Challenges of Zero-Shot Recognition with Vision-Language Models: Granularity and Correctness

This paper investigates the challenges of applying vision-language models (VLMs) to zero-shot visual recognition tasks in an open-world setting, with a focus on contrastive vision-language models such as CLIP. We first examine the performance of VLMs on concepts of different granularity levels. We propose a way to fairly evaluate the performance discrepancy under two experimental setups and find that VLMs are better at recognizing fine-grained concepts. Furthermore, we find that the similarity scores from VLMs do not strictly reflect the correctness of the textual inputs given visual input. We propose an evaluation protocol to test our hypothesis that the scores can be biased towards more informative descriptions, and the nature of the similarity score between embedding makes it challenging for VLMs to recognize the correctness between similar but wrong descriptions. Our study highlights the challenges of using VLMs in open-world settings and suggests directions for future research to improve their zero-shot capabilities

A Novel, Non-Apoptotic Role for Scythe/BAT3: A Functional Switch between the Pro- and Anti-Proliferative Roles of p21 during the Cell Cycle

BACKGROUND: Scythe/BAT3 is a member of the BAG protein family whose role in apoptosis has been extensively studied. However, since the developmental defects observed in Bat3-null mouse embryos cannot be explained solely by defects in apoptosis, we investigated whether BAT3 is also involved in cell-cycle progression. METHODS/PRINCIPAL FINDINGS: Using a stable-inducible Bat3-knockdown cellular system, we demonstrated that reduced BAT3 protein level causes a delay in both G1/S transition and G2/M progression. Concurrent with these changes in cell-cycle progression, we observed a reduction in the turnover and phosphorylation of the CDK inhibitor p21, which is best known as an inhibitor of DNA replication; however, phosphorylated p21 has also been shown to promote G2/M progression. Our findings indicate that in Bat3-knockdown cells, p21 continues to be synthesized during cell-cycle phases that do not normally require p21, resulting in p21 protein accumulation and a subsequent delay in cell-cycle progression. Finally, we showed that BAT3 co-localizes with p21 during the cell cycle and is required for the translocation of p21 from the cytoplasm to the nucleus during the G1/S transition and G2/M progression. CONCLUSION: Our study reveals a novel, non-apoptotic role for BAT3 in cell-cycle regulation. By maintaining a low p21 protein level during the G1/S transition, BAT3 counteracts the inhibitory effect of p21 on DNA replication and thus enables the cells to progress from G1 to S phase. Conversely, during G2/M progression, BAT3 facilitates p21 phosphorylation by cyclin A/Cdk2, an event required for G2/M progression. BAT3 modulates these pro- and anti-proliferative roles of p21 at least in part by regulating cyclin A abundance, as well as p21 translocation between the cytoplasm and the nucleus to ensure that it functions in the appropriate intracellular compartment during each phase of the cell cycle.Dissertatio

BAT3 Guides Misfolded Glycoproteins Out of the Endoplasmic Reticulum

Secretory and membrane proteins that fail to acquire their native conformation within the lumen of the Endoplasmic Reticulum (ER) are usually targeted for ubiquitin-dependent degradation by the proteasome. How partially folded polypeptides are kept from aggregation once ejected from the ER into the cytosol is not known. We show that BAT3, a cytosolic chaperone, is recruited to the site of dislocation through its interaction with Derlin2. Furthermore, we observe cytoplasmic BAT3 in a complex with a polypeptide that originates in the ER as a glycoprotein, an interaction that depends on the cytosolic disposition of both, visualized even in the absence of proteasomal inhibition. Cells depleted of BAT3 fail to degrade an established dislocation substrate. We thus implicate a cytosolic chaperone as an active participant in the dislocation of ER glycoproteins.United States. National Institutes of HealthBoehringer Ingelheim Fond

BAT3 Interacts with Transforming Growth Factor-β (TGF-β) Receptors and Enhances TGF-β1-induced Type I Collagen Expression in Mesangial Cells*

Transforming growth factor-β1 (TGF-β1) plays essential roles in a wide array of cellular processes, such as in development and the pathogenesis of tissue fibrosis, including that associated with progressive kidney diseases. Tight regulation of its signaling pathways is critical, and proteins that associate with the TGF-β receptors may exert positive or negative regulatory effects on TGF-β signaling. In the present study we employed a yeast-based two-hybrid screening system to identify BAT3 (HLA-B-associated transcript 3) as a TGF-β receptor-interacting protein. Analysis of endogenously expressed BAT3 in various tissues including the kidney reveals the existence of ∼140-kDa full-length protein as well as truncated forms of BAT3 whose expression is developmentally regulated. Endogenous BAT3 protein interacts with TGF-β receptors type I and type II in renal mesangial cells. Functional assays show that expression of full-length BAT3 results in enhancement of TGF-β1-stimulated transcriptional activation of p3TP-Lux reporter, and these effects require the presence of functional TGF-β signaling receptors as demonstrated in R-1B and DR-26 mutant cells. Moreover, expression of full-length BAT3, but not C-terminal truncated mutant of BAT3, enhanced TGF-β1-induced type I collagen expression in mesangial cells, whereas knock down of BAT3 protein expression by small interfering RNA suppressed the expression of type I collagen induced by TGF-β1. Our findings suggest that BAT3, a TGF-β receptor-interacting protein, is capable of modulating TGF-β signaling and acts as a positive regulator of TGF-β1 stimulation of type I collagen expression in mesangial cells