Evidence for Archaean lamprophyre from the Kaapvaal Craton, South Africa

A suite of mafic dykes occurs as a late component in a wellcharacterized trondhjemite–tonalite–diorite–granodiorite assemblage in the Johannesburg Dome of the central Kaapvaal Craton, southern Africa. The dykes have been subdivided into two sets, based on their orientation, and major and trace element geochemistry. Set 1 dykes are characterized by elevated SiO2, Al2O3 and TiO2, and particularly by enriched LILE and HSFE (e.g. Zr > 200 ppm, Nb > 20 ppm, Ba > 300 ppm), higher than in any of the accompanying felsic rocks. REE and trace element values for Set 1 dykes are similar to those for calc-alkaline lamprophyres. The Set 2 dykes have similar trace element distributions, but are significantly less enriched in general, and are broadly tholeiitic in composition, with enriched MgO (>11 wt. percentage) indicative of an olivine–phyric tholeiitic basaltic protolith. Field relationships and available U–Pb zircon geochronology indicate that the dykes are contemporaneous with components of the trondhjemitic host rocks, and with late granodiorites. The geochemical, geochronological and field petrological setting indicates partial melting of basaltic and eclogitic lithosphere at c. 3120 Myr ago in the basal Kaapvaal Craton, and subsequent emplacement into pre-existing c. 3430 Myr tonalitic to dioritic crust

Magmatic and hydrothermal behavior of uranium in syntectonic leucogranites: The uranium mineralization associated with the Hercynian Guérande granite (Armorican Massif, France)

Most of the hydrothermal uranium (U) deposits from the European Hercynian belt (EHB) are spatially associated with Carboniferous peraluminous leucogranites. In the southern part of the Armorican Massif (French part of the EHB), the Guérande peraluminous leucogranite was emplaced in an extensional deformation zone at ca. 310 Ma and is spatially associated with several U deposits and occurrences. The apical zone of the intrusion is structurally located below the Pen Ar Ran U deposit, a perigranitic vein-type deposit where mineralization occurs at the contact between black shales and Ordovician acid metavolcanics. In the Métairie-Neuve intragranitic deposit, uranium oxide-quartz veins crosscut the granite and a metasedimentary enclave. Airborne radiometric data and published trace element analyses on the Guérande leucogranite suggest significant uranium leaching at the apical zone of the intrusion. The primary U enrichment in the apical zone of the granite likely occurred during both fractional crystallization and the interaction with magmatic fluids. The low Th/U values (18Owhole rock = 9.7–11.6‰ for deformed samples and δ18Owhole rock = 12.2–13.6‰ for other samples) indicate that the deformed facies of the apical zone underwent sub-solidus alteration at depth with oxidizing meteoric fluids. Fluid inclusion analyses on a quartz comb from a uranium oxide-quartz vein of the Pen Ar Ran deposit show evidence of low-salinity fluids (1–6 wt.% NaCl eq.), in good agreement with the contribution of meteoric fluids. Fluid trapping temperatures in the range of 250–350 °C suggest an elevated geothermal gradient, probably related to regional extension and the occurrence of magmatic activity in the environment close to the deposit at the time of its formation. U-Pb dating on uranium oxides from the Pen Ar Ran and Métairie-Neuve deposits reveals three different mineralizing events. The first event at 296.6 ± 2.6 Ma (Pen Ar Ran) is sub-synchronous with hydrothermal circulations and the emplacement of late leucogranitic dykes in the Guérande leucogranite. The two last mineralizing events occur at 286.6 ± 1.0 Ma (Métairie-Neuve) and 274.6 ± 0.9 Ma (Pen Ar Ran), respectively. Backscattered uranium oxide imaging combined with major elements and REE geochemistry suggest similar conditions of mineralization during the two Pen Ar Ran mineralizing events at ca. 300 Ma and ca. 275 Ma, arguing for different hydrothermal circulation phases in the granite and deposits. Apatite fission track dating reveals that the Guérande granite was still at depth and above 120 °C when these mineralizing events occurred, in agreement with the results obtained on fluid inclusions at Pen Ar Ran. Based on this comprehensive data set, we propose that the Guérande leucogranite is the main source for uranium in the Pen Ar Ran and Métairie-Neuve deposits. Sub-solidus alteration via surface-derived low-salinity oxidizing fluids likely promoted uranium leaching from magmatic uranium oxides within the leucogranite. The leached out uranium may then have been precipitated in the reducing environment represented by the surrounding black shales or graphitic quartzites. As similar mineralizing events occurred subsequently until ca. 275 Ma, meteoric oxidizing fluids likely percolated during the time when the Guérande leucogranite was still at depth. The age of the U mineralizing events in the Guérande region (300–275 Ma) is consistent with that obtained on other U deposits in the EHB and could suggest a similar mineralization condition, with long-term upper to middle crustal infiltration of meteoric fluids likely to have mobilized U from fertile peraluminous leucogranites during the Late Carboniferous to Permian crustal extension events

Complete androgen insensitivity syndrome due to a new frameshift deletion in exon 4 of the androgen receptor gene: Functional analysis of the mutant receptor

We studied the androgen receptor gene in a large kindred with complete androgen insensitivity syndrome and negative receptor-binding activity, single-strand conformation polymorphism (SSCP) analysis and sequencing identified a 13 base pair deletion within exon 4. This was responsible for a predictive frameshift in the open reading frame and introduction of a premature stop codon at position 783 instead of 919. The deletion was reproduced in androgen receptor wildtype cDNA and transfected into mammalian cells. Western blot showed a smaller androgen receptor of 94 kDa for the transfected mutated cDNA instead of 110 kDa. Androgen-binding assay of the mutated transfected cells assessed the lack of androgen-binding. Gel retardation assay demonstrated the ability of the mutant to bind target DNA; however, the mutant was unable to transactivate a reporter gene. Although the role of the partial deletion in the lack of androgen action was expected, in vitro analyses highlight the role of the abnormal C-terminal portion in the inhibition of the receptor transregulatory activity of the protein causing androgen resistance in this family

Evidence for Archaean lamprophyre from the Kaapvaal Craton, South Africa

A suite of mafic dykes occurs as a late component in a wellcharacterized trondhjemite–tonalite–diorite–granodiorite assemblage in the Johannesburg Dome of the central Kaapvaal Craton, southern Africa. The dykes have been subdivided into two sets, based on their orientation, and major and trace element geochemistry. Set 1 dykes are characterized by elevated SiO2, Al2O3 and TiO2, and particularly by enriched LILE and HSFE (e.g. Zr > 200 ppm, Nb > 20 ppm, Ba > 300 ppm), higher than in any of the accompanying felsic rocks. REE and trace element values for Set 1 dykes are similar to those for calc-alkaline lamprophyres. The Set 2 dykes have similar trace element distributions, but are significantly less enriched in general, and are broadly tholeiitic in composition, with enriched MgO (>11 wt. percentage) indicative of an olivine–phyric tholeiitic basaltic protolith. Field relationships and available U–Pb zircon geochronology indicate that the dykes are contemporaneous with components of the trondhjemitic host rocks, and with late granodiorites. The geochemical, geochronological and field petrological setting indicates partial melting of basaltic and eclogitic lithosphere at c. 3120 Myr ago in the basal Kaapvaal Craton, and subsequent emplacement into pre-existing c. 3430 Myr tonalitic to dioritic crust

Intra-Host Evolution Analyses in an Immunosuppressed Patient Supports SARS-CoV-2 Viral Reservoir Hypothesis.

Throughout the SARS-CoV-2 pandemic, several variants of concern (VOCs) have been identified, many of which share recurrent mutations in the spike glycoprotein's receptor-binding domain (RBD). This region coincides with known epitopes and can therefore have an impact on immune escape. Protracted infections in immunosuppressed patients have been hypothesized to lead to an enrichment of such mutations and therefore drive evolution towards VOCs. Here, we present the case of an immunosuppressed patient that developed distinct populations with immune escape mutations throughout the course of their infection. Notably, by investigating the co-occurrence of substitutions on individual sequencing reads in the RBD, we found quasispecies harboring mutations that confer resistance to known monoclonal antibodies (mAbs) such as S:E484K and S:E484A. These mutations were acquired without the patient being treated with mAbs nor convalescent sera and without them developing a detectable immune response to the virus. We also provide additional evidence for a viral reservoir based on intra-host phylogenetics, which led to a viral substrain that evolved elsewhere in the patient's body, colonizing their upper respiratory tract (URT). The presence of SARS-CoV-2 viral reservoirs can shed light on protracted infections interspersed with periods where the virus is undetectable, and potential explanations for long-COVID cases

Carmustine and methotrexate in combination after whole brain radiation therapy in breast cancer patients presenting with brain metastases: a retrospective study

<p>Abstract</p> <p>Background</p> <p>Since 1999, patients presenting with brain metastases (BM) from breast cancer (BC) are treated in our institution with a carmustine (BCNU) - methotrexate (MTX) combination. We report here our clinical experience regarding this combination.</p> <p>Patients and Methods</p> <p>Patients were treated by a combination of BCNU 100 mg/m² on day 1 and MTX 600 mg/m² on day 1 and 15 of a 28 day cycle. Treatment was continued until progression or unacceptable toxicity.</p> <p>Results</p> <p>50 patients were treated between 1999 and 2007. 94% of the patients presented with concomitant extra-cerebral disease. Median number of previous metastatic setting chemotherapy regimens was 2 (0-5). Median number of cycles was 3 (1-20). There were 11 objective responses (23% [95%CI 12-37]) among 48 evaluable patients. Median progression-free survival and overall survival (OS) were 4.2 (95%CI: 2.8-5.3) and 6.9 (4.2-10.7) months respectively, with a one-year OS rate of 32% (20-46). Median Relative Dose Intensity for BCNU and MTX were 0.98 (0.31-1.1) and 0.96 (0.57-1.66) respectively. There were 2 presumed treatment-related deaths. One patient developed febrile neutropenia. Performance status, BS-BM score and presence of liver metastases were associated with OS in univariate analysis.</p> <p>Conclusions</p> <p>This combination appears to be effective and well tolerated in good performance status BC patients presenting with BM.</p

The tree that hides the forest: cryptic diversity and phylogenetic relationships in the Palaearctic vector Obsoletus/Scoticus Complex (Diptera: Ceratopogonidae) at the European level

Abstract Background Culicoides obsoletus is an abundant and widely distributed Holarctic biting midge species, involved in the transmission of bluetongue virus (BTV) and Schmallenberg virus (SBV) to wild and domestic ruminants. Females of this vector species are often reported jointly with two morphologically very close species, C. scoticus and C. montanus, forming the Obsoletus/Scoticus Complex. Recently, cryptic diversity within C. obsoletus was reported in geographically distant sites. Clear delineation of species and characterization of genetic variability is mandatory to revise their taxonomic status and assess the vector role of each taxonomic entity. Our objectives were to characterize and map the cryptic diversity within the Obsoletus/Scoticus Complex. Methods Portion of the cox1 mitochondrial gene of 3763 individuals belonging to the Obsoletus/Scoticus Complex was sequenced. Populations from 20 countries along a Palaearctic Mediterranean transect covering Scandinavia to Canary islands (North to South) and Canary islands to Turkey (West to East) were included. Genetic diversity based on cox1 barcoding was supported by 16S rDNA mitochondrial gene sequences and a gene coding for ribosomal 28S rDNA. Species delimitation using a multi-marker methodology was used to revise the current taxonomic scheme of the Obsoletus/Scoticus Complex. Results Our analysis showed the existence of three phylogenetic clades (C. obsoletus clade O2, C. obsoletus clade dark and one not yet named and identified) within C. obsoletus. These analyses also revealed two intra-specific clades within C. scoticus and raised questions about the taxonomic status of C. montanus. Conclusions To our knowledge, our study provides the first genetic characterization of the Obsoletus/Scoticus Complex on a large geographical scale and allows a revision of the current taxonomic classification for an important group of vector species of livestock viruses in the Palaearctic region

Correction to: The tree that hides the forest : cryptic diversity and phylogenetic relationships in the Palaearctic vector Obsoletus/Scoticus complex (Diptera: Ceratopogonidae) at the European level

An amendment to this paper has been published and can be accessed via the original article

The tree that hides the forest: Cryptic diversity and phylogenetic relationships in the Palaearctic vector Obsoletus/Scoticus Complex (Diptera: Ceratopogonidae) at the European level

Background: Culicoides obsoletus is an abundant and widely distributed Holarctic biting midge species, involved in the transmission of bluetongue virus (BTV) and Schmallenberg virus (SBV) to wild and domestic ruminants. Females of this vector species are often reported jointly with two morphologically very close species, C. scoticus and C. montanus, forming the Obsoletus/Scoticus Complex. Recently, cryptic diversity within C. obsoletus was reported in geographically distant sites. Clear delineation of species and characterization of genetic variability is mandatory to revise their taxonomic status and assess the vector role of each taxonomic entity. Our objectives were to characterize and map the cryptic diversity within the Obsoletus/Scoticus Complex. Methods: Portion of the cox1 mitochondrial gene of 3763 individuals belonging to the Obsoletus/Scoticus Complex was sequenced. Populations from 20 countries along a Palaearctic Mediterranean transect covering Scandinavia to Canary islands (North to South) and Canary islands to Turkey (West to East) were included. Genetic diversity based on cox1 barcoding was supported by 16S rDNA mitochondrial gene sequences and a gene coding for ribosomal 28S rDNA. Species delimitation using a multi-marker methodology was used to revise the current taxonomic scheme of the Obsoletus/Scoticus Complex. Results: Our analysis showed the existence of three phylogenetic clades (C. obsoletus clade O2, C. obsoletus clade dark and one not yet named and identified) within C. obsoletus. These analyses also revealed two intra-specific clades within C. scoticus and raised questions about the taxonomic status of C. montanus. Conclusions: To our knowledge, our study provides the first genetic characterization of the Obsoletus/Scoticus Complex on a large geographical scale and allows a revision of the current taxonomic classification for an important group of vector species of livestock viruses in the Palaearctic region.[Figure not available: See fulltext.

ABO Blood Group and the Risk of Hepatocellular Carcinoma: A Case-Control Study in Patients with Chronic Hepatitis B

BACKGROUND: Studies have observed an association between the ABO blood group and risk of certain malignancies. However, no studies of the association with hepatocellular carcinoma (HCC) risk are available. We conducted this hospital-based case-control study to examine the association with HCC in patients with chronic hepatitis B (CHB). METHODS: From January 2004 to December 2008, a total of 6275 consecutive eligible patients with chronic hepatitis B virus (HBV) infection were recruited. 1105 of them were patients with HBV-related HCC and 5,170 patients were CHB without HCC. Multivariate logistic regression models were used to investigate the association between the ABO blood group and HCC risk. RESULTS: Compared with subjects with blood type O, the adjusted odds ratio (AOR) for the association of those with blood type A and HCC risk was 1.39 [95% confidence interval (CI), 1.05-1.83] after adjusting for age, sex, type 2 diabetes, cirrhosis, hepatitis B e antigen, and HBV DNA. The associations were only statistically significant [AOR (95%CI) = 1.56(1.14-2.13)] for men, for being hepatitis B e antigen positive [AOR (95%CI) = 4.92(2.83-8.57)], for those with cirrhosis [AOR (95%CI), 1.57(1.12-2.20)], and for those with HBV DNA≤10(5)copies/mL [AOR (95%CI), 1.58(1.04-2.42)]. Stratified analysis by sex indicated that compared with those with blood type O, those with blood type B also had a significantly high risk of HCC among men, whereas, those with blood type AB or B had a low risk of HCC among women. CONCLUSIONS: The ABO blood type was associated with the risk of HCC in Chinese patients with CHB. The association was gender-related