Miracle-dz/UniFAR-FTUs huggingface dataset:
Optogenetic Inhibition of Ventral Pallidum Neurons Impairs Context-Driven Salt Seeking

Salt appetite, in which animals can immediately seek out salt when under a novel state of sodium deprivation, is a classic example of how homeostatic systems interface with learned associations to produce an on-the-fly updating of motivated behavior. Neural activity in the ventral pallidum (VP) has been shown to encode changes in the value of salt under such conditions, both the value of salt itself (Tindell et al., 2006) and the motivational value of its predictive cues (Tindell et al., 2009; Robinson and Berridge, 2013). However, it is not known whether the VP is necessary for salt appetite in terms of seeking out salt or consuming salt following sodium depletion. Here, we used a conditioned place-preference procedure to investigate the effects of optogenetically inhibiting the VP on context-driven salt seeking and the consumption of salt following deprivation. Male rats learned to associate one context with sucrose and another context with less-desirable salt. Following sodium depletion, and in the absence of either sucrose or salt, we found that inhibiting the VP selectively reduced the elevation in time spent in the salt-paired context. VP inhibition had minimal effects on the consumption of salt once it was made available. To our knowledge, this is the first evidence that the VP or any brain region is necessary for the ability to use contextual cues to guide salt seeking. These results highlight a dissociation between deficit-driven reward seeking and reward consumption to replenish those deficits, with the former process being particularly sensitive to on-line VP activity. SIGNIFICANCE STATEMENT Salt appetite, in which rats will immediately seek out a once-undesirable concentrated salt solution after being depleted of bodily sodium despite never having tasted salt as a positive reward, is a phenomenon showing how animals can update their motivational goals without any new learning or conditioning. This salt-seeking behavior is also observed when the animal is presented with salt-paired cues. The neural circuitry necessary for context-driven salt-seeking behavior is unknown. We used a novel conditioned place preference procedure to show that optogenetic inhibition of the ventral pallidum (VP), a region known for processing reward, impairs context-driven salt seeking and has minimal effects on the consumption of salt itself following sodium depletion. These results highlight the importance of the VP in context-driven reward-seeking behavior.
Intramolecular Repression of Mouse Heat Shock Factor 1

ABSTRACT The pathway leading to transcriptional activation of heat shock genes involves a step of heat shock factor 1 (HSF1) trimerization required for high-affinity binding of this activator protein to heat shock elements (HSEs) in the promoters. Previous studies have shown that in vivo the trimerization is negatively regulated at physiological temperatures by a mechanism that requires multiple hydrophobic heptad repeats (HRs) which may form a coiled coil in the monomer. To investigate the minimal requirements for negative regulation, in this work we have examined mouse HSF1 translated in rabbit reticulocyte lysate or extracted from Escherichia coli after limited expression. We show that under these conditions HSF1 behaves as a monomer which can be induced by increases in temperature to form active HSE-binding trimers and that mutations of either HR region cause activation in both systems. Furthermore, temperature elevations and acidic buffers activate purified HSF1, and mild proteolysis excises fragments which form HSE-binding oligomers. These results suggest that oligomerization can be repressed in the monomer, as previously proposed, and that repression can be relieved in the apparent absence of regulatory proteins. An intramolecular mechanism may be central for the regulation of this transcription factor in mammalian cells, although not necessarily sufficient.
The effects of sex, menstrual cycle, and oral contraceptives on the number and activity of natural killer cells.

OBJECTIVES The aim of this study was to study the impact of sex, the menstrual cycle, and the use of oral contraceptives (OC) on the number and activity of natural killer (NK) cells. METHODS Both the number and the activity of NK cells were assessed per milliliter of blood, and NK activity (NKA) per NK cell and per lymphocyte was calculated. NKA was measured in each subject using a whole blood assay, which preserves the plasma and all blood cells, and using a washed blood assay, in which plasma is replaced with an artificial medium. The subjects were young (20-29 years old) women with a regular menstrual cycle (n = 39; 26 tested on both the follicular and the luteal phases), age-matched women who use OC (n = 26), and age-matched men (n = 20). RESULTS Men showed markedly and significantly higher NKA than women with regular menstrual cycles or women using OC, who had the lowest levels of NKA. No significant differences in blood concentration of NK cell were found. Differences in NKA were of similar magnitude in the whole and washed blood assays per milliliter of blood, per NK cell, or per lymphocyte. The menstrual cycle had no significant effect on activity levels of NK cells, but during the periovulatory phase, the number of NK cells per milliliter of blood increased significantly. CONCLUSIONS The observed differences are independent of the presence of serum factors during the in vitro assessment of NKA, but may be related to chronic exposure to sex steroids and to fluctuation in the NK cell expression of beta-adrenoceptors.
Expression of mitotic checkpoint proteins BUB1B and MAD2L1 in salivary duct carcinomas.

OBJECTIVE Defects in the mitotic checkpoint lead to aneuploidy and might facilitate tumorigenesis. However, the ploidy status in salivary duct carcinoma (SDC) has been reported to play limited role in prediction of prognosis. Thus, we need more reliable markers to reflect the rapid tumor progression in SDCs. We aimed here to investigate the expression of mitotic checkpoint proteins benzimidazole 1 homolog beta (BUB1B) and mitosis arrest-deficient 2 like 1 (MAD2L1) in SDCs and to determine their possible role as surrogate prognostic markers. METHODS We analyzed the clinical courses, pathologic findings and immunohistochemical profiles of mitotic checkpoint proteins (BUB1B and MAD2L1) in 27 pathologically confirmed SDCs. The expression status of BUB1B and MAD2L1 was compared with clinicopathologic factors and other molecular markers, such as TGF-beta, c-erb-B2, androgen receptor, vascular endothelial growth factor, and epidermal growth factor receptor, for prognostic significance. RESULTS High BUB1B expression was detected in 25.9% of subjects, and high MAD2L1 expression was in 55.6% of subjects. However, survival analysis revealed that mitotic checkpoint expression did not have prognostic significance in SDCs, nor did the other studied markers. Rather, the clinical variable of N classification at diagnosis (in N+ status, hazard ratio 5.19, 95% CI 1.26-21.32 for disease-free survival and hazard ratio 7.18, 95% CI 1.09-46.99 for overall survival) was strongly associated with survival and prognosis based on the Cox proportional hazard model. CONCLUSIONS Mitotic checkpoint proteins appeared to play a limited role in predicting prognosis in SDCs. Further study is required to elucidate the exact role of mitotic checkpoint proteins in SDCs.
Evidence for phosphatidylinositol 3-kinase-Akt-p7S6K pathway activation and transduction of mitogenic signals by platelet-derived growth factor in meningioma cells.

OBJECT The intracellular events transducing mitogenic signals from platelet-derived growth factor-beta (PDGFbeta) receptor tyrosine kinases are not precisely known. In this study the authors evaluated whether the phosphatidylinositol 3-kinase (PI3-K)-Akt-p70S6K pathway is expressed in meningiomas, regulates their growth, and transduces mitogenic signals of PDGF-BB. METHODS Nine meningioma tumors obtained in humans were evaluated using Western blot analysis for phosphorylated (activated) Akt and phosphorylated p70S6K. Cells cultured from seven of these meningiomas were also screened using Western blot analysis for Akt and for phosphorylated Akt and p70S6K. The authors also evaluated whether PDGF-BB stimulation of meningioma cells was associated with the phosphorylation of Akt and p70S6K known to activate these kinases. In addition, the effects of wortmannin, an inhibitor of P13-K, on proliferation and activation of Akt and p70S6K in meningioma cells stimulated with PDGF-BB were evaluated. Western blots of lysates from meningiomas demonstrated phosphorylated Akt and p70S6K. Treatment with PDGF-BB stimulated phosphorylation of Akt and p70S6K in each meningioma cell culture. Wortmannin (500 and 1000 nM) significantly decreased PDGF-BB stimulation of meningioma cells (p < 0.001) while it reduced Akt and p70S6K phosphorylation but not mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) phosphorylation. CONCLUSIONS These findings indicate that Akt and p70S6K are constitutively expressed and activated in meningioma cells and that the PI3-K-Akt-p70S6K pathway may participate in transduction of mitogenic signals in meningiomas independent of the Raf-1-MEK-1-MAPK/ERK cascade.
Does Agricultural Commercialization Affect Food Security: The Case of Crop-Producing Households in the Regions of Post-Reform Vietnam?

Agricultural commercialization remains a widely pursued approach in development projects to improve food security in low-income countries, although there is no clear scientific evidence for it. This study examines the impact of agricultural commercialization on the food security status of crop-producing households in the regions of Vietnam in the 1990s. We used the food system framework including output and input markets. We explore three indicators of commercialization: Cash crop production share (CCPS), crop output market participation share (COMPS), and crop input market participation share (CIMPS) based on fertilizer use. For food security, we looked at caloric intake and dietary diversity (Food Variety Score). We use a balanced panel data sample from the Vietnam Living Standards Survey (VLSS) of 1992/93 and 1997/98. We apply four specifications for all combinations of commercialization indicators and food security indicators for seven regions: OLS 1992/93, OLS 1997/98, pooled sample, and difference estimator. The results show that the effect of commercialization on food security is widely heterogeneous. It depends upon the commercialization indicator and the region in Vietnam. In general, there is no clear evidence for the direction of commercialization on either caloric intake or dietary diversity; however, it is clear that the impacts are generally more positive for southern regions than for northern regions of Vietnam.
Certain Forms of Matrix Metalloproteinase-9 Accumulate in the Extracellular Space after Microdialysis Probe Implantation and Middle Cerebral Artery Occlusion/Reperfusion

Matrix metalloproteinases (MMPs) are activated in focal cerebral ischemia. The activation of MMP-9 is involved in blood—brain barrier breakdown and tissue remodeling. The MMPs are released to the extracellular space, but the form and fate of secreted enzymes in brain are unknown. Using microdialysis in vivo, the authors studied whether ischemia-induced MMP-9 in brain tissue was related to free MMP-9 in the extracellular fluid. A microdialysis probe was placed into the right striatum and microdialysis was initiated 24 hours later in controls (n = 7). One hour prior to microdialysis, a group of rats (n = 7) was subjected to 1-hour occlusion of the right middle cerebral artery, followed by reperfusion. Dialysates were collected at discrete time points up to 24 hours, and subjected to zymography and Western blot analysis. The MMP-9 was released after ischemia and accumulated in the extracellular space at 24 hours (P < 0.05). Free MMP-9 forms include mainly the 95-kd proform, and, to a lesser extent, dimers and cleaved active forms (70 kd), but not the 88-kd form found in tissue. Probe implantation and microdialysis increased free MMP-9 in the dialysate. This increase was concomitant with neutrophil infiltration after the mechanical lesion, as myeloperoxidase was found by means of Western blot analysis in the brain hemisphere subjected to microdialysis (P < 0.005), and immunohistochemistry revealed the presence of myeloperoxidase stain surrounding the site of probe implantation. The results suggest that certain forms of MMP-9 are released and accumulate in the extracellular space after brain injury, and that vascular alterations and neutrophil recruitment elicit MMP-9 activation in the brain after focal ischemia and trauma.
Investigation of response inhibition in obsessive-compulsive disorder using the Hayling task

This study investigates response inhibition deficits in obsessive-compulsive disorder (OCD) by using the Hayling task. Sixteen OCD washers, 16 OCD checkers, 16 social phobic patients and 16 nonanxious controls were asked to complete sentences with either the expected word (section A: “initiation”) or an unrelated word (section B: “inhibition”). The groups did not differ in terms of section B minus section A latencies. However, OCD washers and checkers made significantly more errors (sentence-related responses) in section B than social phobic patients and controls. In the OCD patients, the frequency of these errors correlates with the total OCD severity score and the compulsion subscore, but not with the depression and anxiety scores. These findings suggest that OCD patients might present a specific deficit affecting the inhibition of a prepotent response. (JINS, 2005, 11, 776–783.)
The Role of the Medial Collateral Ligament and Posteromedial Capsule in Controlling Knee Laxity

Background The medial aspect of the knee has a complex capsular structure; the biomechanical roles of specific structures are not well understood. Hypothesis The 3 strong stabilizing structures, the superficial and deep medial collateral ligaments and the posteromedial capsule, make distinct contributions to controlling tibiofemoral laxity. Study Design Controlled laboratory study. Methods Changes in knee laxity under anterior-posterior drawer, valgus, and internal-external rotation loads were found by sequential cutting in 18 cadaveric knees. Three cutting sequences allowed the roles of the 3 structures to be seen in isolation and in combination. Some force contributions were also calculated. Results The posteromedial capsule controlled valgus, internal rotation, and posterior drawer in extension, resisting 42% of a 150-N drawer force when the tibia was in internal rotation. The superficial collateral ligament controlled valgus at all angles and was dominant from 30° to 90° of flexion, plus internal rotation in flexion. The deep collateral ligament controlled tibial anterior drawer of the flexed and externally rotated knee and was a secondary restraint to valgus. Conclusion Distinct roles in controlling tibiofemoral laxity have been found for these structures that vary according to knee flexion and tibial rotation. Clinical Relevance The restraining functions demonstrated provide new information about knee stabilization, which may allow better evaluation of structural damage at the medial aspect of the knee.
Did TARP Reduce or Increase Systemic Risk? The Effects of Government Aid on Financial System Stability

Theory suggests that government aid to banks may either reduce or increase systemic risk. We are the first to address this issue empirically, analyzing the Troubled Assets Relief Program (TARP). Analysis suggests that TARP significantly reduced contributions to systemic risk, particularly for larger and safer banks, and those in better local economies. This occurred primarily through a capital cushion channel that reduced market leverage by increasing the value of common equity. Results are robust to endogeneity and selection bias checks. Findings yield policy conclusions about whether to aid banks, the best targets for future assistance, and short-term versus long-term effects.
Treatment Targets in Inflammatory Bowel Disease: Current Status in Daily Practice.

BACKGROUND AND AIMS Recently, treatment goals in inflammatory bowel disease (IBD) in clinical trials have shifted from mainly symptom-based to more mucosa-driven. Real world data on treatment priorities are lacking. We aimed to investigate the current practice and most commonly used definitions of IBD treatment targets among Dutch gastroenterologists. METHODS Dutch gastroenterologists were asked to participate in a computer-based nation-wide survey. We asked questions on demographics, opinion and current practice regarding IBD treatment targets. RESULTS Twenty-four percent (134/556) of the respondents completed the survey. For both Crohn's disease (CD) (47.3%, 61/129) and ulcerative colitis (UC)(45%, 58/129) the main treatment goal was to achieve and maintain deep remission, defined as clinical, biochemical and endoscopic remission. Seventy-six percent of the participants use mucosal healing (MH) as a potential treatment target for IBD, whereas 22.6% use histological remission. There is no single definition for MH in IBD. The majority use Mayo score ≤ 1 in UC (52%) and 'macroscopic normal mucosa' in CD (66%). CONCLUSION More stringent and mucosa-driven treatment targets as 'deep remission' and 'mucosal healing' have found traction in clinical practice. The most commonly used definition for MH in routine practice is endoscopic MAYO score </= 1 in UC and 'macroscopic normal mucosa' in CD.
Gender differences in depression among the very old

ABSTRACT Objectives: The aim of this study was to investigate factors associated with depression among men and women aged 85 and over. Method: A population-based study was undertaken in northern Sweden. Out of 527 eligible participants, aged 85, 90 or ≥95, 363 were evaluated for depression. Data were collected from structured interviews, assessments and medical charts and from relatives and caregivers. Depression was screened for using the Geriatric Depression Scale-15 and further assessed using the Montgomerysberg Depression Rating Scale (MADRS). Results A higher proportion of women were diagnosed with depression (33% vs. 18.6%, p = 0.006). In both men and women experienced loneliness (OR 3.4 vs. 7.0) and not going outside independently (OR 2.6 vs. 26.0) were associated with depression in the final regression model. Depression among men was also independently associated with loss of a child/children during the preceeding ten years (OR 30.0). Conclusion: Depression was more common among women than among men. Experienced loneliness and not going outside independently seem to be closely related to depression in both men and women. Loss of a child seems to be the most important factor among men.
Mdy2, a ubiquitin-like (UBL)-domain protein, is required for efficient mating in Saccharomyces cerevisiae

MDY2, a gene required for efficient mating of the yeast Saccharomyces cerevisiae, was characterized in this study. The gene encodes a protein of 212 amino acids, which contains a ubiquitin-like (UBL) domain (residues 74-149). Deletion of MDY2 is associated with a five- to sevenfold reduction in mating efficiency, mainly due to defects in nuclear migration and karyogamy at the prezygotic stage. However, prior to mating pair fusion, shmoo formation is reduced by 30%, with a concomitant failure to form mating pairs. Strikingly, migration of the nucleus into the shmoo tip is also delayed or fails to occur. In addition, we show that in mdy2 mutants, microtubule bundles, as well as the microtubule end-binding protein Kar9, fail to localize properly to the shmoo tip, suggesting that the nuclear migration defect could be due to aberrant localization of Kar9. Pheromone signal transduction (as measured by FUS1 induction by α-factor) is not affected in mdy2Δ mutants and mitosis is also normal in these cells. MDY2 is not induced by mating pheromone. In vegetatively growing cells, GFP-Mdy2 is localized in the nucleus, and remains nuclear after exposure of cells to α-factor. His-tagged Mdy2 shows no evidence of the C-terminal processing typical of ubiquitin, and also localizes to the nucleus. Thus MDY2 is a novel gene, whose product plays a role in shmoo formation and in nuclear migration in the pre-zygote, possibly by interacting with other UBL-type proteins that possess ubiquitin association (UBA) domains.
Diagnostic Potential of Three-Dimensional Ultrasound-Based Virtual Cystoscopy: An Experimental Study Using Pig Bladders

Objective:We sought to investigate the feasibility of 3-dimenstional ultrasound (3D US)-based virtual cystoscopy in experimentally designed bladder phantoms using pig bladders. Materials and Methods:Ten bladder phantoms with simulated polypoid tumors of different sizes were constructed to provide 3D US-based virtual cystoscopic images. The simulated polypoid tumors were divided by their location into 2 groups: group 1 included the polyps on the anterior and posterior walls, and group 2 included those on the remaining 4 walls. Two genitourinary radiologists independently interpreted the virtual cystoscopic images, with a consensus reached for cases with discrepant results. Results:In a consensus reading, 3D US-based virtual cystoscopy detected 44 (91.7%) of 48 polypoid lesions. All lesions (n = 4) with false-negative results were 5 mm or smaller in diameter, and so the detection rate was 81.8% (18/22) for lesions 5 mm or smaller whereas it was 100% (26/26) for lesions larger than 5 mm. The detection rate for group 1 (93.8%) was not significantly different from that for group 2 (90.6%; P = 1.000). There were 7 false-positive lesions. Of these, 5 lesions were seen in group 1, and reverberation artifacts were the most common source of these errors (n = 4). Blind areas were present in 19 (31.7%) of 60 virtual cystoscopic images and were seen only in group 2. The differences in the false-positive rate and the incidence of blind area were statistically significant between both groups (P = 0.036, P = 0.00008, respectively). Conclusion:3D US-based virtual cystoscopy may have diagnostic potential in the detection of polypoid bladder tumors.
Citizen support for European Union membership: the role of socialisation experiences

Abstract The article explores whether European Union membership has a socialisation effect on citizens’ attitudes towards their country’s membership of the EU. Using a sample of 15 Western European countries, it is shown that this is the case. First, evidence is provided of a positive lifelong socialisation effect: citizen support for their country’s membership of the EU increases with years spent living in an EU member state. Second, it is shown that those who joined the EU during their formative years are less supportive of the EU, whilst those who spent their formative years in a non-democracy are more positive about EU membership. The size of these effects is very small in comparison to that found for the lifelong socialisation effect, suggesting that the lifelong socialisation process of continued EU membership is much more important for EU attitudes. This study offers new insights into the formation of EU attitudes.