IDH Mutations in Glioma: Molecular, Cellular, Diagnostic, and Clinical Implications.

In 2021, the World Health Organization classified isocitrate dehydrogenase () mutant gliomas as a distinct subgroup of tumors with genetic changes sufficient to enable a complete diagnosis. Patients with an mutant glioma have improved survival which has been further enhanced by the advent of targeted therapies. enzymes contribute to cellular metabolism, and mutations to specific catalytic residues result in the neomorphic production of D-2-hydroxyglutarate (D-2-HG).

Rapid -R132 genotyping panel utilizing locked nucleic acid loop-mediated isothermal amplification.

While the detection of single-nucleotide variants (SNVs) is important for evaluating human health and disease, most genotyping methods require a nucleic acid extraction step and lengthy analytical times. Here, we present a protocol which utilizes the integration of locked nucleic acids (LNAs) into self-annealing loop primers for the allelic discrimination of five isocitrate dehydrogenase 1 R132 (-R132) variants using loop-mediated isothermal amplification (LAMP). This genotyping panel was initially evaluated using purified synthetic DNA to show proof of specific SNV discrimination.

Rapid extraction-free detection of the R132H isocitrate dehydrogenase mutation in glioma using colorimetric peptide nucleic acid-loop mediated isothermal amplification (CPNA-LAMP).

The R132H isocitrate dehydrogenase one (IDH1) mutation is a prognostic biomarker present in a subset of gliomas and is associated with heightened survival when paired with aggressive surgical resection. In this study, we establish proof-of-principle for rapid colorimetric detection of the IDH1-R132H mutation in tumor samples in under 1 hour without the need for a nucleic acid extraction. Colorimetric peptide nucleic acid loop-mediated isothermal amplification (CPNA-LAMP) utilizes 4 conventional LAMP primers, a blocking PNA probe complementary to the wild-type sequence, and a self-annealing loop primer complementary to the single nucleotide variant to only amplify the DNA sequence containing the mutation.

Association of bacterial colonization at the time of presentation to a combat support hospital in a combat zone with subsequent 30-day colonization or infection.

U.S. casualties have developed multidrug-resistant (MDR) bacterial infections.

IEIIS Meeting minireview: Bordetella evolution: lipid A and Toll-like receptor 4.

The evolution of Bordetella pertussis and Bordetella parapertussis from Bordetella bronchiseptica involved changes in host range and pathogenicity. Recent data suggest that the human-adapted Bordetella modified their interaction with host immune systems to effect these changes and that decreased stimulation of Toll-like receptor 4 (TLR4) by lipid A is central to this. We discuss Bordetella lipid A structure and genetics within the context of evolution and host immunity.

Delayed role of tumor necrosis factor- alpha in overcoming the effects of pertussis toxin.

Bordetella pertussis causes whooping cough, an endemic respiratory disease that is increasing in prevalence despite vaccination efforts. Although host immunity is modulated by virulence factors of this pathogen, it is unclear what host factors are required to overcome their effects. Here, we investigate an apparent relationship between the effects of pertussis toxin and tumor necrosis factor (TNF)- alpha .

Acinetobacter skin carriage among US army soldiers deployed in Iraq.

Skin carriage of Acinetobacter calcoaceticus-baumannii complex was not detected among a representative sample of 102 US Army soldiers stationed in Iraq. This observation refutes the hypothesis that preinjury skin carriage serves as the reservoir for the Acinetobacter infections seen in US military combat casualties.

The complex mechanism of antibody-mediated clearance of Bordetella from the lungs requires TLR4.

Although the antibacterial effects of Abs are well studied in in vitro systems, the in vivo effects of Abs cannot always be accurately predicted. Complicated cross-talk between different effector functions of Abs and various arms of the immune system can affect their activities in vivo. Using the mouse respiratory pathogen Bordetella bronchiseptica, we examined the mechanisms of Ab-mediated clearance of bacteria from the respiratory tract.

Comparative toll-like receptor 4-mediated innate host defense to Bordetella infection.

Bordetella pertussis, B. parapertussis, and B. bronchiseptica are closely related species associated with respiratory disease in humans and other mammals.

Toll-like receptor 4-dependent early elicited tumor necrosis factor alpha expression is critical for innate host defense against Bordetella bronchiseptica.

Toll-like receptor 4 (TLR4) mediates the response to lipopolysaccharide, and its activation induces the expression of a large number of inflammatory genes, many of which are also induced by other pathogen-associated molecular patterns. Interestingly, the subset of genes that are dependent on TLR4 for optimal expression during gram-negative bacterial infection has not been determined. We have previously shown that TLR4-deficient mice rapidly develop acute pneumonia after inoculation with Bordetella bronchiseptica, suggesting that TLR4 is required for expression of early elicited gene products in this model.

Toll-like receptor 4 is critical to innate host defense in a murine model of bordetellosis.

Bordetellae are important respiratory pathogens that cause pertussis (whooping cough) in humans and analogous diseases in domestic and wild animals. Immunity to Bordetella is poorly understood, in particular the early innate immune responses that contribute to inflammation, pathology, and the subsequent generation of adaptive immunity. Using B.

Role of antibodies in immunity to Bordetella infections.

The persistence of Bordetella pertussis and B. parapertussis within vaccinated populations and the reemergence of associated disease highlight the need to better understand protective immunity. The present study examined host immunity to bordetellae and addressed potential concerns about the mouse model by using a comparative approach including the closely related mouse pathogen B.