Kefir metabolites in a fly model for Alzheimer’s disease

Alzheimer’s Disease (AD) is the most common cause of dementia among elderly individuals worldwide, leading to a strong motor-cognitive decline and consequent emotional distress and codependence. It is traditionally characterized by amyloidogenic pathway formation of senile plaques, and recent studies indicate that dysbiosis is also an important factor in AD’s pathology. To overcome dysbiosis, probiotics—as kefir—have shown to be a great therapeutic alternative for Alzheimer’s disease. In this present work, we explored kefir as a probiotic and a metabolite source as a modulator of microbiome and amyloidogenic pathway, using a Drosophila melanogaster model for AD (AD-like flies). Kefir microbiota composition was determined through 16S rRNA sequencing, and the metabolome of each fraction (hexane, dichloromethane, ethyl acetate, and n-butanol) was investigated. After treatment, flies had their survival, climbing ability, and vacuolar lesions accessed. Kefir and fraction treated flies improved their climbing ability survival rate and neurodegeneration index. In conclusion, we show that kefir in natura, as well as its fractions may be promising therapeutic source against AD, modulating amyloidogenic related pathways.

The Slit-binding Ig1 domain is required for multiple axon guidance activities of Drosophila Robo2

Drosophila Robo2 is a member of the evolutionarily conserved Roundabout (Robo) family of axon guidance receptors. The canonical role of Robo receptors is to signal midline repulsion in response to their cognate Slit ligands, which bind to the N-terminal Ig1 domain in most Robo family members. In the Drosophila embryonic ventral nerve cord, Robo1 and Robo2 cooperate to signal Slit-dependent midline repulsion, while Robo2 also regulates the medial-lateral position of longitudinal axon pathways and acts non-autonomously to promote midline crossing of commissural axons. Although it is clear that Robo2 signals midline repulsion in response to Slit, it is less clear whether Robo2's other activities are also Slit-dependent. To determine which of Robo2's axon guidance roles depend on its Slit-binding Ig1 domain, we have used a CRISPR/Cas9-based strategy replace the endogenous robo2 gene with a robo2 variant from which the Ig1 domain has been deleted (robo2ΔIg1). We compare the expression and localization of Robo2ΔIg1 protein with that of full-length Robo2 in embryonic neurons in vivo, and examine its ability to substitute for Robo2 to mediate midline repulsion and lateral axon pathway formation. We find that removal of the Ig1 domain from Robo2ΔIg1 disrupts both of these axon guidance activities. In addition, we find that the Ig1 domain of Robo2 is required for its proper subcellular localization in embryonic neurons, a role that is not shared by the Ig1 domain of Robo1. Finally, we report that although FasII-positive lateral axons are misguided in embryos expressing Robo2ΔIg1, the axons that normally express Robo2 are correctly guided to the lateral zone, suggesting that Robo2 may guide lateral longitudinal axons through a cell non-autonomous mechanism.

Influence of Key Strata on the Gas Downward Leakage Law in Dual-System of Coal Seam

In Datong mining area, CO and other harmful gases were discharged from the gob in the Jurassic overburden strata to the panel of Carboniferous coal seam. To this end, panel 8309 of Tongxin coal mine in Datong mining area was taken as the engineering background; the change law of CO concentration in the upper corner of the panel and the law of mining pressure were studied through field measurement, and the influence of periodic movement of key strata on the downward leakage law of harmful gases was analyzed. In this paper, the fracture law of the key strata and fracture development characteristics of overburden strata were further studied by the similar simulation test, and the influence of the periodic movement of the key strata on the pathway formation of gas downward leakage was analyzed. The results show that the main cause of harmful gas downward leakage in the Jurassic gob is through the fracture produced by the fracture of the higher key strata. If the higher key strata fractures in the coal mining in the Carboniferous system, through fracture connecting the Jurassic gob above the open-off cut and the upper part of the panel are formed, and effective pathways for gas downward leakage are generated. The fracture and rotation of the higher key strata are accompanied by the formation and disappearance of the effective pathway for gas downward leakage above the panel. Then the periodic change of harmful gas discharging to the panel is caused and consistent with the law of mining pressure.

Emergent dynamics of neuromorphic nanowire networks

Neuromorphic networks are formed by random self-assembly of silver nanowires. Silver nanowires are coated with a polymer layer after synthesis in which junctions between two nanowires act as resistive switches, often compared with neurosynapses. We analyze the role of single junction switching in the dynamical properties of the neuromorphic network. Network transitions to a high-conductance state under the application of a voltage bias higher than a threshold value. The stability and permanence of this state is studied by shifting the voltage bias in order to activate or deactivate the network. A model of the electrical network with atomic switches reproduces the relation between individual nanowire junctions switching events with current pathway formation or destruction. This relation is further manifested in changes in 1/f power-law scaling of the spectral distribution of current. The current fluctuations involved in this scaling shift are considered to arise from an essential equilibrium between formation, stochastic-mediated breakdown of individual nanowire-nanowire junctions and the onset of different current pathways that optimize power dissipation. This emergent dynamics shown by polymer-coated Ag nanowire networks places this system in the class of optimal transport networks, from which new fundamental parallels with neural dynamics and natural computing problem-solving can be drawn.

Malformations of Cerebral Cortex Development: Molecules and Mechanisms

Malformations of cortical development encompass heterogeneous groups of structural brain anomalies associated with complex neurodevelopmental disorders and diverse genetic and nongenetic etiologies. Recent progress in understanding the genetic basis of brain malformations has been driven by extraordinary advances in DNA sequencing technologies. For example, somatic mosaic mutations that activate mammalian target of rapamycin signaling in cortical progenitor cells during development are now recognized as the cause of hemimegalencephaly and some types of focal cortical dysplasia. In addition, research on brain development has begun to reveal the cellular and molecular bases of cortical gyrification and axon pathway formation, providing better understanding of disorders involving these processes. New neuroimaging techniques with improved resolution have enhanced our ability to characterize subtle malformations, such as those associated with intellectual disability and autism. In this review, we broadly discuss cortical malformations and focus on several for which genetic etiologies have elucidated pathogenesis.

The Role of Lipids in Parkinson’s Disease

Parkinson’s disease (PD) is a neurodegenerative disease characterized by a progressive loss of dopaminergic neurons from the nigrostriatal pathway, formation of Lewy bodies, and microgliosis. During the past decades multiple cellular pathways have been associated with PD pathology (i.e., oxidative stress, endosomal-lysosomal dysfunction, endoplasmic reticulum stress, and immune response), yet disease-modifying treatments are not available. We have recently used genetic data from familial and sporadic cases in an unbiased approach to build a molecular landscape for PD, revealing lipids as central players in this disease. Here we extensively review the current knowledge concerning the involvement of various subclasses of fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterols, and lipoproteins in PD pathogenesis. Our review corroborates a central role for most lipid classes, but the available information is fragmented, not always reproducible, and sometimes differs by sex, age or PD etiology of the patients. This hinders drawing firm conclusions about causal or associative effects of dietary lipids or defects in specific steps of lipid metabolism in PD. Future technological advances in lipidomics and additional systematic studies on lipid species from PD patient material may improve this situation and lead to a better appreciation of the significance of lipids for this devastating disease.

Effect of grafted graphene nanosheets on morphology evolution and conductive behavior of poly(methyl methacrylate)/poly(styrene-co-acrylonitrile) blends during isothermal annealing

The activation energy of conductive pathway formation for PMMA/SAN/PMMA-g-RGO nanocomposites is close to that of flow for PMMA, indicating that DC percolation is mainly related to the mobility of grafted PMMA chains, rather than that of SAN chains.