GERMINATION OF RESTING STAGES OF DIATOMS AND DINOFLAGELLATES IN MARINE SEDIMENTS FROM TWO UPWELLING AREAS OF CHILE

Con el fin de evaluar la potencial germinación de los estados de resistencia de las diatomeas y dinofiagelados preservados en sedimentos superficiales, se cultivaron bajo condiciones de laboratorio sedimentos de las bahías de Mejillones (23° S) y Concepción (36° S), Chile: Ciclo L:0 12:12 h, intensidad de luz 140 umol m²s_1, temperatura ambiente y 35,4 unidades de salinidad. Las principales especies de diatomeas presentes en los sedimentos fueron Skeletonema japonicum y esporas de Chaetoceros. Los quistes de dinofiagelados estuvieron representados por Diplopsalis, Scrippsiella, Woloszynskia y las especies Protoperidinium avellanum y P. leonis. Después de 20 días de cultivo, se registró germinación y crecimiento de S. japonicum y de varias especies de Chaetoceros, sin embargo su abundancia fue baja. Las diatomeas con crecimiento abundante fueron Stauroneis legleri, Pseudostaurosira trainorii, Pseudostaurosira sp.l, Pseudostaurosira sp. 2 y Navícula pseudoreinhardtii. El dinoflagelado Woloszynskia sp. también germinó y creció abundantemente. Este trabajo incluye una breve descripción de las especies cultivadas y algunos aspectos de su ecología. Se discuten las posibles causas de la pobre germinación de las diatomeas planctónicas, siendo la baja concentración de oxígeno disuelto en las aguas de fondo uno de los principales factores que presumiblemente afectaron la sobrevivencia de las esporas de resistencia. With the aim to assess germination of diatom and dinofiagellates resting spores we cultured under laboratory conditions surface sediments collected in the Mejillones Bay (23° S) and off Concepción (36° S), Chile. These sediments were cultured in the laboratory with a 12:12 h L/D cycle, light intensity of 140 umol m² s"¹, at room temperature, and with a salinity of 35.4 units. The main diatom species in the sediments were Skeletonema japonicum and Chaetoceros spores. Dinofiagellate cysts were represented by the genera Diplopsalis, Scrippsiella, and Woloszynskia and the species Protoperidinium avellanum and P. leonis. After 20 days of culturing, germination and growth was recorded for S. japonicum and several of the Chaetoceros species, although their abundance was low. The diatoms with abundant growth were Stauroneis legleri, Pseudostaurosira trainorii, Pseudostaurosira sp.l, Pseudostaurosira sp. 2, and Navícula pseudoreinhardtii. The dinofiagellate Woloszynskia sp. also germinated and grew abundantly in the culture. This study includes a brief description of the cultured species and some aspects of their ecology. In addition, we discuss the possible causes for low levels of germination in planktonic diatoms, finding low dissolved oxygen concentrations in the bottom waters to be one of the main factors that presumably affected the survival of resting spores in the sediment

Risk Factors For Bartonella Species Infection In Blood Donors From Southeast Brazil

Bacteria from the genus Bartonella are emerging blood-borne bacteria, capable of causing long-lasting infection in marine and terrestrial mammals, including humans. Bartonella are generally well adapted to their main host, causing persistent infection without clinical manifestation. However, these organisms may cause severe disease in natural or accidental hosts. In humans, Bartonella species have been detected from sick patients presented with diverse disease manifestations, including cat scratch disease, trench fever, bacillary angiomatosis, endocarditis, polyarthritis, or granulomatous inflammatory disease. However, with the advances in diagnostic methods, subclinical bloodstream infection in humans has been reported, with the potential for transmission through blood transfusion been recently investigated by our group. The objective of this study was to determine the risk factors associated with Bartonella species infection in asymptomatic blood donors presented at a major blood bank in Southeastern Brazil. Five hundred blood donors were randomly enrolled and tested for Bartonella species infection by specialized blood cultured coupled with high-sensitive PCR assays. Epidemiological questionnaires were designed to cover major potential risk factors, such as age, gender, ethnicity, contact with companion animals, livestock, or wild animals, bites from insects or animal, economical status, among other factors. Based on multivariate logistic regression, bloodstream infection with B. henselae or B. clarridgeiae was associated with cat contact (adjusted OR: 3.4, 95% CI: 1.1-9.6) or history of tick bite (adjusted OR: 3.7, 95% CI: 1.3-13.4). These risk factors should be considered during donor screening, as bacteremia by these Bartonella species may not be detected by traditional laboratory screening methods, and it may be transmitted by blood transfusion.103Faculty Grant in Global HealthFAEPEX - UNICAMP (Fundo de Apoio ao Ensino, a Pesquisa e a Extensao - UNICAMP)Office of the Vice President for Research and Biotechnology, Western University, Western University of Health Sciences, Pomona, C

A Poly-N-Acetylglucosamine−Shiga Toxin Broad-Spectrum Conjugate Vaccine for Shiga Toxin-Producing Escherichia coli

ABSTRACT Many pathogens produce the β-(1−6)-linked poly-N-acetylglucosamine (PNAG) surface polysaccharide that is being developed as a broadly protective antimicrobial vaccine. However, it is unknown whether systemically injected PNAG vaccines or antibodies would provide protective immunity against pathogens confined to the gastrointestinal tract such as Shiga toxin (Stx)-producing Escherichia coli (STEC), an important group of gastrointestinal (GI) pathogens for which effective immunotherapeutics are lacking. To ascertain whether systemic IgG antibody to PNAG impacts this infectious situation, a vaccine consisting of a synthetic nonamer of nonacetylated PNAG, 9GlcNH2, conjugated to the Shiga toxin 1b subunit (9GlcNH2-Stx1b) was produced. Rabbit antibodies raised to the conjugate vaccine were tested for bacterial killing and toxin neutralization in vitro and protection against infection in infant mice. Cell surface PNAG was detected on all 9 STEC isolates tested, representing 6 STEC serogroups, including E. coli O157:H7. Antibody to the 9GlcNH2-Stx1b conjugate neutralized Stx1 potently and Stx2 modestly. For O157:H7 and O104:H4 STEC strains, antibodies elicited by the 9GlcNH2-Stx1b conjugate possessed opsonic killing and bactericidal activity. Following intraperitoneal injection, antibodies to both PNAG and Stx were needed for infant mouse protection against O157 STEC. These antibodies also mediated protection against the Stx2-producing O104:H4 strain that was the cause of a recent outbreak in Germany, although sufficient doses of antibody to PNAG alone were protective against this strain in infant mice. Our observations suggest that vaccination against both PNAG and Stx, using a construct such as the 9GlcNH2-Stx1b conjugate vaccine, would be protective against a broad range of STEC serogroups

Cold-Inducible RNA Binding Protein as a Vaccination Platform to Enhance Immunotherapeutic Responses against Hepatocellular Carcinoma

Therapies based on immune checkpoint inhibitors (ICPI) have yielded promising albeit limited results in patients with hepatocellular carcinoma (HCC). Vaccines have been proposed as combination partners to enhance response rates to ICPI. Thus, we analyzed the combined effect of a vaccine based on the TLR4 ligand cold-inducible RNA binding protein (CIRP) plus ICPI. Mice were immunized with vaccines containing ovalbumin linked to CIRP (OVA-CIRP), with or without ICPI, and antigen-specific responses and therapeutic efficacy were tested in subcutaneous and orthotopic mouse models of liver cancer. OVA-CIRP elicited polyepitopic T-cell responses, which were further enhanced when combined with ICPI (anti-PD-1 and anti-CTLA-4). Combination of OVA-CIRP with ICPI enhanced ICPI-induced therapeutic responses when tested in subcutaneous and intrahepatic B16-OVA tumors, as well as in the orthotopic PM299L HCC model. This effect was associated with higher OVA-specific T-cell responses in the periphery, although many tumor-infiltrating lymphocytes still displayed an exhausted phenotype. Finally, a new vaccine containing human glypican-3 linked to CIRP (GPC3-CIRP) induced clear responses in humanized HLA-A2.01 transgenic mice, which increased upon combination with ICPI. Therefore, CIRP-based vaccines may generate anti-tumor immunity to enhance ICPI efficacy in HCC, although blockade of additional checkpoint molecules and immunosuppressive targets should be also considered

Bartonella Clarridgeiae Bacteremia Detected In An Asymptomatic Blood Donor.

Human exposure to Bartonella clarridgeiae has been reported only on the basis of antibody detection. We report for the first time an asymptomatic human blood donor infected with B. clarridgeiae, as documented by enrichment blood culture, PCR, and DNA sequencing.53352-

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer.

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM -/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

A network analysis to identify mediators of germline-driven differences in breast cancer prognosis.

Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis

Prevalence of SARS-CoV-2 and co-occurrence/co-infection with malaria during the first wave of the pandemic (the Burkina Faso case)

Africa accounts for 1.5% of the global coronavirus disease 2019 (COVID-19) cases and 2.7% of deaths, but this low incidence has been partly attributed to the limited testing capacity in most countries. In addition, the population in many African countries is at high risk of infection with endemic infectious diseases such as malaria. Our aim is to determine the prevalence and circulation of SARS-CoV-2 variants, and the frequency of co-infection with the malaria parasite. We conducted serological tests and microscopy examinations on 998 volunteers of different ages and sexes in a random and stratified population sample in Burkina-Faso. In addition, nasopharyngeal samples were taken for RT-qPCR of SARS-COV-2 and for whole viral genome sequencing. Our results show a 3.2% and a 2.5% of SARS-CoV-2 seroprevalence and PCR positivity; and 22% of malaria incidence, over the sampling period, with marked differences linked to age. Importantly, we found 2 cases of confirmed co-infection and 8 cases of suspected co-infection mostly in children and teenagers. Finally, we report the genome sequences of 13 SARS-CoV-2 isolates circulating in Burkina Faso at the time of analysis, assigned to lineages: A.19, A.21, B.1.1.404, B.1.1.118, B.1 and grouped into clades; 19B, 20A and 20B. This is the first population-based study about SARS-CoV-2 and malaria in Burkina Faso during the first wave of the pandemic, providing a relevant estimation of the real prevalence of SARS-CoV-2 and variants circulating in this Sub-Saharan African country. Besides, it highlights the low frequency of co-infection with malaria in African communities.This research work received funding from by the European Commission NextGenerationEU (Regulation EU 2020/2094) and grant 202020E159 through CSIC Global Health Platform (PTI Salud Global).N

Prevalence of occult hepatitis B infection among blood donors in Saint Petersburg

The aim of this study was to assess the prevalence of occult hepatitis B infection among blood donors in St. Petersburg, as well as to characterize the identified virus isolates. The study material was represented by 2800 blood plasma samples collected in 2019 from blood donors living in St. Petersburg. The ELISA study for HBV marker rate consisted of HBsAg, anti-HBs IgG, anti-HBcore IgG. HBV DNA was analyzed by nested PCR with real-time hybridization-fluorescence detection on three targets allowing to determine virus DNA at low viral load, including HBsAg-negative chronic hepatitis B. Hepatitis B serological markers were detected in 69.43% of those surveyed, HBsAg was found in 0.43% of individuals, and all of which donated blood first time. A significant excess of the anti-HBcore IgG antibodies occurrence among primary donors (15.1%) compared with repeated/regular donors (7.48%) was shown. The prevalence of virus DNA in the group was 3.14%, including 2.71% of cases in HBsAg-negative CHB. Based on phylogenetic analysis of 88 isolates, HBV subgenotypes were determined in the following order: D1 and D2, 40.91% each, D3 and A2, 9.09% each. While determining the serological subtype in detected isolates, the serotype ayw3 (52.27%) vs ayw2 (46.59%) and adw2 (10.23%) prevailed. Drug resistance mutations, including compensatory ones, were detected in six examined patients (6.82%). In all genotype D isolates, multiple amino acid substitutions were identified in the RT, SHB, MHB, LHB, and Core regions; mutations in the preCore region were detected in 21.59% samples. In the MHR of the HBV genotype D genome, twenty-six positions were identified in which amino acid substitutions occurred, and all isolates showed modifications at positions 113, 114, 131, 134, 159, 161, 168, in 76 — at position 122, in 68 — at position 127, in 36 — at position 118, in 24 — at position 128. In HBV A2 isolates, mutations T113S, S143T, Y161F were identified. Nine isolates in the preCore region showed a polymorphism including a stop codon W28*W; in five isolates the W28S substitution was shown in the same position, and the W28*S variant was found in one more sample. The high incidence of HBsAg-negative CHB cases among blood donors, as well as the predominance of HBV isolates that simultaneously carry mutations resulting in diagnostic failure of HBsAg tests and prophylactic failure of immunoglobulin or vaccines and virus reactivation, mutations that contribute to disease progression obviously pose a threat to health and require to be further examined

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio