The role of the Rho GTPases in neuronal development

Our brain serves as a center for cognitive function and neurons within the brain relay and store information about our surroundings and experiences. Modulation of this complex neuronal circuitry allows us to process that information and respond appropriately. Proper development of neurons is therefore vital to the mental health of an individual, and perturbations in their signaling or morphology are likely to result in cognitive impairment. The development of a neuron requires a series of steps that begins with migration from its birth place and initiation of process outgrowth, and ultimately leads to differentiation and the formation of connections that allow it to communicate with appropriate targets. Over the past several years, it has become clear that the Rho family of GTPases and related molecules play an important role in various aspects of neuronal development, including neurite outgrowth and differentiation, axon pathfinding, and dendritic spine formation and maintenance. Given the importance of these molecules in these processes, it is therefore not surprising that mutations in genes encoding a number of regulators and effectors of the Rho GTPases have been associated with human neurological diseases. This review will focus on the role of the Rho GTPases and their associated signaling molecules throughout neuronal development and discuss how perturbations in Rho GTPase signaling may lead to cognitive disorders

Multifactorial Remodeling of the Cancer Immunopeptidome by IFNγ.

UNLABELLED: IFNγ alters the immunopeptidome presented on HLA class I (HLA-I), and its activity on cancer cells is known to be important for effective immunotherapy responses. We performed proteomic analyses of untreated and IFNγ-treated colorectal cancer patient-derived organoids and combined this with transcriptomic and HLA-I immunopeptidomics data to dissect mechanisms that lead to remodeling of the immunopeptidome through IFNγ. IFNγ-induced changes in the abundance of source proteins, switching from the constitutive to the immunoproteasome, and differential upregulation of different HLA alleles explained some, but not all, observed peptide abundance changes. By selecting for peptides which increased or decreased the most in abundance, but originated from proteins with limited abundance changes, we discovered that the amino acid composition of presented peptides also influences whether a peptide is upregulated or downregulated on HLA-I through IFNγ. The presence of proline within the peptide core was most strongly associated with peptide downregulation. This was validated in an independent dataset. Proline substitution in relevant core positions did not influence the predicted HLA-I binding affinity or stability, indicating that proline effects on peptide processing may be most relevant. Understanding the multiple factors that influence the abundance of peptides presented on HLA-I in the absence or presence of IFNγ is important to identify the best targets for antigen-specific cancer immunotherapies such as vaccines or T-cell receptor engineered therapeutics. SIGNIFICANCE: IFNγ remodels the HLA-I-presented immunopeptidome. We showed that peptide-specific factors influence whether a peptide is upregulated or downregulated and identified a preferential loss or downregulation of those with proline near the peptide center. This will help selecting immunotherapy target antigens which are consistently presented by cancer cells

Fairness as “appropriate impartiality” and the problem of the self-serving bias

Garrett Cullity contends that fairness is appropriate impartiality (See Cullity (2004) Chapters 8 and 10 and Cullity (2008)). Cullity deploys his account of fairness as a means of limiting the extreme moral demand to make sacrifices in order to aid others that was posed by Peter Singer in his seminal article ‘Famine, Affluence and Morality’. My paper is founded upon the combination of (1) the observation that the idea that fairness consists in appropriate impartiality is very vague and (2) the fact that psychological studies show the self-serving bias is especially likely to infect one’s judgements when the ideas involved are vague. I argue that Cullity’s solution to extreme moral demandingness is threatened by these findings. I then comment on whether some other theories of fairness are vulnerable to the same objection

Collateral Quality and Loan Default Risk: The Case of Vietnam

In the transition economy of Vietnam, financial market is dominated by banking sector but commercial banks heavily rely on collateral-based lending. While the relationship between collateral and implied credit risk is still in debate, this paper provides additional empirical evidence regarding the heterogeneous effects and transmission channels of collateral characteristics on loan delinquency. Applying instrumental variable probit analysis on a unique dataset of 2295 internal loan accounts in Vietnam, we find the significantly negative impact of collateral quality on the probability of default of consumer loans, supporting the dominance of borrower selection and risk-shifting over lender selection effects. The finding implies that high-quality collateral not only signals more credible borrower but also fosters good behavior in using loan, enabling bank to mitigate adverse selection and moral hazard problems

Survey and scoping of wildcat priority areas

This report summarises the findings of three complementary projects commissioned by SNH to inform the selection of Priority Areas for wildcat conservation; as proposed in the Scottish Wildcat Conservation Action Plan 2013. The scoping projects combined field surveys, taxonomic and genetic assessments, population modelling and a questionnaire survey of public attitudes to wildcat conservation measures. The report makes a recommendations for six wildcat Priority Areas from the nine areas pre-selected by SNH for survey. The sites recommended as Priority Areas all had evidence of cats that were classified as wildcats based on their appearance. However, domestic cats or hybrids (between domestic cats and wildcats) were also found, highlighting the need for conservation actions to reduce the risks they pose to wildcats from hybridisation and disease

Two-Way Quantum Time Transfer: A Method for Daytime Space-Earth Links

Remote clock synchronization is crucial for many classical and quantum network applications. Current state-of-the-art remote clock synchronization techniques achieve femtosecond-scale clock stability utilizing frequency combs, which are supplementary to quantum-networking hardware. Demonstrating an alternative, we synchronize two remote clocks across our freespace testbed using a method called two-way quantum time transfer (QTT). In one second we reach picosecond-scale timing precision under very lossy and noisy channel conditions representative of daytime space-Earth links with commercial off-the-shelf quantum-photon sources and detection equipment. This work demonstrates how QTT is potentially relevant for daytime space-Earth quantum networking and/or providing high-precision secure timing in GPS-denied environments.Comment: arXiv admin note: text overlap with arXiv:2211.0073

Semiparametric Efficiency Bound for Models of Sequential Moment Restrictions Containing Unknown Functions

This paper computes the semiparametric efficiency bound for finite dimensional parameters identified by models of sequential moment restrictions containing unknown functions. Our results extend those of Chamberlain (1992b) and Ai and Chen (2003) for semiparametric conditional moment restriction models with identical information sets to the case of nested information sets, and those of Chamberlain (1992a) and Brown and Newey (1998) for models of sequential moment restrictions without unknown functions to cases with unknown functions of possibly endogenous variables. Our bound results are applicable to semiparametric panel data models and semiparametric two stage plug-in problems. As an example, we compute the efficiency bound for a weighted average derivative of a nonparametric instrumental variables (IV) regression, and find that the simple plug-in estimator is not efficient. Finally, we present an optimally weighted, orthogonalized, sieve minimum distance estimator that achieves the semiparametric efficiency bound

Combination Forecasts of Bond and Stock Returns: An Asset Allocation Perspective

We investigate the out-of-sample forecasting ability of the HML, SMB, momentum, short-term and long-term reversal factors along with their size and value decompositions on U.S. bond and stock returns for a variety of horizons ranging from the short run (1 month) to the long run (2 years). Our findings suggest that these factors contain significantly more information for future bond and stock market returns than the typically employed financial variables. Combination of forecasts of the empirical factors turns out to be particularly successful, especially from an an asset allocation perspective. Similar findings pertain to the European and Japanese markets