Brain wiring with composite instructions

The quest for molecular mechanisms that guide axons or specify synaptic contacts has largely focused on molecules that intuitively relate to the idea of an “instruction.” By contrast, “permissive” factors are traditionally considered background machinery without contribution to the information content of a molecularly executed instruction. In this essay, I recast this dichotomy as a continuum from permissive to instructive actions of single factors that provide relative contributions to a necessarily collaborative effort. Individual molecules or other factors do not constitute absolute instructions by themselves; they provide necessary context for each other, thereby creating a composite that defines the overall instruction. The idea of composite instructions leads to two main conclusions: first, a composite of many seemingly permissive factors can define a specific instruction even in the absence of a single dominant contributor; second, individual factors are not necessarily related intuitively to the overall instruction or phenotypic outcome

Psychosoziale Arbeitsbelastungen und Gesundheit: Wie ältere Beschäftigte Arbeitsanforderungen und Belohnungen empfinden

Psychosoziale Arbeitsbelastungen sind ein Risikofaktor für die Gesundheit Erwerbstätiger. Da die Erwerbsbevölkerung immer älter wird, stellen sich in diesem Kontext neue Fragen: In welchem Maße fühlen sich älterwerdende Beschäftigte durch Arbeitsanforderungen und ausbleibende Anerkennung belastet? Wie hängen solche Aspekte psychosozialer Arbeitsbelastungen mit der Gesundheit zusammen? Auf Basis einer aktuellen Befragung von älteren Erwerbstätigen werden diese Zusammenhänge hier näher untersucht

Degradation of small simple and large complex lunar craters: Not a simple scale dependence

The crater record of a planetary surface unit is often analyzed by its cumulative size‐frequency distribution (CSFD). Measuring CSFDs involves traditional approaches, such as traditional crater counting (TCC) and buffered crater counting (BCC), as well as geometric corrections, such as nonsparseness correction (NSC) and buffered nonsparseness correction (BNSC). NSC and BNSC consider the effects of geometric crater obliteration on the CSFD. On the Moon, crater obliteration leads to two distinct states in which obtained CSFDs do not match the production CSFD—crater equilibrium and nonsparseness. Crater equilibrium occurs when each new impact erases a preexisting crater of the same size. It is clearly observed on lunar terrains dominated by small simple craters with steep‐sloped production CSFDs, such as Imbrian to Eratosthenian‐era mare units. Nonsparseness, on the other hand, is caused by the geometric overlap of preexisting craters by a new impact, which is also known as “cookie cutting.” Cookie cutting is most clearly observed on lunar terrains dominated by large craters with shallow‐sloped production CSFDs, such as the pre‐Nectarian lunar highlands. We use the Cratered Terrain Evolution Model (CTEM) to simulate the evolution of a pre‐Nectarian surface unit. The model was previously used to simulate the diffusion‐induced equilibrium for small craters of the lunar maria. We find that relative to their size, large craters contribute less to the diffusion of the surrounding landscape than small craters. Thus, a simple scale dependence cannot account for the per‐crater contribution to degradation by small simple and large complex craters

Neuronal filopodia: From stochastic dynamics to robustness of brain morphogenesis

Brain development relies on dynamic morphogenesis and interactions of neurons. Filopodia are thin and highly dynamic membrane protrusions that are critically required for neuronal development and neuronal interactions with the environment. Filopodial interactions are typically characterized by non-deterministic dynamics, yet their involvement in developmental processes leads to stereotypic and robust outcomes. Here, we discuss recent advances in our understanding of how filopodial dynamics contribute to neuronal differentiation, migration, axonal and dendritic growth and synapse formation. Many of these advances are brought about by improved methods of live observation in intact developing brains. Recent findings integrate known and novel roles ranging from exploratory sensors and decision-making agents to pools for selection and mechanical functions. Different types of filopodial dynamics thereby reveal non-deterministic subcellular decision-making processes as part of genetically encoded brain development

Synaptic promiscuity in brain development

Precise synaptic connectivity is a prerequisite for the function of neural circuits, yet individual neurons, taken out of their developmental context, readily form unspecific synapses. How does the genome encode brain wiring in light of this apparent contradiction? Synaptic specificity is the outcome of a long series of developmental processes and mechanisms before, during and after synapse formation. How much promiscuity is permissible or necessary at the moment of synaptic partner choice depends on the extent to which prior development restricts available partners or subsequent development corrects initially made synapses. Synaptic promiscuity at the moment of choice can thereby play important roles in the development of precise connectivity, but also facilitate developmental flexibility and robustness. In this review, we assess the experimental evidence for the prevalence and roles of promiscuous synapse formation during brain development. Many well-established experimental approaches are based on developmental genetic perturbation and an assessment of synaptic connectivity only in the adult; this can make it difficult to pinpoint when a given defect or mechanism occurred. In many cases, such studies reveal mechanisms that restrict partner availability already prior to synapse formation. Subsequently, at the moment of choice, factors including synaptic competency, interaction dynamics and molecular recognition further restrict synaptic partners. The discussion of the development of synaptic specificity through the lens of synaptic promiscuity suggests an algorithmic process based on neurons capable of promiscuous synapse formation that are continuously prevented from making the wrong choices, with no single mechanism or developmental time point sufficient to explain the outcome

Autophagy in synapse formation and brain wiring

A recent characterization of the role of autophagy in two different neuron types during brain development in Drosophila revealed two different mechanisms to regulate synapse formation. In photoreceptor neurons, autophagosome formation in synaptogenic filopodia destabilizes presumptive synaptic contacts and thereby restricts incorrect synaptic partnerships. In dorsal cluster neurons, autophagy is actively suppressed to keep mature synapses stable during axonal branching. These findings indicate that different neuron types can require activation or suppression of synaptic autophagy during the same developmental period to ensure proper synapse formation and brain connectivity

Ventricular assist device implantation in the elderly

BACKGROUND: Dramatic advances in ventricular assist device (VAD) design and patient management have made mechanical circulatory support an attractive therapeutic option for the growing pool of elderly heart failure patients. METHODS: A literature review of all relevant studies was performed. No time or language restrictions were imposed, and references of the selected studies were checked for additional relevant citations. RESULTS: In concordance with the universal trend in mechanical circulatory support, continuous flow devices appear to have particular benefits in the elderly. In addition, the literature suggests that early intervention before the development of cardiogenic shock, important in all patients, is particularly paramount in older patients. CONCLUSIONS: The ongoing refinement of patient selection, surgical technique, and post-operative care will continue to improve surgical outcomes, and absolute age may become a less pivotal criterion for mechanical circulatory support. However, clear guidelines for the use of mechanical circulatory support in the elderly remain undefined

A Fresh Look at the Stratigraphy of Northern Australe

The roughly circular collection of mare deposits centered at ~38.9S, 93E is often re- ferred to as Mare Australe. It is located outside of the Procellarum KREEP Terrain. The circular arrangement of Australes mare patches has suggested an ancient, heavily degraded or relaxed impact basin roughly 900 km in diameter. The mare deposits are generally thought to have erupted into smaller post- basin craters. The type, volume, and distribution of mare eruptions potentially resembles the early stages of basin-filling mare events, but which are preserved in Australe and some farside locations. Gravity data suggest that if there was a basin, it is much smaller than originally proposed (now ~600 km) and located in the northern part of Mare Australe, between Humboldt, Milne, and Jenner craters. As a whole, Mare Australe lacks the topography typically associated with a basin; however, northern Australe has a slight topographic depression that roughly corresponds to the basin-like Bouguer gravity signature in the same area. The compositions exposed in Humboldt crater suggest that a preexisting basin might have excavated deeper crustal material. However, the underlying cause of the circularity of Mare Australes deposits, particularly those extending outside of the potential impact basin setting, is not yet understood. Thus, Australe may preserve fundamental information about mare volcanism potentially uncoupled from basin formation and structure. The objectives of this study are to use new high- resolution data (images, gravity, topography, and com- position) to reassess Australes mare deposits, deter- mine the timing and style of volcanism, identify discrete basalt deposits, and to further characterize the evolution of magmatism and subsurface structure in this area. Here, we focus on the northern Australe deposits (between Humboldt, Jenner, and Milne). As originally noted by Whitford-Stark (1979), Humboldt crater and its ejecta make an excellent stratigraphic marker that can be traced across much of the Australe region. The ejecta serves as a stratigraphic constraint for absolute model ages (AMAs) derived from crater size-frequency distributions (CSFDs)