bluuebunny/crossref_metadata_2025 huggingface dataset:
Insights into sugar metabolism during bilberry (Vaccinium myrtillus L.) fruit development
Authors: Samkumar Amos , Karppinen Katja , Dhakal Binita , Martinussen Inger , Jaakola Laura
Published: March 2022

Bilberry fruit is regarded as one of the best natural sources of anthocyanins and is widely explored for its health‐beneficial compounds. Besides anthocyanins, one of the major attributes that determine the berry quality is the accumulation of sugars that provide sweetness and flavor to ripening fruit. In this study, we have identified 25 sugar metabolism‐related genes in bilberry, including invertases (INVs), hexokinases (HKs), fructokinases (FKs), sucrose synthases (SSs), sucrose phosphate synthases (SPSs), and sucrose phosphate phosphatases (SPPs). The results indicate that isoforms of the identified genes are expressed differentially during berry development, suggesting specialized functions. The highest sugar content was found in ripe berries, with fructose and glucose dominating accompanied by low sucrose amount. The related enzyme activities during berry development and ripening were further analyzed to understand the molecular mechanism of sugar accumulation. The activity of INVs in the cell wall and vacuole increased toward ripe berries. Amylase activity involved in starch metabolism was not detected in unripe berries but was found in ripe berries. Sucrose resynthesizing SS enzyme activity was detected upon early ripening and had the highest activity in ripe berries. Interestingly, our transcriptome data showed that supplemental irradiation with red and blue light triggered upregulation of several sugar metabolism‐related genes, including α‐ and β‐amylases. Also, differential expression patterns in responses to red and blue light were found across sucrose, galactose, and sugar‐alcohol metabolism. Our enzymological and transcriptional data provide new understanding of the bilberry fruit sugar metabolism having major effect on fruit quality.
The phytohormone abscisic acid modulates protein carbonylation in Arabidopsis thaliana
Authors: Jaballi Amal , Missihoun Tagnon D.
Published: March 2022

Protein carbonylation is a post‐translational modification associated with the reactive oxygen species. It results from the direct oxidation of the side chains of Lys, Arg, Pro, and Thr residues by hydroxyl radical HO• or the addition of reactive carbonyl species including α,β‐unsaturated aldehydes and oxylipins to the side chain of Cys, His, and Lys. Recent findings indicated that the phytohormone abscisic acid (ABA) induces the production of α,β‐unsaturated aldehydes that modulate the effect of ABA on stomatal closure. This indicated that α,β‐unsaturated aldehydes might mediate ABA signaling. In this study, we investigated the ABA‐induced protein carbonylation events by profiling the carbonylated proteome extracted from Arabidopsis thaliana leaves after ABA treatment. The carbonylated proteins were enriched by affinity chromatography and subjected to liquid chromatography–tandem mass spectrometry. We identified 180 carbonylated proteins. Of these, 26 proteins became carbonylated upon ABA treatment, whereas 163 proteins that were carbonylated in untreated samples were no longer detected in the ABA‐treated samples, which points to dynamic control of protein carbonylation by ABA in A. thaliana. A few regulatory stress‐related proteins and enzymes involved in the biosynthesis of the aspartate family of amino acids were overrepresented in the list of proteins, which the carbonylation status changed between untreated and ABA‐treated samples. These results indicated that ABA triggers a change in the pattern of protein carbonylation in A. thaliana. This change is independent of the commonly seen increased levels of carbonylated proteins in the plants subjected to deadly stress conditions.
The miR159‐MYB33‐ABI5 module regulates seed germination in Arabidopsis
Authors: Jiang Youqi , Wu Xi , Shi Min , Yu Jing , Guo Changkui
Published: March 2022

Drought stress restricts crop productivity and exacerbates food shortages. The plant hormone, abscisic acid (ABA), has been shown to be a pivotal player in the regulation of drought tolerance and seed germination in plants. ABA accumulates under abiotic stresses to promote miR159 expression. miR159 is an ancient and conserved plant miRNA that plays diverse roles in plant development, seed germination, and drought response in Arabidopsis. Our previous studies demonstrated that miR159 regulates the vegetative phase change by repressing the ABI5 activation and thereafter preventing hyperactivation of miR156. However, whether the miR159‐MYB33‐ABI5 module plays a role in seed germination and drought response, and if so, how they interact genetically, remain largely unexplored. Here, we show that loss‐of‐function of miR159 (mir159ab) confers enhanced drought tolerance and hypersensitivity of seed germination to ABA. Genetic analyses demonstrated that loss‐of‐function mutation in the ABI5 gene suppresses the hypersensitivity of mir159ab to ABA, and the insensitivity of myb33 seeds to ABA treatment is ABI5 dependent. ABI5 functions downstream of MYB33 and miR159 in response to ABA. Therefore, our results uncover a new role for the miR159‐MYB33‐ABI5 module in the regulation of drought response and seed germination in plants.
Role of Porphyromonas gingivalis in oral and orodigestive squamous cell carcinoma
Authors: Lamont Richard J. , Fitzsimonds Zackary R. , Wang Huizhi , Gao Shegan
Published: March 2022

Oral and esophageal squamous cell carcinomas harbor a diverse microbiome that differs compositionally from precancerous and healthy tissues. Though causality is yet to be definitively established, emerging trends implicate periodontal pathogens such as Porphyromonas gingivalis as associated with the cancerous state. Moreover, infection with P. gingivalis correlates with a poor prognosis, and P. gingivalis is oncopathogenic in animal models. Mechanistically, properties of P. gingivalis that have been established in vitro and could promote tumor development include induction of a dysbiotic inflammatory microenvironment, inhibition of apoptosis, increased cell proliferation, enhanced angiogenesis, activation of epithelial‐to‐mesenchymal transition, and production of carcinogenic metabolites. The microbial community context is also relevant to oncopathogenicity, and consortia of P. gingivalis and Fusobacterium nucleatum are synergistically pathogenic in oral cancer models in vivo. In contrast, oral streptococci, such as Streptococcus gordonii, can antagonize protumorigenic epithelial cell phenotypes induced by P. gingivalis, indicating functionally specialized roles for bacteria in oncogenic communities. Consistent with the notion of the bacterial community constituting the etiologic unit, metatranscriptomic data indicate that functional, rather than compositional, properties of the tumor‐associated communities have more relevance to cancer development. A consistent association of P. gingivalis with oral and orodigestive carcinoma could have diagnostic potential for early detection of these conditions that have a high incidence and low survival rates.
Periodontitis, chronic liver diseases, and the emerging oral‐gut‐liver axis
Authors: Albuquerque‐Souza Emmanuel , Sahingur Sinem E.
Published: March 2022

The liver carries out a wide range of functions ranging from the control of metabolites, nutrient storage, and detoxification to immunosurveillance. While inflammation is essential for the tissue remodeling and maintenance of homeostasis and normal liver physiology, constant exposure to dietary and microbial products creates a niche for potentially prolonged immune activation and unresolved inflammation in susceptible host. Failure to restrain inflammation can lead to development of chronic liver diseases characterized by fibrosis, cirrhosis and eventually liver failure. The liver maintains close interactions with numerous organs which can influence its metabolism and physiology. It is also known that oral cavity microenvironment can influence the physiological conditions of other organs and emerging evidence implicates that this could be true for the liver as well. Presence of chronic inflammation and dysbiotic microbiota is a common feature leading to clinical pathology both in periodontitis and chronic liver diseases (CLDs). In fact, known CLDs appear to have some relationship with periodontitis, which impacts the onset or progression of these conditions in a bidirectional crosstalk. In this review, we explore the emerging association between oral‐gut‐liver axis focusing on periodontitis and common CLDs including nonalcoholic fatty liver disease, chronic viral hepatitis, liver cirrhosis, and hepatocellular cancer. We highlight the immune pathways and oral microbiome interactions which can link oral cavity and liver health and offer perspectives for future research.
Viruses, periodontitis, and comorbidities
Authors: Teles Flavia , Collman Ronald G. , Mominkhan Dana , Wang Yu
Published: March 2022

Seminal studies published in the 1990s and 2000s explored connections between periodontal diseases and systemic conditions, revealing potential contributions of periodontal diseases in the initiation or worsening of systemic conditions. The resulting field of periodontal medicine led to the publication of studies indicating that periodontal diseases can influence the risk of systemic conditions, including adverse pregnancy outcomes, cardiovascular and respiratory diseases, as well as Alzheimer disease and cancers. In general, these studies hypothesized that the periodontal bacterial insult and/or the associated proinflammatory cascade could contribute to the pathogenesis of these systemic diseases. While investigations of the biological basis of the connections between periodontal diseases and systemic conditions generally emphasized the bacteriome, it is also biologically plausible, under an analogous hypothesis, that other types of organisms may have a similar role. Human viruses would be logical “suspects” in this role, given their ubiquity in the oral cavity, association with periodontal diseases, and ability to elicit strong inflammatory response, compromise immune responses, and synergize with bacteria in favor of a more pathogenic microbial consortium. In this review, the current knowledge of the role of viruses in connecting periodontal diseases and systemic conditions is examined. We will also delve into the mechanistic basis for such connections and highlight the importance of those relationships in the management and treatment of patients.
Activin A attenuates apoptosis of granulosa cells in atretic follicles through ERβ‐induced autophagy
Authors: Liu Ning , Wang Shiyou , Yao Qichun , Li Yuanyou , Hu Hai , Tang Xiaorong , Ran Haohan , Price Christopher A. , Jiang Zhongliang
Published: March 2022

It is well known that approximately 99% of ovarian follicles in mammals suffer from a degenerative process known as atresia, which is a huge waste of genetic resource in female animals. Studies have shown that activin A (ACT‐A) is located in ovarian granulosa cells and has different effects in granulosa cell depending on species. Although granulosa cells play a critical role during follicular atresia, the mechanism of action of ACT‐A in bovine ovarian granulosa cells (BGC) is poorly understood. In this study, we first determined the apoptosis of BGCs isolated from growth follicles and atretic follicles respectively. Then, BGC isolated from atretic follicles were used as a model to elucidate the role of ACT‐A in cattle ovary. The results showed that apoptosis occurred in both growing follicles and atretic follicles, and the percentage of apoptotic cells in atretic follicles was higher than that in growing follicles. The current results indicated that ACT‐A can attenuate apoptosis of BGC by maintaining the function of BGC in atretic follicles. Increased ERβ induced by ACT‐A promoted BGC autophagy but had no effect on apoptosis. In summary, this study suggests that ACT‐A attenuates BGC apoptosis in atretic follicles by ERβ‐mediated autophagy signalling.
Comparative transcriptome analysis identifies important maternal molecules and associated biological pathways for pig and human mature oocytes
Authors: Fang Ting , Wu Zi‐Wei , Wang Yi , Wang Fang , Du Zhi‐Qiang , Yang Cai‐Xia
Published: March 2022

Recent researches reveal that during oocyte maturation, species‐specific molecular profile exists and has important functional roles. However, molecular differences between pig (a larger animal model for human reproduction) and human mature oocytes remain unknown. Here, by comparative transcriptome analyses of single‐cell RNA‐seq data, we aimed to identify the common and unique maternal factors and associated biological processes between in vivo and in vitro matured pig oocytes, and between in vitro matured human and pig oocytes. Annotated protein‐coding mRNAs were identified in pig in vivo (11,147) and in vitro (11,997), and human in vitro (14,491) MII oocytes, respectively. For in vivo and in vitro derived pig MII oocytes, 10,551 annotated maternal mRNAs were common, mainly enriched in signalling pathways such as cell cycle, oocyte meiosis, microtubule cytoskeleton, MAPK, RNA processing/binding. Besides, in vivo (596) and in vitro (1446) pig MII‐specific mRNAs and their involved signalling pathways (in vivo: Bmp, calcium‐mediated signalling, PI3K‐Akt; in vitro: growth factor activity, JAK‐STAT, cytokine‐cytokine receptor interaction, calcium signalling pathway) were also found. As for in vitro derived human and pig MII oocytes, 10,285 annotated mRNAs were common, enriched in a variety of signalling pathways (cell cycle, oocyte meiosis, microtubule, AMPK, RNA splicing, protein serine/threonine kinase activity, etc). In vitro MII‐specific mRNAs were found for humans (4206) and pigs (1712), which were also enriched in species‐specific signalling pathways (humans: golgi‐related terms, transcription repressor and hormone activity; pigs: ATP biosynthetic process, G protein‐coupled peptide receptor activity, animoacyl‐tRNA biosynthesis), respectively. These findings improve our understanding on oocyte maturation, and also the limitations of pig model for human oocyte maturation and fertilization.
Identifying scenarios and risk factors for Q fever outbreaks using qualitative analysis of expert opinion
Authors: Tan Tabita Su‐En , Hernandez‐Jover Marta , Hayes Lynne Maree , Wiethoelter Anke Katrin , Firestone Simon Matthew , Stevenson Mark Anthony , Heller Jane
Published: March 2022

Q fever is an important zoonotic disease perceived to be an occupational hazard for those working with livestock. Outbreaks involving large numbers of people are uncommon, but the increasing case incidence coupled with changing environmental and industry conditions that promote transmission of Q fever has raised concerns that large and serious outbreaks could become more frequent. The aim of this study was to use expert opinion to better understand how large Q fever outbreaks might occur in an Australian context and to document factors believed to be drivers of disease transmission. Focus groups were conducted with human and animal health professionals across several Australian states. All discussions were recorded, transcribed verbatim and imported into NVIVO for thematic analysis. Four anthropogenic risk factors (disease awareness, industry practices, land use, human behaviour) and three ecological risk factors (physical environment, agent dissemination, animal hosts) emerged from the data. Analysis of expert opinions pointed to the existence of numerous scenarios in which Q fever outbreaks could occur, many of which depict acquisition in the wider community outside of traditional at‐risk occupations. This perception of the expansion of Q fever from occupational‐acquisition to community‐acquisition is driven by greater overarching economic, political and socio‐cultural influences that govern the way in which people live and work. Findings from this study highlight that outbreaks are complex phenomena that involve the convergence of diverse elements, not just that of the pathogen and host, but also the physical, political and socioeconomic environments in which they interact. A review of the approaches to prevent and manage Q fever outbreaks will require a multisectorial approach and strengthening of community education, communication and engagement so that all stakeholders become an integrated part of outbreak mitigation and response.
Evaluación de la dimensión científico-clínica del cuidado en el personal de enfermería
Authors: Henao Castaño Ángela María , Ávila Myriam Lucía , Ramos Hernández Soraya , Guaqueta-Parada Sandra Rocío , Triana-Restrepo Martha Cecilia
Published: March 2022

La evaluación de la dimensión científico-clínica del cuidado de enfermería basado en el modelo HANC en la Unidad de Cuidado Intensivo (VDCC-UCI) permitió medir la calidad del cuidado en los procesos de atención de enfermería en la Unidad de Cuidado Intensivo. Objetivo: Describir la dimensión científico-clínica del cuidado de enfermería en la Unidad de Cuidado Intensivo, comparando entre enfermeras de instituciones públicas y privadas. Método: Estudio descriptivo de tipo transversal realizado entre de julio y diciembre de 2019. Participaron 186 enfermeros que trabajan en la Unidad de Cuidado Intensivo de instituciones públicas y privadas del país. Los datos fueron recolectados con el instrumento de la dimensión científico-clínica. Resultados: Los participantes, en su mayoría mujeres (74 %) y hombres (48 %), contaban con una especialización (75 %) y con experiencia profesional más de diez años; el tipo de contratación más común fue el de término indefinido. Se encontraron diferencias estadísticamente significativas en 18 de los 46 ítems entre las respuestas de enfermeras de instituciones públicas en comparación con las de instituciones privadas. Conclusiones: La evaluación de la dimensión científico-clínica mostró que algunas etapas del proceso de atención de enfermería se llevan a cabo de manera más rigurosa y completa por parte de las enfermeras de instituciones privadas, mientras las etapas del proceso administrativo e investigativo implementadas por enfermeras de entidades públicas y privadas son similares.
Formación ciudadana en la infancia: reflexiones desde la revisión teórica
Authors: Lara-Salcedo Luz Marina , Suarez-Rivero Neftali David
Published: March 2022

Se brinda un conjunto de reflexiones teóricas que aportan al campo conceptual de la ciudadanía para su práctica en el espacio escolar. Parte de explorar las nociones clásicas y contemporáneas del concepto, y luego se analizan algunas tendencias de la formación ciudadana para ubicar el tipo de ciudadanía que es necesario promover con los niños, a la luz de las pedagogías críticas y de una reconstrucción crítica del concepto. Finaliza señalando la urgencia de formar en ciudadanía desde la infancia, de su reconocimiento como ciudadanos y sujetos políticos, con una mirada renovada de la educación ciudadana desde una perspectiva crítica, decolonial y más incluyente.
Hacia una evaluación de la reflexión pedagógica desde la escritura académica
Authors: Schnitzler-Sommerfeld Nicole , Núñez-Lagos Paulina
Published: March 2022

Este artículo de investigación describe el diseño y aplicación de un instrumento de evaluación del pensamiento crítico desde la escritura académica como método para desarrollar la reflexión pedagógica. A partir de una metodología cuantitativa,con alcance descriptivo, se analizaron 265 ensayos de estudiantes chilenos de pedagogía. La capacidad de relacionar de forma consistente y coherente los argumentos, y la habilidad para articular el punto de vista propio con otras perspectivas sistemáticamente, resultaron los mayores predictores en la elaboración de un texto escrito con un alto nivel de pensamiento crítico (Martin & White, 2003; Snow & Uccelli, 2009; Youngs & Bird, 2010).
Relación entre prácticas pedagógicas de educación inicial con De Cero a Siempre
Authors: Vargas-Gónzalez Ángela Patricia
Published: March 2022

En este artículo de investigación se analiza la relación entre prácticas pedagógicas de la modalidad institucional de la educación inicial colombiana con los lineamientos educativos del programa De Cero a Siempre. Metodológicamente se realizó un estudio de caso comparativo (ECC), en el que se analizaron 36 prácticas pedagógicas con el método de comparación constante de la teoría fundamentada constructivista. Los principales resultados muestran que, aunque en las prácticas pedagógicas se mantiene una tradición mimética, que se contradice con los postulados de la política educativa, se atisban modos de relacionamiento basados en el respeto y reconocimiento del otro.
Strategies for Improved Stability of Methanol-in-Diesel Emulsions
Authors: Ghosh Anupam , Ravikrishna R. V.
Published: March 2022

This study is motivated by the need to present a robust methodology for preparing stable methanol-in-diesel emulsions for use in compression ignition engines with the specific objective of maximizing the methanol content. Specifically, it involved exploring the feasibility of methanol-in-diesel emulsions with conventional surfactants such as Tween-80 and Span-80 and nonconventional surfactants such as 1-dodecanol, pentanol, and butanol. The hydrophilic–lipophilic balance (HLB) values of the surfactant varied from 7 to 15 to investigate the role of the surfactant HLB on the stability of the macroemulsion. It is observed that the macroemulsion with an HLB value of 10 provides the best stability results. Using surfactant HLB value of 10, three macroemulsions with 10 wt%, 15 wt%, and 20 wt% of methanol were prepared using ultrasonication. However, only the macroemulsion with 10 wt% of methanol was observed to be stable for at least 20 days after preparation. Next, the microemulsions of diesel–methanol were produced by using nonconventional surfactants such as 1-dodecanol, pentanol, and butanol. Among these, 1-dodecanol was found out as the most suitable surfactant owing to its ability to form microemulsions with any mixing ratio of diesel–methanol and its high cetane number (63.6). This study has clearly brought out the strategies for preparing both macro and microemulsions. Overall, the results presented in the current work are expected to aid efforts in adapting compression ignition engines for diesel–methanol fuel blends.
Transitional premonocytes emerge in the periphery for host defense against bacterial infections
Authors: Teh Ye Chean , Chooi Ming Yao , Liu Dehua , Kwok Immanuel , Lai Ghee Chuan , Ayub Ow Yong Liyana , Ng Melissa , Li Jackson L. Y. , Tan Yingrou , Evrard Maximilien , Tan Leonard , Liong Ka Hang , Leong Keith , Goh Chi Ching , Chan Andrew Y. J. , Shadan Nurhidaya Binte , Mantri Chinmay Kumar , Hwang You Yi , Cheng Hui , Cheng Tao , Yu Weimiao , Tey Hong Liang , Larbi Anis , St John Ashley , Angeli Veronique , Ruedl Christiane , Lee Bernett , Ginhoux Florent , Chen Swaine L. , Ng Lai Guan , Ding Jeak Ling , Chong Shu Zhen
Published: March 2022

Circulating Ly6C
hi
monocytes often undergo cellular death upon exhaustion of their antibacterial effector functions, which limits their capacity for subsequent macrophage differentiation. This shrouds the understanding on how the host replaces the tissue-resident macrophage niche effectively during bacterial invasion to avert infection morbidity. Here, we show that proliferating transitional premonocytes (TpMos), an immediate precursor of mature Ly6C
hi
monocytes (MatMos), were mobilized into the periphery in response to acute bacterial infection and sepsis. TpMos were less susceptible to apoptosis and served as the main source of macrophage replenishment when MatMos were vulnerable toward bacteria-induced cellular death. Furthermore, TpMo and its derived macrophages contributed to host defense by balancing the proinflammatory cytokine response of MatMos. Consequently, adoptive transfer of TpMos improved the survival outcome of lethal sepsis. Our findings hence highlight a protective role for TpMos during bacterial infections and their contribution toward monocyte-derived macrophage heterogeneity in distinct disease outcomes.
Structural insights into ligand recognition, activation, and signaling of the α
2A
adrenergic receptor
Authors: Xu Jun , Cao Sheng , Hübner Harald , Weikert Dorothée , Chen Geng , Lu Qiuyuan , Yuan Daopeng , Gmeiner Peter , Liu Zheng , Du Yang
Published: March 2022

The α
2A
adrenergic receptor (α
2A
AR) is a G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptor that mediates important physiological functions in response to the endogenous neurotransmitters norepinephrine and epinephrine, as well as numerous chemically distinct drugs. However, the molecular mechanisms of drug actions remain poorly understood. Here, we report the cryo–electron microscopy structures of the human α
2A
AR-GoA complex bound to norepinephrine and three imidazoline derivatives (brimonidine, dexmedetomidine, and oxymetazoline). Together with mutagenesis and functional data, these structures provide important insights into the molecular basis of ligand recognition, activation, and signaling at the α
2A
AR. Further structural analyses uncover different molecular determinants between α
2A
AR and βARs for recognition of norepinephrine and key regions that determine the G protein coupling selectivity. Overall, our studies provide a framework for understanding the signal transduction of the adrenergic system at the atomic level, which will facilitate rational structure-based discovery of safer and more effective medications for α
2A
AR.
Abrogation of self-tolerance by misfolded self-antigens complexed with MHC class II molecules
Authors: Jin Hui , Kishida Kazuki , Arase Noriko , Matsuoka Sumiko , Nakai Wataru , Kohyama Masako , Suenaga Tadahiro , Yamamoto Ken , Sasazuki Takehiko , Arase Hisashi
Published: March 2022

Specific MHC class II alleles are strongly associated with susceptibility to various autoimmune diseases. Although the primary function of MHC class II molecules is to present peptides to helper T cells, MHC class II molecules also function like a chaperone to transport misfolded intracellular proteins to the cell surface. In this study, we found that autoantibodies in patients with Graves’ disease preferentially recognize thyroid-stimulating hormone receptor (TSHR) complexed with MHC class II molecules of Graves’ disease risk alleles, suggesting that the aberrant TSHR transported by MHC class II molecules is the target of autoantibodies produced in Graves’ disease. Mice injected with cells expressing mouse TSHR complexed with MHC class II molecules, but not TSHR alone, produced anti-TSHR autoantibodies. These findings suggested that aberrant self-antigens transported by MHC class II molecules exhibit antigenic properties that differ from normal self-antigens and abrogate self-tolerance, providing a novel mechanism for autoimmunity.
Cortico-striatal circuits for bilaterally coordinated movements
Authors: Pimentel-Farfan Ana K. , Báez-Cordero Ana S. , Peña-Rangel Teresa M. , Rueda-Orozco Pavel E.
Published: March 2022

Movement initiation and control require the orchestrated activity of sensorimotor cortical and subcortical regions. However, the exact contribution of specific pathways and interactions to the final behavioral outcome are still under debate. Here, by combining structural lesions, pathway-specific optogenetic manipulations and freely moving electrophysiological recordings in rats, we studied cortico-striatal interactions in the context of forelimb bilaterally coordinated movements. We provide evidence indicating that bilateral actions are initiated by motor cortical regions where intratelencephalic bilateral cortico-striatal (bcs-IT) projections recruit the sensorimotor striatum to provide stability and duration to already commanded bilateral movements. Furthermore, striatal spiking activity was correlated with movement duration and kinematic parameters of the execution. bcs-IT stimulation affected only the representation of movement duration but spared that of kinematics. Our findings confirm the modular organization of information processing in the striatum and its involvement in moment-to-moment movement control but not initiation or selection.
Ecological regime shift in the Northeast Atlantic Ocean revealed from the unprecedented reduction in marine growth of Atlantic salmon
Authors: Vollset Knut Wiik , Urdal Kurt , Utne Kjell , Thorstad Eva B. , Sægrov Harald , Raunsgard Astrid , Skagseth Øystein , Lennox Robert J. , Østborg Gunnel M. , Ugedal Ola , Jensen Arne J. , Bolstad Geir H. , Fiske Peder
Published: March 2022

Ecological regime shifts are abrupt changes in the structure and function of ecosystems that persist over time, but evidence of contemporary regime shifts are rare. Historical scale data from 52,384 individual wild Atlantic salmon caught in 180 rivers from 1989 to 2017 reveal that growth of Atlantic salmon across the Northeast Atlantic Ocean abruptly decreased following the year 2004. At the same time, the proportion of early maturing Atlantic salmon decreased. These changes occurred after a marked decrease in the extent of Arctic water in the Norwegian Sea, a subsequent warming of spring water temperature before Atlantic salmon entering the sea, and an approximately 50% reduction of zooplankton across large geographic areas of the Northeast Atlantic Ocean. A sudden decrease in growth was also observed among Atlantic mackerel in the Norwegian Sea. Our results point toward an ecosystem-scale regime shift in the Northeast Atlantic Ocean.
Protein chain collapse modulation and folding stimulation by GroEL-ES
Authors: Naqvi Mohsin M. , Avellaneda Mario J. , Roth Andrew , Koers Eline J. , Roland Antoine , Sunderlikova Vanda , Kramer Günter , Rye Hays S. , Tans Sander J.
Published: March 2022

The collapse of polypeptides is thought important to protein folding, aggregation, intrinsic disorder, and phase separation. However, whether polypeptide collapse is modulated in cells to control protein states is unclear. Here, using integrated protein manipulation and imaging, we show that the chaperonin GroEL-ES can accelerate the folding of proteins by strengthening their collapse. GroEL induces contractile forces in substrate chains, which draws them into the cavity and triggers a general compaction and discrete folding transitions, even for slow-folding proteins. This collapse enhancement is strongest in the nucleotide-bound states of GroEL and is aided by GroES binding to the cavity rim and by the amphiphilic C-terminal tails at the cavity bottom. Collapse modulation is distinct from other proposed GroEL-ES folding acceleration mechanisms, including steric confinement and misfold unfolding. Given the prevalence of collapse throughout the proteome, we conjecture that collapse modulation is more generally relevant within the protein quality control machinery.
Specific mesoderm subset derived from human pluripotent stem cells ameliorates microvascular pathology in type 2 diabetic mice
Authors: Gil Chang-Hyun , Chakraborty Dibyendu , Vieira Cristiano P. , Prasain Nutan , Calzi Sergio Li , Fortmann Seth D. , Hu Ping , Banno Kimihiko , Jamal Mohamed , Huang Chao , Sielski Micheli S. , Lin Yang , Huang Xinxin , Dupont Mariana D. , Floyd Jason L. , Prasad Ram , Longhini Ana Leda F. , McGill Trevor J. , Chung Hyung-Min , Murphy Michael P. , Kotton Darrell N. , Boulton Michael E. , Yoder Mervin C. , Grant Maria B.
Published: March 2022

Human induced pluripotent stem cells (hiPSCs) were differentiated into a specific mesoderm subset characterized by KDR
+
CD56
+
APLNR
+
(KNA
+
) expression. KNA
+
cells had high clonal proliferative potential and specification into endothelial colony-forming cell (ECFCs) phenotype. KNA
+
cells differentiated into perfused blood vessels when implanted subcutaneously into the flank of nonobese diabetic/severe combined immunodeficient mice and when injected into the vitreous of type 2 diabetic mice (
db/db
mice). Transcriptomic analysis showed that differentiation of hiPSCs derived from diabetics into KNA
+
cells was sufficient to change baseline differences in gene expression caused by the diabetic status and reprogram diabetic cells to a pattern similar to KNA
+
cells derived from nondiabetic hiPSCs. Proteomic array studies performed on retinas of
db/db
mice injected with either control or diabetic donor–derived KNA
+
cells showed correction of aberrant signaling in
db/db
retinas toward normal healthy retina. These data provide “proof of principle” that KNA
+
cells restore perfusion and correct vascular dysfunction in
db/db
mice.
Ultrastructural visualization of chromatin in cancer pathogenesis using a simple small-molecule fluorescent probe
Authors: Xu Jianquan , Sun Xuejiao , Kim Kwangho , Brand Rhonda M. , Hartman Douglas , Ma Hongqiang , Brand Randall E. , Bai Mingfeng , Liu Yang
Published: March 2022

Imaging chromatin organization at the molecular-scale resolution remains an important endeavor in basic and translational research. Stochastic optical reconstruction microscopy (STORM) is a powerful superresolution imaging technique to visualize nanoscale molecular organization down to the resolution of ~20 to 30 nm. Despite the substantial progress in imaging chromatin organization in cells and model systems, its routine application on assessing pathological tissue remains limited. It is, in part, hampered by the lack of simple labels that consistently generates high-quality STORM images on the highly processed clinical tissue. We developed a fast, simple, and robust small-molecule fluorescent probe—cyanine 5–conjugated Hoechst—for routine superresolution imaging of nanoscale nuclear architecture on clinical tissue. We demonstrated the biological and clinical significance of imaging superresolved chromatin structure in cancer development and its potential clinical utility for cancer risk stratification.
Designing polymeric membranes with coordination chemistry for high-precision ion separations
Authors: DuChanois Ryan M. , Heiranian Mohammad , Yang Jason , Porter Cassandra J. , Li Qilin , Zhang Xuan , Verduzco Rafael , Elimelech Menachem
Published: March 2022

State-of-the-art polymeric membranes are unable to perform the high-precision ion separations needed for technologies essential to a circular economy and clean energy future. Coordinative interactions are a mechanism to increase sorption of a target species into a membrane, but the effects of these interactions on membrane permeability and selectivity are poorly understood. We use a multilayered polymer membrane to assess how ion-membrane binding energies affect membrane permeability of similarly sized cations: Cu
2+
, Ni
2+
, Zn
2+
, Co
2+
, and Mg
2+
. We report that metals with higher binding energy to iminodiacetate groups of the polymer more selectively permeate through the membrane in multisalt solutions than single-salt solutions. In contrast, weaker binding species are precluded from diffusing into the polymer membrane, which leads to passage proportional to binding energy and independent of membrane thickness. Our findings demonstrate that selectivity of polymeric membranes can markedly increase by tailoring ion-membrane binding energy and minimizing membrane thickness.
Supplemental Material: Nanoscale trace-element zoning in pyrite framboids and implications for paleoproxy applications
Authors: Gregory Daniel D. , al. et
Published: March 2022

More-detailed TEM methodology.
Moyamoya syndrome in a young person with Down syndrome: diagnostic and therapeutic considerations
Authors: Rose Deborah Kathleen , Chamberlain Lauren , Ashton Jeffrey , Yaghi Shadi , Hauck Erik F , Mac Grory Brian
Published: March 2022

An 18-year-old woman with a history of Down syndrome (DS) presented with left upper extremity weakness. Neurological examination revealed moderate hypotonia throughout, with mild spasticity of the left ankle. She had 2/5 left upper and lower extremity strength, mild pronation with drift in the left arm and 3+ deep tendon reflexes in the left biceps, brachioradialis, patellar and Achilles. Strength was 5/5 in the right upper and lower extremities. A CT angiography of the head and neck with contrast demonstrated severe narrowing of the bilateral supraclinoid internal carotid arteries (ICAs), suggestive of moyamoya pattern. A diagnostic angiography confirmed stenosis in the right and left supraclinoid ICAs. The patient was started on aspirin therapy and underwent an indirect bypass procedure via encephaloduroarteriosynangiosis 6 weeks after initial presentation. DS is associated with a high risk of congenital heart disease, which in turn increases risk of stroke, namely cardioembolic events, including moyamoya disease. Intellectual disability is nearly ubiquitous in DS, thus adding to the challenges of making a diagnosis of moyamoya in this population.
Correlates of time to clinical presentation for symptomatic individuals with gonorrhoea in South China: results from a cross-sectional study
Authors: Zhao Peizhen , Nie Juan , Cheng Huanhuan , Tang Weiming , Zheng Heping , Yang Bin , Wang Cheng
Published: March 2022

Objectives

This study aimed to determine the variation in the interval between the onset of symptoms and clinical presentation, and its associated factors among symptomatic individuals with gonorrhoea.

Design

A cross-sectional study was conducted between 1 June and 30 July 2017.

Setting

129 sexually transmitted disease clinics from 21 cities of Guangdong, China.

Participants

Using convenience sampling method to recruit symptomatic individuals with gonorrhoea over 18 years old.

Outcome measure

Time to clinical presentation.

Results

Among 1664 participants, the median age was 29 (24–36) years old, and the majority were male (92.5%) and married (52.9%). The median time to clinical presentation was 3 (2–6) days. About 471 (28.3%) patients had sexual contact while symptomatic. After adjusting for covariates, participants who were female (aβ=0.44, 95% CI: 0.22 to 0.80), from east Guangdong region (aβ=0.44, 95% CI: 0.22 to 0.80) and had the absence of dysuria (aβ=0.26, 95% CI: 0.06 to 0.46) had increased time to clinical presentation. Participants who had commercial sex in the past 6 months (aβ=−0.11, 95% CI: −0.21 to –0.01) had decreased time to clinical presentation. Participants who were female (adjusted odds ratio (aOR)=1.66, 95% CI: 1.08 to 2.50) and delayed in seeking healthcare more than 7 days (aOR=46.71, 95% CI: 24.27 to 89.93) were more likely to have sexual contact while symptomatic.

Conclusion

The time to clinical presentation for individuals with symptomatic gonorrhoea is variable and a high proportion of participants continued to have sexual behaviour while symptomatic. Strategies to increase health literacy may help to minimise the sequelae of gonorrhoea and reduce onward transmission.
Disease progression in osteosarcoma: a multistate model for the EURAMOS-1 (European and American Osteosarcoma Study) randomised clinical trial
Authors: Hazewinkel Audinga-Dea , Lancia Carlo , Anninga Jakob , van de Sande Michiel , Whelan Jeremy , Gelderblom Hans , Fiocco Marta
Published: March 2022

Objectives

Investigating the effect of prognostic factors in a multistate framework on survival in a large population of patients with osteosarcoma. Of interest is how prognostic factors affect different disease stages after surgery, with stages of local recurrence (LR), new metastatic disease (NM), LR+NM, secondary malignancy, a second NM, and death.

Design

An open-label, international, phase 3 randomised controlled trial.

Setting

325 sites in 17 countries.

Participants

The subset of 1631 metastases-free patients from 1965 patients with high-grade resectable osteosarcoma, from the European and American Osteosarcoma Study.

Main outcome measures

The effect of prognostic factors on different disease stages, expressed as HRs; predictions of disease progression on an individual patient basis, according to patient-specific characteristics and history of intermediate events.

Results

Of 1631 patients, 526 experienced an intermediate event, and 305 died by the end of follow-up. An axial tumour site substantially increased the risk of LR after surgery (HR=10.84, 95% CI 8.46 to 13.86) and death after LR (HR=11.54, 95% CI 6.11 to 21.8). A poor histological increased the risk of NM (HR=5.81, 95% CI 5.31 to 6.36), which sharply declined after 3 years since surgery. Young patients (<12 years) had a lower intermediate event risk (eg, for LR: HR=0.66, 95% CI 0.51 to 0.86), when compared with adolescents (12–18 years), but had an increased risk of subsequent death, while patients aged >18 had a decreased risk of death after event (eg, for death after LR: HR=2.40, 95% CI 1.52 to 3.90; HR=0.35, 95% CI 0.21 to 0.56, respectively).

Conclusions

Our findings suggest that patients with axial tumours should be monitored for LR and patients with poor histological response for NM, and that for young patients (<12) with an LR additional treatment options should be investigated.

Trial registration number

NCT00134030.
Use of psychoactive substances by night-shift hospital healthcare workers during the first wave of the COVID-19 pandemic: a cross-sectional study based in Parisian public hospitals (ALADDIN)
Authors: Cousin Lorraine , Di Beo Vincent , Marcellin Fabienne , Coscas Sarah , Mahé Véronique , Chavignaud Isabelle , Rousset Torrente Olivia , Chassany Olivier , Duracinsky Martin , Carrieri Maria Patrizia
Published: March 2022

Objectives

This study aimed to estimate the prevalence of psychoactive substance (PAS) use in night-shift healthcare workers (NSHW) during France’s first COVID-19 wave (March–May 2020).

Design

Observational cross-sectional online survey.

Setting

39 public hospitals in the Assitance Publique des Hôpitaux de Paris (AP-HP) network in the Parisian area.

Participants

A total of 1238 nurses, assistant nurses, X-ray technicians, managers, lab technicians, midwives and childcare assistants working at night or alternating between days and nights answered the questionnaire.

Intervention

Online survey.

Outcome measures

PAS use prevalence after weighting data for sex, age and profession using calibration on margins, in order to be representative of all AP-HP NSHW. We used the Fagerström scale and the Alcohol Use Disorders Identification Test Concise to assess PAS use.

Results

The weighted estimated prevalences of daily smoking, alcohol drinking and tranquilliser use in participating NSHW were 21.4, 1.3 and 2.4%, respectively. Twelve per cent (11.7%) of our study sample used opioids. During the first COVID-19 wave, PAS use remained stable except for tobacco use, with 8.6% of participants reporting an increase. Previous 3-month prevalences of tranquilliser and opioid use were significantly higher than in the general population.

Conclusion

Daily smoking (especially in younger men) and tranquilliser and opioid use were highly prevalent in NSHW in the AP-HP network during France’s first COVID-19 wave. Specific interventions for quitting smoking and addressing determinants of tranquilliser and opioid use in NSHW need to be developed and evaluated to improve quality of life in these essential, underdiagnosed and undertreated health personnel.
Examining the association between reported COVID-19 symptoms and testing for COVID-19 in Canada: a cross-sectional survey
Authors: Pongou Roland , Ahinkorah Bright Opoku , Mabeu Marie Christelle , Agarwal Arunika , Maltais Stephanie , Yaya Sanni
Published: March 2022

Objectives

Studies on the management of the COVID-19 pandemic through testing have been conducted in countries that have been hardest hit by this pandemic. Considering the importance of testing in containing the spread of COVID-19, it is useful to have evidence on continuing COVID-19 testing even in countries where the prevalence of COVID-19 is relatively low. We, therefore, examined the association between reported COVID-19 symptoms and testing for COVID-19 in Canada.

Design and settings

We conducted an online survey using the SurveyMonkey platform between July and October 2020 across Canada.

Participants

A nationally representative sample size of 2790 adult individuals was used.

Results

Our findings show that respondents who reported that they and/or members of their households had COVID-19 symptoms were more likely to test for COVID-19 (adjusted OR, aOR 1.91; 95% CI 1.32 to 2.76) as compared with those who did not report COVID-19 symptoms. The likelihood of testing for COVID-19 was lower among male respondents compared with females (aOR 0.69; 95% CI 0.49 to 0.96), respondents aged 65–84 compared with those aged 18–44 (aOR 0.62; 95% CI 0.42 to 0.93), and respondents in British Columbia compared with those residing in Quebec. Higher odds of testing for COVID-19 were found among respondents who lived in Alberta compared with those who lived in Quebec (aOR 0.42; 95% CI 0.23 to 0.75) and respondents who had postgraduate education compared with those with high school or less education (aOR 1.84; 95% CI 1.01 to 3.36). The association between reported COVID-19 symptoms and testing for COVID-19 was statistically significant among female respondents (aOR 1.52; 95% CI 1.81 to 3.52) but not among male respondents.

Conclusions

In conclusion, this study provides evidence in support of the hypothesis that there is significant association between reported COVID-19 symptoms and COVID-19 testing among adult Canadians. The study highlights the need for the Canadian government to prioritise subpopulations (ie, males, those aged 65–85, and those with high school or less education) that have lower likelihood of seeking COVID-19 testing to get tested when they have symptoms.
Prediction models for venous thromboembolism in ambulatory adults with pancreatic and gastro-oesophageal cancer: protocol for systematic review and meta-analysis
Authors: Zaheer Asma , Naumovski Nenad , Toohey Kellie , Niyonsenga Theophile , Yip Desmond , Brown Nicholas , Mortazavi Reza
Published: March 2022

Introduction

Venous thromboembolism (VTE) is a common complication of cancer. Pancreatic and gastro-oesophageal cancers are among malignancies that have the highest rates of VTE occurrence. VTE can increase cancer-related morbidity and mortality and disrupt cancer treatment. The risk of VTE can be managed with measures such as using anticoagulant drugs, although the risk of bleeding may be an impeding factor. Therefore, a VTE risk assessment should be performed before the start of anticoagulation in individual patients. Several prediction models have been published, but most of them have low sensitivity and unknown clinical applicability in pancreatic or gastro-oesphageal cancers. We intend to do this systematic review to identify all applicable published predictive models and compare their performance in those types of cancer.

Methods and analysis

All studies in which a prediction model for VTE have been developed, validated or compared using adult ambulatory patients with pancreatic or gastro-oesphageal cancers will be identified and the reported predictive performance indicators will be extracted. Full text peer-reviewed journal articles of observational or experimental studies published in English will be included. Five databases (Medline, EMBASE, Web of Science, CINAHL and Cochrane) will be searched. Two reviewers will independently undertake each of the phases of screening, data extraction and risk of bias assessment. The quality of the selected studies will be assessed using Prediction model Risk Of Bias Assessment Tool. The results from the review will be used for a narrative information synthesis, and if the same models have been validated in multiple studies, meta-analyses will be done to pool the predictive performance measures.

Ethics and dissemination

There is no need for ethics approval because the review will use previously peer-reviewed articles. The results will be published.

PROSPERO registration number

CRD42021253887.