Parallel in vivo analysis of large-effect autism genes implicates cortical neurogenesis and estrogen in risk and resilience

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Multina from the Late Triassic Luning Formation,Nevada

The discovery of the network trace fossil Multina isp. in the Luning Formation of central Nevada provides new insight into the depositional setting of the Shaly Limestone Member of the Luning Formation. The ichnofossils occur in tabular mudstone beds deposited on a shelf environment or open carbonate platform. Although Multina resembles Paleodictyon, as both share polygonal burrow nets and both frequently occur in deep-water habitats, Multina is less regular and has other morphological traits such as crossing burrow branches not seen in Paleodictyon or Protopaleodictyon.     

Calaminthadiol,a new 3,4-secotriterpenoid from Satureia calamintha and Satureia graeca

A new triterpenoid, calaminthadiol, 3,4-seco-4(23),12-ursadien-3,28-diol, was isolated from the leaves of Satureia calamintha and Satureia graeca. Its structure was elucidated by spectroscopic methods and partial synthesis. The natural occurrence of this compound can be conclusive for the chemotaxonomic characterization of the genus because of the rarity of the 3,4-fission in the α- and β-amyrin skeletons. A biogenetic mechanism for its formation is proposed. Sitosterol, stigmasterol and campesterol were also isolated.     

Tight Turns of Outer Membrane Proteins: An Analysis of Sequence,Structure, and Hydrogen Bonding

As a structural class, tight turns can control molecular recognition, enzymatic activity, and nucleation of folding. They have been extensively characterized in soluble proteins but have not been characterized in outer membrane proteins (OMPs), where they also support critical functions. We clustered the 4 to 6 residue tight turns of 110 OMPs to characterize the phi/psi angles, sequence, and hydrogen bonding of these structures. We find significant differences between reports of soluble protein tight turns and OMP tight turns. Since OMP strands are less twisted than soluble strands, they favor different turn structures types. Moreover, the membrane localization of OMPs yields different sequence hallmarks for their tight turns relative to soluble protein turns. We also characterize the differences in phi/psi angles, sequence, and hydrogen bonding between OMP extracellular loops and OMP periplasmic turns. As previously noted, the extracellular loops tend to be much longer than the periplasmic turns. We find that this difference in length is due to the broader distribution of lengths of the extracellular loops not a large difference in the median length. Extracellular loops also tend to have more charged residues as predicted by the charge-out rule. Finally, in all OMP tight turns, hydrogen bonding between the side chain and backbone 2 to 4 residues away from that side chain plays an important role. These bonds preferentially use an Asp, Asn, Ser, or Thr residue in a beta or pro phi/psi conformation. We anticipate that this study will be applicable to future design and structure prediction of OMPs.     

Nuclear lipid droplets and nuclear damage in Caenorhabditis elegans

Fat stored in the form of lipid droplets has long been considered a defining characteristic of cytoplasm. However, recent studies have shown that nuclear lipid droplets occur in multiple cells and tissues, including in human patients with fatty liver disease. The function(s) of stored fat in the nucleus has not been determined, and it is possible that nuclear fat is beneficial in some situations. Conversely, nuclear lipid droplets might instead be deleterious by disrupting nuclear organization or triggering aggregation of hydrophobic proteins. We show here that nuclear lipid droplets occur normally in C. elegans intestinal cells and germ cells, but appear to be associated with damage only in the intestine. Lipid droplets in intestinal nuclei can be associated with novel bundles of microfilaments (nuclear actin) and membrane tubules that might have roles in damage repair. To increase the normal, low frequency of nuclear lipid droplets in wild-type animals, we used a forward genetic screen to isolate mutants with abnormally large or abundant nuclear lipid droplets. Genetic analysis and cloning of three such mutants showed that the genes encode the lipid regulator SEIP-1/seipin, the inner nuclear membrane protein NEMP-1/Nemp1/TMEM194A, and a component of COPI vesicles called COPA-1/α-COP. We present several lines of evidence that the nuclear lipid droplet phenotype of copa-1 mutants results from a defect in retrieving mislocalized membrane proteins that normally reside in the endoplasmic reticulum. The seip-1 mutant causes most germ cells to have nuclear lipid droplets, the largest of which occupy more than a third of the nuclear volume. Nevertheless, the nuclear lipid droplets do not trigger apoptosis, and the germ cells differentiate into gametes that produce viable, healthy progeny. Thus, our results suggest that nuclear lipid droplets are detrimental to intestinal nuclei, but have no obvious deleterious effect on germ nuclei.     

Listening to mother: Long‐term maternal effects in mammalian development

The oocyte is a complex cell that executes many crucial and unique functions at the start of each life. These functions are fulfilled by a unique collection of macromolecules and other factors, all of which collectively support meiosis, oocyte activation, and embryo development. This review focuses on the effects of oocyte components on developmental processes that occur after the initial stages of embryogenesis. These include long‐term effects on genome function, metabolism, lineage allocation, postnatal progeny health, and even subsequent generations. Factors that regulate chromatin structure, genome programming, and mitochondrial function are elements that contribute to these oocyte functions.