Keratin Isotypes Control Desmosome Stability and Dynamics through PKCα

Expression and interaction of desmosomal components and keratins provide stable cell cohesion and protect the epidermis against various types of stress. The differentiation-specific isotype composition of the keratin cytoskeleton and desmosomes is regarded as a major determinant of adhesive strength. In support, wound healing is characterized by a transient decrease in desmosomal adhesion accompanied by increased expression of keratins K6/K16/K17 at the expense of K1/K10. The significance of altered keratin expression for desmosomal composition and adhesion remains incompletely understood at a mechanistic and functional level. Here, we investigated the respective contribution of K5/K14 or K6/K17 to desmosome adhesion, on their stable re-expression in keratinocytes lacking all keratins. This revealed that K5/K14 filaments support stable desmosomes, whereas “wound healing” keratins K6/K17 induce elevated protein kinase C alpha–mediated desmosome disassembly and subsequent destabilization of epithelial sheets. Moreover, our data suggest that K5/K14 sequester protein kinase C alpha in the cytoplasm, whereas K6/K17 or the absence of all keratins enables protein kinase C alpha translocation to the plasma membrane and induction of desmosome disassembly. Gain- and loss-of-function experiments support a major role of K5 in desmosome stability control via protein kinase C alpha. Our data show that keratin isotypes differently and specifically regulate wound healing and invasion by modulating intercellular adhesion

Food-derived serotonergic modulators: effects on mood and cognition

The most frequently described drugs in the treatment of mood disorders are selective serotonin reuptake and monoamine oxidase (MAO) inhibitors, enhancing serotonin levels in the brain. However, side-effects have been reported for these drugs. Because serotonin levels in the brain are dependent on the availability of the food-derived precursor tryptophan, foods such as chicken, soyabeans, cereals, tuna, nuts and bananas may serve as an alternative to improve mood and cognition. Here we discuss the effects of high- or low-tryptophan-containing food, as well as plant extracts with a modest monoamine reuptake and MAO-A inhibition functional profile, on mood and cognition in healthy and vulnerable human subjects and rodents. Together the studies suggest that there is an inverted U-shaped curve for plasma tryptophan levels, with low and too high tryptophan levels impairing cognition, and moderate to high tryptophan levels improving cognition. This relationship is found for both healthy and vulnerable subjects. Whereas this relationship may also exist for mood, the inverted U-shaped curve for plasma tryptophan levels and mood may be based on different tryptophan concentrations in healthy v. vulnerable individuals. Animal studies are emerging and allow further understanding of effects and the mode of action of food-derived serotonergic components on mood, cognition and mechanisms. Ultimately, insight into the concentrations of tryptophan and other serotonergic components in food having beneficial effects on mood and cognition in healthy, but particularly vulnerable, subjects may support well-being in our highly demanding societ

A Distinct Layer of the Medulla Integrates Sky Compass Signals in the Brain of an Insect

Mass migration of desert locusts is a common phenomenon in North Africa and the Middle East but how these insects navigate is still poorly understood. Laboratory studies suggest that locusts are able to exploit the sky polarization pattern as a navigational cue. Like other insects locusts detect polarized light through a specialized dorsal rim area (DRA) of the eye. Polarization signals are transmitted through the optic lobe to the anterior optic tubercle (AOTu) and, finally, to the central complex in the brain. Whereas neurons of the AOTu integrate sky polarization and chromatic cues in a daytime dependent manner, the central complex holds a topographic representation of azimuthal directions suggesting a role as an internal sky compass. To understand further the integration of sky compass cues we studied polarization-sensitive (POL) neurons in the medulla that may be intercalated between DRA photoreceptors and AOTu neurons. Five types of POL-neuron were characterized and four of these in multiple recordings. All neurons had wide arborizations in medulla layer 4 and most, additionally, in the dorsal rim area of the medulla and in the accessory medulla, the presumed circadian clock. The neurons showed type-specific orientational tuning to zenithal polarized light and azimuth tuning to unpolarized green and UV light spots. In contrast to neurons of the AOTu, we found no evidence for color opponency and daytime dependent adjustment of sky compass signals. Therefore, medulla layer 4 is a distinct stage in the integration of sky compass signals that precedes the time-compensated integration of celestial cues in the AOTu

Six state molecular revolver mounted on a rigid platform

The rotation of entire molecules or large moieties happens at 100 ps time scales and the transition process itself is experimentally inaccessible to scanning probe techniques. However, the reversible switching of a molecule between more than two metastable states allows to assign a rotational switching direction. Rotational switching is a phenomenon that is particularly interesting with regard to possible applications in molecular motors. In this work, single tetraphenylmethane molecules deposited on a Au(111) surface were studied in a low temperature scanning tunneling microscope (STM). These molecules comprise rotational axes mounted on a tripodal sulfur-anchored stand and with the STM tip, we were able to induce transitions between six rotational states of the molecular motif. We were able to identify critical parameters for the onset of rotational switching and to characterize the influence of the local environment. The subtle difference between fcc and hcp stacking and the rotational state of neighboring molecules clearly influence the population of the rotational states

Competition-based model of pheromone component ratio detection in the moth

For some moth species, especially those closely interrelated and sympatric, recognizing a specific pheromone component concentration ratio is essential for males to successfully locate conspecific females. We propose and determine the properties of a minimalist competition-based feed-forward neuronal model capable of detecting a certain ratio of pheromone components independently of overall concentration. This model represents an elementary recognition unit for the ratio of binary mixtures which we propose is entirely contained in the macroglomerular complex (MGC) of the male moth. A set of such units, along with projection neurons (PNs), can provide the input to higher brain centres. We found that (1) accuracy is mainly achieved by maintaining a certain ratio of connection strengths between olfactory receptor neurons (ORN) and local neurons (LN), much less by properties of the interconnections between the competing LNs proper. An exception to this rule is that it is beneficial if connections between generalist LNs (i.e. excited by either pheromone component) and specialist LNs (i.e. excited by one component only) have the same strength as the reciprocal specialist to generalist connections. (2) successful ratio recognition is achieved using latency-to-first-spike in the LN populations which, in contrast to expectations with a population rate code, leads to a broadening of responses for higher overall concentrations consistent with experimental observations. (3) when longer durations of the competition between LNs were observed it did not lead to higher recognition accuracy

Why We Can No Longer Ignore Consecutive Disasters

In recent decades, a striking number of countries have suffered from consecutive disasters: events whose impacts overlap both spatially and temporally, while recovery is still under way. The risk of consecutive disasters will increase due to growing exposure, the interconnectedness of human society, and the increased frequency and intensity of nontectonic hazard. This paper provides an overview of the different types of consecutive disasters, their causes, and impacts. The impacts can be distinctly different from disasters occurring in isolation (both spatially and temporally) from other disasters, noting that full isolation never occurs. We use existing empirical disaster databases to show the global probabilistic occurrence for selected hazard types. Current state‐of‐the art risk assessment models and their outputs do not allow for a thorough representation and analysis of consecutive disasters. This is mainly due to the many challenges that are introduced by addressing and combining hazards of different nature, and accounting for their interactions and dynamics. Disaster risk management needs to be more holistic and codesigned between researchers, policy makers, first responders, and companies

Патопсихологические особенности и закономерности развития органических психических расстройств при болезни Паркинсона

Проанализированы особенности эмоционально−потребностной сферы, выраженность личностных особенностей, типы отношения к болезни у пациентов с болезнью Паркинсона (БП) и психическими расстройствами. Выявлены патопсихологические факторы формирования органического депрессивного расстройства (F06.36), органического тревожного расстройства (F06.4), органического эмоционально−лабильного расстройства (F06.6), описаны механизмы их патогенеза. Относительно деменции (F02.3) у больных БП единого патопсихологического механизма ее формирования не обнаружено, основная роль в ее патогенезе принадлежит органическому поражению головного мозга.Проаналізовано особливості емоційно−потребової сфери, виразність особистісних особливостей, типи ставлення до хвороби у пацієнтів із хворобою Паркінсона (ХП) та психічними розладами. Виявлено патопсихологічні фактори формування органічного депресивного розладу (F06.36), органічного тривожного розладу (F06.4), органічного емоційно−лабільного розладу (F06.6), описано механізми їх патогенезу. Щодо деменції (F02.3) у хворих на ХП єдиного патопсихологічного механізму її формування не виявлено, основна роль в її патогенезі належить органічному ураженню головного мозку.The peculiarities of emotion−need sphere, degree of personality peculiarities, types of attitude to the disease were analyzed in patients with Parkinson's disease (PD) and mental disorders. Pathopsychological factors of forming organic depressive disorder (F06.36), organic anxiety disorder (F06.4), organic emotional−labile disorder (F06.6) were revealed. The mechanisms of their pathogenesis were described. As for dementia (F02.3), uniform pathopsychological mechanism of its formation was not revealed in patients with PD. Main role in its pathogenesis is played by organic brain lesions