Predictive factors for complete pathologic response in luminal breast cancer: impact of ki67 and HER2 low expression.

Background: Complete pathological response to neoadjuvant treatment (NAT) in breast cancer is associated with prolonged survival. Compared to other breast cancer immunophenotypes, luminal tumors are the least chemosensitive with low rates of pathological response within this molecular subtype. Thus, finding predictors of response in this subset remains challenging.

Clinical and molecular features of platinum resistance in ovarian cancer.

Ovarian cancer is the most lethal of all the gynecological tumors despite remarkable advances in our understanding of its molecular biology. The cornerstone treatment remains cytoreductive surgery followed by platinum-based chemotherapy. Recently, the addition of targeted therapies, such as PARP inhibitors, as first-line maintenance has led to outstanding improvements, mainly in BRCA mutated and homologous recombination deficient tumors.

Congenital Cutaneous Candidiasis With Systemic Dissemination in a Preterm Infant.

Congenital cutaneous candidiasis is an infrequent invasive fungal infection that usually appears in the first days of life. Extremely low birth weight infants are the most frequently affected. Classic presentation includes diffuse extensive erythematous rash with papules, plaques, pustules and vesicles, which later undergoes desquamation.

Hematologic Disorders in Children with Continuous Renal Replacement Therapies.

The objective of this study was to analyze hematologic disorders, coagulation disorders, and transfusion requirements in children with continuous renal replacement therapies (CRRT). This is a retrospective analysis of a prospectively collected database of children receiving CRRT between 2010 and 2015. Patient characteristics, CRRT parameters, hematologic and coagulation parameters, and need for transfusions were recorded and analyzed.

Structural characterization of a novel subfamily of leucine-rich repeat proteins from the human pathogen Leptospira interrogans.

Pathogenic Leptospira spp. are the agents of leptospirosis, an emerging zoonotic disease. Analyses of Leptospira genomes have shown that the pathogenic leptospires (but not the saprophytes) possess a large number of genes encoding proteins containing leucine-rich repeat (LRR) domains.

Structural studies suggest a peptidoglycan hydrolase function for the Mycobacterium tuberculosis Tat-secreted protein Rv2525c.

Among the few proteins shown to be secreted by the Tat system in Mycobacterium tuberculosis, Rv2525c is of particular interest, since its gene is conserved in the minimal genome of Mycobacterium leprae. Previous evidence linked this protein to cell wall metabolism and sensitivity to β-lactams. We describe here the crystal structure of Rv2525c that shows a TIM barrel-like fold characteristic of glycoside hydrolases of the GH25 family, which includes prokaryotic and phage-encoded peptidoglycan hydrolases.

Structural and functional characterization of an orphan ATP-binding cassette ATPase involved in manganese utilization and tolerance in Leptospira spp.

Pathogenic Leptospira species are the etiological agents of the widespread zoonotic disease leptospirosis. Most organisms, including Leptospira, require divalent cations for proper growth, but because of their high reactivity, these metals are toxic at high concentrations. Therefore, bacteria have acquired strategies to maintain metal homeostasis, such as metal import and efflux.

Conformational changes upon ligand binding in the essential class II fumarase Rv1098c from Mycobacterium tuberculosis.

rv1098c, an essential gene in Mycobacterium tuberculosis, codes for a class II fumarase. We describe here the crystal structure of Rv1098c in complex with l-malate, fumarate or the competitive inhibitor meso-tartrate. The models reveal that substrate binding promotes the closure of the active site through conformational changes involving the catalytic SS-loop and the C-terminal domain, which likely represents a general feature of this enzyme superfamily.

Structure of Mycobacterium tuberculosis Rv2714, a representative of a duplicated gene family in Actinobacteria.

The gene Rv2714 from Mycobacterium tuberculosis, which codes for a hypothetical protein of unknown function, is a representative member of a gene family that is largely confined to the order Actinomycetales of Actinobacteria. Sequence analysis indicates the presence of two paralogous genes in most mycobacterial genomes and suggests that gene duplication was an ancient event in bacterial evolution. The crystal structure of Rv2714 has been determined at 2.

Recombinant plant gamma carbonic anhydrase homotrimers bind inorganic carbon.

Gamma carbonic anhydrases (gammaCA) are widespread in Prokaryotes. In Eukaryotes, homologous genes were found only in plant genomes. In Arabidopsis and maize, the corresponding gene products are subunits of mitochondrial Complex I.

Genome-wide regulon and crystal structure of BlaI (Rv1846c) from Mycobacterium tuberculosis.

Comparative genomics with Staphylococcus aureus suggested the existence of a regulatory system governing beta-lactamase (BlaC) production in Mycobacterium tuberculosis. The crystal structure of Rv1846c, a winged helix regulator of previously unknown function, was solved thus revealing strong similarity to the BlaI and MecI repressors of S. aureus, which both respond to beta-lactam treatment.

The crystal structure of M. leprae ML2640c defines a large family of putative S-adenosylmethionine-dependent methyltransferases in mycobacteria.

Mycobacterium leprae protein ML2640c belongs to a large family of conserved hypothetical proteins predominantly found in mycobacteria, some of them predicted as putative S-adenosylmethionine (AdoMet)-dependent methyltransferases (MTase). As part of a Structural Genomics initiative on conserved hypothetical proteins in pathogenic mycobacteria, we have determined the structure of ML2640c in two distinct crystal forms. As expected, ML2640c has a typical MTase core domain and binds the methyl donor substrate AdoMet in a manner consistent with other known members of this structural family.

Mapping by site-directed mutagenesis of the region responsible for cohesin-dockerin interaction on the surface of the seventh cohesin domain of Clostridium thermocellum CipA.

To locate the region involved in binding dockerin domains, 15 mutations were introduced across the surface of the seventh cohesin domain of the scaffolding protein CipA, which holds together the cellulosome of Clostridium thermocellum. Mutated residues were located on both faces of the nine-stranded beta-sandwich forming the cohesin domain and on the loops connecting beta-strands 4 and 5, 6 and 7, and 8 and 9. The loop region was previously proposed, on the basis of sequence comparisons, to form a contiguous "recognition strip".

Duplicated dockerin subdomains of Clostridium thermocellum endoglucanase CelD bind to a cohesin domain of the scaffolding protein CipA with distinct thermodynamic parameters and a negative cooperativity.

Mutagenized dockerin domains of endoglucanase CelD (type I) and of the cellulosome-integrating protein CipA (type II) were constructed by swapping residues 10 and 11 of the first or the second duplicated segment between the two polypeptides. These residues have been proposed to determine the specificity of cohesin-dockerin interactions. The dockerin domain of CelD still bound to the seventh cohesin domain of CipA (CohCip7), provided that mutagenesis occurred in one segment only.

Cloning of a genetically unstable cytochrome P-450 gene cluster involved in degradation of the pollutant ethyl tert-butyl ether by Rhodococcus ruber.

Rhodococcus ruber (formerly Gordonia terrae) IFP 2001 is one of a few bacterial strains able to degrade ethyl tert-butyl ether (ETBE), which is a major pollutant from gasoline. This strain was found to undergo a spontaneous 14.3-kbp chromosomal deletion, which results in the loss of the ability to degrade ETBE.

Identification of a region responsible for binding to the cell wall within the S-layer protein of Clostridium thermocellum.

The protomer forming the S-layer of Clostridium thermocellum was identified as a 140 kDa protein which was non-covalently bound to the cell wall. Cloning and sequencing of the corresponding gene revealed an open reading frame of 3108 nucleotides encoding a polypeptide of 1036 amino acids, termed SlpA. The amino acid composition of SlpA matches the composition of a previously described exocellular glycoprotein.

Functions of S-layers.

Although S-layers are being increasingly identified on Bacteria and Archaea, it is enigmatic that in most cases S-layer function continues to elude us. In a few instances, S-layers have been shown to be virulence factors on pathogens (e.g.

Strategy for detection and identification of bacteria based on 16S rRNA genes in suspected cases of Whipple's disease.

The 16S ribosomal RNA (rRNA) gene of the phylogenetic subdivision containing gram-positive bacteria with a high G + C content was detected specifically in clinical specimens from patients suspected of having Whipple's disease. The primary structure of 16S rDNA amplified from clinical samples was determined by cloning and sequencing. Two sorts of sequences were identified: one corresponded exactly to the rRNA sequence of Tropheryma whippelii (GenBank accession no.

Identification of Bartonella henselae and B. quintana 16s rDNA sequences by branch-, genus- and species-specific amplification.

Given the controversy surrounding the aetiology of cat scratch disease and the association of both Bartonella henselae and B. quintana with bacillary angiomatosis, a method for the direct detection in clinical samples of 16S rRNA from the Proteobacteria alpha subgroup was developed. The primary structure of amplified 16S rDNA was determined by cloning and sequencing.

Cloning and expression of plasmid DNA sequences involved in Salmonella serotype typhimurium virulence.

A 22kb region of the 90kb virulence-associated plasmid, pIP1350, of Typhimurium strain C52 was cloned into the mobilizable vector pSUP202, yielding plasmid pIP1352. This recombinant plasmid restored full virulence to plasmidless strain C53 in a mouse model. Transposon Tn5 insertion mutagenesis demonstrated the existence of two DNA sequences in pIP1352 designated VirA and VirB, both of which are essential for the expression of virulence.

Virulence-associated plasmids of Salmonella serotype Typhimurium in experimental murine infection.

The growth pattern of Salmonella enterica subsp. enterica serotype Typhimurium (Typhimurium) was studied in mice to examine the role of the 60-Mdal virulence-associated plasmid in the pathogenesis of mouse typhoid. After repeated subcultures at 45 degrees C, isogenic variants harbouring the virulence-associated plasmid (strains C52, TM122 and TM332) or having lost this large plasmid (strains C53, TM123 and TM333) were obtained from three parental strains (strains C5, TM12 and TM33, respectively).