Foraging in a non-foraging task: Fitness maximization explains human risk preference dynamics under changing environment.

Changes in risk preference have been reported when making a series of independent risky choices or non-foraging economic decisions. Behavioral economics has put forward various explanations for specific changes in risk preference in non-foraging tasks, but a consensus regarding the general principle underlying these effects has not been reached. In contrast, recent studies have investigated human economic risky choices using tasks adapted from foraging theory, which require consideration of past choices and future opportunities to make optimal decisions. In these foraging tasks, human economic risky choices are explained by the ethological principle of fitness maximization, which naturally leads to dynamic risk preference. Here, we conducted two online experiments to investigate whether the principle of fitness maximization can explain risk preference dynamics in a non-foraging task. Participants were asked to make a series of independent risky economic decisions while the environmental richness changed. We found that participants' risk preferences were influenced by the current and past environments, making them more risk-averse during and after the rich environment compared to the poor environment. These changes in risk preference align with fitness maximization. Our findings suggest that the ethological principle of fitness maximization might serve as a generalizable principle for explaining dynamic preferences, including risk preference, in human economic decision-making.

Postpartum loneliness predicts future depressive symptoms: a nationwide Japanese longitudinal study.

PURPOSE: The COVID-19 pandemic has intensified feelings of loneliness, especially among postpartum women. This nationwide Japanese longitudinal study assessed the impact of such feelings on depressive symptoms and mother-to-infant bonding difficulties (MIBD), two pivotal determinants of maternal and infant well-being. METHODS: Starting with a baseline survey conducted between July and August 2021, we tracked 1254 postpartum Japanese women who initially reported minimal depressive symptoms (i.e., Edinburgh Postnatal Depression Scale < 9) and MIBD (i.e., Mother-to-Infant Bonding Scale < 5), over a follow-up period of approximately 6 months. Baseline loneliness was evaluated with the UCLA Loneliness Scale Short-Form (UCLA-LS3-SF3). RESULTS: Forty-nine percent of the sample reported the presence of baseline feelings of loneliness. After propensity score matching on sociodemographics and various pregnancy, childbirth, and COVID-19-related aspects, baseline loneliness was associated with increased risks of later depressive symptoms but not MIBD. Using restricted cubic spline logistic regression and considering loneliness as a continuous variable, we found a positive increasing quadratic relationship with depressive symptoms. As loneliness increased, so did the risk of later depressive symptoms. However, there was no significant association between loneliness and MIBD. These results were confirmed through a sensitivity analysis using inverse probability weighting to address attrition bias. CONCLUSION: Feelings of postpartum loneliness are associated with future risks of depressive symptoms. The data suggests that addressing loneliness in postpartum women early is crucial to safeguarding their well-being and that of their infants.

Toward a computational understanding of how reminiscing about positive autobiographical memories influences decision-making under risk.

Recent computational psychiatric research has dissected decision-making under risk into different underlying cognitive computational constructs and identified disease-specific changes in these constructs. Studies are underway to investigate what kind of behavioral or psychological interventions can restore these cognitive, computational constructs. In our previous study, we showed that reminiscing about positive autobiographical memories reduced risk aversion and affected probability weighting in the opposite direction from that observed in psychiatric disorders. However, in that study, we compared positive versus neutral memory retrieval by using a within-subjects crossover posttest design. Therefore, the change of decision-making from baseline is unclear. Furthermore, we used a hypothetical decision-making task and did not include monetary incentives. We attempt to address these limitations and investigated how reminiscing about positive autobiographical memories influences decision-making under risk using a between-subjects pretest posttest comparison design with performance-contingent monetary incentives. In thirty-eight healthy, young adults, we found that reminiscing about positive memories reinforced the commonly observed inverted S-shaped nonlinear probability weighting (f = 0.345, medium to large in effect size). In contrast, reminiscing about positive memories did not affect risk aversion in general. Given that the change in probability weighting after reminiscing about positive memories is in the opposite direction from that observed in psychiatric disorders, our results indicate that positive autobiographical memory retrieval might be a useful behavioral intervention strategy for amending the altered decision-making under risk in psychiatric diseases.

Prdm16 is crucial for progression of the multipolar phase during neural differentiation of the developing neocortex.

The precise control of neuronal migration and morphological changes during differentiation is essential for neocortical development. We hypothesized that the transition of progenitors through progressive stages of differentiation involves dynamic changes in levels of mitochondrial reactive oxygen species (mtROS), depending on cell requirements. We found that progenitors had higher levels of mtROS, but that these levels were significantly decreased with differentiation. The Prdm16 gene was identified as a candidate modulator of mtROS using microarray analysis, and was specifically expressed by progenitors in the ventricular zone. However, Prdm16 expression declined during the transition into NeuroD1-positive multipolar cells. Subsequently, repression of Prdm16 expression by NeuroD1 on the periphery of ventricular zone was crucial for appropriate progression of the multipolar phase and was required for normal cellular development. Furthermore, time-lapse imaging experiments revealed abnormal migration and morphological changes in Prdm16-overexpressing and -knockdown cells. Reporter assays and mtROS determinations demonstrated that PGC1α is a major downstream effector of Prdm16 and NeuroD1, and is required for regulation of the multipolar phase and characteristic modes of migration. Taken together, these data suggest that Prdm16 plays an important role in dynamic cellular redox changes in developing neocortex during neural differentiation.

Similarity in Neuronal Firing Regimes across Mammalian Species.

UNLABELLED: The architectonic subdivisions of the brain are believed to be functional modules, each processing parts of global functions. Previously, we showed that neurons in different regions operate in different firing regimes in monkeys. It is possible that firing regimes reflect differences in underlying information processing, and consequently the firing regimes in homologous regions across animal species might be similar. We analyzed neuronal spike trains recorded from behaving mice, rats, cats, and monkeys. The firing regularity differed systematically, with differences across regions in one species being greater than the differences in similar areas across species. Neuronal firing was consistently most regular in motor areas, nearly random in visual and prefrontal/medial prefrontal cortical areas, and bursting in the hippocampus in all animals examined. This suggests that firing regularity (or irregularity) plays a key role in neural computation in each functional subdivision, depending on the types of information being carried. SIGNIFICANCE STATEMENT: By analyzing neuronal spike trains recorded from mice, rats, cats, and monkeys, we found that different brain regions have intrinsically different firing regimes that are more similar in homologous areas across species than across areas in one species. Because different regions in the brain are specialized for different functions, the present finding suggests that the different activity regimes of neurons are important for supporting different functions, so that appropriate neuronal codes can be used for different modalities.

A Case of Adenomyoepithelioma of the Breast Showing Strong Uptake of 18 F-Fluorodeoxyglucose on a Positron Emission Tomography.

An adenomyoepithelioma of the breast is a rare tumor characterized by biphasic proliferation of both epithelial and myoepithelial cells. This tumor is generally considered as a benign neoplasm, and there are few reports describing the imaging features of this tumor through 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET). Here, we report a case of an adenomyoepithelioma that showed strong uptake of FDG on PET similar to that observed with a malignant tumor. A 73-year-old woman presented to our hospital with a 3.5-cm, mobile, and elastic hard tumor in the upper area of the left breast. Although the findings of mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging suggested that the tumor was malignant, it was diagnosed as an adenomyoepithelioma by core needle biopsy. An invasive ductal carcinoma, 0.5-cm in size, was detected in the medial upper area of the ipsilateral breast during an examination. Although FDG-PET demonstrated no lymph node or distant metastases from the invasive ductal carcinoma, strong uptake of FDG was detected in the adenomyoepithelioma. Breast conserving surgery and sentinel lymph node biopsy for the invasive ductal carcinoma together with resection of the adenomyoepithelioma was performed. A diagnosis of adenomyoepithelioma was confirmed through histologic examination of the resected specimen. This case indicates that some adenomyoepitheliomas may show a strong uptake of FDG on PET, which resembles a malignant tumor.

Sequential breakdown of 3-phosphorylated phosphoinositides is essential for the completion of macropinocytosis.

Macropinocytosis is a highly conserved endocytic process by which extracellular fluid and solutes are internalized into cells. Macropinocytosis starts with the formation of membrane ruffles at the plasma membrane and ends with their closure. The transient and sequential emergence of phosphoinositides PI(3,4,5)P3 and PI(3,4)P2 in the membrane ruffles is essential for macropinocytosis. By making use of information in the Caenorhabditis elegans mutants defective in fluid-phase endocytosis, we found that mammalian phosphoinositide phosphatase MTMR6 that dephosphorylates PI(3)P to PI, and its binding partner MTMR9, are required for macropinocytosis. INPP4B, which dephosphorylates PI(3,4)P2 to PI(3)P, was also found to be essential for macropinocytosis. These phosphatases operate after the formation of membrane ruffles to complete macropinocytosis. Finally, we showed that KCa3.1, a Ca(2+)-activated K(+) channel that is activated by PI(3)P, is required for macropinocytosis. We propose that the sequential breakdown of PI(3,4,5)P3 → PI(3,4)P2 → PI(3)P → PI controls macropinocytosis through specific effectors of the intermediate phosphoinositides.

Analysis of the subcellular localization of the human histone methyltransferase SETDB1.

SET domain, bifurcated 1 (SETDB1) is a histone methyltransferase that methylates lysine 9 on histone H3. Although it is important to know the localization of proteins to elucidate their physiological function, little is known of the subcellular localization of human SETDB1. In the present study, to investigate the subcellular localization of hSETDB1, we established a human cell line constitutively expressing enhanced green fluorescent protein fused to hSETDB1. We then generated a monoclonal antibody against the hSETDB1 protein. Expression of both exogenous and endogenous hSETDB1 was observed mainly in the cytoplasm of various human cell lines. Combined treatment with the nuclear export inhibitor leptomycin B and the proteasome inhibitor MG132 led to the accumulation of hSETDB1 in the nucleus. These findings suggest that hSETDB1, localized in the nucleus, might undergo degradation by the proteasome and be exported to the cytosol, resulting in its detection mainly in the cytosol.

Phosphatidylinositol 3-phosphatase myotubularin-related protein 6 (MTMR6) is regulated by small GTPase Rab1B in the early secretory and autophagic pathways.

A large family of myotubularin phosphatases dephosphorylates phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate, which are known to play important roles in vesicular trafficking and autophagy. The family is composed of 16 members, and understanding their regulatory mechanisms is important to understand their functions and related genetic diseases. We prepared anti-myotubularin-related protein 6 (MTMR6) monoclonal antibody and used it to study the regulatory mechanism of MTMR6. Endogenous MTMR6 was present in the cytoplasm and was condensed in the perinuclear region in a microtubule-dependent manner. MTMR6 preferentially interacted with GDP-bound Rab1B via the GRAM domain and partly overlapped with Rab1B in the pericentrosomal and peri-Golgi regions in normal rat kidney cells. Overexpression of GDP-bound Rab1B and the reduction of Rab1B disrupted the localization of MTMR6, suggesting that Rab1B regulates the localization of MTMR6. The reduction of MTMR6 accelerated the transport of vesicular stomatitis virus glycoprotein in which Rab1B is involved. Furthermore, reduction of MTMR6 or Rab1B inhibited the formation of the tubular omegasome that is induced by overexpression of DFCP1 in autophagy. Our results indicate that the cellular localization of MTMR6 is regulated by Rab1B in the early secretory and autophagic pathways. We propose a new regulatory mechanism of myotubularin phosphatase by the small GTPase Rab1B.

Inhibition of DNA damage-induced apoptosis through Cdc7-mediated stabilization of Tob.

BACKGROUND: Preventing unnecessary cell death is essential for DNA-damaged cells to carry out the DNA repair process. RESULTS: Cdc7 inhibits the Cul4-DDB1(Cdt2)-dependent Tob degradation. CONCLUSION: Cdc7 enables mild DNA-damaged cells to keep their viability by competing with the Tob degradation system. SIGNIFICANCE: Cells deal with moderate DNA damage not only by cessation of the cell cycle but also through direct mediated pro-survival signaling. Cells respond to DNA damage by activating alternate signaling pathways that induce proliferation arrest or apoptosis. The correct balance between these two pathways is important for maintaining genomic integrity and preventing unnecessary cell death. The mechanism by which DNA-damaged cells escape from apoptosis during DNA repair is poorly understood. We show that the DNA replication-initiating kinase Cdc7 actively prevents unnecessary death in DNA-damaged cells. In response to mild DNA damage, Tob levels increase through both a transcriptional mechanism and protein stabilization, resulting in inhibition of pro-apoptotic signaling. Cells lacking Cdc7 expression undergo apoptosis after mild DNA damage, where Cul4-DDB1(Cdt2) induces Tob ubiquitination and subsequent degradation. Cdc7 phosphorylates and interacts with Tob to inhibit the Cul4-DDB1(Cdt2)-dependent Tob degradation. Thus, Cdc7 defines an essential pro-survival signaling pathway by contributing to stabilization of Tob, thereby the viability of DNA-damaged cells being maintained.

Nonlinear Probability Weighting in Depression and Anxiety: Insights From Healthy Young Adults.

Both depressive and anxiety disorders have been associated with excessive risk avoidant behaviors, which are considered an important contributor to the maintenance and recurrence of these disorders. However, given the high comorbidity between the two disorders, their independent association with risk preference remains unclear. Furthermore, due to the involvement of multiple cognitive computational factors in the decision-making tasks employed so far, the precise underlying mechanisms of risk preference are unknown. In the present study, we set out to investigate the common versus unique cognitive computational mechanisms of risk preference in depression and anxiety using a reward-based decision-making task and computational modeling based on economic theories. Specifically, in model-based analysis, we decomposed risk preference into utility sensitivity (a power function) and probability weighting (the one-parameter Prelec weighting function). Multiple linear regression incorporating depression (BDI-II) and anxiety (STAI state anxiety) simultaneously indicated that only depression was associated with one such risk preference parameter, probability weighting. As the symptoms of depression increased, subjects' tendency to overweight small probabilities and underweight large probabilities decreased. Neither depression nor anxiety was associated with utility sensitivity. These associations remained even after controlling covariates or excluding anxiety-relevant items from the depression scale. To our knowledge, this is the first study to assess risk preference due to a concave utility function and nonlinear probability weighting separately for depression and anxiety using computational modeling. Our results provide a mechanistic account of risk avoidance and may improve our understanding of decision-making deficits in depression and anxiety.

Computational markers of experience- but not description-based decision-making are associated with future depressive symptoms in young adults.

BACKGROUND: Early prediction of high depressive symptoms is crucial for selective intervention and the minimization of functional impairment. Recent cross-sectional studies indicated decision-making deficits in depression, which may be an important contributor to the disorder. Our goal was to test whether description- and experience-based decision making, two major neuroeconomic paradigms of decision-making under uncertainty, predict future depressive symptoms in young adults. METHODS: One hundred young adults performed two decision-making tasks, one description-based, in which subjects chose between two gambling options given explicitly stated rewards and their probabilities, and the other experience-based, in which subjects were shown rewards but had to learn the probability of those rewards (or cue-outcome contingencies) via trial-and-error experience. We evaluated subjects' depressive symptoms with BDI-II at baseline (T1) and half a year later (T2). RESULTS: Comparing subjects with low versus high levels of depressive symptoms at T2 showed that the latter performed worse on the experience- but not description-based task at T1. Computational modeling of the decision-making process suggested that subjects with high levels of depressive symptoms had a more concave utility function, indicating enhanced risk aversion. Furthermore, a more concave utility function at T1 increased the odds of high depressive symptoms at T2, even after controlling depressive symptoms at T1, perceived stress at T2, and several covariates (OR = 0.251, 95% CI [0.085, 0.741]). CONCLUSIONS: This is the first study to demonstrate a prospective link between experience-based decision-making and depressive symptoms. Our results suggest that enhanced risk aversion in experience-based decision-making may be an important contributor to the development of depressive symptoms.

The effect of positive autobiographical memory retrieval on decision-making under risk: A computational model-based analysis.

Psychiatric disorders such as depressive and anxiety disorders are associated with altered decision-making under risk. Recent advances in neuroeconomics and computational psychiatry have further discomposed risk-based decision-making into distinct cognitive computational constructs and showed that there may be disorder-specific alterations in these constructs. As a result, it has been suggested these cognitive computational constructs may serve as useful behavioral biomarkers for these disorders. However, to date, little is known about what psychological or behavioral interventions can help to reverse and manage the altered cognitive computational constructs underlying risk-based decision-making. In the present study, we set out to investigate whether recalling positive autobiographical memories may affect risk-based decision-making in healthy volunteers using a description-based task. Specifically, based on theories of behavioral economics, we dissected risk preference into two cognitive computational constructs, utility sensitivity and probability weighting. We found that compared to recalling neutral memories, retrieving positive autobiographical memories increased utility sensitivity (Cohen's d = 0.447), indicating reduced risk aversion. Meanwhile, we also tested the influence of memory retrieval on probability weighting, the effect, however, was unreliable and requires further in-depth investigation. Of clinical relevance, the change in risk aversion after recalling positive memories was in the opposite direction compared to those reported in psychiatric disorders. These results argue for the potential therapeutic effect of positive autobiographical memory retrieval for the amendment of altered risk-based decision-making in psychiatric disorders.

Basophil-derived mouse mast cell protease 11 induces microvascular leakage and tissue edema in a mast cell-independent manner.

Mouse mast cell protease 11 (mMCP-11) is the most recently identified member of the mouse mast cell tryptase family. This tryptase is preferentially produced by basophils in contrast to other members that are expressed by mast cells but not basophils. Although blood-circulating basophils have long been considered as minor and redundant relatives of tissue-resident mast cells, recent studies illustrated that basophils and mast cells play distinct roles in vivo. To explore the in vivo role of basophil-derived mMCP-11, here we prepared recombinant mMCP-11 and its protease-dead mutant. Subcutaneous injection of the wild-type mMCP-11 but not the mutant induced edematous skin swelling with increased microvascular permeability in a dose-dependent manner. No apparent infiltration of proinflammatory cells including neutrophils and eosinophils was detected in the skin lesions. The cutaneous swelling was abolished by the pretreatment of mice with indomethacin, a cyclooxygenase inhibitor, suggesting the major contribution of prostaglandins to the microvascular leakage. Of note, the cutaneous swelling was elicited even in mast cell-deficient mice, indicating that mast cells are dispensable for the mMCP-11-induced cutaneous swelling. Thus, basophil-derived mMCP-11 can induce microvascular leakage via prostaglandins in a mast cell-independent manner, and may contribute to the development of basophil-mediated inflammatory responses.

CSLEX (Sialyl Lewis X) is a useful tumor marker for monitoring of breast cancer patients.

BACKGROUND: CSLEX is a type II carbohydrate antigen that interacts with the CSLEX-1 monoclonal antibody. CSLEX in combination with carbohydrate antigen 15-3 may be more useful than Carcinoembryonic Antigen with carbohydrate antigen 15-3 as tumor markers for monitoring of breast cancer. METHODS: The serum levels of tumor markers, including CSLEX, were measured in 480 consecutive breast cancer patients with or without metastasis who visited the outpatient clinic of the Division of Breast and Endocrine Surgery, Shinshu University Hospital, between April 2007 and September 2007. RESULTS: Serum levels of each of the tumor markers correlated significantly with the status of metastasis (P < 0.01). Combinations of Carcinoembryonic Antigen and carbohydrate antigen 15-3, Carcinoembryonic Antigen and Nation Cancer Center-Stomach-439, Carcinoembryonic Antigen and CSLEX, carbohydrate antigen 15-3 and Nation Cancer Center-Stomach-439, and carbohydrate antigen 15-3 and CSLEX levels also correlated significantly with the status of metastasis (P < 0.01). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were almost the same for CSLEX and Nation Cancer Center-Stomach-439, which are both type II carbohydrate antigens. The cutoff indexes of serum CSLEX and Nation Cancer Center-Stomach-439 for detection of breast cancer metastasis were 38.8 ± 52.7-fold and 22.1 ± 27.8-fold, respectively (P = 0.16). CONCLUSIONS: These data suggest that the diagnostic values of CSLEX and Nation Cancer Center-Stomach-439 are similar in single or combined use. However, the cutoff index of serum CSLEX tended to be higher than that of Nation Cancer Center-Stomach-439, which may make CSLEX more useful for detection of breast cancer metastasis.

Full-thickness chest-wall resection followed by thorax reconstruction for recurrent malignant phyllodes tumor.

We present a case of a 39-year-old woman with a giant recurrent malignant phyllodes tumor accompanied with bleeding and infection. She underwent full-thickness chest-wall resection. Bony thorax reconstruction and stabilization was accomplished using a Composix mesh™, and soft tissue reconstruction was performed with a musculocutaneous flap of latissimus dorsi muscle. The patient had a good postoperative outcome, and the surgical treatment remarkably improved her quality of life. Because chemotherapy and radiation are not established for treating malignant phyllodes tumors, an aggressive surgical approach should be considered for patients with a locally advanced malignant phyllodes tumor.

[A retrospective study of high-dose toremifene treatment for patients with aromatase inhibitor refractory advanced or metastatic hormone receptor-positive breast cancer].

Aromatase inhibitors (AI) have largely replaced tamoxifen as the first-line of treatment for postmenopausal women with advanced or metastatic hormone-receptor-positive breast cancer. However, there is no established strategy for treating AI refractory cases. In this study, we investigated the efficacy of high-dose Toremifene therapy (HD-TOR). From January 2001 through April 2010, nineteen patients received 120 mg of TOR daily. The overall response rate was 36.8% (CR; 1, PR; 6), and the clinical benefit was 47.4%. The clinical benefit rate to each of the metastatic organs were: lung, 42.9%; bone, 13%; liver, 25%; and lymph node, 40%. A higher clinical benefit rate was observed in lung or lymph node metastases. The clinical benefit rate of HD-TOR as first to third-line therapy was 50%, which was more effective than that of fourth-line therapy. Our data suggests that HD-TOR may be one of the effective treatment strategies for patients with AI refractory advanced or metastatic hormone receptor-positive breast cancer.

Regular Vigorous-Intensity Physical Activity and Walking Are Associated with Divergent but not Convergent Thinking in Japanese Young Adults.

The beneficial effects of regular physical activity (PA) on cognitive functions have received much attention. Recent research suggests that regular PA may also enhance creative thinking, an indispensable cognitive factor for invention and innovation. However, at what intensity regular PA brings the most benefits to creative thinking remains uninvestigated. Furthermore, whether the levels of regular PA affect the acute PA effects on creative thinking is also unclear. In the present study, using a previous dataset that investigated the effects of an acute bout of aerobic exercise on creative thinking in healthy Japanese young adults (22.98 ± 1.95 years old) in the year 2020, we tested the association between different intensities of regular PA (i.e., vigorous, moderate, and walking) and creative thinking with the cross-sectional baseline data using multiple linear regression. We also investigated whether regular PA levels were associated with the acute aerobic exercise intervention effects on creative thinking. The results showed that cross-sectionally, the regular PAs were differentially associated with divergent but not convergent thinking. Specifically, whereas the amount of vigorous-intensity PA was positively associated with fluency and flexibility, the amount of walking was positively associated with novelty on the alternate uses test (AUT) measuring divergent thinking. Importantly, the explained variances of fluency, flexibility, and novelty were 20.3% (p = 0.040), 18.8% (p = 0.055), and 20.1% (p = 0.043), respectively. None of the regular PAs predicted convergent thinking (i.e., an insight problem-solving task), nor were they associated with the acute aerobic exercise intervention effects on divergent and convergent thinking. These findings suggest that engaging in regular vigorous-intensity PA and walking may be useful strategies to enhance different aspects of divergent thinking in daily life.

Sex difference in the weighting of expected uncertainty under chronic stress.

The neurobiological literature implicates chronic stress induced decision-making deficits as a major contributor to depression and anxiety. Given that females are twice as likely to suffer from these disorders, we hypothesized the existence of sex difference in the effects of chronic stress on decision-making. Here employing a decision-making paradigm that relies on reinforcement learning of probabilistic predictive relationships, we show female volunteers with a high level of perceived stress in the past month are more likely to make suboptimal choices than males. Computational characterizations of this sex difference suggest that while under high stress, females and males differ in their weighting but not learning of the expected uncertainty in the predictive relationships. These findings provide a mechanistic account of the sex difference in decision-making under chronic stress and may have important implications for the epidemiology of sex difference in depression and anxiety.