Seh1 targets GATOR2 and Nup153 to mitotic chromosomes

In metazoa the Nup107-160 nucleoporin Y complex plays a major role in formation of the nuclear pore complex in interphase and is localised to kinetochores in mitosis. The Nup107-160 complex shares a single highly conserved subunit, Seh1, with the GATOR2 complex, an essential activator of mTORC1 kinase. mTORC1/GATOR2 has a central role in the coordination of cell growth and proliferation. Here we use chemical genetics and quantitative chromosome proteomics to study the role of the Seh1 protein in mitosis. Surprisingly, Seh1 is not required for the association of the Nup107-160 complex with mitotic chromosomes, but it is essential for the association of both GATOR2 complex and nucleoporin Nup153 with mitotic chromosomes. Our analysis also reveals a role for Seh1 at human centromeres, where it is required for efficient localisation of the chromosomal passenger complex (CPC). Furthermore this analysis detects a functional interaction between the Nup107-160 complex and the small kinetochore protein SKAP.</jats:p

A pathway for mitotic chromosome formation

Mitotic chromosomes fold as compact arrays of chromatin loops. To identify the pathway of mitotic chromosome formation, we combined imaging and Hi-C analysis of synchronous DT40 cell cultures with polymer simulations. Here we show that in prophase, the interphase organization is rapidly lost in a condensin-dependent manner, and arrays of consecutive 60-kilobase (kb) loops are formed. During prometaphase, ~80-kb inner loops are nested within ~400-kb outer loops. The loop array acquires a helical arrangement with consecutive loops emanating from a central spiral staircase condensin scaffold. The size of helical turns progressively increases to ~12 megabases during prometaphase. Acute depletion of condensin I or II shows that nested loops form by differential action of the two condensins, whereas condensin II is required for helical winding

Two distinct regions of Mto1 are required for normal microtubule nucleation and efficient association with the gamma-tubulin complex in vivo

Cytoplasmic microtubule nucleation in the fission yeast Schizosaccharomyces pombe involves the interacting proteins Mto1 and Mto2, which are thought to recruit the γ-tubulin complex (γ-TuC) to prospective microtubule organizing centers. Mto1 contains a short amino-terminal region (CM1) that is conserved in higher eukaryotic proteins implicated in microtubule organization, centrosome function and/or brain development. Here we show that mutations in the Mto1 CM1 region generate mutant proteins that are functionally null for cytoplasmic microtubule nucleation and interaction with the γ-TuC (phenocopying mto1Δ), even though the Mto1-mutant proteins localize normally in cells and can bind Mto2. Interestingly, the CM1 region is not sufficient for efficient interaction with the γ-TuC. Mutation within a different region of Mto1, outside CM1, abrogates Mto2 binding and also impairs cytoplasmic microtubule nucleation and Mto1 association with the γ-TuC. However, this mutation allows limited microtubule nucleation in vivo, phenocopying mto2Δ rather than mto1Δ. Further experiments suggest that Mto1 and Mto2 form a complex (Mto1/2 complex) independent of the γ-TuC and that Mto1 and Mto2 can each associate with the γ-TuC in the absence of the other, albeit extremely weakly compared to when both Mto1 and Mto2 are present. We propose that Mto2 acts cooperatively with Mto1 to promote association of Mto1/2 complex with the γ-TuC

Neural computations underlying action-based decision making in the human brain

Action-based decision making involves choices between different physical actions to obtain rewards. To make such decisions the brain needs to assign a value to each action and then compare them to make a choice. Using fMRI in human subjects, we found evidence for action-value signals in supplementary motor cortex. Separate brain regions, most prominently ventromedial prefrontal cortex, were involved in encoding the expected value of the action that was ultimately taken. These findings differentiate two main forms of value signals in the human brain: those relating to the value of each available action, likely reflecting signals that are a precursor of choice, and those corresponding to the expected value of the action that is subsequently chosen, and therefore reflecting the consequence of the decision process. Furthermore, we also found signals in the dorsomedial frontal cortex that resemble the output of a decision comparator, which implicates this region in the computation of the decision itself

Hyperarousal symptoms after traumatic and nontraumatic births

Background: Measurement is critical in postnatal posttraumatic stress disorder (PTSD) because symptoms may be influenced by normal postnatal phenomena such as physiological changes and fatigue. Objective: This study examined: (1) whether hyperarousal symptoms differ between women who have traumatic or nontraumatic births; (2) whether the construct of hyperarousal is coherent in postnatal women; and (3) whether hyperarousal symptoms are useful for identifying women who have traumatic births or PTSD. Methods: A survey of PTSD symptoms in 1,078 women recruited via the community or Internet who completed an online or paper questionnaire measuring childbirth-related PTSD symptoms between 1 and 36 months after birth. Women who had a traumatic birth as defined by DSM-IV criterion A (n = 458) were compared with women who did not have a traumatic birth (n = 591). Results: A one-factor dimension of hyperarousal was identified that included all five hyperarousal items. Diagnostic criteria of two or more hyperarousal symptoms in the previous week were reported by 75.3% of women with traumatic birth and 50.5% of women with nontraumatic births. The difference in mean hyperarousal symptoms between groups was substantial at 0.76 of a standard deviation (Hedge’s g, CI = 0.64, 0.89). A larger difference was observed between women with and without diagnostic PTSD (g = 1.64, CI 1.46, 1.81). However, receiver operating characteristic analyses showed hyperarousal symptoms have poor specificity and alternative ways of calculating symptoms did not improve this. Comparison with other PTSD symptoms found re-experiencing symptoms were most accurate at identifying women with traumatic births. Conclusions: Results suggest hyperarousal symptoms are associated with traumatic birth and are a coherent construct in postnatal women. However, they have poor specificity and should only be used as part of diagnostic criteria, not as a sole indicator

Structural, item, and test generalizability of the psychopathology checklist - revised to offenders with intellectual disabilities

The Psychopathy Checklist–Revised (PCL-R) is the most widely used measure of psychopathy in forensic clinical practice, but the generalizability of the measure to offenders with intellectual disabilities (ID) has not been clearly established. This study examined the structural equivalence and scalar equivalence of the PCL-R in a sample of 185 male offenders with ID in forensic mental health settings, as compared with a sample of 1,212 male prisoners without ID. Three models of the PCL-R’s factor structure were evaluated with confirmatory factor analysis. The 3-factor hierarchical model of psychopathy was found to be a good fit to the ID PCL-R data, whereas neither the 4-factor model nor the traditional 2-factor model fitted. There were no cross-group differences in the factor structure, providing evidence of structural equivalence. However, item response theory analyses indicated metric differences in the ratings of psychopathy symptoms between the ID group and the comparison prisoner group. This finding has potential implications for the interpretation of PCL-R scores obtained with people with ID in forensic psychiatric settings

Economic choices can be made using only stimulus values

Decision-making often involves choices between different stimuli, each of which is associated with a different physical action. A growing consensus suggests that the brain makes such decisions by assigning a value to each available option and then comparing them to make a choice. An open question in decision neuroscience is whether the brain computes these choices by comparing the values of stimuli directly in goods space or instead by first assigning values to the associated actions and then making a choice over actions. We used a functional MRI paradigm in which human subjects made choices between different stimuli with and without knowledge of the actions required to obtain the different stimuli. We found neural correlates of the value of the chosen stimulus (a postdecision signal) in ventromedial prefrontal cortex before the actual stimulus–action pairing was revealed. These findings provide support for the hypothesis that the brain is capable of making choices in the space of goods without first transferring values into action space

Coming down from the trees: is terrestrial activity in Bornean orangutans natural or disturbance driven?

The orangutan is the world's largest arboreal mammal, and images of the red ape moving through the tropical forest canopy symbolise its typical arboreal behaviour. Records of terrestrial behaviour are scarce and often associated with habitat disturbance. We conducted a large-scale species-level analysis of ground-based camera-trapping data to evaluate the extent to which Bornean orangutans Pongo pygmaeus come down from the trees to travel terrestrially, and whether they are indeed forced to the ground primarily by anthropogenic forest disturbances. Although the degree of forest disturbance and canopy gap size influenced terrestriality, orangutans were recorded on the ground as frequently in heavily degraded habitats as in primary forests. Furthermore, all age-sex classes were recorded on the ground (flanged males more often). This suggests that terrestrial locomotion is part of the Bornean orangutan's natural behavioural repertoire to a much greater extent than previously thought, and is only modified by habitat disturbance. The capacity of orangutans to come down from the trees may increase their ability to cope with at least smaller-scale forest fragmentation, and to cross moderately open spaces in mosaic landscapes, although the extent of this versatility remains to be investigated