Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of SREBP-1c in Nutritional Regulation of Lipogenic Enzyme Gene Expression*

A high carbohydrate diet up-regulates the transcription of enzymes of triglyceride biosynthesis (lipogenesis) in the mammalian liver. This treatment stimulates hepatic insulin signaling, leading to transcription of sterol regulatory element-binding protein-1c (SREBP-1c). SREBP-1c has been implicated as a major factor that up-regulates lipogenic genes in response to carbohydrate feeding. However, we presented evidence for another factor, carbohydrate response factor, which is also involved in this response, and we proposed a model wherein SREBP-1c and carbohydrate response factor are independent transcription factors that act in response to insulin and glucose, respectively. In this study, we examined the contribution of SREBP-1c to the expression of lipogenic genes in glucose- and insulin-treated primary rat hepatocytes using an inducible adenovirus system. We found that SREBP-1c overexpression leads to a modest induction of fatty acid synthase, S14, and acetyl-CoA carboxylase mRNAs to 20% (fatty acid synthase), 10% (S14), and 5% (acetyl-CoA carboxylase) of the induction seen by high glucose and insulin treatment. Restoring insulin to cells overexpressing SREBP-1c did not further increase these mRNA levels. In contrast, adenovirus-expressed SREBP-1c did not induce pyruvate kinase mRNA, suggesting that induction of this gene is SREBP-1c-independent. SREBP-1c does indeed play a role in the induction of lipogenic enzyme genes in response to insulin treatment, but it is not sufficient for the induction seen when hepatocytes are treated with insulin and high glucose.
Heat shock protein 27 delays Ca2+-induced cell death in a caspase-dependent and -independent manner in rat retinal ganglion cells.

PURPOSE Hsp27 is a well-characterized and studied antiapoptotic protein. A recent study reported that Hsp27 is upregulated in the retina after retinal ischemic preconditioning. The timing of this upregulation of Hsp27 correlates with the protective effects of the treatment. It was the goal of the current study to determine what role Hsp27 plays in this protection. METHODS The rat homologue of Hsp27 (rHsp27) was overexpressed in a transformed rat retinal ganglion cell line and subjected to ischemic stress and calcium overload. RESULTS The overexpression of rHsp27 increased cell survival and inhibited caspase-3 activation. However, the inhibition of caspase-3 alone had no effect on cell survival. Proteomic analysis after Ca(2+) overload identified four proteins that were repeatedly associated with rHsp27. These proteins include actin, Hsp70, eEF-1alpha, and SPIN-2. No association with cytochrome c or any caspase enzymes was detected. CONCLUSIONS The results indicate that Hsp27 protects the retinal cells by both caspase-dependent and -independent mechanisms.
Intuitive Toxicology: Expert and Lay Judgments of Chemical Risks

Human beings have always been intuitive toxicologists, relying on their senses of sight, taste, and smell to detect harmful or unsafe food, water, and air. As we have come to recognize that our senses are not adequate to assess the dangers inherent in exposure to a chemical substance, we have created the sciences of toxicology and risk assessment to perform this function. Yet despite this great effort to overcome the limitations of intuitive toxicology, it has become evident that even our best scientific methods still depend heavily on extrapolations and judgments in order to infer human health risks from animal data. Many observers have acknowledged the inherent subjectivity in the assessment of chemical risks and have indicated a need to examine the subjective or intuitive elements of expert and lay risk judgments. Such an examination was begun by surveying members of the Society of Toxicology and the lay public about basic toxicological concepts, assumptions, and interpretations. The results demonstrated large differences between toxicologists and laypeople, as well as differences among toxicologists working in industry, academia, and government. In addition, toxicologists were found to be sharply divided in their opinions about the ability to predict a chemical's effect on human health on the basis of animal studies. These results place the problems of risk communication in a new light. Although the survey identifies misconceptions that experts should clarify for the public, it also suggests that controversies over chemical risks may be fueled as much by limitations of the science of risk assessment and disagreements among experts as by public misconceptions.
Cell cycle and melanoma – two different tumours from the same cell type

Melanoma of the uvea of the eye and melanoma of the skin share a common cell of origin, but differ substantially in their behaviour and response to chemotherapy. There is increasing evidence that this is related to differences in their molecular phenotype, particularly in relation to the expression of cell cycle‐associated proteins. Since many cytotoxic agents act by damaging DNA, resistance is often associated with intact mechanisms which allow the neoplastic cells to arrest their growth while DNA is repaired, or to resist apoptosis in response to detection of DNA damage. p53 is important to these processes, but mutation appears to be a less common event in uveal melanoma than in skin melanoma, probably due to the lack of UV exposure in the uvea. There are also differences in proliferation‐associated proteins such as c‐myc and cyclin D1. Overexpression of the former molecule is associated with a poor prognosis in skin melanoma, but is associated with a good prognosis in uveal melanoma, although there is considerable genetic heterogeneity within each type. While prognostic studies may therefore be of little relevance to individual patients, they continue to inform our understanding of tumour biology. Copyright © 2000 John Wiley & Sons, Ltd.
DIFFERENCES BETWEEN LIPOPOLYSACCHARIDE AND DOUBLE-STRANDED RNA IN INNATE IMMUNE RESPONSES OF BV2 MICROGLIAL CELLS

Microglial cells are thought to be major inflammatory cells in the central nervous system; however, sufficient information about the effects of double-stranded RNA (dsRNA) in microglial cells is lacking. The present study compared the innate immune responses of the murine microglial cell line BV2 to dsRNA and lipopolysaccharide (LPS). It showed that the effect of dsRNA was similar to that of LPS treatment. The dsRNA induced several pro-inflammatory factors such as TNF-α, IL-6, IL-1β, and IL-1Ra. Furthermore, the expression level of COX-2 was increased after treatment with dsRNA. However, the induction level of IL-1β by dsRNA was less than those of the other cytokines that were measured. These results suggest that, although both dsRNA and LPS trigger pro-inflammatory responses, the intracellular signaling pathway and inflammation pattern of dsRNA and LPS may be different. Therefore, dsRNA produced during viral infection could precipitate neurological abnormalities through chronic inflammation.
Selective, Sustained, and Shift in Attention in Patients with Diagnoses of Schizophrenia

Attentional deficits are a prominent aspect of cognitive dysfunction in schizophrenia. The present study was designed to investigate attention deficit in a group of patients with diagnosis of schizophrenia. According to the segmental set theory suggested by Hogarty and Flesher, three aspects of attention problems, selective, sustained, and shift in attention, were studied. The 30 patients hospitalized on three psychiatric wards at Shiraz and Isfahan and 30 normal healthy subjects matched for age, sex, and years of education were administered a computerized Continuous Performance Test, Stroop Color-word Test, and Wisconsin Card Sorting test. Analysis showed patients performed more poorly than control subjects on measured aspects of attention. The acute/chronic classification did not predict differences in attention scores between subtypes of schizophrenia, while the positive/negative classification did. Paranoid, undifferentiated, and residual groups by subtypes of schizophrenia showed similar performance on the Continuous Performance Test, but were significantly different on errors on the Wisconsin Card Sorting test and on reaction time to Stroop stimuli in the incongruent color-word condition. Patients with paranoid diagnosis performed better than other subtypes on these tasks. Present results suggest that the Continuous Performance Test is valuable for differentiating of schizophrenia spectrum disorder, while scores on Stroop and Wisconsin card sorting may have better diagnostic value for differentiating subtypes of the disorder.
The political economy of cash transfers: a comparative analysis of Latin American and sub-Saharan African experiences

This paper compares the consolidated experience of conditional cash transfers in Latin America with a variety of models of cash transfers in middle- and low-income countries in sub-Saharan Africa. We review the recent literature with the aim to highlight the underlying political economy factors that have underpinned the emergence and scaling-up of various kinds of social protection strategies in the two regions. From this review, some implications and policy suggestions are drawn regarding the opportunities and challenges for cash transfers in the future.
Necrostatin‐1 inhibits Hmgb1‐IL‐23/IL‐17 pathway and attenuates cardiac ischemia reperfusion injury

Ischemia reperfusion (IR) injury is a major issue in cardiac transplantation and inflammatory processes play a major role in myocardial IR injury. Necrostatin‐1 (Nec‐1) is a small molecule capable of inhibiting RIP1 kinase activity and attenuates inflammation‐mediated tissue injury. In our study, hearts of C57Bl/6 mice were flushed and stored in cold Bretschneider solution for 8 h and then transplanted into syngeneic recipients. We found that Nec‐1 decreased cardiomyocyte necrosis and recruitment of neutrophils and macrophages. Troponin T (TnT) production on 24 h after myocardial IR injury was reduced by Nec‐1 administration. Cardiac output at 60 mmHg of afterload pressure was significantly increased in hearts with Nec‐1 administration and the cardiac allograft survival in Nec‐1‐treated animals was significantly prolonged (MST = 90 days in IR + Nec‐1 group, P < 0.05 as compared with IR group, MST = 83.5 days). Nec‐1 treatment attenuated ROS generation and increased expression of NOS2 and COX‐2. The expression of Hmgb1, IL‐23, and IL‐17A were also decreased with Nec‐1 administration. Furthermore, the decreased TnT expression induced by Nec‐1 was abrogated with exogenous Hmgb1 administration. In conclusion, Nec‐1 played a protective role in cardiomyocyte IR injury, and this was associated with inhibited Hmgb1‐IL‐23/IL‐17 pathway.
When Do Expert Teams Fail to Create Impactful Inventions?

We investigate the salience of expertise in creating high impact inventions and question experts&#8217; ability to deploy novel ideas. Specifically, we examine the relationships between expertise, component originality, and a team's structural holes&#8217; position in the collaborative network and propose that, in relative terms, expert teams create lower impact inventions if they deploy more original components and if they occupy structural holes. We test and confirm our hypotheses in a sample of semiconductor firms. In post&#8208;hoc analyses, we find a three&#8208;way interaction where the negative effect of structural holes almost disappears when an expert team experiments with original components whereas an increase in non&#8208;redundancy is detrimental when teams with high expertise use familiar components. Our findings inform a foundational view of the invention process and provide novel insights into the contingent benefits of domain expertise.
Different Brain Activation Patterns to Pain and Pain-related Unpleasantness during the Menstrual Cycle

Background:The changes in the functional magnetic resonance imaging signal during anticipation, pain stimulation, and the poststimulation periods were investigated to determine whether changes in sex hormones affect brain activity. Methods:Eighteen participants were examined twice, once in the follicular phase and once in the luteal phase. Half the participants were tested first during the follicular phase, and the other half were tested first in the luteal phase. Results:The pain and unpleasantness ratings were significantly higher in the luteal phase than in the follicular. During the anticipation of pain, the prefrontal cortices were activated during the follicular phase, whereas the parahippocampal gyrus and amygdala were activated during the luteal phase. During the pain stimulation, putamen and cerebellum and precentral gyrus involving motor preparation and defense mechanism related to antinociceptive behavior were activated during the follicular phase, whereas the thalamus was activated during the luteal phase. During the poststimulation periods, the prefrontal cortices were activated during the follicular phase, whereas parahippocampal gyrus was activated during the luteal phase. The temporal pole was activated during the anticipation, pain stimulation, and poststimulation periods of the luteal phase. Conclusions:During surgical and medical procedures, requirements of anesthetic and analgesic and anxiolytic drugs may be reduced during the follicular phase and increased during the luteal phase. These results highlight the need to consider the effects of the sex hormones in women when designing clinical or neuroimaging studies or when treating patients for pain and pain-related unpleasantness.
Discovering the structure of nerve tissue: Part 3: From Jan Evangelista Purkyně to Ludwig Mauthner

ABSTRACT The previous works of Purkyně, Valentin, and Remak showed that the central and peripheral nervous systems contained not only nerve fibers but also cellular elements. The use of microscopes and new fixation techniques enabled them to accurately obtain data on the structure of nerve tissue and consequently in many European universities microscopes started to become widely used in histological and morphological studies. The present review summarizes important discoveries concerning the structure of neural tissue, mostly from vertebrates, during the period from 1838 to 1865. This review describes the discoveries of famous as well as less well-known scholars of the time, who contributed significantly to current understandings about the structure of neural tissue. The period is characterized by the first descriptions of different types of nerve cells and the first attempts of a cytoarchitectonic description of the spinal cord and brain. During the same time, the concept of a neuroglial tissue was introduced, first as a tissue for “gluing” nerve fibers, cells, and blood capillaries into one unit, but later some glial cells were described for the first time. Questions arose as to whether or not cells in ganglia and the central nervous system had the same morphological and functional properties, and whether nerve fibers and cell bodies were interconnected. Microscopic techniques started to be used for the examination of physiological as well as pathological nerve tissues. The overall state of knowledge was just a step away from the emergence of the concept of neurons and glial cells.
Functional characterization of the human tumor necrosis factor receptor p75 in a transfected rat/mouse T cell hybridoma

We investigated the biological role of the human tumor necrosis factor p75 (hTNF-R75), making use of the species specificity of TNF responses in murine (m) T cell lines. Several TNF-mediated activities on mouse T cells, such as cytokine induction or proliferation, showed a 100-500- fold difference in specific biological activity between mTNF and hTNF. After transfection of hTNF-R75 cDNA in a rat/mouse T cell hybridoma (PC60), however, the 100-fold lower specific biological activity of hTNF was converted to the same specific biological activity as mTNF. The TNF-mediated induction of granulocyte/macrophage colony-stimulating factor was strongly synergized by the addition of interleukin 1. In the presence of the latter cytokine, ligand-competing monoclonal antibodies against hTNF-R75 (utr-1, utr-2, utr-3) were agonistic on transfected PC60 cells. This agonistic activity was further enhanced by crosslinking with sheep anti-murine immunoglobulin antibodies. These data provide direct evidence for a functional role of TNF-R75, without ligand-dependent TNF-R55 involvement, in the induction of cytokine secretion in T cells.
Mechanisms of Arsenic Hyperaccumulation in Pteris vittata. Uptake Kinetics, Interactions with Phosphate, and Arsenic Speciation1

The mechanisms of arsenic (As) hyperaccumulation inPteris vittata, the first identified As hyperaccumulator, are unknown. We investigated the interactions of arsenate and phosphate on the uptake and distribution of As and phosphorus (P), and As speciation in P. vittata. In an 18-d hydroponic experiment with varying concentrations of arsenate and phosphate, P. vittata accumulated As in the fronds up to 27,000 mg As kg−1 dry weight, and the frond As to root As concentration ratio varied between 1.3 and 6.7. Increasing phosphate supply decreased As uptake markedly, with the effect being greater on root As concentration than on shoot As concentration. Increasing arsenate supply decreased the P concentration in the roots, but not in the fronds. Presence of phosphate in the uptake solution decreased arsenate influx markedly, whereas P starvation for 8 d increased the maximum net influx by 2.5-fold. The rate of arsenite uptake was 10% of that for arsenate in the absence of phosphate. Neither P starvation nor the presence of phosphate affected arsenite uptake. Within 8 h, 50% to 78% of the As taken up was distributed to the fronds, with a higher translocation efficiency for arsenite than for arsenate. In fronds, 49% to 94% of the As was extracted with a phosphate buffer (pH 5.6). Speciation analysis using high-performance liquid chromatography-inductively coupled plasma mass spectroscopy showed that >85% of the extracted As was in the form of arsenite, and the remaining mostly as arsenate. We conclude that arsenate is taken up by P. vittata via the phosphate transporters, reduced to arsenite, and sequestered in the fronds primarily as As(III).
Bioactivity and Platelet Adhesion Study of a Human Thrombomodulin-Immobilized Nitinol Surface

Nitinol is a newly developed biomaterial that is gaining popularity in many biomedical applications. It has been reported that nitinol would not induce an inflammatory response and repulsion by the immunization after implantation in the human body. Besides, nitinol is a kind of shape memory alloy, which can memorize shapes at different temperatures. This can improve the convenience in surgery. However, nitinol has poor blood compatibility, so that further modification was needed to improve the antithrombogenicity. Human thrombomodulin (hTM), an endothelial-cell-associated glycoprotein, can be considered as a natural potent anticoagulant by converting thrombin from a procoagulant protease to an anticoagulant. In this study, the surface of nitinol was pre-activated by utilizing silanization with amino-terminated silane. The incorporated amino groups were available for the subsequent covalent immobilization of hTM by 2,4,6-trichloro-1,3,5-triazine (TCT), the coupling reagent. The surface density of immobilized hTM was determined by the Bradford method. The bioactivity of immobilized hTM and blood compatibility of various nitinol substrates were evaluated by the protein C activation assay and platelet adhesion test. It was observed that the immobilized hTM still had the ability to enhance protein C activation, though its activity was lower than the free hTM in solution. Furthermore, the platelet adhesion test showed that only a few platelets were adhered on the hTM-immobilized nitinol substrate. Therefore, the immobilization of thrombomodulin onto nitinol substrate could improve the blood compatibility of nitinol and might have the potential of application in antithrombogenic medical applications.
Phase 2 study of the safety and efficacy of vicriviroc, a CCR5 inhibitor, in HIV-1-Infected, treatment-experienced patients: AIDS clinical trials group 5211.

BACKGROUND Vicriviroc, an investigational CCR5 inhibitor, demonstrated short-term antiretroviral activity in a phase 1 study. METHODS The present study was a double-blind, randomized phase 2 study of vicriviroc in treatment-experienced, human immunodeficiency virus (HIV)-infected subjects experiencing virologic failure while receiving a ritonavir-containing regimen with an HIV-1 RNA level >or=5000 copies/mL and CCR5-using virus. Vicriviroc at 5, 10, or 15 mg or placebo was added to the failing regimen for 14 days, after which the antiretroviral regimen was optimized. The primary end point was the change in plasma HIV-1 RNA levels at day 14; secondary end points included safety/tolerability and HIV-1 RNA changes at week 24. RESULTS One hundred eighteen subjects were randomized with a median HIV-1 RNA level of 36,380 (4.56 log(10)) copies/mL and a median CD4 cell count of 146 cells/mm(3). At 14 days and 24 weeks, mean changes in HIV-1 RNA level (log(10) copies/mL) were greater in the vicriviroc groups (-0.87 and -1.51 [5 mg], -1.15 and -1.86 [10 mg], and -0.92 and -1.68 [15 mg]) than in the placebo group (+0.06 and -0.29) (P<.01). Grade 3/4 adverse events were similar across groups. Malignancies occurred in 6 subjects randomized to vicriviroc and in 2 to placebo. CONCLUSIONS In HIV-1-infected, treatment-experienced patients, vicriviroc demonstrated potent virologic suppression through 24 weeks. The relationship of vicriviroc to malignancy is uncertain. Further development of vicriviroc in treatment-experienced patients is warranted.
Differential Cardiovascular and Renal Responses Produced by Microinjection of the κ-Opioid U-50488H [(trans-3,4-Dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzene-acetamide) Methane Sulfonate] into Subregions of the Paraventricular Nucleus

κ-Opioids produce a centrally mediated diuresis, antinatriuresis, and renal sympathoexcitation in vivo; however, the specific brain sites mediating these responses are unknown. This study examined the role of the hypothalamic paraventricular nucleus (PVN) and the renal sympathetic nerves in mediating the cardiovascular and renal responses to central κ-opioid receptor activation. In ketamine/xylazine-anesthetized rats, bilateral microinjection of the selective κ-agonist U-50488H [(trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzene-acetamide) methane sulfonate; 100 ng] into the posterior magnocellular division of the PVN significantly increased urine flow rate (control, 47 ± 9 μl/min; 40 min, 108 ± 10 μl/min) without changing urinary sodium excretion or cardiovascular function. In other animals, microinjection of U-50488H into the same site elicited a similar water diuresis without a change in renal sympathetic nerve activity. In contrast, microinjection of U-50488H (100 ng) into the parvocellular PVN produced an immediate pressor response (Δ 16 ± 3 mm Hg) that occurred with a potential baroreflex evoked bradycardia (Δ -26 ± 8 beats per minute), renal sympathoinhibition (Δ -18 ± 4%), natriuresis (Δ 38 ± 1%), and delayed (30-min) antidiuresis (Δ -22 ± 9%). These results were prevented by pretreatment with the κ-receptor antagonist nor-binaltorphimine and were not obtained when U-50488H was injected outside the PVN, or when vehicle was injected into the PVN. Together, these results demonstrate that the posterior magnocellular PVN is a brain site where central κ-opioids act to produce diuresis, presumably by inhibiting the secretion of arginine vasopressin. Alternatively, central κ-opioids evoke antinatriuresis via augmenting renal sympathetic nerve activity and/or other neurohumoral sodium retaining pathways at brain sites other than the hypothalamic PVN.