In this paper we revisit the process of constructing a high resolution 3D morphable model of face shape variation. We demonstrate how the statistical tools of thin-plate splines and Procrustes analysis can be used to construct a morphable model that is both more efficient and generalises to novel face surfaces more accurately than previous models. We also reformulate the probabilistic prior that the model provides on the distribution of parameter vector lengths. This distribution is determined solely by the number of model dimensions and can be used as a regularisation constraint in fitting the model to data without the need to empirically choose a parameter controlling the trade off between plausibility and quality of fit. As an example application of this improved model, we show how it may be fitted to a sparse set of 2D feature points (approximately 100). This provides a rapid means to estimate high resolution 3D face shape for a face in any pose given only a single face image. We present experimental results using ground truth data and hence provide absolute reconstruction errors. On average, the per vertex error of the reconstructed faces is less than 3.6mm.

The mechanisms underlying violence and aggression and its control remain poorly understood. Using the Resident-Intruder paradigm, we have discovered that resident mice with combined deletion of TNF receptor type 1 (TNF-R1) and type 2 (TNF-R2) genes show a striking absence of aggressive behavior, which includes fighting, sideways postures, and tail rattling. In parallel, resident TNF-R1 and TNF-R2 knockout mice show an increase in non-aggressive exploration of the intruder mice. Given the relationship between aggression and anxiety, we also measured anxiety-related behavior, as reflected by performance in the Open Field and the Light-Dark Choice Test. Compared with wild type mice, TNF-R1 and TNF-R2 deficient mice spent significantly more time and showed increased movement in the center of the Open Field and in the illuminated compartment of the light-dark box, suggesting an anxiolytic-like profile. Together, these data show that combined deletion of TNF-R1 and TNF-R2 results in a striking absence of aggressive behavior, an increase in non-aggressive exploration, and anxiolytic-like effects. These findings identify potent roles for TNF in regulating aggression and anxiety-related behavior, and suggest that TNF receptor signaling tonically modulates activity in brain regions underlying these behaviors.

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Staphylococcus aureus causes most skin infections in humans, and the emergence of methicillin-resistant S. aureus (MRSA) strains is a serious public health threat. There is an urgent clinical need for nonantibiotic immunotherapies to treat MRSA infections and prevent the spread of antibiotic resistance. Here, we investigated the pan-caspase inhibitor quinoline–valine–aspartic acid–difluorophenoxymethyl ketone (Q-VD-OPH) for efficacy against MRSA skin infection in mice. A single systemic dose of Q-VD-OPH decreased skin lesion sizes and reduced bacterial burden compared with vehicle-treated or untreated mice. Although Q-VD-OPH inhibited inflammasome-dependent apoptosis-associated speck-like protein containing caspase activation and recruitment domain (ASC) speck formation and caspase-1–mediated interleukin-1β (IL-1β) production, Q-VD-OPH maintained efficacy in mice deficient in IL-1β, ASC, caspase-1, caspase-11, or gasdermin D. Thus, Q-VD-OPH efficacy was independent of inflammasome-mediated pyroptosis. Rather, Q-VD-OPH reduced apoptosis of monocytes and neutrophils. Moreover, Q-VD-OPH enhanced necroptosis of macrophages with concomitant increases in serum TNF and TNF-producing neutrophils, monocytes/macrophages, and neutrophils in the infected skin. Consistent with this, Q-VD-OPH lacked efficacy in mice deficient in TNF (with associated reduced neutrophil influx and necroptosis), in mice deficient in TNF/IL-1R and anti-TNF antibody-treated WT mice. In vitro studies revealed that combined caspase-3, caspase-8, and caspase-9 inhibition reduced apoptosis, and combined caspase-1, caspase-8, and caspase-11 inhibition increased TNF, suggesting a mechanism for Q-VD-OPH efficacy in vivo. Last, Q-VD-OPH also had a therapeutic effect against Streptococcus pyogenes and Pseudomonas aeruginosa skin infections in mice. Collectively, pan-caspase inhibition represents a potential host-directed immunotherapy against MRSA and other bacterial skin infections.