Degradation of human kininogens with the release of kinin peptides by extracellular proteinases of Candida spp.

The secretion of proteolytic enzymes by pathogenic microorganisms is one of the most successful strategies used by pathogens to colonize and infect the host organism. The extracellular microbial proteinases can seriously deregulate the homeostatic proteolytic cascades of the host, including the kinin-forming system, repeatedly reported to he activated during bacterial infection. The current study assigns a kinin-releasing activity to secreted proteinases of Candida spp. yeasts, the major fungal pathogens of humans. Of several Candida species studied, C. parapsilosis and C. albicans in their invasive filamentous forms are shown to produce proteinases which most effectively degrade proteinaceous kinin precursors, the kininogens. These enzymes, classified as aspartyl proteinases, have the highest kininogen-degrading activity at low pH (approx. 3.5), but the associated production of bradykinin-related peptides from a small fraction of kininogen molecules is optimal at neutral pH (6.5). The peptides effectively interact with cellular B2-type kinin receptors. Moreover, kinin-related peptides capable of interacting with inflammation-induced B1-type receptors are also formed, but with a reversed pH dependence. The presented variability of the potential extracellular kinin production by secreted aspartyl proteinases of Candida spp. is consistent with the known adaptability of these opportunistic pathogens to different niches in the host organism

Positive effects of a novel non-peptidyl low molecular weight radical scavenger in renal ischemia/reperfusion: a preliminary report

Ischemia/reperfusion (I/R) is one of the most common causes of acute kidney injury. Reactive oxygen species have been recognized to be an important contributor to the pathogenesis of I/R injury. We hypothesize that a non-peptidyl low molecular weight radical scavenger (IAC) therapy may counteract this factor, ultimately providing some protection after acute phase renal I/R injury. The aim of this preliminary study was to assess the ability of IAC to reduce acute kidney injury in C57BL/6 mice after 30-minute of bilateral ischemia followed by reperfusion. The rise in serum creatinine level was higher in C57BL/6 control mice after I/R when compared to IAC (1 mg)-treated mice. Control mice showed greater body weight loss compared to IAC-treated mice, and at pathology, reduced signs of tubular necrosis were also evident in IAC-treated mice. These preliminary evidences lay the basis for more comprehensive studies on the positive effects of IAC as a complementary therapeutic approach for acute phase renal I/R injury

Genomic profiling of malignant peritoneal mesothelioma reveals recurrent alterations in epigenetic regulatory genes BAP1, SETD2, and DDX3X.

Malignant mesothelioma is a rare cancer that arises from the mesothelial cells that line the pleural cavity and less commonly from the peritoneal lining of the abdomen and pelvis. Most pleural mesotheliomas arise in patients with a history of asbestos exposure, whereas the association of peritoneal mesotheliomas with exposure to asbestos and other potential carcinogens is less clear, suggesting that the genetic alterations that drive malignant peritoneal mesothelioma may be unique from those in pleural mesothelioma. Treatment options for all malignant mesotheliomas are currently limited, with no known targeted therapies available. To better understand the molecular pathogenesis of malignant peritoneal mesothelioma, we sequenced 510 cancer-related genes in 13 patients with malignant mesothelioma arising in the peritoneal cavity. The most frequent genetic alteration was biallelic inactivation of the BAP1 gene, which occurred in 9/13 cases, with an additional two cases demonstrating monoallelic loss of BAP1. All 11 of these cases demonstrated loss of BAP1 nuclear staining by immunohistochemistry, whereas two tumors without BAP1 alteration and all 42 cases of histologic mimics in peritoneum (8 multilocular peritoneal inclusion cyst, 6 well-differentiated papillary mesothelioma of the peritoneum, 16 adenomatoid tumor, and 12 low-grade serous carcinoma of the ovary) demonstrated intact BAP1 nuclear staining. Additional recurrently mutated genes in this cohort of malignant peritoneal mesotheliomas included NF2 (3/13), SETD2 (2/13), and DDX3X (2/13). While these genes are known to be recurrently mutated in pleural mesotheliomas, the frequencies are distinct in peritoneal mesotheliomas, with nearly 85% of peritoneal tumors harboring BAP1 alterations versus only 20-30% of pleural tumors. Together, these findings demonstrate the importance of epigenetic modifiers including BAP1, SETD2, and DDX3X in mesothelial tumorigenesis and suggest opportunities for targeted therapies

Egg parasitoids of the genus Trichogramma (Hymenoptera, Trichogrammatidae) in olive groves of the Mediterranean region

A survey of egg parasitoids of the genus Trichogramma (Hymenoptera, Trichogrammatidae) was carried out in olive groves in Portugal, Greece, Egypt, and Tunisia during the years 2002–2004. Parasitoids were obtained either by exposing sentinel eggs (Sitotroga cerealella Olivier or Ephestia kuehniella Zeller) on olive trees or by collecting eggs of lepidopterous olive pests. Parasitized egg samples were reared separately in the laboratory for emergence of parasitoids. These were further reared in separate lines and processed by morphological and molecular biology techniques for species characterization. The recorded fauna of Trichogramma parasitoids in olive groves was species poor and consisted of species mainly known from the Mediterranean region. Trichogramma bourarachae Pintureau and Babault was found in Tunisia and Egypt, T. cordubensis Vargas and Cabello, and T. euproctidis Girault in Egypt, Trichogramma cacoeciae Marchal in Portugal, Greece, Egypt, Tunisia and Trichogramma nerudai Pintureau and Gerding in Portugal. Apart from that, Trichogramma oleae Voegele´ and Pointel was collected in Tunisia. This species is probably not indigenous, but has established after several releases of a French strain were made in recent years. For selected strains, the sequence of the internal transcribed spacer 2 (ITS-2) region of rDNA was determined and deposited in the GenBank database. Differences in important biological attributes were found among collected strains of T. bourarachae, suggesting the existence of biotypes. The results contribute to the limited knowledge on distribution and biodiversity of the genus Trichogramma in the Mediterranean region. They can be helpful for the preservation and use of indigenous Trichogramma species in biological control of lepidopterous pests in olive and other local crops

Compressed gas domestic aerosol valve design using high viscous product

Most of the current universal consumer aerosol products using high viscous product such as cooking oil, antiperspirants, hair removal cream are primarily used LPG (Liquefied Petroleum Gas) propellant which is unfriendly environmental. The advantages of the new innovative technology described in this paper are: i. No butane or other liquefied hydrocarbon gas is used as a propellant and it replaced with Compressed air, nitrogen or other safe gas propellant. ii. Customer acceptable spray quality and consistency during can lifetime iii. Conventional cans and filling technology There is only a feasible energy source which is inert gas (i.e. compressed air) to replace VOCs (Volatile Organic Compounds) and greenhouse gases, which must be avoided, to improve atomisation by generating gas bubbles and turbulence inside the atomiser insert and the actuator. This research concentrates on using “bubbly flow” in the valve stem, with injection of compressed gas into the passing flow, thus also generating turbulence. The new valve designed in this investigation using inert gases has advantageous over conventional valve with butane propellant using high viscous product (> 400 Cp) because, when the valving arrangement is fully open, there are negligible energy losses as fluid passes through the valve from the interior of the container to the actuator insert. The use of valving arrangement thus permits all pressure drops to be controlled, resulting in improved control of atomising efficiency and flow rate, whereas in conventional valves a significant pressure drops occurs through the valve which has a complex effect on the corresponding spray