Asteroid g-2 experiments: new fifth force and ultralight dark sector tests

We study for the first time the possibility of probing long-range fifth forces utilizing asteroid astrometric data, via the fifth force-induced orbital precession. We examine nine Near-Earth Object (NEO) asteroids whose orbital trajectories are accurately determined via optical and radar astrometry. Focusing on a Yukawa-type potential mediated by a new gauge field (dark photon) or a baryon-coupled scalar, we estimate the sensitivity reach for the fifth-force coupling strength and mediator mass in the mass range $m \simeq 10^{-21}-10^{-15}\,{\rm eV}$. Our estimated sensitivity is comparable to leading limits from torsion balance experiments, potentially exceeding these in a specific mass range. The fifth forced-induced precession increases with the orbital semi-major axis in the small $m$ limit, motivating the study of objects further away from the Sun. We discuss future exciting prospects for extending our study to more than a million asteroids (including NEOs, main-belt asteroids, Hildas, and Jupiter Trojans), as well as trans-Neptunian objects and exoplanets.Comment: 2 figures, 1 table, 5 pages + reference

NARRATE: A Normal Assisted Free-View Portrait Stylizer

In this work, we propose NARRATE, a novel pipeline that enables simultaneously editing portrait lighting and perspective in a photorealistic manner. As a hybrid neural-physical face model, NARRATE leverages complementary benefits of geometry-aware generative approaches and normal-assisted physical face models. In a nutshell, NARRATE first inverts the input portrait to a coarse geometry and employs neural rendering to generate images resembling the input, as well as producing convincing pose changes. However, inversion step introduces mismatch, bringing low-quality images with less facial details. As such, we further estimate portrait normal to enhance the coarse geometry, creating a high-fidelity physical face model. In particular, we fuse the neural and physical renderings to compensate for the imperfect inversion, resulting in both realistic and view-consistent novel perspective images. In relighting stage, previous works focus on single view portrait relighting but ignoring consistency between different perspectives as well, leading unstable and inconsistent lighting effects for view changes. We extend Total Relighting to fix this problem by unifying its multi-view input normal maps with the physical face model. NARRATE conducts relighting with consistent normal maps, imposing cross-view constraints and exhibiting stable and coherent illumination effects. We experimentally demonstrate that NARRATE achieves more photorealistic, reliable results over prior works. We further bridge NARRATE with animation and style transfer tools, supporting pose change, light change, facial animation, and style transfer, either separately or in combination, all at a photographic quality. We showcase vivid free-view facial animations as well as 3D-aware relightable stylization, which help facilitate various AR/VR applications like virtual cinematography, 3D video conferencing, and post-production.Comment: 14 pages,13 figures https://youtu.be/mP4FV3evmy

Identification of critical residues of influenza neuraminidase in viral particle release

BACKGROUND: Influenza neuraminidase (NA) is essential for virus release from its host cells and it is one of the targets for structure-based antiviral drug design. RESULTS: In this report, we established a pseudoviral particle release assay to study NA function, which is based on lentiviral particles pseudotyped with influenza glycoproteins HA and NA as a surrogate system. Through an extensive molecular analysis, we sought to characterize important residues governing NA function. We identified five residues of NA, 234, 241, 257, 286 and 345, four of which (except 345) map away from the active site of NA when projected onto the three-dimensional structure of avian influenza H5N1 NA, and substitutions of these residues adversely affected the NA-mediated viral particle release, suggesting that these residues are critical for NA enzymatic activity. CONCLUSION: Through extensive chimeric and mutational analyses, we have identified several residues, which map away from the active site and are critical for NA function. These findings provide new insights into NA-mediated pseudoviral particle release and may have important implications in drug design and therapeutics against influenza infection

Fine-grained Appearance Transfer with Diffusion Models

Image-to-image translation (I2I), and particularly its subfield of appearance transfer, which seeks to alter the visual appearance between images while maintaining structural coherence, presents formidable challenges. Despite significant advancements brought by diffusion models, achieving fine-grained transfer remains complex, particularly in terms of retaining detailed structural elements and ensuring information fidelity. This paper proposes an innovative framework designed to surmount these challenges by integrating various aspects of semantic matching, appearance transfer, and latent deviation. A pivotal aspect of our approach is the strategic use of the predicted $x_0$ space by diffusion models within the latent space of diffusion processes. This is identified as a crucial element for the precise and natural transfer of fine-grained details. Our framework exploits this space to accomplish semantic alignment between source and target images, facilitating mask-wise appearance transfer for improved feature acquisition. A significant advancement of our method is the seamless integration of these features into the latent space, enabling more nuanced latent deviations without necessitating extensive model retraining or fine-tuning. The effectiveness of our approach is demonstrated through extensive experiments, which showcase its ability to adeptly handle fine-grained appearance transfers across a wide range of categories and domains. We provide our code at https://github.com/babahui/Fine-grained-Appearance-TransferComment: 14 pages, 15 figure

Analysis of hemagglutinin-mediated entry tropism of H5N1 avian influenza

<p>Abstract</p> <p>Background</p> <p>Avian influenza virus H5N1 is a major concern as a potential global pandemic. It is thought that multiple key events must take place before efficient human-to-human transmission of the virus occurs. The first step in overcoming host restriction is viral entry which is mediated by HA, responsible for both viral attachment and viral/host membrane fusion. HA binds to glycans-containing receptors with terminal sialic acid (SA). It has been shown that avian influenza viruses preferentially bind to α2,3-linked SAs, while human influenza A viruses exhibit a preference for α2,6-linked SAs. Thus it is believed the precise linkage of SAs on the target cells dictate host tropism of the viruses.</p> <p>Results</p> <p>We demonstrate that H5N1 HA/HIV pseudovirus can efficiently transduce several human cell lines including human lung cells. Interestingly, using a lectin binding assay we show that the presence of both α2,6-linked and α2,3-linked SAs on the target cells does not always correlate with efficient transduction. Further, HA substitutions of the residues implicated in switching SA-binding between avian and human species did not drastically affect HA-mediated transduction of the target cells or target cell binding.</p> <p>Conclusion</p> <p>Our results suggest that a host factor(s), which is yet to be identified, is required for H5N1 entry in the host cells.</p

NLRP6 deficiency expands a novel CD103 + B cell population that confers immune tolerance in NOD mice

Introduction: Gut microbiota have been linked to modulating susceptibility to Type 1 diabetes; however, there are many ways in which the microbiota interact with host cells, including through microbial ligand binding to intracellular inflammasomes (large multi-subunit proteins) to initiate immune responses. NLRP6, a microbe-recognizing inflammasome protein, is highly expressed by intestinal epithelial cells and can alter susceptibility to cancer, obesity and Crohn’s disease; however, the role of NLRP6 in modulating susceptibility to autoimmune diabetes, was previously unknown. Methods: We generated NLRP6-deficient Non-obese diabetic (NOD) mice to study the effect of NLRP6-deficiency on the immune cells and susceptibility to Type 1 diabetes development. Results: NLRP6-deficient mice exhibited an expansion of CD103+ B cells and were protected from type 1 diabetes. Moreover, NLRP6-deficient CD103+ B cells express regulatory markers, secreted higher concentrations of IL-10 and TGFb1 cytokines and suppressed diabetogenic T cell proliferation, compared to NLRP6-sufficient CD103+ B cells. Microarray analysis of NLRP6-sufficient and -deficient CD103+ B cells identified 79 significantly different genes including genes regulated by lipopolysaccharide (LPS), tretinoin, IL-10 and TGFb, which was confirmed in vitro following LPS stimulation. Furthermore, microbiota from NLRP6-deficient mice induced CD103+ B cells in colonized NLRP6-sufficient germ-free mice; however, the long-term maintenance of the CD103+ B cells required the absence of NLRP6 in the hosts, or continued exposure to microbiota from NLRP6-deficient mice. Discussion: Together, our data indicate that NLRP6 deficiency promotes expansion and maintenance of a novel TGF -dependent CD103+ Breg population. Thus, targeting NLRP6 therapeutically may prove clinically useful

Aristolochic Acid I Induced Autophagy Extenuates Cell Apoptosis via ERK 1/2 Pathway in Renal Tubular Epithelial Cells

Autophagy is a lysosomal degradation pathway that is essential for cell survival and tissue homeostasis. However, limited information is available about autophagy in aristolochic acid (AA) nephropathy. In this study, we investigated the role of autophagy and related signaling pathway during progression of AAI-induced injury to renal tubular epithelial cells (NRK52E cells). The results showed that autophagy in NRK52E cells was detected as early as 3–6 hrs after low dose of AAI (10 µM) exposure as indicated by an up-regulated expression of LC3-II and Beclin 1 proteins. The appearance of AAI-induced punctated staining of autophagosome-associated LC3-II upon GFP-LC3 transfection in NRK52E cells provided further evidence for autophagy. However, cell apoptosis was not detected until 12 hrs after AAI treatment. Blockade of autophagy with Wortmannin or 3-Methyladenine (two inhibitors of phosphoinositede 3-kinases) or small-interfering RNA knockdown of Beclin 1 or Atg7 sensitized the tubular cells to apoptosis. Treatment of NRK52E cells with AAI caused a time-dependent increase in extracellular signal-regulated kinase 1 and 2 (ERK1/2) activity, but not c-Jun N-terminal kinase (JNK) and p38. Pharmacological inhibition of ERK1/2 phosphorylation with U0126 resulted in a decreased AAI-induced autophagy that was accompanied by an increased apoptosis. Taken together, our study demonstrated for the first time that autophagy occurred earlier than apoptosis during AAI-induced tubular epithelial cell injury. Autophagy induced by AAI via ERK1/2 pathway might attenuate apoptosis, which may provide a protective mechanism for cell survival under AAI-induced pathological condition

PDlim2 Selectively Interacts with the PDZ Binding Motif of Highly Pathogenic Avian H5N1 Influenza A Virus NS1

The multi-functional NS1 protein of influenza A virus is a viral virulence determining factor. The last four residues at the C-terminus of NS1 constitute a type I PDZ domain binding motif (PBM). Avian influenza viruses currently in circulation carry an NS1 PBM with consensus sequence ESEV, whereas human influenza viruses bear an NS1 PBM with consensus sequence RSKV or RSEV. The PBM sequence of the influenza A virus NS1 is reported to contribute to high viral pathogenicity in animal studies. Here, we report the identification of PDlim2 as a novel binding target of the highly pathogenic avian influenza virus H5N1 strain with an NS1 PBM of ESEV (A/Chicken/Henan/12/2004/H5N1, HN12-NS1) by yeast two-hybrid screening. The interaction was confirmed by in vitro GST pull-down assays, as well as by in vivo mammalian two-hybrid assays and bimolecular fluorescence complementation assays. The binding was also confirmed to be mediated by the interaction of the PDlim2 PDZ domain with the NS1 PBM motif. Interestingly, our assays showed that PDlim2 bound specifically with HN12-NS1, but exhibited no binding to NS1 from a human influenza H1N1 virus bearing an RSEV PBM (A/Puerto Rico/8/34/H1N1, PR8-NS1). A crystal structure of the PDlim2 PDZ domain fused with the C-terminal hexapeptide from HN12-NS1, together with GST pull-down assays on PDlim2 mutants, reveals that residues Arg16 and Lys31 of PDlim2 are critical for the binding between PDlim2 and HN12-NS1. The identification of a selective binding target of HN12-NS1 (ESEV), but not PR8-NS1 (RSEV), enables us to propose a structural mechanism for the interaction between NS1 PBM and PDlim2 or other PDZ-containing proteins

Reduced miR-144-3p expression in serum and bone mediates osteoporosis pathogenesis by targeting RANK

Osteoblasts and osteoclasts are responsible for the formation and resorption of bone, respectively. An imbalance between these two processes results in a disease called osteoporosis, in which a decreased level of bone strength increases the risk of a bone fracture. MicroRNAs (miRNAs) are small non-coding RNA molecules of 18â 25 nucleotides that have been previously shown to control bone metabolism by regulating osteoblast and osteoclast differentiation. In the present study, we detected the expression pattern of 10 miRNAs in patient serum samples, and identified six miRNAs altered expression in patients with osteoporosis relative to non-osteoporosis. We selected miR-144-3p for further investigation, and showed that it regulates osteoclastogenesis by targeting RANK and that it is conserved amongst vertebrates. Disrupted expression of miR-144-3p in CD14+ PBMCs changed TRAP activity and the osteoclast-specific genes TRAP, cathepsin K (CTSK), and NFATC. TRAP stainingďź CCK-8 and flow cytometry analyses revealed that miR-144-3p also affects osteoclast formation, proliferation and apoptosis. Together, these results indicate that miR-144-3p critically mediates bone homeostasis, and thus, represents a promising novel therapeutic candidate for the treatment of this disease.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author