Neurophysiological Defects and Neuronal Gene Deregulation in Drosophila mir-124 Mutants

miR-124 is conserved in sequence and neuronal expression across the animal kingdom and is predicted to have hundreds of mRNA targets. Diverse defects in neural development and function were reported from miR-124 antisense studies in vertebrates, but a nematode knockout of mir-124 surprisingly lacked detectable phenotypes. To provide genetic insight from Drosophila, we deleted its single mir-124 locus and found that it is dispensable for gross aspects of neural specification and differentiation. On the other hand, we detected a variety of mutant phenotypes that were rescuable by a mir-124 genomic transgene, including short lifespan, increased dendrite variation, impaired larval locomotion, and aberrant synaptic release at the NMJ. These phenotypes reflect extensive requirements of miR-124 even under optimal culture conditions. Comparison of the transcriptomes of cells from wild-type and mir-124 mutant animals, purified on the basis of mir-124 promoter activity, revealed broad upregulation of direct miR-124 targets. However, in contrast to the proposed mutual exclusion model for miR-124 function, its functional targets were relatively highly expressed in miR-124–expressing cells and were not enriched in genes annotated with epidermal expression. A notable aspect of the direct miR-124 network was coordinate targeting of five positive components in the retrograde BMP signaling pathway, whose activation in neurons increases synaptic release at the NMJ, similar to mir-124 mutants. Derepression of the direct miR-124 target network also had many secondary effects, including over-activity of other post-transcriptional repressors and a net incomplete transition from a neuroblast to a neuronal gene expression signature. Altogether, these studies demonstrate complex consequences of miR-124 loss on neural gene expression and neurophysiology

Method for the determination of aldehyde residues on flexible endoscopes

Het Rijksinstituut voor Volksgezondheid en Milieu heeft een methode ontwikkeld voor de extractie van formaldehyde en glutaaraldehyde residuen op flexibele endoscopen en de daarbij behorende analyse van deze extractiemonsters. Om inzicht te krijgen in de hoeveelheden aldehyde residuen op endoscopen uit de dagelijkse praktijk is de methode toegepast op 38 gastroscopen uit 13 ziekenhuizen. De extractie van het distale uiteinde van endoscopen werd met water uitgevoerd bij 40 graden C in een glazen buis met een verwarmingsmantel. Voor de analyse reageerden de aldehyden met het reagent DNPH. De ontstane verbindingen konden worden gescheiden en gedetecteerd met HPLC-technieken. De ontwikkelde methode is gevoelig genoeg om de aanwezige hoeveelheden aldehyden op het distale einde van endoscopen te detecteren en kwantificeren. De maximaal gedetecteerde hoeveelheden formaldehyde en glutaaraldehyde op een gastroscoop bedroegen respectievelijk 11,0 plus of min 4,4 ug en 68,0 plus of min 27,2 ug. Er waren significante verschillen tussen de hoeveelheden residueel formaldehyde en glutaaraldehyde op endoscopen in de bezochte ziekenhuizen. Bovendien was er een significant verschil tussen de hoeveelheden residueel formaldehyde op endoscopen die met verschillende desinfectantia waren gedesinfecteerd. De ontwikkelde methode kan worden gebruikt voor de procesontwikkeling van endoscopendesinfectoren, wanneer er twijfel is over de staat van een endoscoop en om de hoeveelheden aldehyden te vergelijken wanneer verschillende desinfectantia worden gebruikt.The Dutch National Institute for Public Health and the Environment has developed a method for the extraction of formaldehyde and glutaraldehyde residues on flexible endoscopes and for the analysis of these extraction samples. This method was used on 38 gastroscopes in 13 hospitals to gain an insight into the amount of aldehyde residues on endoscopes used in daily routine. The extraction of the distal end of endoscopes was performed at 40 degrees C in a jacketed glass tube using water as the extraction fluid. The aldehydes combined with the reagent DNPH, allowing these compounds to be separated and detected using HPLC techniques. The method is sensitive enough to detect and quantify residues of formaldehyde and glutaraldehyde present at the distal end of flexible endoscopes. The maximum amounts of formaldehyde and glutaraldehyde on a gastroscope during this investigation came to 11.0 plus or minus 4.4 ug and 68.0 plus or minus 27.2 ug, respectively. There were significant differences between the amount of residual formaldehyde and glutaraldehyde on the endoscopes, depending on the hospital it came from. Moreover, there was a significant difference between the amount of residual formaldehyde on endoscopes that had been disinfected using different disinfectants. This method can be used for process development of endoscope washer-disinfectors, when there is doubt about the condition of an endoscope and to compare the levels of residual aldehydes when using different disinfectants.IGZVWS-GM

Method for the determination of aldehyde residues on flexible endoscopes

The Dutch National Institute for Public Health and the Environment has developed a method for the extraction of formaldehyde and glutaraldehyde residues on flexible endoscopes and for the analysis of these extraction samples. This method was used on 38 gastroscopes in 13 hospitals to gain an insight into the amount of aldehyde residues on endoscopes used in daily routine. The extraction of the distal end of endoscopes was performed at 40 degrees C in a jacketed glass tube using water as the extraction fluid. The aldehydes combined with the reagent DNPH, allowing these compounds to be separated and detected using HPLC techniques. The method is sensitive enough to detect and quantify residues of formaldehyde and glutaraldehyde present at the distal end of flexible endoscopes. The maximum amounts of formaldehyde and glutaraldehyde on a gastroscope during this investigation came to 11.0 plus or minus 4.4 ug and 68.0 plus or minus 27.2 ug, respectively. There were significant differences between the amount of residual formaldehyde and glutaraldehyde on the endoscopes, depending on the hospital it came from. Moreover, there was a significant difference between the amount of residual formaldehyde on endoscopes that had been disinfected using different disinfectants. This method can be used for process development of endoscope washer-disinfectors, when there is doubt about the condition of an endoscope and to compare the levels of residual aldehydes when using different disinfectants.Het Rijksinstituut voor Volksgezondheid en Milieu heeft een methode ontwikkeld voor de extractie van formaldehyde en glutaaraldehyde residuen op flexibele endoscopen en de daarbij behorende analyse van deze extractiemonsters. Om inzicht te krijgen in de hoeveelheden aldehyde residuen op endoscopen uit de dagelijkse praktijk is de methode toegepast op 38 gastroscopen uit 13 ziekenhuizen. De extractie van het distale uiteinde van endoscopen werd met water uitgevoerd bij 40 graden C in een glazen buis met een verwarmingsmantel. Voor de analyse reageerden de aldehyden met het reagent DNPH. De ontstane verbindingen konden worden gescheiden en gedetecteerd met HPLC-technieken. De ontwikkelde methode is gevoelig genoeg om de aanwezige hoeveelheden aldehyden op het distale einde van endoscopen te detecteren en kwantificeren. De maximaal gedetecteerde hoeveelheden formaldehyde en glutaaraldehyde op een gastroscoop bedroegen respectievelijk 11,0 plus of min 4,4 ug en 68,0 plus of min 27,2 ug. Er waren significante verschillen tussen de hoeveelheden residueel formaldehyde en glutaaraldehyde op endoscopen in de bezochte ziekenhuizen. Bovendien was er een significant verschil tussen de hoeveelheden residueel formaldehyde op endoscopen die met verschillende desinfectantia waren gedesinfecteerd. De ontwikkelde methode kan worden gebruikt voor de procesontwikkeling van endoscopendesinfectoren, wanneer er twijfel is over de staat van een endoscoop en om de hoeveelheden aldehyden te vergelijken wanneer verschillende desinfectantia worden gebruikt

Aspergillus niger causing tracheobronchitis and invasive pulmonary aspergillosis in a lung transplant recipient: case report

A case of invasive aspergillosis caused by Aspergillus niger in a lung transplant recipient is described. The patient presented hyperglycemia starting postoperatively, with other complications such as cytomegalovirus infection. The associated predisposing factors and other implications are discussed. Aspergillus niger seems to be a fungal species of low virulence that requires the presence of a severely immunosuppressed host to cause invasive disease.Descreve-se um caso de aspergilose invasiva causada por Aspergillus niger em um paciente transplantado de pulmão com quadros hiperglicêmicos desde o pós-operatório e outras complicações como infecção por citomegalovírus. Os fatores predisponentes associados e outras implicações são discutidos. Aspergillus niger parece ser uma espécie fúngica de baixa virulência, necessitando a presença de um hospedeiro gravemente imunodeprimido para causar doença invasiva

Locking alleviation in the large displacement analysis of beam elements: the strain split method

This paper proposes a new locking alleviation technique for absolute nodal coordinate formulation (ANCF) beam and plate elements based on a strain split approach. The paper also surveys classical finite element (FE) and ANCF locking alleviation techniques discussed in the literature. Because ANCF beam elements, which allow for the cross-sectional stretch fully capture the Poisson effect, Poisson locking is an issue when such beam elements are considered. The two-dimensional fully parameterized ANCF beam element is primarily used in this investigation because such an element can serve as a good surrogate model for three-dimensional ANCF beams and plates as far as membrane, bending and transverse shearing behavior is concerned. In addition to proposing the strain split method (SSM) for ANCF locking alleviation, this work assesses the ANCF element performance in the cases of higher-order interpolation, enhanced assumed strain method, elastic line method, and the enhanced continuum mechanics approach, and demonstrates the design of the enhanced strain interpolation function by using the shape functions of higher-order ANCF elements. Additionally, a new higher-order ANCF two-dimensional beam element is proposed in order to compare its performance with other finite elements that require the use of other locking alleviation techniques proposed and reviewed in the paper. Finally, several numerical examples are shown to demonstrate the effectiveness of the locking alleviation methods applied to ANCF elements. The purpose of this investigation, apart from proposing a new locking alleviation technique, a new higher-order beam element, and comparing several existing locking alleviation techniques, is to show that dealing with locking in fully parameterized ANCF elements is feasible and that several methods exist to effectively improve the ANCF element performance without sacrificing important ANCF element properties and features including position vector gradient continuity. Because of the use of ANCF position vector gradients as nodal coordinates, complex stress-free initially-curved geometries can be systematically obtained. Such initially-curved geometries require special attention when attempting to solve locking problems, as will be discussed in this paper

Mechanism of CDK5 activation revealed by steered molecular dynamics simulations and energy calculations

10.1007/s00894-009-0629-4Journal of Molecular Modeling1661159-1168JMMO