A dynamical measure of the black hole mass in a quasar 11 billion years ago.

Tight relationships exist in the local Universe between the central stellar properties of galaxies and the mass of their supermassive black hole (SMBH)1-3. These suggest that galaxies and black holes co-evolve, with the main regulation mechanism being energetic feedback from accretion onto the black hole during its quasar phase4-6. A crucial question is how the relationship between black holes and galaxies evolves with time; a key epoch to examine this relationship is at the peaks of star formation and black hole growth 8-12 billion years ago (redshifts 1-3)7. Here we report a dynamical measurement of the mass of the black hole in a luminous quasar at a redshift of 2, with a look back in time of 11 billion years, by spatially resolving the broad-line region (BLR). We detect a 40-µas (0.31-pc) spatial offset between the red and blue photocentres of the Hα line that traces the velocity gradient of a rotating BLR. The flux and differential phase spectra are well reproduced by a thick, moderately inclined disk of gas clouds within the sphere of influence of a central black hole with a mass of 3.2 × 108 solar masses. Molecular gas data reveal a dynamical mass for the host galaxy of 6 × 1011 solar masses, which indicates an undermassive black hole accreting at a super-Eddington rate. This suggests a host galaxy that grew faster than the SMBH, indicating a delay between galaxy and black hole formation for some systems.

Test of the Einstein Equivalence Principle near the Galactic Center Supermassive Black Hole.

During its orbit around the four million solar mass black hole Sagittarius A* the star S2 experiences significant changes in gravitational potential. We use this change of potential to test one part of the Einstein equivalence principle: the local position invariance (LPI). We study the dependency of different atomic transitions on the gravitational potential to give an upper limit on violations of the LPI. This is done by separately measuring the redshift from hydrogen and helium absorption lines in the stellar spectrum during its closest approach to the black hole. For this measurement we use radial velocity data from 2015 to 2018 and combine it with the gravitational potential at the position of S2, which is calculated from the precisely known orbit of S2 around the black hole. This results in a limit on a violation of the LPI of |ß_{He}-ß_{H}|=(2.4±5.1)×10^{-2}. The variation in potential that we probe with this measurement is six magnitudes larger than possible for measurements on Earth, and a factor of 10 larger than in experiments using white dwarfs. We are therefore testing the LPI in a regime where it has not been tested before.

Ureaplasma urealyticum and U. parvum in sexually active women attending public health clinics in Brazil.

Ureaplasma urealyticum and U. parvum have been associated with genital infections. The purpose of this study was to detect the presence of ureaplasmas and other sexually transmitted infections in sexually active women from Brazil and relate these data to demographic and sexual health, and cytokines IL-6 and IL-1ß. Samples of cervical swab of 302 women were examined at the Family Health Units in Vitória da Conquista. The frequency of detection by conventional PCR was 76·2% for Mollicutes. In qPCR, the frequency found was 16·6% for U. urealyticum and 60·6% U. parvum and the bacterial load of these microorganisms was not significantly associated with signs and symptoms of genital infection. The frequency found for Trichomonas vaginalis, Neisseria gonorrhoeae, Gardnerella vaginalis and Chlamydia trachomatis was 3·0%, 21·5%, 42·4% and 1·7%, respectively. Higher levels of IL-1ß were associated with control women colonized by U. urealyticum and U. parvum. Increased levels of IL-6 were associated with women who exhibited U. parvum. Sexually active women, with more than one sexual partner in the last 3 months, living in a rural area were associated with increased odds of certain U. parvum serovar infection.

Unpredictable susceptibility of emerging clinical moulds to tri-azoles: review of the literature and upcoming challenges for mould identification.

Tri-azoles represent the front-line drugs for the treatment of mould diseases; nevertheless, some emerging moulds, such as Fusarium spp., Scedosporium spp., Mucorales and others, may be less susceptible or resistant to these antifungals. A review of the literature was conducted on the susceptibility of rare moulds to the tri-azoles itraconazole, posaconazole and voriconazole. Particular attention was paid to isolates identified by molecular analyses. The range of susceptibility values described for the three tri-azoles was frequently large (from 0.06 to >16), and a high variability was found within each species; isolates were rarely reported as entirely susceptible to all tri-azoles. In addition, the susceptibility of 76 emerging moulds from our collection (including Hypocreales, Dothideomycetes, Scedosporium spp., Mucorales and rare Aspergillus spp.) to itraconazole and voriconazole was determined by the Clinical and Laboratory Standards Institute (CLSI) M38-A2 and European Committee for Antimicrobial Susceptibility Testing (EUCAST) methods. Susceptibility discrepancies (of two dilutions) were found comparing CLSI and EUCAST for Dothideomycetes; the values for the remaining moulds were similar. More practical, faster and inexpensive susceptibility tools are welcome for testing emerging moulds, as these tests still represent a critical tool to support clinicians on the selection of proper antifungal treatment. The susceptibility of emerging moulds to tri-azoles cannot be predicted exclusively following mould identification, as the isolates' susceptibilities showed highly variable values. Some emerging moulds still remain very difficult to identity, even following standard molecular analyses which result in complex fungal collections. This fact limits the definition of epidemiological cut-offs and clinical breakpoints that are still imperative for emerging moulds.

Qualitative analysis of the vaginal microbiota of healthy cattle and cattle with genital-tract disease.

The microbial community of the reproductive appara-tus, when known, can provide information about the health of the host. Metagenomics has been used to characterize and obtain genetic infor-mation about microbial communities in various environments and can relate certain diseases with changes in this community composition. In this study, samples of vaginal surface mucosal secretions were col-lected from five healthy cows and five cows that showed symptoms of reproductive disorders. Following high-throughput sequencing of the isolated microbial DNA, data were processed using the Mothur soft-ware to remove low-quality sequences and chimeras, and released to the Ribosomal Database Project for classification of operational taxo-nomic units (OTUs). Local BLASTn was performed and results were loaded into the MEGAN program for viewing profiles and taxonomic microbial attributes. The control profile comprised a total of 15 taxa, with Bacteroides, Enterobacteriaceae, and Victivallis comprising the highest representation of OTUs; the reproductive disorder-positive profile comprised 68 taxa, with Bacteroides, Enterobacteriaceae, His-tophilus, Victivallis, Alistipes, and Coriobacteriaceae being the taxa with the most OTU representation. A change was observed in both the community composition as well as in the microbial attributes of the profiles, suggesting that a relationship might exist between the patho-gen and representative taxa, reflecting the production of metabolites to disease progression.

Mirandese language and genetic differentiation in Iberia: a study using X chromosome markers.

BACKGROUND: In the Iberian Peninsula, the Mirandese dialect, spoken in Miranda do Douro (Portugal) close to the north-eastern border with Spain, has attracted much attention. Aim, subjects and methods: This study focuses on providing further insight into the connections forged between Miranda do Douro and regions in the nearby Province of Zamora. This is in order to better assess the extent to which such relations could have been detained by the current patterns of genetic diversity of the populations, whilst contributing to refining the knowledge on patterns of micro-differentiation within the Peninsula. The genetic characterization of both populations was performed through the analysis of X-chromosomal markers: X-STRs and X-indels. RESULTS AND CONCLUSION: The results showed that Miranda do Douro tended to present slightly lower levels of diversity in comparison to the other studied regions, which can be a discreet sign of isolation of that population over the years that might have led the way to the preservation of a language not spoken anywhere else in the country. The analysis of X-STRs particularly brought to light the presence of a subtle population sub-structure at the micro-geographical area encompassing the north-eastern border, which seems to portray the importance of the political border as a mechanism withholding gene flow between the two countries.

Five new records of Luvarus imperialis (Acanthuroidei: Luvaridae) in the south-west Atlantic Ocean.

Five new records of louvars Luvarus imperialis are documented for the south-west Atlantic Ocean, extending its distribution range in this ocean. The presence of one ripe specimen, associated with the previous records of larvae and juveniles, suggests that L. imperialis spawn in this region. The possible association of juveniles with shoals of skipjack tuna Katsuwonus pelamis is discussed.

Evaluation of the acute and sublethal toxicity of Mancozeb in Pacamã (Lophiosilurus alexandri).

The toxic potential of dithiocarbamates fungicides widely used in world agriculture is well known, among which Mancozeb is one of the most used. This study aimed to evaluate the toxicity of Mancozeb, determining the LC50% of the product and the behavioral and histological changes observed in fish of the Pacamã species through acute and sublethal toxicity tests. The first experiment was carried out on Pacamã fingerlings exposed to dosages of 0.5, 1, 2, 4, and 8mg/L of Mancozeb under the form ManzateWG®, for a total period of 96 hours in the acute experiment, and in the second experiment, fish were subjected to concentrations of 1/10 of those used in the acute experiment (0.05, 0.1, 0.2, 0.4 and 0.8mg/L, respectively), for 15 days in total. The 50% lethal concentration of ManzateWG® was calculated at the end of the acute experiment, presenting a value of 2.29mg/L at 96h for Pacamã fingerlings. A behavioral assessment was carried out through daily observation of the fish during both experiments, and an increase in mucus production was observed, as well as atypical social behavior in those exposed to the toxic agent. Histopathological evaluation was performed on livers collected after the end of the sublethal experiment, and the main hepatic alterations observed were cytoplasmic vacuolization, inflammatory infiltrate, and necrosis. Mancozeb has toxic potential and is capable of generating behavioral changes, as well as increasing the risk of liver damage in Pacamãs exposed to this compound.

Mitochondrial lineages reveal intense gene flow between Iberian wild boars and South Iberian pig breeds.

The phylogeography of wild boars (WB) and domestic pigs (Sus scrofa) has contributed important insights into where and when domestication occurred. The geographic distribution of two core haplotypes (E1a and E1c) of the main European phylogenetic clade suggests that Central Europe was an early domestication centre, although the complexity of the pattern does not exclude the possibility that multiple domestication events occurred in different regions. To investigate the relationships among WB and domestic pig breeds in Iberia, a fragment of the mitochondrial DNA control region from a large sample (n=409) of WB and local pig breeds was co-analysed with published sequences from other European populations. The Iberian sample revealed a high frequency of a sub-cluster (E1c) of the European haplogroup E1 in 77% of total Iberian samples, 96% of WB, 90% of Alentejano (Portugal) and 87% of Iberian breed pigs (Spain; Black Hairy, Black Hairless and Red varieties). Low genetic distance (F'(ST) = 0.105) was observed between Alentejano (Portugal) and Iberian breed pigs (Spain). Alentejano and Iberian breed pigs showed low genetic distances to both Iberian and Central European WB (average F'(ST) =0.345 and 0.215, respectively). This pattern suggests that early pig husbandry in the Iberian Peninsula did not solely rely on imported Central European stock, but also included the recruitment of local WB.

Spatio-temporal dynamics of phytoplankton community in a well-mixed temperate estuary (Sado Estuary, Portugal).

Estuaries are highly productive ecosystems, which are strongly affected by several anthropogenic pressures. Phytoplankton is a key element for assessing the ecological quality status in these transitional waters. Moreover, understanding physico-chemical and biological drivers is crucial to disentangle their effect on the structure of phytoplankton community. The present work aims to study the effect of the main physico-chemical drivers on the phytoplankton community structure and dynamics in a temperate well-mixed estuary (Sado Estuary). Four sampling stations were analyzed monthly in three regions of the estuary, from 2018 to 2019. Surface water samples were collected to analyze the phytoplankton community and several concomitant physico-chemical parameters. Temperature, turbidity, salinity, and nutrients availability were the drivers that best explained the spatio-temporal patterns observed in the phytoplankton community. The upper estuary was characterized by higher phytoplankton cell abundances and biomass. Three phytoplankton groups stood out in the characterization of the estuarine assemblages: diatoms, cryptophytes, and dinoflagellates. Diatoms were the dominant group most of the year, being dominated by small cell species (single and chain-forming) upstream, and by larger chain-forming species downstream. Cryptophytes had a high contribution to the community in the inner regions of the estuary, while dinoflagellates contributed more for the community composition downstream, where high abundances of harmful algal species were sporadically found. Previous studies on the phytoplankton community dynamics in this estuary are limited to the 1990s. Thus, the present study provides insight into changes in the dominant phytoplankton groups of the Sado Estuary in the last 25 years, namely an increase in cryptophytes over diatoms in the inner estuarine regions, and an increase in dinoflagellates near the estuary mouth.

Transcriptional profiling of azole-resistant Candida parapsilosis strains.

Herein we describe the changes in the gene expression profile of Candida parapsilosis associated with the acquisition of experimentally induced resistance to azole antifungal drugs. Three resistant strains of C. parapsilosis were obtained following prolonged in vitro exposure of a susceptible clinical isolate to constant concentrations of fluconazole, voriconazole, or posaconazole. We found that after incubation with fluconazole or voriconazole, strains became resistant to both azoles but not to posaconazole, although susceptibility to this azole decreased, whereas the strain incubated with posaconazole displayed resistance to the three azoles. The resistant strains obtained after exposure to fluconazole and to voriconazole have increased expression of the transcription factor MRR1, the major facilitator transporter MDR1, and several reductases and oxidoreductases. Interestingly, and similarly to what has been described in C. albicans, upregulation of MRR1 and MDR1 is correlated with point mutations in MRR1 in the resistant strains. The resistant strain obtained after exposure to posaconazole shows upregulation of two transcription factors (UPC2 and NDT80) and increased expression of 13 genes involved in ergosterol biosynthesis. This is the first study addressing global molecular mechanisms underlying azole resistance in C. parapsilosis; the results suggest that similarly to C. albicans, tolerance to azoles involves the activation of efflux pumps and/or increased ergosterol synthesis.

The role of feedback projections in feature tuning and neuronal excitability in the early primate visual system.

A general assumption in visual neuroscience is that basic receptive field properties such as orientation and direction selectivity are constructed within intrinsic neuronal circuits and feedforward projections. In addition, it is assumed that general neuronal excitability and responsiveness in early visual areas is to a great extent independent of feedback input originating in areas higher in the stream. Here, we review the contribution of feedback projections from MT, V4 and pulvinar to the receptive field properties of V2 neurons in the anesthetized and paralyzed monkey. Importantly, our results contradict both of these assumptions. We separately inactivated each of these three brain regions using GABA pressure injections, while simultaneously recording V2 single unit activity before and hours after inactivation. Recordings and GABA injections were carried out in topographically corresponding regions of the visual field. We outline the changes in V2 activity, responsiveness and receptive field properties for early, mid and late post-injection phases. Immediately after injection, V2 activity is globally suppressed. Subsequently, there is an increase in stimulus-driven relative to spontaneous neuronal activity, which improves the signal-to-noise coding for the oriented moving bars. Notably, V2 tuning properties change substantially relative to its pre-injection selectivity profile. The resulting increase or decrease in selectivity could not be readily predicted based on the selectivity profile of the inactivated site. Finally, V2 activity rebounds before returning to it pre-injection profile Our results show that feedback projections profoundly impact neuronal circuits in early visual areas, and may have been heretofore largely underestimated in their physiological role.

Real-time PCR in clinical practice: a powerful tool for evaluating Leishmania chagasi loads in naturally infected dogs.

The performance of the less expensive SYBR-Green-based PCR assay, for quantifying Leishmania chagasi in smears of bone-marrow aspirates from naturally infected, mongrel dogs, was recently compared with that of a similar PCR based on TaqMan chemistry. Aspirates were obtained from 36 infected dogs and examined for parasites by direct examination, culture, and quantitative PCR (qPCR) using specific primers (based on the parasite's kinetoplast DNA), DNA extracted from a smear, and either the SYBR-Green or TaqMan chemistries. Every aspirate smear was found PCR-positive for L. chagasi (whether the assay employed SYBR Green or TaqMan) but only 74% of the aspirates were found positive by culture and only 33% by direct, microscopical examination. There was no evidence of PCR inhibition when the DNA was collected from smears, and the parasite loads estimated using the SYBR-Green PCR were almost identical to those estimated using the TaqMan PCR (r=0.99). As a method for quantifying parasite loads in dogs infected with L. chagasi (and, probably, other mammals infected with other leishmanial parasites), PCR based on SYBR Green may therefore be an appropriate and inexpensive alternative to PCR based on TaqMan, and a reliable clinical tool.

Middle eastern genetic legacy in the paternal and maternal gene pools of Chuetas.

Chuetas are a group of descendants of Majorcan Crypto-Jews (Balearic Islands, Spain) who were socially stigmatized and segregated by their Majorcan neighbours until recently; generating a community that, although after the seventeenth century no longer contained Judaic religious elements, maintained strong group cohesion, Jewishness consciousness, and endogamy. Collective memory fixed 15 surnames as a most important defining element of Chueta families. Previous studies demonstrated Chuetas were a differentiated population, with a considerable proportion of their original genetic make-up. Genetic data of Y-chromosome polymorphism and mtDNA control region showed, in Chuetas' paternal lineages, high prevalence of haplogroups J2-M172 (33%) and J1-M267 (18%). In maternal lineages, the Chuetas hallmark is the presence of a new sub-branching of the rare haplogroup R0a2m as their modal haplogroup (21%). Genetic diversity in both Y-chromosome and mtDNA indicates the Chueta community has managed to avoid the expected heterogeneity decrease in their gene pool after centuries of isolation and inbreeding. Moreover, the composition of their uniparentally transmitted lineages demonstrates a remarkable signature of Middle Eastern ancestry-despite some degree of host admixture-confirming Chuetas have retained over the centuries a considerable degree of ancestral genetic signature along with the cultural memory of their Jewish origin.

Size-dependent influence of NOx on the growth rates of organic aerosol particles.

Atmospheric new-particle formation (NPF) affects climate by contributing to a large fraction of the cloud condensation nuclei (CCN). Highly oxygenated organic molecules (HOMs) drive the early particle growth and therefore substantially influence the survival of newly formed particles to CCN. Nitrogen oxide (NOx) is known to suppress the NPF driven by HOMs, but the underlying mechanism remains largely unclear. Here, we examine the response of particle growth to the changes of HOM formation caused by NOx. We show that NOx suppresses particle growth in general, but the suppression is rather nonuniform and size dependent, which can be quantitatively explained by the shifted HOM volatility after adding NOx. By illustrating how NOx affects the early growth of new particles, a critical step of CCN formation, our results help provide a refined assessment of the potential climatic effects caused by the diverse changes of NOx level in forest regions around the globe.

In search of the pre- and post-neolithic genetic substrates in Iberia: evidence from Y-chromosome in Pyrenean populations.

The male-mediated genetic legacy of the Pyrenean population was assessed through the analysis of 12 Y-STR and 27 Y-SNP loci in a sample of 169 males from 5 main geographical areas in the Spanish Pyrenees: Cinco Villas (Western Pyrenees), Jacetania and Valle de Arán (Central Pyrenees) and Alto Urgel and Cerdaña (Eastern Pyrenees). In the Iberian context, the Pyrenean samples present some specificities, being characterizeded by a high proportion of chromosomes R1b1b2-M269 (including the usually uncommon R1b1b2d-SRY(2627) and R1b1b2c-M153 types) or I2a2-M26 and low proportions of other haplogroups. Our results indicate that an old pre-Neolithic substrate is preponderant in populations of the whole Pyrenean fringe. However, AMOVA revealed a high level of substructure within Pyrenean populations, partially explained by drift effects as well as by the signature of an ancient genetic differentiation between Western and Eastern Pyrenees.

Molecular mechanisms underlying large genomic deletions in ornithine transcarbamylase (OTC) gene.

Ornithine transcarbamylase deficiency (OTCD) is an X-linked urea cycle error causing hyperammonemia and orotic aciduria. Clinical diagnosis is generally confirmed by mutation detection. However, in approximately 20% of the patients, no mutation is found by conventional mutation-searching strategies, which fail to detect deletions spanning at least a whole exon, large rearrangements, or mutations at non-coding regions. To detect large deletions or duplications, we have applied the multiplex ligation-dependent probe amplification (MLPA) methodology to three OTCD patients (two females and one male). MLPA revealed copy number alterations of OTC exons in all of them. The two females were found to be heterozygous for deletions of either exon 2 or exons 6-9, and the male was confirmed to lack all OTC exons. Females' characterization of the deletion breakpoints by long polymerase chain reaction and sequencing revealed the mutations c.78-3544_217-129del5921 and c.541-600_1005 + 1880del10862 corresponding to exon 2 and exon 6-9 deletions, respectively. Examination of the deletion-flanking regions suggests that exon 2 deletion probably resulted from replication slippage facilitated by a secondary structure formed by two inverted Alu repeats, whereas an Alu-Alu homologous recombination was probably responsible for the exon 6-9 deletion. This work contributes to the identification of novel disease-causing mutations in OTCD and increases the knowledge on possible mutational mechanisms generating deletions in OTC.

Sub-two-cycle pulses by soliton self-compression in highly nonlinear photonic crystal fibers.

We demonstrate the direct generation of sub-two-cycle pulses by soliton self-compression of femtosecond pulses from a Ti:sapphire laser at 85 MHz using a 4.85-mm-long highly nonlinear photonic crystal fiber. Sub-nanojoule, 41 fs input pulses were compressed down to 4.6 fs without additional phase compensation schemes. To our knowledge, these are the shortest pulses obtained by soliton-effect compression of a laser oscillator. Efficient, near-dispersionless collimation of the fiber output was achieved with a simple lens and an octave-spanning double-chirped mirror pair. The full electric field of the compressed pulses was retrieved with a genetic algorithm applied to spectral and interferometric autocorrelation measurements, and the results are well described by numerical simulations.

Transport of fluorescent phospholipid analogues from the erythrocyte membrane to the parasite in Plasmodium falciparum-infected cells.

The asexual development of the human malaria parasite Plasmodium falciparum is largely intraerythrocytic. When 1-palmitoyl-2-[6-[(7-nitro-2-1,3-benzoxadiazole-4-yl)amino]caproyl] phosphatidylcholine (NBD-PC) was incorporated into infected and uninfected erythrocyte membranes at 0 degrees C, it remained at the cell surface. At 10 degrees C, the lipid was rapidly internalized in infected erythrocytes at all stages of parasite growth. Our results indicate that the internalization of NDB-PC was not because of endocytosis but rapid transbilayer lipid flip-flop at the infected erythrocyte membrane, followed by monomer diffusion to the parasite. Internalization of the lipid was inhibited by (a) depleting cellular ATP levels; (b) pretreating the cells with N-ethyl maleimide or diethylpyrocarbonate; and (c) 10 mM L-alpha-glycerophosphorylcholine. The evidence suggests protein-mediated and energy dependent transmembrane movement of the PC analogue. The conditions for the internalization of another phospholipid analogue N-4-nitrobenzo-2-oxa-1,3-diazoledipalmitoyl phosphatidylethanolamine (N-NBD-PE) were distinct from that of NBD-PC and suggest the presence of additional mechanism(s) of parasite-mediated lipid transport in the infected host membrane. In spite of the lack of bulk, constitutive endocytosis at the red cell membrane, the uptake of Lucifer yellow by mature infected cells suggests that microdomains of pinocytotic activity are induced by the intracellular parasite. The results indicate the presence of parasite-induced mechanisms of lipid transport in infected erythrocyte membranes that modify host membrane properties and may have important implications on phospholipid asymmetry in these membranes.

An unusual ZZ/ZW sex chromosome system in Characidium fishes (Crenuchidae, Characiformes) with the presence of rDNA sites.

Characidium fishes with a sex chromosome system form a monophyletic group. This work presents data of Characidium lanei from the South Atlantic basin (Brazil), including an unknown type of ZW sex chromosome system for the groups including the presence of rDNA sites on sex chromosomes.