Single Cell Transcriptomic Analysis of Spinal Dmrt3 Neurons in Zebrafish and Mouse Identifies Distinct Subtypes and Reveal Novel Subpopulations Within the dI6 Domain

The spinal locomotor network is frequently used for studies into how neuronal circuits are formed and how cellular activity shape behavioral patterns. A population of dI6 interneurons, marked by the Doublesex and mab-3 related transcription factor 3 (Dmrt3), has been shown to participate in the coordination of locomotion and gaits in horses, mice and zebrafish. Analyses of Dmrt3 neurons based on morphology, functionality and the expression of transcription factors have identified different subtypes. Here we analyzed the transcriptomes of individual cells belonging to the Dmrt3 lineage from zebrafish and mice to unravel the molecular code that underlies their subfunctionalization. Indeed, clustering of Dmrt3 neurons based on their gene expression verified known subtypes and revealed novel populations expressing unique markers. Differences in birth order, differential expression of axon guidance genes, neurotransmitters, and their receptors, as well as genes affecting electrophysiological properties, were identified as factors likely underlying diversity. In addition, the comparison between fish and mice populations offers insights into the evolutionary driven subspecialization concomitant with the emergence of limbed locomotion.

Continued dysregulation of the B cell lineage promotes multiple sclerosis activity despite disease modifying therapies

A clear understanding of the origin and role of the different subtypes of the B cell lineage involved in the activity or remission of multiple sclerosis (MS) is important for the treatment and follow-up of patients living with this disease. B cells, however, are dynamic and can play an anti-inflammatory or pro-inflammatory role, depending on their milieu. Depletion of B cells has been effective in controlling the progression of MS, but it can have adverse side effects. A better understanding of the role of the B cell subtypes, through the use of surface biomarkers of cellular activity with special attention to the function of memory and regulatory B cells (Bregs), will be necessary in order to offer specific treatments without inducing undesirable effects.

A Multiparametric Activity Profiling Platform for Neuron Disease Phenotyping and Drug Screening

Patient stem cell-derived models enable imaging of complex disease phenotypes and the development of scalable drug discovery platforms. Current preclinical methods for assessing cellular activity do not, however, capture the full intricacies of disease-induced disturbances, and instead typically focus on a single parameter, which impairs both the understanding of disease and the discovery of effective therapeutics. Here, we describe a cloud-based image processing and analysis platform that captures the intricate activity profile revealed by GCaMP fluorescent recordings of intracellular calcium changes and enables the discovery of molecules that correct 153 parameters that define the amyotrophic lateral sclerosis motor neuron disease phenotype. In a high-throughput screen, we identified compounds that revert the multiparametric disease profile to that found in healthy cells, a novel and robust measure of therapeutic potential quite distinct from unidimensional screening. This platform can guide the development of therapeutics that counteract the multifaceted pathological features of diseased cellular activity.

Taxonomic history, comparative morphology, and variation in Astrophytum myriostigma and its subspecies tulense (Cactaceae)

Astrophytum myriostigma subsp. myriostigma and subsp. tulense are distinguished by both vegetative and reproductive characters. The stem of the nominotypical subspecies is broad and depressed becoming broadly cylindrical in age, reaching a known maximum height of ca. 52 cm. In subsp. tulense, the stem is relatively slen-der and columnar and can reach a maximum height of ca. 90 cm. Both taxa show variation in the angle and profile of the ribs. In the nominotypical subspecies, the ribs are usually obtuse with a rounded or angular profile, or moderately acute with an angular profile. In subsp. tulense, the ribs are typically moderately to very acute with an angular profile. There are exceptions to these generalities. Both taxa have a modal number of five ribs, and both have the tendency to insert additional ribs with age, although the tendency seems more pronounced in subsp. tulense. The flower of the nominotypical subspecies differs from that of subsp. tulense in having a significantly larger mean perianth diameter (P <= 0.01), a significantly higher mean number of stigma lobes (P <= 0.05), and more tepal rows (3–5 vs. 1–3). The color of the tepals is pale yellow to whitish yellow in subsp. tulense, but brighter yellow or golden yellow in the nominotypical subspecies. The seeds of the nominotypical subspecies are significantly larger (P <= 0.01) than the seeds of subsp. tulense. Morphological variation was studied in nine populations of the subsp. myriostigma and six populations of the subsp. tulense. The nominotypical subspecies displays rib angle and rib profile differences among individual plants within a population. Plants with a depressed stem and obtuse, rounded ribs are predominant at some localities. At other localities, plants with more moderately acute, angular ribs are predominant, or at least common. Populations of subsp. tulense show individual variation in stem morphology. The stem varies from attenuated (tapered) to non-attenuated and from relatively slender (diameter ca. 20% of height) to relatively broad (diameter ca. 77% of height). The plants from near Mama León and adjacent localities in Tamaulipas, have very robust stems and are the least typical of the columnar subspecies. The rela-tionships of this population to other columnar populations warrant further study. The population near Las Tablas, San Luis Potosí, shows considerable variation in the stem and rib morphology. Some plants resemble the nominotypical subspecies whereas others are similar morphologically to subsp. tulense. The perianth diameter is intermediate between those of the two subspecies. The evidence suggests that this is an area of past or ongoing hybridization between the two taxa; the question of hybridization warrants further investigation. Attenuated and non-attenuated stems are the result of differential rates of vertical and lateral growth due to cellular activity in the apical and lateral meristems, respectively. The attenuated (tapered) stem is produced by a gradually increasing lateral growth rate which remains slower than the vertical rate. A non-attenuated stem is produced by the lateral growth rate exceeding the vertical rate early in development, then stabilizing at some point and not surpassing the vertical rate.

The effect of optogenetic activation of astrocytes on the hippocampal neurons activity

The method of optogenetics has spread widely in neurobiology over the past 10 years and has found extensive application in various fields of this sciences. It allows to control and regulate cellular activity with high spatial and temporal resolution. In this study, optogenetic activation was applied to astrocytes expressing ChR2. Optogenetic stimulation parameters were determined, in which the frequency of spontaneous currents of hippocampal pyramidal neurons significantly changed. In the future, it is planned to use the obtained data on the modes of optogenetic stimulation of astrocytes to normalize the functions of the hippocampus in mice-models of Alzheimer’s disease.

Brain transcriptomes of zebrafish and mouse Alzheimer's disease knock-in models imply early disrupted energy metabolism

Energy production is the most fundamentally important cellular activity supporting all other functions, particularly in highly active organs such as brains, Here we summarise transcriptome analyses of young adult (pre-disease) brains from a collection of eleven early-onset familial Alzheimer's disease (EOfAD)-like and non-EOfAD-like mutations in three zebrafish genes. The one cellular activity consistently predicted as affected by only the EOfAD-like mutations is oxidative phosphorylation that produces most of the brain's energy. All the mutations were predicted to affect protein synthesis. We extended our analysis to knock-in mouse models of APOE alleles and found the same effect for the late onset Alzheimer's disease risk allele ε4. Our results support a common molecular basis for initiation of the pathological processes leading to both early and late onset forms of Alzheimer's disease and illustrate the utility of zebrafish and of knock-in, single EOfAD mutation models for understanding the causes of this disease.

The Roles and Mechanisms of lncRNAs in Liver Fibrosis

Long non-coding RNAs (lncRNAs) can potentially regulate all aspects of cellular activity including differentiation and development, metabolism, proliferation, apoptosis, and activation, and benefited from advances in transcriptomic and genomic research techniques and database management technologies, its functions and mechanisms in physiological and pathological states have been widely reported. Liver fibrosis is typically characterized by a reversible wound healing response, often accompanied by an excessive accumulation of extracellular matrix. In recent years, a range of lncRNAs have been investigated and found to be involved in several cellular-level regulatory processes as competing endogenous RNAs (ceRNAs) that play an important role in the development of liver fibrosis. A variety of lncRNAs have also been shown to contribute to the altered cell cycle, proliferation profile associated with the accelerated development of liver fibrosis. This review aims to discuss the functions and mechanisms of lncRNAs in the development and regression of liver fibrosis, to explore the major lncRNAs involved in the signaling pathways regulating liver fibrosis, to elucidate the mechanisms mediated by lncRNA dysregulation and to provide new diagnostic and therapeutic strategies for liver fibrosis.