DMBT1 expression distinguishes anorectal from cutaneous melanoma

Aims:  Anorectal melanoma (AM) forms a rare but highly malignant subset of mucosal melanoma with an extremely poor prognosis. Although AMs display histological and immunohistochemical features very similar to cutaneous melanoma (CM), no association exists either with exposure to ultraviolet light or with melanocytic naevi. While AMs are clearly distinguished from CM by displaying few BRAF mutations, they are commonly indistinguishable from CM at the level of gene expression. The aim was to carry out expression analyses of classical immunohistochemical markers and of the protein deleted in malignant brain tumours 1 (DMBT1) in cases of primary anorectal malignant melanoma and CM.
Methods and results:  Expression analyses of classical immunohistochemical markers (S100, HMB45, Melan A and MiTF) and of the protein DMBT1 were carried out in 27 cases of primary anorectal malignant melanoma and 26 cases of CM. All AM cases analysed showed expression of at least three of the classical markers for melanoma. However, immunohistochemistry showed 19 out of 27 AM to be positive for DMBT1, which represented a statistically significant difference ( P  = 0.0009) compared with CM (six out of 26), which more commonly are negative for DMBT1 expression.
Conclusion:  These results identify DMBT1 as a molecular feature that may allow distinction between AM and CM and support the notion that AM represents an entity molecularly distinct from CM.     

Phagocytosis of mycobacteria by zebrafish macrophages is dependent on the scavenger receptor Marco,a key control factor of pro-inflammatory signalling

Scavenger receptors on the cell surface of macrophages play an important role in host defence through their ability to bind microbial ligands and induce phagocytosis. Concurrently, signal transduction pathways are initiated that aid in defence mechanisms against the invading microbe. Here we report on the function of scavenger receptor Marco (Macrophage receptor with collagenous structure) during infection of zebrafish embryos with Mycobacterium marinum, a close relative of M. tuberculosis. Morpholino knockdown demonstrates that Marco is required for the rapid phagocytosis of M. marinum following intravenous infection. Furthermore, gene expression analysis shows that Marco controls the initial transient pro-inflammatory response to M. marinum and remains a determining factor for the immune response signature at later stages of infection. Increased bacterial burden following marco knockdown indicates that this scavenger receptor is important for control of M. marinum growth, likely due to delayed phagocytosis and reduced pro-inflammatory signalling observed under conditions of Marco deficiency.     

Thickness distribution of the glenohumeral joint cartilage: a quantitative study using computed tomography

Purpose

Among late signs like sclerosis, cysts and osteophytes, alteration of cartilage is a common problem in osteoarthritis. To detect abnormal states in the glenohumeral joint, the physiologic distribution of the cartilage thickness must be known, which will allow physicians to better advise patients. High-resolution computed tomography (CT) data in soft tissue kernel provide highly accurate quantitative results and are a useful method to determine the geometrical situation of the glenohumeral joint. The objective of this study was to characterize the distribution of the thickness of the glenohumeral joint cartilage using CT.

Methods

To investigate the distribution of thickness of the joint cartilage, CT images in soft tissue kernel of nine specimens were analyzed using image visualization software. Statistical analysis of the obtained data was performed using the ANOVA test.

Results

Results showed different patterns in the glenoid cavity than in humeral head. Cartilage thickness in all glenoids showed maxima in the inferior and anterior portion, whereas central areas are covered with the thinnest cartilage layer. Maximum cartilage thickness in the humeral head was found in the central and superior parts.

Conclusion

We could show that the distribution of cartilage thickness in the glenohumeral joint is not homogenous and that there exist several reproducible patterns. Evaluation of cartilage thickness in the glenohumeral joint is of high interest in basic and clinical research.     

Vespertilionid bats control the width of their biosonar sound beam dynamically during prey pursuit

Animals using sound for communication emit directional signals, focusing most acoustic energy in one direction. Echolocating bats are listening for soft echoes from insects. Therefore, a directional biosonar sound beam greatly increases detection probability in the forward direction and decreases off-axis echoes. However, high directionality has context-specific disadvantages: at close range the detection space will be vastly reduced, making a broad beam favorable. Hence, a flexible system would be very advantageous. We investigated whether bats can dynamically change directionality of their biosonar during aerial pursuit of insects. We trained five Myotis daubentonii and one Eptesicus serotinus to capture tethered mealworms and recorded their echolocation signals with a multimicrophone array. The results show that the bats broaden the echolocation beam drastically in the terminal phase of prey pursuit. M. daubentonii increased the half-amplitude angle from approximately 40° to approximately 90° horizontally and from approximately 45° to more than 90° vertically. The increase in beam width is achieved by lowering the frequency by roughly one octave from approximately 55 kHz to approximately 27.5 kHz. The E. serotinus showed beam broadening remarkably similar to that of M. daubentonii. Our results demonstrate dynamic control of beam width in both species. Hence, we propose directionality as an explanation for the frequency decrease observed in the buzz of aerial hawking vespertilionid bats. We predict that future studies will reveal dynamic control of beam width in a broad range of acoustically communicating animals.     

Rapid assessment of blood pressure in the obstetric day unit using Microlife MaM technology.

OBJECTIVE: To compare MaM technology with current methods of assessing blood pressure (BP) over time on the obstetric day unit. BACKGROUND: It is recommended that the average of repeated measures is used to confirm hypertension in pregnancy. The Microlife 3AC1 is a validated oscillometric device featuring "MaM" mode using the average of at least 3 BP readings 15 seconds apart. This allows rapid assessment of BP. The difference between each measurement is calculated and influences the percentage contribution to the final average reading. We compared MaM with readings taken in a conventional manner. METHODS: Blood pressure was measured in 30 hypertensive pregnant patients recruited from the obstetric day unit of a large teaching hospital. Single BP measurements were taken at 0, 15, 30, 60, and 90 minutes using the Microlife BP 3BT0-A[2]. Simultaneous measurements (in the opposite arm) were also taken at 0 and 90 minutes using MaM technology. RESULTS: Systolic BP fell over 90 minutes (p = 0.035) compared with the first single reading, but diastolic BP did not (p = 0.54). The difference between the first MaM and the first single reading was significantly different for systolic BP (5.6 mm Hg, p = 0.017), but not for diastolic (0.6 mm Hg, p = 0.39). The mean of all single readings and the first MaM reading were similar for both systolic and diastolic BP (SBP:0.3 mm Hg, p = 0.75, DBP: 0.2 mm Hg, p = 0.87). Conclusions: White-coat hypertension exists for systolic BP in the obstetric day unit. The MaM technology allows rapid and accurate characterization of blood pressure equivalent to repeated measures over 90 minutes.     

Preschool children’s attachment security is associated with their sharing with others

The current study examined relations between preschool children’s attachment pattern and their sharing behavior. To this end, 26 German children aged five years (15 girls) were first administered an Attachment Story Completion Task to assess their attachment pattern and the degree of their attachment security. Immediately thereafter, they participated in an established paradigm, a mini-dictator game, that assessed their inclination to share costly as well as noncostly with a friend, a disliked other, and a stranger. Analyses showed that degree of attachment security was positively correlated with children’s generosity towards a disliked other and their inclination to engage in costly sharing. Moreover, the absence of an organized attachment pattern was related to a general decrease in generosity towards all recipients. The results point to the functional role of children’s attachment for the early development of sharing behavior.     

USH2A mutation analysis in 70 Dutch families with Usher syndrome type II

Usher syndrome type II (USH2) is characterised by moderate to severe high-frequency hearing impairment, progressive visual loss due to retinitis pigmentosa and intact vestibular responses. Three loci are known for USH2, however, only the gene for USH2a (USH2A) has been identified. Mutation analysis of USH2A was performed in 70 Dutch USH2 families. Ten mutations in USH2A were detected, of which three are novel, c.949C>A, c.2242C>T (p.Gln748X) and c.4405C>T (p.Gln1468X). Including 9 previously published Dutch USH2a families, estimates of the prevalence of USH2a in the Dutch USH2 population were made. Mutations were identified in 62% of the families. In 28% both mutated alleles were identified, whereas in 34% the mutation in only one allele was found. It is estimated that about 28% of the Dutch USH2 families have a different causative gene. Analysis of deduced haplotypes suggests that c.1256G>T (p.Cys419Phe) is a Dutch ancestral mutation, occurring in 16% of the alleles.     

How neutrophils kill fungi

Neutrophils play a critical role in the prevention of invasive fungal infections. Whereas mouse studies have demonstrated the role of various neutrophil pathogen recognition receptors (PRRs), signal transduction pathways, and cytotoxicity in the murine antifungal immune response, much less is known about the killing of fungi by human neutrophils. Recently, novel primary immunodeficiencies have been identified in patients with a susceptibility to fungal infections. These human ‘knock-out’ neutrophils expand our knowledge to understand the role of PRRs and signaling in human fungal killing. From the studies with these patients it is becoming clear that neutrophils employ fundamentally distinct mechanisms to kill Candida albicans or Aspergillus fumigatus.