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author:("klenova, A")
1.  A case of Exophiala dermatitidis infection in a child after allogeneic stem cell transplantation: case report and literature review of paediatric cases 
JMM Case Reports  2017;4(6):e005102.
Introduction. Exophiala dermatitidisis a relatively common environmental black yeast with worldwide distribution and is a rare cause of fungal infection, mostly in patients with certain predisposing factors. Due to the rarity of the infection, little is known about the specific predisposing factors, way of infection or treatment.
Case presentation. Here, we report what is to our knowledge the first case of E. dermatitidis infection in a child after allogeneic stem cell transplantation. We also review all paediatric cases reported in the literature since 1993.
Conclusion. This is, to our knowledge, the first reported case of E. dermatitidis infection in a child after allogeneic stem cell transplantation. This report should increase the awareness of E. dermatitidis in immunocompromised paediatric patients, particularly after stem cell transplantation.
doi:10.1099/jmmcr.0.005102
PMCID: PMC5630971
Exophiala dermatitidis; child; stem cell transplantation; grey sputum; posaconazole
2.  First case of invasive Magnusiomyces capitatus infection in Slovakia 
Magnusiomyces capitatus (previously known as Geotrichum capitatum or Blastoschizomyces capitatus or Trichosporon capitatum) is a rare cause of fungal infection in immunocompromised patients. Most of these cases (87%) have been reported from the Mediterranean region, as it is extremely rare to recognize it in other regions. Here we report a first case of disseminated M. capitatus infection in Slovakia. The patient – 19 year old woman with myelodysplastic syndrome was diagnosed with M. capitatus fungemia after allogeneic stem cell transplantation. The infection occurred despite antifungal prophylaxis with micafungin, which was in vitro sensitive to the yeast. The treatment according to minimal inhibitory concentrations (micafungin, voriconazol) and granulocyte transfusions were administered. M. capitatus was cleared out from the bloodstream. However, patient died of multiple organ failure. Autopsy showed multiple lesions in organs, but did not prove presence of yeast by histopathology. M. capitatus was confirmed by polymerase chain reaction from all tested organs: heart, brain, lungs, spleen, liver and kidneys. We present the post mortem pictures showing the yeast lesions in affected organs. 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.mmcr.2017.03.004
PMCID: PMC5379865  PMID: 28409093
Blastoschizomyces; Geotrichum; Magnusiomyces; Stem cell transplantation
3.  Future paradigms for precision oncology 
Oncotarget  2016;7(29):46813-46831.
Research has exposed cancer to be a heterogeneous disease with a high degree of inter-tumoral and intra-tumoral variability. Individual tumors have unique profiles, and these molecular signatures make the use of traditional histology-based treatments problematic. The conventional diagnostic categories, while necessary for care, thwart the use of molecular information for treatment as molecular characteristics cross tissue types.
This is compounded by the struggle to keep abreast the scientific advances made in all fields of science, and by the enormous challenge to organize, cross-reference, and apply molecular data for patient benefit. In order to supplement the site-specific, histology-driven diagnosis with genomic, proteomic and metabolomics information, a paradigm shift in diagnosis and treatment of patients is required.
While most physicians are open and keen to use the emerging data for therapy, even those versed in molecular therapeutics are overwhelmed with the amount of available data. It is not surprising that even though The Human Genome Project was completed thirteen years ago, our patients have not benefited from the information. Physicians cannot, and should not be asked to process the gigabytes of genomic and proteomic information on their own in order to provide patients with safe therapies. The following consensus summary identifies the needed for practice changes, proposes potential solutions to the present crisis of informational overload, suggests ways of providing physicians with the tools necessary for interpreting patient specific molecular profiles, and facilitates the implementation of quantitative precision medicine. It also provides two case studies where this approach has been used.
doi:10.18632/oncotarget.9488
PMCID: PMC5216837  PMID: 27223079
precision medicine; targeted therapy; genomics; metronomic chemotherapy
4.  The Active Site of a Carbohydrate Esterase Displays Divergent Catalytic and Noncatalytic Binding Functions 
PLoS Biology  2009;7(3):e1000071.
Multifunctional proteins, which play a critical role in many biological processes, have typically evolved through the recruitment of different domains that have the required functional diversity. Thus the different activities displayed by these proteins are mediated by spatially distinct domains, consistent with the specific chemical requirements of each activity. Indeed, current evolutionary theory argues that the colocalization of diverse activities within an enzyme is likely to be a rare event, because it would compromise the existing activity of the protein. In contrast to this view, a potential example of multifunctional recruitment into a single protein domain is provided by CtCel5C-CE2, which contains an N-terminal module that displays cellulase activity and a C-terminal module, CtCE2, which exhibits a noncatalytic cellulose-binding function but also shares sequence identity with the CE2 family of esterases. Here we show that, unlike other CE2 members, the CtCE2 domain displays divergent catalytic esterase and noncatalytic carbohydrate binding functions. Intriguingly, these diverse activities are housed within the same site on the protein. Thus, a critical component of the active site of CtCE2, the catalytic Ser-His dyad, in harness with inserted aromatic residues, confers noncatalytic binding to cellulose whilst the active site of the domain retains its esterase activity. CtCE2 catalyses deacetylation of noncellulosic plant structural polysaccharides to deprotect these substrates for attack by other enzymes. Yet it also acts as a cellulose-binding domain, which promotes the activity of the appended cellulase on recalcitrant substrates. The CE2 family encapsulates the requirement for multiple activities by biocatalysts that attack challenging macromolecular substrates, including the grafting of a second, powerful and discrete noncatalytic binding functionality into the active site of an enzyme. This article provides a rare example of “gene sharing,” where the introduction of a second functionality into the active site of an enzyme does not compromise the original activity of the biocatalyst.
Author Summary
Proteins that display multiple activities have typically evolved through the recruitment of different domains, each of which has a specific function. Thus, in a multifunctional protein, the different activities are mediated by spatially distinct domains such that a single domain can provide the specific chemical requirements for one activity. Indeed, current evolutionary theory argues that the colocalization of diverse activities within a single-domain enzyme is likely to be a rare event, as it would compromise the existing activity of the protein when a new function evolves. Nonetheless, a potential example of multifunctional recruitment into a single protein domain is provided by an enzyme that contains a cellulase enzyme module and a discrete noncatalytic cellulose-binding module. In this article, we show that the cellulose-binding module displays esterase activity and that these diverse activities are housed within the same site on the protein. Structural analysis of the enzyme reveals that its catalytic residues also contribute to the noncatalytic cellulose-binding function. This report provides a rare example of “gene sharing,” whereby the introduction of a second functionality into the active site of an enzyme does not compromise the original activity of the catalyst.
The active of site of an esterase enzyme has acquired a noncatalytic carbohydrate-binding function without compromising its catalytic activity, providing support for the "gene sharing" model of protein diversification.
doi:10.1371/journal.pbio.1000071
PMCID: PMC2661963  PMID: 19338387
5.  The MLL recombinome of acute leukemias in 2013 
Leukemia  2013;27(11):2165-2176.
Chromosomal rearrangements of the human MLL (mixed lineage leukemia) gene are associated with high-risk infant, pediatric, adult and therapy-induced acute leukemias. We used long-distance inverse-polymerase chain reaction to characterize the chromosomal rearrangement of individual acute leukemia patients. We present data of the molecular characterization of 1590 MLL-rearranged biopsy samples obtained from acute leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and novel TPGs identified. All patients were classified according to their gender (852 females and 745 males), age at diagnosis (558 infant, 416 pediatric and 616 adult leukemia patients) and other clinical criteria. Combined data of our study and recently published data revealed a total of 121 different MLL rearrangements, of which 79 TPGs are now characterized at the molecular level. However, only seven rearrangements seem to be predominantly associated with illegitimate recombinations of the MLL gene (∼90%): AFF1/AF4, MLLT3/AF9, MLLT1/ENL, MLLT10/AF10, ELL, partial tandem duplications (MLL PTDs) and MLLT4/AF6, respectively. The MLL breakpoint distributions for all clinical relevant subtypes (gender, disease type, age at diagnosis, reciprocal, complex and therapy-induced translocations) are presented. Finally, we present the extending network of reciprocal MLL fusions deriving from complex rearrangements.
doi:10.1038/leu.2013.135
PMCID: PMC3826032  PMID: 23628958
MLL; chromosomal translocations; translocation partner genes; acute leukemia; ALL; AML

Results 1-5 (5)