Association of Liver X Receptor Alpha and Beta Genes with Carcass Lean and Fat Content in Pigs

A three-generation resource family of a cross between the Berkshire and Yorkshire (BY) pig breeds and four pig commercial populations were used to investigate whether the Liver X Receptor Alpha (LXRA) and Beta (LXRB) genes play a role in influencing lean and fat growth in pigs. Our current findings from this study have suggested that LXRA and LXRB might have potential effects, especially for loin lean and fat content

Extreme stability in de novo-designed repeat arrays is determined by unusually stable short-range interactions

Designed helical repeats (DHRs) are modular helix–loop–helix–loop protein structures that are tandemly repeated to form a superhelical array. Structures combining tandem DHRs demonstrate a wide range of molecular geometries, many of which are not observed in nature. Understanding cooperativity of DHR proteins provides insight into the molecular origins of Rosetta-based protein design hyperstability and facilitates comparison of energy distributions in artificial and naturally occurring protein folds. Here, we use a nearest-neighbor Ising model to quantify the intrinsic and interfacial free energies of four different DHRs. We measure the folding free energies of constructs with varying numbers of internal and terminal capping repeats for four different DHR folds, using guanidine-HCl and glycerol as destabilizing and solubilizing cosolvents. One-dimensional Ising analysis of these series reveals that, although interrepeat coupling energies are within the range seen for naturally occurring repeat proteins, the individual repeats of DHR proteins are intrinsically stable. This favorable intrinsic stability, which has not been observed for naturally occurring repeat proteins, adds to stabilizing interfaces, resulting in extraordinarily high stability. Stable repeats also impart a downhill shape to the energy landscape for DHR folding. These intrinsic stability differences suggest that part of the success of Rosetta-based design results from capturing favorable local interactions

Dynabench: Rethinking Benchmarking in NLP

We introduce Dynabench, an open-source platform for dynamic dataset creation and model benchmarking. Dynabench runs in a web browser and supports human-and-model-in-the-loop dataset creation: annotators seek to create examples that a target model will misclassify, but that another person will not. In this paper, we argue that Dynabench addresses a critical need in our community: contemporary models quickly achieve outstanding performance on benchmark tasks but nonetheless fail on simple challenge examples and falter in real-world scenarios. With Dynabench, dataset creation, model development, and model assessment can directly inform each other, leading to more robust and informative benchmarks. We report on four initial NLP tasks, illustrating these concepts and highlighting the promise of the platform, and address potential objections to dynamic benchmarking as a new standard for the field

SKA2 regulated hyperactive secretory autophagy drives neuroinflammation-induced neurodegeneration

High levels of proinflammatory cytokines induce neurotoxicity and catalyze inflammation-driven neurodegeneration, but the specific release mechanisms from microglia remain elusive. Here we show that secretory autophagy (SA), a non-lytic modality of autophagy for secretion of vesicular cargo, regulates neuroinflammation-mediated neurodegeneration via SKA2 and FKBP5 signaling. SKA2 inhibits SA-dependent IL-1β release by counteracting FKBP5 function. Hippocampal Ska2 knockdown in male mice hyperactivates SA resulting in neuroinflammation, subsequent neurodegeneration and complete hippocampal atrophy within six weeks. The hyperactivation of SA increases IL-1β release, contributing to an inflammatory feed-forward vicious cycle including NLRP3-inflammasome activation and Gasdermin D-mediated neurotoxicity, which ultimately drives neurodegeneration. Results from protein expression and co-immunoprecipitation analyses of male and female postmortem human brains demonstrate that SA is hyperactivated in Alzheimer's disease. Overall, our findings suggest that SKA2-regulated, hyperactive SA facilitates neuroinflammation and is linked to Alzheimer's disease, providing mechanistic insight into the biology of neuroinflammation

Constant Velocity Constraints for Self-Supervised Monocular Depth Estimation

We present a new method for self-supervised monocular depth estimation. Contemporary monocular depth estimation methods use a triplet of consecutive video frames to estimate the central depth image. We make the assumption that the ego-centric view progresses linearly in the scene, based on the kinematic and physical properties of the camera. During the training phase, we can exploit this assumption to create a depth estimation for each image in the triplet. We then apply a new geometry constraint that supports novel synthetic views, thus providing a strong supervisory signal. Our contribution is simple to implement, requires no additional trainable parameter, and produces competitive results when compared with other state-of-the-art methods on the popular KITTI corpus

Stress-primed secretory autophagy promotes extracellular BDNF maturation by enhancing MMP9 secretion

The stress response is an essential mechanism for maintaining homeostasis, and its disruption is implicated in several psychiatric disorders. On the cellular level, stress activates, among other mechanisms, autophagy that regulates homeostasis through protein degradation and recycling. Secretory autophagy is a recently described pathway in which autophagosomes fuse with the plasma membrane rather than with lysosomes. Here, we demonstrate that glucocorticoid-mediated stress enhances secretory autophagy via the stress-responsive co-chaperone FK506-binding protein 51. We identify the matrix metalloproteinase 9 (MMP9) as one of the proteins secreted in response to stress. Using cellular assays and in vivo microdialysis, we further find that stress-enhanced MMP9 secretion increases the cleavage of pro-brain-derived neurotrophic factor (proBDNF) to its mature form (mBDNF). BDNF is essential for adult synaptic plasticity and its pathway is associated with major depression and posttraumatic stress disorder. These findings unravel a cellular stress adaptation mechanism that bears the potential of opening avenues for the understanding of the pathophysiology of stress-related disorders

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016