bluuebunny/crossref_metadata_2025 huggingface dataset:
Coronavirus and the Colonisation of Private Life
Authors: Thornton Margaret
Published: June 2021

The idea of a distinction between public and private life has a long history in political thought, but the boundary between them has become increasingly blurred as a result of temporal flexibility. Technological change lies at the heart of the ability to choose when and where work is performed, including ‘working at home’. This refers only to productive work so that the unpaid domestic and caring work that women disproportionately undertake has been excluded. Its invisibility has led to it ‘counting for nothing’ in the computation of the Gross National Product. With particular regard to the gender ramifications of working at home, this article analyses the responses to an on-line survey conducted in Australia when lockdown was a key prong of the government response to COVID-19 in 2020. As unpaid work was integrated with productive work, it is suggested that the rationale for discounting it in national accounts no longer holds, especially as the sphere of intimacy is insidiously being colonised by capitalism.
The Views of Turkish Science Teachers About Gender Equity within Science Education
Authors:   Ministry of National Education, Turkey, Idin Sahin , Donmez Ismail ,   Ministry of National Education, Turkey
Published: June 2021

The aim of this study was to investigate Turkish Science teachers' views about gender equity in the scope of Science education. This study was conducted with quantitative methodology. Within this scope, a 35-item 5-point Likert scale survey was developed to determine Science teachers' views concerning gender equity issues. 160 Turkish Science teachers completed the survey. Their reponses were analysed using SPSS. It was revealed that many Turkish Science teachers did not think there was any gender equity in Science teaching programmes or their science textbooks. These science teachers' views also indicated that there were no gender policies in Turkish science education. They believed gender equity issues were important for students' science achievement. It is recommended that Science teachers have some in-service training on gender equity.
Learners' Perspectives on Pure Science Content in Vocational Degree Programmes: Chemistry for Pharmacists
Authors:   University of Portsmouth, Smith James R. , Chungh Melleisha K. ,   University of Portsmouth, Sadouq Sara ,   University of Portsmouth, Kandiah Asarthan ,   University of Portsmouth
Published: June 2021

The objective of this study was to enquire how the chemistry experience of pharmacy students can be enhanced and how the virtual learning environment (VLE) for chemistry-related pharmacy modules might be improved. All MPharm students at the University of Portsmouth UK were asked to complete a project-designed online questionnaire. Data from University course module feedback questionnaires were also analysed. Qualitative and quantitative analyses were performed, using appropriate statistical evaluation. Pre-university chemistry was not correlated with current perceived relevance, difficulty or workload (p > 0.05). The latter two were positively correlated (p = 0.003). Students realised their study of chemistry was important (89%). Chemistry- and biology-related areas were rated equally enjoyable (p > 0.05), but less than pharmacy practice areas (p < 0.0001). Students' preferred choices for VLE development were video lectures > VLE quizzes > audio content. Keeping chemistry content relevant on pharmacy programmes is important. Strategies for improving learning through extended use of the VLE have been identified.
Orientações à pais e professores sobre a medicalização da infância: desenvolver para não medicar
Authors: Tuleski Silvana Calvo
Published: June 2021

O livro didático em tela tem a pretensão de, em uma linguagem acessível, socializar os estudos teóricos e o levantamento de dados sobre a medicalização da infância em municípios do Paraná, realizados no período de 2013 a 2019. A pesquisa contou com a participação de representantes das secretarias municipais de educação dos municípios e os estudos realizados ao longo destes sete anos culminaram na elaboração de dois documentos, um voltado à orientação e formação de professores e outro voltado aos pais. Aos professores, procura-se elucidar as dúvidas mais frequentes, por exemplo, no que se refere ao desenvolvimento infantil e suas manifestações críticas, bem como a partir de que momento é possível se pensar em algum tipo de transtorno no desenvolvimento, que mereça um acompanhamento diferenciado. Além disso, aborda-se sobre os índices de crianças medicadas com psicotrópicos no Brasil e no mundo, quais medicamentos são mais utilizados para o transtorno que vem se destacando quantitativamente nos diagnósticos, como o Transtorno de Déficit de Atenção e Hiperatividade. Em linguagem simples, procura-se demonstrar os cuidados necessário tanto com os diagnósticos como com a prescrição de medicamentos que incidem no Sistema Nervoso Central e, portanto, os efeitos colaterais dos mesmos que precisam ser considerados. Demonstra-se a complexidade do processo educativo tendo em vista a promoção do desenvolvimento infantil, principalmente em uma sociedade complexa e contraditória como a atual, que muitas vezes prima pelo imediatismo de determinadas práticas, imediatismo impossível de ser alcançado em termos de uma educação que produza novas formas de desenvolvimento, como o comportamento atento e autorregulado. O texto em sua totalidade instiga à reflexão sobre o que se quer alcançar com nossas crianças, seja como pais ou como professores, considerando que elas serão o futuro. Deste modo, uma pergunta que não se deve ignorar é: que futuro almejamos para as novas gerações? A resposta a esta pergunta faz com que os esforços se dirijam para a construção agora de alternativas saudáveis, criativas e criadoras. Com este objetivo, o material didático oferecido em forma de livro, traz alternativas, reflexões, apontamentos, unindo o conhecimento científico, mas também ilustrações por meio de músicas, poemas e charges. A diferença entre o texto oferecido aos professores e pais não se encontra apenas na quantidade de páginas, mas na forma de redação dialogada, que objetiva produzir o encontro entre escritores e leitores, ambos com a mesma preocupação em pauta: educar e desenvolver as crianças.
Decoupling Growth and Protein Production in CHO Cells: A Targeted Approach
Authors: Donaldson James S. , Dale Matthew P. , Rosser Susan J.
Published: June 2021

Fed-batch cultures of Chinese Hamster Ovary cells have been used to produce high quantities of biotherapeutics, particularly monoclonal antibodies. However, a growing number of next-generation biotherapeutics, such as bi-specific antibodies and fusion proteins, are difficult to express using standard fed-batch processes. Decoupling cell growth and biotherapeutic production is becoming an increasingly desired strategy for the biomanufacturing industry, especially for difficult-to-express products. Cells are grown to a high cell density in the absence of recombinant protein production (the growth phase), then expression of the recombinant protein is induced and cell proliferation halted (the production phase), usually by combining an inducible gene expression system with a proliferation control strategy. Separating the growth and production phases allows cell resources to be more efficiently directed toward either growth or production, improving growth characteristics and enhancing the production of difficult to express proteins. However, current mammalian cell proliferation control methods rely on temperature shifts and chemical agents, which interact with many non-proliferation pathways, leading to variable impacts on product quality and culture viability. Synthetic biology offers an alternative approach by strategically targeting proliferation pathways to arrest cell growth but have largely remained unused in industrial bioproduction. Due to recent developments in microbial decoupling systems and advances in available mammalian cell engineering tools, we propose that the synthetic biology approach to decoupling growth and production needs revisiting.
Untargeted Global Metabolomic Analysis Reveals the Mechanism of Tripropylamine-Enhanced Lycopene Accumulation in Blakeslea trispora
Authors: Wang Yanlong , Wang Yulong , Wang Yicun , Chen Xin , Liu Cunping , Zhang Meng , Liu Keying , Zhao Yuechao , Li Zexu
Published: June 2021

We previously determined that the cyclase inhibitor tripropylamine (TPA) significantly enhances lycopene accumulation in Blakeslea trispora. To elucidate the mechanism of TPA-enhanced lycopene accumulation, the untargeted metabolome of B. trispora treated with TPA was analyzed by UHPLC-Q-TOF/MS. Forty-two differential metabolites were identified, of which 15 significantly differential metabolites meeting the following parameters were screened: variable importance for the projection > 1, P < 0.05, and fold change > 1.5. The down-regulated metabolites were mainly cyclic dipeptides, bacteriostatic compounds, and lipids, while the up-regulated metabolites were mainly unsaturated fatty acid. Furthermore, the bacteriostatic ability was poor, the extracellular and intracellular pH levels were high, and hyphae with vesicles were swollen locally in B. trispora after treatment with TPA. Our data suggest that the TPA enhances lycopene accumulation not only by inhibiting the cyclization of β-carotene but also by down-regulating cyclic dipeptides for quorum sensing; up-regulating unsaturated fatty acids, 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphoethanolamine, and 4-hydroxybenzoate and down-regulating choline, resulting in locally swelling mycelium with vacuoles; and down-regulating bacteriostatic metabolites for metabolic flux redistribution.
Loss of Wiz Function Affects Methylation Pattern in Palate Development and Leads to Cleft Palate
Authors: Bukova Ivana , Szczerkowska Katarzyna Izabela , Prochazkova Michaela , Beck Inken M. , Prochazka Jan , Sedlacek Radislav
Published: June 2021

WIZ (Widely Interspaced Zinc Finger) is associated with the G9a-GLP protein complex, a key H3K9 methyltransferase suggesting a role in transcriptional repression. However, its role in embryonic development is poorly described. In order to assess the loss of function of WIZ, we generated CRISPR/Cas9 WIZ knockout mouse model with 32 nucleotide deletion. Observing the lethality status, we identified the WIZ knockouts to be subviable during embryonic development and non-viable after birth. Morphology of developing embryo was analyzed at E14.5 and E18.5 and our findings were supported by microCT scans. Wiz KO showed improper development in multiple aspects, specifically in the craniofacial area. In particular, shorter snout, cleft palate, and cleft eyelids were present in mutant embryos. Palatal shelves were hypomorphic and though elevated to a horizontal position on top of the tongue, they failed to make contact and fuse. By comparison of proliferation pattern and histone methylation in developing palatal shelves we brought new evidence of importance WIZ dependent G9a-GLP methylation complex in craniofacial development, especially in palate shelf fusion.
Overexpression of PTPRN Promotes Metastasis of Lung Adenocarcinoma and Suppresses NK Cell Cytotoxicity
Authors: Song Xinyue , Jiao Xue , Yan Han , Yu Lifeng , Jiang Longyang , Zhang Ming , Chen Lianze , Ju Mingyi , Wang Lin , Wei Qian , Zhao Lin , Wei Minjie
Published: June 2021

Background

Lung adenocarcinoma (LUAD) is the most common diagnostic histologic subtype of non-small cell lung cancer, but the role of receptor-type tyrosine-protein phosphatase-like N (PTPRN) in LUAD has not been studied.

Methods

We conducted a bioinformatic analysis to identify the expression of PTPRN on LUAD data from the Cancer Genome Atlas (TCGA) and the relationship between PTPRN and overall survival of LUAD patients. The effects of PTPRN on the migration ability of LUAD cells and the underlying mechanisms were investigated by in vitro and in vivo assays (i.e., wound healing assay, transwell assay, western blotting, xenograft model, and immunohistochemistry). Gene-set enrichment analysis and computational resource were used to analyze the correlation between PTPRN and different tumor-infiltrating immune cells (TIICs). Lactate dehydrogenase assay and Enzyme-linked immunosorbent assay were conducted to examine natural killer (NK) cell cytotoxicity.

Results

In our study, we found that PTPRN was up-regulated in LUAD and related to metastasis of LUAD patients. Besides, PTPRN was correlated with poor prognosis in the TCGA-LUAD dataset. PTPRN overexpression promoted LUAD cell migration and the expression of EMT markers by influencing MEK/ERK and PI3K/AKT signaling. Moreover, PTPRN expression was significantly associated with TIICs, especially NK cells. A549 and H1299 cells overexpressed PTPRN inhibited NK cell cytotoxicity.

Conclusion

Taken together, these findings demonstrated that PTPRN might be a potential and novel therapeutic target modulating antitumor immune response in treatment of LUAD.
Macrophages Derived From Human Induced Pluripotent Stem Cells: The Diversity of Protocols, Future Prospects, and Outstanding Questions
Authors: Lyadova Irina , Gerasimova Tatiana , Nenasheva Tatiana
Published: June 2021

Macrophages (Mφ) derived from induced pluripotent stem cells (iMphs) represent a novel and promising model for studying human Mφ function and differentiation and developing new therapeutic strategies based on or oriented at Mφs. iMphs have several advantages over the traditionally used human Mφ models, such as immortalized cell lines and monocyte-derived Mφs. The advantages include the possibility of obtaining genetically identical and editable cells in a potentially scalable way. Various applications of iMphs are being developed, and their number is rapidly growing. However, the protocols of iMph differentiation that are currently used vary substantially, which may lead to differences in iMph differentiation trajectories and properties. Standardization of the protocols and identification of minimum required conditions that would allow obtaining iMphs in a large-scale, inexpensive, and clinically suitable mode are needed for future iMph applications. As a first step in this direction, the current review discusses the fundamental basis for the generation of human iMphs, performs a detailed analysis of the generalities and the differences between iMph differentiation protocols currently employed, and discusses the prospects of iMph applications.
Post-Translational Modifications in Oocyte Maturation and Embryo Development
Authors: Wu Yu , Li Mo , Yang Mo
Published: June 2021

Mammalian oocyte maturation and embryo development are unique biological processes regulated by various modifications. Since de novo mRNA transcription is absent during oocyte meiosis, protein-level regulation, especially post-translational modification (PTM), is crucial. It is known that PTM plays key roles in diverse cellular events such as DNA damage response, chromosome condensation, and cytoskeletal organization during oocyte maturation and embryo development. However, most previous reviews on PTM in oocytes and embryos have only focused on studies of Xenopus laevis or Caenorhabditis elegans eggs. In this review, we will discuss the latest discoveries regarding PTM in mammalian oocytes maturation and embryo development, focusing on phosphorylation, ubiquitination, SUMOylation and Poly(ADP-ribosyl)ation (PARylation). Phosphorylation functions in chromosome condensation and spindle alignment by regulating histone H3, mitogen-activated protein kinases, and some other pathways during mammalian oocyte maturation. Ubiquitination is a three-step enzymatic cascade that facilitates the degradation of proteins, and numerous E3 ubiquitin ligases are involved in modifying substrates and thus regulating oocyte maturation, oocyte-sperm binding, and early embryo development. Through the reversible addition and removal of SUMO (small ubiquitin-related modifier) on lysine residues, SUMOylation affects the cell cycle and DNA damage response in oocytes. As an emerging PTM, PARlation has been shown to not only participate in DNA damage repair, but also mediate asymmetric division of oocyte meiosis. Each of these PTMs and external environments is versatile and contributes to distinct phases during oocyte maturation and embryo development.
Semiconducting Nanoparticles: Single Entity Electrochemistry and Photoelectrochemistry
Authors: Mathuri S. , Zhu Yuanhang , Margoni Mudaliar Mahesh , Li Xiuting
Published: June 2021

Semiconducting nanoparticles (SC NPs) play vital roles in several emerging technological applications including optoelectronic devices, sensors and catalysts. Recent research focusing on the single entity electrochemistry and photoelectrochemistry of SC NPs is a fascinating field which has attained an increasing interest in recent years. The nano-impact method provides a new avenue of studying electron transfer processes at single particle level and enables the discoveries of intrinsic (photo) electrochemical activities of the SC NPs. Herein, we review the recent research work on the electrochemistry and photoelectrochemistry of single SC NPs via the nano-impact technique. The redox reactions and electrocatalysis of single metal oxide semiconductor (MOS) NPs and chalcogenide quantum dots (QDs) are first discussed. The photoelectrochemistry of single SC NPs such as TiO2 and ZnO NPs is then summarized. The key findings and challenges under each topic are highlighted and our perspectives on future research directions are provided.
The Classroom Impact of Trained Special Needs Education Teachers in Selected Schools: An Evaluation Study
Authors: Yuwono Imam , Okech John Baptist
Published: June 2021

This study sought to find out factors that influence special needs education trained teachers’ performance in class. It was conducted between January and June 2019, involving a target population which comprised 3 government universal primary schools, with a total of 94 teachers and 2,386 learners. Study samples were selected, involving special needs education teachers (N = 73) and LwDs and OSNs (N = 30). Purposive sampling method was used to choose the required samples. A descriptive study design, involving qualitative approach was used. Open ended questionnaires and interview guides were used for collecting data on the critical role that teachers play in supporting LwDs and OSNs who experience barriers to learning under inclusive setting. One of the findings reveals that class size poses a serious challenge to teachers who are not well trained when they have LwDs and OSNs in large classes. Another finding indicates that teachers face challenges with the way the curriculum is designed—posing challenge to them on how to best handle it. It is also found that teachers face challenge to manage the average class number (teacher-learner ratio). It is also found that class room environment, resources and implementation of policies on education for LwDs and OSNs have both direct and indirect influence on the teachers’ impact in class. Basing on the findings, recommendations were made that: relevant authorities should increase support for teacher training and retraining for LwDs and OSNs. That curriculum modification should be done regularly. Classroom environments need regular improvement to be more disability friendly. Lastly, implementation of policies on disabilities and other special needs should be carried out on regular basis.
FKBPL and SIRT-1 Are Downregulated by Diabetes in Pregnancy Impacting on Angiogenesis and Endothelial Function
Authors: Alqudah Abdelrahim , Eastwood Kelly-Ann , Jerotic Djurdja , Todd Naomi , Hoch Denise , McNally Ross , Obradovic Danilo , Dugalic Stefan , Hunter Alyson J. , Holmes Valerie A. , McCance David R. , Young Ian S. , Watson Chris J. , Robson Tracy , Desoye Gernot , Grieve David J. , McClements Lana
Published: June 2021

Diabetes in pregnancy is associated with adverse pregnancy outcomes including preterm birth. Although the mechanisms leading to these pregnancy complications are still poorly understood, aberrant angiogenesis and endothelial dysfunction play a key role. FKBPL and SIRT-1 are critical regulators of angiogenesis, however, their roles in pregnancies affected by diabetes have not been examined before in detail. Hence, this study aimed to investigate the role of FKBPL and SIRT-1 in pre-gestational (type 1 diabetes mellitus, T1D) and gestational diabetes mellitus (GDM). Placental protein expression of important angiogenesis proteins, FKBPL, SIRT-1, PlGF and VEGF-R1, was determined from pregnant women with GDM or T1D, and in the first trimester trophoblast cells exposed to high glucose (25 mM) and varying oxygen concentrations [21%, 6.5%, 2.5% (ACH-3Ps)]. Endothelial cell function was assessed in high glucose conditions (30 mM) and following FKBPL overexpression. Placental FKBPL protein expression was downregulated in T1D (FKBPL; p<0.05) whereas PlGF/VEGF-R1 were upregulated (p<0.05); correlations adjusted for gestational age were also significant. In the presence of GDM, only SIRT-1 was significantly downregulated (p<0.05) even when adjusted for gestational age (r=-0.92, p=0.001). Both FKBPL and SIRT-1 protein expression was reduced in ACH-3P cells in high glucose conditions associated with 6.5%/2.5% oxygen concentrations compared to experimental normoxia (21%; p<0.05). FKBPL overexpression in endothelial cells (HUVECs) exacerbated reduction in tubule formation compared to empty vector control, in high glucose conditions (junctions; p<0.01, branches; p<0.05). In conclusion, FKBPL and/or SIRT-1 downregulation in response to diabetic pregnancies may have a key role in the development of vascular dysfunction and associated complications affected by impaired placental angiogenesis.
Is a Two-Year Growth Response to Growth Hormone Treatment a Better Predictor of Poor Adult Height Outcome Than a First-Year Growth Response in Prepubertal Children With Growth Hormone Deficiency?
Authors: Straetemans Saartje , Rooman Raoul , De Schepper Jean
Published: June 2021

Objective

The first year response to growth hormone (GH) treatment is related to the total height gain in GH treated children, but an individual poor first year response is a weak predictor of a poor total GH effect in GH deficient (GHD) children. We investigated whether an underwhelming growth response after 2 years might be a better predictor of poor adult height (AH) outcome after GH treatment in GHD children.

Design and methods

Height data of GHD children treated with GH for at least 4 consecutive years of which at least two prepubertal and who attained (near) (n)AH were retrieved from the Belgian Register for GH treated children (n = 110, 63% boys). In ROC analyses, the change in height (ΔHt) SDS after the first and second GH treatment years were tested as predictors of poor AH outcome defined as: (1) nAH SDS <−2.0, or (2) nAH SDS minus mid-parental height SDS <−1.3, or (3) total ΔHt SDS <1.0. The cut-offs for ΔHt SDS and its sensitivity at a 95% specificity level to detect poor AH outcome were determined.

Results

Eleven percent of the cohort had a total ΔHt SDS <1.0. ROC curve testing of first and second years ΔHt SDS as a predictor for total ΔHt SDS <1.0 had an AUC >70%. First-year ΔHt SDS <0.41 correctly identified 42% of the patients with poor AH outcome at a 95% specificity level, resulting in respectively 5/12 (4.6%) correctly identified poor final responders and 5/98 (4.5%) misclassified good final responders (ratio 1.0). ΔHt SDS after 2 prepubertal years had a cut-off level of 0.65 and a sensitivity of 50% at a 95% specificity level, resulting in respectively 6/12 (5.5%) correctly identified poor final responders and 5/98 (4.5%) misclassified good final responders (ratio 1.2).

Conclusion

In GHD children the growth response after 2 prepubertal years of GH treatment did not meaningfully improve the prediction of poor AH outcome after GH treatment compared to first-year growth response parameters. Therefore, the decision to re-evaluate the diagnosis or adapt the GH dose in case of poor response after 1 year should not be postponed for another year.
Leveraging Methylation Alterations to Discover Potential Causal Genes Associated With the Survival Risk of Cervical Cancer in TCGA Through a Two-Stage Inference Approach
Authors: Zhang Jinhui , Lu Haojie , Zhang Shuo , Wang Ting , Zhao Huashuo , Guan Fengjun , Zeng Ping
Published: June 2021

Background

Multiple genes were previously identified to be associated with cervical cancer; however, the genetic architecture of cervical cancer remains unknown and many potential causal genes are yet to be discovered.

Methods

To explore potential causal genes related to cervical cancer, a two-stage causal inference approach was proposed within the framework of Mendelian randomization, where the gene expression was treated as exposure, with methylations located within the promoter regions of genes serving as instrumental variables. Five prediction models were first utilized to characterize the relationship between the expression and methylations for each gene; then, the methylation-regulated gene expression (MReX) was obtained and the association was evaluated via Cox mixed-effect model based on MReX. We further implemented the aggregated Cauchy association test (ACAT) combination to take advantage of respective strengths of these prediction models while accounting for dependency among thep-values.

Results

A total of 14 potential causal genes were discovered to be associated with the survival risk of cervical cancer in TCGA when the five prediction models were separately employed. The total number of potential causal genes was brought to 23 when conducting ACAT. Some of the newly discovered genes may be novel (e.g.,YJEFN3,SPATA5L1,IMMP1L,C5orf55,PPIP5K2,ZNF330,CRYZL1,PPM1A,ESCO2,ZNF605,ZNF225,ZNF266,FICD, andOSTC). Functional analyses showed that these genes were enriched in tumor-associated pathways. Additionally, four genes (i.e.,COL6A1,SYDE1,ESCO2, andGIPC1) were differentially expressed between tumor and normal tissues.

Conclusion

Our study discovered promising candidate genes that were causally associated with the survival risk of cervical cancer and thus provided new insights into the genetic etiology of cervical cancer.
Invasive Group B Streptococcus Disease With Recurrence and in Multiples: Towards a Better Understanding of GBS Late-Onset Sepsis
Authors: Freudenhammer Mirjam , Karampatsas Konstantinos , Le Doare Kirsty , Lander Fabian , Armann Jakob , Acero Moreno Daniel , Boyle Margaret , Buxmann Horst , Campbell Ruth , Chalker Victoria , Cunney Robert , Doherty Lorraine , Davies Eleri , Efstratiou Androulla , Elling Roland , Endmann Matthias , Essers Jochen , Hentschel Roland , Jones Christine E. , Kallsen Steffen , Kapatai Georgia , Krüger Marcus , Ladhani Shamez , Lamagni Theresa , Lindsay Diane , Meehan Mary , O’Sullivan Catherine P. , Patel Darshana , Reynolds Arlene J. , Roll Claudia , Schulzke Sven , Smith Andrew , Stein Anja , von der Wense Axel , Voss Egbert , Wieg Christian , Härtel Christoph , Heath Paul T. , Henneke Philipp
Published: June 2021

Group B Streptococcus (GBS) is a common intestinal colonizer during the neonatal period, but also may cause late-onset sepsis or meningitis in up to 0.5% of otherwise healthy colonized infants after day 3 of life. Transmission routes and risk factors of this late-onset form of invasive GBS disease (iGBS) are not fully understood. Cases of iGBS with recurrence (n=25) and those occurring in parallel in twins/triplets (n=32) from the UK and Ireland (national surveillance study 2014/15) and from Germany and Switzerland (retrospective case collection) were analyzed to unravel shared (in affected multiples) or fixed (in recurrent disease) risk factors for GBS disease. The risk of iGBS among infants from multiple births was high (17%), if one infant had already developed GBS disease. The interval of onset of iGBS between siblings was 4.5 days and in recurrent cases 12.5 days. Disturbances of the individual microbiome, including persistence of infectious foci are suggested e.g. by high usage of perinatal antibiotics in mothers of affected multiples, and by the association of an increased risk of recurrence with a short term of antibiotics [aOR 4.2 (1.3-14.2), P=0.02]. Identical GBS serotypes in both recurrent infections and concurrently infected multiples might indicate a failed microbiome integration of GBS strains that are generally regarded as commensals in healthy infants. The dynamics of recurrent GBS infections or concurrent infections in multiples suggest individual patterns of exposure and fluctuations in host immunity, causing failure of natural niche occupation.
Cytokine Overproduction and Immune System Dysregulation in alloHSCT and COVID-19 Patients
Authors: Lange Andrzej , Lange Janusz , Jaskuła Emilia
Published: June 2021

The COVID-19 pathomechanism depends on (i) the pathogenicity of the virus, (ii) ability of the immune system to respond to the cytopathic effect of the virus infection, (iii) co-morbidities. Inflammatory cytokine production constitutes a hallmark of COVID-19 that is facilitated by inability of adaptive immunity to control virus invasion. The effect of cytokine release syndrome is deleterious, but the severity of it depends on other confounding factors: age and comorbidities. In this study, we analyze the literature data on the post-transplant course of allogeneic hematopoietic stem cell transplanted (alloHSCT) patients, which is affected by generated inflammatory cytokines. The sequence of events boosting cytokine production was analyzed in relation to clinical and laboratory data highlighting the impact of cytokine generation on the post-transplant course. The collected data were compared to those from studies on COVID-19 patients. The similarities are: (i) the damage/pathogen-associated molecular pattern (DAMP/PAMP) stage is similar except for the initiation hit being sterile in alloHSCT (toxic damage of conditioning regimen) and viral in COVID-19; (ii) genetic host-derived factors play a role; (iii) adaptive immunity fails, DAMP signal(s) increases, over-production of cytokines occurs; (iv) monocytes lacking HLADR expression emerge, being suppressor cells hampering adaptive immunity; (v) immune system homeostasis is broken, the patient’s status deteriorates to bed dependency, leading to hypo-oxygenation and malnutrition, which in turn stimulates the intracellular alert pathways with vigorous transcription of cytokine genes. All starts with the interaction between DAMPs with appropriate receptors, which leads to the production of pro-inflammatory cytokines, the inflammatory process spreads, tissue is damaged, DAMPs are released and a vicious cycle occurs. Attempts to modify intracellular signaling pathways in patients with post-alloHSCT graft vs host disease have already been undertaken. The similarities documented in this study show that this approach may also be used in COVID-19 patients for tuning signal transduction processes to interrupt the cycle that powers the cytokine overproduction.
Laboratory Mice – A Driving Force in Immunopathology and Immunotherapy Studies of Human Multiple Myeloma
Authors: Pisano Michael , Cheng Yan , Sun Fumou , Dhakal Binod , D’Souza Anita , Chhabra Saurabh , Knight Jennifer M. , Rao Sridhar , Zhan Fenghuang , Hari Parameswaran , Janz Siegfried
Published: June 2021

Mouse models of human cancer provide an important research tool for elucidating the natural history of neoplastic growth and developing new treatment and prevention approaches. This is particularly true for multiple myeloma (MM), a common and largely incurable neoplasm of post-germinal center, immunoglobulin-producing B lymphocytes, called plasma cells, that reside in the hematopoietic bone marrow (BM) and cause osteolytic lesions and kidney failure among other forms of end-organ damage. The most widely used mouse models used to aid drug and immunotherapy development rely onin vivopropagation of human myeloma cells in immunodeficient hosts (xenografting) or myeloma-like mouse plasma cells in immunocompetent hosts (autografting). Both strategies have made and continue to make valuable contributions to preclinical myeloma, including immune research, yet are ill-suited for studies on tumor development (oncogenesis). Genetically engineered mouse models (GEMMs), such as the widely known Vκ*MYC, may overcome this shortcoming because plasma cell tumors (PCTs) developde novo(spontaneously) in a highly predictable fashion and accurately recapitulate many hallmarks of human myeloma. Moreover, PCTs arise in an intact organism able to mount a complete innate and adaptive immune response and tumor development reproduces the natural course of human myelomagenesis, beginning with monoclonal gammopathy of undetermined significance (MGUS), progressing to smoldering myeloma (SMM), and eventually transitioning to frank neoplasia. Here we review the utility of transplantation-based and transgenic mouse models of human MM for research on immunopathology and -therapy of plasma cell malignancies, discuss strengths and weaknesses of different experimental approaches, and outline opportunities for closing knowledge gaps, improving the outcome of patients with myeloma, and working towards a cure.
Eosinophils and Chronic Respiratory Diseases in Hospitalized COVID-19 Patients
Authors: Valverde-Monge Marcela , Cañas José A. , Barroso Blanca , Betancor Diana , Ortega-Martin Laura , Gómez-López Alicia , Rodríguez-Nieto María Jesús , Mahíllo-Fernández Ignacio , Sastre Joaquín , Del Pozo Victoria
Published: June 2021

Background

Studies on the role of eosinophils in coronavirus disease 2019 (COVID-19) are scarce, though available findings suggest a possible association with disease severity. Our study analyzes the relationship between eosinophils and COVID-19, with a focus on disease severity and patients with underlying chronic respiratory diseases.

Methods

We performed a retrospective analysis of 3018 subjects attended at two public hospitals in Madrid (Spain) with PCR-confirmed SARS-CoV-2 infection from January 31 to April 17, 2020. Patients with eosinophil counts less than 0.02×109/L were considered to have eosinopenia. Individuals with chronic respiratory diseases (n=384) were classified according to their particular underlying condition, i.e., asthma, chronic pulmonary obstructive disease, or obstructive sleep apnea.

Results

Of the 3018 patients enrolled, 479 were excluded because of lack of information at the time of admission. Of 2539 subjects assessed, 1396 patients presented an eosinophil count performed on admission, revealing eosinopenia in 376 cases (26.93%). Eosinopenia on admission was associated with a higher risk of intensive care unit (ICU) or respiratory intensive care unit (RICU) admission (OR:2.21; 95%CI:1.42-3.45; p<0.001) but no increased risk of mortality (p>0.05).

Conclusions

Eosinopenia on admission conferred a higher risk of severe disease (requiring ICU/RICU care), but was not associated with increased mortality. In patients with chronic respiratory diseases who develop COVID-19, age seems to be the main risk factor for progression to severe disease or death.
Regulatory Effects of Histone Deacetylase Inhibitors on Myeloid-Derived Suppressor Cells
Authors: Cui Yudan , Cai Jingshan , Wang Wenxin , Wang Shengjun
Published: June 2021

Histone deacetylase inhibitors (HDACIs) are antitumor drugs that are being developed for use in clinical settings. HDACIs enhance histone or nonhistone acetylation and promote gene transcription via epigenetic regulation. Importantly, these drugs have cytotoxic or cytostatic properties and can directly inhibit tumor cells. However, how HDACIs regulate immunocytes in the tumor microenvironment, such as myeloid-derived suppressor cells (MDSCs), has yet to be elucidated. In this review, we summarize the effects of different HDACIs on the immunosuppressive function and expansion of MDSCs based on the findings of relevant studies.
Offshore Wind Farm Footprint on Organic and Mineral Particle Flux to the Bottom
Authors: Ivanov Evgeny , Capet Arthur , De Borger Emil , Degraer Steven , Delhez Eric J. M. , Soetaert Karline , Vanaverbeke Jan , Grégoire Marilaure
Published: June 2021

Offshore wind farms (OWFs) are an important source of renewable energy accounting for 2.3% of the European Union's electricity demand. Yet their impact on the environment needs to be assessed. Here, we couple a hydrodynamic (including tides and waves) and sediment transport model with a description of the organic carbon and mineral particle dynamics in the water column and sediments. The model is applied to the Belgian Coastal Zone (BCZ) where OWFs currently occupy 7% of its surface area which is estimated to double in the next 5 years. The impact of OWFs on the environment is represented through the filtration of the water column and fecal pellets production by the blue mussel, the dominant fouling organism. Our model simulations show that the impact of biodeposition on the mud particle sedimentation and on sediment composition is small compared to the fluxes associated with tidal deposition and resuspension and the lateral inputs. In contrast, the total organic carbon (TOC) flux to the sediment is significantly altered inside the OWF perimeters and TOC deposition is increased up to 50% in an area 5 km around the monopiles. Further away, the TOC flux to the bottom decreases with a notable effect up to 30 km away. The major changes are found along the direction of the main residual current and tidal ellipse's major axis. In addition, sub-mesoscale gyres act as retention areas with increased carbon deposition. A future OWF in the BCZ will be located close to gravel beds in a Natura 2000 area, considered as vulnerable habitats and biodiversity hotspots. The different scenarios for this OWF, varying in turbine number and positioning, are compared in terms of impact on the carbon and mineral particle deposition flux in the BCZ and, particularly, to these gravel beds. The scenarios show that the number of turbines has only a slight impact on the TOC deposition flux, unlike their positioning that significantly alters the TOC flux to the gravel beds. The TOC deposition flux exceeds 50%, when the turbines are placed next to the gravel beds; while a limited increase is simulated, when the turbines are located the farthest possible from them.
Niche-Relationships Within and Among Intertidal Reef Fish Species
Authors: Andrades Ryan , Joyeux Jean-Christophe , Macieira Raphael M. , Godoy Bruno Spacek , Reis-Filho José Amorim , Jackson Andrew L. , Giarrizzo Tommaso
Published: June 2021

Niche-related processes (e.g., density or niche-breadth compensation and competition) are fundamental to a broad understanding of community ecology and ecosystem functioning. Most evidences of competition are from controlled indoor trials with few species, and it remains a challenge to estimate competition among multiple species in the field. Here, we analyze stable isotopes and distributional data from 51 fish taxa in six locations in the southwestern Atlantic to predict intraspecific trophic pressure (ITP) and the potential competitive strength among species in a trophic-based framework. We used two proxies built upon 2-dimensional isotopic space (δ13C vs. δ15N), its predicted overlap, and fish density to calculate winner and loser taxa in potential paired interspecific competitive interactions. The intraspecific proxy indicated that cryptobenthic fishes are under high among-individual trophic pressure (high densities and small niche sizes). Also, cryptobenthic behavior together with feeding specialization and extremely small-sizes were the most important traits related to low success in interspecific simulations. Although cryptobenthic fishes face strong competitive pressures, there are some known inherent trade-offs to cryptobenthic life such as trophic and habitat use specializations. These seem to compensate and ensure coexistence among cryptobenthic fishes and non-cryptobenthic species. Habitat loss/degradation via urbanization, invasive species and climate-change-driven sea-level rise can reduce the suitability of habitat and increase competition on cryptobenthic species, especially in shallow reefs and intertidal shores.
The Eastern Tropical Pacific Marine Corridor (CMAR): The Emergence of a Voluntary Regional Cooperation Mechanism for the Conservation and Sustainable Use of Marine Biodiversity Within a Fragmented Regional Ocean Governance Landscape
Authors: Enright Sarah Ryan , Meneses-Orellana Ricardo , Keith Inti
Published: June 2021

The San Jose Declaration formally established the Eastern Tropical Pacific Marine Corridor (CMAR) in 2004, a voluntary regional cooperation mechanism created by the coastal States of Ecuador, Costa Rica, Colombia, and Panama in response to anthropogenic pressures in the Eastern Tropical Pacific, one of the most productive and biodiverse oceans in the world. This article will explain how, in the absence of a coherent, overarching regional ocean governance framework, these four coastal States came together to create a regional cooperation mechanism for the conservation and sustainable use of marine biodiversity in the Eastern Tropical Pacific. The key normative features of CMAR will be examined, as well as legal and governance challenges, such as its non-binding nature, large scale, limited sectoral engagement, and insufficient resources. The analysis will be couched within a discussion of the wider regional ocean governance framework, which remains fragmented, with gaps and overlaps in terms of membership, mandates and geographic coverage. Possibilities for integration, and the potential impact of a new treaty protecting biodiversity beyond national jurisdiction (BBNJ), will also be considered.
Population Genomics and Lagrangian Modeling Shed Light on Dispersal Events in the Mediterranean Endemic Ericaria zosteroides (=Cystoseira zosteroides) (Fucales)
Authors: Reynes Lauric , Aurelle Didier , Chevalier Cristele , Pinazo Christel , Valero Myriam , Mauger Stéphane , Sartoretto Stéphane , Blanfuné Aurélie , Ruitton Sandrine , Boudouresque Charles-François , Verlaque Marc , Thibaut Thierry
Published: June 2021

Dispersal is a central process that affects population growth, gene flow, and ultimately species persistence. Here we investigate the extent to which gene flow occurs between fragmented populations of the deep-water brown algae Ericaria zosteroides (Turner) Greville (Sargassaceae, Fucales). These investigations were performed at different spatial scales from the bay of Marseille (western Provence) to Corsica. As dispersal of zygotes is shown to be limited over distances beyond a few meters, we used a multidisciplinary approach, based on Lagrangian modeling and population genomics to test the hypothesis that drifting of fertile parts of thallus (eggs on fertile branches), mediated by ocean currents, enable occasional gene flow between populations. Therefore we assessed the respective contribution of oceanographic connectivity, geographical isolation, and seawater temperatures to the genetic structure of this species. The genetic structure was assessed using 10,755 neutral SNPs and 12 outlier SNPs genotyped by dd-RAD sequencing in 261 individuals of E. zosteroides. We find that oceanographic connectivity is the best predictor of genetic structure, while differentiation in outlier SNPs can be explained by the depth of populations, as emphasized by the minimum seawater temperature predictor. However, further investigations will be necessary for clarifying how depth drives adaptive genetic differentiation in E. zosteroides. Our analyses revealed that local hydrodynamic conditions are correlated with the very high divergence of one population in the Bay of Marseille. Overall, the levels of gene flow mediated by drifting were certainly not sufficient to counteract differentiation by local genetic drift, but enough to allow colonization several kilometers away. This study stresses the need to consider secondary dispersal mechanisms of presumed low dispersal marine species to improve inference of population connectivity.
Strategies in Primary Care to Face the SARS-CoV-2 / COVID-19 Pandemic: An Online Survey
Authors: Eisele Marion , Pohontsch Nadine Janis , Scherer Martin
Published: June 2021

Background: Primary care plays a key role in pandemics like the SARS-CoV-2 pandemic in 2020. We aimed to investigate the challenges faced and the solutions implemented in primary care.

Methods: One hundred and twenty-one general practitioners in Germany completed the online survey. We used open questions to examine challenges experienced and solutions implemented during the early pandemic and chose qualitative content analysis to extract and describe the meaning of the answers. We derived deductive categories from the research questions and formed inductive categories during the material reviews.

Results: Main challenges were: insufficient information, lack of protective equipment, need to restructure practice procedures and insufficient individual and structural pandemic preparedness, resulting in secondary challenges: fear of infection, impaired patient care, aggravated steering of patients, difficult cooperation with external entities and a not viable hygiene concept advised by authorities. Strategies to address these challenges included establishing regular team-meetings to develop new solutions, focusing on few reliable sources of information, working in alternating shifts, increasing telemedicine, establishing window and open-air practices and building networks with other health care providers. Respondents criticized the lack of consideration of their experiences in planning pandemic measures within primary care.

Conclusions: General practitioners successfully applied pragmatic and creative strategies in their practices during the early phase of the pandemic. Among these, communication within and between practices emerged as a key strategy. These strategies should be provided with pandemic preparedness plans. The lacking consideration of the primary care providers' experiences in planning and implementing pandemic measures needs to be addressed by stakeholders.