolysis, yielding the corresponding amino alcohols. Furthermore, it was found that MurD, but not MurC, catalyses the synthesis of adenosine 5′‐tetraphosphate from the acyl phosphate, thereby substantiating its existence and pointing out a difference between the two enzymes.
Molecular architecture of Manduca sexta midgut V1 ATPase visualized by electron microscopy
Authors: Radermacher Michael , Ruiz Teresa , Harvey William R. , Wieczorek Helmut , Grüber Gerhard
Published: July 2002

The structure of the V1 ATPase from the tobacco hornworm Manduca sexta has been determined from electron micrographs of isolated, negatively stained specimens. The resulting images clearly show a pseudohexagonal arrangement of six equal‐sized protein densities, presumably representing the three copies each of subunits A and B, which comprise the headpiece of the enzyme. A seventh density could be observed either centrally or asymmetrically to the hexamer. The maximum diameter of the V1 complex in the hexagonal projection is 13 nm with each of the six peripheral densities being 3–4 nm in diameter.
Comparison of the effects of bax‐expression in yeast under fermentative and respiratory conditions: investigation of the role of adenine nucleotides carrier and cytochrome c
Authors: Priault Muriel , Camougrand Nadine , Chaudhuri Bhabatosh , Schaeffer Jacques , Manon Stéphen
Published: July 2002

A new system for bax‐expression in yeast has been devised to investigate bax's effect under fermentative and respiro‐fermentative conditions. This has allowed us to show unambiguously that the ability of bax to kill yeast is higher under respiratory conditions than under purely fermentative conditions. The extent of killing under respiro‐fermentative conditions (non‐repressive sugars) is intermediate. It has been proposed that the two proteins adenine nucleotides carrier (ANC) and cytochrome c play a crucial role in bax‐induced cell death. We have investigated the effects of deletion of the genes encoding the two proteins on the toxicity induced by bax, using this new system. The absence of ANC did not modify bax‐induced lethality in any way. Moreover, the absence of cytochrome c also did not prevent bax‐induced death. Only the kinetics of lethality were altered. All these effects are prevented by co‐expression of bcl‐x
L.
Low temperature and aging‐promoted expression of PUMP in potato tuber mitochondria
Authors: Nantes Iseli L. , Fagian Marcia M. , Catisti Rosana , Arruda Paulo , Maia Ivan G. , Vercesi Anibal E.
Published: July 2002

In this communication, we show that the plant uncoupling mitochondrial protein (PUMP) present in potato tuber mitochondria is induced by aging at 28°C and that this induction is strongly stimulated when the potato tubers are stored at low temperature (4°C). PUMP activity was detected by the degree of linoleic acid (LA)‐induced ATP‐sensitive mitochondrial uncoupling measured as a function of the decrease in membrane potential (ΔΨ). The PUMP content was evaluated by immunoblot analysis using polyclonal antibodies raised against potato PUMP that specifically detected a 32 kDa band. In agreement with the effect of LA on ΔΨ, the content of the 32 kDa band increased during storage and was stimulated by low temperature. These results support the proposed role of PUMP in plant thermogenesis and possibly in fruit ripening and senescence.
Concomitant activation of Gi protein‐coupled receptor and protein kinase C or phospholipase C is required for platelet aggregation
Authors: Pulcinelli Fabio M , Ciampa Maria Teresa , Favilla Mara , Pignatelli Pasquale , Riondino Silvia , Gazzaniga Pier Paolo
Published: July 2002

It has recently been suggested that the concomitant activation of two distinct G protein‐coupled receptors (Gi and Gq) is essential for platelet aggregation: in fact, the thromboxane A2 synthetic agonist, U46619, which causes the selective activation of Gq, is not able to elicit fibrinogen receptor exposure unless ADP or epinephrine is present. In the present study we demonstrate that a direct Gq activation is not required for platelet aggregation and that the activation of an enzyme downstream of Gq, such as phospholipase C (PLC) or protein‐kinase C (PKC), is sufficient for such a process. In fact, platelet aggregation occurred in response to the snake venom toxin convulxin, which activates the PLC isoform PLCγ2 or to cytosolic PKC activator phorbol 12‐myristate 13‐acetate (PMA) provided a Gi protein‐coupled receptor was activated by ADP or epinephrine. The evidence that the PKC inhibitor, Ro 31‐8220 did not suppress platelet aggregation in response to convulxin plus ADP or epinephrine led us to conclude that PLC and PKC are both involved in platelet aggregation, although not concomitantly, provided a Gi protein‐coupled receptor is activated.
Cloning and expression analysis of a Petunia hybrida flower specific mitotic‐like cyclin
Authors: Porceddu Andrea , Reale Lara , Lanfaloni Luisa , Moretti Chiaraluce , Sorbolini Silvia , Tedeschini Emma , Ferranti Francesco , Pezzotti Mario
Published: July 2002

A cyclin cDNA clone (Pethy;CycB1;1) was isolated from a Petunia hybrida ovary specific cDNA library. Sequence comparison revealed that Pethy;CYCB1;1 protein is highly homologous to mitotic B1 cyclins. Northern analysis and in situ hybridisation experiments showed that its expression is developmentally regulated and restricted to flower organs. We have attempted to define some of the cell division patterns which contribute to shaping each floral organ by analysing Pethy;CycB1;1 expression on Petunia flower sections. While in sepals, epidermis and parenchyma cell division patterns were comparable, there were two distinct cell division patterns in petals. In the epidermis, Pethy;CYCB1;1 expression was found both at the petal tip and along epidermis, whereas in the parenchyma only at the petal tips. In reproductive organs cell divisions were detected only in sporophytic tissues. No signals were detected inside meiotic cells.
Gender-related distribution of personality disorders in a sample of patients with panic disorder
Authors: Barzega G. , Maina G. , Venturello S. , Bogetto F.
Published: July 2002

Objective

We examined gender differences in the frequency of DSM-IV personality disorder diagnoses in a sample of patients with a diagnosis of panic disorder (PD).

Method

One hundred and eighty-four outpatients with a principal diagnosis of PD (DSM-IV) were enrolled. All patients were evaluated with a semi-structured interview to collect demographic and clinical data and to generate Axis I and Axis II diagnoses in accordance with DSM-IV criteria.

Results

Males were significantly more likely than females to meet diagnoses for schizoid and borderline personality disorder. Compared to males, females predominated in histrionic and cluster C diagnoses, particularly dependent personality disorder diagnoses. A significant interaction was found between female sex and agoraphobia on personality disorder (PD) distribution.

Conclusions

Male PD patients seem to be characterized by more severe personality disorders, while female PD patients, particularly with co-morbid agoraphobia, have higher co-morbidity rates with personality disorders belonging to the ‘anxious-fearful cluster’.
Increased soluble platelet / endothelial cellular adhesion molecule‐1 and osteonectin levels in patients with severe congestive heart failure. Independence of disease etiology, and antecedent aspirin therapy
Authors: Serebruany Victor L. , Murugesan Selva R. , Pothula Anitha , Atar Dan , Lowry David R. , O'Connor Christopher M. , Gurbel Paul A.
Published: July 2002

Background:

Platelet–endothelial interactions modulated by adhesion molecules, may play an important role in the pathogenesis of congestive heart failure (CHF). Soluble levels of these molecules and platelet‐derived substances are reportedly elevated in patients with CHF. However, no data are available on the plasma levels of Platelet / Endothelial Cell Adhesion Molecule‐1 (PECAM‐1), and platelet‐derived osteonectin in this growing population.

Methods and Results:

Soluble levels by ELISA were prospectively determined in patients with severe CHF (n = 37) and correlated to etiology and antecedent aspirin use, and compared with 14 healthy control subjects. Left ventricular dysfunction was attributed to idiopathic dilated cardiomyopathy in 18 and coronary artery disease in 19 patients. Twenty‐one patients were aspirin‐free and 16 patients were using aspirin (81–500 mg daily). Elevated soluble PECAM‐1 (51.31 ± 2.44 ng/ml, P = 0.0001), and osteonectin (826.27 ± 22.37 ng/ml, P = 0.0001) were observed in patients with CHF, as compared to healthy controls (32.56 ± 1.21 ng/ml, and 478.02 ± 31.32 ng/ml, respectively). Neither etiology of CHF, nor antecedent aspirin therapy significantly affects the levels of PECAM‐1 or osteonectin.

Conclusions:

Despite long‐term aspirin therapy and independently of the etiology of the disease, soluble PECAM‐1 and osteonectin were elevated in the majority of patients with severe CHF, suggesting platelet–endothelial activation. The present data provide additional evidence that more potent anti‐platelet and endothelial preservation regimens deserve further study in the heart failure population.
MIDWIVES AND MATERNAL AND CHILD HEALTH: BUILDING RESOURCE CAPACITY
Authors: Lydon‐Rochelle Mona , West Margaret , Hayes Maxine , Taylor Polly
Published: July 2002

With dramatic changes in health, social services, and welfare systems and escalating pressure to increase clinical productivity, midwives need to enhance their capacity to work with federal, regional, and state partners to promote and protect comprehensive, culturally competent, and community‐based quality health care for pregnant women and their families. Information about maternal and child health (MCH) regional and state resources is provided, and strategies for obtaining additional MCH resources are suggested, so that midwives and other women's health care providers can more effectively improve health care programs and systems that benefit women and their families. In addition, ways to work with MCH programs at the regional and state levels are described.
Geographic Variation in the Prevalence of Rheumatoid Arthritis in Alberta, Canada
Authors: Liu Xiaoxiao , Barber Claire E. H. , Katz Steven , Homik Joanne , Bertazzon Stefania , Patel Alka B. , Robert Jill , Smith Christopher , Mosher Dianne , Marshall Deborah A.
Published: April 2021

Objectives

Timely access to rheumatologists remains a challenge in Alberta, a Canadian province with vast rural areas, whereas rheumatologists are primarily clustered in metro areas. To address the goal of timely and equitable access to rheumatoid arthritis (RA) care, health planners require information at the regional and local level to determine the RA prevalence and the associated health care needs.

Methods

Using Alberta Health administrative databases, we identified RA‐prevalent cases (April 1, 2015‐March 31, 2016) on the basis of a validated case definition. Age‐ and sex‐standardized prevalence rates per 1000 population members and the standardized rates ratio (SRR) were calculated. We applied Global Moran’sIand Gi* hotspot analysis using three different weight matrices to explore the geospatial pattern of RA prevalence in Alberta.

Results

Among 38 350 RA cases (68% female; n = 26 236), the prevalence rate was 11.81 cases per 1000 population members (95% confidence interval [CI] 11.80‐11.81) after age and sex standardization. Approximately 60% of RA cases resided in metro (Calgary and Edmonton) and moderate metro areas. The highest rate was observed in rural areas (14.46; 95% CI 14.45‐14.47; SRR 1.28), compared with the lowest in metro areas (10.69; 95% CI 10.68‐10.69; SRR 0.82). The RA prevalence across local geographic areas ranged from 4.7 to 30.6 cases. The Global Moran’sIindex was 0.15 using three different matrices (z‐score 3.96‐4.24). We identified 10 hotspots in the south and north rural areas and 18 cold spots in metro and moderate metro Calgary.

Conclusion

The findings highlight notable rural–urban variation in RA prevalence in Alberta. Our findings can inform strategies aimed at reducing geographic disparities by targeting areas with high health care needs.
Localized Surface Plasmon Enhanced Laser Reduction of Graphene Oxide for Wearable Strain Sensor
Authors: Wan Zhengfen , Wang Shujun , Haylock Ben , Wu Zhiqing , Nguyen Tuan‐Khoa , Phan Hoang‐Phuong , Sang Robert , Nguyen Nam‐Trung , Thiel David , Koulakov Sergio , Trinchi Adrian , Gao Yongsheng , Lobino Mirko , Li Qin
Published: April 2021

Laser reduced graphene has been increasingly attracting broad attention owing to its unique properties and potential applications in energy conversion and storage, flexible electronics, optoelectronics, and nanocomposites. In this study, graphene sheets decorated with Au nanoparticles are fabricated in situ using milliwatt femtosecond laser reduction. The findings reveal an enhancement in both the reduction of graphene oxide sheets and the nucleation and growth of the Au nanoparticles during the in situ laser treatment. Three stages of reactions are considered, namely, (i) the spontaneous redox reaction between HAuCl4 and graphene oxide, (ii) the laser‐induced decomposition of HAuCl4 and reduction of graphene oxide, and (iii) the localized surface plasmon resonance enhanced photoreduction in the presence of Au particles. Moreover, the Au nanoparticles form densely and evenly distributed square‐lattice‐like microcrack networks that ensure a linear resistance change over the tested strain range. This microcrack network architecture enables the development of flexible graphene/Au strain sensors with gauge factors up to 52.5, and linear behaviour up to 25.4% strain. This strain sensor is demonstrated to effectively monitor human motions. The findings leverage the resistive properties of graphene/metal nanoparticle composites with fundamental mechanisms, laying a critical step toward highly functional, low‐cost, flexible, and wearable graphene‐based electronics.
Short caregiver interview and play observation for early screening of autism spectrum disorder: Behavior development screening for toddlers (BeDevel)
Authors: Bong Guiyoung , Kim So Yoon , Song Da‐Yea , Kim Jeong‐heun , Hong Yoohwa , Yoon Nan‐He , Sunwoo Hyunjung , Jang Jeong Yun , Oh Miae , Kim Jong Myeong , Lee Kyung‐Sook , Jung Seokjin , Choi Chang Won , Ryu Ju Seok , Yoo Hee Jeong
Published: April 2021

This study validates behavior development screening for toddlers (BeDevel), which utilizes a combination of short caregiver interviews (BeDevel‐I) and semistructured play observations (BeDevel‐P). The data of 431 toddlers (male 66.2%; mean age (SD) = 29.11 (8.59) months; ASD, n = 201; developmental delay, n = 46; typically developing, n = 184), aged 18 ~ 42 months, were included in the validation of BeDevel. The best clinical estimate diagnosis, screening rate, validity, sensitivity, and reliability of BeDevel were determined based on data cross‐sectionally collected using BeDevel and existing diagnostic/screening instruments: autism diagnostic observation schedule (ADOS), autism diagnostic interview (ADI‐R), Vineland adaptive behavior scales‐II (VABS‐II), social response scales (SRS), sequenced language scale for infants (SELSI), Korean childhood autism rating scale (K‐CARS), and Korean social communication questionnaire (K‐SCQ). The k values of BeDevel‐I and BeDevel‐P were 0.055 ~ 0.732 and 0.291 ~ 0.752, respectively. Items related to social referencing in BeDevel‐P had a particularly high diagnostic validity (k = 0.483 ~ 0.684). Reliabilities of BeDevel‐I and BeDevel‐P were sufficient (Cronbach's alpha = 0.86 ~ 0.88 and 0.92 ~ 0.95, respectively). BeDevel‐I and BeDevel‐P showed high sensitivity (BeDevel‐I: 85.00 ~ 89.29%; BeDevel‐P: 85.00 ~ 91.75%), specificity (BeDevel‐I: 77.55 ~ 89.55%; BeDevel‐P: 85.09 ~ 97.01%), PPV (BeDevel‐I: 70.83 ~ 88.54%; BeDevel‐P: 81.52 ~ 94.68%), and NPV (BeDevel‐I: 76.00 ~ 95.24%; BeDevel‐P: 84.62 ~ 95.45%). The agreement between the composite BeDevel score and ADOS, ADI‐R, K‐CARS, and K‐SCQ was >67.6% (range = 67.6 ~ 90.8%). Combining a short caregiver interview and direct play observation is a valid and reliable screening process. More studies on social referencing as an important early marker are needed. BeDevel can be utilized as a secondary screening instrument before diagnostic confirmation in clinical and community settings.

Lay summary

BeDevel, which consists of a short caregiver interview and direct play observation, is a valid and reliable screening instrument for autism spectrum disorder (ASD). We suggest that BeDevel can be utilized as a secondary instrument before administering diagnostic assessments in clinical and community settings. More studies examining social referencing as a potential behavioral marker of ASD are needed.
Greenness profile assessment of selective liquid chromatographic methods for determination of a quaternary antimigraine combination along with three of their related official impurities
Authors: Marzouk Hoda M. , Ibrahim Engy A. , Hegazy Maha A. , Saad Samah S.
Published: April 2021

Two selective, sensitive and environmentally safe LC methods were developed and validated for determination of paracetamol, caffeine, ergotamine tartrate and metoclopramide in coformulated antimigraine tablets along with p‐aminophenol, p‐nitrophenol and theophylline as officially specified impurities. The first is based on high‐performance thin‐layer chromatography (HPTLC) coupled with densitometric quantitation. Separation was achieved on HPTLC silica gel 60 F254 plates as stationary phase using ethyl acetate:aqueous ammonium hydroxide solution:glacial acetic acid (10.0:0.4:0.1, by volume) as a developing system followed by scanning of the separated bands at 210.0 nm. The subsequent method depends on HPLC with diode array detection. The LC separation was accomplished on a Scharlau C18 (250 × 4.6 mm, 5 μm) column using a mixture of 20.0 mm sodium dihydrogen phosphate, pH 3.0, adjusted with o‐phosphoric acid and methanol, at a flow rate of 1.3 mL/min in a gradient elution program. The separated peaks were detected at 210.0 nm. The proposed methods have been validated and proven to meet the requirements outlined in the International Council for Harmonisation (ICH) guidelines. The greenness profile evaluation was carried out using three tools, namely, the National Environmental Method Index, the Analytical EcoScale and the Green Analytical Procedure Index tool, and a comparative study was then conducted. Successful application of the developed methods for determination of the cited quaternary mixture in Metograine tablets confirms their suitability regarding the analytical performance and ecological impact in quality control assay and impurity profiling purposes.
Multiple nodular opacities only involving the right middle pulmonary lobe: Unusual manifestation of tuberculosis
Authors: Okazaki Akihito , Takeda Yoshihiro , Matsuda Yasuhiko , Fujita Kentaro , Shibata Kazuhiko
Published: April 2021

Bronchoscopy should be actively performed to differentiate pulmonary tuberculosis in patients with lesions in the middle lobe, which are unaccompanied by bronchiectasis or present without obvious lesions in other lobes.
Recent Advances in Nanoparticles Confined in Two‐Dimensional Materials as High‐Performance Electrocatalysts for Energy‐Conversion Technologies
Authors: Zhang Ling , Chen Hongmei , Wei Zidong
Published: April 2021

Recently, the fast‐growing advanced electrochemical energy‐conversion technologies for environmentally friendly production or utilization of energy requires highly active and stable electrocatalysts and many strategies have been accordingly proposed to achieve this goal. Of them, confinement strategy holds great potential because it can create unique microenvironment for electrocatalysts. Thanks to the exceptional physical and chemical properties, the two‐dimensional materials (2D materials) as building block are powerful in constructing inimitable “confined space” which will endow electrocatalysts with many intriguing characteristics, such as admirable electron conductivity, enhanced stability and anti‐poisoning capability, and more accessible active sites as well. Despite numerous efforts have been devoted and some progress has been made in confinement research, there exist substantial challenges to be tackled with regard to respectable activity, stability, and mass production of the confined electrocatalysts. In this Minireview, the concept of “nanoparticles confined in two‐dimensional materials (denoted as NCTDM)” and their up‐to‐date synthetical strategies, including host‐guest assembly method and in‐situ formation method have been firstly discussed. In addition, with special emphasis on their application, the NCTDM as a new type of high‐performance electrocatalysts for electrochemical energy‐conversion technologies such as water splitting, fuel cells and electrochemical reduction of CO2 to C1 molecules have been systematically introduced.
Racial differences in no‐show rates for screening mammography
Authors: Hensing Whitney L. , Poplack Steven P. , Herman Cheryl R. , Sutcliffe Siobhan , Colditz Graham A. , Ademuyiwa Foluso O.
Published: April 2021

Background

Differences in utilization of screening mammography partly explain the increased breast cancer mortality observed in African American (AA) women compared with non‐Hispanic White women. However, the contribution of noncompliance from women who do not come for their scheduled screening mammography appointment (ie, no‐shows) is unknown. The purpose of this study was to investigate racial differences in no‐show rates for screening mammography.

Methods

Women scheduled for routine screening mammograms between January 2018 and March 2018 were identified from the Joanne Knight Breast Health Center at Siteman Cancer Center in St. Louis, Missouri. Using a case‐control design, this study retrospectively identified patients who no‐showed for their mammograms (cases) and randomly sampled an equal number of patients who completed their mammograms (controls). These participants were compared by race. The main outcome measure was whether AA race was associated with no‐shows for screening mammography.

Results

During the study period, 5060 women were scheduled for screening mammography, and 316 (6.2%) did not keep their appointment (ie, they no‐showed). Women who no‐showed were more likely to be AA than women who kept their appointment (odds ratio, 2.64; 95% confidence interval, 1.90‐3.67). Even after adjustments for marital status, insurance type, and place of residence, AA race was still significantly associated with no‐shows for screening mammography.

Conclusions

This study identified a no‐show rate of 6.2% for screening mammography at the authors' institution. Women who no‐showed were more likely to be AA than women who completed their mammogram even after adjustments for multiple factors. These data can be leveraged for future studies aimed at improving mammography attendance rates among AA women.
High CD8/CD33 ratio in peritoneal metastatic lesions is associated with favorable prognosis in gastric cancer
Authors: Yamaguchi Takahisa , Kinoshita Jun , Saito Hiroto , Shimada Mari , Terai Siro , Moriyama Hideki , Okamoto Koichi , Makino Isamu , Nakamura Keishi , Tajima Hidehiro , Ninomiya Itasu , Fushida Sachio
Published: April 2021

Background

Tumor‐infiltrating lymphocytes (TILs) and other immune cells have been reported as a prognostic factor in several tumors, including gastric cancer, and they play an important role in antitumor effect at the primary site. There were few reports on the immune status in peritoneal metastatic lesions for gastric cancer.

Aims

The aims of this study were to assess the prognostic significance of TILs (CD4, CD8, CD19, regulatory T cells [Tregs]), and myeloid‐derived suppressor cells (MDSCs) in peritoneal metastatic lesions.

Methods

We retrospectively investigated 60 patients for gastric cancer with peritoneal metastasis who were treated between 2009 and 2016 in our institute. Immunohistochemistry for CD4, CD8, CD19, FOXP3, and CD33 was performed in the peritoneal metastatic lesions. The absolute numbers of immune cells and ratios were evaluated, and the relationship between immune‐related marker and overall survival (OS) was investigated.

Results

A high infiltration of CD8+ lymphocytes or high CD8/CD33 ratio was a better prognosis for OS in univariate analysis using all immunologic variables (P = .012, P = .001). In multivariate analysis for clinical and immunologic variables, high CD8/CD33 ratio was identified as an independent prognostic factor for OS (Hazard ratio: 0.291, 95% confidence interval: 0.126‐0.670, P = .004).

Conclusion

High CD8/CD33 ratio and high infiltration of CD8+ lymphocytes in peritoneal metastatic lesions were favorable prognoses for gastric cancer patients with peritoneal metastasis. It is necessary to modify the immune microenvironment result to increase the level of CD8+ lymphocytes in the peritoneal metastatic lesions.
α,β‐Unsaturated γ‐Peptide Foldamers
Authors: Legrand Baptiste , Maillard Ludovic T.
Published: April 2021

Despite their concomitant emergence in the 1990s, γ‐peptide foldamers have not developed as fast as β‐peptide foldamers and to date, only a few γ‐oligomer structures have been reported, and with sparse applications. Among these examples, sequences containing α,β‐unsaturated γ‐amino acids have recently drawn attention since the Z/E configurations of the double bond provide opposite planar restrictions leading to divergent conformational behaviors, from helix to extended structures. In this Review, we give a comprehensive overview of the developments of γ‐peptide foldamers containing α,β‐unsaturated γ‐amino acids with examples of applications for health and catalysis, as well as materials science.
Prognostic Factors and Treatment‐Effect Modifiers in Spinal Muscular Atrophy
Authors: Baranello Giovanni , Gorni Ksenija , Daigl Monica , Kotzeva Anna , Evans Rachel , Hawkins Neil , Scott David A. , Mahajan Anadi , Muntoni Francesco , Servais Laurent
Published: April 2021

Spinal muscular atrophy (SMA) is a rare, progressive neuromuscular disease characterized by loss of motor neurons and muscle atrophy. Untreated infants with type 1 SMA do not achieve major motor milestones, and death from respiratory failure typically occurs before 2 years of age. Individuals with types 2 and 3 SMA exhibit milder phenotypes and have better functional and survival outcomes. Herein, a systematic literature review was conducted to identify factors that influence the prognosis of types 1, 2, and 3 SMA. In untreated infants with type 1 SMA, absence of symptoms at birth, a later symptom onset, and a higher survival of motor neuron 2 (SMN2) copy number are all associated with increased survival. Disease duration, age at treatment initiation, and, to a lesser extent, baseline function were identified as potential treatment‐modifying factors for survival, emphasizing that early treatment with disease‐modifying therapies (DMT) is essential in type 1 SMA. In patients with types 2 and 3 SMA, factors considered prognostic of changes in motor function were SMN2 copy number, age, and ambulatory status. Individuals aged 6–15 years were particularly vulnerable to developing complications (scoliosis and progressive joint contractures) which negatively influence functional outcomes and may also affect the therapeutic response in patients. Age at the time of treatment initiation emerged as a treatment‐effect modifier on the outcome of DMTs. Factors identified in this review should be considered prior to designing or analyzing studies in an SMA population, conducting population matching, or summarizing results from different studies on the treatments for SMA.
Adding cognition to AT(N) models improves prediction of cognitive and functional decline
Authors: O'Shea Deirdre M. , Thomas Kelsey R. , Asken Breton , Lee Athene K.W. , Davis Jennifer D. , Malloy Paul F. , Salloway Stephen P. , Correia Stephen ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: April 2021

Introduction

This study sought to determine whether adding cognition to a model with Alzheimer's disease biomarkers based on the amyloid, tau, and neurodegeneration/neuronal injury—AT(N)—biomarker framework predicts rates of cognitive and functional decline in older adults without dementia.

Methods

The study included 465 participants who completed amyloid positron emission tomography, cerebrospinal fluid phosphorylated tau, structural magnetic resonance imaging, and serial neuropsychological testing. Using the AT(N) framework and a newly validated cognitive metric as the independent variables, we used linear mixed effects models to examine a 4‐year rate of change in cognitive and functional measures.

Results

The inclusion of baseline cognitive status improved model fit in predicting rate of decline in outcomes above and beyond biomarker variables. Specifically, those with worse cognitive functioning at baseline had faster rates of memory and functional decline over a 4‐year period, even when accounting for AT(N).

Discussion

Including a newly validated measure of baseline cognition may improve clinical prognosis in non‐demented older adults beyond the use of AT(N) biomarkers alone.
Spindle cell tumour with thymus‐like differentiation (SETTLE) on fine needle aspiration cytology: A case report highlighting diagnostic pitfalls
Authors: Adegun Oluyori K. , Proctor Ian , Falzon Mary , Pomplun Sabine
Published: April 2021

A 7‐year‐old girl presented with a painless neck swelling localised near the left lobe of the thyroid gland, which was initially investigated by fine needle aspiration cytology. This raised a differential diagnosis of medullary thyroid carcinoma and small round blue cell tumour. Only after several additional clinical investigations and a total thyroidectomy was a definitive diagnosis of spindle cell tumour with thymus‐like differentiation (SETTLE) reached. This case report highlights how contemporaneous clinical and investigation findings made arriving at a definitive diagnosis challenging, contributed to diagnostic delay, and ultimately influenced choice of treatment.
miR‐148a weaves its thread into the plasma cell fate
Authors: Tellier Julie
Published: April 2021

The plasma cells (PC) are characterized by their rarity, their formidable capacity to continuously secrete massive amounts of antibodies and the potential to live through the whole life span of the organism that houses them. Because of the potency of their effector function, their differentiation and survival are tightly regulated. The PC identity is implemented and maintained by a transcriptional program that allow them to face the challenges entailed by their longevity and high metabolic activity. The main transcription factors overseeing this transcriptional network have been identified (BLIMP1, IRF4, XBP1), but new players, like miRNA, continue to emerge and bring new layers of complexity to the regulatory loops.

In the current issue of the European Journal of Immunology [Eur. J. Immunol. 2021. 51: 1089–1109], Pracht et al. identify miR‐148a as a significant actor of the PC program that favors the differentiation through the inhibition of competitor fates, and supports the survival and fitness of the long‐lived PC. In this commentary, we will discuss the place of miR‐148a in the PC transcriptional network and its potential as a therapeutic target in PC‐driven diseases.
A chip off the (im)moral block? Lay beliefs about genetic heritability predicts whether family members’ actions affect self‐judgments
Authors: Peetz Johanna , Wohl Michael J. A. , Wilson Anne E. , Dawson Andrew
Published: April 2021

The idea of heritability may have consequences for individuals’ sense of self by connecting identity to the actions of others who happen to share genetic ties. Across seven experimental studies (total N = 2,628), recalling morally bad or good actions by family members influenced individuals’ moral self among those who endorse a lay belief that moral character is genetically heritable, but not among those who did not endorse this belief (Study 1–5). In contrast, recalling actions by unrelated individuals had no effect, regardless of lay beliefs (Study 2, 5), the endorsement of other relevant lay beliefs did not moderate the effect of parent's actions on self‐judgments (Study 3). Individuals who endorsed heritability beliefs also chose less helpful responses to hypothetical helping scenarios if they had recalled unhelpful (vs. helpful) acts by a genetically related family member (Study 5). Taken together, these studies suggest that lay beliefs in the role of genetics are important for self‐perceptions.
Mega‐scale glacial lineations formed by ice shelf grounding in the Canadian Beaufort Sea during multiple glaciations
Authors: Riedel Michael , Dallimore Scott , Wamsteeker Michael , Taylor Gary , King Edward L. , Rohr Kristin M. M. , Hong Jong Kuk , Jin Young Keun
Published: April 2021

Mega‐scale glacial lineations formed by the raking of ice shelves across the seafloor have been reported from multiple polar regions. Here, we present the first evidence of continental slope situated buried lineations in the southern Canadian Beaufort Sea in present‐day water depths of 220 to 800 m. Three separate surfaces with lineations are defined at sub‐seafloor depths of 40 m to 390 m. All lineations are mostly parallel to the general trend of slope contours. The uppermost surface is recognized over a distance of 56 km. In water depths > 500 m the lineations are parallel to each other at a consistent direction (43°–44°). The second lineated surface is a regionally occurring erosional unconformity. This event has two sub‐sets of lineations: mid‐slope situated lineations oriented at 42°–48°, and lineations closer to the continental shelf break at 55°–59°. The third lineated surface is an unconformable horizon buried up to 390 m below seafloor with lineaments oriented between 30° and 55°. All three sets of lineations are interpreted to have been produced by ice‐ploughing on the paleo‐seafloor through the grounding of an ice shelf. Our observations are similar to those documented along the slope off northern Alaska, Chukchi Rise, and Lomonosov Ridge. Collectively, these observations support the concept of an extensive ice shelf across the Arctic Ocean that grounded locally along its margins during multiple glaciations, including during the penultimate (or an earlier) glaciation. The youngest set of lineations indicates ice movement to the southwest with a suggested source in Amundsen Gulf and/or M'Clure Strait. Tentative age considerations for these youngest lineations indicate the first evidence for an analogous extensive ice shelf configuration for the Last Glacial Maximum.
Diagnostic value of loop‐mediated isothermal amplification assay for hand, foot, and mouth disease
Authors: Chen Ying‐Zhou , Zhan Zhi‐Qing , Zhou Li‐Quan , Chen Min‐Shan , Cao Xun‐Jie , Li Ya‐Ping , Guo Xu‐Guang
Published: April 2021

Background

Nowadays, hand, foot, and mouth disease (HFMD) has a significant negative impact on children's health, especially in the Asia‐Pacific region. Loop‐mediated isothermal amplification assay (LAMP) is a highly efficient and convenient novel tool. However, its diagnostic accuracy for HFMD is still not clear. Therefore, we conducted a meta‐analysis in order to evaluate the potential of LAMP assay for the diagnosis of HFMD, in which the reference standard was polymerase chain reaction (PCR).

Methods

A protocol was predetermined (CRD42020212882) in PROSPERO. We retrieved seven databases including PubMed for relevant studies published before October 2020. Articles were included if they compared the diagnostic efficiency of LAMP with PCR for HFMD through detecting clinical samples which was more than 15. Statistical analysis was performed by STATA 15.1 software. Risk of bias and applicability were assessed using Quality Assessment of Diagnostic Accuracy Studies. No funding was used for the study.

Results

A total of 18 retrospective studies including 2495 samples from China were finally included. Reference standards of them included RT‐PCR and non‐RT‐PCR. The merged sensitivity and specificity with 95% confidence interval (95% CI) were 1.00 (0.97–1.00) and 0.97 (0.88–0.99), respectively. The pooled PLR, NLR, and DOR with 95% CI were 11.17 (5.91–21.11), 0.05 (0.03–0.09), and 538.12 (183.17–1580.83), respectively. The AUC of SROC was 1.00 (95% CI: 0.99–1.00).

Conclusion

In conclusion, our research revealed high sensitivity and specificity of LAMP in diagnosing HFMD. However, more high‐quality research is required to prove this conclusion.
Professional killers: The role of extracellular vesicles in the reciprocal interactions between natural killer, CD8+ cytotoxic T‐cells and tumour cells
Authors: Del Vecchio Filippo , Martinez‐Rodriguez Verena , Schukking Monique , Cocks Alexander , Broseghini Elisabetta , Fabbri Muller
Published: April 2021

Extracellular vesicles (EVs) mediate the cross‐talk between cancer cells and the cells of the surrounding Tumour Microenvironment (TME). Professional killer cells include Natural Killer (NK) cells and CD8+ Cytotoxic T‐lymphocytes (CTLs), which represent some of the most effective immune defense mechanisms against cancer cells. Recent evidence supports the role of EVs released by NK cells and CTLs in killing cancer cells, paving the road to a possible therapeutic role for such EVs. This review article provides the state‐of‐the‐art knowledge on the role of NK‐ and CTL‐derived EVs as anticancer agents, focusing on the different functions of different sub‐types of EVs. We also reviewed the current knowledge on the effects of cancer‐derived EVs on NK cells and CTLs, identifying areas for future investigation in the emerging new field of EV‐mediated immunotherapy of cancer.
Staphylococcus aureus membrane vesicles contain immunostimulatory DNA, RNA and peptidoglycan that activate innate immune receptors and induce autophagy
Authors: Bitto Natalie J. , Cheng Lesley , Johnston Ella L. , Pathirana Rishi , Phan Thanh Kha , Poon Ivan K. H. , O'Brien‐Simpson Neil M. , Hill Andrew F. , Stinear Timothy P. , Kaparakis‐Liaskos Maria
Published: April 2021

Gram‐positive bacteria ubiquitously produce membrane vesicles (MVs), and although they contribute to biological functions, our knowledge regarding their composition and immunogenicity remains limited. Here we examine the morphology, contents and immunostimulatory functions of MVs produced by three Staphylococcus aureus strains; a methicillin resistant clinical isolate, a methicillin sensitive clinical isolate and a laboratory‐adapted strain. We observed differences in the number and morphology of MVs produced by each strain and showed that they contain microbe‐associated molecular patterns (MAMPs) including protein, nucleic acids and peptidoglycan. Analysis of MV‐derived RNA indicated the presence of small RNA (sRNA). Furthermore, we detected variability in the amount and composition of protein, nucleic acid and peptidoglycan cargo carried by MVs from each S. aureus strain. S. aureus MVs activated Toll‐like receptor (TLR) 2, 7, 8, 9 and nucleotide‐binding oligomerization domain containing protein 2 (NOD2) signalling and promoted cytokine and chemokine release by epithelial cells, thus identifying that MV‐associated MAMPs including DNA, RNA and peptidoglycan are detected by pattern recognition receptors (PRRs). Moreover, S. aureus MVs induced the formation of and colocalized with autophagosomes in epithelial cells, while inhibition of lysosomal acidification using bafilomycin A1 resulted in accumulation of autophagosomal puncta that colocalized with MVs, revealing the ability of the host to degrade MVs via autophagy. This study reveals the ability of DNA, RNA and peptidoglycan associated with MVs to activate PRRs in host epithelial cells, and their intracellular degradation via autophagy. These findings advance our understanding of the immunostimulatory roles of Gram‐positive bacterial MVs in mediating pathogenesis, and their intracellular fate within the host.
Structural Investigation of Diol and Triol Poly(oxypropylene)‐Poly(oxyethylene) Block Copolymers Micelles: Composition Dependence, Temperature Response and Clouding Behavior
Authors: Teixeira Cilâine Verônica , Alencar Marques Yuri , Carvalho de Abreu Fantini Márcia , da Rocha Santos Bittencourt Diomar , Pinto Oliveira Cristiano Luís
Published: April 2021

Solution behavior of two commercially used polyether glycols with poly(oxyethylene) (PEO)‐poly(oxypropylene) (PPO)‐poly(oxyethylene) (PEO) triblock composition—Diol (linear) and Triol (star‐like)—was studied, concerning the concentration and temperature effects until the cloud point (CP). 2‐(2‐butoxyetoxy) ethanol (DB) increased their miscibility with water. The structural study was performed with 25% DB in water, which produced isotropic solutions at room temperature at all polymer concentrations. Micelle's formation was only observed above 40% of polymer, when reversed micelles were formed. The solvent nuclei of the reversed micelles increased with increasing polymer concentrations, caused by dehydration of the PPO chains, then decreased at further higher concentrations, with completely dehydrated hydrophobic chains. When CP is reached, the solvent nuclei are separated by large polymer domains, without phase separation. Neither ordered nor gel phase was formed, probably due to a combination of high miscibility and short hydrophobic segments. The study was performed by Small‐Angle X‐ray scattering (SAXS) and complemented by Fourier‐transformed infrared spectroscopy (FTIR) and dynamic light scattering (DLS). The main contribution of this work is based on the fact that the knowledge of the solubility behavior of Diol and Triol, by changing the solvent or temperature, opens up new possibilities of their use to phase separation processes in industrial applications and delivery systems. Moreover, the elucidation of mechanisms of solubility allows for the design of novel polyether glycols with tailored solution behavior for efficient performance in its target use. All applications rely on their solution behavior and can be benefited from the present results.
Synthesis and Evaluation of Charge Transport Property of Ethynylene‐Bridged Anthracene Oligomers
Authors: Zhu Juanjuan , Hayashi Hironobu , Chen Meng , Xiao Chengyi , Matsuo Kyohei , Aratani Naoki , Zhang Lei , Yamada Hiroko
Published: April 2021

A set of ethynylene‐bridged anthracene oligomers from monomer to tetramer is synthesized and characterized. The red‐shifts in the UV–vis absorption and fluorescence spectra indicate the π‐extension with elongation of the linear chain. Cyclic voltammetric measurements suggest that their highest occupied molecular orbitals are located lower than –5.0 eV, indicating high air stability. Single‐crystal X‐ray analysis of a trimer needle crystal indicates that anthracene units display a twisted arrangement, adopting a face‐to‐face packing structure. The dip‐coating method with a very slow pulling rate provides crystalline films of dimer and trimer. The top‐contact bottom‐gate organic field‐effect transistor devices reveal that trimer shows better charge transport property (8.0 × 10–3 cm2 V–1 s–1) than dimer (8.9 × 10–4 cm2 V–1 s–1). Furthermore, the single‐crystal field‐effect transistor of trimer shows mobility up to 0.14 cm2 V–1 s–1, which is higher than that of tetramer (3.3 × 10–2 cm2 V–1 s–1). This is likely due to the larger amount of defects in tetramer crystals that are caused by the free rotation of ethynylene units, while the trimer achieves a good balance between the effective π‐conjugation and defectless crystal formation.
Deficient topological measures on locally compact spaces
Authors: Butler S. V.
Published: April 2021

Topological measures and quasi‐linear functionals generalize measures and linear functionals. We define and study deficient topological measures on locally compact spaces. A deficient topological measure on a locally compact space is a set function on open and closed sets which is finitely additive on compact sets, inner regular on open sets, and outer regular on closed sets. Deficient topological measures generalize measures and topological measures. First we investigate positive, negative, and total variation of a signed set function that is only assumed to be finitely additive on compact sets. These positive, negative, and total variations turn out to be deficient topological measures. Then we examine finite additivity, superadditivity, smoothness, and other properties of deficient topological measures. We obtain methods for generating new deficient topological measures. We provide necessary and sufficient conditions for a deficient topological measure to be a topological measure and to be a measure. The results presented are necessary for further study of topological measures, deficient topological measures, and corresponding non‐linear functionals on locally compact spaces.
Pilot Study to Evaluate Pimavanserin for the Treatment of Motor and Behavioral Symptoms of Tourette Syndrome
Authors: Billnitzer Andrew , Jankovic Joseph
Published: April 2021

Background

Pimavanserin is a serotonin 2A receptor inverse agonist and antagonist used for the treatment of hallucinations and delusions in Parkinson's disease psychosis. Numerous studies support a modulatory role of serotonin in Tourette syndrome (TS).

Objectives

To determine whether or not pimavanserin affects TS symptoms.

Methods

In this open‐label study of TS adult patients, pimavanserin was titrated to 34 mg/day over 1 week and continued for an additional 7 weeks followed by a 2‐week washout. Tic severity, the primary outcome measure, was assessed by the Yale Global Tic Severity Scale Total Tic Severity score (YGTSS‐TTS). Secondary outcome measures included changes in the Yale‐Brown Obsessive Compulsive Scale (Y‐BOCS), the Tourette Syndrome Clinical Global Impression of Change (TS‐CGIC), the Tourette Syndrome‐Patient Global Impression of Impact (TS‐PGII), and the Gilles de la Tourette Syndrome – Quality of Life scale (GTS‐QOL).

Results

We enrolled 12 patients, but 2 dropped out after week 2 due to non‐serious side effects. In the 10 patients, mean (standard deviation (SD)) age 34 (12.9) who completed the study the mean (SD) baseline YGTSS‐TTS was 34 (9.3). This decreased by 3.6 (4.9) points at week 8, a 12% reduction in tic severity (P = 0.03). This improvement is small and may not be clinically important. Significant improvement was noted in the TS‐CGIC, TS‐PGII and GTS‐QO. No serious adverse events were reported.

Conclusions

The results of this study suggest that pimavanserin is safe and associated with improvement in motor and non‐motor TS symptoms. These findings warrant further study by a larger, placebo‐controlled, trial.