Farnesylated Nuclear Proteins Kugelkern and Lamin Dm0 Affect Nuclear Morphology by Directly Interacting with the Nuclear Membrane

Nuclear shape changes are observed during a variety of developmental processes, pathological conditions and ageing. Here, the molecular mechanism is analyzed how the farnesylated nuclear proteins interact with the nuclear envelope and deform the phospholipid bilayer

The SUN Protein Mps3 Is Required for Spindle Pole Body Insertion into the Nuclear Membrane and Nuclear Envelope Homeostasis

The budding yeast spindle pole body (SPB) is anchored in the nuclear envelope so that it can simultaneously nucleate both nuclear and cytoplasmic microtubules. During SPB duplication, the newly formed SPB is inserted into the nuclear membrane. The mechanism of SPB insertion is poorly understood but likely involves the action of integral membrane proteins to mediate changes in the nuclear envelope itself, such as fusion of the inner and outer nuclear membranes. Analysis of the functional domains of the budding yeast SUN protein and SPB component Mps3 revealed that most regions are not essential for growth or SPB duplication under wild-type conditions. However, a novel dominant allele in the P-loop region, MPS3-G186K, displays defects in multiple steps in SPB duplication, including SPB insertion, indicating a previously unknown role for Mps3 in this step of SPB assembly. Characterization of the MPS3-G186K mutant by electron microscopy revealed severe over-proliferation of the inner nuclear membrane, which could be rescued by altering the characteristics of the nuclear envelope using both chemical and genetic methods. Lipid profiling revealed that cells lacking MPS3 contain abnormal amounts of certain types of polar and neutral lipids, and deletion or mutation of MPS3 can suppress growth defects associated with inhibition of sterol biosynthesis, suggesting that Mps3 directly affects lipid homeostasis. Therefore, we propose that Mps3 facilitates insertion of SPBs in the nuclear membrane by modulating nuclear envelope composition

The effect of DSM-5

OBJECTIVE: To determine the effect of the changing fifth edition of the Diagnostic and Statistical Manual (DSM-5) criteria on the developmental profiles of children diagnosed with an Autism spectrum disorder (ASD). METHODS: This study examines the effect of DSM-5 changes on impairment profiles of a population of 2054 at-risk toddlers aged 17-36 months using the Battelle Developmental Inventory, Second Edition. RESULTS: Toddlers diagnosed with an ASD according to the DSM-5 were found to represent a more impaired population compared to those who qualified for a diagnosis of an ASD based on the DSM-IV-TR, but not the DSM-5. The group diagnosed according to the DSM-IV-TR represented a population of toddlers who were more impaired than atypically developing peers. CONCLUSIONS: The proposed changes to the DSM will likely result in those diagnosed with an ASD according to the new criteria representing a more functionally impaired group. Implications of this proposed change are discussed

Factor Structure for Autism Spectrum Disorders with Toddlers Using DSM-IV and DSM-5 Criteria

With the publication of the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition, autism spectrum disorders are defined by two symptom clusters (social communication and restricted/repetitive behaviors) instead of the current three clusters. The current study examined the structure of the Baby and Infant Screen for Children with aUtIsm Traits (BISCUIT). First, an exploratory factor analysis was replicated whose results were largely comparable to the previous findings. Then, confirmatory factor analyses compared a two and three factor structure for the BISCUIT. Measures of model fit supported both the two and three factor models relatively well. When directly compared, the three factor model was found to be preferred over the two factor model. Implications are discussed

Nuclear Fusion and Genome Encounter during Yeast Zygote Formation

When haploid cells of Saccharomyces cerevisiae are crossed, parental nuclei congress and fuse with each other. To investigate underlying mechanisms, we have developed assays that evaluate the impact of drugs and mutations. Nuclear congression is inhibited by drugs that perturb the actin and tubulin cytoskeletons. Nuclear envelope (NE) fusion consists of at least five steps in which preliminary modifications are followed by controlled flux of first outer and then inner membrane proteins, all before visible dilation of the waist of the nucleus or coalescence of the parental spindle pole bodies. Flux of nuclear pore complexes occurs after dilation. Karyogamy requires both the Sec18p/NSF ATPase and ER/NE luminal homeostasis. After fusion, chromosome tethering keeps tagged parental genomes separate from each other. The process of NE fusion and evidence of genome independence in yeast provide a prototype for understanding related events in higher eukaryotes