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To guide social interaction, people often rely on expectations about the traits of other people, based on markers of social group membership (i.e., stereotypes). Although the influence of stereotypes on social behavior is widespread, key questions remain about how traits inferred from social-group membership are instantiated in the brain and incorporated into neural computations that guide social behavior. Here, we show that the human lateral orbitofrontal cortex (OFC) represents the content of stereotypes about members of different social groups in the service of social decision-making. During functional MRI scanning, participants decided how to distribute resources across themselves and members of a variety of social groups in a modified Dictator Game. Behaviorally, we replicated our recent finding that inferences about others' traits, captured by a two-dimensional framework of stereotype content (warmth and competence), had dissociable effects on participants' monetary-allocation choices: recipients' warmth increased participants’ aversion to advantageous inequity (i.e., earning more than recipients), and recipients’ competence increased participants’ aversion to disadvantageous inequity (i.e., earning less than recipients). Neurally, representational similarity analysis revealed that others' traits in the two-dimensional space were represented in the temporoparietal junction and superior temporal sulcus, two regions associated with mentalizing, and in the lateral OFC, known to represent inferred features of a decision context outside the social domain. Critically, only the latter predicted individual choices, suggesting that the effect of stereotypes on behavior is mediated by inference-based decision-making processes in the OFC.

Regulatory T cells (Tregs) that promote tumor immune evasion are enriched in certain tumors and correlate with poor prognosis. However, mechanisms for Treg enrichment remain incompletely understood. We described a mechanism for Treg enrichment in mouse and human tumors mediated by the αvβ8 integrin. Tumor cell αvβ8 bound to latent transforming growth factor-β (L-TGF-β) presented on the surface of T cells, resulting in TGF-β activation and immunosuppressive Treg differentiation in vitro. In vivo, tumor cell αvβ8 expression correlated with Treg enrichment, immunosuppressive Treg gene expression, and increased tumor growth, which was reduced in mice by αvβ8 inhibition or Treg depletion. Structural modeling and cell-based studies suggested a highly geometrically constrained complex forming between αvβ8-expressing tumor cells and L-TGF-β-expressing T cells, facilitating TGF-β activation, independent of release and diffusion, and providing limited access to TGF-β inhibitors. These findings suggest a highly localized tumor-specific mechanism for Treg enrichment.

Adaptive information seeking is critical for goal-directed behavior. Growing evidence suggests the importance of intrinsic motives such as curiosity or need for novelty, mediated through dopaminergic valuation systems, in driving information-seeking behavior. However, valuing information for its own sake can be highly suboptimal when agents need to evaluate instrumental benefit of information in a forward-looking manner. Here we show that information-seeking behavior in humans is driven by subjective value that is shaped by both instrumental and noninstrumental motives, and that this subjective value of information (SVOI) shares a common neural code with more basic reward value. Specifically, using a task where subjects could purchase information to reduce uncertainty about outcomes of a monetary lottery, we found information purchase decisions could be captured by a computational model of SVOI incorporating utility of anticipation, a form of noninstrumental motive for information seeking, in addition to instrumental benefits. Neurally, trial-by-trial variation in SVOI was correlated with activity in striatum and ventromedial prefrontal cortex. Furthermore, cross-categorical decoding revealed that, within these regions, SVOI and expected utility of lotteries were represented using a common code. These findings provide support for the common currency hypothesis and shed insight on neurocognitive mechanisms underlying information-seeking behavior.

Cigarette smoke (CS)-induced accumulation of mitochondrial damage has been widely implicated in chronic obstructive pulmonary disease (COPD) pathogenesis. Mitophagy plays a crucial role in eliminating damaged mitochondria, and is governed by the PINK1 (PTEN induced putative protein kinase 1)-PRKN (parkin RBR E3 ubiquitin protein ligase) pathway. Although both increased PINK1 and reduced PRKN have been implicated in COPD pathogenesis in association with mitophagy, there are conflicting reports for the role of mitophagy in COPD progression. To clarify the involvement of PRKN-regulated mitophagy in COPD pathogenesis, prkn knockout (KO) mouse models were used. To illuminate how PINK1 and PRKN regulate mitophagy in relation to CS-induced mitochondrial damage and cellular senescence, overexpression and knockdown experiments were performed in airway epithelial cells (AEC). In comparison to wild-type mice, prkn KO mice demonstrated enhanced airway wall thickening with emphysematous changes following CS exposure. AEC in CS-exposed prkn KO mice showed accumulation of damaged mitochondria and increased oxidative modifications accompanied by accelerated cellular senescence. In vitro experiments showed PRKN overexpression was sufficient to induce mitophagy during CSE exposure even in the setting of reduced PINK1 protein levels, resulting in attenuation of mitochondrial ROS production and cellular senescence. Conversely PINK1 overexpression failed to recover impaired mitophagy caused by PRKN knockdown, indicating that PRKN protein levels can be the rate-limiting factor in PINK1-PRKN-mediated mitophagy during CSE exposure. These results suggest that PRKN levels may play a pivotal role in COPD pathogenesis by regulating mitophagy, suggesting that PRKN induction could mitigate the progression of COPD. Abbreviations: AD: Alzheimer disease; AEC: airway epithelial cells; BALF: bronchoalveolar lavage fluid; AKT: AKT serine/threonine kinase; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CDKN1A: cyclin dependent kinase inhibitor 1A; CDKN2A: cyclin dependent kinase inhibitor 2A; COPD: chronic obstructive pulmonary disease; CS: cigarette smoke; CSE: CS extract; CXCL1: C-X-C motif chemokine ligand 1; CXCL8: C-X-C motif chemokine ligand 8; HBEC: human bronchial epithelial cells; 4-HNE: 4-hydroxynonenal; IL: interleukin; KO: knockout; LF: lung fibroblasts; LPS: lipopolysaccharide; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; 8-OHdG: 8-hydroxy-2'-deoxyguanosine; OPTN: optineurin; PRKN: parkin RBR E3 ubiquitin protein ligase; PCD: programmed cell death; PFD: pirfenidone; PIK3C: phosphatidylinositol-4:5-bisphosphate 3-kinase catalytic subunit; PINK1: PTEN induced putative kinase 1; PTEN: phosphatase and tensin homolog; RA: rheumatoid arthritis; ROS: reactive oxygen species; SA-GLB1/β-Gal: senescence-associated-galactosidase, beta 1; SASP: senescence-associated secretory phenotype; SNP: single nucleotide polymorphism; TNF: tumor necrosis factor.

A non-destructive method for detecting sub-micrometer-sized micropipes on an entire wafer surface is investigated. Since it is difficult to detect sub-micrometer-sized micropipes due to their small core size, a non-destructively and accurately detecting method is required. To solve the issue, we focus on a characteristic depression generated around micropipes, namely, line-shaped depressions. In this paper, the location of line-shaped depressions is identified by using optical inspection, and the line-shaped depressions are distinguished whether micropipes exhibit line-shaped depression or not by using mirror electron microscope observation as high-resolution inspection. The accuracy of the distinction results is confirmed by scanning electron microscope observation, and electrical characteristics of the P–N diode are fabricated using the inspected wafer. Furthermore, the sub-micrometer-sized micropipes are observed at the sites of leakage current identified by emission microscopy. Additionally, device simulation of the blocking-voltage characteristics of P–N diodes suggests that the increase in leakage current depends on the electric field at the sub-micrometer-sized micropipes, regardless of their core size. [ABSTRACT FROM AUTHOR]

Alexander disease (AxD) is an intractable neurodegenerative disease caused by mutations in glial fibrillary acidic protein (GFAP), which is predominantly expressed in astrocytes. Thus, AxD is a primary astrocyte disease. However, it remains unclear how GFAP mutations affect astrocytes and cause AxD pathology. Three features are characteristic of AxD astrocytes in vivo: (1) Rosenthal fibers (RFs), the hallmark of AxD; (2) aberrant Ca2+ signals (AxCa); and (3) upregulation of disease-associated genes (AxGen). We established a primary culture system for astrocytes from an AxD transgenic mouse model, and used it to analyze the above features of AxD pathogenesis in astrocytes in vitro. We observed the formation of RFs in AxD primary cultures. The abundance of RFs was greater in AxD-transgene-homozygous compared with -hemizygous astrocytes, indicating a gene dosage effect, and this abundance increased with time in culture, indicating a developmental process effect. However, cultured AxD astrocytes did not exhibit changes in either AxCa or AxGen. We therefore conclude that RFs in astrocytes form via a cell-autonomous mechanism, whereas AxCa and AxGen are likely to occur via a non-cell-autonomous mechanism through interactions with other cells, such as neurons, microglia, and vascular cells. Although primary cultured AxD astrocytes are suitable for elucidating the mechanisms of RFs formation and for intervention studies, it should be noted that they cannot reflect the pathophysiology of non-cell-autonomous events in astrocytes. [ABSTRACT FROM AUTHOR]

A survey meter was developed to reliably detect and visualize surface contamination of suits and objects by α-nuclides in high γ/n-rays background radiation environment. The survey meter features a semi-opaque ZnS:Ag scintillator mounted directly onto a multi-anode photomultiplier tube (MA-PMT) and amplification circuits, ensuring output gain equalization for all channels. α-ray events induce localized light emission in thin-film scintillators. By directly mounting the scintillator, diffusion of light before reaching the MA-PMT is suppressed, concentrating it in just a few channels, thereby facilitating discrimination from background radiation. This design also enables clear visualization of the shape of surface contamination. The prototyped survey meter is capable of responding up to 2.1 × 107 cpm, with no γ-ray response even in high-radiation environments exceeding 1 Sv/h. In actual environments with high background radiation, contamination of ~1/100th of the surface contamination density limit of 4 Bq/cm2 could be reliably detected. [ABSTRACT FROM AUTHOR]

Adaptive decision making depends on an agent's ability to use environmental signals to reduce uncertainty. However, because of multiple types of uncertainty, agents must take into account not only the extent to which signals violate prior expectations but also whether uncertainty can be reduced in the first place. Here we studied how human brains of both sexes respond to signals under conditions of reducible and irreducible uncertainty. We show behaviorally that subjects' value updating was sensitive to the reducibility of uncertainty, and could be quantitatively characterized by a Bayesian model where agents ignore expectancy violations that do not update beliefs or values. Using fMRI, we found that neural processes underlying belief and value updating were separable from responses to expectancy violation, and that reducibility of uncertainty in value modulated connections from belief-updating regions to value-updating regions. Together, these results provide insights into how agents use knowledge about uncertainty to make better decisions while ignoring mere expectancy violation.SIGNIFICANCE STATEMENT To make good decisions, a person must observe the environment carefully, and use these observations to reduce uncertainty about consequences of actions. Importantly, uncertainty should not be reduced purely based on how surprising the observations are, particularly because in some cases uncertainty is not reducible. Here we show that the human brain indeed reduces uncertainty adaptively by taking into account the nature of uncertainty and ignoring mere surprise. Behaviorally, we show that human subjects reduce uncertainty in a quasioptimal Bayesian manner. Using fMRI, we characterize brain regions that may be involved in uncertainty reduction, as well as the network they constitute, and dissociate them from brain regions that respond to mere surprise.