bluuebunny/crossref_metadata_2025 huggingface dataset:
Genotypes analysis of Candida albicans species complex from healthy individual saliva in Ahvaz, Iran
Authors: Kianifar S. , Rezaei-Matehkolaei A. , Zarei-Mahmoudabadi A.
Published: June 2022

Although Candida albicans is a part of the mycoflora of healthy individuals, it is causing mild to severe forms of candidiasis in patients with underlying diseases. The recent molecular investigations were classified three genotypes, A, B and C for C. albicans. The aim of the present study was to detect different genotypes of C. albicans complex species in a normal population in Iran. Saliva was randomly collected from a normal population, homogenized and cultured on CHROMagar Candida. Classical and molecular methods were used for the detection of isolates. Candida 25S rDNA gene was amplified using the primer pairs of CA-INT-L and CA-INT-R for ABC genotyping of C. albicans. Candida albicans complex was recovered from 103/194 (53·1%) normal papulation. Genotype A with a frequency of 41·7% was the most common isolate, followed by genotype C (34%), genotype B (20·4%) and genotype D (3·9%). Genotyping of C. albicans species complex from healthy individuals showed the presence of three A, B and C genotypes of C. albicans and one D genotype of C. dubliniensis.
CO2‐induced biochemical changes in leaf volatiles decreased fire‐intensity in the run‐up to the Triassic–Jurassic boundary
Authors: Baker Sarah J. , Dewhirst Rebecca A. , McElwain Jennifer C. , Haworth Matthew , Belcher Claire M.
Published: June 2022

The Triassic–Jurassic boundary marks the third largest mass extinction event in the Phanerozoic, characterized by a rise in CO2‐concentrations from c. 600 ppm to c. 2100–2400 ppm, coupled with a c. 3.0–4.0°C temperature rise. This is hypothesized to have induced major floral turnover, altering vegetation structure, composition and leaf morphology, which in turn are hypothesized to have driven changes in wildfire. However, the effects of elevated CO2 on fuel properties, such as chemical composition of leaves, are also important in influencing fire behaviour, but yet have not been considered.

We test this by selecting three Triassic analogue species grown experimentally in different atmospheric compositions, and analyse variations in leaf chemistry, and leaf level flammability. These data were used to inform a fire behaviour model.

We find that all three species tested showed a reduction in their volatile component, leading to lower flammability. Accounting for these variations in a model, our results suggest that leaf intrinsic flammability has a measurable impact on modelled fire behaviour.

If scaled up to ecosystem level, periods of elevated CO2 may therefore be capable of inducing both biochemical and morphological changes in fuel properties, and thus may be capable of influencing fire behaviour.
Unique and redundant functions of cytoplasmic actins and nonmuscle myosin II isoforms at epithelial junctions
Authors: Ivanov Andrei I. , Lechuga Susana , Marino‐Melendez Armando , Naydenov Nayden G.
Published: June 2022

The integrity and functions of epithelial barriers depend on the formation of adherens junctions (AJs) and tight junctions (TJs). A characteristic feature of AJs and TJs is their association with the cortical cytoskeleton composed of actin filaments and nonmuscle myosin II (NM‐II) motors. Mechanical forces generated by the actomyosin cytoskeleton are essential for junctional assembly, stability, and remodeling. Epithelial cells express two different actin proteins and three NM‐II isoforms, all known to be associated with AJs and TJs. Despite their structural similarity, different actin and NM‐II isoforms have distinct biochemical properties, cellular distribution, and functions. The diversity of epithelial actins and myosin motors could be essential for the regulation of different steps of junctional formation, maturation, and disassembly. This review focuses on the roles of actin and NM‐II isoforms in controlling the integrity and barrier properties of various epithelia. We discuss the effects of the depletion of individual actin isoforms and NM‐II motors on the assembly and barrier function of AJs and TJs in model epithelial monolayers in vitro. We also describe the functional consequences of either total or tissue‐specific gene knockout of different actins and NM‐II motors, with a focus on the development and integrity of different epithelia in vivo.
Are Women Doing It for Themselves? Female Managers and the Gender Wage Gap*
Authors: Theodoropoulos Nikolaos , Forth John , Bryson Alex
Published: June 2022

Using linked employer‐employee data for Britain, we find a robust association between the share of female managers in the workplace and the size of the gender wage gap. In workplace fixed‐effects estimates, the gap is eradicated when more than 60% of workplace managers are women, a scenario that obtains in around one fifth of all workplaces. The association between the share of female managers and the gender wage gap is more pronounced when workplace managers set pay at the workplace, and where employees are paid for performance. These findings are consistent with the proposition that women are more likely to be paid equitably when managers have discretion in the way they set pay or reward performance and those managers are women. They suggest that a stronger presence of women in managerial positions can help tackle the gender wage gap.
De novo transcriptome sequencing of Capsicum frutescens. L and comprehensive analysis of salt stress alleviating mechanism by Bacillus atrophaeusWU‐9
Authors: Wang Wenfei , He Yanhui , Wu Zhansheng , Li Tao , Xu Xiaolin , Liu Xiaochen
Published: June 2022

Salt stress, as one of the most severe environmental stresses, can cause a series of changes in plants. However, the explanation of plant salt stress alleviating mechanism of plant growth–promoting rhizobacteria (PGPR) was hindered by the limited availability of transcriptomic information for salt stress‐treated plants grown in a microorganism‐controlled environment. Our previous reports have selected Bacillus atrophaeus WU‐9 as PGPR significantly alleviating pepper (Capsicum frutescens. L) salt stress. In this work, the RNA‐seq analysis of salt stress‐treated and untreated plants, grown with and without WU‐9 in a microorganism‐controlled environment, was used to reveal the plant salt stress alleviating mechanisms of WU‐9. Twelve sequencing libraries, prepared by treating with WU‐9 and salt (150 mM NaCl for 36 h), were constructed by RNA‐Seq technique. Non‐inoculated seedlings mainly respond to salt stress through regulation of signal transduction, such as ethylene‐activated signaling pathway, signaling and cell communication, etc. And ethylene signal participated in salt stress response in pepper through regulating defense responses, fruit ripening and senescence. WU‐9 inoculation under salt stress mainly improves salt tolerance and plant growth by regulating salt stress‐responding ethylene and auxin signal transduction, utilization of proline, photosynthesis, antioxidant enzyme activities and cell enlargement. Furthermore, 86 differentially expressed genes and 20 transcription factors were identified as associated with salt stress response and tolerance. Thus, this innovative transcriptomic study identified the salt stress response and alleviation in C. frutescens. L with PGPR inoculation. This result provided novel insights into the salinity alleviation in pepper regulated by PGPR.
Parents' pension eligibility and migrant consumption in urban China: Evidence from a quasi‐experiment
Authors: He Yuke , Niu Geng , Zhao Guochang
Published: June 2022

This article analyzes data from the 2009 and 2014 waves of the Survey on Rural Urban Migration in China (RUMiC) to investigate the impact of parents' pension status on migrants' consumption in cities. Exploiting the introduction of the new rural pension scheme (NRPS), we perform a difference‐in‐differences (DID) analysis. We find that having a parent in a rural area that is pension eligible increases migrants' consumption level by 9.4%. However, this effect is constrained to survival consumption. Furthermore, the positive impact of parents' pension eligibility is more pronounced for migrants who earn a lower income, receive less education, suffer from poorer health, have stronger economic ties with their parents, and have a parent in poorer health. Our results suggest that improving rural social welfare has a spillover effect on urban consumption.
A chromosome‐level genome of Syringa oblata provides new insights into chromosome formation in Oleaceae and evolutionary history of lilacs
Authors: Wang Yi , Lu Limin , Li Jingrui , Li Huayang , You Yichen , Zang Shuying , Zhang Yongqing , Ye Jianfei , Lv Zemin , Zhang Zhaoyu , Qin Yongsheng , Zhang Hongling , Xia Fei , Li Hui , Zhang Huijin , Fan Peige , Shi Lei , Liang Zhenchang , Cui Hongxia
Published: June 2022

Lilacs (Syringa L.), a group of well‐known ornamental and aromatic woody plants, have long been used for gardening, essential oils and medicine purposes in East Asia and Europe. The lack of knowledge about the complete genome of Syringa not only hampers effort to better understand its evolutionary history, but also prevents genome‐based functional gene mining that can help in the variety improvement and medicine development. Here, a chromosome‐level genome of Syringa oblata is presented, which has a size of 1.12 Gb including 53 944 protein coding genes. Synteny analysis revealed that a recent duplication event and parallel evolution of two subgenomes formed the current karyotype. Evolutionary analysis, transcriptomics and metabolic profiling showed that segment and tandem duplications contributed to scent formation in the woody aromatic species. Moreover, phylogenetic analysis indicated that S. oblata shared a common ancestor with Osmanthus fragrans and Olea europaea approximately 27.61 million years ago (Mya). Biogeographic reconstruction based on a resequenced data set of 26 species suggested that Syringa originated in the northern part of East Asia during the Miocene (approximately 14.73 Mya) and that the five Syringa groups initially formed before the Late Miocene (approximately 9.97 Mya). Furthermore, multidirectional dispersals accompanied by gene introgression among Syringa species from Northern China during the Miocene were detected by biogeographic reconstruction. Taken together, the results showed that complex gene introgression, which occurred during speciation history, greatly contributed to Syringa diversity.
B vitamin supply in plants and humans: the importance of vitamer homeostasis
Authors: Liu Zeguang , Farkas Peter , Wang Kai , Kohli Morgan‐Océane , Fitzpatrick Teresa B.
Published: June 2022

B vitamins are a group of water‐soluble micronutrients that are required in all life forms. With the lack of biosynthetic pathways, humans depend on dietary uptake of these compounds, either directly or indirectly, from plant sources. B vitamins are frequently given little consideration beyond their role as enzyme accessory factors and are assumed not to limit metabolism. However, it should be recognized that each individual B vitamin is a family of compounds (vitamers), the regulation of which has dedicated pathways. Moreover, it is becoming increasingly evident that individual family members have physiological relevance and should not be sidelined. Here, we elaborate on the known forms of vitamins B1, B6 and B9, their distinct functions and importance to metabolism, in both human and plant health, and highlight the relevance of vitamer homeostasis. Research on B vitamin metabolism over the past several years indicates that not only the total level of vitamins but also the oft‐neglected homeostasis of the various vitamers of each B vitamin is essential to human and plant health. We briefly discuss the potential of plant biology studies in supporting human health regarding these B vitamins as essential micronutrients. Based on the findings of the past few years we conclude that research should focus on the significance of vitamer homeostasis – at the organ, tissue and subcellular levels – which could improve the health of not only humans but also plants, benefiting from cross‐disciplinary approaches and novel technologies.
Educar por medio del arte en una escuela multicultural
Authors: Álvarez-Valdivia Ibis Marlene , Morón-Velasco Mar
Published: June 2022

Este artículo ilustra las oportunidades que ofrece el aprendizaje por medio del arte para vincular el patrimonio cultural del alumnado de origen inmigrado a los objetivos del currículum. Se siguió un modelo de investigación-acción educativa en la que participaron futuros docentes durante las prácticas en escuelas de educación primaria en Cataluña (España), en las que prevalece una composición social desfavorecida. Los resultados aportan una metodología interdisciplinar e inclusiva de educación mediante las artes, que promueve el desarrollo de competencias fundamentales para el aprendizaje. Se sugieren ideas para incluir la propuesta en la formación inicial docente.
Inclusión y migraciones: intervenciones educativas desde la sociedad civil
Authors: Ramírez-Iñiguez Alma Arcelia
Published: June 2022

Se analizan las alternativas educativas que, desde las organizaciones de la sociedad civil (OSC), se han generado para atender y mejorar la calidad de vida de niñas, niños y adolescentes migrantes. La metodología consistió en un análisis de contenido cualitativo de carácter inductivo, a partir del cual se identificaron los factores que han favorecido el desarrollo personal y social de esta población. Los resultados muestran que las estrategias de intervención se centran en tres aspectos: el compromiso por el bienestar de la población migrante, las estrategias de atención a la diversidad y las estrategias de evaluación continua.
Percepciones del aprendizaje y emociones de estudiantes nóveles en pandemia
Authors: Chiecher-Costa Analía-Claudia
Published: June 2022

El artículo compara percepciones del aprendizaje y emociones de estudiantes con alto y bajo rendimiento académico durante el periodo de la pandemia. Se realizó un sondeo exploratorio, desde un enfoque cualitativo, siguiendo una lógica inductiva de construcción de categorías a partir de los datos ofrecidos por 132 estudiantes universitarios nóveles. Los resultados señalan una percepción positiva de la clase sincrónica virtual, así como la percepción negativa en relación con la falta de tareas prácticas debido a la virtualidad. Las emociones experimentadas fueron estrés e incertidumbre entre los estudiantes de alto rendimiento y frustración en los de bajo desempeño.
Performance Optimization of the High-Pressure Compressor in Series Two-Stage Turbocharging System Based on Low-Speed Performance Requirements of Diesel Engine
Authors: Liang Dingkun , Yang Hanqian , Li Qingbin , Xu Cheng , Xie Qiuyuan
Published: June 2022

The performance of the high-pressure (HP) compressor is very important for the two-stage turbocharging system. However, the performance of HP compressor on the engine most of the time is poor at low speed and low mass flow conditions. These will lead to poor engine performance at low engine speed. The purpose of this paper is to improve the performance of the HP compressor at low speed and low mass flow conditions. The Latin hypercube design of the experiment method is used to establish the Kriging model and global optimization by multi-objective genetic algorithm NSGA-II to optimal HP compressor. The simulation results indicated that the flow field within the compressor was improved and the high entropy generation area was reduced. The new design delayed the mixing between the tip clearance leakage vortex flow and main flow. The low-speed performance of the HP compressor was improved. The turbocharger gas stand tests and engine bench tests were carried out. The results showed that the efficiency and pressure ratio of the optimized design is increased by 2.1% and 3%, respectively. The engine achieved better performance in low-speed conditions. The pumping means effective pressure (PMEP) and intake airflow increased by 7% and 4.98%, respectively, while brake specific fuel consumption (BSFC) and soot emissions decreased by 0.56% and 32.8%, respectively.
Off-Design Performance Comparison Between Single and Two-Shaft Engines Part 1—Fixed Geometry
Authors: Nikolaidis Theoklis , Pellegrini Alvise , Saravanamuttoo Herbert I. H. , Aslanidou Ioanna , Kalfas Anestis , Pilidis Pericles
Published: June 2022

This paper describes an investigation into the off-design performance comparison of single and two-shaft gas turbine engines. A question that has been asked for a long time is which gas turbine delivers a better thermal efficiency at part load. The authors, notwithstanding their intensive searches, were unable to find a comprehensive answer to this question. A detailed investigation was carried out using a state-of-the-art performance evaluation method and the answer was found to be: It depends! In this work, the performance of two engine configurations is assessed. In the first one, the single-shaft gas turbine operates at constant shaft rotational speed. Thus, the shape of the compressor map rotational speed line will have an important influence on the performance of the engine. To explore the implications of the shape of the speed line, two single-shaft cases are examined. The first case is when the speed line is curved and as the compressor pressure ratio falls, the nondimensional mass flow increases. The second case is when the speed line is vertical and as the compressor pressure ratio falls, the nondimensional mass flow remains constant. In the second configuration, the two-shaft engine, the two shafts can be controlled to operate at different rotational speeds and also varying relationships between the rotational speeds. The part-load operation is characterized by a reduction in the gas generator rotational speed. The tool, which was used in this study, is a 0-D whole engine simulation tool, named Turbomatch. It was developed at Cranfield and it is based on mass and energy balance, carried out through an iterative method, which is based on component maps. These generic, experimentally derived maps are scaled to match the design point of a particular engine before an off-design calculation is performed. The code has been validated against experimental data elsewhere, it has been used extensively for academic purposes and the research activities that have taken place at Cranfield University. For an ideal cycle, the single-shaft engine was found to be a clear winner in terms of part-load thermal efficiency. However, this picture changed when realistic component maps were utilized. The basic cycle and the shape of component maps had a profound influence on the outcome. The authors explored the influence of speed line shapes, levels of component efficiencies, and the variation of these component efficiencies within the operating range. This paper describes how each one of these factors, individually, influences the outcome.
Ubiquitous defect-induced density wave instability in monolayer graphene
Authors: Qu A. C. , Nigge P. , Link S. , Levy G. , Michiardi M. , Spandar P. L. , Matthé T. , Schneider M. , Zhdanovich S. , Starke U. , Gutiérrez C. , Damascelli A.
Published: June 2022

Quantum materials are notoriously sensitive to their environments, where small perturbations can tip a system toward one of several competing ground states. Graphene hosts a rich assortment of such competing phases, including a bond density wave instability (“Kekulé distortion”) that couples electrons at the K/K′ valleys and breaks the lattice symmetry. Here, we report observations of a ubiquitous Kekulé distortion across multiple graphene systems. We show that extremely dilute concentrations of surface atoms (less than three adsorbed atoms every 1000 graphene unit cells) can self-assemble and trigger the onset of a global Kekulé density wave phase. Combining complementary momentum-sensitive angle-resolved photoemission spectroscopy (ARPES) and low-energy electron diffraction (LEED) measurements, we confirm the presence of this density wave phase and observe the opening of an energy gap. Our results reveal an unexpected sensitivity of the graphene lattice to dilute surface disorder and show that adsorbed atoms offer an attractive route toward designing novel phases in two-dimensional materials.
A reference tissue atlas for the human kidney
Authors: Hansen Jens , Sealfon Rachel , Menon Rajasree , Eadon Michael T. , Lake Blue B. , Steck Becky , Anjani Kavya , Parikh Samir , Sigdel Tara K. , Zhang Guanshi , Velickovic Dusan , Barwinska Daria , Alexandrov Theodore , Dobi Dejan , Rashmi Priyanka , Otto Edgar A. , Rivera Miguel , Rose Michael P. , Anderton Christopher R. , Shapiro John P. , Pamreddy Annapurna , Winfree Seth , Xiong Yuguang , He Yongqun , de Boer Ian H. , Hodgin Jeffrey B. , Barisoni Laura , Naik Abhijit S. , Sharma Kumar , Sarwal Minnie M. , Zhang Kun , Himmelfarb Jonathan , Rovin Brad , El-Achkar Tarek M. , Laszik Zoltan , He John Cijiang , Dagher Pierre C. , Valerius M. Todd , Jain Sanjay , Satlin Lisa M. , Troyanskaya Olga G. , Kretzler Matthias , Iyengar Ravi , Azeloglu Evren U. ,   Kidney Precision Medicine Project
Published: June 2022

Kidney Precision Medicine Project (KPMP) is building a spatially specified human kidney tissue atlas in health and disease with single-cell resolution. Here, we describe the construction of an integrated reference map of cells, pathways, and genes using unaffected regions of nephrectomy tissues and undiseased human biopsies from 56 adult subjects. We use single-cell/nucleus transcriptomics, subsegmental laser microdissection transcriptomics and proteomics, near-single-cell proteomics, 3D and CODEX imaging, and spatial metabolomics to hierarchically identify genes, pathways, and cells. Integrated data from these different technologies coherently identify cell types/subtypes within different nephron segments and the interstitium. These profiles describe cell-level functional organization of the kidney following its physiological functions and link cell subtypes to genes, proteins, metabolites, and pathways. They further show that messenger RNA levels along the nephron are congruent with the subsegmental physiological activity. This reference atlas provides a framework for the classification of kidney disease when multiple molecular mechanisms underlie convergent clinical phenotypes.
Deployable mechanical metamaterials with multistep programmable transformation
Authors: Meng Zhiqiang , Liu Mingchao , Yan Hujie , Genin Guy M. , Chen Chang Qing
Published: June 2022

Transformations in shape are critical to actuation in engineered metamaterials. Existing engineering metamaterials are typically limited to a small number of shape transformations that must be built-in during material synthesis. Here, inspired by the multistability and programmability of kirigami-based self-folding elements, a robust framework is introduced for the construction of sequentially programmable and reprogrammable mechanical metamaterials. The materials can be locked into multiple stable deployed configurations and then, using tunable bistability enabled by temperature-responsive constituent materials, return to their original reference configurations or undergo mode bifurcation. The framework provides a platform to design metamaterials with multiple deployable and reversible configurations in response to external stimuli.
Epigenetic reactivation of transcriptional programs orchestrating fetal lung development in human pulmonary hypertension
Authors: Chelladurai Prakash , Kuenne Carsten , Bourgeois Alice , Günther Stefan , Valasarajan Chanil , Cherian Anoop V. , Rottier Robbert J. , Romanet Charlotte , Weigert Andreas , Boucherat Olivier , Eichstaedt Christina A. , Ruppert Clemens , Guenther Andreas , Braun Thomas , Looso Mario , Savai Rajkumar , Seeger Werner , Bauer Uta-Maria , Bonnet Sébastien , Pullamsetti Soni Savai
Published: June 2022

Phenotypic alterations in resident vascular cells contribute to the vascular remodeling process in diseases such as pulmonary (arterial) hypertension [P(A)H]. How the molecular interplay between transcriptional coactivators, transcription factors (TFs), and chromatin state alterations facilitate the maintenance of persistently activated cellular phenotypes that consequently aggravate vascular remodeling processes in PAH remains poorly explored. RNA sequencing (RNA-seq) in pulmonary artery fibroblasts (FBs) from adult human PAH and control lungs revealed 2460 differentially transcribed genes. Chromatin immunoprecipitation sequencing (ChIP-seq) revealed extensive differential distribution of transcriptionally accessible chromatin signatures, with 4152 active enhancers altered in PAH-FBs. Integrative analysis of RNA-seq and ChIP-seq data revealed that the transcriptional signatures for lung morphogenesis were epigenetically derepressed in PAH-FBs, including coexpression of T-box TF 4 (
TBX4
),
TBX5
, and SRY-box TF 9 (
SOX9
), which are involved in the early stages of lung development. These TFs were expressed in mouse fetuses and then repressed postnatally but were maintained in persistent PH of the newborn and reexpressed in adult PAH. Silencing of
TBX4
,
TBX5
,
SOX9
, or E1A-associated protein P300 (
EP300
) by RNA interference or small-molecule compounds regressed PAH phenotypes and mesenchymal signatures in arterial FBs and smooth muscle cells. Pharmacological inhibition of the P300/CREB-binding protein complex reduced the remodeling of distal pulmonary vessels, improved hemodynamics, and reversed established PAH in three rodent models in vivo, as well as reduced vascular remodeling in precision-cut tissue slices from human PAH lungs ex vivo. Epigenetic reactivation of TFs associated with lung development therefore underlies PAH pathogenesis, offering therapeutic opportunities.
Delivery of an ectonucleotidase inhibitor with ROS-responsive nanoparticles overcomes adenosine-mediated cancer immunosuppression
Authors: Mao Chengqiong , Yeh Stacy , Fu Juan , Porosnicu Mercedes , Thomas Alexandra , Kucera Gregory L. , Votanopoulos Konstantinos I. , Tian Shaomin , Ming Xin
Published: June 2022

Tumor evasion of immune destruction is associated with the production of immunosuppressive adenosine in the tumor microenvironment (TME). Anticancer therapies can trigger adenosine triphosphate (ATP) release from tumor cells, causing rapid formation of adenosine by the ectonucleotidases CD39 and CD73, thereafter exacerbating immunosuppression in the TME. The goal of this study was to develop an approach to facilitate cancer therapy–induced immunogenic cell death including ATP release and to limit ATP degradation into adenosine, in order to achieve durable antitumor immune response. Our approach was to construct reactive oxygen species (ROS)–producing nanoparticles that carry an ectonucleotidase inhibitor ARL67156 by electronic interaction and phenylboronic ester. Upon near-infrared irradiation, nanoparticle-produced ROS induced ATP release from MOC1 cancer cells in vitro and triggered the cleavage of phenylboronic ester, facilitating the release of ARL67156 from the nanoparticles. ARL67156 prevented conversion of ATP to adenosine and enhanced anticancer immunity in an MOC1-based coculture model. We tested this approach in mouse tumor models. Nanoparticle-based ROS-responsive drug delivery reprogramed the immunogenic landscape in tumors, eliciting tumor-specific T cell responses and tumor regression, conferring long-term survival in mouse models. We demonstrated that TME reprograming sets the stage for response to anti-programmed cell death protein 1 (PD1) immunotherapy, and the combination resulted in tumor regression in a 4T1 breast cancer mouse model that was resistant to PD1 blockade. Furthermore, our approach also induced immunological effects in patient-derived organotypic tumor spheroid model, suggesting potential translation of our nanoparticle approach for treating human cancers.
Preclinical and clinical evaluation of the LRRK2 inhibitor DNL201 for Parkinson’s disease
Authors: Jennings Danna , Huntwork-Rodriguez Sarah , Henry Anastasia G. , Sasaki Jennifer C. , Meisner René , Diaz Dolores , Solanoy Hilda , Wang Xiang , Negrou Elvira , Bondar Vitaliy V. , Ghosh Rajarshi , Maloney Michael T. , Propson Nicholas E. , Zhu Yuda , Maciuca Romeo D. , Harris Laura , Kay Angela , LeWitt Peter , King T. Alex , Kern Drew , Ellenbogen Aaron , Goodman Ira , Siderowf Andrew , Aldred Jason , Omidvar Omid , Masoud Shababa T. , Davis Sonnet S. , Arguello Annie , Estrada Anthony A. , de Vicente Javier , Sweeney Zachary K. , Astarita Giuseppe , Borin Marie T. , Wong Bradley K. , Wong Harvey , Nguyen Hoang , Scearce-Levie Kimberly , Ho Carole , Troyer Matthew D.
Published: June 2022

Mutations in leucine-rich repeat kinase 2 (
LRRK2
) are the most common genetic risk factors for Parkinson’s disease (PD). Increased LRRK2 kinase activity is thought to impair lysosomal function and may contribute to the pathogenesis of PD. Thus, inhibition of LRRK2 is a potential disease-modifying therapeutic strategy for PD. DNL201 is an investigational, first-in-class, CNS-penetrant, selective, ATP-competitive, small-molecule LRRK2 kinase inhibitor. In preclinical models, DNL201 inhibited LRRK2 kinase activity as evidenced by reduced phosphorylation of both LRRK2 at serine-935 (pS935) and Rab10 at threonine-73 (pT73), a direct substrate of LRRK2. Inhibition of LRRK2 by DNL201 demonstrated improved lysosomal function in cellular models of disease, including primary mouse astrocytes and fibroblasts from patients with Gaucher disease. Chronic administration of DNL201 to cynomolgus macaques at pharmacologically relevant doses was not associated with adverse findings. In phase 1 and phase 1b clinical trials in 122 healthy volunteers and in 28 patients with PD, respectively, DNL201 at single and multiple doses inhibited LRRK2 and was well tolerated at doses demonstrating LRRK2 pathway engagement and alteration of downstream lysosomal biomarkers. Robust cerebrospinal fluid penetration of DNL201 was observed in both healthy volunteers and patients with PD. These data support the hypothesis that LRRK2 inhibition has the potential to correct lysosomal dysfunction in patients with PD at doses that are generally safe and well tolerated, warranting further clinical development of LRRK2 inhibitors as a therapeutic modality for PD.
A step forward for LRRK2 inhibitors in Parkinson’s disease
Authors: Lewis Patrick A.
Published: June 2022

A phase 1 clinical trial for kinase inhibitors targeting LRRK2 provides the foundation for testing the efficacy of LRRK2 kinase inhibitors in Parkinson’s disease.
Gut Microbiome 16S rRNA Gene Amplicon Taxonomic Profiling of Hospitalized Moroccan COVID-19 Patients
Authors: Sehli Sofia , Idrissi Azami Abdellah , Dini Nouzha , Habib Nihal , Chaouni Bouchra , Hamdi Salsabil , Al Idrissi Najib , Amzazi Saaid , Allali Imane , Nejjari Chakib , Ghazal Hassan
Published: June 2022

We explored the gut microbiome composition in four Moroccan patients with coronavirus disease 2019 (COVID-19) during hospitalization and treatment, using 16S rRNA gene amplicon metataxonomic profiling, and compared it with that in four healthy severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-free control subjects.
Allelic Polymorphism of Anthrax Pathogenicity Factor Genes as a Means of Estimating Microbiological Risks Associated with Climate Change
Authors: Goncharova Y. O. , Bogun A. G. , Bahtejeva I. V. , Titareva G. M. , Mironova R. I. , Kravchenko T. B. , Ostarkov N. A. , Brushkov A. V. , Timofeev V. S. , Ignatov S. G.
Published: June 2022

Climate change brings new risks of emergence of especially dangerous diseases. The paper reports the possibility of assessing the pathogenic potential of bacteria as demonstrated by studying the allelic polymorphism of anthrax bacterium pathogenicity factor genes, which is a prerequisite for assessing the associated microbiological risks. The allelic polymorphism of the capBCADE operon (capB, capC, capA, capD, and capE genes) encoding the capsule biosynthesis proteins of Bacillus anthracis, and the acpA and acpB genes encoding the expression regulators of this operon have been studied for the first time. A number of single nucleotide polymorphisms (SNPs) were described in the strains of the studied sample, including 5 SNPs in the capB gene, 3 in capC, 4 in capA, 14 in capD, 2 in capE, and 15 in acpB, as well as 7 SNPs and one insertion in the acpA gene. As a result, the sample has been divided into sequence types for each gene and 17 genotypes, which are combinations of the identified sequence types. In silico translation of the detected alleles of the studied genes revealed three isoforms of the CapB and CapA proteins, two isoforms of the CapC and CapE proteins, six isoforms of the CapD protein, five isoforms of the AcpA protein, and four isoforms in the AcpB protein. It has been demonstrated that the SNP in the 351A → G position of capC is a marker of A.Br.Aust94 group strains. Based on the results, A.Br.Vollum group strains were divided into two subgroups. The strains in the evolutionary lines B and C differed from the line A strains by the presence of an 853G → A SNP in the acpA gene. In addition, a previously unknown variable number tandem repeat (VNTR), has been found in the acpA gene and the possibility of using it for differentiating and genotyping of B. anthracis strains has been demonstrated.
Leptomeningeal disease in BRIP1-mutated pancreatic adenocarcinoma
Authors: Yim Eunji , Leung Denise
Published: June 2022

Leptomeningeal disease is rare in pancreatic cancer and prognosis remains poor. Mutation profiles are now directing therapy to improve survival. We describe a case of leptomeningeal and brain metastasis in BRCA1 interacting protein 1, or BRIP1-mutated pancreatic adenocarcinoma with progression through several lines of chemotherapy and immunotherapy. A woman in her late 50s presented with metastatic pancreatic adenocarcinoma on liver biopsy. She achieved complete response after modified FOLFIRINOX and started a poly (ADP-ribose) polymerase (PARP) inhibitor for a BRIP1 mutation. She had recurrence at 9 months and started pembrolizumab (programmed cell death protein 1, or PD-1receptor antibody) for tumour mutational burden of 10 muts/Mb. At 10 months, she presented with lower extremity weakness and back pain. MRI revealed leptomeningeal metastases from T11 to cauda equina roots and right occipital metastasis. Cerebrospinal fluid studies revealed elevated pressure (290 mm H2O) and protein (73 mg/dL) with negative cytology. Leptomeningeal carcinomatosis was diagnosed. She began palliative radiation but died at 11 months from initial diagnosis.
Systematic review on the measurement properties of diabetes-specific patient-reported outcome measures (PROMs) for measuring physical functioning in people with type 2 diabetes
Authors: Elsman Ellen B M , Mokkink Lidwine B , Langendoen-Gort Marlous , Rutters Femke , Beulens Joline , Elders Petra J M , Terwee Caroline B
Published: June 2022

We aimed to systematically assess the measurement properties of diabetes-specific patient-reported outcome measures (PROMs) for measuring physical functioning, one of the core outcomes, in adults with type 2 diabetes.

We performed a systematic literature search for PROMs or subscales measuring physical function that were validated to at least some extent in EMBASE and MEDLINE. Measurement properties were evaluated according to the COSMIN guideline for systematic reviews of PROMs.

In total 21 articles were included, describing 12 versions of 7 unique diabetes-specific PROMs or subscales measuring physical functioning. In general, there were few high-quality studies on measurement properties of PROMs measuring physical functioning in adults with type 2 diabetes. The Dependence/Daily Life subscale of the Diabetic Foot Ulcer Scale—Short Form (DFS-SF) and the Impact of Weight on Activities of Daily Living Questionnaire (IWADL) were most extensively evaluated. Both had sufficient ratings for aspects of content validity, although with mostly very low-quality evidence. Sufficient ratings for structural validity, internal consistency, and reliability were also found for both instruments, but responsiveness was rated inconsistent for both instruments. The other PROMs or subscales often had insufficient aspects of content validity, or their unidimensionality could not be confirmed.

This systematic review showed that the Dependence/Daily Life subscale of the DFS-SF and the IWADL could be used to measure physical functioning in people with type 2 diabetes in research or clinical practice, while keeping the limitations of these instruments in mind. The measurement properties that have not been evaluated extensively for these PROMs should be evaluated in future studies.

The study protocol was registered in the PROSPERO database, number CRD42021234890.
First in-human modified atrial septostomy combining radiofrequency ablation and balloon dilation
Authors: Yan Chaowu , Wan Linyuan , Li Hua , Wang Cheng , Guo Tingting , Niu Hanxu , Li Shiguo , Yundan Pingcuo , Wang Lei , Fang Wei
Published: June 2022

Objective

Preclinical research suggests that the combined use of radiofrequency ablation and balloon dilation (CURB) could create stable interatrial communications without device implantation. This study examined the first in-human use of CURB for modified atrial septostomy in patients with severe pulmonary arterial hypertension (PAH).

Methods

Between July 2018 and October 2021, CURB was performed in 19 patients with severe PAH (age: 31.5±9.1 years; mean pulmonary artery pressure: 73 mm Hg (IQR: 66–92); pulmonary vascular resistance: 18.7 Wood units (IQR: 17.8–23.3)). Under guidance of intracardiac echocardiography and three-dimensional location system, (1) fossae ovalis was reconstructed and ablated point-by-point with radiofrequency; (2) then graded balloon dilation was performed after transseptal puncture and the optimal size was determined according to the level of arterial oxygen saturation (SatO2); (3) radiofrequency ablation was repeated around the rims of the created fenestration. The interatrial fenestrations were followed-up serially.

Results

After CURB, the immediate fenestration size was 4.4 mm (IQR: 4.1–5.1) with intracardiac echocardiography, systolic aortic pressure increased by 10.2±6.9 mm Hg, cardiac index increased by 0.7±0.3 L/min/m2and room-air resting SatO2 decreased by 6.2±1.9% (p<0.001). One patient experienced increased pericardiac effusion postoperatively; the others had no complications. On follow-up (median: 15.5 months), all interatrial communications were patent with stable size (intraclass correlation coefficient=0.96, 95%CI:0.89 to 0.99). The WHO functional class increased by 1 (IQR: 1–2) (p<0.001) with improvement of exercise capacity (+159.5 m, P<0.001).

Conclusion

The interatrial communications created with CURB in patients with severe PAH were stable and the mid-term outcomes were satisfactory.

Trial registration number

NCT03554330.
Reaction of bis(dialkylphosphino)amines R2PNHPR2 (R = i-Pr, t-Bu, Ph) with halogens X2 (X = Cl, Br, I): different solvents – different stories
Authors: Riley Robert D. , Robertson Katherine N. , Clyburne Jason A.C.
Published: June 2022

The bis(dialkylphosphino)amines R2PNHPR2 react with elemental halogens X2 in dichloromethane to produce cationic products of the general form [(R)2P(X)-N-(R)2P(X)]+ (R =  i-Pr, Ph, and t-Bu; X = Cl, Br, and I). All of the nine possible products have been isolated and characterized using X-ray diffraction. The dichloro compounds crystallize as [HCl2]− salts, while the dibromo and diiodo products have been isolated as trihalides, [X3]−. A number of these compounds have been shown to react further with methanol to produce salts containing [(R)2P(OCH3)N(R)2P(OCH3)]+ cations, some of which have also been characterized using X-ray crystallography. The conversion of [(Ph)2P(I)-N-(Ph)2P(I)][I3] to [(Ph)2P(OCH3)-N-(Ph)2P(OCH3)][I3] was monitored using 31P NMR spectroscopy that revealed a stepwise reaction of the former compound with methanol. The results are discussed within the context of coupled reactions; this is then used to rationalize a mechanism for the formation of a rare catenated bismuth compound we reported previously. We suggest that the formation of the weak Bi–Bi bonds is offset by a coupled or a connected reaction mechanism , involving an irreversible reaction forming strong P–OR bonds in another of the isolated products.
Anatomy of a platform margin during a carbonate factory collapse: implications for the sedimentary record and sequence stratigraphic interpretation of poisoning events
Authors: Andrieu Simon , Krencker François-Nicolas , Bodin Stéphane
Published: June 2022

Sequence stratigraphic interpretations are limited in their prediction of sedimentary architecture and changes in sea-level when used in systems characterized by marked fluctuations in sediment supply, particularly in carbonate-dominated environments. Pronounced variations in sediment supply occurred during the Pliensbachian–Toarcian transition, when significant perturbations of the carbon cycle and intense environmental disturbances led to a global shutdown of carbonate production. We studied the impact of this event on sedimentation and stratal stacking patterns in the Moroccan central High Atlas. We reconstructed the lateral variations in facies and sedimentary geometries along a carbonate platform margin and slope in the field by tracking six key discontinuity surfaces covering the Pliensbachian–Toarcian transition from the platform margin to the toe-of-slope. This work highlights the difficulties in sequence stratigraphic interpretations in cases of neritic carbonate factory collapse without assessments of shoreline movement because the stacking patterns in open marine environments do not necessary reflect the regional variation in base level in disturbed carbonate systems. This study also emphasizes the uncertainties associated with focusing solely on lower offshore strata to assess the history and causes of palaeoenvironmental perturbations because decreases in the rate of carbonate production dampen neritic carbonate shedding and therefore favour the creation of a hiatus in deep water settings.
Electrochemistry of Praseodymium in Aqueous Solution Using a Liquid Gallium Cathode
Authors: Engmann Eugene , Diaz Luis A. , Lister Tedd E. , Palasyuk Olena , Zhao Haiyan
Published: June 2022

The electrochemistry of liquid Ga electrodes in aqueous media was examined in the presence of praseodymium acetate (PrOAc) as an alternate path for low temperature reduction of rare earth elements (REE). This study investigated the aqueous electrochemistry of Ga with and without REEs (Pr). Cyclic voltammetry experiments showed that in the presence of PrOAc, an order of magnitude increase in cathodic current was observed for the Ga electrode, compared to that in the absence of Pr. Decrease in the reduction current with the increase of scan rate, with and without Pr, suggests catalytic reactions following electron transfer, which was attributed to the Ga2O disproportionation reaction. Chronoamperometric experiments performed in Pr containing solutions formed a precipitate. Over 50% of the Pr ions from the aqueous electrolyte were immobilized in the precipitate; a solid Ga-rich phase. Formation of this precipitate was only possible when Ga oxidation was induced. This condition was achieved by circulation of liquid Ga from the pool via external pump and returned dropwise to the liquid Ga pool. When the collected precipitate was leached in dilute HCl, Pr was released with H2 evolved as a byproduct, and Ga returned to its initial liquid metallic state. These preliminary results show encouraging new routes that could be applied for the recovery of diluted REE leachates, such as those obtained from magnets, coal fly ash, and ores.
Facile Single Step Electrochemical Growth of Ni3P on Carbon Cloth for Highly Efficient Hydrogen Evolution Reaction
Authors: Das Manisha , Khan Zubair Bashir , Kamboj Navpreet , Banerjee Manami , Dey Ramendra Sundar
Published: June 2022

The exploration of facile synthesis, a highly active and cost-effective noble metal-free durable electrocatalyst for hydrogen production through water electrolysis is an essential job in the arena of sustainable and clean energy production. In this context, it is crucially desired to look for an inexpensive noble metal-free electrocatalyst for practical use. In recent studies, nickel phosphides are the widely investigated hydrogen evolution reaction (HER) electrocatalysts owing to their extraordinary electronic properties, corrosion-resistant ability and superior electrocatalytic response. In this study, a highly ordered single-phase Ni3P is grown on activated carbon cloth (CC*) via a one-step electrochemical deposition method, which offers a facile synthesis route for the development of a highly durable electrocatalyst active towards HER. The hierarchical porous structure of Ni3P provides effluent ion dynamic channels that encourage expeditious kinetics, superior activity and extraordinary stability. The resulting electrocatalyst (Ni3P@CC*) shows astonishing electrochemical activity towards HER under alkaline conditions and delivers an overpotential of 150 mV at a current density of 10 mA cm−2 with high durability and large electrochemically active surface area (ECSA) that favours the large-scale hydrogen production for future energy systems.
The legacy of Gerald L. Gottlieb in human movement neuroscience
Authors: Corcos Daniel M. , Myklebust Barbara M. , Latash Mark L.
Published: June 2022

In this paper, we review the legacy of Gerald (Gerry) Gottlieb in various fields related to the neural control of human movement. His studies on the myotatic (stretch) reflex and postmyotatic responses to ankle joint perturbations paved the way for current explorations of long-loop reflexes and their role in the control of movement. The dual-strategy hypothesis introduced order into a large body of literature on the triphasic muscle activation patterns seen over a variety of voluntary movements in healthy persons. The dual-strategy hypothesis continues to be important for understanding the performance of subjects with disordered motor control. The principle of linear synergy (covariance of joint torques) was an attempt to solve one of the notorious problems of motor redundancy, which remains an important topic in the field. Gerry’s attitude toward the equilibrium-point hypothesis varied between rejection and using it to explore patterns of hypothetical control variables and movement variability. The discovery of reciprocal excitation in healthy neonates fostered other studies of changes in spinal cord physiology as motor skills develop. In addition, studies of people with spasticity and the effects of treatment with intrathecal baclofen were crucial in demonstrating the possibility of unmasking voluntary movements after suppression of the hyperreflexia of spasticity. Gerry Gottlieb contributed a significant body of knowledge that formed a solid foundation from which to study a variety of neurological diseases and their treatments, and a more comprehensive and parsimonious foundation to describe the neural control of human movement.