Miracle-dz/UniFAR-FTUs huggingface dataset:
Bidirectional electric communication between the inferior occipital gyrus and the amygdala during face processing

Faces contain multifaceted information that is important for human communication. Neuroimaging studies have revealed face‐specific activation in multiple brain regions, including the inferior occipital gyrus (IOG) and amygdala; it is often assumed that these regions constitute the neural network responsible for the processing of faces. However, it remains unknown whether and how these brain regions transmit information during face processing. This study investigated these questions by applying dynamic causal modeling of induced responses to human intracranial electroencephalography data recorded from the IOG and amygdala during the observation of faces, mosaics, and houses in upright and inverted orientations. Model comparisons assessing the experimental effects of upright faces versus upright houses and upright faces versus upright mosaics consistently indicated that the model having face‐specific bidirectional modulatory effects between the IOG and amygdala was the most probable. The experimental effect between upright versus inverted faces also favored the model with bidirectional modulatory effects between the IOG and amygdala. The spectral profiles of modulatory effects revealed both same‐frequency (e.g., gamma–gamma) and cross‐frequency (e.g., theta–gamma) couplings. These results suggest that the IOG and amygdala communicate rapidly with each other using various types of oscillations for the efficient processing of faces. Hum Brain Mapp 38:4511–4524, 2017. © 2017 Wiley Periodicals, Inc.
The global burden of urinary bladder cancer

Statistics on the incidence of bladder cancer are particularly hard to interpret, because of changing classification, variations in counting of multiple cancers in the same individual and, most importantly, the variable inclusion of non-invasive cancers in different data sets. Mortality statistics are almost certainly more comparable, but as indirect estimators of disease risk, require some cautious interpretation, because of differing survival between populations, and over time. Cancer of the bladder is estimated to be the ninth most common cause of cancer worldwide (357000 cases in 2002) and the 13th most numerous cause of death from cancer (145000 deaths). Rates in males are three to four times those in females. Incidence rates are high in many southern and eastern European countries, in parts of Africa and the Middle East, and in North America. The highest estimated mortality is in Egypt, where rates are more than three times greater than the highest rates in Europe and eight times those in the USA. In the USA, the incidence in whites is higher than in blacks. In general, in Western countries, incidence rates have been rising, but the increase has slowed or stopped in many. Mortality rates are, for the most part, decreasing. Trends are more variable in developing countries. To some extent, the geography and time trends are related to prevalence of known risk factors, especially exposure to tobacco (responsible for almost one-third of bladder cancer deaths) and, in some specific areas, schistosomiasis.
Thiopental bolus during carotid endarterectomy-rational drug therapy?

Ten studies were performed to examine the time course of arterial and venous thiopental concentrations following the administration of thiopental (4 mg X kg-1 over 3 min) for cerebral protection during carotid occlusion in nine patients undergoing elective carotid endarterectomy; in five patients the time course of EEG change was also studied. The arterial and venous thiopental concentrations were similar with no evidence of a sustained arterial-venous gradient. The average arterial concentration was 20.1 microgram X ml-1 +/- 10 (SD) at 2 min after thiopental, and fell rapidly to 13.0 micrograms X ml-1 +/- 3.2 at 5 min, 10.7 micrograms X ml-1 +/- 4.4 at 10 min and 6.2 micrograms X ml-1 at 30 min. After thiopental the EEG record showed an increase in delta activity and in four patients a burst suppression pattern was seen. The duration of burst suppression activity was variable (130 to 367 seconds) but in all instances cortical activity had returned to the pre-thiopental level by five to ten minutes. Thus concentrations of thiopental of 10-30 micrograms X ml-1 were associated with EEG burst suppression and both were seen only within the first five minutes after drug administration. In contrast the carotid artery was occluded for considerably longer (26 +/- 4) minutes. We conclude that, since there was no sustained arterial-venous gradient, either arterial or venous concentrations are adequate for the study of thiopental pharmacokinetics. (ABSTRACT TRUNCATED AT 250 WORDS)
Expression of Constitutively Active Phosphatidylinositol 3-Kinase Inhibits Activation of Caspase 3 and Apoptosis of Cardiac Muscle Cells*

Apoptosis of cardiac muscle cells contributes to the development of cardiomyopathy. Recent studies showed that insulin-like growth factor I (IGF-I) inhibits apoptosis of cardiac muscle cells and improves myocardial function in experimental heart failure. This study was carried out to elucidate the role of phosphatidylinositol 3-kinase (PI 3-kinase) in the anti-apoptotic actions of IGF-I in cardiomyocytes and to explore whether expression of constitutively active PI 3-kinase can inhibit apoptosis in cardiomyocytes. Apoptosis of primary cardiomyocytes was induced by doxorubicin treatment and serum withdrawal. Transduction of cardiomyocytes with constitutively active PI 3-kinase specifically lead to serine phosphorylation of Akt, whereas phosphorylation of IGF-I receptor, IRS1/2 and p44/42 mitogen-activated protein kinase were not increased. In the cardiomyocytes transduced with constitutively active PI 3-kinase, activation of the pro-apoptotic caspase 3 was attenuated and fragmentation of DNA was reduced. Preincubating cells with PI 3-kinase inhibitor LY294002 was associated with loss of anti-apoptotic actions of IGF-I and PI 3-kinase. Neither IGF-I nor constitutively active PI 3-kinase lead to serine phosphorylation of Bad, suggesting that the anti-apoptotic effects of PI 3-kinase are not mediated through Bad phosphorylation in cardiac muscle cells. To determine whether activation of caspase 3 is sufficient to induce apoptosis in cardiomyocytes, an engineered TAT-caspase 3 protein was introduced to cardiomyocytes. Significant reduction of cell viability occurred in the cardiomyocytes transduced with active caspase 3, indicating that activation of caspase 3 is sufficient to cause cardiomyocyte death. These findings indicate the existence of an IGF-I receptor-PI 3-kinase-caspase 3 pathway in cardiomyocytes that plays an important role in the anti-apoptotic actions of IGF-I in heart. Moreover, these data suggest that modulation of PI 3-kinase activities may represent a potential therapeutic strategy to counteract the occurrence of apoptosis in cardiomyopathy.
Bridging gender gaps

In the 1960s two out of ten adult women in Brazil were in the labor force, either employed or actively seeking for a job; half a century later this figure has changed dramatically, climbing to seven out of ten. This pattern has been typical of all Latin American countries, although with different intensities. Compared to the situation some decades ago, women in the region now allocate a larger share of their time to market activities rather than working at home. The gap with men in labor market participation remains far from being closed, and it is still larger than in several regions of the world, but its width has been substantially reduced. Arguably, the strong increase in female labor force participation (LFP) is among the most salient socioeconomic changes in Latin America in the last half-century. This fact not only implies a profound transformation in the daily life of millions of Latin American women and families, but also has substantial economy-wide labor and social consequences. Poverty, inequality, unemployment and education –just to mention a few social issues– are all affected by a more intense entry of women into the workforce. Although remarkable, the long-run pattern of female gains has been insufficient to close the gap with males in most labor variables, such as wages, employment and labor force participation. Gender equality in the labor market remains a difficult challenge in the region. While gender gaps in education attainment have been substantially reduced or even eliminated, the region stills performs poorly in guaranteeing equality in the economic and labor dimensions. For instance, while Latin America ranks among the regions with relatively small gender gaps based on the Global Index of the World Economic Forum,1 the performance becomes more mediocre in the Economic Participation and Opportunity Sub index, which captures the gender gap in labor force participation rates, earned incomes, and employment in top positions. This book highlights a change in the trend of female labor force participation that makes the situation potentially more worrisome: after around half a century of sustained growth, there are signs of a widespread and significant deceleration in the entry of women into the Latin American labor markets. That deceleration seems to have been taking place since the early/mid-2000s, and it applies to all groups of women, but particularly to those married2, and in more vulnerable households. The slower entry of women into the workforce has delayed the closing of the gender gap in labor participation, and makes improbable the fulfillment of the gender-equity Millennium Development Goals (MDGs) related to female employment. Although this book provides a general view of the issue of female LFP, the recent deceleration is highlighted in several of its chapters.
HP1γ associates with euchromatin and heterochromatin in mammalian nuclei and chromosomes

Heterochromatin protein 1 (HP1) is a nonhistone chromosomal protein, first identified in Drosophila, that plays a dose-dependent role in gene silencing. Three orthologs, HP1α, HP1β, and HP1γ, have been characterized in mammals. While HP1α and HP1β have been unambiguously localized in heterochromatin by immunocytochemical methods, HP1γ has been found either exclusively associated with euchromatin or present in both euchromatin and heterochromatin. Here, using an antibody directed against a peptide epitope at the carboxyl-terminal end of the molecule, we localize HP1γ in both euchromatin and heterochromatin compartments of interphase nuclei, as well as in the pericentromeric chromatin and arms of mitotic chromosomes of 3T3 cells. This dual location was also observed in nuclei expressing HP1γ as a fusion protein with green fluorescent protein. In contrast, when the distribution of HP1γ was analyzed with antibodies directed against an amino-terminal epitope, the protein was detectable in euchromatin and not in heterochromatin, except for transient heterochromatin staining during the late S phase, when the heterochromatin undergoes replication. These data suggest that the controversial immunolocalization of HP1γ in chromatin is due to the use of antibodies directed against topologically distinct epitopes, those present at the amino-terminal end of the molecule being selectively masked in nonreplicative heterochromatin.
Role of engineered metal oxide nanoparticle agglomeration in reactive oxygen species generation and cathepsin B release in NLRP3 inflammasome activation and pulmonary toxicity

Abstract Incomplete understanding of the contributions of dispersants and engineered nanoparticles/materials (ENM) agglomeration state to biological outcomes presents an obstacle for toxicological studies. Although reactive oxygen species (ROS) production is often regarded as the primary indicator of ENM bioactivity and toxicity, it remains unclear whether ENM produce ROS or whether ROS is an outcome of ENM-induced cell injury. Phagolysosomal disruption and cathepsin B release also promote bioactivity through inflammasome activation. Therefore, specific particle parameters, i.e. preexposure dispersion status and particle surface area, of two ENM (NiO and CeO2) were used to evaluate the role of ROS generation and cathepsin B release during ENM-induced toxicity. Male C57BL/6J mice were exposed to 0, 20, 40, or 80 μg of poorly or well-dispersed NiO-NP or CeO2-NP in four types of dispersion media. At 1- and 7-day postexposure, lung lavage fluid was collected to assess inflammation, cytotoxicity, and inflammasome activation. Results showed that preexposure dispersion status correlated with postexposure pulmonary bioactivity. The differences in bioactivity of NiO-NP and CeO2-NP are likely due to NiO-NP facilitating the release of cathepsin B and in turn inflammasome activation generating proinflammatory cytokines. Further, both metal oxides acted as free radical scavengers. Depending on the pH, CeO2-NP acted as a free radical scavenger in an acidic environment (an environment mimicking the lysosome) while the NiO-NP acted as a scavenger in a physiological pH (an environment that mimics the cytosol of the cell). Therefore, results from this study suggest that ENM-induced ROS is not likely a mechanism of inflammasome activation.
Cerebral herniation during bacterial meningitis in children.

OBJECTIVE--To see whether the incidence of cerebral herniation is increased immediately after lumbar puncture in children with bacterial meningitis and whether any children with herniation have normal results on cranial computed tomography. DESIGN--Retrospective review of case notes; computed tomograms were read again. SETTING--Large paediatric teaching hospital. SUBJECTS--445 children over 30 days old admitted to hospital with bacterial meningitis. MAIN OUTCOME MEASURES--Timing of herniation in relation to lumbar puncture; findings on computed tomography in children with herniation. RESULTS--Cerebral herniation was detected in 19 (4.3%) of the 445 children (21 episodes; herniation occurred twice in two children). Herniation occurred in 14 (45%) of the 31 children who died. Nineteen episodes of herniation occurred in the 17 children who had a lumbar puncture; 12 of the episodes occurred in the first 12 hours after the lumbar puncture and seven over six other 12 hour periods (odds ratio 32.6 (95% confidence interval 8.5 to 117.3); p < 0.001). The results of cranial computed tomography were normal in five (36%) of the 14 episodes of herniation in which scanning was performed at about the time of herniation. CONCLUSIONS--The temporal relation between lumbar puncture and herniation strongly suggests that a lumbar puncture may cause herniation in some patients, and normal results on computed tomography do not mean that it is safe to do a lumbar puncture in a child with bacterial meningitis.
Bladder exstrophy: An epidemiologic study from the International Clearinghouse for Birth Defects Surveillance and Research, and an overview of the literature

Bladder exstrophy (BE) is a complex congenital anomaly characterized by a defect in the closure of the lower abdominal wall and bladder. We aimed to provide an overview of the literature and conduct an epidemiologic study to describe the prevalence, and maternal and case characteristics of BE. We used data from 22 participating member programs of the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR). All cases were reviewed and classified as isolated, syndrome, and multiple congenital anomalies. We estimated the total prevalence of BE and calculated the frequency and odds ratios for various maternal and case characteristics. A total of 546 cases with BE were identified among 26,355,094 births. The total prevalence of BE was 2.07 per 100,000 births (95% CI: 1.90–2.25) and varied between 0.52 and 4.63 among surveillance programs participating in the study. BE was nearly twice as common among male as among female cases. The proportion of isolated cases was 71%. Prevalence appeared to increase with increasing categories of maternal age, particularly among isolated cases. The total prevalence of BE showed some variations by geographical region, which is most likely attributable to differences in registration of cases. The higher total prevalence among male cases and older mothers, especially among isolated cases, warrants further attention. © 2011 Wiley Periodicals, Inc.
In situ Activated Intestinal T Cells Expanded in vitro – without Addition of Antigen – Produce IFN-γ and IL-10 and Preserve Their Function during Growth

Objective: The balance between mucosal CD4+ T cells producing IFN-γ or IL-10 is essential in the maintenance of intestinal homeostasis. We aimed to investigate how in situ activated T cells were expanded in vitro according to a new cell culture protocol and if it selected for continuous clonal CD4+ T cells capable of producing mainly IFN-γ or IL-10. Methods: T cell cultures were established from colonic biopsy specimens of 27 patients with Crohn’s disease and from 10 healthy controls in a medium supplemented with IL-2 and IL-4 but without addition of exogenous antigen or mitogen. Cytokine production was measured after stimulation (IL-12, super antigen) and inhibition (ciclosporin and methylprednisolone). Results: Cytokine production was increased in cultures from patients with Crohn’s disease compared to controls (IFN-γ, p = 0.005; IL-10, p = 0.003; TNF-α, p = 0.03). Early cultures were highly responsive to IL-12 stimulation. We established CD4+ T-cell clones escaping cellular senescence with an inflammatory or regulatory cytokine profile. Discussion: The data indicate that cultures of in situ activated inflammatory and regulatory subpopulations of intestinal T lymphocytes with pathogenic importance in Crohn’s disease can be established preserving their functional properties during growth.
Part of the Series: From Dietary Antioxidants to Regulators in Cellular Signalling and Gene ExpressionRole of reactive oxygen species and (phyto)oestrogens in the modulation of adaptive response to stress

There is increasing evidence that reactive oxygen species (ROS) are not only toxic but play an important role in cellular signalling and in the regulation of gene expression. We, here, discuss two examples of improved adaptive response to an altered cellular redox state. First, differences in longevity between males and females may be explained by a higher expression of antioxidant enzymes in females resulting in a lower yield of mitochondrial ROS. Oestrogens are made responsible for these phenomena. Oestradiol induces glutathione peroxidase-1 and MnSOD by processes requiring the cell surface oestrogen receptor (ER) and the activation of pathways usually involved in oxidative stress response. Second, oxygen radicals produced during moderate exercise as performed during training up-regulate the expression of antioxidant enzymes in muscle cells. An increased level of these enzymes might prevent oxidative damage during exhaustive exercise and should, therefore, not be prevented by antioxidants. The relevance of these findings is discussed in the context with observations made in transgenic animals overexpressing MnSOD or catalase.
Preclinical review of anti‐tumor necrosis factor monoclonal antibodies

Objective: To review the preclinical evidence for the role of tumor necrosis factor (TNF) in the pathogenesis of septic shock and to assess the preclinical efficacy of anti-TNF therapies for this clinical problem. Data Sources: The international English language literature from 1986 to the present formed the basis for this review. MEDLINE was used to identify pertinent in vitro and animal studies pertaining to the pathobiology of TNF and the use of anti-TNF therapies, with special emphasis on antibody approaches. Study Selection: Those studies that focused on the mechanisms of action of TNF, its role in the inflammatory cascade, and the potential uses of anti-TNF therapies were emphasized. Investigations that described animal and human results served as the primary database. Data Extraction: Animal studies were selected based on the relevance of the model to the pathogenesis of the human clinical sepsis syndrome. Where they provided supportive evidence, patient studies were selected on the basis of study design. Data Synthesis: The administration of anti-TNF antibodies in baboons, monkeys, and other species that were administered lethal doses of bacteria or endotoxin suggest that this approach may limit organ damage and decrease the mortality rate caused by the septic shock syndrome. Therapy with anti-TNF monoclonal antibodies is reviewed. Conclusions: Bacterial challenge induces the release of TNF (among other mediators), which exerts both physiologic and toxic effects that may ultimately lead to organ dysfunction and death. New anti-TNF therapies such as anti-TNF antibodies appear to attenuate the injurious effects of TNF and promote survival in otherwise lethal septic shock animal models, suggesting a similar benefit might be obtained in the treatment of human septic shock. (Crit Care Med 1993; 21:S441-S446)
Organelle size control – increasing vacuole content activates SNAREs to augment organelle volume through homotypic fusion

ABSTRACT Cells control the size of their compartments relative to cell volume, but there is also size control within each organelle. Yeast vacuoles neither burst nor do they collapse into a ruffled morphology, indicating that the volume of the organellar envelope is adjusted to the amount of content. It is poorly understood how this adjustment is achieved. We show that the accumulating content of yeast vacuoles activates fusion of other vacuoles, thus increasing the volume-to-surface ratio. Synthesis of the dominant compound stored inside vacuoles, polyphosphate, stimulates binding of the chaperone Sec18/NSF to vacuolar SNAREs, which activates them and triggers fusion. SNAREs can only be activated by lumenal, not cytosolic, polyphosphate (polyP). Control of lumenal polyP over SNARE activation in the cytosol requires the cytosolic cyclin-dependent kinase Pho80–Pho85 and the R-SNARE Nyv1. These results suggest that cells can adapt the volume of vacuoles to their content through feedback from the vacuole lumen to the SNAREs on the cytosolic surface of the organelle. Highlighted Article: Accumulation of organelle content is signaled to the surface of yeast vacuoles in order to increase their storage capacity by homotypic membrane fusion.