Mitochondrial inheritance in haploid × non-haploid crosses in Cryptococcus neoformans

In the basidiomycetous yeast Cryptococcus neoformans, fusants and meiotic progeny from haploid–haploid (HH) crosses between strains of mating type a (MAT a) and mating type alpha (MATα) typically inherit mitochondrial DNA (mtDNA) from the MAT a parent. In this study, we investigated the mtDNA inheritance pattern in haploid × non-haploid crosses. A total of 420 meiotic progeny and 173 fusants were obtained from five crosses and analyzed for two polymorphic mitochondrial markers. The percentage of meiotic progeny and fusants inheriting mtDNA from MATα or MATα/α parents ranged from 8 to 50%. The leakage was significantly greater than those observed in HH crosses, indicating that mtDNA inheritance is not uniparental in haploid × non-haploid crosses in C. neoformans. In addition, mtDNA leakage in the fusants, but not the meiotic progeny, of the MATα/α × MAT a cross was significantly higher than that in the MAT a/a × MATα cross, suggesting that the diploid parents with different mating types contribute differently in determining fusant mtDNA genotype in these crosses. Flow cytometry analysis revealed that meiotic progeny population of each cross was of mixed ploidy while the ploidy level of the selected fusants ranged from diploid to triploid.     

Multi-functional graphene as an in vitro and in vivo imaging probe

A strategy has been developed for the synthesis of multi-functional graphene (MFG) using green synthetic approach and explored its biomedical application as a promising fluorescent marker for in vitro and in vivo imaging. In-situ microwave-assisted reduction and magnetization process was adopted to convert the graphene oxide into magnetic graphene within 1 min, which was further covalently modified to build a polyacrylic acid (PAA) bridge for linking the fluorescein o-methacrylate (FMA) to yield MFG with water-dispersibility (∼2.5 g/l) and fluorescence property (emission maximum at 526 nm). The PAA bridges also functions to prevent graphene-induced fluorescence quenching of conjugated FMA. The extent of reduction, magnetization, and functionalization was confirmed with TEM, AFM, Raman, XPS, FT-IR, TGA, and SQUID measurements. In vitro cytotoxicity study of HeLa cells reveal that MFG could stand as a biocompatible imaging probe with an IC₅₀ value of ∼100 μg/ml; whereas in vivo zebrafish study does not induce any significant abnormalities nor affects the survival rate after microinjection of MFG. Confocal laser scanning microscopy images reveals that MFG locates only in the cytoplasm region and exhibits excellent co-localization and biodistribution from the head to tail in the zebrafish. Our results demonstrate the applicability of graphene based fluorescence marker for intracellular imaging and, more significantly, as well as whole-animal imaging. Hence, MFG could preferentially serve as a dual functional probe in biomedical diagnostics.     

Candida auris: An emerging drug resistant yeast – A mini-review

Candida auris is an emerging fungal pathogen responsible for nosocomial invasive infection outbreaks on five continents. Large healthcare-related outbreaks of C. auris infection and colonization have been reported from different countries. Whole genome sequence analysis identified strong phylogeographic C. auris clades specific to particular geographical areas suggesting transmission of particular clades within countries. However, the mode of transmission within the healthcare environment is not clear and is likely to be multifactorial. The emergence of C. auris is alarming because this organism can harbor or develop multidrug resistance. This explains why C. auris infections are difficult to treat. In addition, difficulties in its identification in the routine diagnostic laboratory have a significant impact on outbreak detection and management. This mini-review highlights the available literature on C. auris, with particular insight into its epidemiology and the problems caused by its antifungal resistance.     

In vitro and in vivo antibacterial activity of tigecycline against Vibrio vulnificus

Background/purpose

The aim of this study is to investigate the role of tigecycline in Vibrio vulnificus infection.

RNA interference inhibits yellow fever virus replication in vitro and in vivo

RNA interference (RNAi) is a process that is induced by double stranded RNA and involves the degradation of specific sequences of mRNA in the cytoplasm of the eukaryotic cells. It has been used as an antiviral tool against many viruses, including flaviviruses. The genus Flavivirus contains the most important arboviruses in the world, i.e., dengue (DENV) and yellow fever (YFV). In our study, we investigated the in vitro and in vivo effect of RNAi against YFV. Using stable cell lines that expressed RNAi against YFV, the cell lines were able to inhibit as much as 97% of the viral replication. Two constructions (one against NS1 and the other against E region of YFV genome) were able to protect the adult Balb/c mice against YFV challenge. The histopathologic analysis demonstrated an important protection of the central nervous system by RNAi after 10 days of viral challenge. Our data suggests that RNAi is a potential viable therapeutic weapon against yellow fever.

Indocyanine green-loaded biodegradable tumor targeting nanoprobes for in vitro and in vivo imaging

Indocyanine green (ICG) is a near-infrared (NIR) ?uorescence dye for extensive biological application, but limited by its poor aqueous stability in?vitro, concentration-dependent aggregation, rapid elimination from the body, and lack of target specificity. In this paper, to overcome these limitations, folate receptor-targeted, ICG dye-doped poly(d,l-lactide-co-glycolide) (PLGA) lipid nanoparticles (FA-ICG-PLGA-lipid NPs) were constructed by a single-step self-assemble and nanoprecipitation method. The prepared FA-ICG-PLGA-lipid NPs exhibited good biocompatibility, monodispersity, excellent NIR penetration ability, significant stability against photobleaching and long circulation time. The intracellular uptake experiment proved the targeting efficacy of the FA-ICG-PLGA-lipid NPs was more effective in folate receptor over-expressing MCF-7 cells than folate receptor negative A549 cells. Furthermore, the in?vivo experiments showed the FA-ICG-PLGA-lipid NPs were specifically targeted to the tumor, and its circulation time was much longer than free ICG. These biocompatible and biodegradable NIR-NPs prove a potential application in tumor diagnosis and targeted imaging due to its high aqueous stability, excellent NIR optical properties and significantly targeting property in?vivo.     

Multiple endokrine Neoplasien Typ 2

Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant inherited cancer syndrome with the major components medullary thyroid carcinoma, pheochromocytoma and hyperparathyroidism. Due to the clinical course three distinct subtypes are distinguished, MEN 2A, MEN 2B and familial medullary thyroid carcinoma. The disease is caused by germ-line mutations of the RET proto-oncogene and the localization of these mutations correlates with the onset of the development of medullary thyroid carcinoma, which is crucial for the clinical course and outcome of the disease. It therefore has a substantial influence on the clinical management of the affected patients and their relatives. This review summarizes the morphology and clinic of MEN 2-associated tumors and their respective precursor lesions.     

Antihistamine therapy in allergic rhinitis

Antihistamines have long been a mainstay in the therapy for allergic rhinitis. Many different oral antihistamines are available for use, and they are classified as first generation or second generation based on their pharmacologic properties and side-effect profiles. The recent introduction of intranasal antihistamines has further expanded the role of antihistamines in the treatment of allergic rhinitis. Certain patient populations, such as children and pregnant or lactating women, require special consideration regarding antihistamine choice and dosing as part of rhinitis therapy.     

Intestinale neuronale Dysplasie Typ B

Intestinal neuronal dysplasia type B (IND B) is currently considered to be a subtle malformation of the submucosal plexus, leading to an increased proportion of over-sized ganglia and potentially accompanied by a mild, chronic gastrointestinal motility disturbance. The diagnosis of IND B is morphologically based and involves the demonstration of an increased proportion of giant ganglia in the submucous plexus related to the patient's age. Giant ganglia are physiologically frequent in the neonatal period. Therefore, IND B should not be diagnosed prior to 1 year of age. Morphological features of IND B may occur as an isolated finding or may be observed proximal to an aganglionic segment. IND B and constipation may resolve spontaneously up to the age of 4 years. Treatment of IND B is usually conservative, surgical resection is currently deemed necessary only in a minority of patients. The pathogenesis of IND B is still incompletely understood and the etiology unknown. Future research on the basis of standardized diagnostic conditions is expected to result in a better understanding of this disease, and to reveal the cause of aberrant ganglion development.     

Ultrabright and ultrastable near-infrared dye nanoparticles for in vitro and in vivo bioimaging

We report a new strategy of using carrier-free pure near-infrared (NIR) dye nanoparticles (NPs) to achieve highly luminescent NIR fluorescent probes for in?vitro and in?vivo imaging. Bis(4-(N-(2-naphthyl)phenylamino) phenyl)-fumaronitrile (NPAPF) NPs are shown to exhibit favorable biocompatibility, wide-range pH stability (pH 4-10) and much more superior photostability than conventional dyes. Importantly, the combined merits of high dye loading content and aggregation-induced emission enhancement properties, endow the NIR probes with high brightness and a high quantum yield up to 14.9%. The NPAPF NPs can be readily conjugated with folic acid for targeted in?vitro cell imaging. Applications of the NPs probes in high efficiency in?vivo and ex?vivo imaging were successfully demonstrated. Intense fluorescent signals of NPAPF NPs can be distinctly, selectively and spatially resolved in tumor sites with ultrahigh sensitivity, even with 5?ms exposure time, due to the preferentially accumulation of NPs in tumor sites through passive enhanced permeability and retention effect. The totality of results clearly demonstrate the exciting potential of the functionalized NPAPF NPs as a NIR fluorescent probe for in?vitro and in?vivo imaging and diagnostics.