Skin microbiota analysis in human 3D skin models—“Free your mice”

In the May issue of Experimental Dermatology 2018, we published a review article focusing on human 3D skin models in the context of microbiota research. The principal intention was to provide an overview of present and future concepts to use skin models in microbiota analyses. With the present viewpoint, we would like to draw the reader's attention again to the use of human skin models in microbiota research with the aim to highlight the benefits and necessity of human skin models to analyse the human skin-microbiota interaction. This is accompanied by a critical view on mice models that often are not suitable to analyse the functional impact of the human skin microbiota. In addition, we present novel and future concepts highlighting the benefits of human 3D skin models in microbiota research.     

Screening for Blunt Cerebrovascular Injuries: The Essential Role of Computed Tomography Angiography

The implementation of aggressive diagnostics refuted the thesis that blunt cerebrovascular injuries (BCVI) are rare events. Given the estimates from recent studies, the prevalence may be as high as 1 per 100 among blunt multiple trauma patients. The morbidity and mortality of unrecognized and untreated BCVI is exceptionally high and warrants distinct efforts to detect these injuries during the primary trauma survey. The primary goal is to detect BCVI before neurological symptoms occur, and to introduce anticoagulation or antiplatelet therapy as appropriate. Index injuries such as cervical spine fractures increase the prior probability of disease, but are not helpful in ruling BCVI out. Computed tomography angiography (CTA) may represent the screening tool of choice, although there is still limited evidence about its accuracy. Pooled data from six studies (1368 patients) published between 2002 and 2006 suggest a sensitivity of 79% and a specificity of 97% in the trauma setting. In the two largest investigations, no false negative results were observed. Further research is needed to determine the efficacy of CTA for disclosing BCVI, and to evaluate the potential benefits to patients.     

A Humanistic Approach to Understanding Child Consumer Socialization in US Homes

We present findings from a qualitative, multisite, multi-method, longitudinal study of parents and their preschool-aged children that explores the intersections of marketing influences in the home and in the larger outside world of children. Findings indicate that preschoolers represent complicated and nuanced “consumers in training” beyond predictions based on their “perceptual stage of development.” Specifically, our data revealed interesting ways in which marketing and consumer culture can foster a number of pro-social consumer outcomes (e.g., charity, gift-giving, financial literacy). We also noted an emerging understanding by preschoolers of the social meanings of goods for identity construction and product evaluation. Finally, through a presentation of an idiographic case, we show how consumer socialization cannot be attributed to one factor such as media but is based on multiple and concurrent factors—parents, siblings, peers, and home environment—that act to moderate, mediate, and provide meaning for marketing messages.     

Relationship between intracochlear electrode position and tinnitus in cochlear implantees

Conclusion: Cochlear implant electrode position has an impact on the rate of tinnitus suppression and generation. Objective: Suppression of pre-operative tinnitus or a generation of a new tinnitus in cochlear implantees is a known effect of cochlear implantation. The aim of the current study was to evaluate different cochlear implant electrode positions and their relationship with tinnitus suppression and tinnitus generation. Method: This study retrospectively evaluated four groups of CI recipients with radiologically evaluated electrode positions in relation to their subjective tinnitus quality, as evaluated by an analogue loudness scale (ALS) and a questionnaire. Group 1 consisted of 19 patients with a scalar change of the electrode position. Group 2 consisted of 18 patients with a scala tympani position and a perimodiolar electrode. Group 3 consisted of 10 patients with a scala tympani position and a lateral wall electrode. Group 4 consisted of eight patients with a scala vestibuli position. Results: An overall tinnitus suppression rate of 45.9% and a generation of a new tinnitus or the deterioration of an existing one of 5.6% were observed. A significant difference in tinnitus suppression was found between groups 1 and groups 2, 3, and 4 in tinnitus suppression and tinnitus generation.     

Evidence from pupillometry and fMRI indicates reduced neural response during vicarious social pain but not physical pain in autism

Autism spectrum disorder (ASD) is characterized by substantial social deficits. The notion that dysfunctions in neural circuits involved in sharing another's affect explain these deficits is appealing, but has received only modest experimental support. Here we evaluated a complex paradigm on the vicarious social pain of embarrassment to probe social deficits in ASD as to whether it is more potent than paradigms currently in use. To do so we acquired pupillometry and fMRI in young adults with ASD and matched healthy controls. During a simple vicarious physical pain task no differences emerged between groups in behavior, pupillometry, and neural activation of the anterior insula (AIC) and anterior cingulate cortex (ACC). In contrast, processing complex vicarious social pain yielded reduced responses in ASD on all physiological measures of sharing another's affect. The reduced activity within the AIC was thereby explained by the severity of autistic symptoms in the social and affective domain. Additionally, behavioral responses lacked correspondence with the anterior cingulate and anterior insula cortex activity found in controls. Instead, behavioral responses in ASD were associated with hippocampal activity. The observed dissociation echoes the clinical observations that deficits in ASD are most pronounced in complex social situations and simple tasks may not probe the dysfunctions in neural pathways involved in sharing affect. Our results are highly relevant because individuals with ASD may have preserved abilities to share another's physical pain but still have problems with the vicarious representation of more complex emotions that matter in life. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.     

Synergistic interaction of the histone deacetylase inhibitor SAHA with the proteasome inhibitor bortezomib in mantle cell lymphoma

Objectives:  Mantle cell lymphoma (MCL) is an incurable B cell lymphoma, and novel treatment strategies are urgently needed. We evaluated the effects of combined treatment with the proteasome inhibitor bortezomib and the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA) on MCL. Bortezomib acts by targeting the proteasome, and – among other mechanisms – results in a reduced nuclear factor-kappa B (NF-κB) activity. HDACi promote histone acetylation, and also interfere with NF-κB signaling.
Methods:  Human MCL cell lines (JeKo-1, Granta-519 and Hbl-2) were exposed to bortezomib and/or SAHA. Cell viability and apoptosis were quantified by the MTT and annexin-V assay, respectively. Reactive oxygen species (ROS) were analyzed using the fluorophore H₂DCFDA. In addition, activated caspases, proteasome- and NF-κB activity were quantified.
Results:  Combined incubation with bortezomib and SAHA resulted in synergistic cytotoxic effects, as indicated by combination index values <1 using the median effect method of Chou and Talalay. The combination of both inhibitors led to a strong increase in apoptosis as compared to single agents and was accompanied by enhanced ROS generation, while each agent alone only modestly induced ROS. The free radical scavenger N -acetyl- l -cysteine blocked the ROS generation and reduced the apoptosis significantly. In addition, coexposure of bortezomib and SAHA led to increased caspase-3, -8 and -9 activity, marked reduction of proteasome activity and decrease of NF-κB activity.
Conclusions:  This is the first report giving evidence that SAHA and bortezomib synergistically induce apoptosis in MCL cells. These data build the framework for clinical trials using combined proteasome and histone deacetylase inhibition in the treatment of MCL.     

Multiple-step relayed correlation spectroscopy: sequential resonance assignments in oligosaccharides.

A general property of the high-resolution proton NMR spectra of oligosaccharides is the appearance of low-field well-resolved resonances corresponding to the anomeric (H1) and H2 protons. The remaining skeletal protons resonate in the region 3-4 ppm, giving rise to an envelope of poorly resolved resonances. Assignments can be made from the H1 and H2 protons to their J-coupled neighbors (H2 and H3) within this main envelope by using 1H-1H correlated spectroscopy. However, the tight coupling (J congruent to delta) between further protons results in poor spectral dispersion with consequent assignment ambiguities. We describe here three-step two-dimensional relayed correlation spectroscopy and show how it can be used to correlate the resolved anomeric (H1) and H2 protons with remote (H4, H5) protons directly through a linear network of couplings using sequential magnetization transfer around the oligosaccharide rings. Resonance assignments are then obtained by inspection of cross-peaks that appear in well-resolved regions of the two-dimensional spectrum. This offers a general solution to the assignment problem in oligosaccharides and, importantly, these assignments will subsequently allow for the three-dimensional solution conformation to be determined by using one-dimensional and two-dimensional nuclear Overhauser experiments.     

Retrieval of contextual memories increases activity-regulated cytoskeleton-associated protein in the amygdala and hippocampus

Activity-regulated cytoskeleton-associated protein (Arc) integrates information from multiple intracellular signaling cascades and, in turn, regulates cytoskeletal proteins involved in structural synaptic modifications. The purposes of the present study were: (1) to determine if the retrieval of contextual memories would induce Arc in hippocampal and amygdalar neurons; (2) use unbiased stereology at the ultrastructural level to quantify synapses contacting Arc-labeled (Arc+) and unlabeled (Arc?) postsynaptic structures in brain regions in which the amount of Arc integrated density (ID) correlated strongly with the degree of amphetamine conditioned place preference (AMPH CPP). The retrieval of contextual memories increased the Arc ID in the dentate gyrus, cornu ammonis (CA)1, and CA3 fields of the hippocampus and the basolateral, lateral, and central nuclei of the amygdala but not the primary auditory cortex, a control region. Stereological quantification of Arc+ and Arc? synapses in the basolateral nucleus of the amygdala (BLA) was undertaken because the strongest relationship between the amount of Arc ID and AMPH CPP was observed in the BLA. The retrieval of contextual memories increased the number and density of asymmetric (presumed excitatory) synapses contacting Arc+ spines and dendrites of BLA neurons, symmetric (presumed inhibitory or modulatory) synapses contacting Arc+ dendrites of BLA neurons, and multisynaptic boutons contacting Arc+ postsynaptic structures. Thus, the retrieval of contextual memories increases Arc in the amygdala and hippocampus, an effect that could be important for approach behavior to a drug-associated context.