Long stretches of glutamine (Q) residues are found in many cellular proteins. Expansion of these polyglutamine (polyQ) sequences is the underlying cause of several neurodegenerative diseases (e.g. Huntington's disease). Eukaryotic proteasomes have been found to digest polyQ sequences in proteins very slowly, or not at all, and to release such potentially toxic sequences for degradation by other peptidases. To identify these key peptidases, we investigated the degradation in cell extracts of model Q-rich fluorescent substrates and peptides containing 10-30 Q's. Their degradation at neutral pH was due to a single aminopeptidase, the puromycin-sensitive aminopeptidase (PSA, cytosol alanyl aminopeptidase). No other known cytosolic aminopeptidase or endopeptidase was found to digest these polyQ peptides. Although tripeptidyl peptidase II (TPPII) exhibited limited activity, studies with specific inhibitors, pure enzymes and extracts of cells treated with siRNA for TPPII or PSA showed PSA to be the rate-limiting activity against polyQ peptides up to 30 residues long.(PSA digests such Q sequences, shorter ones and typical (non-repeating) peptides at similar rates.) Thus, PSA, which is induced in neurons expressing mutant huntingtin, appears critical in preventing the accumulation of polyQ peptides in normal cells, and its activity may influence susceptibility to polyQ diseases.

This review focuses on recent insights into the mechanisms and the biological functions of the proteasome. This large ATP-dependent proteolytic complex is the main site for protein degradation in mammalian cells and catalyses the rapid degradation of ubiquitinated proteins, and is the source of most antigenic peptides used by the immune system to screen for viruses and cancer. ATP is required to unfold globular proteins to open the gated channel into the 20S proteasome and to facilitate protein translation into it. Inhibitors of its proteolytic activity are widely used as research tools and have proven effective in cancer therapy.

Changing environment is a reason, that many saprotrophic fungi became opportunists and in the end also maybe a pathogenic. Host specific adaptation is not so strong among fungi, so there are many common fungal pathogens for people and for animals. Animals suffering from dermatomycosis are well recognize as source of human superficial mycoses. Breeding of different exotic animals such as parrots, various Reptiles and Amphibians, miniature Rodents and keeping them as a pets in the peoples houses, have become more and more popular in the recent years. This article is shortly presenting which animals maybe a potential source of fungal infections for humans. Looking for the other mycoses as systemic mycoses, especially candidiasis or aspergilosis there are no data, which allow excluding sick animals as a source of infection for human, even if those deep mycoses have endogenic reactivation mechanism. Immunocompromised people are in high-risk group when they take care of animals. Another important source of potentially pathogenic, mostly air-born fungi may be animal use in experimental laboratory work. During the experiments is possible that laboratory workers maybe hurt and these animals and their environment, food and house boxes could be the possible source of microorganisms, pathogenic for humans or other animals. Unusual way to inoculate these potentially pathogens into the skin of laboratory personnel may cause granulomatous, local lesions on their hands.

The species composition of pathogenic fungi isolated from various clinical materials was studied in the diagnosis of respiratory mycotic infections in patients with tuberculosis. The paper presents data on the composition of detected opportunistic microscopic fungi from a group of likely pathogens of bronchopulmonary mycoses, as well as fungi that have pronounced toxicogenic and allergenic properties.

BACKGROUND: The number of diseases caused by yeast and fungi has been increasing recently. The primary disease is caused by dermatophytes and Cryptococcus neoformans. Other types of yeast and fungi can cause secondary infections of patients with predisposition factors. Among the mycotic diseases diagnosed in our laboratory can be included candidosis, cryptococcosis, aspergillosis and mucormycosis. METHODS AND RESULTS: In haematological patients Candida albicans, Candida glabrata, Candida krusei, Candida tropicalis and Saccharomyces cerevisiae are the most frequently diagnosed. CONCLUSIONS: Together with the increased number of examined samples, the rising number of strains resistant to azole antimycotics can be observed.

Invasive mycoses pose a major diagnostic and therapeutic challenge. Advances in antifungal agents and diagnostic methods offer the potential for improved outcomes in patients with these infections, which are often lethal. Many fungal pathogens occur almost exclusively in opportunistic settings--in the immunocompromised host--and these infections are the focus of this review. Several areas of ongoing challenge remain, including the emergence of resistant organisms and the absence of reliable markers for early identification of patients at risk of developing invasive fungal disease. This Seminar reviews the changing epidemiology of invasive mycoses, new diagnostic methods, and recent therapeutic options and current management strategies for these opportunistic pathogens.

In recent years, mycoses have emerged as important infections in clinical practice. This phenomenon is explained by the ever growing number of immunocompromised patients and the increasing number of people travelling in areas where fungal diseases are endemic. Head and neck infections are common in disseminated mycoses and may simulate carcinoma or cause upper airway obstruction. The most frequent causative yeasts or yeast-like organisms include Candida albicans, Cryptococcus neoformans, Histoplasma capsulatum var capsulatum, Blastomyces dermatitidis, Paracoccidioides brasiliensis and Coccidioides immitis. Other causative fungal pathogens include Aspergillus fumigatus and less frequently, Rhizopus oryzae and Rhinosporidium seeberi. Since in most cases their pathophysiology is similar, those microorganisms share a common clinical pathological presentation. Symptoms such as dysphonia or dysphagia associated with hyperplastic and ulcerative lesions on endoscopic examination should prompt biopsies. A purulent or granulomatous inflammatory tissue reaction with pseudoepitheliomatous hyperplasia warrants caution since it may lead to a mistaken diagnosis of carcinoma. The pathologist must look carefully for microorganisms with Grocott and PAS stains. The causative agent can be identified if the pathologist is aware of the risk. Positive culture is needed to institute adequate treatment.