Pneumocystis jiroveci Dihydropteroate Synthase Genotypes in Immunocompetent Infants and Immunosuppressed Adults, Amiens, France

To date, investigations of Pneumocystis jiroveci circulation in the human reservoir through the dihydropteroate synthase (DHPS) locus analysis have only been conducted by examining P. jirovecii isolates from immunosuppressed patients with Pneumocystis pneumonia (PCP). Our study identifies P. jirovecii genotypes at this locus in 33 immunocompetent infants colonized with P. jirovecii contemporaneously with a bronchiolitis episode and in 13 adults with PCP; both groups of patients were monitored in Amiens, France. The results have pointed out identical features of P. jirovecii DHPS genotypes in the two groups, suggesting that in these two groups, transmission cycles of P. jirovecii infections are linked. If these two groups represent sentinel populations for P. jirovecii infections, our results suggest that all persons parasitized by P. jirovecii, whatever their risk factor for infection and the form of parasitism they have, act as interwoven circulation networks of P. jirovecii

New Antibody-Free Mass Spectrometry-Based Quantification Reveals That C9ORF72 Long Protein Isoform Is Reduced in the Frontal Cortex of Hexanucleotide-Repeat Expansion Carriers

Frontotemporal dementia (FTD) is a fatal neurodegenerative disease characterized by behavioral and language disorders. The main genetic cause of FTD is an intronic hexanucleotide repeat expansion (G4C2)n in the C9ORF72 gene. A loss of function of the C9ORF72 protein associated with the allele-specific reduction of C9ORF72 expression is postulated to contribute to the disease pathogenesis. To better understand the contribution of the loss of function to the disease mechanism, we need to determine precisely the level of reduction in C9ORF72 long and short isoforms in brain tissue from patients with C9ORF72 mutations. In this study, we developed a sensitive and robust mass spectrometry (MS) method for quantifying C9ORF72 isoform levels in human brain tissue without requiring antibody or affinity reagent. An optimized workflow based on surfactant-aided protein extraction and pellet digestion was established for optimal recovery of the two isoforms in brain samples. Signature peptides, common or specific to the isoforms, were targeted in brain extracts by multiplex MS through the parallel reaction monitoring mode on a Quadrupole–Orbitrap high resolution mass spectrometer. The assay was successfully validated and subsequently applied to frontal cortex brain samples from a cohort of FTD patients with C9ORF72 mutations and neurologically normal controls without mutations. We showed that the C9ORF72 short isoform in the frontal cortices is below detection threshold in all tested individuals and the C9ORF72 long isoform is significantly decreased in C9ORF72 mutation carriers

Mineralogy at DSDP Leg 78A Holes

This chapter deals with the evolution of clay minerals in Cenozoic sediments from DSDP Sites 541, 542, and 543 east of the Lesser Antilles arc on and near the edge of the Barbados Ridge complex. Throughout the Miocene, smectite exceeds all other minerals at all three sites. From the Pliocene onward, however, illite becomes dominant and chlorite well-represented. Quantitative mineral differences among the three sites are significant up until the top of the Pliocene. But in the Pleistocene, the mineralogical composition becomes exactly the same at all sites. Data from the Caribbean region are used to interpret the results obtained. These involve two supply sources: (1) the adjacent islands that supply smectites and kaolinites, and (2) South America, which is the major source of illite and chlorite. The apparent northward migration of illite and chlorite on the Barbados Ridge complex and the changes reported in the quantitative distribution of the four clay minerals are most probably controlled by northerly currents along the northern coast of South America

Mineralogy at DSDP Site 82-558 and Hole 82-563

Downhole bulk-sample and clay-mineral analytical results for Sites 558 and 563 are presented in this chapter. These results show a Tertiary climatic and hydrologic evolution similar to that at other DSDP drill sites in the northeastern Atlantic Ocean (Sites 398, 403-406, 548-550, 552-555). The sediments recovered at both sites are primarily calcareous and chalky oozes characterized by >90% carbonate and minor quartz and plagioclase feldspar. Clay minerals smectite, kaolinite, illite, and chlorite are present throughout the cores; upsection, illite increases at the expense of smectite. The clay mineralogy suggests climatic cooling and increased ocean circulation during the Miocene. Intervals rich in very fine grained (<2 µm) quartz suggest times of increased eolian input. This could have resulted from development, during Oligocene and late Miocene time, of an arid, desertlike sediment provenance that lasted until the present day