Miracle-dz/UniFAR-FTUs huggingface dataset:
Involvement of Toll-like receptor 2 in the cerebral immune response and behavioral changes caused by latent Toxoplasma infection in mice

Subacute and chronic infections with the intracellular protozoan parasite Toxoplasma gondii are associated with an increased risk of psychiatric diseases like schizophrenia. However, little is known about the mechanisms involved in T. gondii-induced neuronal disorders. Recently, we reported that Toll-like receptor 2 (TLR2) was required to initiate the innate immune response in cultured mouse brain cells. However, how TLR2 contributes to latent infection with T. gondii remains unclear. Therefore, we examined the role of TLR2 in brain pathology and behavior using wild-type (TLR2+/+) and TLR2-deficient (TLR2-/-) mice. The behavioral analyses showed that TLR2 deficiency increased the anxiety state of the uninfected and infected animals alike, and TLR2 deficiency showed no relationship with the infection. In the contextual and cued fear-conditioning tests, T. gondii infection decreased the mouse freezing reaction while TLR2 deficiency increased it, but there was no interaction between the two factors. Our histopathological analysis showed that the TLR2+/+ and TLR2-/- mice had similar brain lesions at 30 days post infection (dpi) with T. gondii. Higher numbers of parasites were detected in the brains of the TLR2-/- mice than in those from the TLR2+/+ mice at 30 dpi, but not at 7 and 14 dpi. No significant differences were observed in the proinflammatory gene expression levels in the TLR2+/+ and TLR2-/- mice. Therefore, it appears that TLR2 signaling in the brain might contribute to the control of parasite growth, but not to brain pathology or the impaired fear memory response induced by infection with T. gondii.
Sudden Cardiac Deaths in Adults with Congenital Heart Disease with Structural Abnormalities: A Retrospective Review of Cases in the Cook County Medical Examiner's Office

Sudden cardiac death is a significant cause of mortality in adults with congenital heart disease (CHD). The Cook County Medical Examiner's Office database was queried for cases of CHD as a cause of death in the period between July 2008 and April 2019. Twenty‐two cases were identified, including 11 decedents with simple defects and 10 decedents with complex defects. All of the subjects were in apparent good health at the time of death. In the absence of other obvious causes of death, simple defects were considered cases of sudden cardiac death. Significant cardiac morphological changes were common in complex defects. While 16 cases had known, diagnosed/treated CHD, 5 cases had no diagnosis prior to autopsy. In these cases, the ability to recognize CHD (sometimes subtle) helped in determining the causes of death. Therefore, forensic pathologists must be able to properly recognize various forms of CHD and request consultations, when needed.
The impact of SOCS1 mutations in diffuse large B‐cell lymphoma

Mutations in SOCS1 are frequent in primary mediastinal B‐cell lymphoma and classical Hodgkin lymphoma. In the latter, SOCS1 mutations affect the length of the encoded protein (major mutations) and are associated with shorter patient survival. Two independent studies examined the prognostic impact of SOCS1 mutations in diffuse large B‐cell lymphoma (DLBCL) and showed differing results. This may be due to the small number of included patients, the heterogeneity of patients’ demographics and the distinct treatment schemes in these studies. To overcome the size limitations of these previous studies, we assessed SOCS1 mutations in the RICOVER‐60 cohort. The cohort uniformly consists of elderly patients (aged 61–80 years) treated with the CHOP‐14 scheme (cyclophosphamide, hydroxydaunorubicin, vincristine, prednisolone at 14‐day intervals) with or without an additional rituximab treatment. Patient outcomes were analysed with regard to overall SOCS1 mutation frequency, major and minor mutations and a novel impact‐based classifier – against the treatment modalities. Patients harbouring putative pathogenic SOCS1 mutations showed significant reduced overall survival within the CHOP plus rituximab group. Hence, putative pathogenic SOCS1 mutations seem to efface the beneficial effect of the therapeutic CD20 antibody. Comparing published data of whole exome and transcriptome sequencing of a large DLBCL cohort confirmed that predicted deleterious SOCS1 mutations forecast pre‐eminent survival in early onset DLBCL.
Cancer Metabolism and the Evasion of Apoptotic Cell Death

Cellular growth and proliferation depend upon the acquisition and synthesis of specific metabolites. These metabolites fuel the bioenergy, biosynthesis, and redox potential required for duplication of cellular biomass. Multicellular organisms maintain tissue homeostasis by balancing signals promoting proliferation and removal of cells via apoptosis. While apoptosis is in itself an energy dependent process activated by intrinsic and extrinsic signals, whether specific nutrient acquisition (elevated or suppressed) and their metabolism regulates apoptosis is less well investigated. Normal cellular metabolism is regulated by lineage specific intrinsic features and microenvironment driven extrinsic features. In the context of cancer, genetic abnormalities, unconventional microenvironments and/or therapy engage constitutive pro-survival signaling to re-program and rewire metabolism to maintain survival, growth, and proliferation. It thus becomes particularly relevant to understand whether altered nutrient acquisition and metabolism in cancer can also contribute to the evasion of apoptosis and consequently therapy resistance. Our review attempts to dissect a causal relationship between two cancer hallmarks, i.e., deregulated cellular energetics and the evasion of programmed cell death with primary focus on the intrinsic pathway of apoptosis.
Lingering Impact of Starting Working Life During a Recession: Health Outcomes of Survivors of the “Employment Ice Age” (1993–2004) in Japan

Background A growing amount of evidence demonstrates the adverse impacts of economic downturns on population health. However, the extent to which the macroeconomic conditions at labor market entry affect health outcomes in later life remains relatively understudied. This study focused on the health outcomes of the cohort who entered the labor market during the “employment ice age” (EIA; 1993–2004) in Japan, when young people had difficulty finding jobs after graduating from college or high school. Methods We used repeated cross-sectional data (N = 3,054,782; 1,500,618 men and 1,554,164 women) obtained from an 11-wave population-based nationwide survey conducted every 3 years from 1986 through 2016. We considered three health outcomes: being in hospital, subjective symptoms, and self-rated health (SRH). We employed two types of statistical analyses: an age-period-cohort (APC) analysis, which controlled for age and period (wave) effects, and a difference-in-differences (DiD) analysis, in which the EIA experience was regarded as a treatment. Results The APC analysis confirmed the relative disadvantage of the EIA cohort for all three outcomes; for instance, the odds ratio of poor SRH for the EIA cohort was 1.29 (95% confidence interval [CI], 1.21–1.38) for men and 1.25 (95% CI, 1.17–1.34) for women. The DiD analysis confirmed the robustness of these results, especially for men. Conclusions The results underscored the lingering impact of the macroeconomic conditions at labor market entry on health outcomes in later life in Japan.
Tubulin detyrosination promotes human trophoblast syncytium formation

Abstract Human trophoblast syncytialization is one of the most important yet least understood events during placental development. In this study, we found that detyrosinated α-tubulin (detyr-α-tub), which is negatively regulated by tubulin tyrosine ligase (TTL), was elevated during human placental cytotrophoblast fusion. Correspondingly, relatively high expression of TTL protein was observed in first-trimester human placental cytotrophoblast cells, but fusing trophoblast cells exhibited much lower levels of TTL. Notably, fusion of preeclamptic cytotrophoblast cells was compromised but could be partially rescued by knockdown of TTL levels. Mechanistically, chronic downregulation of TTL in trophoblast cells resulted in significantly elevated expression of detyr-α-tub. Restoration of detyr-α-tub thus contributed to the cell surface localization of the fusogenic protein Syncytin-2 and the gap junction protein Connexin 43 (Cx43), which in turn promoted successful fusion between trophoblast cells. Taken together, the results suggest that tubulin detyrosination plays an essential role in human trophoblast fusogenic protein aggregation and syncytialization. Insufficient tubulin detyrosination leads to defects in syncytialization and potentially to the onset of preeclampsia.
The molecular chaperone Hsp90α deficiency causes retinal degeneration by disrupting Golgi organization and vesicle transportation in photoreceptors

Abstract Heat shock protein 90 (Hsp90) is an abundant molecular chaperone with two isoforms, Hsp90α and Hsp90β. Hsp90β deficiency causes embryonic lethality, whereas Hsp90α deficiency causes few abnormities except male sterility. In this paper, we reported that Hsp90α was exclusively expressed in the retina, testis, and brain. Its deficiency caused retinitis pigmentosa (RP), a disease leading to blindness. In Hsp90α-deficient mice, the retina was deteriorated and the outer segment of photoreceptor was deformed. Immunofluorescence staining and electron microscopic analysis revealed disintegrated Golgi and aberrant intersegmental vesicle transportation in Hsp90α-deficient photoreceptors. Proteomic analysis identified microtubule-associated protein 1B (MAP1B) as an Hsp90α-associated protein in photoreceptors. Hspα deficiency increased degradation of MAP1B by inducing its ubiquitination, causing α-tubulin deacetylation and microtubule destabilization. Furthermore, the treatment of wild-type mice with 17-DMAG, an Hsp90 inhibitor of geldanamycin derivative, induced the same retinal degeneration as Hsp90α deficiency. Taken together, the microtubule destabilization could be the underlying reason for Hsp90α deficiency-induced RP.
Role of coprophagy in the cecal microbiome development of an herbivorous bird Japanese rock ptarmigan

The transgenerational maintenance of symbiotic microbes that benefit host nutrition and health is evolutionarily advantageous. In some vertebrate lineages, coprophagy is used as a strategy for effectively transmitting microbes across generations. However, this strategy has still not been studied in birds. Accordingly, the aim of the present study was to evaluate the role of maternal cecal feces consumption by Japanese rock ptarmigan (Lagopus muta japonica) chicks as a strategy for acquiring essential gut microbes. Both the duration of coprophagy behavior by the chicks and the development process of the chick cecal microbiome (n=20 one- to three-week-old chicks, from three broods) were investigated. In all three broods, coprophagy behavior was only observed from 3 to 18 days of age. Furthermore, there was no significant difference in the number of bacterial operational taxonomic units (OTUs) in 1-week-old chicks (n=651) and adults (n=609), and most of the main OTUs observed in the adults were already present in the 1-week-old chicks. These results indicate that, in this precocial bird species, coprophagy may contribute to the early establishment of cecal bacteria that are essential for food digestion and, thus, chick survival. In fact, Japanese rock ptarmigan chicks consume the same food as their hens from the time of hatching. This behavior may have applications to ex-situ conservation.
Determining the Volume Expansion at Grain Boundaries Using Extended Energy-Loss Fine Structure Analysis

Abstract Grain boundaries (GBs) play an important role in material behavior, so considerable effort has gone into determining their structure and properties. Studies of GBs have revealed a correlation between the GB energy and expansion of the planes normal to the GB, or the so-called normal volume expansion. In this investigation, the volume expansion at several GBs was experimentally determined using extended energy-loss fine structure (EXELFS) analysis in a scanning/transmission electron microscope, allowing changes in the nearest-neighbor (n.n.) distances to be determined with nanometer spatial resolution. EXELFS performed on three-model GBs showed that the average n.n. distances at the GBs increased with increasing GB energy. Additionally, the total volume expansion at the GBs, calculated using complementary plasmon energy profiles, showed excellent agreement with volume expansions measured using other experimental techniques. Hence, this study demonstrates that EXELFS is a useful technique to measure the normal volume expansion at GBs. When combined with the results from complementary studies on the same GBs using valence electron energy-loss spectroscopy, this work further shows that the GB energy increases in relation to both the decrease in electron density at the GB and an accompanying increase in specific volume expansion at the GB.
Daytime physical activity at admission is associated with improvement of gait independence 1 month later in people with subacute stroke: a longitudinal study

ABSTRACT Background: Little is known about the benefits of daytime physical activity on gait ability in subacute stroke. Objectives: We investigated association between daytime physical activity at hospital admission and improvement of gait independence 1 month later in subacute stroke. Methods: Thirty-four participants with subacute stroke who could not walk independently were assessed. An accelerometer (HJA 350-IT, OMRON) was used to record the mean duration of light-intensity physical activity (LIPA) and moderate-to-vigorous-intensity physical activity (MVPA). LIPA and MVPA were recorded for 12 h per day for 7 consecutive days, and at three different time periods (daytime, therapy time, non-therapy time) at rehabilitation hospital admission (baseline). Gait independence was assessed by the functional ambulation category (FAC) at baseline and 1 month later. Participants were categorized into two groups based on the change of gait independence, as follows: the improved group, in which the FAC increased by ≥1; the non-improved group, in which the FAC did not increase. Results: Compared with the non-improved group, the improved group demonstrated significantly higher values of all physical activity variables, except for non-therapy time MVPA (p < .05). Logistic regression analysis showed that higher daytime LIPA was significantly associated with FAC improvement (OR = 1.068, 95% CI 1.009 to 1.140). In particular, higher non-therapy time LIPA was closely associated with FAC improvement (OR = 1.253, 95% CI 1.002 to 1.568). Conclusions: To promote recovery of gait independence in first month from admission, increasing daytime physical activity, especially LIPA during daytime or non-therapy time, is an important treatment target in subacute stroke.
Between persistently active and activity‐silent frameworks: novel vistas on the cellular basis of working memory

Recent work has revealed important new discoveries on the cellular mechanisms of working memory (WM). These findings have motivated several seemingly conflicting theories on the mechanisms of short‐term memory maintenance. Here, we summarize the key insights gained from these new experiments and critically evaluate them in light of three hypotheses: classical persistent activity, activity‐silent, and dynamic coding. The experiments discussed include the first direct demonstration of persistently active neurons in the human medial temporal lobe that form static attractors with relevance to WM, single‐neuron recordings in the macaque prefrontal cortex that show evidence for both persistent and more dynamic types of WM representations, and noninvasive neuroimaging in humans that argues for activity‐silent representations. A key insight that emerges from these new results is that there are several neural mechanisms that support the maintenance of information in WM. Finally, based on established cognitive theories of WM, we propose a coherent model that encompasses these seemingly contradictory results. We propose that the three neuronal mechanisms of persistent activity, activity‐silent, and dynamic coding map well onto the cognitive levels of information processing (within focus of attention, activated long‐term memory, and central executive) that Cowan's WM model proposes.
Normalizing Plasma Renin Activity in Experimental Dilated Cardiomyopathy: Effects on Edema, Cachexia, and Survival

Heart failure (HF) patients frequently have elevated plasma renin activity. We examined the significance of elevated plasma renin activity in a translationally-relevant model of dilated cardiomyopathy (DCM), which replicates the progressive stages (A–D) of human HF. Female mice with DCM and elevated plasma renin activity concentrations were treated with a direct renin inhibitor (aliskiren) in a randomized, blinded fashion beginning at Stage B HF. By comparison to controls, aliskiren treatment normalized pathologically elevated plasma renin activity (p < 0.001) and neprilysin levels (p < 0.001), but did not significantly alter pathological changes in plasma aldosterone, angiotensin II, atrial natriuretic peptide, or corin levels. Aliskiren improved cardiac systolic function (ejection fraction, p < 0.05; cardiac output, p < 0.01) and significantly reduced the longitudinal development of edema (extracellular water, p < 0.0001), retarding the transition from Stage B to Stage C HF. The normalization of elevated plasma renin activity reduced the loss of body fat and lean mass (cachexia/sarcopenia), p < 0.001) and prolonged survival (p < 0.05). In summary, the normalization of plasma renin activity retards the progression of experimental HF by improving cardiac systolic function, reducing the development of systemic edema, cachexia/sarcopenia, and mortality. These data suggest that targeting pathologically elevated plasma renin activity may be beneficial in appropriately selected HF patients.
In Vivo Endomicroscopy of Lung Injury and Repair in ARDS: Potential Added Value to Current Imaging

Background: Standard clinical imaging of the acute respiratory distress syndrome (ARDS) lung lacks resolution and offers limited possibilities in the exploration of the structure–function relationship, and therefore cannot provide an early and clear discrimination of patients with unexpected diagnosis and unrepair profile. The current gold standard is open lung biopsy (OLB). However, despite being able to reveal precise information about the tissue collected, OLB cannot provide real-time information on treatment response and is accompanied with a complication risk rate up to 25%, making longitudinal monitoring a dangerous endeavor. Intravital probe-based confocal laser endomicroscopy (pCLE) is a developing and innovative high-resolution imaging technology. pCLE offers the possibility to leverage multiple and specific imaging probes to enable multiplex screening of several proteases and pathogenic microorganisms, simultaneously and longitudinally, in the lung. This bedside method will ultimately enable physicians to rapidly, noninvasively, and accurately diagnose degrading lung and/or fibrosis without the need of OLBs. Objectives and Methods: To extend the information provided by standard imaging of the ARDS lung with a bedside, high-resolution, miniaturized pCLE through the detailed molecular imaging of a carefully selected region-of-interest (ROI). To validate and quantify real-time imaging to validate pCLE against OLB. Results: Developments in lung pCLE using fluorescent affinity- or activity-based probes at both preclinical and clinical (first-in-man) stages are ongoing—the results are promising, revealing correlations with OLBs in problematic ARDS. Conclusion: It can be envisaged that safe, high-resolution, noninvasive pCLE with activatable fluorescence probes will provide a “virtual optical biopsy” and will provide decisive information in selected ARDS patients at the bedside.
Reexamining effects of urbanization on population structure of freshwater turtles: response to Bowne et al. 2018

Through a creative collaboration combining education with research, Bowne et al. (2018) explored how urbanization affects freshwater turtle demography across the United States. The study’s conclusions interested us because they are inconsistent with previous work. Although exceptions exist (Mali et al. 2013; Dorland et al. 2014), nesting migrations are generally thought to make female freshwater turtles relatively vulnerable to road mortality, leading to male-biased populations (Wood & Herlands 1997; Marchand & Litvaitis 2004; Steen & Gibbs 2004; Aresco 2005; Steen et al. 2006; DeCatanzaro & ChowFraser 2010; Patrick & Gibbs 2010). This phenomenon is thought to have increased over time with expanding road networks (Gibbs & Steen 2005) and is likely sufficient to impact population sizes (Gibbs & Shriver 2002). However, Bowne et al. (2018) conclude that adult painted turtle (Chrysemys picta) sex ratios are not affected by roads and that urbanization produces female-biased populations. Human activities are serious threats to turtles, one of the most imperiled groups of vertebrates (Stanford et al. 2018). Although money for conservation is limited, much has been used to mitigate the impacts of roads and urbanization on turtles. However, Bowne et al.’s (2018) results could be used to suggest that resources may be better allocated elsewhere. Therefore, we felt it necessary to better understand why this study’s conclusions differed from our expectations.
Knowledge and Attitudes about the Flu Vaccine among Pregnant Women in the Valencian Community (Spain)

Background and Objectives: To describe the knowledge and attitudes related to the acceptance of the flu vaccine during pregnancy in women, from two Health Departments of the Valencian Community (VC), during the 2015–2016 season, after receiving prenatal care. Materials and Methods: A prospective observational study was conducted during the annual vaccine season of women ascribed to prenatal care. A midwife offered flu vaccine advice and afterwards conducted a telephone poll of a representative sample, in order to find out the reason for accepting or rejecting the vaccine. Results: Of the 1017 expectant women who received advice about the vaccine, 77.4% (95% CI: 74.8–79.9%) declared their intention to vaccinate. After the recommendation, the vaccine coverage was 61.6%, with a percentage of accordance of 98.8% (95% CI: 98.0–99.6%) between the coverage declared and the Nominal Vaccination Registry (NVR) of the VC. Additionally, 67.2% of the expectant women were interviewed (n = 683). Most were aware of the recommendation and identified the health center and the midwife as the main sources of information. The internet was a consistent source in favor of vaccination 80.8% (n = 42). The obstetric variables (risk during the pregnancy, end of pregnancy, and feeding the newborn) did not have a statistically significant relationship with the vaccination. The women declared a high adherence to the vaccinations present in the child vaccination calendar, but rejected (31.3%) the flu vaccine, as they had not received it previously and did not want it because of their expectant state. Conclusions: The women positively evaluated the effectiveness and safety of the vaccines. However, with the flu vaccine, “not being previously vaccinated” and the “doubts about its safety” represented more than half of the reasons put forth for its rejection. Ensuring that the flu vaccine is perceived as more effective and acceptable through the messages directed towards the expectant mothers, directly through the midwives or through the communication media and social networks, will result in an increase of vaccine coverage.