Transformations of Group 7 Carbonyl Complexes: Possible Intermediates in a Homogeneous Syngas Conversion Scheme

A variety of C−H and C−C bond forming reactions of group 7 carbonyl complexes have been studied as potential steps in a homogeneously catalyzed conversion of syngas to C_(2+) compounds. The metal formyl complexes M(CO)_3(PPh_3)_2(CHO) (M = Mn, Re) are substantially stabilized by coordination of boranes BX_3 (X = F, C_6F_5) in the form of novel boroxycarbene complexes M(CO)_3(PPh_3)_2(CHOBX_3), but these boron-stabilized carbenes do not react with hydride sources to undergo further reduction to metal alkyls. The related manganese methoxycarbene cations [Mn(CO)_(5−x)(PPh_3)_x(CHOMe)]+ (x = 1 or 2), obtained by methylation of the formyls, do react with hydrides to form methoxymethyl complexes, which undergo further migratory insertion under an atmosphere of CO. The resulting acyls, cis- and trans-Mn(PPh_3)(CO)_4(C(O)CH_2OMe), can be alkylated to form the cationic carbene complex [Mn(PPh_3)(CO)_4(C(OR)CH_2OMe)]^+, which undergoes a 1,2 hydride shift to form 1,2-dialkoxyethylene, which is displaced from the metal, releasing triflate or diethyl ether adducts of [Mn(PPh_3)(CO)_4]^+. The acyl can also be protonated with HOTf to form a hydroxycarbene complex, which rearranges to Mn(PPh_3)(CO)_4(CH_2COOMe) and is protonolyzed to yield methyl acetate and [Mn(PPh_3)(CO)_4]^+; addition of L (L = PPh_3, CO) to the manganese cation regenerates [Mn(PPh_3)(CO)_4(L)]^+. Since the original formyl complex can be obtained by the reaction of [Mn(PPh_3)(CO)_5]^+ with [PtH(dmpe)_2]^+, which in turn can be generated from H_2, this set of transformations amounts to a stoichiometric cycle for selectively converting H_2 and CO into a C_2 compound under mild conditions

Nitrogen-Linked Diphosphine Ligands with Ethers Attached to Nitrogen for Chromium-Catalyzed Ethylene Tri- and Tetramerizations

A series of bis(diphenylphosphino)amine ligands with a donor group attached to the nitrogen linker have been prepared. Metalation of these ligands with chromium trichloride provides precursors to highly active, relatively stable, and selective catalysts for trimerization and tetramerization of ethylene. It has been demonstrated in oligomerization reactions performed at 1 and 4 atm of ethylene that these new systems increase total productivity by enhancing catalyst stability, as compared with those lacking a donor group on the diphosphine ligand. Furthermore, the use of chlorobenzene solvent (rather than toluene) significantly improves productivity, stability, and selectitvity. The product distributions and minor byproducts provide information relevant to mechanistic issues surrounding these types of reactions

Duration of untreated psychosis: Impact of the definition of treatment onset on its predictive value over three years of treatment.

While reduction of DUP (Duration of Untreated Psychosis) is a key goal in early intervention strategies, the predictive value of DUP on outcome has been questioned. We planned this study in order to explore the impact of three different definition of "treatment initiation" on the predictive value of DUP on outcome in an early psychosis sample. 221 early psychosis patients aged 18-35 were followed-up prospectively over 36 months. DUP was measured using three definitions for treatment onset: Initiation of antipsychotic medication (DUP1); engagement in a specialized programme (DUP2) and combination of engagement in a specialized programme and adherence to medication (DUP3). 10% of patients never reached criteria for DUP3 and therefore were never adequately treated over the 36-month period of care. While DUP1 and DUP2 had a limited predictive value on outcome, DUP3, based on a more restrictive definition for treatment onset, was a better predictor of positive and negative symptoms, as well as functional outcome at 12, 24 and 36 months. Globally, DUP3 explained 2 to 5 times more of the variance than DUP1 and DUP2, with effect sizes falling in the medium range according to Cohen. The limited predictive value of DUP on outcome in previous studies may be linked to problems of definitions that do not take adherence to treatment into account. While they need replication, our results suggest effort to reduce DUP should continue and aim both at early detection and development of engagement strategies

Exploring Role Method as an Identity Building Tool with Adolescent Adoptees: Development of a Method

The developmental task for adolescents concerns identity formation. Adoption literature indicates that for adolescent adoptees, the task of identity formation is often complex. As compared to their non-adopted peers, adolescent adoptees must contemplate their identity with informational factors and with potential gaps in their life stories. Though it is acknowledged in the literature that identity formation for adolescent adoptees is complex, and that adolescent adoptees seek mental health services in high percentages, little formal research has been conducted to investigate the usefulness of drama therapy in the treatment of adolescent adoptees, or the adoptee population overall. In response to a lack of prior research, this thesis asks: In what ways might the drama therapy approach of role method support identity formation in adolescent adoptees? After implementing a role method intervention with one adolescent adoptee client over three 50-minute sessions, results indicate that role method supported the client with self-perception and integration of identity as an adoptee. Implications include ways in which the structure and flexibility of role method align with the unifying and individual experiences of adolescent adoptees

Circadian and Circatidal Rhythms of Protein Abundance in the Intertidal Mussel Mytilus californianus

The intertidal zone is a dynamic environment that fluctuates with the 12.4-h tidal and 24-h light/dark cycle to predictably alter food availability, temperature, air exposure, wave action, oxygen partial pressure, and osmotic conditions. Intertidal sessile bivalves exhibit behavioral or physiological changes to minimize the persistent challenges of fluctuating environmental conditions, such as adjusting gaping behavior and heart rate. At the cellular level, transcriptomic studies on mussels’ baseline circadian and circatidal rhythms have determined that the circadian rhythm is the dominant transcriptional rhythm. However, as proteins reflect the basic molecular phenotype of an organism and their abundance may differ greatly from that of mRNA, these methods could fail to detect important cyclical changes in the proteome that cope with the regular stress of tidal rhythms. For this study, we acclimated intertidal Mytilus californianus to circadian (12:12 h light/dark cycle) and circatidal (6:6 h tidal cycle) conditions in a tidal simulator and sampled gill tissue from mussels every 2 h for 48 h for proteomic analysis. Approximately 86% of the proteins that were detected exhibited rhythmicity over the time course. The circadian cycle primarily determined the cyclic abundance of energy metabolism proteins, pivoting around the transition to the nighttime high tide. The tidal cycle contributed to alterations in cytoskeletal components, ER protein processing and vesicular trafficking, extracellular matrix and immune proteins, and oxidative stress and chaperoning proteins. We also found evidence that post-translational modifications may be important for driving these rhythms, as acetylation and phosphorylation motifs were enriched in the rhythmic proteins and we identified rhythms in elements of methylation, mitochondrial peptide processing, and acylation. These dynamic changes in proteins across numerous functional categories indicate that the combination of circadian and tidal cycles drive complex cellular changes to coordinate processes in a changing environment. This variation clearly shows that differential expression studies and biomonitoring efforts cannot assume a static baseline of cellular conditions in intertidal mussels

Age at the time of onset of psychosis: A marker of specific needs rather than a determinant of outcome?

While there is suggestion that early onset of psychosis is a determinant of outcome; knowledge regarding correlates of later onset age is more limited. This study explores the characteristics of patients developing psychosis after age 26, towards the end of the usual age range of early intervention programs, in order to identify potential specific needs of such patients. Two hundred and fifty-six early psychosis patients aged 18-35 were followed-up prospectively over 36 months. Patients with onset after 26 ("later onset", LO) were compared to the rest of the sample. LO patients (32% of the sample) had shorter DUP, were less likely to be male, had better premorbid functioning and were more likely to have been exposed to trauma. They had greater insight at presentation and less negative symptoms overall. The trajectories for positive and depressive symptoms were similar in both groups. Evolution of functional level was similar in both groups, but while LO patients recovered faster, they were significantly less likely to return to premorbid functional level. Later psychosis onset correlates with better premorbid functioning and higher rate of trauma exposure; the latter should therefore be a treatment focus in such patients. LO patients were less likely to return to premorbid functional level, which suggests that current treatment strategies may not be efficient to help patients maintain employment. The possibility of distinct illness mechanisms according to onset age and the more central role for trauma in patients with onset after age 26 needs to be further explored

Are Circadian cycles the dominant proteome rhythym in the intertidal mussel Mytilus californianus?

Mytilus californianus, also known as the California mussel, is a marine bivalve that is abundant along the West coast from Alaska to southern Baja California. They mainly reside in the upper-middle intertidal zone and cling to pier pilings and surf exposed rocks. They create multi-layered beds, which form a habitat for algae and many species of invertebrates. Intertidal mussels live in a naturally dynamic environment. It has previously been reported (Connor and Gracey, 2011) that the 24-hour circadian (day to night) rhythm of the intertidal mussel Mytilus californianus is primarily responsible for its rhythmic gene expression, as opposed to the 12.4-hour tidal cycles. Because tidal cycles challenge intertidal mussels through heat stress, salinity stress, hypoxia, and food availability, the dominance of the circadian cycle is surprising. However, transcriptomics may fail to detect up to half of the variation in the proteins that comprise the final functional phenotype of the organism. Using two-dimensional gel electrophoresis and mass spectrometry, we aimed to identify whether the proteome—the protein expression—of this organism also followed the same circadian rhythmic expression as its transcriptome

Structural analysis reveals features of the spindle checkpoint kinase Bub1–kinetochore subunit Knl1 interaction

The function of the essential checkpoint kinases Bub1 and BubR1 requires their recruitment to mitotic kinetochores. Kinetochore recruitment of Bub1 and BubR1 is proposed to rely on the interaction of the tetratricopeptide repeats (TPRs) of Bub1 and BubR1 with two KI motifs in the outer kinetochore protein Knl1. We determined the crystal structure of the Bub1 TPRs in complex with the cognate Knl1 KI motif and compared it with the structure of the equivalent BubR1TPR–KI motif complex. The interaction developed along the convex surface of the TPR assembly. Point mutations on this surface impaired the interaction of Bub1 and BubR1 with Knl1 in vitro and in vivo but did not cause significant displacement of Bub1 and BubR1 from kinetochores. Conversely, a 62-residue segment of Bub1 that includes a binding domain for the checkpoint protein Bub3 and is C terminal to the TPRs was necessary and largely sufficient for kinetochore recruitment of Bub1. These results shed light on the determinants of kinetochore recruitment of Bub1

PP1 and PP2A use opposite phospho-dependencies to control distinct processes at the kinetochore

PP1 and PP2A-B56 are major serine/threonine phosphatase families that achieve specificity by colocalizing with substrates. At the kinetochore, however, both phosphatases localize to an almost identical molecular space and yet they still manage to regulate unique pathways and processes. By switching or modulating the positions of PP1/PP2A-B56 at kinetochores, we show that their unique downstream effects are not due to either the identity of the phosphatase or its precise location. Instead, these phosphatases signal differently because their kinetochore recruitment can be either inhibited (PP1) or enhanced (PP2A) by phosphorylation inputs. Mathematical modeling explains how these inverse phospho-dependencies elicit unique forms of cross-regulation and feedback, which allows otherwise indistinguishable phosphatases to produce distinct network behaviors and control different mitotic processes. Furthermore, our genome-wide analysis suggests that these major phosphatase families may have evolved to respond to phosphorylation inputs in opposite ways because many other PP1 and PP2A-B56-binding motifs are also phospho-regulated