CSF hypocretin levels are normal in Huntington's disease patients.
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Adult↗
Biomedical subjects
Ling Lin
Publications and source records attributed to Ling Lin.
[Recognition and study of susceptible gene to ankylosing spondylitis].
To study the potential correlations between variances of TNFalpha gene and onset of ankylosing spondylitis in Chinese population, We scanned and analyzed the promoters of TNFalpha genes in 75 AS patients from south of China and found -850 T mutation allele frequency rather high (39.3%).By case-control study, the distribution of TT genotype is significantly higher in AS patients than that in normal subjects (10.7% VS 2.1%,P=0.003); Mutation T allele has a remarkable difference between AS group and normal control (72.2% vs 21.4%,P=2.729 x 10(-9)). The difference in distribution of TX genotype and non -TX genotype is also significant statistically between different genders(male: P=3.42 x 10(-9);female: P=0.001). The result suggests that this variation has a strong association with AS in males and females. No similar reports about the association between AS and the T mutation allele have been acquired. Therefore, our hypothesis can be supported by our results on the whole and the -850 C-->T mutation allele in the region on promoter of TNFalpha gene is likely one of susceptible genes to AS.
Adolescent↗
[Fluorescent characters of optical BOD sensing film].
We characterized an optical BOD sensing film used to immobilize three kinds of microorganisms from seawater. The sensing film for BOD measurement consists of an optical oxygen sensor and the microorganisms immobilized on poly(vinyl alcohol) ormosils matrix. The fluorescent responses of the BOD sensing film were obviously affected by the thickness of the oxygen film and the concentration of microorganisms in the film. Some other experimental conditions, such as pH, measurement temperature, and the concentration of sodium chloride, were studied. BOD values estimated by this optical BOD sensing film correlate well with those determined by the conventional BOD5 method for seawater samples.
Hydrogen-Ion Concentration↗
Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index.
BACKGROUND: Sleep duration may be an important regulator of body weight and metabolism. An association between short habitual sleep time and increased body mass index (BMI) has been reported in large population samples. The potential role of metabolic hormones in this association is unknown. METHODS AND FINDINGS: Study participants were 1,024 volunteers from the Wisconsin Sleep Cohort Study, a population-based longitudinal study of sleep disorders. Participants underwent nocturnal polysomnography and reported on their sleep habits through questionnaires and sleep diaries. Following polysomnography, morning, fasted blood samples were evaluated for serum leptin and ghrelin (two key opposing hormones in appetite regulation), adiponectin, insulin, glucose, and lipid profile. Relationships among these measures, BMI, and sleep duration (habitual and immediately prior to blood sampling) were examined using multiple variable regressions with control for confounding factors. A U-shaped curvilinear association between sleep duration and BMI was observed. In persons sleeping less than 8 h (74.4% of the sample), increased BMI was proportional to decreased sleep. Short sleep was associated with low leptin (p for slope = 0.01), with a predicted 15.5% lower leptin for habitual sleep of 5 h versus 8 h, and high ghrelin (p for slope = 0.008), with a predicted 14.9% higher ghrelin for nocturnal (polysomnographic) sleep of 5 h versus 8 h, independent of BMI. CONCLUSION: Participants with short sleep had reduced leptin and elevated ghrelin. These differences in leptin and ghrelin are likely to increase appetite, possibly explaining the increased BMI observed with short sleep duration. In Western societies, where chronic sleep restriction is common and food is widely available, changes in appetite regulatory hormones with sleep curtailment may contribute to obesity.
Adult↗
Insights into dynamics of the S2 state of thiophosgene from ab initio calculations.
The S2 potential energy surface for Cl2CS dissociation has been characterized with a combined complete active space self-consistent field and multireference configuration interaction method. The S3/S2 minimum-energy intersection has been determined with the state-averaged complete active space self-consistent field method. The S2 direct dissociation was found to have a barrier of 6.0 kcal/mol, leading to formation of Cl(X2P)+ClCS(A2A") in the excited electronic state. Dynamics of the S2 state of Cl2CS can be summarized as follows: (1) The S2-S0 fluorescence occurs with high quantum yield at low excess energies; (2) Both the S(2) dissociation and the S2-->S3 internal conversion cause the loss of the S2-S0 fluorescence upon photoexcitation at 235-253 nm; (3) The S2-->S3 internal conversion (IC) followed by the direct IC to the ground electronic state results in the fragments produced in the ground state, while the S2 dissociation leads to formation of the fragments in excited electronic states.
Journal Article↗
Angiotensin-converting enzyme, sleep-disordered breathing, and hypertension.
The angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism influences ACE activity, cardiovascular risk, blood pressure, and possibly the risk of developing Alzheimer's dementia. We explored the association of the insertion/deletion polymorphism with sleep-disordered breathing (SDB) and hypertension in 1,100 subjects of the Wisconsin Sleep Cohort. The polymorphism did not influence body mass index or the occurrence of SDB, but was dose-dependently associated with blood pressure. Interestingly, SDB and the insertion/deletion polymorphism interacted significantly to modulate blood pressure independently of age, sex, ethnicity, and body mass index. Most specifically, the association of the deletion allele with hypertension was most pronounced in subjects with mild to moderate degrees of sleep apnea (5 < or = apnea-hypopnea index < or = 30). We hypothesize that in the absence of SDB the effect of the deletion allele alone may not be sufficient to increase blood pressure. At severe levels of SDB, the effect of sleep apnea on blood pressure overwhelms any association of the deletion allele with hypertension and occurs independent of any ACE gene genotype.
Adult↗
Amygdala enterostatin induces c-Fos expression in regions of hypothalamus that innervate the PVN.
Enterostatin selectively inhibits the intake of the dietary fat after both central and peripheral administration. Our previous studies have shown that a central site of action is the central nucleus of amygdala. Serotonergic agonists administered into the paraventricular nucleus (PVN) inhibit fat intake and serotonergic antagonists block the feeding suppression induced by amygdala enterostatin, suggesting that there are functional connections between the PVN and amygdala that affect the feeding response to enterostatin. Our purpose was to identify the anatomic and functional projections from the amygdala to the PVN and hypothalamic area that are responsive to enterostatin, by using a retrograde tracer fluorogold (FG) and c-Fos expression. Rats were injected with fluorogold unilaterally into the PVN and a chronic amygdala cannula was implanted ipsilaterally. After 10 days recovery, rats were injected with either enterostatin (0.1 nmol) or saline vehicle (0.1 microl) into the amygdala and sacrificed 2 h later by cardiac perfusion under anesthesia. The brains were subjected to dual immunohistochemistry to visualize both FG and c-Fos-positive cells. FG/c-Fos double-labeled cells were found in forebrain regions including the PVN, amygdala, lateral hypothalamus (LH), ventral medial hypothalamus (VMH) and arcuate nucleus (ARC). The data provides the first anatomical evidence that enterostatin activates amygdala neurons that have functional and anatomic projections directly to the PVN and also activates neurons in the arcuate, LH and VMH, which innervate the PVN.
Amygdala↗
The diurnal rhythm of hypocretin in young and old F344 rats.
STUDY OBJECTIVES: Hypocretins (HCRT-1 and HCRT-2), also known as orexins, are neuropeptides localized in neurons surrounding the perifornical region of the posterior hypothalamus. These neurons project to major arousal centers in the brain and are implicated in regulating wakefulness. In young rats and monkeys, levels of HCRT-1 are highest at the end of the wake-active period and lowest toward the end of the sleep period. However, the effects of age on the diurnal rhythm of HCRT-1 are not known. DESIGN: To provide such data, cerebrospinal fluid (CSF) was collected from the cisterna magna of young (2-month-old, n = 9), middle-aged (12 months, n = 10), and old (24 months, n = 10) F344 rats at 4-hour intervals, (beginning at zeitgeber [ZT]0, lights on). CSF was collected once from each rat every 4 days at 1 ZT point. After collecting the CSF at all of the time points, the rats were kept awake by gentle handling for 8 hours (ZT 0-ZT8), and the CSF was collected again at the end of the sleep-deprivation procedure. HCRT-1 levels in the CSF were determined by radioimmunoassay SETTINGS: Basic neuroscience research lab. MEASUREMENTS AND RESULTS: Old rats had significantly less HCRT-1 in the CSF versus young and middle-aged rats (P < .002) during the lights-on and lights-off periods and over the 24-hour period. In old rats, significantly low levels of HCRT-1 were evident at the end of the lights-off period (predominantly wake-active period). The old rats continued to have less HCRT-1 even after 8 hours of prolonged waking. Northern blot analysis did not show a difference in pre-proHCRT mRNA between age groups. CONCLUSIONS: In old rats there is a 10% decline in CSF HCRT-1 over the 24-hour period. Functionally, if there is less HCRT-1, which our findings indicated, and there is also a decline in HCRT receptor mRNA, as has been previously found, then the overall consequence would be diminished action of HCRT at target sites. This would diminish the waking drive, which in the elderly could contribute to the increased tendency to fall asleep during the normal wake period.
Aging↗
Active inhibition of plasma cell development in resting B cells by microphthalmia-associated transcription factor.
B cell terminal differentiation involves development into an antibody-secreting plasma cell, reflecting the concerted activation of proplasma cell transcriptional regulators, such as Blimp-1, IRF-4, and Xbp-1. Here, we show that the microphthalmia-associated transcription factor (Mitf) is highly expressed in naive B cells, where it antagonizes the process of terminal differentiation through the repression of IRF-4. Defective Mitf activity results in spontaneous B cell activation, antibody secretion, and autoantibody production. Conversely, ectopic Mitf expression suppresses the expression of IRF-4, the plasma cell marker CD138, and antibody secretion. Thus, Mitf regulates B cell homeostasis by suppressing the antibody-secreting fate.
Animals↗
Increased hypocretin-1 (orexin-a) levels in cerebrospinal fluid of rats after short-term forced activity.
The hypocretins (orexins) are recently discovered neuropeptides initially associated with feeding behavior and sleep regulation. However, the normal function of these peptides is unclear and a number of studies have reported a role in energy homeostasis and locomotor activity. Exercise (or physical activity) is the most powerful way of challenging the internal homeostatic process. This study examines the circadian differences in response to forced activity and homeostatic challenges on hypocretin-1 (Hcrt-1) levels in the cerebrospinal fluid (CSF) of rats. Hcrt-1 levels were decreased after long-term immobilization at the end of active phase (zeigeber time-0, ZT-0) and increased after short-term forced swimming in the rest phase (ZT-8). Nevertheless, no effects were observed after short-term immobilization, total sleep deprivation or cold exposure. We concluded that despite the relation between hypocretins, stress and sleep regulation reported in the literature, short-term total sleep deprivation, immobilization and cold exposure did not induce increases in CSF Hcrt-1 levels at ZT-0 and ZT-8. On the other hand, the relationship between hypocretinergic system activation and motor activation is reinforced by decrease in Hcr-1 levels after long-term immobilization at ZT-0 and its increased levels after short-term forced swimming at ZT-8 in CSF of rats.
Animals↗
Susceptibility of mast cell-deficient W/Wv mice to pristane-induced experimental lupus nephritis.
In many models of organ-specific autoimmune diseases, mast cells provide a critical cellular link between autoantibodies and end-organ inflammation, both initiating and propagating disease. However, their role in systemic autoimmunity remains speculative. We therefore examined the role of mast cells in a murine model of systemic immune complex-related autoimmune disease, lupus nephritis, expecting to observe the development of humoral autoimmunity in the absence of end-organ disease. Surprisingly, not only did mast cell-deficient animals develop characteristic humoral features of lupus, including hypergammaglobulinemia and autoantibodies, they also developed immune complex glomerulonephritis, as evidenced by renal immune deposits, glomerular disease, and proteinuria. These findings implicate the presence of distinct effector pathways to end-organ damage in humoral autoimmune diseases: one involving the interaction between autoantibodies and mast cells to recruit inflammation in organ-specific autoimmunity, and another involving a more direct--mast cell-independent--interaction between autoantibodies and circulating inflammatory mediators in systemic autoimmunity.
Animals↗
Modulation of Th1 activation and inflammation by the NF-kappaB repressor Foxj1.
Forkhead transcription factors play key roles in the regulation of immune responses. Here, we identify a role for one member of this family, Foxj1, in the regulation of T cell activation and autoreactivity. Foxj1 deficiency resulted in multiorgan systemic inflammation, exaggerated Th1 cytokine production, and T cell proliferation in autologous mixed lymphocyte reactions. Foxj1 suppressed NF-kappaB transcription activity in vitro, and Foxj1-deficient T cells possessed increased NF-kappaB activity in vivo, correlating with the ability of Foxj1 to regulate IkappaB proteins, particularly IkappaBbeta. Thus, Foxj1 likely modulates inflammatory reactions and prevents autoimmunity by antagonizing proinflammatory transcriptional activities. These results suggest a potentially general role for forkhead genes in the enforcement of lymphocyte quiescence.
Animals↗
CpG DNA redirects class-switching towards "Th1-like" Ig isotype production via TLR9 and MyD88.
Unmethylated CpG-containing DNA plays a critical role in immunity via the augmentation of Th1 but suppression of Th2 T cell responses. We describe here that CpG motifs also redirect isotype production by murine B cells to "Th1-like" Ig isotypes (IgG2a, IgG2b, and IgG3) while suppressing Th2 isotypes (IgG1 and IgE). Using genetically mutant B cells, we find that the IgG2a, IgG2b and IgG3 isotypes are transcriptionally regulated via the promotion of class-switching, in a manner critically dependent upon TLR9 and MyD88. Thus, CpG DNA redirects Ig isotype production by regulating the specificity of class-switch recombination.
Adaptor Proteins, Signal Transducing↗
Regulation of NF-kappaB, Th activation, and autoinflammation by the forkhead transcription factor Foxo3a.
Forkhead (Fox) transcription factors play key roles in immunoregulation. Members of the Foxo subfamily have been implicated in the regulation of the cell cycle and/or apoptosis, but their specific immunological contexts remain largely undefined. We demonstrate here that Foxo3a, the predominant Foxo member expressed in peripheral lymphoid organs, plays a critical role in lymphoid homeostasis. Foxo3a deficiency leads to spontaneous lymphoproliferation, associated with inflammation of several organs, in the absence of overt apoptotic defects. These findings correlated with the presence of hyperactivated helper T cells, which proliferated more vigorously and produced more Th1 and Th2 cytokines than their wild-type counterparts. Foxo3a inhibits NF-kappaB activation, whose overactivity was responsible for T cell hyperactivity in Foxo3a-deficient mice. Thus, Foxo3a regulates helper T cell activation and tolerance by inhibiting NF-kappaB activity, reinforcing a generalized role for the forkhead proteins in the maintenance of T cell tolerance through the inhibition of inflammatory transcriptional activities.
Animals↗
The F1-ATPase beta-subunit is the putative enterostatin receptor.
It has been suggested that the F1-ATPase beta-subunit is the enterostatin receptor. We investigated the binding activity of the purified protein with a labeled antagonist, beta-casomorphin1-7, in the absence and presence of cold enterostatin. 125I-beta-casomorphin1-7 weakly binds to the rat F1-ATPase beta-subunit. Binding was promoted by low concentrations of cold enterostatin but displaced by higher concentrations. To study the relationship between binding activity and feeding behavior, we examined the ability of a number of enterostatin analogs to affect beta-casomorphin1-7 binding to the F1-ATPase beta-subunit. Peptides that suppressed food intake promoted beta-casomorphin1-7 binding whereas peptides that stimulated food intake or did not affect the food intake displaced beta-casomorphin1-7 binding. Surface plasmon resonance measurements show that the beta-subunit of F1-ATPase binds immobilized enterostatin with a dissociation constant of 150 nM, where no binding could be detected for the assembled F1-ATPase complex. Western blot analysis showed the F1-ATPase beta-subunit was present on plasma and mitochondrial membranes of rat liver and amygdala. The data provides evidence that the F1-ATPase beta-subunit is the enterostatin receptor and suggests that enterostatin and beta-casomorphin1-7 bind to distinct sites on the protein.
Animals↗
An innate cell-mediated, murine ulcerative colitis-like syndrome in the absence of nuclear factor of activated T cells.
BACKGROUND & AIMS: Nuclear factor of activated T cells transcription factors plays a central role in immunity by regulating the expression of multiple cytokines and other regulatory molecules, many of which have been heavily implicated in the pathogenesis of inflammatory bowel disease. However, few studies have directly investigated the nuclear factor of activated T cells proteins in inflammatory bowel disease. We describe here a specific role for nuclear factor of activated T cells c2 in the pathogenesis of murine inflammatory bowel disease. METHODS: Mice deficient for nuclear factor of activated T cells c2, recombinase activating gene-2, or both and transgenic or nontransgenic for an anti-ovalbumin T-cell receptor or an anti-hen egg lysozyme B-cell receptor were studied. Adoptive transfers were performed of T or B cells or both from nuclear factor of activated T cells c2-deficient mice into nuclear factor of activated T cells c2-deficient recombinase activating gene-deficient animals, in the presence or absence of antibodies that neutralize interleukin-10 activity. RESULTS: Nuclear factor of activated T cells c2-deficient, recombinase activating gene-deficient animals spontaneously developed a severe inflammatory bowel syndrome that resembled ulcerative colitis but was composed entirely of nonlymphocytes. The disease was suppressed by the adoptive transfer of polyclonal B-cell populations, even on neutralization of interleukin-10, but not by the presence of monoclonal T or B cells. CONCLUSIONS: Nuclear factor of activated T cells plays a critical role in the regulation of bowel inflammation by nonlymphoid immune cells, and B cells suppress bowel inflammation by innate immune cells. Such findings indicate a novel, interleukin-10-independent role for nuclear factor of activated T cells in the regulation of innate immunity and in intestinal immune tolerance.
Animals↗
[Establishment and characterization of a neural stem cell line (RNSC-FMU 1) from rat brain].
A neural stem cell line (RNSC-FMU 1) from rat brain have been established successfully by isolating and culturing neural stem cells from newborn SD rat brain in vitro with free-serum medium and passaging with mechanical division. The cell line cultured can continuously generate in vitro for long-term and it is 21 months (>100 passages) so far. These cells keep the feature of neural stem cell and normal karyotype. These neural stem cells can be induced to differentiate into neurons, astrocytes and oligodendrocytes. The cells have an extensive self-renewal capacity; its doubling time of proliferation is about 20 h. The cells are also cryopreservable. Tumor formation is not observed in nude mice that explanted with the cells. This cell line is a good tool for research of neural stem cell.
Animals↗
Normal hypocretin-1 levels in the cerebrospinal fluid of patients with fatal familial insomnia.
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Aged↗