Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential Expression and Activity Status of MMP-1, MMP-2 and MMP-9 in Tumor and Stromal Cells of Squamous Cell Carcinomas of the Lung

Matrix metalloproteinases (MMPs) play a key role in cancer progression. Interstitial collagenase (MMP-1) and type IV collagenases (MMP-2, MMP-9) are involved in the initial breakdown of collagen and basement membrane components during tumor growth and invasion. Besides tumor cells, fibroblasts are especially involved in MMP production. The aim of this study was to quantify MMP-1, MMP-2 and MMP-9 within tumor cells and tumor-surrounding fibroblasts compared to normal lung epithelial cells to gain an insight into the function of these MMPs in squamous cell carcinomas of the lung. The expression and activity of MMP-1, MMP-2 and MMP-9 were analyzed in 30 squamous cell carcinomas and in normal lung tissue from the same patients by immunohistology and gelatin zymography. The majority of tumor cells were positive for MMP-1 (mean ± SD: 67.3 ± 26.7%) and MMP-9 (64.7 ± 22.8%), whereas a significantly lower percentage of normal bronchoepithelial cells (47.3 ± 25.4 and 40.3 ± 24.2%, respectively; p < 0.01) and fibroblasts located in the tumor-surrounding tissue (39.7 ± 14.3 and 38.1 ± 24.1%, respectively; p < 0.01) expressed these MMPs. Only a few tumor cells showed any immunoreactivity for MMP-2 (4.4 ± 6.7%), whereas a higher percentage of fibroblasts tested positive for this enzyme (8.6 ± 13.1%; p < 0.01). Using gelatin zymography, we could demonstrate that MMP-2 is activated in the tumor only, not in normal lung tissue. The coordinated expression of MMP-1, MMP-2 and MMP-9 in tumor cells and/or their induction in tumor-surrounding fibroblasts and further activation in the tumor tissue may be involved in the high invasive and metastatic potential of squamous cell carcinomas of the lung. Comparing the results from immunohistology and zymography can give indications for distribution and activity of proteinases, especially certain MMPs such as MMP-2.
Validation and Psychometric Properties of the Alcohol Positive and Negative Affect Schedule: Are Drinking Emotions Distinct From General Emotions?

People vary in experiences of positive and negative emotions from consuming alcohol, but no validated measurement instrument exclusively devoted to assessing drinking emotions exists in the literature. The current research validated and evaluated the psychometric properties of an alcohol affect scale based on adjectives from the Positive and Negative Affect Schedule (PANAS) and tested the extent that emotions incurred from drinking were distinct from general trait-based emotions. Three studies tested independent samples of adult alcohol users. In Study 1 (N = 494), exploratory factor analyses of the Alcohol PANAS revealed that both the 20-item model and the 9-parcel model (represented by similar mood content) supported the 2-factor dimensionality of alcohol positive and negative affect. In Study 2 (N = 302), confirmatory factor analyses corroborated the measurement structure of alcohol positive and negative affect, and both constructs evidenced statistical independence from general positive and negative affect. In Study 3 (N = 452), alcohol positive and negative affect exhibited discriminant, convergent, and criterion validity with established alcohol scales. Incremental validity tests demonstrated that alcohol positive and negative affect uniquely contributed (beyond general positive and negative affect) to alcohol expectancies, use, and problems. Findings support that alcohol emotions are conceptually distinct from trait emotions, and underscore the necessity of an assessment instrument tailored to the former to examine associations with alcohol beliefs and behaviors. The Alcohol PANAS confers theoretical and practical applications to understand the emotional consequences of drinking.
A theoretical approach to facilitating transition phase motion in a positively buoyant autonomous underwater vehicle

Positively buoyant autonomous underwater vehicles (AUVs) operate at survey speeds with a pitch angle that is maintained through application of the control surfaces, sufficient to generate hydrodynamic forces to counteract the excess buoyancy. To facilitate lower forward speeds and the ability to hover requires some additional method of control. This paper reviews possible options and then indicates how control can be achieved using a single or pair of through-body tunnel thrusters. New equations appropriate to AUVs are proposed and experimental results are used to estimate the equation parameters. These equations are used within a simulation of the Autosub AUV to determine the response of the AUV during the transition between survey and low speed operation. The results obtained from the simulations are analysed in terms of the performance of the AUV and the demanded energy levels to assess the feasibility of using tunnel thrusters as a low speed control device.
Distinct Neocortical Progenitor Lineages Fine‐tune Neuronal Diversity in a Layer‐specific Manner

&NA; How the variety of neurons that organize into neocortical layers and functional areas arises is a central question in the study of cortical development. While both intrinsic and extrinsic cues are known to influence this process, whether distinct neuronal progenitor groups contribute to neuron diversity and allocation is poorly understood. Using in vivo genetic fate‐mapping combined with whole‐cell patch clamp recording, we show that the firing pattern and apical dendritic morphology of excitatory neurons in layer 4 of the barrel cortex are specified in part by their neural precursor lineage. Further, we show that separate precursors contribute to unique features of barrel cortex topography including the intralaminar position and thalamic innervation of the neurons they generate. Importantly, many of these lineage‐specified characteristics are different from those previously measured for pyramidal neurons in layers 2‐3 of the frontal cortex. Collectively, our data elucidate a dynamic temporal program in neuronal precursors that fine‐tunes the properties of their progeny according to the lamina of destination.
Differential sites of action of 8OHDPAT, a 5HT1A agonist, on ACTH and PRL secretion in the rat.

We recently obtained evidence that activation of the 5HT1A subtype receptor enhances both plasma ACTH and prolactin (PRL) concentrations in rats. In order to explore the possible neuroanatomical structures involved in this interaction, we examined ACTH and PRL responses to intracerebral infusions of the 5HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8OHDPAT). In addition we also tested in vitro effects of 8OHDPAT added to the perifusion medium of pituitary cells or of hypothalamic slices on hormone or neurotransmitter release, respectively. The ACTH response to 8OHDPAT (0.1 mg/kg) was decreased after depletion of endogenous 5HT stores by p-chlorophenylalanine (PCPA) treatment. In contrast, the PRL response was markedly increased under that condition. Infusion of 8OHDPAT (1 microgram/microliter/15 min) into the dorsal raphe nucleus induced a slow elevation of ACTH release but was ineffective on PRL secretion while infusion of 8OHDPAT into the PVN induced a moderate elevation of both ACTH and PRL. After bilateral destruction of the PVN, PRL response to 8OHDPAT (0.1 and 0.25 mg/kg) was markedly potentiated. In contrast, PVN-lesioned animals showed a blunted ACTH response to 8OHdPAT. Basal or CRF-stimulated ACTH secretion rates from perifused dispersed adenohypophyseal cells were not affected by 8OHDPAT but the 5HT1A agonist induced a very slight and transient inhibition of PRL release. 8OHDPAT antagonized, in a dose-dependent manner, the K(+)-induced release of 3H-DA previously taken up in neurons of mediobasal hypothalamic slices. This data suggests that major sites of 5HT1A interaction in PRL and ACTH regulation are located within the CNS and not in the pituitary. (ABSTRACT TRUNCATED AT 250 WORDS)
Double Jeopardy: Workplace Hazards and Behavioral Risks for Craftspersons and Laborers

Purpose. To address three specific questions in a sample of craftspersons and laborers: (1) Do craftspersons and laborers exposed to workplace hazards have higher behavioral risks, such as smoking and high-fat diets, than those with few job risks? (2) Compared to workers with few job risks, do workers exposed to risks on the job have higher intentions to reduce their behavioral risks? (3) Does concern about the level of exposure to risks on the job increase workers' intentions to reduce behavioral risks? Design. A cross-sectional self-administered survey was conducted in participating worksites. Setting. Twenty-two predominantly manufacturing worksites in Massachusetts. Subjects. Craftspersons and laborers responding to the survey and employed in these 22 worksites (completion rate = 61%, N = 1841). Measures. By using standardized items, this survey measured self-reported exposure to workplace hazards, concern about job exposures, smoking status, fat and fiber intake, readiness to quit smoking, plans to reduce fat intake, plans to eat more fruits and vegetables, and sociodemographic variables. Results. Workers reporting exposure to chemical hazards on the job were significantly more likely to be smokers than were unexposed workers, even when results were controlled for gender. Compared with unexposed workers, smokers exposed to chemical hazards were significantly more likely to be thinking of quitting or taking action to quit, when results were controlled for gender, race, and education. Among workers exposed to occupational chemical hazards, concern about this exposure was significantly associated with intentions to decrease fat intake and increase fruit and vegetable intake, and, among men, intentions to quit smoking. Conclusions. Efforts aimed at integrating health promotion and health protection are needed to address simultaneously the job risks and personal risks these workers face.
In vitro and ex vivo 13C-NMR Spectroscopy Studies of Pyruvate Recycling in Brain

Pyruvate recycling is a well established pathway in the liver, but in the brain, the cellular localization of pyruvate recycling remains controversial and its physiological significance is unknown. In cultured cortical astrocytes, pyruvate formed from [U-13C]glutamate was shown to re-enter the TCA cycle after conversion to acetyl-CoA, as demonstrated by the labelling patterns in aspartate C-2 and C-3, lactate C-2, and glutamate C-4, which provides evidence for pyruvate recycling in astrocytes. This finding is in agreement with previous studies of astrocytic cultures, in which pyruvate recycling has been described from [U-13C]glutamine, in the presence of glutamate, and from [U-13C]aspartate. Pyruvate recycling in brain was studied in fasted rats receiving either an intraperitoneal or a subcutaneous injection of [1,2-13C]acetate followed by decapitation 30 min later. Extracts of cortical tissue were analysed with 13C-NMR spectroscopy and total amounts of amino acids quantified by HPLC. Plasma extracts were analysed with 1H- and 13C-NMR spectroscopy, and showed a significantly larger amount of [1,2-13C]acetate in the intraperitoneal group compared to the subcutaneous group. Furthermore, a small amount of label was detected in glucose in both groups. In the subcutaneously injected rats, [4-13C]glutamate and [2-13C]GABA were less enriched than plasma glucose, which might have been the precursor. In the intraperitoneally injected rats, however, pyruvate formation from [1,2-13C]acetate, and re-entry of this pyruvate into the TCA cycle was demonstrated by the presence of greater 13C enrichment in [4-13C]glutamate and [4-13C]glutamine compared to the subcutaneous group, probably resulting from the significantly higher [1,2-13C]acetate concentration in brain and plasma.
Association Between Stress-Related Sleep Reactivity and Metacognitive Beliefs About Sleep in Insomnia Disorder: Preliminary Results

To evaluate the relation between stress-related sleep reactivity and metacognitive beliefs about sleep in subjects with insomnia disorder (93) and in a group of healthy controls (30) a set of variables, including Ford Insomnia Response to Stress Test (FIRST) and Metacognition Questionnaire–Insomnia (MCQ-I), have been used. Internal consistency of the Italian version of FIRST was studied. Univariate correlation, regression analysis, and principal component analysis were also performed. The Italian version of FIRST showed good internal consistency and discriminant validity. Sleep reactivity was higher in women (p < .05) and correlates positively in both genders with metacognitive beliefs about sleep (p < .01) in insomnia. In insomnia, metacognitive beliefs may play a key role in modulating sleep reactivity. Therapeutic strategies acting selectively on metacognition to reduce stress-related sleep reactivity in insomnia may be useful.
Basal blood DHEA-S/cortisol levels predicts EMDR treatment response in adolescents with PTSD

Abstract Objective: In literature, recent evidence has shown that the hypothalamic–pituitary–adrenal (HPA) axis can be dysregulated in patients with post-traumatic stress disorder (PTSD) and HPA axis hormones may predict the psychotherapy treatment response in patients with PTSD. In this study, it was aimed to investigate changing cortisol and DHEA-S levels post-eye movement desensitization and reprocessing (EMDR) therapy and the relationship between treatment response and basal cortisol, and DHEA-S levels before treatment. Method: The study group comprised 40 adolescents (age, 12–18 years) with PTSD. The PTSD symptoms were assessed using the Child Depression Inventory (CDI) and Child Post-traumatic Stress Reaction Index (CPSRI) and the blood cortisol and DHEA-S were measured with the chemiluminescence method before and after treatment. A maximum of six sessions of EMDR therapy were conducted by an EMDR level-1 trained child psychiatry resident. Treatment response was measured by the pre- to post-treatment decrease in self-reported and clinical PTSD severity. Results: Pre- and post-treatment DHEA-S and cortisol levels did not show any statistically significant difference. Pre-treatment CDI scores were negatively correlated with pre-treatment DHEA-S levels (r: −0.39). ROC analysis demonstrated that the DHEA-S/cortisol ratio predicts treatment response at a medium level (AUC: 0.703, p: .030, sensitivity: 0.65, specificity: 0.86). Conclusion: The results of this study suggested that the DHEA-S/cortisol ratio may predict treatment response in adolescents with PTSD receiving EMDR therapy. The biochemical parameter of HPA-axis activity appears to be an important predictor of positive clinical response in adolescent PTSD patients, and could be used in clinical practice to predict PTSD treatment in the future.
Graspable Objects Grab Attention More Than Images Do

The opportunity an object presents for action is known as an affordance. A basic assumption in previous research was that images of objects, which do not afford physical action, elicit effects on attention and behavior comparable with those of real-world tangible objects. Using a flanker task, we compared interference effects between real graspable objects and matched 2-D or 3-D images of the items. Compared with both 2-D and 3-D images, real objects yielded slower response times overall and elicited greater flanker interference effects. When the real objects were positioned out of reach or behind a transparent barrier, the pattern of response times and interference effects was comparable with that for 2-D images. Graspable objects exert a more powerful influence on attention and manual responses than images because of the affordances they offer for manual interaction. These results raise questions about whether images are suitable proxies for real objects in psychological research.
Effects of triclosan on Japanese medaka (Oryzias latipes) during embryo development, early life stage and reproduction

Triclosan has been shown to have endocrine‐disrupting effects in aquatic organisms. In 2016, the US Food and Drug Administration banned the use of triclosan in consumer soaps. Before the ban, triclosan was reported at low concentrations in the aquatic environment, although the effect of triclosan on reproduction in teleost fish species is yet to be clarified. Here we investigated the effects of triclosan on embryo development and reproduction, and during the early life stage, in Japanese medaka (Oryzias latipes) by using Organisation for Economic Co‐operation and Development tests 229, 212 and 210, with minor modifications. In adult medaka, exposure to 345.7 μg l–1 suppressed fecundity and increased mortality but had no effect on fertility. Exposure to 174.1 or 345.7 μg l–1 increased liver vitellogenin concentration in females but decreased liver vitellogenin concentration in males. With triclosan exposure, mortality was increased dose dependently during the embryonic and early larval stages, and a particularly steep increase in mortality was observed soon after hatching. The lowest observed effect concentrations of triclosan in Japanese medaka obtained in the present study (mortality [embryonic and larval stages, 276.3 μg l–1; early life stage, 134.4 μg l–1; adult stage, 174.1 μg l–1], growth [134.4 μg l–1], vitellogenin [174.1 μg l–1], fecundity [345.7 μg l–1] and fertility [>345.7 μg l–1]) were at least 55 times (compared with the USA) and up to 13 400 times (compared with Germany) greater than the detected triclosan levels in the aquatic environment. These results suggest that triclosan may not be affecting fish populations in the aquatic environment.
Early Verb-Action and Noun-Object Mapping Across Sensory Modalities: A Neuro-Developmental View

ABSTRACT The authors provide an alternative to the traditional view that verbs are harder to learn than nouns by reviewing three lines of behavioral and neurophysiological evidence in word-mapping development across cultures. First, preverbal infants tune into word-action and word-object pairings using domain-general mechanisms. Second, while post-verbal infants from noun-friendly language environments experience verb-action mapping difficulty, infants from verb-friendly language environments do not. Third, children use language-specific conventions to learn all types of words, although still strongly influenced by their language environment. Additionally, the authors suggest neurophysiological research to advance these lines of evidence beyond traditional views of word learning.
Data‐driven analysis of simultaneous EEG/fMRI reveals neurophysiological phenotypes of impulse control

Response inhibition is the ability to suppress inadequate but prepotent or ongoing response tendencies. A fronto‐striatal network is involved in these processes. Between‐subject differences in the intra‐individual variability have been suggested to constitute a key to pathological processes underlying impulse control disorders. Single‐trial EEG/fMRI analysis allows to increase sensitivity for inter‐individual differences by incorporating intra‐individual variability. Thirty‐eight healthy subjects performed a visual Go/Nogo task during simultaneous EEG/fMRI. Of 38 healthy subjects, 21 subjects reliably showed Nogo‐related ICs (Nogo‐IC‐positive) while 17 subjects (Nogo‐IC‐negative) did not. Comparing both groups revealed differences on various levels: On trait level, Nogo‐IC‐negative subjects scored higher on questionnaires regarding attention deficit/hyperactivity disorder; on a behavioral level, they displayed slower response times (RT) and higher intra‐individual RT variability while both groups did not differ in their inhibitory performance. On the neurophysiological level, Nogo‐IC‐negative subjects showed a hyperactivation of left inferior frontal cortex/insula and left putamen as well as significantly reduced P3 amplitudes. Thus, a data‐driven approach for IC classification and the resulting presence or absence of early Nogo‐specific ICs as criterion for group selection revealed group differences at behavioral and neurophysiological levels. This may indicate electrophysiological phenotypes characterized by inter‐individual variations of neural and behavioral correlates of impulse control. We demonstrated that the inter‐individual difference in an electrophysiological correlate of response inhibition is correlated with distinct, potentially compensatory neural activity. This may suggest the existence of electrophysiologically dissociable phenotypes of behavioral and neural motor response inhibition with the Nogo‐IC‐positive phenotype possibly providing protection against impulsivity‐related dysfunction. Hum Brain Mapp 37:3114–3136, 2016. © 2016 Wiley Periodicals, Inc.
Sunitinib represses regulatory T cells to overcome immunotolerance in a murine model of hepatocellular cancer

ABSTRACT Successful development of immunotherapeutic strategies for hepatocellular cancer (HCC) has been impeded by limited understanding of tumor-induced profound tolerance and lack of a clinically faithful HCC model. Recently, we developed a novel model that recapitulates typical features of human HCC. Using this clinically relevant model, we demonstrate that tumor growth impairs host immunity and causes a profound exhaustion of tumor antigen-specific (TAS) CD8+ T cells. Increase in frequency and suppressive function of regulatory T cells (Tregs) is critically involved in this tumor-induced immune dysfunction. We further demonstrate that sunitinib suppresses Tregs and prevents tumor-induced immune tolerance, allowing TAS immunization to activate endogenous CD8+ T cells. As a result, this combinational strategy delays tumor growth. Importantly, the additional integration of exogenous naïve TAS CD8+ T cells by adoptive cell transfer (ACT) leads to the elimination of the established tumors without recurrence and promotes long-term survival of the treated mice. Mechanistically, sunitinib treatment primes the antitumor immune response by significantly decreasing Treg frequency, reducing TGF-β and IL-10 production by Tregs, and also protecting TAS CD8+ T cells from tumor-induced deletion in the setting of HCC. Taken together, sunitinib quantitatively and qualitatively modifies Tregs to overcome tumor-induced immune deficiency, suggesting the potential of sunitinib as a therapeutic immune activator for HCC control.
Dynamics of liver enzymes in rabbits experimentally infected with Fasciola sp. (Intermediate form from Japan)

Dynamics of serum liver enzymes in rabbits experimentally infected with metacercariae of Fasciola sp. (intermediate form between Fasciola hepatica and F. gigantica) were monitored. Gradual increase of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were observed from 3 weeks post-inoculation (WPI) and peaked at 6 WPI, which corresponded well to the period of migration and development of juvenile fluke in the liver parenchyma and the time when the young adult flukes migrated to the bile duct. However, no significant increase in serum gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) were observed. This could reflect reduced or minimal injury of bile ducts and biliary epithelia as the flukes had reached the adult stage. Alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) were not detected in the infected rabbit during the course of the experiment. Serum liver enzymes monitoring might be useful for understanding the host-parasite relationship in fascioliasis.