bluuebunny/crossref_metadata_2025 huggingface dataset:
Anthropization Affects the Assembly of Bat-Bat Fly Interaction Networks
Authors: Ramalho Daniel F. , Diniz Ugo M. , Aguiar Ludmilla M. S.
Published: October 2021

Increasing anthropization is detrimental to the natural environment and the quality of life, affecting populations, communities, and the relationships between organisms. One of the most unique relationships in the animal world is parasitism, which often involves tightly specialized interactions between pairs of species. Bat flies, for example, are obligate ectoparasites represented by two highly adapted dipteran families that usually parasite a single bat species or genus. Recent studies have shown that bat flies could carry pathogens such as bacteria and viruses, transmitting them among bat individuals in a colony. Because host roost characteristics can influence bat-fly parasitism, we aimed to assess whether the ecological networks between parasites and their host bats are influenced by the degree of habitat anthropization. Our hypothesis was that bat-fly interaction networks would be less specialized and more nested in highly anthropized sites. We collected bat fly individuals from bats captured at 21 sampling sites located in the Federal District of Brazil and quantified the amount of natural and anthropized area within a 3-km buffer from the sampling site. Areas consisting of agriculture, construction, mining, roads, or any man-made structure were considered anthropized. Sites presented different degrees of anthropization, with areas ranging from 100% anthropized to areas retaining full natural cover. We built bat-bat fly networks for each of the sites and excluded those with sampling completeness values smaller than 0.7. We calculated key weighted structural metrics for each network, such as nestedness, specialization, and modularity. The effect of the reduction in natural cover on structural metrics was assessed through GLMMs, controlling for network size and ectoparasite diversity. Nestedness increased with the amount of anthropization, while specialization and modularity did not change and were overall high in all networks. This result suggests that anthropization may influence the assembly of bat-bat fly networks, leading to the emergence of a hierarchical assembly of interactions as parasites become less specialized and interact with a wider variety of hosts. Less specialized relationships could influence parasite fitness or even increase the likelihood of transmitting pathogens between populations of different bat species.
Including Host Availability and Climate Change Impacts on the Global Risk Area of Carpomya pardalina (Diptera: Tephritidae)
Authors: Qin Yujia , Zhang Yuan , Clarke Anthony R. , Zhao Zihua , Li Zhihong
Published: October 2021

Fruit flies are a well-known invasive species, and climate-based risk modeling is used to inform risk analysis of these pests. However, such research tends to focus on already well-known invasive species. This paper illustrates that appropriate risk modeling can also provide valuable insights for flies which are not yet “on the radar.”Carpomya pardalinais a locally important cucurbit-infesting fruit fly of western and central Asia, but it may present a risk to other temperate countries where melons are grown. MaxEnt models were used to map the risk area for this species under historical and future climate conditions averaged from three global climate models under two shared socio-economic pathways in 2030 and 2070 from higher climate sensitivity models based on the upcoming 2021 IPCC sixth assessment report. The results showed that a total of 47.64% of the world’s land mass is climatically suitable for the fly; it could establish widely around the globe both under current and future climates with host availability. Our MaxEnt modeling highlights particularly that Western China, Russia, and other European countries should pay attention to this currently lesser-known melon fly and the melons exported from the present countries. The current and expanding melon trade could offer direct invasion pathways to those regions. While this study offers specific risk information onC. pardalina, it also illustrates the value of applying climate-based distribution modeling to species with limited geographic distributions.
Using Free-Range Laboratory Mice to Explore Foraging, Lifestyle, and Diet Issues in Cancer
Authors: Makin Douglas F. , Agra Ella , Prasad Manu , Brown Joel S. , Elkabets Moshe , Menezes Jorge Fernando Saraiva , Sargunaraj Franklin , Kotler Burt P.
Published: October 2021

As cancer progresses, its impact should manifest in the foraging behavior of its host much like the effects of endo-parasites that hinder foraging aptitudes and risk management abilities. Furthermore, the lifestyle of the host can impact tumor growth and quality of life. To approach these questions, we conducted novel experiments by letting C57BL/6 laboratory mice, with or without oral squamous cell carcinoma, free range in a large outdoor vivarium. Our goals were to: (1) determine whether one could conduct experiments with a mouse model under free range conditions, (2) measure effects of cancer burden on foraging metrics, (3) compare tumor growth rates with laboratory housed mice, and (4) begin to sort out confounding factors such as diet. With or without cancer, the C57BL/6 laboratory mice dealt with natural climatic conditions and illumination, found shelter or dug burrows, sought out food from experimental food patches, and responded to risk factors associated with microhabitat by foraging more thoroughly in food patches under bush (safe) than in the open (risky). We quantified foraging using giving-up densities of food left behind in the food patches. The mice’s patch use changed over time, and was affected by disease status, sex, and microhabitat. Males, which were larger, consumed more food and had lower giving-up densities than females. Relative to cancer-free mice, mice with growing tumors lost weight, harvested more food, and increasingly relied on patches in the bush microhabitat. The tumors of free-ranging mice in the vivarium grew slower than those of their cohort that were housed in mouse cages in animal facilities. Numerous interesting factors could explain the difference in tumor growth rates: activity levels, stress, weather, food intake, diet, and more. To tease apart one of these intertwined factors, we found that tumors grew faster when mice in the laboratory were fed on millet rather than laboratory mouse chow. While just a start, these novel experiments and framework show how free-ranging mice provide a model that can test a broader range of hypotheses and use a broader range of metrics regarding cancer progression and its consequences for the host.
Structural Characteristics of the Tallest Mangrove Forests of the American Continent: A Comparison of Ground-Based, Drone and Radar Measurements
Authors: Castellanos-Galindo Gustavo A. , Casella Elisa , Tavera Hector , Zapata Padilla Luis Alonso , Simard Marc
Published: October 2021

The Panama Bight eco-region along the Pacific coast of central and South America is considered to have one of the best-preserved mangrove ecosystems in the American continent. The regional climate, with rainfall easily reaching 5–8 m every year and weak wind conditions, contribute to the exceptionally tall mangroves along the southern Colombian and northern Ecuadorian Pacific coasts (Nariño Department and Esmeraldas Province areas). Here we evaluate the use of different methods (ground-based measurements, drone imagery and radar data [Shuttle Radar Topography mission-SRTM and TanDEM-X]) to characterize the structure of the tallest of these forests. In November 2019, three mangrove sites with canopy heights between 50 and 60 m, previously identified with SRTM data, were sampled close to the town of Guapi, Colombia. In addition to in situ field measurements of trees, we conducted airborne drone surveys in order to generate georeferenced orthomosaics and digital surface models (DSMs). We found that the extensive mangrove forests in this area of the Colombian Pacific are almost entirely composed of Rhizophora spp. trees. The tallest mangrove tree measured in the three plots was 57 m. With ca. 900 drone photographs, three orthomosaics (2 cm pixel–1 resolution) and digital surface models (3.5 cm pixel–1) with average area of 4,0 ha were generated. The field-measured canopy heights were used to validate the drone-derived and radar-derived data, confirming these mangrove forests as the tallest in the Americas. The drone-derived orthomosaics showed significant patches of the Golden Leather Fern, Acrostichum aureum, an opportunistic species that can be associated to mangrove degradation, indicating that the mangrove forests investigated here may be threatened from increased selective logging requiring improvements and effective implementation of the current mangrove management plans in Colombia. The techniques used here are highly complementary and may represent the three tiers for carbon reporting, whereby the drone-derived canopy height maps, calibrated with local in situ measurements, provides cheap but reliable Tier 3 estimates of carbon stocks at the project level.
Integrative Systems Biology Analysis Elucidates Mastitis Disease Underlying Functional Modules in Dairy Cattle
Authors: Ghahramani Nooshin , Shodja Jalil , Rafat Seyed Abbas , Panahi Bahman , Hasanpur Karim
Published: October 2021

Background: Mastitis is the most prevalent disease in dairy cattle and one of the most significant bovine pathologies affecting milk production, animal health, and reproduction. In addition, mastitis is the most common, expensive, and contagious infection in the dairy industry.

Methods: A meta-analysis of microarray and RNA-seq data was conducted to identify candidate genes and functional modules associated with mastitis disease. The results were then applied to systems biology analysis via weighted gene coexpression network analysis (WGCNA), Gene Ontology, enrichment analysis for the Kyoto Encyclopedia of Genes and Genomes (KEGG), and modeling using machine-learning algorithms.

Results: Microarray and RNA-seq datasets were generated for 2,089 and 2,794 meta-genes, respectively. Between microarray and RNA-seq datasets, a total of 360 meta-genes were found that were significantly enriched as “peroxisome,” “NOD-like receptor signaling pathway,” “IL-17 signaling pathway,” and “TNF signaling pathway” KEGG pathways. The turquoise module (n = 214 genes) and the brown module (n = 57 genes) were identified as critical functional modules associated with mastitis through WGCNA. PRDX5, RAB5C, ACTN4, SLC25A16, MAPK6, CD53, NCKAP1L, ARHGEF2, COL9A1, and PTPRC genes were detected as hub genes in identified functional modules. Finally, using attribute weighting and machine-learning methods, hub genes that are sufficiently informative in Escherichia coli mastitis were used to optimize predictive models. The constructed model proposed the optimal approach for the meta-genes and validated several high-ranked genes as biomarkers for E. coli mastitis using the decision tree (DT) method.

Conclusion: The candidate genes and pathways proposed in this study may shed new light on the underlying molecular mechanisms of mastitis disease and suggest new approaches for diagnosing and treating E. coli mastitis in dairy cattle.
Heat Stress After Pollination Reduces Kernel Number in Maize by Insufficient Assimilates
Authors: Niu Shiduo , Du Xiong , Wei Dejie , Liu Shanshan , Tang Qian , Bian Dahong , Zhang Yarong , Cui Yanhong , Gao Zhen
Published: October 2021

Global warming has increased the occurrence of high temperature stress in plants, including maize, resulting in decreased the grain number and yield. Previous studies indicate that heat stress mainly damages the pollen grains and thus lowered maize grain number. Other field studies have shown that heat stress after pollination results in kernel abortion. However, the mechanism by which high temperature affect grain abortion following pollination remains unclear. Hence, this study investigated the field grown heat-resistant maize variety “Zhengdan 958” (ZD958) and heat-sensitive variety “Xianyu 335” (XY335) under a seven-day heat stress treatment (HT) after pollination. Under HT, the grain numbers of XY335 and ZD958 were reduced by 10.9% (p = 0.006) and 5.3% (p = 0.129), respectively. The RNA sequencing analysis showed a higher number of differentially expressed genes (DEGs) between HT and the control in XY335 compared to ZD958. Ribulose diphosphate carboxylase (RuBPCase) genes were downregulated by heat stress, and RuBPCase activity was significantly lowered by 14.1% (p = 0.020) in XY335 and 5.3% (p = 0.436) in ZD958 in comparison to CK. The soluble sugar and starch contents in the grains of XY335 were obviously reduced by 26.1 and 58.5%, respectively, with no distinct change observed in ZD958. Heat stress also inhibited the synthesis of grain starch, as shown by the low activities of metabolism-related enzymes. Under HT, the expression of trehalose metabolism genes in XY335 were upregulated, and these genes may be involved in kernel abortion at high temperature. In conclusion, this study revealed that post-pollination heat stress in maize mainly resulted in reduced carbohydrate availability for grain development, though the heat-resistant ZD958 was nevertheless able to maintain growth.
Improving Chromatin-Interaction Prediction Using Single-Cell Open-Chromatin Profiles and Making Insight Into the Cis-Regulatory Landscape of the Human Brain
Authors: Pandey Neetesh , Omkar Chandra  , Mishra Shreya , Kumar Vibhor
Published: October 2021

Single-cell open-chromatin profiles have the potential to reveal the pattern of chromatin-interaction in a cell type. However, currently available cis-regulatory network prediction methods using single-cell open-chromatin profiles focus more on local chromatin interactions despite the fact that long-range interactions among genomic sites play a significant role in gene regulation. Here, we propose a method that predicts both short and long-range interactions among genomic sites using single-cell open chromatin profiles. Our method, termed as single-cell epigenome based chromatin-interaction analysis (scEChIA) exploits signal imputation and refined L1 regularization. For a few single-cell open-chromatin profiles, scEChIA outperformed other tools even in terms of accuracy of prediction. Using scEChIA, we predicted almost 0.7 million interactions among genomic sites across seven cell types in the human brain. Further analysis revealed cell type for connection between genes and expression quantitative trait locus (eQTL) in the human brain and making insight about target genes of human-accelerated-elements and disease-associated mutations. Our analysis enabled by scEChIA also hints about the possible action of a few transcription factors (TFs), especially through long-range interaction in brain endothelial cells.
Community Perceptions of Person-Centered Maternity Care in Migori County, Kenya
Authors: Odiase Osamuedeme , Akinyi Beryl , Kinyua Joyceline , Afulani Patience
Published: October 2021

Background: Community perceptions of quality of maternal healthcare services—including Person-centered maternity care (PCMC)—influences the health-seeking behavior of women. Yet few studies have examined this quantitatively. This study aims to examine community perceptions of PCMC and its associated factors.

Materials and Methods: We used data from a survey on community perceptions of PCMC in Migori County, Kenya conducted in August 2016. Community members were relatives or friends of women aged 15 to 49 years who gave birth in the 9 wk preceding the survey (N = 198). PCMC was measured using a 30-item scale with three sub-scales for dignity and respect, communication and autonomy, and supportive care. PCMC scores were standardized to range from 0 to 100, with higher scores indicative of higher PCMC. Descriptive, bivariate, and multivariate analyses were performed in STATA (version 14).

Results: The average total PCMC score was 62 (SD = 15.7), with scores of 74, 63, and 53 for dignity and respect, supportive care, and communication and autonomy, respectively. Controlling for other factors, respondents who were employed and literate had higher PCMC perception scores than those who were less literate and unemployed. Respondents who rated their health as very good had higher PCMC perception scores than those who rated their health as poor. Female respondents who previously gave birth at a health facility had lower perceptions of dignity and respect than those with no prior facility birth.

Conclusion: The findings imply that community perceptions of PCMC, particularly related to communication and autonomy, are poor. Given the effects of these perceptions on use of maternal health services, there is a need to improve PCMC.
Serum IgG anti-SARS-CoV-2 Binding Antibody Level Is Strongly Associated With IgA and Functional Antibody Levels in Adults Infected With SARS-CoV-2
Authors: Ye Xunyan , Angelo Laura S. , Nicholson Erin G. , Iwuchukwu Obinna P. , Cabral de Rezende Wanderson , Rajan Anubama , Aideyan Letisha O. , McBride Trevor J. , Bond Nanette , Santarcangelo Patricia , Rayford Yolanda J. , Ferlic-Stark Laura , Fragoso Sonia , Momin Zoha , Liu Hongbing , Truong Khanghy , Lopez Brianna , Conner Margaret E. , Rice Andrew P. , Kimata Jason T. , Avadhanula Vasanthi , Piedra Pedro A.
Published: October 2021

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019 in Wuhan, China, and then rapidly spread causing an unprecedented pandemic. A robust serological assay is needed to evaluate vaccine candidates and better understand the epidemiology of coronavirus disease (COVID-19).

Methods

We used the full-length spike (S) protein of SARS-CoV-2 for the development of qualitative and quantitative IgG and IgA anti-S enzyme linked immunosorbent assays (ELISA). A total of 320 sera used for assay development were comprised of pandemic sera from SARS-CoV-2 infected adults (n=51) and pre-pandemic sera (n=269) including sera from endemic human coronavirus infected adults. Reverse cumulative curves and diagnostic test statistics were evaluated to define the optimal serum dilution and OD cutoff value for IgG anti-S and IgA anti-S ELISAs. The IgG and IgA anti-S, and three functional antibodies (ACE-2 receptor blocking antibody, lentipseudovirus-S neutralizing antibody, and SARS-CoV-2 neutralizing antibody) were measured using additional SARS-CoV-2 PCR positive sera (n=76) and surveillance sera (n=25). Lastly, the IgG and IgA anti-S levels were compared in different demographic groups.

Results

The optimal serum dilution for the qualitative IgG anti-S ELISA was at 1:1024 yielding a 99.6% specificity, 92.2% sensitivity, 92.9% positive predictive value (PPV), and 99.6% negative predictive value (NPV) at a SARS-CoV-2 seroprevalence of 5%. The optimal serum dilution for the qualitative IgA anti-S ELISA was at 1:128 yielding a 98.9% specificity, 76.5% sensitivity, 78.3% PPV, and 98.8% NPV at the same seroprevalence. Significant correlations were demonstrated between the IgG and IgA (r=0.833 for concentrations, r=0.840 for titers) as well as between IgG and three functional antibodies (r=0.811-0.924 for concentrations, r=0.795-0.917 for titers). The IgG and IgA anti-S levels were significantly higher in males than females (p<0.05), and in adults with moderate/severe symptoms than in adults with mild/moderate symptoms (p<0.001).

Conclusion

We developed a highly specific and sensitive IgG anti-S ELISA assay to SARS-CoV-2 using full length S protein. The IgG anti-S antibody level was strongly associated with IgA and functional antibody levels in adults with SARS-CoV-2 infection. Gender and disease severity, rather than age, play an important role in antibody levels.
IL-27 Mediates Pro-Inflammatory Effects via the ERK Signaling Pathway During Preterm Labor
Authors: Huang Dongni , Ran Yuxin , Liu Zheng , He Jie , Yin Nanlin , Qi Hongbo
Published: October 2021

Preterm labor (PTL) is a multifactorial syndrome that results in birth prior to 37 weeks of gestation. However, the specific molecular mechanisms underlying this condition have yet to be elucidated. Previous research demonstrated that the abnormal expression of IL-27, and its receptors, played a role in the pathophysiology of preterm labor. In the present study, we established a Lipopolysaccharide (LPS)-stimulated, infection-induced, preterm mouse model based on wild-type C57BL/6 mice and WSX-1-/-C57BL/6 mice. WSX-1 knockdown led to a significant delay in birth by 11.32 ± 2.157h. In addition, compared with wild-type C57B/6 mice, the expression levels of IFN-γ, IL-1β, IL-6, TNF-α, and CXCL10, in the fetal membrane and myometrium of WSX-1-/-mice were significantly lower, particularly in the myometrium. We also confirmed similar pro-inflammatory effects arising from IL-27 in human amniotic cell line (WISH) and human myometrial smooth muscle cell line (HMSMC). Once stimulated by LPS, the pro-inflammatory action exhibited a synergistic effect and appeared to be time-dependent. Finally, we demonstrated that LY3214996, an inhibitor of the ERK pathway, significantly inhibited the pro-inflammatory effect mediated by IL-27. Overall, our data confirmed that the inflammatory effect mediated by the IL-27/IFN-r/ERK axis is involved in preterm labor. Our findings, therefore, provide an enhancement in our etiological understanding of the mechanisms underlying PTL.
Epstein Barr Virus: Development of Vaccines and Immune Cell Therapy for EBV-Associated Diseases
Authors: Cui Xinle , Snapper Clifford M.
Published: October 2021

Epstein-Barr virus (EBV) is the first human tumor virus discovered and is strongly implicated in the etiology of multiple lymphoid and epithelial cancers. Each year EBV associated cancers account for over 200,000 new cases of cancer and cause 150,000 deaths world-wide. EBV is also the primary cause of infectious mononucleosis, and up to 70% of adolescents and young adults in developed countries suffer from infectious mononucleosis. In addition, EBV has been shown to play a critical role in the pathogenesis of multiple sclerosis. An EBV prophylactic vaccine that induces neutralizing antibodies holds great promise for prevention of EBV associated diseases. EBV envelope proteins including gH/gL, gB and gp350 play key roles in EBV entry and infection of target cells, and neutralizing antibodies elicited by each of these proteins have shown to prevent EBV infection of target cells and markedly decrease EBV titers in the peripheral blood of humanized mice challenged with lethal dose EBV. Recent studies demonstrated that immunization with the combination of gH/gL, gB and/or gp350 induced markedly increased synergistic EBV neutralizing activity compared to immunization with individual proteins. As previous clinical trials focused on gp350 alone were partially successful, the inclusion of gH/gL and gB in a vaccine formulation with gp350 represents a promising approach of EBV prophylactic vaccine development. Therapeutic EBV vaccines have also been tested clinically with encouraging results. Immunization with various vaccine platforms expressing the EBV latent proteins EBNA1, LMP1, and/or LMP2 promoted specific CD4+ and CD8+ cytotoxic responses with anti-tumor activity. The addition of EBV envelope proteins gH/gL, gB and gp350 has the potential to increase the efficacy of a therapeutic EBV vaccine. The immune system plays a critical role in the control of tumors, and immune cell therapy has emerged as a promising treatment of cancers. Adoptive T-cell therapy has been successfully used in the prevention and treatment of post-transplant lymphoproliferative disorder. Chimeric antigen receptor T cell therapy and T cell receptor engineered T cell therapy targeting EBV latent proteins LMP1, LMP2 and/or EBNA1 have been in development, with the goal to increase the specificity and efficacy of treatment of EBV associated cancers.
Plasma Exosome-Enriched Extracellular Vesicles From Lactating Mothers With Type 1 Diabetes Contain Aberrant Levels of miRNAs During the Postpartum Period
Authors: Frørup Caroline , Mirza Aashiq H. , Yarani Reza , Nielsen Lotte B. , Mathiesen Elisabeth R. , Damm Peter , Svare Jens , Engelbrekt Christian , Størling Joachim , Johannesen Jesper , Mortensen Henrik B. , Pociot Flemming , Kaur Simranjeet
Published: October 2021

Type 1 diabetes is an immune-driven disease, where the insulin-producing beta cells from the pancreatic islets of Langerhans becomes target of immune-mediated destruction. Several studies have highlighted the implication of circulating and exosomal microRNAs (miRNAs) in type 1 diabetes, underlining its biomarker value and novel therapeutic potential. Recently, we discovered that exosome-enriched extracellular vesicles carry altered levels of both known and novel miRNAs in breast milk from lactating mothers with type 1 diabetes. In this study, we aimed to characterize exosomal miRNAs in the circulation of lactating mothers with and without type 1 diabetes, hypothesizing that differences in type 1 diabetes risk in offspring from these groups are reflected in the circulating miRNA profile. We performed small RNA sequencing on exosome-enriched extracellular vesicles extracted from plasma of 52 lactating mothers around 5 weeks postpartum (26 with type 1 diabetes and 26 age-matched controls), and found a total of 2,289 miRNAs in vesicles from type 1 diabetes and control libraries. Of these, 176 were differentially expressed in plasma from mothers with type 1 diabetes (167 upregulated; 9 downregulated, using a cut-off of abs(log2FC) >1 and FDR adjusted p-value <0.05). Extracellular vesicles were verified by nanoparticle tracking analysis, transmission electron microscopy and immunoblotting. Five candidate miRNAs were selected based on their involvement in diabetes and immune modulation/beta-cell functions: hsa-miR-127-3p, hsa-miR-146a-5p, hsa-miR-26a-5p, hsa-miR-24-3p and hsa-miR-30d-5p. Real-time qPCR validation confirmed that hsa-miR-146a-5p, hsa-miR-26a-5p, hsa-miR-24-3p, and hsa-miR-30d-5p were significantly upregulated in lactating mothers with type 1 diabetes as compared to lactating healthy mothers. To determine possible target genes and affected pathways of the 5 miRNA candidates, computational network-based analyses were carried out with TargetScan, mirTarBase, QIAGEN Ingenuity Pathway Analysis and PantherDB database. The candidates showed significant association with inflammatory response and cytokine and chemokine mediated signaling pathways. With this study, we detect aberrant levels of miRNAs within plasma extracellular vesicles from lactating mothers with type 1 diabetes during the postpartum period, including miRNAs with associations to disease pathogenesis and inflammatory responses.
Pandemic Preparedness Against Influenza: DNA Vaccine for Rapid Relief
Authors: Andersen Tor Kristian , Bodin Johanna , Oftung Fredrik , Bogen Bjarne , Mjaaland Siri , Grødeland Gunnveig
Published: October 2021

The 2009 “swine flu” pandemic outbreak demonstrated the limiting capacity for egg-based vaccines with respect to global vaccine supply within a timely fashion. New vaccine platforms that efficiently can quench pandemic influenza emergences are urgently needed. Since 2009, there has been a profound development of new vaccine platform technologies with respect to prophylactic use in the population, including DNA vaccines. These vaccines are particularly well suited for global pandemic responses as the DNA format is temperature stable and the production process is cheap and rapid. Here, we show that by targeting influenza antigens directly to antigen presenting cells (APC), DNA vaccine efficacy equals that of conventional technologies. A single dose of naked DNA encoding hemagglutinin (HA) from influenza/A/California/2009 (H1N1), linked to a targeting moiety directing the vaccine to major histocompatibility complex class II (MHCII) molecules, raised similar humoral immune responses as the adjuvanted split virion vaccine Pandemrix, widely administered in the 2009 pandemic. Both vaccine formats rapidly induced serum antibodies that could protect mice already 8 days after a single immunization, in contrast to the slower kinetics of a seasonal trivalent inactivated influenza vaccine (TIV). Importantly, the DNA vaccine also elicited cytotoxic T-cell responses that reduced morbidity after vaccination, in contrast to very limited T-cell responses seen after immunization with Pandemrix and TIV. These data demonstrate that DNA vaccines has the potential as a single dose platform vaccine, with rapid protective effects without the need for adjuvant, and confirms the relevance of naked DNA vaccines as candidates for pandemic preparedness.
SERS Sensing of Bacterial Endotoxin on Gold Nanoparticles
Authors: Verde Alessandro , Mangini Maria , Managò Stefano , Tramontano Chiara , Rea Ilaria , Boraschi Diana , Italiani Paola , De Luca Anna Chiara
Published: October 2021

Engineered gold nanoparticles (AuNPs) find application in several fields related to human activities (i.e., food and cosmetic industry or water purification) including medicine, where they are employed for diagnosis, drug delivery and cancer therapy. As for any material/reagent for human use, the safety of AuNPs needs accurate evaluation. AuNPs are prone to contamination by bacterial endotoxin (lipopolysaccharide, LPS), a potent elicitor of inflammatory responses in mammals. It is therefore important, when assessing AuNP immunosafety and immune-related effects, to discriminate between inflammatory effects intrinsic to the NPs from those caused by an undeliberate and undetected LPS contamination. Detection of LPS contamination in AuNP preparations poses different problems when using the current LPS detection assays, given the general interference of NPs, similar to other particulate agents, with the assay reagents and endpoints. This leads to time-consuming search for optimal assay conditions for every NP batch, with unpredictable results, and to the use in parallel of different assays, each with its weaknesses and unpredictability. Thus, the development of highly sensitive, quantitative and accurate assays able to detect of LPS on AuNPs is very important, in view of their medical applications. Surface-enhanced Raman spectroscopy (SERS) is a label-free, sensitive, chemical-specific, nondestructive and fast technique that can be used to directly obtain molecular fingerprint information and a quantitative analysis of LPS adsorbed on AuNPs. Within this study, we describe the use of SERS for the label-free identification and quantitative evaluation - down to few attograms - of the LPS adsorbed on the surface of 50 nm AuNPs. We thus propose SERS as an efficient tool to detect LPS on the AuNP surface, and as the basis for the development of a new sensitive and specific LPS-detection sensor based on the use of AuNPs and SERS.
Innate Lymphoid Cells in Skin Homeostasis and Malignancy
Authors: Wagner Marek , Koyasu Shigeo
Published: October 2021

Innate lymphoid cells (ILCs) are mostly tissue resident lymphocytes that are preferentially enriched in barrier tissues such as the skin. Although they lack the expression of somatically rearranged antigen receptors present on T and B cells, ILCs partake in multiple immune pathways by regulating tissue inflammation and potentiating adaptive immunity. Emerging evidence indicates that ILCs play a critical role in the control of melanoma, a type of skin malignancy thought to trigger immunity mediated mainly by adaptive immune responses. Here, we compile our current understanding of ILCs with regard to their role as the first line of defence against melanoma development and progression. We also discuss areas that merit further investigation. We envisage that the possibility to harness therapeutic potential of ILCs might benefit patients suffering from skin malignancies such as melanoma.
Role of B Cell Profile for Predicting Secondary Autoimmunity in Patients Treated With Alemtuzumab
Authors: Walo-Delgado Paulette Esperanza , Monreal Enric , Medina Silvia , Quintana Ester , Sainz de la Maza Susana , Fernández-Velasco José Ignacio , Lapuente Paloma , Comabella Manuel , Ramió-Torrentà Lluis , Montalban Xavier , Midaglia Luciana , Villarrubia Noelia , Carrasco-Sayalero Angela , Rodríguez-Martín Eulalia , Roldán Ernesto , Meca-Lallana José , Alvarez-Lafuente Roberto , Masjuan Jaime , Costa-Frossard Lucienne , Villar Luisa Maria
Published: October 2021

Objective

To explore if baseline blood lymphocyte profile could identify relapsing remitting multiple sclerosis (RRMS) patients at higher risk of developing secondary autoimmune adverse events (AIAEs) after alemtuzumab treatment.

Methods

Multicenter prospective study including 57 RRMS patients treated with alemtuzumab followed for 3.25 [3.5-4.21] years, (median [interquartile range]). Blood samples were collected at baseline, and leukocyte subsets determined by flow cytometry. We had additional samples one year after the first cycle of alemtuzumab treatment in 39 cases.

Results

Twenty-two patients (38.6%) developed AIAEs during follow-up. They had higher B-cell percentages at baseline (p=0.0014), being differences mainly due to plasmablasts/plasma cells (PB/PC, p=0.0011). Those with no AIAEs had higher percentages of CD4+ T cells (p=0.013), mainly due to terminally differentiated (TD) (p=0.034) and effector memory (EM) (p=0.031) phenotypes. AIAEs- patients also showed higher values of TNF-alpha-producing CD8+ T cells (p=0.029). The percentage of PB/PC was the best variable to differentiate both groups of patients. Baseline values >0.10% closely associated with higher AIAE risk (Odds ratio [OR]: 5.91, 95% CI: 1.83-19.10, p=0.004). When excluding the 12 patients with natalizumab, which decreases blood PB/PC percentages, being the last treatment before alemtuzumab, baseline PB/PC >0.1% even predicted more accurately the risk of AIAEs (OR: 11.67, 95% CI: 2.62-51.89, p=0.0007). The AIAEs+ group continued having high percentages of PB/PC after a year of alemtuzumab treatment (p=0.0058).

Conclusions

A PB/PC percentage <0.1% at baseline identifies MS patients at low risk of secondary autoimmunity during alemtuzumab treatment.​
Bycatch Estimates From a Pacific Tuna Longline Fishery Provide a Baseline for Understanding the Long-Term Benefits of a Large, Blue Water Marine Sanctuary
Authors: Jaiteh Vanessa , Peatman Tom , Lindfield Steve , Gilman Eric , Nicol Simon
Published: October 2021

Bycatch on pelagic tuna longlines has contributed to population declines in several far-ranging, oceanic species and presents a conservation challenge that area-based management tools are increasingly promoted to address. In January 2020 the Republic of Palau, concerned about the impacts of longline fishing in its waters, closed 80% of its exclusive economic zone to all extractive activities, reserving the remaining 20% for a domestic fishing zone (DFZ). One of a growing number of very large marine protected areas, the Palau National Marine Sanctuary (PNMS) spans ∼500,000 km2 and was established inter alia to allow for the recovery of fish stocks adversely impacted by tuna longline fleets. Given that the main tuna stocks targeted in the western Pacific are not overexploited, the benefits of protection potentially afforded by the sanctuary are likely greater for vulnerable bycatch species. Evaluations of the sanctuary’s performance require, in part, a baseline of historical catch rates and effort distribution in the distant-water fleet (DWF) and locally based fleet (LBF) operating in Palau prior to sanctuary implementation. We describe the fishing effort, catch rates, catch estimates and fishing mortality in Palau’s longline fishery based on logbook, observer and electronic monitoring data. We defined bycatch as any species, retained or discarded, other than targeted tunas. Between 2010 and 2020, 104.8 million hooks were deployed, catching over 2 million individuals from 117 taxa at an overall target:bycatch ratio of 1:1, with a retention rate of ∼62%. Pronounced differences in fishing strategies and spatial distribution of effort between fleets were associated with large variations in catch rates and composition. The LBF had a larger effect on populations of at-risk species relative to the DWF, with higher catch rates and magnitudes for several vulnerable species and higher observable fishing mortality rates (64% vs 50% in the DWF). The sanctuary reshaped Palau’s longline fishery, contracting the fishery’s area and capacity. The relocation of the DFZ eliminated the LBF and constrained the DWF to an area where the fleet’s total catch rates and those of a number of vulnerable species were historically lower relative to former fishing grounds now closed by the sanctuary. Our results highlight the importance of consistent bycatch monitoring and emphasize the need for regional area-based approaches for managing longline fisheries.
Genomics-Based Phylogenetic and Population Genetic Analysis of Global Samples Confirms Halophila johnsonii Eiseman as Halophila ovalis (R.Br.) Hook.f.
Authors: Waycott Michelle , van Dijk Kor-jent , Calladine Ainsley , Bricker Eric , Biffin Ed
Published: October 2021

Halophila johnsonii is an endangered seagrass species that is restricted to the southeast coast of Florida, United States. Its taxonomic status has been called into question, in particular, given the close morphological and genetic similarity of H. johnsonii and the widely distributed and morphologically variable Halophila ovalis, which is largely restricted to the Indo-Pacific region. While a close relationship to H. ovalis is uncontroversial, it remains uncertain whether H. johnsonii represents a distinct lineage or is a recent introduction to the Florida region. Given the conservation status of H. johnsonii, distinguishing these alternatives has important implications for the management of the species and its habitat. Here, we develop molecular data sets for samples of H. johnsonii and H. ovalis including DNA sequences, genome-wide SNPs and microsatellites with the view to resolving the affinities of H. johnsonii with respect to the wider H. ovalis complex. Phylogenetic hypotheses based upon plastid (∼18000 bp) and low copy nuclear DNA (∼6500 bp) sequences derived from hybrid capture, along with 990 genome-wide ddRAD SNPs consistently resolved H. johnsonii within H. ovalis. Specifically, we found a close affinity between H. johnsonii and H. ovalis sampled from the east coast of Africa. In addition, Halophila specimens collected in Antigua, which are within the range of morphological variation typical for H. ovalis, are virtually identical to H. johnsonii and the East African H. ovalis samples based upon DNA sequence analyses and these group together using Bayesian clustering analyses of microsatellites and ddRAD SNPs. We conducted population genetic analyses using large number of H. johnsonii samples collected over a 17-year period. Genotypic data generated through microsatellites and ddRAD SNPs revealed genetic uniformity for all 132 H. johnsonii samples across the Indian River Lagoon, Florida, while samples of H. ovalis from Antigua shared the same genotype as H. johnsonii. We conclude that the lack of genetic diversity and the absence of sexual reproduction strongly indicates that the total range of H. johnsonii is actually one clone that is closely related to populations in Africa and Antigua and may be derived from a recent introduction from one of those regions.
Delta-Like Protein 3 Expression in Paired Chemonaive and Chemorelapsed Small Cell Lung Cancer Samples
Authors: Kuempers Christiane , Jagomast Tobias , Krupar Rosemarie , Paulsen Finn-Ole , Heidel Carsten , Ribbat-Idel Julika , Idel Christian , Märkl Bruno , Anlauf Martin , Berezowska Sabina , Tiemann Markus , Bösmüller Hans , Fend Falko , Kalsdorf Barbara , Bohnet Sabine , Dreyer Eva , Sailer Verena , Kirfel Jutta , Perner Sven
Published: October 2021

Rovalpituzumab tesirine (Rova-T), an antibody-drug conjugate directed against Delta-like protein 3 (DLL3), is under development for patients with small cell lung cancer (SCLC). DLL3 is expressed on the majority of SCLC samples. Because SCLC is rarely biopsied in the course of disease, data regarding DLL3 expression in relapses is not available. The aim of this study was to investigate the expression of DLL3 in chemorelapsed (but untreated with Rova-T) SCLC samples and compare the results with chemonaive counterparts. Two evaluation methods to assess DLL3 expression were explored. Additionally, we assessed if DLL3 expression of chemorelapsed and/or chemonaive samples has prognostic impact and if it correlates with other clinicopathological data. The study included 30 paired SCLC samples, which were stained with an anti DLL3 antibody. DLL3 expression was assessed using tumor proportion score (TPS) and H-score and was categorized as DLL3 low (TPS < 50%, H-score ≤ 150) and DLL3 high (TPS ≥ 50%, H-score > 150). Expression data were correlated with clinicopathological characteristics. Kaplan–Meier curves were used to illustrate overall survival (OS) depending on DLL3 expression in chemonaive and chemorelapsed samples, respectively, and depending on dynamics of expression during course of therapy. DLL3 was expressed in 86.6% chemonaive and 80% chemorelapsed SCLC samples without significant differences between the two groups. However, the extent of expression varied in a substantial proportion of pairs (36.6% with TPS, 43.3% with H-score), defined as a shift from low to high or high to low expression. TPS and H-score provided comparable results. There were no profound correlations with clinicopathological data. Survival analysis revealed a trend toward a more favorable OS in DLL low-expressing chemonaive SCLC (p = 0.57) and, in turn, in DLL3 high-expressing chemorelapsed SCLC (p = 0.42) as well as in SCLC demonstrating a shift from low to high expression (p = 0.56) without being statistically significant. This is the first study to investigate DLL3 expression in a large cohort of rare paired chemonaive-chemorelapsed SCLC specimens. Comparative analysis revealed that DLL3 expression was not stable during the course of therapy, suggesting therapy-based alterations. Unlike in chemonaive samples, a high DLL3 expression in chemorelapsed samples indicated a trend for a more favorable prognosis. Our results highlight the importance to investigate DLL3 in latest chemorelapsed SCLC tumor tissue.
BNT162b2 and ChAdOx1 SARS-CoV-2 Post-vaccination Side-Effects Among Saudi Vaccinees
Authors: Alghamdi Ahmed N. , Alotaibi Mohammed I. , Alqahtani Adel S. , Al Aboud Daifullah , Abdel-Moneim Ahmed S.
Published: October 2021

Background:Vaccination against SARS-CoV-2 is important for reducing hospitalization and mortalities. Both Pfizer-BioNTech (BNT162b2) and the Oxford-AstraZeneca (ChAdOx1 nCoV-19) vaccines are used in Saudi Arabia and in many parts of the world. Post-vaccinal side effects were recorded, so we aimed to screen different complaints after vaccination among vaccinees in Saudi Arabia.

Methods:An online questionnaire was designed to screen the local, systemic, and allergic post vaccination reactions for vaccinees who received either one or two doses of the BNT162b2 vaccine or one dose of the ChAdOx1 vaccine. The number and percentage were recorded for each response and analyzed using cross-tab and Chi square tests. The degree of the severity of post vaccination reactions were analyzed using Roc curve. The cofactors that may affect the severity of post-vaccinal reactions including previous COVID-19 infection, age, sex, body mass index, and comorbidities were investigated.

Results:During our study, 4,170 individuals reported their responses: 2,601 received one dose of BNT162b2, of whom 456 completed the second dose, and 1,569 received a single dose of ChAdOx1. The side effects were reported in 85.6% of BNT162b2 vaccinees and 96.05% of ChAdOx1 vaccinees who voluntarily responded to a survey about post-vaccination side effects. The side effects were more severe in BNT162b2 than ChAdOx1. ChAdOx1 vaccinees reported mild, moderate, severe and critical side effects in 30.13, 28.62, 29.73, and 1.53%, respectively. In contrast, mild side effects were recorded among the majority of BNT162b2 vaccinees (63.92%) while moderate, severe, and critical side effects were 27.67, 7.68, and 0.72%, respectively. Both local and systemic side effects were recorded more frequently in ChAdOx1 in comparison to BNT162b2 vaccinees. Palpitation was among the new systemic side effects reported in the current study in high frequency. Abnormal menstrual cycle (delaying/increase hemorrhages or pain) was also reported in 0.98% (18/1846) of Pfizer-BioNTech and 0.68% (7/1028) of ChAdOx1 vaccinees, while deep vein thrombosis was only reported in a single case vaccinated with BNT162b2 vaccine.

Conclusion:Both vaccines induced post-vaccinal side effects; however, ChAdOx1 induces a higher frequency of post-vaccinal systemic side effects than BNT162b2.
Living With Assistive Robotics: Exploring the Everyday Use of Exoskeleton for Persons With Spinal Cord Injury
Authors: Lusardi Roberto , Tomelleri Stefano , Wherton Joseph
Published: October 2021

Background: Recent advancements in sensor technology and artificial intelligence mechanisms have led to a rapid increase in research and development of robotic orthoses or “exoskeletons” to support people with mobility problems. The purpose of this case study was to provide insight into the lived reality of using the assistive robotic exoskeleton ReWalk.

Method: We used ethnographic techniques to explore the everyday experience and use of the assistive robotic device.

Results: We found that the appropriation and integration of the technology within the patient's everyday lives required a social and collaborative effort, which continued into use. The decisions to utilise the technology (or not) was closely tied to physical, social, cultural, environmental, and psychological factors. Consequently, there was much variation in patients' perception of the technology and opportunities for support. Four themes emerged:

(a) Meaning of mobility—physical mobility represents more than functional ability. Its present socio-cultural meaning is associated with an individual's self-identity and life priorities.

(b) Accomplishing body-technique—integration with the body requires a long process of skill acquisition and re-embodiment.

(c) Adaptation and adjustment in use—successful use of the technology was characterised by ongoing adjustment and adaptation of the technology and ways of using it.

(d) Human element—introduction and sustained use of the exoskeleton demand a social and collaborative effort across the user's professional and lay resources.

Conclusions: This study highlights that the development and implementation of the technology need to be grounded in a deep understanding of the day-to-day lives and experiences of the people that use them.