Brain Ventricular System and Cerebrospinal Fluid Development and Function: Light at the End of the Tube

The brain ventricular system is a series of connected cavities, filled with cerebrospinal fluid (CSF), that forms within the vertebrate central nervous system (CNS). The hollow neural tube is a hallmark of the chordate CNS, and a closed neural tube is essential for normal development. Development and function of the ventricular system is examined, emphasizing three interdigitating components that form a functional system: ventricle walls, CSF fluid properties, and activity of CSF constituent factors. The cellular lining of the ventricle both can produce and is responsive to CSF. Fluid properties and conserved CSF components contribute to normal CNS development. Anomalies of the CSF/ventricular system serve as diagnostics and may cause CNS disorders, further highlighting their importance. This review focuses on the evolution and development of the brain ventricular system, associated function, and connected pathologies. It is geared as an introduction for scholars with little background in the field.     

Will Lynx Lose Their Edge? Canada Lynx Occupancy in Washington

Populations of species located at southern range edges may be particularly vulnerable to the effects of climate change as warming temperatures and subsequent changes to ecosystems exceed species-specific tolerances. One such species is Canada lynx (Lynx canadensis), a cold-adapted mesocarnivore that maintains a large core population in Alaska, USA, and Canada but exists within several peripheral populations in the contiguous United States. Increases in temperature, declines in snow pack, and climate-influenced increases in fire frequency and intensity, could negatively affect lynx populations, threatening their long-term persistence in the continental United States. Despite these threats, our understanding of broad-scale effects on lynx occupancy and the extent of current lynx distribution in many of these peripheral populations is minimal. We conducted an occupancy survey of lynx in Washington, USA, using a spatially extensive camera-trapping array covering 7,000 km² of potential lynx habitat. We used the resulting database of detection data to develop single-season occupancy models to examine the abiotic and biotic effects on current lynx occupancy and predict future lynx distribution based on climate change forecasts. Our results show lynx occupancy across the Washington landscape is restricted and dictated largely by abiotic factors, disturbance regimes, and distance from source populations in Canada. Predictions of future distribution suggest lynx will be increasingly challenged by climatic changes, particularly at the southern and lower elevation portions of their range in Washington. Our results paint an alarming picture for lynx persistence in Washington that is relevant to current deliberations regarding lynx delisting from the Endangered Species Act. Our simple camera design was a highly effective method for surveying lynx across broad spatial scales, and could be a key monitoring tool for lynx that is easy to implement by researchers and government agencies. © 2020 The Wildlife Society.     

NCAM regulates the proliferation,apoptosis, autophagy,EMT, and migration of human melanoma cells via the Src/Akt/mTOR/cofilin signaling pathway

The neural cell adhesion molecule (NCAM) plays critical roles in multiple cellular processes in neural cells, mesenchymal stem cells, and various cancer cells. However, the effect and mechanism of NCAM in human melanoma cells are still unclear. In this study, we found that NCAM regulated the proliferation, apoptosis, autophagy, migration, and epithelial-to-mesenchymal transition of human melanoma cells by determining the biological behavior of NCAM knockdown A375 and M102 human melanoma cells. Further studies revealed that NCAM knockdown impaired the organization of actin cytoskeleton and reduced the phosphorylation of cofilin, an actin-cleaving protein. When cells were transfected with cofilin S3A (dephosphorylated cofilin), biological behavior similar to that of NCAM knockdown cells was observed. Research on the underlying molecular mechanism showed that NCAM knockdown suppressed activation of the Src/Akt/mTOR pathway. Specific inhibitors of Src and PI3K/Akt were employed to further verify the relationship between Src/Akt/mTOR signaling and cofilin, and the results showed that the phosphorylation level of cofilin decreased following inhibition of the Src/Akt/mTOR pathway. These results indicated that NCAM may regulate the proliferation, apoptosis, autophagy, migration, and epithelial-to-mesenchymal transition of human melanoma cells via the Src/Akt/mTOR/cofilin pathway-mediated dynamics of actin cytoskeleton.     

ProDCoNN: Protein design using a convolutional neural network

Designing protein sequences that fold to a given three-dimensional (3D) structure has long been a challenging problem in computational structural biology with significant theoretical and practical implications. In this study, we first formulated this problem as predicting the residue type given the 3D structural environment around the C _α atom of a residue, which is repeated for each residue of a protein. We designed a nine-layer 3D deep convolutional neural network (CNN) that takes as input a gridded box with the atomic coordinates and types around a residue. Several CNN layers were designed to capture structure information at different scales, such as bond lengths, bond angles, torsion angles, and secondary structures. Trained on a very large number of protein structures, the method, called ProDCoNN (protein design with CNN), achieved state-of-the-art performance when tested on large numbers of test proteins and benchmark datasets.     

The genetic program to specify ectodermal cells in ascidian embryos

The ascidian belongs to the sister group of vertebrates and shares many features with them. The gene regulatory network (GRN) controlling gene expression in ascidian embryonic development leading to the tadpole larva has revealed evolutionarily conserved gene circuits between ascidians and vertebrates. These conserved mechanisms are indeed useful to infer the original developmental programs of the ancestral chordates. Simultaneously, these studies have revealed which gene circuits are missing in the ascidian GRN; these gene circuits may have been acquired in the vertebrate lineage. In particular, the GRN responsible for gene expression in ectodermal cells of ascidian embryos has revealed the genetic programs that regulate the regionalization of the brain, formation of palps derived from placode-like cells, and differentiation of sensory neurons derived from neural crest-like cells. We here discuss how these studies have given insights into the evolution of these traits.     

MFN2 silencing promotes neural differentiation of embryonic stem cells via the Akt signaling pathway

Mitofusin 2 (MFN2) is a regulatory protein participating in mitochondria dynamics, cell proliferation, death, differentiation, and so on. This study aims at revealing the functional role of MFN2 in the pluripotency maintenance and primitive differetiation of embryonic stem cell (ESCs). A dox inducible silencing and routine overexpressing approach was used to downregulate and upregulate MFN2 expression, respectively. We have compared the morphology, cell proliferation, and expression level of pluripotent genes in various groups. We also used directed differentiation methods to test the differentiation capacity of various groups. The Akt signaling pathway was explored by the western blot assay. MFN2 upregulation in ESCs exhibited a typical cell morphology and similar cell proliferation, but decreased pluripotent gene markers. In addition, MFN2 overexpression inhibited ESCs differentiation into the mesendoderm, while MFN2 silencing ESCs exhibited a normal cell morphology, slower cell proliferation and elevated pluripotency markers. For differentiation, MFN2 silencing ESCs exhibited enhanced three germs' differentiation ability. Moreover, the protein levels of phosphorylated Akt308 and Akt473 decreased in MFN2 silenced ESCs, and recovered in the neural differentiation process. When treated with the Akt inhibitor, the neural differentiation capacity of the MFN2 silenced ESCs can reverse to a normal level. Taken together, the data indicated that the appropriate level of MFN2 expression is essential for pluripotency and differentiation capacity in ESCs. The increased neural differentiation ability by MFN2 silencing is strongly related to the Akt signaling pathway.     

Death receptors and mitochondria: Two prime triggers of neural apoptosis and differentiation

Background

Stem cell therapy is a strategy far from being satisfactory and applied in the clinic. Poor survival and differentiation levels of stem cells after transplantation or neural injury have been major problems. Recently, it has been recognized that cell death-relevant proteins, notably those that operate in the core of the executioner apoptosis machinery are functionally involved in differentiation of a wide range of cell types, including neural cells.

Scope of review

This article will review recent studies on the mechanisms underlying the non-apoptotic function of mitochondrial and death receptor signaling pathways during neural differentiation. In addition, we will discuss how these major apoptosis-regulatory pathways control the decision between differentiation, self-renewal and cell death in neural stem cells and how levels of activity are restrained to prevent cell loss as final outcome.

Major conclusions

Emerging evidence suggests that, much like p53, caspases and Bcl-2 family members, the two prime triggers of cell death pathways, death receptors and mitochondria, may influence proliferation and differentiation potential of stem cells, neuronal plasticity, and astrocytic versus neuronal stem cell fate decision.

General significance

A better understanding of the molecular mechanisms underlying key checkpoints responsible for neural differentiation as an alternative to cell death will surely contribute to improve neuro-replacement strategies.     

Phenotype and Micro-array characterization of duplication 11q22.1-q25 and review of the literature

Partial duplication of 11q is related to several malformations like growth retardation, intellectual disability, hypoplasia of corpus callosum, short nose, palate defects, cardiac, urinary tract abnormalities and neural tube defects. We have studied the clinical and molecular characteristics of a patient with severe intellectual disabilities, dysmorphic features, congenital inguinal hernia and congenital cerebral malformation which is referred to as cytogenetic exploration. We have used FISH and array CGH analysis for a better understanding of the double chromosomic aberration involving a 7p microdeletion along with a partial duplication of 11q due to adjacent segregation of a paternal reciprocal translocation t(7;11)(p22;q21) revealed after banding analysis. The patient's karyotype formula was: 46,XY,der(7)t(7;11)(p22;q21)pat. FISH study confirmed these rearrangement and array CGH technique showed precisely the loss of at least 140 Kb on chromosome7p22.3pter and 33.4 Mb on chromosome11q22.1q25. Dysmorphic features, severe intellectual disability and brain malformations could result from the 11q22.1q25 trisomy. Our study provides an additional case for better understanding and delineating the partial duplication 11q.