microPublication biology最新文献

Bryant-Li-Bhoj syndrome (BLBS) is associated with germline mutations in the genes encoding human histone H3.3. While to date 70 H3.3 mutants have been associated with BLBS, the molecular mechanisms underpinning this condition remain undefined. We recently showed that in yeast the H3-L61R BLBS mutant causes trapping of yFACT at 3' ends of genes, raising the possibility that this defect could be a contributing factor to disease across all H3-BLBS mutants. Here, we show that of nine additional yeast H3-BLBS mutants analyzed, only one causes yFACT 3' end-trapping, thus indicating that this defect is not a universal feature of H3-BLBS mutants. We also present additional phenotypic data that could provide insights into the molecular mechanisms contributing to BLBS in human patients.

Dictyostelium amoebae store surplus fatty acids from the diet in form of lipid droplets. Some of the enzymes governing neutral lipid synthesis are already known. For the phosphatidic acid-specific phosphatases, six genes were found, one of which was automatically annotated as LPIN2. Two GFP-tagged variants of LPIN2 homogeneously distribute in the cytoplasm and no organelle association was observed. LPIN2 ^- mutants contain less than 17% residual amount of the major neutral lipid species, but phospholipid amounts are not obviously affected. A growth retardation on bacteria as food source may suggest that lipid droplets serve to detoxify excess free fatty acids.

In adverse conditions, Caenorhabditis elegans larvae can enter the alternative L2d stage. If conditions remain poor, L2d larvae can molt into stress-resistant dauer larvae. The FOXO ortholog daf-16 promotes dauer formation, but daf-16 mutants can enter dauer with incomplete penetrance in combination with a mutation in daf-7 /TGFβ. The degree to which daf-16 ; daf-7 larvae enter L2d is unknown. Here we show that many daf-16 ; daf-7 mutants express intermediate levels of the ets-10p::gfp L2d marker, suggesting incomplete entry into L2d. Furthermore, lack of ets-10p::gfp expression early in the second larval stage partially predicts which daf-16 ; daf-7 larvae will bypass dauer formation.

Cytokinesis, the physical division of one cell into two, is typically assumed to use the same molecular process across animal cells. However, regulation of cell division can vary significantly among different cell types, even within the same multicellular organism. Using six fast-acting temperature-sensitive (ts) cytokinesis-defective mutants, we found that each had unique cell type-specific profiles in the early 2-cell through 8-cell C. elegans embryo. Certain cell types were more sensitive than others to actomyosin and spindle signaling disruptions, disrupting two members of the same complex could result in different phenotypes, and protection against actomyosin inhibition did not always protect against spindle signaling inhibition.

Cells have evolved an elaborate network of folding and degradation pathways to maintain the native state of proteins. If these pathways are disrupted (e.g., mutation) or their capacity is exceeded then protein aggregates form in cells. Cells sequester these aggregated proteins into aggresome or aggresome-like bodies as a protective mechanism. In this study, we co-expressed two model misfolded proteins in HEK293 cells and measured aggresome formation upon proteasomal inhibition. We observed spatial differences in early time points of aggresome formation upon co-expression of the misfolded proteins compared to individual expression in cells.

Two genomic genes, which rescue ammonium assimilation defect in the glutamate-requiring Schizosaccharomyces pombe glu1 mutant, were identified. The maa1 , encoding a mitochondrial aspartate aminotransferase, is the causative gene of glu1 mutation because an inseparable linkage between maa1 and glu1 on the chromosome, and also the glu1 mutant strain has a nonsense mutation within the maa1 coding region, which is responsible for its defective phenotype. The yhm2 , a mitochondrial 2-oxoglutarate carrier, was also isolated as a weak multicopy suppressor gene. These findings reiterate the importance of the mitochondria in utilizing the amino acids for cellular nitrogen metabolism.

Mitochondria are essential for supporting the high metabolic demands that are required for brain function. Impairments in mitochondria have been linked to age-related decline in brain functions. Here, we investigate whether the mitochondrial respiratory capacity of brain cells is changed in cognitive aging. We used a rat model of normal cognitive aging and analyzed mitochondrial oxidative phosphorylation in frozen brain samples. Mitochondrial oxygen consumption rate analysis of the frontal cortex did not show any differences between young rats and aged rats with either intact memory or impaired spatial memory. Mitochondrial ATP synthase activity and quantity also did not differ between young and aged rats. These results suggest that the total level of mitochondrial respiratory capacity is preserved in the frontal cortex of aged rats and may not explain aging-associated cognitive impairment.

The coffee industry reaches over 80 billion US dollars in revenue partially due to the numerous chemicals that allow for coffee's highly attractive aroma and overall flavor. Many people integrate coffee into their everyday routine; therefore, understanding the attraction to coffee can facilitate, 1) the characterization of its attractive nature, and, 2) allow further understanding of how humans interpret taste and smell on a molecular and cellular level, from initial sensation to higher processing of these complex neural signals. We report that the model worm, C. elegans , can smell and perform strong attraction behavior using chemotaxis towards various types of coffee odors. In this study, we show that the nematode C. elegans is strongly attracted to various forms of coffee. We have also identified neuronal molecules that mediate this sensory-dependent behavior. Overall, we provide a platform to more thoroughly dissect the mechanisms and neuronal circuits that mediate odor-guided behavior to a complex human-sensed stimulus.

Development of the Drosophila melanogaster central nervous system midline depends on the gene single-minded ( sim ). Although sim regulation has been studied extensively, the fact that an enhancer mediating late embryonic sim transcription has not been identified suggests that additional regulatory sequences remain unknown. We tested several evolutionarily conserved sequences in the sim downstream region and isolated sim_3pB , whose midline activity in a reporter gene assay begins later than previously characterized sim enhancers. Its activity shares several key similarities with the Aedes aegypti sim _ 5P3 enhancer, though is sufficiently different to warrant further investigation into how sim_3pB functions in its native context.

MicroRNAs are small noncoding nucleotides that serve as intracellular and extracellular signaling molecules. A previous collaboration found miR-127/3p circulation in the blood of breast cancer patients correlated with improved patient recovery and prognosis. While this study exclusively focused on breast cancer patients, data mining of the TCGA databases indicated that miR-127/3p may be positively associated with outcomes in other cancer types. In our study, A549 lung adenocarcinoma cells were transfected with miR-127/3p using Cell Block protocols produced by the Cell Biology Education Consortium (CBEC). After transfection, cell migration (scratch/wound healing) assays were used to determine the role miR-127/3p plays in the tumor microenvironment. To mimic and test this environment, transfected cells were incubated in normal oxygen (normoxic) and low oxygen (hypoxic) environments. We found that miR-127/3p inhibited cell migration in both normal oxygen and hypoxic environments. These results help elucidate the role miR-127/3p plays in the prevention of metastasis and further highlight its potential as a positive biomarker.