Miracle-dz/UniFAR-FTUs huggingface dataset:
The effects of dietary lipid manipulation on the production of murine T cell-derived cytokines.

Lymphocytes play an important part in the development and progression of a number of autoimmune and inflammatory disorders, which are characterized by the presence of activated T cells and cytokines at the site of tissue injury and in the circulation. There has been considerable interest in using dietary polyunsaturated fatty acids (PUFA), particularly the n-3 PUFA found in fish oils, in the therapy of these conditions; such therapies aim, primarily, to suppress T-lymphocyte activity. While several studies have investigated the effects of fatty acids on the production of monocyte- and macrophage-derived cytokines, few have investigated their effects on the production of T cell-derived cytokines. Each of these studies have been restricted to IL-2 and have produced results which are not entirely clear. Moreover, there have been no studies to investigate the effects of dietary lipids other than fish oils on IL-2 production or the effects of dietary lipids on lymphokines other than IL-2. To investigate the effects of dietary lipid manipulation on the production of IL-2, IL-4, IL-10 and IFN-gamma by lymphocytes, mice were fed for 8 weeks on a low fat (LF) diet or one of 4 high fat diets, which contained 20% (by weight) hydrogenated coconut oil (HCO), olive oil (OO), safflower oil (SO) or menhaden oil (MO). Culture medium of lymphocytes from mice fed the OO or SO diets contained significantly more IL-2 than that of lymphocytes from mice fed the LF or HCO diets. (ABSTRACT TRUNCATED AT 250 WORDS)
Activation of Hypoxic Response in Human Embryonic Stem Cell–Derived Embryoid Bodies

Oxygen tension can provide an important determinant for differentiation and development of many cells and tissues. Genetic regulation of hemato-endothelial commitment is known to respond to oxygen deprivation via stimulation of hypoxia inducible factors (HIFs). Here, we use a closed bioreactor system to monitor and control the dissolved oxygen during differentiation of human embryonic stem cells (hESCs) via formation of embryoid bodies (hEBs). Exposing hESC-derived EBs to ambient oxygen at or below 5% results in stabilization of HIF-1α and increased transcription of hypoxic responsive genes. Interestingly, we find that rather than HIF-1α expression being stable over prolonged (7–16 days) culture in hypoxic conditions, HIF-1α expression peaks after approximately 48 hours of hypoxic exposure, and then declines to near undetectable levels, despite constant hypoxic exposure. This transient stabilization of HIF-1α during hESC-derived EB culture is demonstrated for four distinct stages of differentiation. Furthermore, we demonstrate hEB cell expansion is slowed by hypoxic exposure, with increased apoptosis. However, hEB cell proliferation returns to normal rates upon return to normoxic conditions. Therefore, although hypoxia effectively stimulates hypoxic responsive genes, this single variable was not sufficient to improve development of hemato-endothelial cells from hESCs.
Effects of krill oil and lean and fatty fish on cardiovascular risk markers: a randomised controlled trial

Fish consumption and supplementation with n-3 fatty acids reduce CVD risk. Krill oil is an alternative source of marine n-3 fatty acids and few studies have investigated its health effects. Thus, we compared krill oil supplementation with the intake of fish with similar amounts of n-3 fatty acids on different cardiovascular risk markers. In an 8-week randomised parallel study, thirty-six healthy subjects aged 18–70 years with fasting serum TAG between 1·3 and 4·0 mmol/l were randomised to receive either fish, krill oil or control oil. In the fish group, subjects consumed lean and fatty fish, according to dietary guidelines. The krill and control group received eight capsules per d containing 4 g oil per d. The weekly intake of marine n-3 fatty acids from fish given in the fish group and from krill oil in the krill group were 4103 and 4654 mg, respectively. Fasting serum TAG did not change between the groups. The level of total lipids (P = 0·007), phospholipids (P = 0·015), cholesterol (P = 0·009), cholesteryl esters (P = 0·022) and non-esterified cholesterol (P = 0·002) in the smallest VLDL subclass increased significantly in response to krill oil supplementation. Blood glucose decreased significantly (P = 0·024) in the krill group and vitamin D increased significantly in the fish group (P = 0·024). Furthermore, plasma levels of marine n-3 fatty acids increased significantly in the fish and krill groups compared with the control (all P ≤ 0·0003). In conclusion, supplementation with krill oil and intake of fish result in health-beneficial effects. Although only krill oil reduced fasting glucose, fish provide health-beneficial nutrients, including vitamin D.
Fibroblast Growth Factor Promotes Recruitment of Skeletal Muscle Satellite Cells in Young and Old Rats

Although the role of satellite cells in muscle growth and repair is well recognized, understanding of the molecular events that accompany their activation and proliferation is limited. In this study, we used the single myofiber culture model for comparing the proliferative dynamics of satellite cells from growing (3-week-old), young adult (8- to 10-week-old), and old (9- to 11-month-old) rats. In these fiber cultures, the satellite cells are maintained in their in situ position underneath the fiber basement membrane. We first demonstrate that the cytoplasm of fiber-associated satellite cells can be monitored with an antibody against the extracellular signal regulated kinases 1 and 2 (ERK1 and ERK2), which belong to the mitogen-activated protein kinase (MAPK) superfamily. With this immunocytological marker, we show that the satellite cells from all three age groups first proliferate and express PCNA and MyoD, and subsequently, about 24 hr later, exit the PCNA+/MyoD+ state and become positive for myogenin. For all three age groups, fibroblast growth factor 2 (FGF2) enhances by about twofold the number of satellite cells that are capable of proliferation, as determined by monitoring the number of cells that transit from the MAPK+ phenotype to the PCNA+/MAPK+ or MyoD+/MAPK+ phenotype. Furthermore, contrary to the commonly accepted convention, we show that in the fiber cultures FGF2 does not suppress the subsequent transition of the proliferating cells into the myogenin+ compartment. Although myogenesis of satellite cells from growing, young adult, and old rats follows a similar program, two distinctive features were identified for satellite cells in fiber cultures from the old rats. First, a large number of MAPK+ cells do not appear to enter the MyoD-myogenin expression program. Second, the maximal number of proliferating satellite cells is attained a day later than in cultures from the young adults. This apparent “lag” in proliferation was not affected by hepatocyte growth factor (HGF), which has been implicated in accelerating the first round of satellite cell proliferation. HGF and FGF2 were equally efficient in promoting proliferation of satellite cells in fibers from old rats. Collectively, the investigation suggests that FGF plays a critical role in the recruitment of satellite cells into proliferation.
P 2 purinoceptors regulate calcium-activated chloride and fluid transport in 31 EG 4 mammary epithelia

Blaug, Sasha, Jodi Rymer, Stephen Jalickee, and Sheldon S. Miller. P2 purinoceptors regulate calcium-activated chloride and fluid transport in 31EG4 mammary epithelia. Am J Physiol Cell Physiol 284: C897–C909, 2003. First published November 27, 2002; 10.1152/ajpcell.00238. 2002. —It has been reported that secretory mammary epithelial cells (MEC) release ATP, UTP, and UDP upon mechanical stimulation. Here we examined the physiological changes caused by ATP/UTP in nontransformed, clonal mouse mammary epithelia (31EG4 cells). In control conditions, transepithelial potential (apical side negative) and resistance were 4.4 1.3 mV (mean SD, n 12) and 517.7 39.4 cm2, respectively. The apical membrane potential was 43.9 1.7 mV, and the ratio of apical to basolateral membrane resistance (RA/RB) was 3.5 0.2. Addition of ATP or UTP to the apical or basolateral membranes caused large voltage and resistance changes with an EC50 of 24 M (apical) and 30 M (basal). Apical ATP/ UTP (100 M) depolarized apical membrane potential by 17.6 0.8 mV (n 7) and decreased RA/RB by a factor of 3. The addition of adenosine to either side (100 M) had no effect on any of these parameters. The ATP/UTP responses were partially inhibited by DIDS and suramin and mediated by a transient increase in free intracellular Ca2 concentration (427 206 nM; 15–25 M ATP, apical; n 6). This Ca2 increase was blocked by cyclopiazonic acid, by BAPTA, or by xestospongin C. 31EG4 MEC monolayers also secreted or absorbed fluid in the resting state, and ATP or UTP increased fluid secretion by 5.6 3 l cm 2 h 1 (n 10). Pharmacology experiments indicate that 31EG4 epithelia contain P2Y2 purinoceptors on the apical and basolateral membranes, which upon activation stimulate apical Ca2 dependent Cl channels and cause fluid secretion across the monolayer. This suggests that extracellular nucleotides could play a fundamental role in mammary gland paracrine signaling and the regulation of milk composition in vivo.
Mechanisms of sympathetic activation in obesity-related hypertension.

Obesity prevalence is soaring in industrialized countries and progressively increasing in the developing world. Altered patterns of nutrition and reduction in work-related energy expenditure have led to obesity becoming a truly global health issue. The central thermodynamic formulation for the origins of obesity, a mismatched energy balance equation, with an excess of dietary calorie intake over body energy expenditure, is a first step in the understanding of this phenomenon but leaves the diverse causal issues unexplored. Dietary calorie intake is modified by multiple social, economic, and cultural issues. Similarly, the reduction in energy expenditure in recent decades has complex origins, deriving from demographic and social change, which includes third-world transition from a labor-intensive agricultural economy to an industrial base, the introduction of household labor-saving devices, the popularity of transportation modes not reliant on physical effort, and from changed recreational habits, particularly in childhood (computer games instead of physical games). The prevalence of childhood obesity is escalating, having whimsically but not entirely unrealistically been attributed to “potato chips and computer chips. ” Obesity and hypertension are intimately associated, and both very commonly coexist in individual patients with insulin resistance, hyperinsulinemia, and hyperlipidemia, this clustering of adverse health factors1 being designated the metabolic syndrome. The pathophysiological mechanisms by which obesity leads to hypertension remain uncertain. Understanding these processes might, perhaps, provide a more rational basis for drug treatment of obesity-related hypertension. Attempts at reduction in body weight, although pivotal in the treatment of obesity-related hypertension, more often than not fail, so that antihypertensive drug therapy is often needed. This review analyses the proposition that obesity is characterized by activation of the sympathetic nervous system and that obesity-related hypertension is, in fact, neurogenic, being initiated and sustained by neural mechanisms. At one time, this idea would have been held to fly in the …
Permanent inhibition of viral replication induced by low dosage of human leukocyte interferon in patients with chronic hepatitis B.

Fourteen out of 28 HBsAg/HBeAg-positive carriers with chronic persistent and active hepatitis were randomly assigned to human leukocyte interferon (a-IFN) treatment for three months. The remaining 14 patients served as controls. Each treated subject received a standard i.m. dose of 0.7-1.0 X 10(5)/kg/day reference units of a-IFN for 28 consecutive days, and then the same dose twice a week for two months. This treatment regimen was well tolerated, and no remarkable side effects were recorded. At six months the number of patients who permanently lost HBV-DNA from serum was significantly higher in the treated group (p = 0.006) than in the untreated group. These results suggest that a less expensive and well tolerated treatment regimen based on low dosage of a-IFN may be as effective in producing permanent inhibition of hepatitis B virus replication as a treatment regimen based on larger dosage.
Predominance of a single genotype of Mycobacterium tuberculosis in regions of Southern Africa.

SETTING Zimbabwe and Zambia. OBJECTIVE To determine the genetic diversity of Mycobacterium tuberculosis strains isolated from tuberculosis (TB) patients in Zimbabwe and Zambia. DESIGN M. tuberculosis isolates cultured from TB patients presenting at referral hospitals in Zimbabwe and health care clinics in Zambia were characterised by IS6110 genotyping and/or spoligotyping using internationally standardised methods. Genotypic data were compared to those from Cape Town and the SpolDB3.0 database. RESULTS A predominant group of strains could be identified among 116/246 (47.2%) Zimbabwean isolates by their characteristic IS6110-banding pattern and unique spoligotype signature, where spacers 21-24, 27-30 and 33-36 were deleted. Comparison with strains from Cape Town showed that they were closely related to a family of strains present in 2.3% of Cape Town patients. Comparison of the spoligotypes with those obtained from 114 isolates from Zambia showed that 74 (65%) of these isolates had the same spoligotype signature. Spoligotypes in the SpolDB3.0 database showed that this group of strains was rarely isolated in other parts of the world, but was commonly isolated in Southern Africa. CONCLUSION A predominant group of strains infecting approximately half of the patients in the study are major contributors to the TB epidemic in this region. We have designated this group of strains the Southern Africa 1 (SAF1) family.
Conjugal Transfer of the Salmonella enterica Virulence Plasmid in the Mouse Intestine

ABSTRACT BALB/c mice were infected with two Salmonella enterica serovar Typhimurium strains, one of which lacked the virulence plasmid. Transconjugants were found at high frequencies in the mouse feces and at low frequencies in the liver and the spleen, suggesting that mating occurred in the gut. Laboratory conditions that mimic those of the small intestine (microaerophilic growth in the presence of 0.3 M NaCl) increased the frequency of virulence plasmid transfer. Sodium deoxycholate, which is found at high concentrations in the duodenum, and sodium propionate, which is abundant in the large intestine, reduced the conjugation frequency. Feces inhibited conjugation. Altogether, these observations suggested that transfer of the virulence plasmid occurred in the distal portion of the small intestine. Conjugation trials in ileal loops provided direct evidence that conjugal transfer of the Salmonella virulence plasmid occurs in the ileum in mice.
A method for studying the variability of users' thematic profile

This document aims at introducing a method for studying thematic profile variations of Internet surfer. These profiles are characterised by the extraction from a proxy cache of web pages consulted by each user. A semantic analysis of the content of these pages allows us to generate a vector that represents users’ mains interests. This way of processing is close to the Salton representation method [SAL74]. One vector is a sequence of words whose weight reflects the co-occurrence of word sets in pages. These weights are computed and updated as the learning stage analysis of pages progress. Vector is a multidimensional magnitude. To evaluate the semantic closeness between two vectors, we can apply the basic rules of linear algebra such as computing the Euclidean distance the vectors. Some works already published on this subject showed that the level of objectivity of this semantic metric was close to the judgement of real human users [LAN99]. Our goal is to study the temporal evolution of these characterised magnitudes.
A space-efficient algorithm for local similarities

Existing dynamic-programming algorithms for identifying similar regions of two sequences require time and space proportional to the product of the sequence lengths. Often this space requirement is more limiting than the time requirement. We describe a dynamic-programming local-similarity algorithm that needs only space proportional to the sum of the sequence lengths. The method can also find repeats within a single long sequence. To illustrate the algorithm's potential, we discuss comparison of a 73,360 nucleotide sequence containing the human beta-like globin gene cluster and a corresponding 44,594 nucleotide sequence for rabbit, a problem well beyond the capabilities of other dynamic-programming software.
A group‐sequential design for clinical trials with treatment selection

A group‐sequential design for clinical trials that involve treatment selection was proposed by Stallard and Todd (Statist. Med. 2003; 22:689–703). In this design, the best among a number of experimental treatments is selected on the basis of data observed at the first of a series of interim analyses. This experimental treatment then continues together with the control treatment to be assessed in one or more further analyses. The method was extended by Kelly et al. (J. Biopharm. Statist. 2005; 15:641–658) to allow more than one experimental treatment to continue beyond the first interim analysis. This design controls the familywise type I error rate under the global null hypothesis, that is in the weak sense, but may not strongly control the error rate, particularly if the treatments selected are not the best‐performing ones. In some cases, for example when additional safety data are available, the restriction that the best‐performing treatments continue may be unreasonable. This paper describes an extension of the approach of Stallard and Todd that enables construction of a group‐sequential design for comparison of several experimental treatments with a control treatment. The new method controls the type I error rate in the strong sense if the number of treatments included at each stage is specified in advance, and is indicated by simulation studies to be conservative when the number of treatments is chosen based on the observed data in a practically relevant way. Copyright © 2008 John Wiley & Sons, Ltd.
RELATIONSHIP BETWEEN POSTPRANDIAL ENDOTOXEMIA IN PRE- AND POST MENOPAUSAL WOMEN AFTER A FAT OVERLOAD

Bacterial endotoxemia has been associated with postprandial lipemia, though this relation is not fully understood. The objective of this study was designed to test the hypothesis that young premenopausal (PrW) and postmenopausal women (PoW) may be independently associated with postprandial endotoxemia and indirectly associated with atherosclerosis. The lipopolysaccharide (LPS) levels and circulating lipopolysaccharide-binding protein (LBP) were determined in serum at fasting, 1 hr, 2 hrs, 3 hrs, and 4 hrs after a fat overload and their levels related with postprandial lipid levels in 70 premenopausal women and 70 post-menopausal women. The postmenopausal women with the highest postprandial hypertriglceridemia showed a significant increase in LPS levels and circulating LBP in serum after the fat overload. Elevated LPS and circulating LBP was associated significantly with PoW, especially after a fat overload. These findings suggested a role of LPS and LBP in atherosclerosis. Prospective studies are needed to confirm these results.
Diabetic Macular Edema

Diabetic retinopathy is one of the major complications of diabetes mellitus and a leading cause of visual loss. Diabetic macular edema (DME) is an ocular manifestation of the disease causing visual deterioration. The prevalence of visual impairment due to DME is estimated to be 5.4% in Europe. Vascular endothelial growth factor (VEGF) is overexpressed in diabetic eyes and plays a key role in the development of DME. VEGF levels were proven to be elevated in the vitreous and retina in patients with diabetic retinopathy. VEGF causes a breakdown of the blood-retinal barrier by influencing the tight junctions of retinal endothelial cells and leading to accumulation of fluid in the macula. Therefore, intravitreal VEGF inhibitors are ideal candidates to treat DME by counteracting VEGF overexpression. This review summarizes the results of the most recent prospective, controlled studies on DME with promising novel VEGF inhibitors. It focuses on the efficacy and safety aspects of anti-VEGF treatment of DME.
Mutational Analysis of the Roles of Residues in Escherichia coli Elongation Factor Ts in the Interaction with Elongation Factor Tu*

The crystal structure of the Escherichia coli elongation factor (EF)-Tu·Ts complex indicates that there are extensive contacts between EF-Tu and EF-Ts. To determine the importance of these contacts in the interaction between E. coli EF-Tu and EF-Ts, residues in EF-Ts at the interface of these two proteins were mutated. The binding constants governing the interaction of the resulting EF-Ts variants with E. coliEF-Tu were determined. The effects of these mutations on the ability of EF-Ts to stimulate GDP exchange with EF-Tu·GDP and on its ability to stimulate the activity of EF-Tu in polymerization were tested. The results indicate that Arg-12, Met-19, and Met-20 in the N-terminal domain of EF-Ts and His-147 and Lys-166 and/or His-167 in subdomain C of EF-Ts are crucial in the interaction between EF-Tu and EF-Ts. Lys-23, Val-234, Met-235, and the C-terminal helix h13 are less important. The binding constants of the EF-Ts variants governing their interactions with EF-Tu correlate well with their activities in stimulating GDP exchange with EF-Tu. Mutations prepared in EF-Tu indicate that His-19 and Gln-114 but not Glu-348 in EF-Tu are moderately important for its interaction with EF-Ts.
Death-associated Protein 6 (Daxx) Mediates cAMP-dependent Stimulation of Cyp11a1 (P450scc) Transcription*

Background: HIPK3 mediates cAMP signaling and stimulates SF-1 activity to activate Cyp11a1 transcription. Results: In response to cAMP, HIPK3 phosphorylates Daxx, leading to JNK/c-Jun activation and the enhancement of SF-1-dependent Cyp11a1 expression. Conclusion: Daxx mediates HIPK3 effect to activate JNK/c-Jun for SF-1-dependent Cyp11a1 expression. Significance: The cAMP signaling pathway for the activation of the steroidogenic gene Cyp11a1 uses the apoptotic pathway components HIPK3/Daxx/JNK/c-Jun. SF-1 is a key transcription factor for all steroidogenic genes. It up-regulates the expression of the steroidogenic Cyp11a1 gene in the adrenal in a pathway stimulated by cAMP through HIPK3-mediated JNK/c-Jun phosphorylation. In the present study, we have investigated the factors mediating cAMP-dependent HIPK3 action to potentiate the activity of SF-1 for Cyp11a1 transcription in mouse adrenocortical Y1 cells. We found Daxx, a HIPK kinase substrate in the apoptosis pathway, was phosphorylated by HIPK3 at Ser-669 in response to cAMP stimulation. Daxx participated in SF-1-dependent Cyp11a1 expression as shown by experiments involving both overexpression and down-regulation via a dominant negative Daxx mutant. The S669A mutant of Daxx, which could not be phosphorylated by HIPK3, lost the ability to potentiate SF-1 activity for Cyp11a1 expression. The enhancement of SF-1 activity by Daxx required JNK and c-Jun phosphorylation. Thus, Daxx functioned as a signal transducer linking cAMP-stimulated HIPK3 activity with JNK/c-Jun phosphorylation and SF-1-dependent Cyp11a1 transcription for steroid synthesis.