Reciprocal Signaling between Glioblastoma Stem Cells and Differentiated Tumor Cells Promotes Malignant Progression

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ULTRASTRUCTURE OF MEIOSIS IN DASYA BAILLOUVIANA (RHODOPHYTA). II. PROMETAPHASE I—TELOPHASE II AND POST-DIVISION NUCLEAR BEHAVIOR1

This is the second of two papers which together are the first comprehensive ultrastructural report of meiosis in a red alga. Many details of the meiotic process in Dasya baillouviana (Gmelin) Montagne are the same as those reported previously for mitotic cells in ceramialian red algae, but several characteristics seem unique to meiotic cells. The nucleus and nucleolus of meiotic cells are larger than those of mitotic cells and large accumulations of smooth ER are often found at the division poles during meiosis 1. The function of the ER accumulations is unknown. Importantly, both interkinesis and a simultaneous division of two separate nuclei during meiosis II was demonstrated. These new observations fail to support earlier speculation on higher red algae for a “uninuclear” meiosis (both nuclear divisions within the same nuclear envelope). However, following meiosis II the four nuclei migrate centripetally and possibly fuse in the center of the tetrasporangium. This post-division nuclear maneuvering is not understood, but our interpretation accounts for the earlier and erroneous impression of “uninuclear” meiosis. Perhaps the most important aspect of meiosis observed in Dasya is its basic adherence to the pattern commonly seen in higher plants and animals. This conservatism of the meiotic process lends further skepticism to the belief that red algae are extremely “primitive” organisms, although they undoubtedly represent a very “ancient” group of eukaryotic plants.     

MicroDNA levels are dependent on MMEJ,repressed by c-NHEJ pathway,and stimulated by DNA damage

Extrachromosomal circular DNA (eccDNA) are present within all eukaryotic organisms and actively contribute to gene expression changes. MicroDNA (200-1000bp) are the most abundant type of eccDNA and can amplify tRNA, microRNA, and novel si-like RNA sequences. Due to the heterogeneity of microDNA and the limited technology to directly quantify circular DNA molecules, the specific DNA repair pathways that contribute to microDNA formation have not been fully elucidated. Using a sensitive and quantitative assay that quantifies eight known abundant microDNA, we report that microDNA levels are dependent on resection after double-strand DNA break (DSB) and repair by Microhomology Mediated End Joining (MMEJ). Further, repair of DSB without resection by canonical Non-Homologous End Joining (c-NHEJ) diminishes microDNA formation. MicroDNA levels are induced locally even by a single site-directed DSB, suggesting that excision of genomic DNA by two closely spaced DSB is not necessary for microDNA formation. Consistent with all this, microDNA levels accumulate as cells undergo replication in S-phase, when DNA breaks and repair are elevated, and microDNA levels are decreased if DNA synthesis is prevented. Thus, formation of microDNA occurs during the repair of endogenous or induced DNA breaks by resection-based DNA repair pathways.     

Mito‐nuclear discordance at a mimicry color transition zone in bumble bee Bombus melanopygus

As hybrid zones exhibit selective patterns of gene flow between otherwise distinct lineages, they can be especially valuable for informing processes of microevolution and speciation. The bumble bee, Bombus melanopygus, displays two distinct color forms generated by Müllerian mimicry: a northern “Rocky Mountain''’ color form with ferruginous mid‐abdominal segments (B. m. melanopygus) and a southern “Pacific''’ form with black mid‐abdominal segments (B. m. edwardsii). These morphs meet in a mimetic transition zone in northern California and southern Oregon that is more narrow and transitions further west than comimetic bumble bee species. To understand the historical formation of this mimicry zone, we assessed color distribution data for B. melanopygus from the last 100 years. We then examined gene flow among the color forms in the transition zone by comparing sequences from mitochondrial COI barcode sequences, color‐controlling loci, and the rest of the nuclear genome. These data support two geographically distinct mitochondrial haplogroups aligned to the ancestrally ferruginous and black forms that meet within the color transition zone. This clustering is also supported by the nuclear genome, which, while showing strong admixture across individuals, distinguishes individuals most by their mitochondrial haplotype, followed by geography. These data suggest the two lineages most likely were historically isolated, acquired fixed color differences, and then came into secondary contact with ongoing gene flow. The transition zone, however, exhibits asymmetries: mitochondrial haplotypes transition further south than color pattern, and both transition over shorter distances in the south. This system thus demonstrates alternative patterns of gene flow that occur in contact zones, presenting another example of mito‐nuclear discordance. Discordant gene flow is inferred to most likely be driven by a combination of mimetic selection, dominance effects, and assortative mating.     

Whole genome sequencing reveals a 7 base-pair deletion in DMD exon 42 in a dog with muscular dystrophy

Mammalian Genome - Dystrophin is a key cytoskeletal protein coded by the Duchenne muscular dystrophy (DMD) gene located on the X-chromosome. Truncating mutations in the DMD gene cause loss of...     

Membrane-associated DNA Transport Machines

DNA pumps play important roles in bacteria during cell division and during the transfer of genetic material by conjugation and transformation. The FtsK/SpoIIIE proteins carry out the translocation of double-stranded DNA to ensure complete chromosome segregation during cell division. In contrast, the complex molecular machines that mediate conjugation and genetic transformation drive the transport of single stranded DNA. The transformation machine also processes this internalized DNA and mediates its recombination with the resident chromosome during and after uptake, whereas the conjugation apparatus processes DNA before transfer. This article reviews these three types of DNA pumps, with attention to what is understood of their molecular mechanisms, their energetics and their cellular localizations.The transport of DNA across membranes by bacteria occurs during sporulation, during cytokinesis, directly from other cells and from the environment. This review addresses the question “how is the DNA polyanion transferred processively across the hydrophobic membrane barrier”?DNA transport must occur through water-filled channels, at least conceptually addressing the problem posed by the hydrophobic membrane. DNA transporters presumably use metabolic energy directly or a coupled-flow (symporter or antiporter) mechanism to drive DNA processively through the channel. It is possible that a Brownian ratchet mechanism, in which directionality is imposed on a diffusive process, also contributes to transport.In this article, we will consider several DNA transport systems. We will begin with the simplest one, namely the FtsK/SpoIIIE system that is involved in cell division and sporulation. We will then turn to the more complex, multiprotein DNA uptake systems that accomplish genetic transformation (the uptake of environmental DNA from the environment) and the conjugation systems of Gram-negative bacteria that mediate the unidirectional transfer of DNA between cells. In each case we will discuss the proteins involved, their actions and the sources of energy that drive transport. Space limitations prevent discussion of other relevant topics, such as DNA transport during bacteriophage infection and more than a brief reference to conjugation in Gram-positive bacteria.     

Alteration of NCoR Corepressor Splicing in Mice Causes Increased Body Weight and Hepatosteatosis without Glucose Intolerance

Alternative mRNA splicing is an important means of diversifying function in higher eukaryotes. Notably, both NCoR and SMRT corepressors are subject to alternative mRNA splicing, yielding a series of distinct corepressor variants with highly divergent functions. Normal adipogenesis is associated with a switch in corepressor splicing from NCoRω to NCoRδ, which appears to help regulate this differentiation process. We report here that mimicking this development switch in mice by a splice-specific whole-animal ablation of NCoRω is very different from a whole-animal or tissue-specific total NCoR knockout and produces significantly enhanced weight gain on a high-fat diet. Surprisingly, NCoRω^−/− mice are protected against diet-induced glucose intolerance despite enhanced adiposity and the presence of multiple additional, prodiabetic phenotypic changes. Our results indicate that the change in NCoR splicing during normal development both helps drive normal adipocyte differentiation and plays a key role in determining a metabolically appropriate storage of excess calories. We also conclude that whole-gene “knockouts” fail to reveal how important gene products are customized, tailored, and adapted through alternative mRNA splicing and thus do not reveal all the functions of the protein products of that gene.