Shattered Silence: Unmuting the Voices of Syrian Refugees

The Syrian conflict has affected over 12 million people in the past five years resulting in one of the most devastating forced migrations in global history. Through literature reviews and further research, this presentation will define the context that fostered the refugee crisis, as well as outline the current conditions experienced by refugees remaining in and outside of Syria. After exposing the cause of this catastrophe as well as highlighting present injustices, presenters will examine the impact of this event on refugees and explore future implications of the crisis. Finally, insight will be provided as to how individuals can become involved with advocating for justice and supporting refugees as they resettle in new communities

Deriving erosion thresholds of freshly deposited cohesive sediments from the port of Hamburg using a closed microcosm system

The quantification of the erodibility of cohesive sediments is fundamental for an advanced understanding of estuarine sediment transport processes. In this study, the surface erosion threshold τc for cohesive sediments collected from two sites in the area of the Port of Hamburg in the River Elbe is investigated in laboratory experiments. An improved closed microcosm system (C-GEMS) is used for the erosion experiments, which allows the accumulation of suspended sediment concentration (SSC) over an experimental run. A total of 34 erosion experiments has been conducted with homogenized samples and bulk densities between 1050 kg/m³ and 1250 kg/m³. The covered range of bulk densities is seen to represent the values commonly exhibited by freshly deposited cohesive sediments. Two approaches to derive τc based on the erosion rate (ε-method) and the SSC (SSC-method) were elaborated and compared. For both approaches, only one parameter has to be set in order to facilitate transferability to other devices. The results show a better performance of the SSC-method in terms of lower uncertainties, especially at the upper application limits of the utilized C-GEMS. The application of the SSC method yields values for τc between 0.037 N/m² and 0.305 N/m², continuously increasing with bulk density. Repetition tests proved the repeatability of the experimental procedure and utilized methods to derive τc. The derived data for τc is used to fit two mathematical models: i) a highly empirical model relating τc to dry bulk density and ii) a recently proposed model relating τc to the physical properties of the sediment-mixture. While the derived parameters for the first model vary widely for the two sampling sites, the fit-parameter for the latter model is virtually independent of the investigated site, suggesting the superiority of this approach

Exponential Replication of Patterns in the Signal Tile Assembly Model

Chemical self-replicators are of considerable interest in the field of nanomanufacturing and as a model for evolution. We introduce the problem of self-replication of rectangular two-dimensional patterns in the practically motivated Signal Tile Assembly Model (STAM) [9]. The STAM is based on the Tile Assembly Model (TAM) which is a mathematical model of self-assembly in which DNA tile monomers may attach to other DNA tile monomers in a programmable way. More abstractly, four-sided tiles are assigned glue types to each edge, and self-assembly occurs when singleton tiles bind to a growing assembly, if the glue types match and the glue binding strength exceeds some threshold. The signal tile extension of the TAM allows signals to be propagated across assemblies to activate glues or break apart assemblies. Here, we construct a pattern replicator that replicates a two-dimensional input pattern over some fixed alphabet of size φ with O(φ) tile types, O(φ) unique glues, and a signal complexity of O(1). Furthermore, we show that this replication system displays exponential growth in n, the number of replicates of the initial patterned assembly

Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults.

New neurons continue to be generated in the subgranular zone of the dentate gyrus of the adult mammalian hippocampus. This process has been linked to learning and memory, stress and exercise, and is thought to be altered in neurological disease. In humans, some studies have suggested that hundreds of new neurons are added to the adult dentate gyrus every day, whereas other studies find many fewer putative new neurons. Despite these discrepancies, it is generally believed that the adult human hippocampus continues to generate new neurons. Here we show that a defined population of progenitor cells does not coalesce in the subgranular zone during human fetal or postnatal development. We also find that the number of proliferating progenitors and young neurons in the dentate gyrus declines sharply during the first year of life and only a few isolated young neurons are observed by 7 and 13 years of age. In adult patients with epilepsy and healthy adults (18-77 years; n = 17 post-mortem samples from controls; n = 12 surgical resection samples from patients with epilepsy), young neurons were not detected in the dentate gyrus. In the monkey (Macaca mulatta) hippocampus, proliferation of neurons in the subgranular zone was found in early postnatal life, but this diminished during juvenile development as neurogenesis decreased. We conclude that recruitment of young neurons to the primate hippocampus decreases rapidly during the first years of life, and that neurogenesis in the dentate gyrus does not continue, or is extremely rare, in adult humans. The early decline in hippocampal neurogenesis raises questions about how the function of the dentate gyrus differs between humans and other species in which adult hippocampal neurogenesis is preserved

The distribution of doublecortin-immunopositive cells in the brains of four afrotherian mammals : the Hottentot golden mole (Amblysomus hottentotus), the rock hyrax (Procavia capensis), the eastern rock sengi (Elephantulus myurus) and the four-toed sengi (Petrodromus tetradactylus)

Adult neurogenesis in the mammalian brain is now a widely accepted phenomenon, typically occurring in two forebrain structures: the subgranular zone (SGZ) of the hippocampal dentate gyrus and the subventricular zone (SVZ). Until recently, the majority of studies have focused on laboratory rodents, and it is under debate whether the process of adult neurogenesis occurs outside of the SGZ and the SVZ in other mammalian species. In the present study, we investigated potential adult neurogenetic sites in the brains of two elephant shrews/sengis, a golden mole and a rock hyrax, all members of the superorder Afrotheria. Doublecortin (DCX) immunoreactivity was used as a proxy to visualise adult neurogenesis, which is expressed in neuronal precursor cells and immature neurons. In all four species, densely packed DCX-positive cells were present in the SVZ, from where cells appear to migrate along the rostral migratory stream towards the olfactory bulb (OB). DCX-immunopositive cells were present in the granular cell layer and the glomerular layer of the OB. In the hippocampus, DCX-immunopositive cells were observed in the SGZ and in the granular layer of the dentate gyrus, with DCX-immunopositive processes extending into the molecular layer. In addition to these well-established adult neurogenic regions, DCX-immunopositive cells were also observed in layer II of the neocortex and the piriform cortex. While the present study reveals a similar pattern of adult neurogenesis to that reported previously in other mammals, further studies are needed to clarify if the cortical DCX-immunopositive cells are newly generated neurons or cells undergoing cortical remodelling.South African National Research Foundation, the Swiss-South African Joint Research Program, the Belgian co-operation service at the Royal Museum for Central Africa and by a fellowship within the Postdoctoral-Program of the German Academic Exchange Service, DAAD.http://www.karger.com/Journal/Home/223831hb201

Generation of NSE-MerCreMer Transgenic Mice with Tamoxifen Inducible Cre Activity in Neurons

To establish a genetic tool for conditional deletion or expression of gene in neurons in a temporally controlled manner, we generated a transgenic mouse (NSE-MerCreMer), which expressed a tamoxifen inducible type of Cre recombinase specifically in neurons. The tamoxifen inducible Cre recombinase (MerCreMer) is a fusion protein containing Cre recombinase with two modified estrogen receptor ligand binding domains at both ends, and is driven by the neural-specific rat neural specific enolase (NSE) promoter. A total of two transgenic lines were established, and expression of MerCreMer in neurons of the central and enteric nervous systems was confirmed. Transcript of MerCreMer was detected in several non-neural tissues such as heart, liver, and kidney in these lines. In the background of the Cre reporter mouse strain Rosa26R, Cre recombinase activity was inducible in neurons of adult NSE-MerCreMer mice treated with tamoxifen by intragastric gavage, but not in those fed with corn oil only. We conclude that NSE-MerCreMer lines will be useful for studying gene functions in neurons for the conditions that Cre-mediated recombination resulting in embryonic lethality, which precludes investigation of gene functions in neurons through later stages of development and in adult

CSPP1 stabilizes growing microtubule ends and damaged lattices from the luminal side

Microtubules are dynamic cytoskeletal polymers, and their organization and stability are tightly regulated by numerous cellular factors. While regulatory proteins controlling the formation of interphase microtubule arrays and mitotic spindles have been extensively studied, the biochemical mechanisms responsible for generating stable microtubule cores of centrioles and cilia are poorly understood. Here, we used in vitro reconstitution assays to investigate microtubule-stabilizing properties of CSPP1, a centrosome and cilia-associated protein mutated in the neurodevelopmental ciliopathy Joubert syndrome. We found that CSPP1 preferentially binds to polymerizing microtubule ends that grow slowly or undergo growth perturbations and, in this way, resembles microtubule-stabilizing compounds such as taxanes. Fluorescence microscopy and cryo-electron tomography showed that CSPP1 is deposited in the microtubule lumen and inhibits microtubule growth and shortening through two separate domains. CSPP1 also specifically recognizes and stabilizes damaged microtubule lattices. These data help to explain how CSPP1 regulates the elongation and stability of ciliary axonemes and other microtubule-based structures

Bi-allelic variants in TSPOAP1, encoding the active zone protein RIMBP1, cause autosomal recessive dystonia

Dystonia is a debilitating hyperkinetic movement disorder, which can be transmitted as a monogenic trait. Here, we describe homozygous frameshift, nonsense and missense variants in TSPOAP1, encoding the active zone RIM-binding protein 1 (RIMBP1), as a novel genetic cause of autosomal recessive dystonia in seven subjects from three unrelated families. Subjects carrying loss-of-function variants presented with juvenile-onset progressive generalized dystonia, associated with intellectual disability and cerebellar atrophy. Conversely, subjects carrying a pathogenic missense variant (p.Gly1808Ser) presented with isolated adult-onset focal dystonia. In mice, complete loss of RIMBP1, known to reduce neurotransmission, led to motor abnormalities reminiscent of dystonia, decreased Purkinje cell dendritic arborization, and reduced numbers of cerebellar synapses. In vitro analysis of the p.Gly1808Ser variant showed larger spike-evoked calcium transients and enhanced neurotransmission, suggesting that RIMBP1-linked dystonia can be caused by either reduced or enhanced rates of spike-evoked release in relevant neural networks. Our findings establish a direct link between dysfunction of the presynaptic active zone and dystonia and highlight the critical role played by well-balanced neurotransmission in motor control and disease pathogenesis

Biallelic variants in TSPOAP1, encoding the active-zone protein RIMBP1, cause autosomal recessive dystonia.

Dystonia is a debilitating hyperkinetic movement disorder, which can be transmitted as a monogenic trait. Here, we describe homozygous frameshift, nonsense, and missense variants in TSPOAP1, which encodes the active-zone RIM-binding protein 1 (RIMBP1), as a genetic cause of autosomal recessive dystonia in 7 subjects from 3 unrelated families. Subjects carrying loss-of-function variants presented with juvenile-onset progressive generalized dystonia, associated with intellectual disability and cerebellar atrophy. Conversely, subjects carrying a pathogenic missense variant (p.Gly1808Ser) presented with isolated adult-onset focal dystonia. In mice, complete loss of RIMBP1, known to reduce neurotransmission, led to motor abnormalities reminiscent of dystonia, decreased Purkinje cell dendritic arborization, and reduced numbers of cerebellar synapses. In vitro analysis of the p.Gly1808Ser variant showed larger spike-evoked calcium transients and enhanced neurotransmission, suggesting that RIMBP1-linked dystonia can be caused by either reduced or enhanced rates of spike-evoked release in relevant neural networks. Our findings establish a direct link between dysfunction of the presynaptic active zone and dystonia and highlight the critical role played by well-balanced neurotransmission in motor control and disease pathogenesis