bluuebunny/crossref_metadata_2025 huggingface dataset:
Bad neighbours: amphibian chytrid fungus Batrachochytrium dendrobatidis infection dynamics in three co-occurring frog species of southern Sydney, Australia
Authors: Crawford-Ash J , Rowley JJL
Published: November 2020

Wildlife disease is a major cause of global biodiversity loss. Amongst the most devastating is the disease chytridiomycosis, caused by the amphibian chytrid fungusBatrachochytrium dendrobatidis(Bd). This disease has contributed to declines and extinctions in hundreds of amphibian species, but not all species are affected equally. Some amphibian hosts are capable of carrying high levels ofBdinfection without population declines, acting as reservoir species for the pathogen and driving population declines in sympatric species. In Australia, several species have been proposed as reservoir species; however, our understanding ofBdis derived from studies that are highly geographically and taxonomically biased, and our ability to extrapolate from these systems is unknown. We examined the prevalence and intensity ofBdinfection in 3 frog species in a previously unstudied host-pathogen system in temperate eastern Australia: the Blue Mountains tree frogLitoria citropa, a poorly-known species predicted to be susceptible toBdinfection; and the common eastern frogletCrinia signiferaand the stony creek frogL. lesueuri, which have both been identified as reservoir species in other regions. We found thatL. citropaandL. lesueuriwere infected withBdat a high prevalence and often high intensity, while the reverse was true forC. signifera. All species were detected at moderate abundance and there was no evidence of morbidity and mortality. Our findings do not supportC. signiferaandL. lesueuribeing reservoir species in this system, highlighting the importance of region-specific studies to inform conservation management.
Biogeography of polychaete worms (Annelida) of the world
Authors: Pamungkas J , Glasby CJ , Costello MJ
Published: November 2020

The global biogeography of polychaete worms has never been assessed previously. In the present study, we studied the world distribution patterns of polychaetes based on datasets obtained from the Global Biodiversity Information Facility, the Ocean Biogeographic Information System and our recently published checklist of Indonesian polychaete species. Polychaete biogeographic regions were visualized using ‘Infomap Bioregions’, and the latitudinal species richness gradient of the animals was examined using 3 metrics, i.e. alpha, gamma and estimated species richness (the last metric was adjusted for sampling bias). We identified 11 major polychaete biogeographic regions. The North Atlantic, Australia and Indonesia were the top 3 species-rich biogeographic regions in the world. The total number of polychaete species was higher in the southern hemisphere (~2100 species, 67 families) than in the northern hemisphere (~1800 species, 75 families) despite significantly more data in the latter (>500000 records compared to >26000 records). Contrary to the classical idea of a unimodal distribution pattern, the latitudinal gradient of polychaetes was generally bimodal with a pronounced dip north of the Equator (15°N). We suggest that the slightly higher peak of species richness in the southern (30°S) than in the northern (60°N) hemisphere reflects higher southern endemicities. These patterns are unlikely to be due to sampling bias but rather represent a natural phenomenon, and we found them most significantly correlated with sea temperature.
Fifteen years in a global warming hotspot: changes in subtidal mobile invertebrate communities
Authors: Mulders YR , Wernberg T
Published: November 2020

Temperate subtidal reefs are increasingly exposed to gradual warming and short periods of high temperatures (marine heatwaves; MHWs). These pressures can directly and indirectly affect the mobile invertebrate communities on these reefs. We investigate changes in mobile invertebrate communities from benthic surveys 15 yr apart (1999-2001 vs 2016-2019), spanning a 4° latitudinal gradient in Western Australia (30-34°S), expecting the biggest changes to the communities in the lower latitudes, where the cumulative effect of MHWs and warming is largest. The urchinsCentrostephanus tenuispinus(warm temperate affinity) andPhyllacanthus irregularis(cool temperate affinity) showed trends toward opposite responses over time; whileP. irregularisdensities declined (non-significantly at all sites),C. tenuispinusdensities increased (significantly at one of 3 sites). The magnitude of the responses appeared to decrease with increasing latitude, withC. tenuispinusrecorded in significantly higher densities only at the lowest latitude location. Neither the densities, nor change in density over time of cool temperate gastropodLunella torquatusand urchinHeliocidaris erythrogrammareflected a latitudinal gradient, suggesting other localized factors play a larger role in determining abundances of these species. However, size distributions ofL. torquatuspopulations at the lower latitude locations were clearly impacted by the 2011 MHW, while those at higher latitudes remained relatively consistent. Overall, the biggest changes over time were seen at the warm edge of the temperate ecosystem. As temperatures continue to rise, the magnitude of these changes is not only expected to increase, but also to occur at higher latitudes.
Paleolityczna kolonizacja południowych rubieży zachodniomałopolskiej wyżyny lessowej / Palaeolithic colonization of the southern border of the Western Lesser Poland loess highlands
Authors: Wilczyński Jarosław
Published: November 2020

This text presents the oldest traces of human settlement from the area of Igołomia and Wawrzeńczyce, Kraków district and adjacent areas. It covers a period of time from about 35,000 to 10,000 years ago, which is the end of the Last Ice Age, when areas of Europe were inhabited by hunter-gatherer groups. Unfortunately, only a very small number of finds come from Poland, and in particular from the area in question. Most often these are single discoveries of Pleistocene megafauna, mainly bones and teeth of a mammoth and a woolly rhinoceros. This study presents, among others, finds from Stręgoborzyce, remains of Pleistocene fauna from Wawrzeńczyce, and a cluster of flint products from Glew discovered on the surface of a field. In addition, the text contains information on sites from the areas of Kraków-Nowa Huta and Jaksice, which are of great importance for learning about Upper Palaeolithic settlement encompassing the microregion, whose central place is now occupied by the commune of Igołomia-Wawrzeńczyce.
/ Schyłek epoki kamienia i początki epoki brązu w okolicach Igołomi i Wawrzeńczyc The end of the Stone Age and the beginning of the Bronze Age in the vicinity of Igołomia and Wawrzeńczyce
Authors: Włodarczak Piotr
Published: November 2020

The borderland of the Vistula Plain and the Proszowice Plateau is part of the loess zone extending mainly to the north of the Vistula River, known for numerous discoveries of archaeological sites from the Eneolithic period and the early Bronze Age. The state of reconnaissance of settlement is far from satisfactory here. From the final Eneolithic period primarily cemeteries of the Corded Ware culture (around 2800–2300 BC) are known. Falling within this age range is probably the only burial mound in the area, in Igołomia, which yielded a niche grave of the Corded Ware culture within the eastern part of its cover. Another cemetery was investigated in Rudno Górne, where niche graves of the culture in question were found dug into the embankments of Funnel Beaker culture megalithic graves from the middle Eneolithic period. From the early Bronze Age, the richest and most cognitively significant sites of the Mierzanowice culture (around 2200–1600 BC) are concentrated on loess hills rising above the valleys of Ropotek and Rudnik. They are both cemeteries and large settlements. Particularly valuable results were obtained during research on the cemetery in Szarbia, where as many as 44 graves were found. These findings enable the reconstruction of funeral rite rules from the early Bronze Age.
Pierwsi Słowianie nad Wisłą w rejonie Krakowa / The first Slavs on the Vistula River in the area of Kraków
Authors: Szmoniewski Bartłomiej
Published: November 2020

The decline of antiquity, the Migration Period, was in Central Europe a time of fundamental changes, the content of which we are only gradually discovering. Stable settlement structures that existed here for centuries have mostly “disappeared” from the archaeological record. A new cultural quality has appeared: the Slavs. Eleven settlements dating back to the Early Slavic phase were discovered between Kraków-Mogiła and Wawrzeńczyce. Residents of these settlements began to arrive on the upper Vistula probably after the middle of the 5th century from eastern Europe, or more precisely from the upper Dnieper basin. In Poland, the earliest early Slavic sites, including those from the vicinity of Igołomia, are referred to as Prague culture. These small settlements consisted of a few semi-sunken dwellings, free-standing ovens and household pits. Handmade pottery has survived in their relics, and much less frequently other products, including “luxury” ones, such as combs, brooches and pendants. The population engaged mainly in agriculture, and non-agricultural production satisfied only domestic needs. Pots were made, wool was spun, fabrics were woven, wood tar was made, unsophisticated ornaments were cast, and iron was smelted from the ore, mainly for tools.
Krew germańska – krew polska. Badania antropologiczne i medyczne mieszkańców Wawrzeńczyc podczas II wojny światowej Germanic blood – Polish blood. Anthropological and medical research of the inhabitants of Wawrzeńczyce during the Second World War
Authors: Maj Małgorzata
Published: November 2020

The text is devoted to anthropological and medical research conducted in 1943 in Wawrzeńczyce, today in Kraków district, by scientists employed at the Institut für Deutsche Ostarbeit (Institute for German Works in the East), a Nazi institution created by Governor Hans Frank in occupied Kraków. One of the sections of this Institute was to review human races within the General Government. Thus, in many localities of southern Poland, people representing various ethnic groups were subjected to anthropological measurements and medical surgeries. Among others, 378 adults were examined in Wawrzeńczyce. This place was selected as an example of a native Polish village. This event was not permanently remembered in the collective memory of the residents, but thanks to the extensive collection of materials from German research discovered after several decades in the National Anthropological Archives in Washington, the basic facts about this event could be reconstructed and the value of the documentation collected at that time could be recovered.
Zagłada Żydów z Wawrzeńczyc w czasie II wojny światowej w świetle akt gminnych / The extermination of the Jews from Wawrzeńczyce during the Second World War in the light of community records
Authors: Swałtek-Niewińska Dagmara
Published: November 2020

The chapter discusses the fate of Jews who lived in Wawrzeńczyce, east of Kraków during the Nazi occupation. It is based mostly on the documentation of the local administration. The fonds were preserved almost intact, which is uncommon for this kind of records from the occupation period. The text explains what kind of information about the situation of Jews can be found in those records, and what was deliberately omitted or conveyed through the use of euphemisms. The information from these records is supplemented by the testimony of survivors and Polish witnesses, submitted after the war. Before the war, only a few Jewish families lived there. In 1940, over 100 Jews from Kraków were relocated to Wawrzeńczyce. One characteristic of the rural area was that no ghettos were established. Therefore, Jews lived among Polish neighbours until the extermination operation of the fall of 1942. The last part of the article discusses the fate of those few Jews who sought shelter among Polish neighbours and the various reactions of Poles to Jews looking for help. The chapter is supplemented by a register of all Jews residing in Wawrzeńczyce in the autumn of 1941. In some cases, it is the last record of those who were killed in the Holocaust.
Persistent spatial gaps in ornithological study in Australia, 1901–2011
Authors: Weston Michael A. , Yarwood Maree R. , Whisson Desley A. , Symonds Matthew R. E.
Published: November 2020

At the continental scale, ecological research effort is not spatially uniform. We used a century-long bibliometric database of the journal Emu – Austral Ornithology to index the spatial patterns in bird research in Australia (from articles with explicit study locations). Studies have been concentrated in Tasmania and the southwest, southeast and coastal parts of the mainland. Large spatial gaps exist in ornithological study, which are similar to those identified by Arnold Robert McGill in his 1948 review paper ( McGill 1948 ). Pre-1948 only 9.4% of articles [n = 2,107] fell within the gaps mapped by McGill in 1948, indicating that his mapping was largely accurate. These gaps have largely persisted; only 11.2% of the 1,498 articles published since 1948 came from within those gaps. We present a complementary spatial gap analysis, which focuses on studies of areas with broadly similar biogeographies (Interim Biogeographical Regions of Australia (IBRAs)). Of 85 mainland IBRAs (of 89 defined), five have no bird studies from within them (368,380 km2; 4.9% of Australia), and 34 have less than 10 studies (3,335,498 km2; 43.9%). We intersect IBRAs with McGill's gaps and show that some IBRAs within McGill's gaps are now better-studied, but 64.8% of the area within the McGill gaps boundaries comprises IBRAs where there have been no post-1948 studies in Emu. We also present an updated map of key geographical gaps in the study of Australian birds, which apparently remain extensive 60 years after they were first identified.
Klein with Lacan: A Study on the Reception of Lacanian Ideas in Uruguay and Its Effects on Clinical Practices (1955–82)
Authors: Grau-Pérez Gonzalo , Milán J. Guillermo
Published: November 2020

In Uruguay, Lacanian ideas arrived in the 1960s, into a context of Kleinian hegemony. Adopting a discursive approach, this study researched the initial reception of these ideas and its effects on clinical practices. We gathered a corpus of discursive data from clinical cases and theoretical-doctrinal articles (from the 1960s, 1970s and 1980s). In order to examine the effects of Lacanian ideas, we analysed the difference in the way of interpreting the clinical material before and after Lacan's reception. The results of this research illuminate some epistemological problems of psychoanalysis, especially the relationship between theory and clinical practice.
Epitranscriptomic(N6-methyladenosine) Modification of Viral RNA and Virus-Host Interactions
Authors: Imam Hasan , Kim Geon-Woo , Siddiqui Aleem
Published: November 2020

N6-methyladenosine (m6A) is the most prevalent and internal modification of eukaryotic mRNA. Multiple m6A methylation sites have been identified in the viral RNA genome and transcripts of DNA viruses in recent years. m6A modification is involved in all the phases of RNA metabolism, including RNA stability, splicing, nuclear exporting, RNA folding, translational modulation, and RNA degradation. Three protein groups, methyltransferases (m6A-writers), demethylases (m6A-erasers), and m6A-binding proteins (m6A-readers) regulate this dynamic reversible process. Here, we have reviewed the role of m6A modification dictating viral replication, morphogenesis, life cycle, and its contribution to disease progression. A better understanding of the m6A methylation process during viral pathogenesis is required to reveal novel approaches to combat the virus-associated diseases.
Coexistence of Pseudomonas aeruginosa With Candida albicans Enhances Biofilm Thickness Through Alginate-Related Extracellular Matrix but Is Attenuated by N-acetyl-l-cysteine
Authors: Phuengmaung Pornpimol , Somparn Poorichaya , Panpetch Wimonrat , Singkham-In Uthaibhorn , Wannigama Dhammika Leshan , Chatsuwan Tanittha , Leelahavanichkul Asada
Published: November 2020

Bacteria and Candidaalbicans are prominent gut microbiota, and the translocation of these organisms into blood circulation might induce mixed-organism biofilms, which warrants the exploration of mixed- versus single-organism biofilms in vitro and in vivo. In single-organism biofilms, Acinetobacter baumannii and Pseudomonas aeruginosa (PA) produced the least and the most prominent biofilms, respectively. C. albicans with P. aeruginosa (PA+CA) induced the highest biofilms among mixed-organism groups as determined by crystal violet straining. The sessile form of PA+CA induced higher macrophage responses than sessile PA, which supports enhanced immune activation toward mixed-organism biofilms. In addition, Candida incubated in pre-formed Pseudomonas biofilms (PA>CA) produced even higher biofilms than PA+CA (simultaneous incubation of both organisms) as determined by fluorescent staining on biofilm matrix (AF647 color). Despite the initially lower bacteria during preparation, bacterial burdens by culture in mixed-organism biofilms (PA+CA and PA>CA) were not different from biofilms of PA alone, supporting Candida-enhanced Pseudomonas growth. Moreover, proteomic analysis in PA>CA biofilms demonstrated high AlgU and mucA with low mucB when compared with PA alone or PA+CA, implying an alginate-related mucoid phenotype in PA>CA biofilms. Furthermore, mice with PA>CA biofilms demonstrated higher bacteremia with more severe sepsis compared with mice with PA+CA biofilms. This is possibly due to the different structures. Interestingly, l-cysteine, a biofilm matrix inhibitor, attenuated mixed-organism biofilms both in vitro and in mice. In conclusion, Candida enhanced Pseudomonas alginate–related biofilm production, and Candida presentation in pre-formed Pseudomonas biofilms might alter biofilm structures that affect clinical manifestations but was attenuated by l-cysteine.
A System Dynamics Approach to Understanding the deep Magma Plumbing System Beneath Dominica (Lesser Antilles)
Authors: Solaro Clara , Balcone-Boissard Hélène , Morgan Daniel Joseph , Boudon Georges , Martel Caroline , Ostorero Léa
Published: November 2020

To understand the dynamics of magmatic systems, one must first seek to characterize the time-dependent behavior of magma storage and ascent. Herein, we do this through a combination of the Crystal System Approach and careful study of Fe-Mg interdiffusion in orthopyroxene. This allows us to trace the pre-eruptive dynamics of magma plumbing systems, both in space and time. We apply this novel approach on two large silicic eruptions (about 3–5 km3 DRE/eruption) that occurred in the central part of Dominica Island (Lesser Antilles Arc): the eruptions of Layou (∼51 ka) from Morne Diablotins, and Roseau (∼33 ka) from Morne Trois Pitons-Micotrin. For the Roseau eruption, two magmatic environments (MEs) are identified on the basis of orthopyroxene composition, with a dominant reverse-zoning pattern from 50 to 54 to 54–59 mol% enstatite (En), indicating interaction with hotter magma. For the Layou eruption, three MEs are observed as represented by three populations of pyroxenes: En47-51, En51-53 and En53-58. The normal-zoning pathway from En51-53 to En47-51 is significantly registered by crystals, interpreted as convective mixing in a zoned reservoir. The reverse-zoning pathway from En47-51 to En51-53 and also En53-58 is also significantly present, supporting the mixing within the zoned reservoir but also suggesting mixing with a hotter magma, possibly stored in another part of a sub-volcanic mush. The crystal and glass compositions (melt inclusion and matrix glass) from both studied eruptions suggest heating and mixing between different magma pockets located within the mush that were the dominant process for mobilizing eruptible magma. In parallel, we constrain the associated pre-eruptive timescales by modeling the diffusive relaxation of Fe-Mg chemical gradients that originated within the zonation of the same orthopyroxene crystals. Diffusion modeling was considered along the b-axis of 66 zoned orthopyroxene crystals for these two eruptions, at a magmatic temperature of 850 ± 25°C. In light of these results, we propose that the Layou and the Roseau magma reservoirs were rejuvenated and heated by ∼25–50°C about 10 years prior to eruption by the injection of an underplating, hotter magma, creating the observed dominant reverse-zoning patterns of the erupted orthopyroxenes. We thus have evidence that silicic mush can be re-mobilized over timescales of decades prior to eruption, as previously suggested for Santorini and Taupo volcanoes.
GmNAC81 Inversely Modulates Leaf Senescence and Drought Tolerance
Authors: Ferreira Dalton O. , Fraga Otto T. , Pimenta Maiana R. , Caetano Hanna D. N. , Machado João Paulo B. , Carpinetti Paola A. , Brustolini Otávio J. B. , Quadros Iana P. S. , Reis Pedro A. B. , Fontes Elizabeth P. B.
Published: November 2020

Glycine max NAC81 (GmNAC81) is a downstream effector of the DCD/NRP-mediated cell death signaling, which interacts with GmNAC30 to fully induce the caspase 1-like vacuolar processing enzyme (VPE) expression, the executioner of the cell death program. GmNAC81 has been previously shown to positively modulate leaf senescence via the NRP/GmNAC81/VPE signaling module. Here, we examined the transcriptome induced by GmNAC81 overexpression and leaf senescence and showed that GmNAC81 further modulates leaf senescence by regulating an extensive repertoire of functionally characterized senescence-associated genes (SAGs). Because the NRP/GmNAC81/VPE signaling circuit also relays stress-induced cell death signals, we examined the effect of GmNAC81 overexpression in drought responses. Enhanced GmNAC81 expression in the transgenic lines increased sensitivity to water deprivation. Under progressive drought, the GmNAC81-overexpressing lines displayed severe leaf wilting, a larger and faster decline in leaf Ψw, relative water content (RWC), photosynthesis rate, stomatal conductance, and transpiration rate, in addition to higher Ci/Ca and lower Fm/Fv ratios compared to the BR16 control line. Collectively, these results indicate that the photosynthetic activity and apparatus were more affected by drought in the transgenic lines. Consistent with hypersensitivity to drought, chlorophyll loss, and lipid peroxidation were higher in the GmNAC81-overexpressing lines than in BR16 under dehydration. In addition to inducing VPE expression, GmNAC81 overexpression uncovered the regulation of typical drought-responsive genes. In particular, key regulators and effectors of ABA signaling were suppressed by GmNAC81 overexpression. These results suggest that GmNAC81 may negatively control drought tolerance not only via VPE activation but also via suppression of ABA signaling.
Distinguishing Glioblastoma Subtypes by Methylation Signatures
Authors: Zhang Yu-Hang , Li Zhandong , Zeng Tao , Pan Xiaoyong , Chen Lei , Liu Dejing , Li Hao , Huang Tao , Cai Yu-Dong
Published: November 2020

Glioblastoma, also called glioblastoma multiform (GBM), is the most aggressive cancer that initiates within the brain. GBM is produced in the central nervous system. Cancer cells in GBM are similar to stem cells. Several different schemes for GBM stratification exist. These schemes are based on intertumoral molecular heterogeneity, preoperative images, and integrated tumor characteristics. Although the formation of glioblastoma is remarkably related to gene methylation, GBM has been poorly classified by epigenetics. To classify glioblastoma subtypes on the basis of different degrees of genes’ methylation, we adopted several powerful machine learning algorithms to identify numerous methylation features (sites) associated with the classification of GBM. The features were first analyzed by an excellent feature selection method, Monte Carlo feature selection (MCFS), resulting in a feature list. Then, such list was fed into the incremental feature selection (IFS), incorporating one classification algorithm, to extract essential sites. These sites can be annotated onto coding genes, such asCXCR4, TBX18, SP5, andTMEM22, and enriched in relevant biological functions related to GBM classification (e.g., subtype-specific functions). Representative functions, such as nervous system development, intrinsic plasma membrane component, calcium ion binding, systemic lupus erythematosus, and alcoholism, are potential pathogenic functions that participate in the initiation and progression of glioblastoma and its subtypes. With these sites, an efficient model can be built to classify the subtypes of glioblastoma.
Aspirin and 5-Aminoimidazole-4-carboxamide Riboside Attenuate Bovine Ephemeral Fever Virus Replication by Inhibiting BEFV-Induced Autophagy
Authors: Tseng Hsu-Hung , Huang Wei-Ru , Cheng Ching-Yuan , Chiu Hung-Chuan , Liao Tsai-Ling , Nielsen Brent L. , Liu Hung-Jen
Published: November 2020

Recent study in our laboratory has demonstrated that BEFV-induced autophagyviaactivation of the PI3K/Akt/NF-κB and Src/JNK pathways and suppression of the PI3K-AKt-mTORC1 pathway is beneficial for virus replication. In the current study, we found that both aspirin and 5-aminoimidazole-4-carboxamide-1-β-riboside (AICAR) siginificantly attenuated virus replication by inhibiting BEFV-induced autophagyviasuppressing the BEFV-activated PI3K/Akt/NF-κB and Src/JNK pathways as well as inducing reversion of the BEFV-suppressed PI3K-Akt-mTORC1 pathway. AICAR reversed the BEFV-activated PI3K/Akt/NF-κB and Src/JNK pathways at the early to late stages of infection and induced reversion of the BEFV-suppressed PI3K-AKt-mTORC1 pathway at the late stage of infection. Our findings reveal that inhibition of BEFV-induced autophagy by AICAR is independent of AMPK. Furthermore, we found that AICAR transcriptionally downregulates the ATG related genes ULK1, Beclin 1, and LC3 and enhances Atg7 degradation by the proteasome pathway. Aspirin suppresses virus replication by inhibiting BEFV-induced autophagy. It directly suppressed the NF-κB pathway and reversed the BEFV-activated Src/JNK pathway at the early stage of infection and reversed the BEFV-suppressed PI3K/Akt/mTOR pathway at the late stage of infection. The current study provides mechanistic insights into the effects of aspirin and AICAR on BEFV replication through suppression of BEFV-induced autophagy.
Host Genetics Background Influence in the Intragastric Trypanosoma cruzi Infection
Authors: Domingues Carolina Salles , Cardoso Flávia de Oliveira , Hardoim Daiana de Jesus , Pelajo-Machado Marcelo , Bertho Alvaro Luiz , Calabrese Kátia da Silva
Published: November 2020

Background

Considering the complexity of the factors involved in the immunopathology of Chagas disease, which influence the Chagas’ disease pathogenesis, anti-T. cruzi immune response, and chemotherapy outcome, further studies are needed to improve our understanding about these relationships. On this way, in this article we analyzed the host genetic influence on hematological, histopathological and immunological aspects after T. cruzi infection.

Methods

BALB/c and A mice were intragastrically infected with T. cruzi SC2005 strain, isolated from a patient of an outbreak of Chagas disease. Parameters such as parasite load, survival rates, cytokines production, macrophages, T and B cell frequencies, and histopathology analysis were carried out.

Results

BALB/c mice presented higher parasitemia and mortality rates than A mice. Both mouse lineages exhibited hematological alterations suggestive of microcytic hypochromic anemia and histopathological alterations in stomach, heart and liver. The increase of CD8+ T cells, in heart, liver and blood, and the increase of CD19+ B cells, in liver, associated with a high level of proinflammatory cytokines (IL-6, TNF-α, IFN-γ), confer a resistance profile to the host. Although BALB/c animals exhibited the same findings observed in A mice, the response to infection occurred later, after a considerable parasitemia increase. By developing an early response to the infection, A mice were found to be less susceptible to T. cruzi SC2005 infection.

Conclusions

Host genetics background shaping the response to infection. The early development of a cytotoxic cellular response profile with the production of proinflammatory cytokines is important to lead a less severe manifestation of Chagas disease.
Cytomegalovirus-Specific T Cell Epitope Recognition in Congenital Cytomegalovirus Mother-Infant Pairs
Authors: Materne Emma C. , Lilleri Daniele , Garofoli Francesca , Lombardi Giuseppina , Furione Milena , Zavattoni Maurizio , Gibson Laura
Published: November 2020

Background: Congenital cytomegalovirus (cCMV) infection is the most common infection acquired before birth and from which about 20% of infants develop permanent neurodevelopmental effects regardless of presence or absence of symptoms at birth. Viral escape from host immune control may be a mechanism of CMV transmission and infant disease severity. We sought to identify and compare CMV epitopes recognized by mother-infant pairs. We also hypothesized that if immune escape were occurring, then one pattern of longitudinal CD8 T cell responses restricted by shared HLA alleles would be maternal loss (by viral escape) and infant gain (by viral reversion to wildtype) of CMV epitope recognition.

Methods: The study population consisted of 6 women with primary CMV infection during pregnancy and their infants with cCMV infection. CMV UL83 and UL123 peptides with known or predicted restriction by maternal MHC class I alleles were identified, and a subset was selected for testing based on several criteria. Maternal or infant cells were stimulated with CMV peptides in the IFN-γ ELISpot assay.

Results: Overall, 14 of 25 (56%; 8 UL83 and 6 UL123) peptides recognized by mother-infant pairs were not previously reported as CD8 T cell epitopes. Of three pairs with longitudinal samples, one showed maternal loss and infant gain of responses to a CMV epitope restricted by a shared HLA allele.

Conclusions: CD8 T cell responses to multiple novel CMV epitopes were identified, particularly in infants. Moreover, the hypothesized pattern of CMV immune escape was observed in one mother-infant pair. These findings emphasize that knowledge of paired CMV epitope recognition allows exploration of viral immune escape that may operate within the maternal-fetal system. Our work provides rationale for future studies of this potential mechanism of CMV transmission during pregnancy or clinical outcomes of infants with cCMV infection.
CD4+CD8+ T-Lymphocytes in Xenogeneic and Human Graft-versus-Host Disease
Authors: Alhaj Hussen Kutaiba , Michonneau David , Biajoux Vincent , Keita Seydou , Dubouchet Laetitia , Nelson Elisabeth , Setterblad Niclas , Le Buanec Helene , Bouaziz Jean-David , Guimiot Fabien , Socié Gérard , Canque Bruno
Published: November 2020

Mechanisms driving acute graft-versus-host disease (aGVHD) onset in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are still poorly understood. To provide a detailed characterization of tissue-infiltrating T lymphocytes (TL) and search for eventual site-specific specificities, we developed a xenogeneic model of aGVHD in immunodeficient mice. Phenotypic characterization of xenoreactive T lymphocytes (TL) in diseased mice disclosed a massive infiltration of GVHD target organs by an original CD4+CD8+TL subset. Immunophenotypic and transcriptional profiling shows that CD4+CD8+TL comprise a major PD1+CD62L−/+transitional memory subset (>60%) characterized by low level expression of cytotoxicity-related transcripts. CD4+CD8+TL produce high IL-10 and IL-13 levels, and low IL-2 and IFN-γ, suggestive of regulatory function. In vivo tracking of genetically labeled CD4+or CD8+TL subsequently found that CD4+CD8+TL mainly originate from chronically activated cytotoxic TL (CTL). On the other hand, phenotypic profiling of CD3+TL from blood, duodenum or rectal mucosa in a cohort of allo-HSCT patients failed to disclose abnormal expansion of CD4+CD8+TL independent of aGVHD development. Collectively, our results show that acquisition of surface CD4 by xenoreactive CD8+CTL is associated with functional diversion toward a regulatory phenotype, but rule out a central role of this subset in the pathogenesis of aGVHD in allo-HSCT patients.
Immuno-Modulation of Hematopoietic Stem and Progenitor Cells in Inflammation
Authors: Sezaki Maiko , Hayashi Yoshikazu , Wang Yuxin , Johansson Alban , Umemoto Terumasa , Takizawa Hitoshi
Published: November 2020

Lifelong blood production is maintained by bone marrow (BM)-residing hematopoietic stem cells (HSCs) that are defined by two special properties: multipotency and self-renewal. Since dysregulation of either may lead to a differentiation block or extensive proliferation causing dysplasia or neoplasia, the genomic integrity and cellular function of HSCs must be tightly controlled and preserved by cell-intrinsic programs and cell-extrinsic environmental factors of the BM. The BM had been long regarded an immune-privileged organ shielded from immune insults and inflammation, and was thereby assumed to provide HSCs and immune cells with a protective environment to ensure blood and immune homeostasis. Recently, accumulating evidence suggests that hemato-immune challenges such as autoimmunity, inflammation or infection elicit a broad spectrum of immunological reactions in the BM, and in turn, influence the function of HSCs and BM environmental cells. Moreover, in analogy with the emerging concept of “trained immunity”, certain infection-associated stimuli are able to train HSCs and progenitors to produce mature immune cells with enhanced responsiveness to subsequent challenges, and in some cases, form an inflammatory or infectious memory in HSCs themselves. In this review, we will introduce recent findings on HSC and hematopoietic regulation upon exposure to various hemato-immune stimuli and discuss how these challenges can elicit either beneficial or detrimental outcomes on HSCs and the hemato-immune system, as well as their relevance to aging and hematologic malignancies.
Dynamics of Transforming Growth Factor (TGF)-β Superfamily Cytokine Induction During HIV-1 Infection Are Distinct From Other Innate Cytokines
Authors: Dickinson Matthew , Kliszczak Anna E. , Giannoulatou Eleni , Peppa Dimitra , Pellegrino Pierre , Williams Ian , Drakesmith Hal , Borrow Persephone
Published: November 2020

Human immunodeficiency virus type 1 (HIV-1) infection triggers rapid induction of multiple innate cytokines including type I interferons, which play important roles in viral control and disease pathogenesis. The transforming growth factor (TGF)-β superfamily is a pleiotropic innate cytokine family, some members of which (activins and bone morphogenetic proteins (BMPs)) were recently demonstrated to exert antiviral activity against Zika and hepatitis B and C viruses but are poorly studied in HIV-1 infection. Here, we show that TGF-β1is systemically induced with very rapid kinetics (as early as 1–4 days after viremic spread begins) in acute HIV-1 infection, likely due to release from platelets, and remains upregulated throughout infection. Contrastingly, no substantial systemic upregulation of activins A and B or BMP-2 was observed during acute infection, although plasma activin levels trended to be elevated during chronic infection. HIV-1 triggered production of type I interferons but not TGF-β superfamily cytokines from plasmacytoid dendritic cells (DCs)in vitro, putatively explaining their differingin vivoinduction; whilst lipopolysaccharide (but not HIV-1) elicited activin A production from myeloid DCs. These findings underscore the need for better definition of the protective and pathogenic capacity of TGF-β superfamily cytokines, to enable appropriate modulation for therapeutic purposes.
Multiphase Model for the Prediction of Shrinkage Cavity, Inclusion and Macrosegregation in a 36-Ton Steel Ingot
Authors: Xie Mengye , Shen Houfa
Published: November 2020

A five-phase model consisting of a liquid phase, columnar dendrites, equiaxed grains, air, and inclusion (discrete phase) is developed to predict the shrinkage cavity, inclusion distribution and macrosegregation simultaneously during solidification of a 36-ton steel ingot. The air phase is introduced to feed the shrinkage cavity and no mass or species exchange with other phases occurs. The transport and entrapment of inclusions are simulated using a Lagrangian approach. The predicted results agree well with the experimental results. The characteristics of inclusion distribution are better understood. A thin layer of inclusions tends to form close to the mold wall, and more inclusions reside in the last solidified segregation channels. The inclusion is easy to aggregate near the riser neck, and it is dragged by the solidification shrinkage. The influence of the inclusion on macrosegregation is comparatively small, while the solidification shrinkage affects the formation of macrosegregation significantly and makes the simulation result more accurate.
Severity of Anosmia as an Early Symptom of COVID-19 Infection May Predict Lasting Loss of Smell
Authors: Lechien Jerome R. , Journe Fabrice , Hans Stephane , Chiesa-Estomba Carlos M. , Mustin Vincent , Beckers Eline , Vaira Luigi A. , De Riu Giacomo , Hopkins Claire , Saussez Sven
Published: November 2020

Introduction:To evaluate the recovery rate of loss of smell (LOS) with objective olfactory testing in COVID-19 patients.

Methods:Adults with confirmed COVID-19 and self-reported sudden LOS were prospectively recruited through a public call from the University of Mons (Belgium). Epidemiological and clinical data were collected using online patient-reported outcome questionnaires. Patients benefited from objective olfactory evaluation (Sniffin-Sticks-test) and were invited to attend for repeated evaluation until scores returned to normal levels.

Results:From March 22 to May 22, 2020, 88 patients with sudden-onset LOS completed the evaluations. LOS developed after general symptoms in 44.6% of cases. Regarding objective evaluation, 22 patients (25.0%) recovered olfaction within 14 days following the onset of LOS. The smell function recovered between the 16th and the 70th day post-LOS in 48 patients (54.5%). At the time of final assessment at 2 months, 20.5% of patients (N= 18) had not achieved normal levels of olfactory function. Higher baseline severity of olfactory loss measured using Sniffin-Sticks was strongly predictive of persistent loss (p< 0.001).

Conclusion:In the first 2 months, 79.5% of patients may expect to have complete recovery of their olfactory function. The severity of olfactory loss, as detected at the first Sniffin-Sticks-test, may predict the lack of mid-term recovery.
Fibrotic Changes Depicted by Thin-Section CT in Patients With COVID-19 at the Early Recovery Stage: Preliminary Experience
Authors: Yang Zhen Lu , Chen Chong , Huang Lu , Zhou Shu Chang , Hu Yu Na , Xia Li Ming , Li Yan
Published: November 2020

Objectives: To analyze follow-up CTs of patients recovering from COVID-19 in Wuhan, focusing on fibrotic change and its relevant risk factors.

Methods: From January 13 to February 27, 2020, 166 hospitalized patients meeting our criteria were included. The scores of fibrotic patterns on follow-up CT were evaluated. Patients were designated as group 1 (with CT evidence of fibrotic pattern) and group 2 (without CT evidence of fibrotic pattern). Multivariate logistic regression was performed to explore risk factors for fibrotic change in patients with COVID-19.

Results: The follow-up CTs were obtained on 56 days (median, IQR 51–63 days) after symptom onset. Of the 166 patients (mean age, 57 ± 15 years; 69/166 male), 46% (76/166) had CT evidence of fibrotic change and 77% (127/166) were severe or critical cases. Among patients with fibrotic change on CT, 84% (64/76) got a minimal or mild score of fibrosis. The high total score on peak CT, peak eosinophils, erythrocyte sedimentation rate (ESR) and advancing age were related to lung fibrotic change in patients with COVID-19.

Conclusion: Forty six percentages of patients (mainly severe or critical cases) with COVID-19 showed fibrotic change on follow-up CT at early recovery phase, while the extent of fibrosis was not large. The advancing age, high total score on peak CT, peak eosinophils and ESR were associated with fibrotic change depicted by CT in patients recovering from COVID-19. An extended follow up by CT imaging and pulmonary function testing is necessary to fully assess the sequela of COVID-19.
Fecal Klebsiella pneumoniae Carriage Is Intermittent and of High Clonal Diversity
Authors: Lepuschitz Sarah , Hauser Kathrin , Schriebl Agnes , Schlagenhaufen Claudia , Stöger Anna , Chakeri Ali , Vötsch Kornelia , Pekard-Amenitsch Shiva , Springer Burkhard , Allerberger Franz , Ruppitsch Werner
Published: November 2020

The Klebsiella pneumoniae complex comprises several closely related entities, which are ubiquitous in the natural environment, including in plants, animals, and humans. K. pneumoniae is the major species within this complex. K. pneumoniae strains are opportunistic pathogens and a common cause of healthcare-associated infections. K. pneumoniae can colonize the human gastrointestinal tract, which may become a reservoir for infection. The aim of this study was to investigate the fecal K. pneumoniae carriage in six healthy individuals during a 1 year period. Stool samples were obtained once a week. Using direct and pre-enriched cultures streaked on ampicillin-supplemented agar plates, up to eight individual colonies per positive sample were selected for further characterization. Whole genome sequencing (WGS) was performed for strain characterization. Sequence type (ST), core genome complex type (CT), K and O serotypes, virulence traits, antibiotic resistance profiles, and plasmids were extracted from WGS data. In total, 80 K. pneumoniae isolates were obtained from 48 positive cultures of 278 stool samples from five of the six test subjects. The samples of the five colonized volunteers yielded at most two, three, four (two persons), and five different strains, respectively. These 80 K. pneumoniae isolates belonged to 60 STs, including nine new STs; they were of 70 CTs, yielded 48 K serotypes, 11 O serotypes, and 39 wzc and 51 wzi alleles. Four of the five subjects harbored serotypes K20 and K47, as well as STs ST37, ST101, ST1265, and ST20, which had previously been linked to high-risk K. pneumoniae clones. In total, 25 genes conferring antibiotic resistance and 42 virulence genes were detected among all 80 isolates. Plasmids of 15 different types were found among 65 of the isolates. Fecal carriage of individual strains was of short duration: 70 strains were found on a single sampling day only, and 5 strains were isolated in samples collected over two consecutive weeks. Two of the five colonized individuals—working colleagues having meals together—shared identical K. pneumoniae types four times during the study period. Our findings point toward the potential role of food as a reservoir for K. pneumoniae in humans.
Genome Organization of a New Double-Stranded RNA LA Helper Virus From Wine Torulaspora delbrueckii Killer Yeast as Compared With Its Saccharomyces Counterparts
Authors: Ramírez Manuel , Velázquez Rocío , Maqueda Matilde , Martínez Alberto
Published: November 2020

Wine killer yeasts such as killer strains ofTorulaspora delbrueckiiandSaccharomyces cerevisiaecontain helper large-size (4.6 kb) dsRNA viruses (V-LA) required for the stable maintenance and replication of killer medium-size dsRNA viruses (V-M) which bear the genes that encode for the killer toxin. The genome of the new V-LA dsRNA from theT. delbrueckiiKbarr1 killer yeast (TdV-LAbarr1) was characterized by high-throughput sequencing (HTS). The canonical genome of TdV-LAbarr1 shares a high sequence identity and similar genome organization with itsSaccharomycescounterparts. It contains all the known conserved motifs predicted to be necessary for virus translation, packaging, and replication. Similarly, the Gag-Pol amino-acid sequence of this virus contains all the features required for cap-snatching and RNA polymerase activity, as well as the expected regional variables previously found in other LA viruses. Sequence comparison showed that two main clusters (99.2–100% and 96.3–98.8% identity) include most LA viruses fromSaccharomyces, with TdV-LAbarr1 being the most distant from all these viruses (61.5–62.5% identity). Viral co-evolution and cross transmission between different yeast species are discussed based on this sequence comparison. Additional 5′ and 3′ sequences were found in the TdV-LAbarr1 genome as well as in some newly sequenced V-LA genomes fromS. cerevisiae. A stretch involving the 5′ extra sequence of TdV-LAbarr1 is identical to a homologous stretch close to the 5′ end of the canonical sequence of the same virus (self-identity). Our modeling suggests that these stretches can form single-strand stem loops, whose unpaired nucleotides could anneal to create an intramolecular kissing complex. Similar stem loops are also found in the 3′ extra sequence of the same virus as well as in the extra sequences of some LA viruses fromS. cerevisiae. A possible origin of these extra sequences as well as their function in obviating ssRNA degradation and allowing RNA transcription and replication are discussed.
High Levels of Within-Host Variations of Human Papillomavirus 16 E1/E2 Genes in Invasive Cervical Cancer
Authors: Hirose Yusuke , Yamaguchi-Naka Mayuko , Onuki Mamiko , Tenjimbayashi Yuri , Tasaka Nobutaka , Satoh Toyomi , Tanaka Kohsei , Iwata Takashi , Sekizawa Akihiko , Matsumoto Koji , Kukimoto Iwao
Published: November 2020

Human papillomavirus type 16 (HPV16) is the most common HPV genotype found in invasive cervical cancer (ICC). Recent comprehensive genomics studies of HPV16 have revealed that a large number of minor nucleotide variations in the viral genome are present in each infected woman; however, it remains unclear whether such within-host variations of HPV16 are linked to cervical carcinogenesis. Here, by employing next-generation sequencing approaches, we explored the mutational profiles of the HPV16 genome within individual clinical specimens from ICC (n= 31) and normal cervix (n= 21) in greater detail. A total of 367 minor nucleotide variations (167 from ICC and 200 from the normal cervix) were detected throughout the viral genome in both groups, while nucleotide variations at high frequencies (>10% abundance in relative read counts in a single sample) were more prevalent in ICC (10 in ICC versus 1 in normal). Among the high-level variations found in ICC, six were located in theE1/E2genes, and all of them were non-synonymous substitutions (Q142K, M207I, and L262V for E1; D153Y, R302T, and T357A for E2).In vitrofunctional analyses of these E1/E2 variants revealed that E1/M207I, E2/D153Y, and E2/R302T had reduced abilities to support viral replication, and that E2/D153Y and E2/R302T failed to suppress the viral early promoter. These results imply that some within-host variations ofE1/E2present at high levels in ICC may be positively selected for and contribute to cervical cancer development through dysfunction or de-stabilization of viral replication/transcription proteins.