bluuebunny/crossref_metadata_2025 huggingface dataset:
Stability Analysis of Delayed Age-Structured Resource-Consumer Model of Population Dynamics With Saturated Intake Rate
Authors: Akimenko Vitalii V.
Published: February 2021

This article studies nonlinear n-resource-consumer autonomous system with age-structured consumer population. The model of consumer population dynamics is described by a delayed transport equation, and the dynamics of resource patches are described by ODE with saturated intake rate. The delay models the digestion period of generalist consumer and is included in the calorie intake rate, which impacts the consumer’s fertility and mortality. Saturated intake rate models the inhibition effect from the behavioral change of the resource patches when they react to the consumer population growing or from the crowding effect of the consumer. The conditions for the existence of trivial, semi-trivial, and non-trivial equilibria and their local asymptotic stability were obtained. The local asymptotic stability/instability of non-trivial equilibrium of a system with depleted patches is defined by new derived criteria, which relate the demographic characteristics of consumers with their search rate, growth rate of resource in patches, and behavioral change of the food resource when consumer population grows. The digestion period of a generalist consumer does not cause local asymptotical instabilities of consumer population at the semi-trivial and nontrivial equilibria. These theoretical results may be used in the study of metapopulation dynamics, desert locust populations dynamics, prey-predator interactions in fisheries, etc. The paper uses numerical experiments to confirm and illustrate all dynamical regimes of the n-resource-consumer population.
The Circulation of Ancient Animal Resources Across the Yellow River Basin: A Preliminary Bayesian Re-evaluation of Sr Isotope Data From the Early Neolithic to the Western Zhou Dynasty
Authors: Wang Xueye , Roberts Patrick , Tang Zihua , Yang Shiling , Storozum Michael , Groß Marcus , Fernandes Ricardo
Published: February 2021

Many questions still remain regarding the acquisition and circulation of ancient domesticated animals across the Yellow River Basin, one of the key areas for the development of complex societies in ancient China. Here, we re-evaluate previously published strontium isotope data (87Sr/86Sr, n = 167) from tooth enamel of domesticated animals at 10 archaeological sites in the Yellow River Basin to shed new light on the transition between the Neolithic (7000–5000 BCE) and the Western Zhou Dynasty (1046–771 BCE). The results show that from the Late Neolithic to the Western Zhou Dynasty, some domesticated animals, mostly cattle and sheep, were increasingly sourced from non-local areas. We employed Bayesian methods to define an isoscape of bioavailable Sr for the Yellow River Basin and to show the considerable diversity in the origins of non-local domesticated animals, some of which may have come from locations hundreds of kilometers away from the site as early as the Late Neolithic. The increasingly variable 87Sr/86Sr ratios of domesticated animals from the Neolithic to the Western Zhou Dynasty are consistent with that of associated human remains, and also match the archaeological and zooarchaeological evidence for increased circulation of animal products in the Yellow River Basin. Therefore, we infer that local economies increasingly incorporated non-local animals as part of wider circulation networks that emerged with the development of complex societies since the Late Neolithic.
Complex Small-Holder Agriculture in Rainforest Buffer Zone, Sri Lanka, Supports Endemic Birds
Authors: Hanle Juliana , Singhakumara Balangoda M. P. , Ashton Mark S.
Published: February 2021

The Sinharaja rainforest in southwestern Sri Lanka is a protected forest in a largely agriculture-dominated landscape. In keeping with global UNESCO global biosphere reserves planning, the Sinharaja is surrounded by a buffer zone of regenerating forest and villages with small tea plots and multi-strata tree gardens (homegardens). Globally, however, conservation planning lacks standards on buffer zone management. We ask what relationships exist between village land use and bird assemblages, which are effective ecosystem indicators. Birds have been little studied across land use and vegetation structure in actively managed, large, protected forest buffer zones. To that end, we ran spatially- and temporally-replicated bird point counts across tree gardens, forest fragments, and tea plots within a Sinharaja village. Tree gardens held a greater abundance of birds across habitat association, conservation concern, diet, and endemic species than forest fragments or tea plots. Forest fragments and tree gardens hosted statistically similar numbers of birds in some subsets, but their species assemblages differed. In tea plots, greater shade tree species richness correlated with greater bird abundance and species richness. Our results support the argument for programs to support complex small-scale tree-based agroforestry embedded in buffer zone regenerating forest.
Dams Change Beta Diversity of Aquatic Communities in the Veredas of the Brazilian Cerrado
Authors: Brasil Leandro Schlemmer , Ferreira Victor Rennan Santos , Resende Bethânia Oliveira de , Juen Leandro , Batista Joana Darc , Castro Lourivaldo Amâncio de , Giehl Nubia França da Silva
Published: February 2021

The veredas are wetland ecosystems responsible for supplying most of the water for rivers and streams in the Cerrado. The veredas’ hydromorfic soils retain a large amount of rainwater, releasing it slowly during drier periods. Therefore, these habitats are often used to build dams for cattle raising. Here we assessed the environmental conditions and beta-diversity of Odonata and Heteroptera on veredas impacted by dams in the Brazilian Cerrado. We sampled biological communities and a set of environmental variables in 13 veredas, six with dams and seven without dams. One limnological variable [oxidation–reduction potential (ORP)] and one landscape metric (% of the altered area) differed among veredas with and without dams. These variables were important predictors of the beta-diversity of both Odonata (R2= 0.650;p< 0.001) and Heteroptera (R2= 0.740;p< 0.001). The veredas stand among the most sensitive wetland ecosystems of the Cerrado. In this study, we show, for the first time, that veredas with dams may lose environmental quality resulting in changes in biological communities, especially ecologically unique species. Because the Cerrado naturally goes through approximately 5 months of severe drought, the veredas are critical for the Cerrado’s hydric safety. Therefore, we recommend that cattle-raising activities should rely on artificial water tanks instead of using dams for water storage since it affects ecologically unique species in this poorly known ecosystem.
The Biology and Evolution of Calcite and Aragonite Mineralization in Octocorallia
Authors: Conci Nicola , Vargas Sergio , Wörheide Gert
Published: February 2021

Octocorallia (class Anthozoa, phylum Cnidaria) is a group of calcifying corals displaying a wide diversity of mineral skeletons. This includes skeletal structures composed of different calcium carbonate polymorphs (aragonite and calcite). This represents a unique feature among anthozoans, as scleractinian corals (subclass Hexacorallia), main reef builders and focus of biomineralization research, are all characterized by an aragonite exoskeleton. From an evolutionary perspective, the presence of aragonitic skeletons in Octocorallia is puzzling as it is observed in very few species and has apparently originated during a Calcite sea (i.e., time interval characterized by calcite-inducing seawater conditions). Despite this, octocorals have been systematically overlooked in biomineralization studies. Here we review what is known about octocoral biomineralization, focusing on the evolutionary and biological processes that underlie calcite and aragonite formation. Although differences in research focus between octocorals and scleractinians are often mentioned, we highlight how strong variability also exists between different octocoral groups. Different main aspects of octocoral biomineralization have been in fact studied in a small set of species, including the (calcitic) gorgonianLeptogorgia virgulataand/or the precious coralCorallium rubrum.These include descriptions of calcifying cells (scleroblasts), calcium transport and chemistry of the calcification fluids. With the exception of few histological observations, no information on these features is available for aragonitic octocorals. Availability of sequencing data is also heterogeneous between groups, with no transcriptome or genome available, for instance, for the clade Calcaxonia. Although calcite represents by far the most common polymorph deposited by octocorals, we argue that studying aragonite-forming could provide insight on octocoral, and more generally anthozoan, biomineralization. First and foremost it would allow to compare calcification processes between octocoral groups, highlighting homologies and differences. Secondly, similarities (exoskeleton) betweenHelioporaand scleractinian skeletons, would provide further insight on which biomineralization features are driven by skeleton characteristics (shared by scleractinians and aragonitic octocorals) and those driven by taxonomy (shared by octocorals regardless of skeleton polymorph). Including the diversity of anthozoan mineralization strategies into biomineralization studies remains thus essential to comprehensively study how skeletons form and evolved within this ecologically important group of marine animals.
Evaluating DNA Barcoding for Species Identification and Discovery in European Gracillariid Moths
Authors: Lopez-Vaamonde Carlos , Kirichenko Natalia , Cama Alain , Doorenweerd Camiel , Godfray H. Charles J. , Guiguet Antoine , Gomboc Stanislav , Huemer Peter , Landry Jean-François , Laštůvka Ales , Laštůvka Zdenek , Lee Kyung Min , Lees David C. , Mutanen Marko , van Nieukerken Erik J. , Segerer Andreas H. , Triberti Paolo , Wieser Christian , Rougerie Rodolphe
Published: February 2021

Gracillariidae is the most species-rich leaf-mining moth family with over 2,000 described species worldwide. In Europe, there are 263 valid named species recognized, many of which are difficult to identify using morphology only. Here we explore the use of DNA barcodes as a tool for identification and species discovery in European gracillariids. We present a barcode library including 6,791 COI sequences representing 242 of the 263 (92%) resident species. Our results indicate high congruence between morphology and barcodes with 91.3% (221/242) of European species forming monophyletic clades that can be identified accurately using barcodes alone. The remaining 8.7% represent cases of non-monophyly making their identification uncertain using barcodes. Species discrimination based on the Barcode Index Number system (BIN) was successful for 93% of species with 7% of species sharing BINs. We discovered as many as 21 undescribed candidate species, of which six were confirmed from an integrative approach; the other 15 require additional material and study to confirm preliminary evidence. Most of these new candidate species are found in mountainous regions of Mediterranean countries, the South-Eastern Alps and the Balkans, with nine candidate species found only on islands. In addition, 13 species were classified as deep conspecific lineages, comprising a total of 27 BINs with no intraspecific morphological differences found, and no known ecological differentiation. Double-digest restriction-site associated DNA sequencing (ddRAD) analysis showed strong mitonuclear discrepancy in four out of five species studied. This discordance is not explained by Wolbachia-mediated genetic sweeps. Finally, 26 species were classified as “unassessed species splits” containing 71 BINs and some involving geographical isolation or ecological specialization that will require further study to test whether they represent new cryptic species.
Seven Questions on the Chemical Ecology and Neurogenetics of Resource-Mediated Speciation
Authors: Wang Xiaocui , Verschut Thomas A. , Billeter Jean-Christophe , Maan Martine E.
Published: February 2021

Adaptation to different environments can result in reproductive isolation between populations and the formation of new species. Food resources are among the most important environmental factors shaping local adaptation. The chemosensory system, the most ubiquitous sensory channel in the animal kingdom, not only detects food resources and their chemical composition, but also mediates sexual communication and reproductive isolation in many taxa. Chemosensory divergence may thus play a crucial role in resource-mediated adaptation and speciation. Understanding how the chemosensory system can facilitate resource-mediated ecological speciation requires integrating mechanistic studies of the chemosensory system with ecological studies, to link the genetics and physiology of chemosensory properties to divergent adaptation. In this review, we use examples of insect research to present seven key questions that can be used to understand how the chemosensory system can facilitate resource-mediated ecological speciation in consumer populations.
Genomics Armed With Diversity Leads the Way in Brassica Improvement in a Changing Global Environment
Authors: Mohd Saad Nur Shuhadah , Severn-Ellis Anita A. , Pradhan Aneeta , Edwards David , Batley Jacqueline
Published: February 2021

Meeting the needs of a growing world population in the face of imminent climate change is a challenge; breeding of vegetable and oilseedBrassicacrops is part of the race in meeting these demands. Available genetic diversity constituting the foundation of breeding is essential in plant improvement. Elite varieties, land races, and crop wild species are important resources of useful variation and are available from existing genepools or genebanks. Conservation of diversity in genepools, genebanks, and even the wild is crucial in preventing the loss of variation for future breeding efforts. In addition, the identification of suitable parental lines and alleles is critical in ensuring the development of resilientBrassicacrops. During the past two decades, an increasing number of high-quality nuclear and organellarBrassicagenomes have been assembled. Whole-genome re-sequencing and the development of pan-genomes are overcoming the limitations of the single reference genome and provide the basis for further exploration. Genomic and complementary omic tools such as microarrays, transcriptomics, epigenetics, and reverse genetics facilitate the study of crop evolution, breeding histories, and the discovery of loci associated with highly sought-after agronomic traits. Furthermore, in genomic selection, predicted breeding values based on phenotype and genome-wide marker scores allow the preselection of promising genotypes, enhancing genetic gains and substantially quickening the breeding cycle. It is clear that genomics, armed with diversity, is set to lead the way inBrassicaimprovement; however, a multidisciplinary plant breeding approach that includes phenotype = genotype × environment × management interaction will ultimately ensure the selection of resilientBrassicavarieties ready for climate change.
Association Between miR-148a and DNA Methylation Profile in Individuals Exposed to Lead (Pb)
Authors: Araújo Marília Ladeira de , Gomes Bruno Costa , Devóz Paula Pícoli , Duarte Nathália de Assis Aguilar , Ribeiro Diego Luis , Araújo Adriana Ladeira de , Batista Bruno Lemos , Antunes Lusânia Maria Greggi , Barbosa Fernando , Rodrigues António Sebastião , Rueff José , Barcelos Gustavo Rafael Mazzaron
Published: February 2021

Experimental and epidemiologic studies have shown that lead (Pb) is able to induce epigenetic modifications, such as changes in DNA methylation profiles, in chromatin remodeling, as well as the expression of non-coding RNAs (ncRNAs). However, very little is known about the interactions between microRNAs (miRNAs) expression and DNA methylation status in individuals exposed to the metal. The aim of the present study was to investigate the impact of hsa-miR-148a expression on DNA methylation status, in 85 workers exposed to Pb. Blood and plasma lead levels (BLL and PLL, respectively) were determined by ICP-MS; expression of the miRNA-148a was quantified by RT-qPCR (TaqMan assay) and assessment of the global DNA methylation profile (by measurement of 5-methylcytosine; % 5-mC) was performed by ELISA. An inverse association was seen between miR-148a and % 5-mC DNA, as a function of BLL and PLL (β = −3.7; p = 0.071 and β = −4.1; p = 0.049, respectively) adjusted for age, BMI, smoking, and alcohol consumption. Taken together, our study provides further evidence concerning the interactions between DNA methylation profile and miR-148a, in individuals exposed to Pb.
Between a Rock and a Hard Place: Considering “Freebirth” During Covid-19
Authors: Greenfield Mari , Payne-Gifford Sophie , McKenzie Gemma
Published: February 2021

Background: The global coronavirus (Covid-19) pandemic concerns all people, but has a specific effect on those who are expecting a baby during this time. The advice in the UK changed rapidly, with 14 different sets of national guidance issued within 1 month. Individual NHS Trusts released various guidance relating to the withdrawal of homebirth services, the closure of birth centers, restrictions on the number of birth partners (if any) allowed during labor, and whether any visitors were allowed to attend after birth. With the landscape of maternity care changing so rapidly, research was carried out to provide real-time data to capture the lived experiences of expectant families.

Methods: A mixed methods online survey was carried out over 2 weeks between 10th and 24th April 2020. The survey was open to those in the third trimester of pregnancy, those who had given birth since the beginning of the “lockdown” period in the UK, and the partners of pregnant women and people who were in these circumstances. The survey asked questions about how respondents' holistic antenatal experiences had been affected, whether their plans for birth had changed, and the effect of these changes on respondents' emotional wellbeing. Of the 1,700 responses received, 72 mentioned that they had seriously considered “freebirthing” (giving birth without a healthcare professional present).

Findings: An analysis of the respondents' reasons for considering freebirth was conducted, finding that reasons for considering freebirth were complex and multifaceted. Lesbian, bisexual, pansexual, and queer women were more likely to have considered freebirth than heterosexual people (p < 0.001).

Conclusions: Considering giving birth without a healthcare professional present is unusual in the Global North and represents an emerging field of study. The literature examining the reasons that people consider freebirth shows a variety of underlying motivations. A global pandemic represents a new factor in such considerations. The findings from this research can help inform maternity service planning in future crises.
The Cholinergic System Contributes to the Immunopathological Progression of Experimental Pulmonary Tuberculosis
Authors: Islas-Weinstein Leon , Marquina-Castillo Brenda , Mata-Espinosa Dulce , Paredes-González Iris S. , Chávez Jaime , Balboa Luciana , Marín Franco José Luis , Guerrero-Romero Daniel , Barrios-Payan Jorge Alberto , Hernandez-Pando Rogelio
Published: February 2021

The cholinergic system is present in both bacteria and mammals and regulates inflammation during bacterial respiratory infections through neuronal and non-neuronal production of acetylcholine (ACh) and its receptors. However, the presence of this system during the immunopathogenesis of pulmonary tuberculosis (TB) in vivo and in its causative agent Mycobacterium tuberculosis (Mtb) has not been studied. Therefore, we used an experimental model of progressive pulmonary TB in BALB/c mice to quantify pulmonary ACh using high-performance liquid chromatography during the course of the disease. In addition, we performed immunohistochemistry in lung tissue to determine the cellular expression of cholinergic system components, and then administered nicotinic receptor (nAChR) antagonists to validate their effect on lung bacterial burden, inflammation, and pro-inflammatory cytokines. Finally, we subjected Mtb cultures to colorimetric analysis to reveal the production of ACh and the effect of ACh and nAChR antagonists on Mtb growth. Our results show high concentrations of ACh and expression of its synthesizing enzyme choline acetyltransferase (ChAT) during early infection in lung epithelial cells and macrophages. During late progressive TB, lung ACh upregulation was even higher and coincided with ChAT and α7 nAChR subunit expression in immune cells. Moreover, the administration of nAChR antagonists increased pro-inflammatory cytokines, reduced bacillary loads and synergized with antibiotic therapy in multidrug resistant TB. Finally, in vitro studies revealed that the bacteria is capable of producing nanomolar concentrations of ACh in liquid culture. In addition, the administration of ACh and nicotinic antagonists to Mtb cultures induced or inhibited bacterial proliferation, respectively. These results suggest that Mtb possesses a cholinergic system and upregulates the lung non-neuronal cholinergic system, particularly during late progressive TB. The upregulation of the cholinergic system during infection could aid both bacterial growth and immunomodulation within the lung to favor disease progression. Furthermore, the therapeutic efficacy of modulating this system suggests that it could be a target for treating the disease.
A Novel Anti-HER2 Bispecific Antibody With Potent Tumor Inhibitory Effects In Vitro and In Vivo
Authors: Mohammadi Mehdi , Jeddi-Tehrani Mahmood , Golsaz-Shirazi Forough , Arjmand Mohammad , Bahadori Tannaz , Judaki Mohammad Ali , Shiravi Fariba , Zare Hengameh Ahmadi , Haghighat Farzaneh Notash , Mobini Maryam , Amiri Mohammad Mehdi , Shokri Fazel
Published: February 2021

Overexpression of HER2 has been reported in many types of cancer, making it a perfect candidate for targeted immunotherapy. The combination of two FDA approved monoclonal antibodies (mAbs), trastuzumab and pertuzumab, has more robust anti-tumor activity in patients with HER2-overexpressing breast cancer. We recently produced a new humanized anti-HER2 mAb, hersintuzumab, which recognizes a different epitope than trastuzumab and pertuzumab on HER2. This mAb, in combination with trastuzumab, exhibits more potent anti-tumor activity than each parental mAb alone. Here we have developed a novel bispecific anti-HER2 antibody (BsAb) designated as trasintuzumab, composed of trastuzumab and hersintuzumab, using dual variable domain immunoglobulin (DVD-Ig) technology. Both variable domains of trasintuzumab are fully functional and have similar affinities to the parental mAbs and are also able to bind to natural HER2 on the surface of several HER2-expressing cell lines. Trasintuzumab was found to inhibit the growth of different types of tumor cell lines through suppression of the AKT and ERK signaling pathways as efficiently as the combination of the parental mAbs. It also induced tumor regression as potently as the combination of the two mAbs in nude mice bearing ovarian and gastric cancer xenografts. Our data suggest that trasintuzumab may be a promising BsAb therapeutic candidate for the treatment of HER2-overexpressing cancers.
Prevention of Chronic Rejection of Marginal Kidney Graft by Using a Hydrogen Gas-Containing Preservation Solution and Adequate Immunosuppression in a Miniature Pig Model
Authors: Nishi Kotaro , Iwai Satomi , Tajima Kazuki , Okano Shozo , Sano Motoaki , Kobayashi Eiji
Published: February 2021

In clinical kidney transplantation, the marginal kidney donors are known to develop chronic allograft rejection more frequently than living kidney donors. In our previous study, we have reported that the hydrogen gas-containing organ preservation solution prevented the development of acute injuries in the kidney of the donor after cardiac death by using preclinical miniature pig model. In the present study, we verified the impact of hydrogen gas treatment in transplantation with the optimal immunosuppressive protocol based on human clinical setting by using the miniature pig model. Marginal kidney processed by hydrogen gas-containing preservation solution has been engrafted for long-term (longer than 100 days). A few cases showed chronic rejection reaction; however, most were found to be free of chronic rejection such as graft tissue fibrosis or renal vasculitis. We concluded that marginal kidney graft from donor after cardiac death is an acceptable model for chronic rejection and that if the transplantation is carried out using a strict immunosuppressive protocol, chronic rejection may be alleviated even with the marginal kidney.
The Clinical Significance of Iron Overload and Iron Metabolism in Myelodysplastic Syndrome and Acute Myeloid Leukemia
Authors: Weber Sarah , Parmon Anastasia , Kurrle Nina , Schnütgen Frank , Serve Hubert
Published: February 2021

Myelodysplasticsyndrome (MDS) and acute myeloid leukemia (AML) are clonal hematopoietic stem cell diseases leading to an insufficient formation of functional blood cells. Disease-immanent factors as insufficient erythropoiesis and treatment-related factors as recurrent treatment with red blood cell transfusions frequently lead to systemic iron overload in MDS and AML patients. In addition, alterations of function and expression of proteins associated with iron metabolism are increasingly recognized to be pathogenetic factors and potential vulnerabilities of these diseases. Iron is known to be involved in multiple intracellular and extracellular processes. It is essential for cell metabolism as well as for cell proliferation and closely linked to the formation of reactive oxygen species. Therefore, iron can influence the course of clonal myeloid disorders, the leukemic environment and the occurrence as well as the defense of infections. Imbalances of iron homeostasis may induce cell death of normal but also of malignant cells. New potential treatment strategies utilizing the importance of the iron homeostasis include iron chelation, modulation of proteins involved in iron metabolism, induction of leukemic cell death via ferroptosis and exploitation of iron proteins for the delivery of antileukemic drugs. Here, we provide an overview of some of the latest findings about the function, the prognostic impact and potential treatment strategies of iron in patients with MDS and AML.
Intact Glucocorticoid Receptor Dimerization Is Deleterious in Trauma-Induced Impaired Fracture Healing
Authors: Hachemi Yasmine , Rapp Anna E. , Lee Sooyeon , Dorn Ann-Kristin , Krüger Benjamin T. , Kaiser Kathrin , Ignatius Anita , Tuckermann Jan
Published: February 2021

Following severe trauma, fracture healing is impaired because of overwhelming systemic and local inflammation. Glucocorticoids (GCs), acting via the glucocorticoid receptor (GR), influence fracture healing by modulating the trauma-induced immune response. GR dimerization-dependent gene regulation is essential for the anti-inflammatory effects of GCs. Therefore, we investigated in a murine trauma model of combined femur fracture and thoracic trauma, whether effective GR dimerization influences the pathomechanisms of trauma-induced compromised fracture healing. To this end, we used mice with decreased GR dimerization ability (GRdim). The healing process was analyzed by cytokine/chemokine multiplex analysis, flow cytometry, gene-expression analysis, histomorphometry, micro-computed tomography, and biomechanical testing. GRdim mice did not display a systemic or local hyper-inflammation upon combined fracture and thorax trauma. Strikingly, we discovered that GRdim mice were protected from fracture healing impairment induced by the additional thorax trauma. Collectively and in contrast to previous studies describing the beneficial effects of intact GR dimerization in inflammatory models, we report here an adverse role of intact GR dimerization in trauma-induced compromised fracture healing.
Elafin as a Predictive Biomarker of Acute Skin Graft-Versus-Host Disease After Haploidentical Stem Cell Transplantation Using Post-Transplant High-Dose Cyclophosphamide
Authors: Solán Laura , Carbonell Diego , Muñiz Paula , Dorado Nieves , Landete Elena , Chicano-Lavilla María , Anguita Javier , Gayoso Jorge , Kwon Mi , Díez-Martín José Luis , Martínez-Laperche Carolina , Buño Ismael
Published: February 2021

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has shown favorable results in the treatment of hematological malignancies. Despite the use of post-transplant cyclophosphamide (PTCy), graft versus host disease (GVHD) remains as one of the main complications in this setting. Since the skin appears affected in up to 80% of cases of acute GVHD (aGVHD), its prognosis and diagnosis are essential for the correct management of these patients. Plasma concentration of elafin, an elastase inhibitor produced by keratinocytes, has been described elevated at the diagnosis of skin GVHD, correlated with the grade of GVHD, and associated with an increased risk of death. In this study we explored elafin plasma levels in the largest series reported of T cell–replete haplo-HSCT with PTCy. Plasma samples drawn from 87 patients at days +15 and +30 were analyzed (“discovery cohort”). Elafin levels at days +15 were no associated with chronic GVHD, non-relapse mortality, relapse, therapy-resistant GVHD, or overall survival. In our series, elafin levels at day +30 were not associated with post-transplant complications. On the other hand, elafin plasma levels at day +15 were higher in patients with severe skin aGVHD (21,313 vs.14,974 pg/ml; p = 0.01). Of note, patients with higher elafin plasma levels at day +15 presented a higher incidence of stage III-IV skin aGVHD (HR = 18.9; p < 0.001). These results were confirmed (HR = 20.6; p < 0.001) in an independent group of patients (n = 62), i.e. the “validation cohort.” These data suggest that measurement of elafin in patients undergoing haplo-HSCT with PTCy might be useful for an early identification of those patients who are at higher risk of suffering severe skin aGVHD and thus, improve their treatment and prognosis.
Terminally Differentiated CD4+ T Cells Promote Myocardial Inflammaging
Authors: Delgobo Murilo , Heinrichs Margarete , Hapke Nils , Ashour DiyaaElDin , Appel Marc , Srivastava Mugdha , Heckel Tobias , Spyridopoulos Ioakim , Hofmann Ulrich , Frantz Stefan , Ramos Gustavo Campos
Published: February 2021

The cardiovascular and immune systems undergo profound and intertwined alterations with aging. Recent studies have reported that an accumulation of memory and terminally differentiated T cells in elderly subjects can fuel myocardial aging and boost the progression of heart diseases. Nevertheless, it remains unclear whether the immunological senescence profile is sufficient to cause age-related cardiac deterioration or merely acts as an amplifier of previous tissue-intrinsic damage. Herein, we sought to decompose the causality in this cardio-immune crosstalk by studying young mice harboring a senescent-like expanded CD4+ T cell compartment. Thus, immunodeficient NSG-DR1 mice expressing HLA-DRB1*01:01 were transplanted with human CD4+ T cells purified from matching donors that rapidly engrafted and expanded in the recipients without causing xenograft reactions. In the donor subjects, the CD4+ T cell compartment was primarily composed of naïve cells defined as CCR7+CD45RO-. However, when transplanted into young lymphocyte-deficient mice, CD4+ T cells underwent homeostatic expansion, upregulated expression of PD-1 receptor and strongly shifted towards effector/memory (CCR7- CD45RO+) and terminally-differentiated phenotypes (CCR7-CD45RO-), as typically seen in elderly. Differentiated CD4+ T cells also infiltrated the myocardium of recipient mice at comparable levels to what is observed during physiological aging. In addition, young mice harboring an expanded CD4+ T cell compartment showed increased numbers of infiltrating monocytes, macrophages and dendritic cells in the heart. Bulk mRNA sequencing analyses further confirmed that expanding T-cells promote myocardial inflammaging, marked by a distinct age-related transcriptomic signature. Altogether, these data indicate that exaggerated CD4+ T-cell expansion and differentiation, a hallmark of the aging immune system, is sufficient to promote myocardial alterations compatible with inflammaging in juvenile healthy mice.
Protein-Based Vaccine Protect Against Piscirickettsia salmonis in Atlantic Salmon (Salmo salar)
Authors: Pontigo Juan Pablo , Espinoza Carla , Hernandez Mauricio , Nourdin Guillermo , Oliver Cristian , Avendaño-Herrera Rubén , Figueroa Jaime , Rauch Cecilia , Troncoso José M. , Vargas-Chacoff Luis , Yáñez Alejandro J.
Published: February 2021

An effective and economical vaccine against the Piscirickettsia salmonis pathogen is needed for sustainable salmon farming and to reduce disease-related economic losses. Consequently, the aquaculture industry urgently needs to investigate efficient prophylactic measures. Three protein-based vaccine prototypes against Piscirickettsia salmonis were prepared from a highly pathogenic Chilean isolate. Only one vaccine effectively protected Atlantic salmon (Salmo salar), in correlation with the induction of Piscirickettsia-specific IgM antibodies and a high induction of transcripts encoding pro-inflammatory cytokines (i.e., Il-1β and TNF-α). In addition, we studied the proteome fraction protein of P. salmonis strain Austral-005 using multidimensional protein identification technology. The analyzes identified 87 proteins of different subcellular origins, such as the cytoplasmic and membrane compartment, where many of them have virulence functions. The other two prototypes activated only the innate immune responses, but did not protect Salmo salar against P. salmonis. These results suggest that the knowledge of the formulation of vaccines based on P. salmonis proteins is useful as an effective therapy, this demonstrates the importance of the different research tools to improve the study of the different immune responses, resistance to diseases in the Atlantic salmon. We suggest that this vaccine can help prevent widespread infection by P. salmonis, in addition to being able to be used as a booster after a primary vaccine to maintain high levels of circulating protective antibodies, greatly helping to reduce the economic losses caused by the pathogen.
Chemokine Receptor-6 Promotes B-1 Cell Trafficking to Perivascular Adipose Tissue, Local IgM Production and Atheroprotection
Authors: Srikakulapu Prasad , Upadhye Aditi , Drago Fabrizio , Perry Heather M. , Bontha Sai Vineela , McSkimming Chantel , Marshall Melissa A. , Taylor Angela M. , McNamara Coleen A.
Published: February 2021

Chemokine receptor-6 (CCR6) mediates immune cell recruitment to inflammatory sites and has cell type-specific effects on diet-induced atherosclerosis in mice. Previously we showed that loss of CCR6 in B cells resulted in loss of B cell-mediated atheroprotection, although the B cell subtype mediating this effect was unknown. Perivascular adipose tissue (PVAT) harbors high numbers of B cells including atheroprotective IgM secreting B-1 cells. Production of IgM antibodies is a major mechanism whereby B-1 cells limit atherosclerosis development. Yet whether CCR6 regulates B-1 cell number and production of IgM in the PVAT is unknown. In this present study, flow cytometry experiments demonstrated that both B-1 and B-2 cells express CCR6, albeit at a higher frequency in B-2 cells in both humans and mice. Nevertheless, B-2 cell numbers in peritoneal cavity (PerC), spleen, bone marrow and PVAT were no different inApoE−/−CCR6−/−compared toApoE−/−CCR6+/+mice. In contrast, the numbers of atheroprotective IgM secreting B-1 cells were significantly lower in the PVAT ofApoE−/−CCR6−/−compared toApoE−/−CCR6+/+mice. Surprisingly, adoptive transfer (AT) of CD43−splenic B cells into B cell-deficient μMT−/−ApoE−/−mice repopulated the PerC with B-1 and B-2 cells and reduced atherosclerosis when transferred intoApoE−/−CCR6+/+sIgM−/−mice only when those cells expressed both CCR6 and sIgM. CCR6 expression on circulating human B cells in subjects with a high level of atherosclerosis in their coronary arteries was lower only in the putative human B-1 cells. These results provide evidence that B-1 cell CCR6 expression enhances B-1 cell number and IgM secretion in PVAT to provide atheroprotection in mice and suggest potential human relevance to our murine findings.
Common Peripheral Immunity Mechanisms in Multiple Sclerosis and Alzheimer's Disease
Authors: Rossi Barbara , Santos-Lima Bruno , Terrabuio Eleonora , Zenaro Elena , Constantin Gabriela
Published: February 2021

Neurodegenerative diseases are closely related to inflammatory and autoimmune events, suggesting that the dysregulation of the immune system is a key pathological factor. Both multiple sclerosis (MS) and Alzheimer's disease (AD) are characterized by infiltrating immune cells, activated microglia, astrocyte proliferation, and neuronal damage. Moreover, MS and AD share a common pro-inflammatory signature, characterized by peripheral leukocyte activation and transmigration to the central nervous system (CNS). MS and AD are both characterized by the accumulation of activated neutrophils in the blood, leading to progressive impairment of the blood–brain barrier. Having migrated to the CNS during the early phases of MS and AD, neutrophils promote local inflammation that contributes to pathogenesis and clinical progression. The role of circulating T cells in MS is well-established, whereas the contribution of adaptive immunity to AD pathogenesis and progression is a more recent discovery. Even so, blocking the transmigration of T cells to the CNS can benefit both MS and AD patients, suggesting that common adaptive immunity mechanisms play a detrimental role in each disease. There is also growing evidence that regulatory T cells are beneficial during the initial stages of MS and AD, supporting the link between the modulatory immune compartments and these neurodegenerative disorders. The number of resting regulatory T cells declines in both diseases, indicating a common pathogenic mechanism involving the dysregulation of these cells, although their precise role in the control of neuroinflammation remains unclear. The modulation of leukocyte functions can benefit MS patients, so more insight into the role of peripheral immune cells may reveal new targets for pharmacological intervention in other neuroinflammatory and neurodegenerative diseases, including AD.
Immunological Impact of Intestinal T Cells on Metabolic Diseases
Authors: Zhou Haiyan , Wang Liwen , Liu Feng
Published: February 2021

Emerging evidence accumulated over the past several years has uncovered intestinal CD4+T cells as an essential mediator in modulating intestinal immunity in health and diseases. It has also been increasingly recognized that dietary and microbiota-derived factors play key roles in shaping the intestinal CD4+T-cell compartment. This review aims to discuss the current understanding on how the intestinal T cell immune responses are disturbed by obesity and metabolic stress. In addition, we review how these changes influence systemic metabolic homeostasis and the T-cell-mediated crosstalk between gut and liver or brain in the progression of obesity and its related diseases. Lastly, we highlight the potential roles of some drugs that target intestinal T cells as a therapeutic treatment for metabolic diseases. A better understanding of the interaction among metabolites, bacterial signals, and T cell immune responses in the gut and their roles in systemic inflammation in metabolic tissues should shed new light on the development of effective treatment of obesity and related disorders.
Changes in Rocky Intertidal Community Structure During a Marine Heatwave in the Northern Gulf of Alaska
Authors: Weitzman Benjamin , Konar Brenda , Iken Katrin , Coletti Heather , Monson Daniel , Suryan Robert , Dean Thomas , Hondolero Dominic , Lindeberg Mandy
Published: February 2021

Marine heatwaves are global phenomena that can have major impacts on the structure and function of coastal ecosystems. By mid-2014, the Pacific Marine Heatwave (PMH) was evident in intertidal waters of the northern Gulf of Alaska and persisted for multiple years. While offshore marine ecosystems are known to respond to these warmer waters, the response of rocky intertidal ecosystems to this warming is unclear. Intertidal communities link terrestrial and marine ecosystems and their resources are important to marine and terrestrial predators and to human communities for food and recreation, while simultaneously supporting a growing coastal tourism industry. Given that current climate change projections suggest increased frequency and duration of marine heatwaves, monitoring and understanding the impacts of heatwaves on intertidal habitats is important. As part of the Gulf Watch Alaska Long-Term Monitoring program, we examined rocky intertidal community structure at 21 sites across four regions spanning 1,200 km of coastline: Western Prince William Sound, Kenai Fjords National Park, Kachemak Bay, and Katmai National Park and Preserve. Sites were monitored annually from 2012 to 2019 at mid and low tidal strata. Before-PMH (2012–2014), community structure differed among regions. We found macroalgal foundation species declined during this period mirroring patterns observed elsewhere for subtidal habitat formers during heatwave events. The region-wide shift from an autotroph-macroalgal dominated rocky intertidal to a heterotroph-filter-feeder dominated state concurrent with the changing environmental conditions associated with a marine heatwave event suggests the PMH had Gulf-wide impacts to the structure of rocky intertidal communities. During/after-PMH (2015–2019), similarities in community structure increased across regions, leading to a greater homogenization of these communities, due to declines in macroalgal cover, driven mostly by a decline in the rockweed,Fucus distichus, and other fleshy red algae in 2015, followed by an increase in barnacle cover in 2016, and an increase in mussel cover in 2017. Strong, large-scale oceanographic events, like the PMH, may override local drivers to similarly influence patterns of intertidal community structure.
Minding the Data-Gap Trap: Exploring Dynamics of Abundant Dolphin Populations Under Uncertainty
Authors: Ashe Erin , Williams Rob , Clark Christopher , Erbe Christine , Gerber Leah R. , Hall Ailsa J. , Hammond Philip S. , Lacy Robert C. , Reeves Randall , Vollmer Nicole L.
Published: February 2021

Preventing declines in common species is key to sustaining the structure and function of marine ecosystems. Yet for many common marine mammals, including oceanic dolphins, statistical power to detect declines remains low due to patchy distribution and large variability in group sizes. In this study, population viability analyses (PVA) were used to model the dynamics of four oceanic dolphin populations off the United States West Coast: eastern North Pacific long-beaked common dolphins (Delphinus delphis capensis), short-beaked common dolphins (D. delphis delphis), Pacific white-sided dolphins (Lagenorhynchus obliquidens), and “offshore” common bottlenose dolphins (Tursiops truncatus). We calibrated the PVA with life-history tables, studies on proxy species, and stock assessment reports. We explored the sensitivity of populations to demographic variation and projected how they may respond to changes in three sublethal threats (prey limitation, ocean noise, and chemical pollution) and one lethal threat (fisheries bycatch). We found the most serious projected declines in long-beaked common dolphins, which showed the lowest birth rate. Most threat scenarios resulted in declines that would not be detected by existing monitoring programs in the United States, which are among the most data-rich surveys of their kind. The cumulative effects of the three sublethal stressors exceeded the effect of the one lethal stressor (fisheries bycatch). To implement pro-active management and monitoring programs, anticipating which cetaceans are more at risk and which anthropogenic threats could cause declines is paramount. Our study highlights the value of model testing with PVA when monitoring data are poor, thereby identifying priorities for future research, monitoring, and management.
Observations of Breaking Internal Tides on the Australian North West Shelf Edge
Authors: Lauton Gustavo , Pattiaratchi Charitha Bandula , Lentini Carlos A. D.
Published: February 2021

A comprehensive observational data set was used to examine shoreward propagating semidiurnal internal tides as they shoal, break and run-up as turbulent boluses across the edge of the Australian North West Shelf (NWS), offshore Dampier, during late winter 2013. The measured waveforms and wavefields supported the grouping of events into two distinct categories: (1) pre-; and, (2) post- wave breaking. It was found that the transition from (1) to (2) was marked by the rise of nonlinear steepening (α) and reduction in dispersion (β), both coefficients that parameterize nonlinear wave effects on the Korteweg-de Vries (KdV) equation. We introduced a criterion for wave breaking from the dimensionless parameter (δ) that relates these two terms: wave breaking occurs when δ < 1. In the first group, dispersive effects were dominant to spread energy out of the semidiurnal wave to a dispersive wave packet of short-period internal solitary waves (ISWs). In the second, dispersion was considered small compared to the cumulative effect of nonlinear steepening. Here, the semidiurnal wave built sufficient energy at its rear face to generate wave breaking, which has been known to produce multiple turbulent boluses. Similar observations have not been described for this region during winter months and highlight that the nonlinear internal wave field is an important feature on the NWS throughout the year. Additionally, measurements obtained through autonomous ocean glider profiles revealed some of the post-breaking characteristics that included intensive vertical mixing and transport of dense water and suspended material onshore of the shelf break.