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R Lin

Publications and source records attributed to R Lin.

At least 55 records · Page 3Linked to original sources
PubMed2000

MEX-5 and MEX-6 function to establish soma/germline asymmetry in early C. elegans embryos.

An asymmetrical network of cortically localized PAR proteins forms shortly after fertilization of the C. elegans egg. This network is required for subsequent asymmetries in the expression patterns of several proteins that are encoded by nonlocalized, maternally expressed mRNAs. We provide evidence that two nearly identical genes, mex-5 and mex-6, link PAR asymmetry to those subsequent protein asymmetries. MEX-5 is a novel, cytoplasmic protein that is localized through PAR activities to the anterior pole of the 1-cell stage embryo. MEX-5 localization is reciprocal to that of a group of posterior-localized proteins called germline proteins. Ectopic expression of MEX-5 is sufficient to inhibit the expression of germline proteins, suggesting that MEX-5 functions to inhibit anterior expression of the germline proteins.

Amino Acid Sequence↗
PubMed2000

Electronic mechanism of STM-induced diffusion of hydrogen on Si(100).

We have observed a scanning tunneling microscopy (STM) induced lateral transfer of a single hydrogen atom on the Si(100) surface. The transfer rate of the hydrogen atom is proportional to the electron dose, indicating an electron-assisted transfer mechanism. Measurements of the relations between the transfer rate and the sample bias and temperature give further support for an electronic mechanism. The bias dependence of the transfer rate shows a peak, and from a first principles electronic structure calculation we show that the position of the peak is related to the energy of a localized surface resonance. We propose that the hydrogen transfer is related to inelastic hole scattering with this surface resonance. We develop a microscopic model for the hydrogen transfer, and using the experimental data we extract information on the resonance lifetime and the transfer yield per resonant electron. The transfer takes place by tunneling through a small excited state transfer barrier. The transfer rate is increased if the hydrogen atom before the resonant excitation is vibrationally excited, and this gives rise to an increasing transfer rate with increasing sample temperature.

Journal Article↗
PubMed2000

The consequences of growth of a mutator strain of Escherichia coli as measured by loss of function among multiple gene targets and loss of fitness.

We have examined the composition of members of mutator populations of Escherichia coli by employing an extensive set of phenotypic screens that allow us to monitor the function of >700 genes, constituting approximately 15% of the genome. We looked at mismatch repair deficient cells after repeated cycles of single colony isolation on rich medium to generate lineages that are forced through severe bottlenecks, and compared the results to those for wild-type strains. The mutator lineages continued to accumulate mutations rapidly with each increasing cycle of colony isolation. By the end of the 40th cycle, after approximately 1000 generations, most of the lineages had reduced colony size, 4% had died out, 55% had auxotrophic requirements (increasing to 80% after 60 cycles), and 70% had defects in at least one sugar or catabolic pathway. In addition, 33% had a defect in cell motility, and 26% were either temperature-sensitive or cold-sensitive lethals. On the other hand, only 3% of the wild-type lineages had detectable mutations of any type after 40 cycles. By the 60th cycle, the typical mutator cell carried 4-5 inactive genes among the 15% of the genome being monitored, indicating that the average cell carried at least 24-30 inactivated genes distributed throughout the genome. Remarkably, 30% of the lineages had lost the ability to utilize xylose as a carbon source. DNA sequencing revealed that most of the Xyl(-) mutants had a frameshift in a run of eight G's (GGGGGGGG) in the xylB gene, either adding or deleting one -G-. Further analysis indicated that rendering E. coli deficient in mismatch repair unmasks hypermutable sites in certain genes or intergenic regions. Growth curves and competition tests on lineages that passed through 90 cycles of single colony isolation showed that all lineages suffered reduced fitness. We discuss these results in terms of the value of mutators in cellular evolution.

Adaptation, Biological↗
PubMed2000

Microvascular response in patients with cardiogenic shock.

OBJECTIVE: To examine the mechanisms contributing to decreased microvascular blood flow in cardiogenic shock by comparing patients with cardiogenic shock with critically ill controls and with patients with septic shock. DESIGN: Prospective, consecutive entry of patients meeting the criteria for septic shock, cardiogenic shock, and critical illness without coexisting infection or shock. SETTING: University hospital, medical intensive care unit, coronary care unit, and respiratory care unit. PATIENTS: Eight patients with cardiogenic shock secondary to acute myocardial infarction, six critically ill controls, and six patients with septic shock. MEASUREMENTS AND MAIN RESULTS: Forearm blood flow was measured at rest and during reactive hyperemia by venous air plethysmography. Red cell deformability was determined by filtration. Leukocyte aggregation was detected by the leukergy test. Neutrophil CD11b/CD18 expression and soluble intercellular adhesion molecule-1 levels were also measured. In cardiogenic shock, forearm arterial resistance was significantly increased at rest and during reactive hyperemia compared with controls and patients with septic shock. The response to reactive hyperemia was attenuated in cardiogenic and septic shock patients, as measured by the absolute change in forearm blood flow from baseline, which was significantly less as compared with controls (p < .01). The percent change in forearm blood flow during reactive hyperemia compared with forearm blood flow at rest was significantly lower in cardiogenic shock (60+/-10) and in septic shock (50+/-11) compared with controls at baseline (145+/-20; p < .01). Red cell deformability was significantly decreased in cardiogenic shock (1.2+/-0.2 mL/min; p < .05) and septic shock (1.1+/-0.2 mL/min; p < .05), compared with controls (1.8+/-0.1 mL/min). Neutrophil CD11b/CD18 expression, leukergy, and serum intercellular adhesion molecule-1 levels in cardiogenic shock patients were not significantly different from controls. CONCLUSION: These data suggest that the response to reactive hyperemia is attenuated in cardiogenic shock. This appears to reflect increased vasoconstriction and an impaired capacity for vasodilation. Decreased erythrocyte deformability may also be important in limiting systemic microvascular flow. However, evidence supporting a role for neutrophil-endothelial cell interactions was not observed.

Critical Care↗
PubMed2000

The dopamine D3 receptor interacts with itself and the truncated D3 splice variant d3nf: D3-D3nf interaction causes mislocalization of D3 receptors.

We have generated a stable cell line expressing FLAG epitope-tagged D3 dopamine receptors and used this cell line to study D3 receptor-protein interactions. To analyze protein interactions, we separately introduced into the stable cell line either D3 receptors carrying an hemagglutinin (HA) epitope tag, or an HA-tagged version of the D3 receptor splice variant D3nf. A combination of confocal laser microscopy and coimmunoprecipitation was used to assay the formation and expression pattern of D3-D3 homodimers or D3-D3nf heterodimers. When coexpressed in HEK 293 cells, FLAG- and HA-tagged D3 receptors exhibited a similar plasma membrane distribution. Using an HA epitope tag-specific antibody, we coimmunoprecipitated HA- and FLAG-tagged D3 receptors, suggesting that D3 receptors are capable of forming homodimers. Epitope-tagged D3nf polypeptides exhibited a markedly different cellular distribution than D3 receptors. When expressed in HEK 293 cells, either alone or in combination with FLAG-tagged D3 receptors, D3nf exhibited a punctate perinuclear distribution. When D3nf was introduced into the stable D3-expressing cell line, D3 receptors were no longer visualized at the plasma membrane. Instead, D3 and D3nf showed a similar, predominantly cytosolic, localization. Using the HA-specific antibody, we were able to coimmunoprecipitate D3 and D3nf polypeptides from transfected cells. These data suggest the existence of physical interaction between D3 and D3nf. This interaction appears to result in the mislocalization of D3 receptors from the plasma membrane to an intracellular compartment, a finding that could be of significance in the etiology of schizophrenia.

Alternative Splicing↗
PubMed2000

The IRF-3 transcription factor mediates Sendai virus-induced apoptosis.

Virus infection of target cells can result in different biological outcomes: lytic infection, cellular transformation, or cell death by apoptosis. Cells respond to virus infection by the activation of specific transcription factors involved in cytokine gene regulation and cell growth control. The ubiquitously expressed interferon regulatory factor 3 (IRF-3) transcription factor is directly activated following virus infection through posttranslational modification. Phosphorylation of specific C-terminal serine residues results in IRF-3 dimerization, nuclear translocation, and activation of DNA-binding and transactivation potential. Once activated, IRF-3 transcriptionally up regulates alpha/beta interferon genes, the chemokine RANTES, and potentially other genes that inhibit viral infection. We previously generated constitutively active [IRF-3(5D)] and dominant negative (IRF-3 DeltaN) forms of IRF-3 that control target gene expression. In an effort to characterize the growth regulatory properties of IRF-3, we observed that IRF-3 is a mediator of paramyxovirus-induced apoptosis. Expression of the constitutively active form of IRF-3 is toxic, preventing the establishment of stably transfected cells. By using a tetracycline-inducible system, we show that induction of IRF-3(5D) alone is sufficient to induce apoptosis in human embryonic kidney 293 and human Jurkat T cells as measured by DNA laddering, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling assay, and analysis of DNA content by flow cytometry. Wild-type IRF-3 expression augments paramyxovirus-induced apoptosis, while expression of IRF-3 DeltaN blocks virus-induced apoptosis. In addition, we demonstrate an important role of caspases 8, 9, and 3 in IRF-3-induced apoptosis. These results suggest that IRF-3, in addition to potently activating cytokine genes, regulates apoptotic signalling following virus infection.

Apoptosis↗
PubMed2000

Selective DNA binding and association with the CREB binding protein coactivator contribute to differential activation of alpha/beta interferon genes by interferon regulatory factors 3 and 7.

Recent studies implicate the interferon (IFN) regulatory factors (IRF) IRF-3 and IRF-7 as key activators of the alpha/beta IFN (IFN-alpha/beta) genes as well as the RANTES chemokine gene. Using coexpression analysis, the human IFNB, IFNA1, and RANTES promoters were stimulated by IRF-3 coexpression, whereas the IFNA4, IFNA7, and IFNA14 promoters were preferentially induced by IRF-7 only. Chimeric proteins containing combinations of different IRF-7 and IRF-3 domains were also tested, and the results provided evidence of distinct DNA binding properties of IRF-3 and IRF-7, as well as a preferential association of IRF-3 with the CREB binding protein (CBP) coactivator. Interestingly, some of these fusion proteins led to supraphysiological levels of IFN promoter activation. DNA binding site selection studies demonstrated that IRF-3 and IRF-7 bound to the 5'-GAAANNGAAANN-3' consensus motif found in many virus-inducible genes; however, a single nucleotide substitution in either of the GAAA half-site motifs eliminated IRF-3 binding and transactivation activity but did not affect IRF-7 interaction or transactivation activity. These studies demonstrate that IRF-3 possesses a restricted DNA binding site specificity and interacts with CBP, whereas IRF-7 has a broader DNA binding specificity that contributes to its capacity to stimulate delayed-type IFN gene expression. These results provide an explanation for the differential regulation of IFN-alpha/beta gene expression by IRF-3 and IRF-7 and suggest that these factors have complementary rather than redundant roles in the activation of the IFN-alpha/beta genes.

Amino Acid Sequence↗
PubMed2000

The mechanistic basis of aerobic performance variation in red junglefowl.

We examined aerobic performance, organ and muscle mass and enzymatic activity in red junglefowl (Gallus gallus). We tested three models of performance limitation (central limits, peripheral limits, symmorphosis) and explored relationships between basal metabolic rate (BMR), aerobic capacity ( V (O2max)) and social rank. Males had a lower BMR, a higher V (O2max) and a greater aerobic scope than females. Females possessed larger peritoneal and reproductive organs, while males had larger hearts, lungs and leg muscles. In females, BMR was correlated with spleen mass and V (O2max) was correlated with hematocrit and large intestine mass. Male BMR was correlated with intestinal tract and lung mass, and V (O2max) was correlated with heart and pectoralis mass. Male citrate synthase activity averaged 57 % higher than that of females and was correlated with V (O2max) (this correlation was not significant in females). Female social status was not correlated with any variable, but male dominance was associated with higher aerobic scope, larger heart and lungs, smaller peritoneal organs and greater leg citrate synthase activity. We conclude that aerobic capacity is controlled by system-wide limitations (symmorphosis) in males, while in females it is controlled by central organs. In neither sex is elevated aerobic capacity associated with increased maintenance costs.

Aerobiosis↗
PubMed2000

Routine screening for Chlamydia trachomatis in subfertile women--is it time to start?

UNLABELLED: Genital Chlamydia trachomatis infection has long been recognised as the major cause of pelvic disease and subsequently infertility. The diagnosis of this infection has traditionally relied on tissue culture. The availability of DNA amplification methods like ligase chain reaction promises faster and more sensitive results. This study was conducted to evaluate the prevalence of chlamydial infection in a subfertile population subgroup. AIM: A case control longitudinal study of 100 subfertile women in a tertiary teaching hospital were analyzed for the prevalence of genital Chlamydia trachomatis infection using ligase chain reaction test kit. RESULTS: A prevalence rate of 8% was detected, the majority being 25 years old or less (33.3%), p = 0.007. All patients gave no prior history of abnormal PAP smears, hospitalisation for pelvic inflammatory disease or abnormal vaginal discharge at the time of investigation. CONCLUSION: Our infertile group of patients has a relatively high incidence of silent genital Chlamydia trachomatis infection. This being highest in the below 25 years old age group. This finding indicates that screening for chlamydia may be necessary for the subfertile couple presenting to clinic. This is especially so if the patient is of the younger age group.

Adult↗
PubMed2000

Buckwheat allergy and reports on asthma and atopic disorders in Taiyuan City, Northern China.

Allergy to common buckwheat (Fagopyrum esculentum) has been reported from Europe and Japan, and a 24 kDa globulin protein has been identified as one of the major allergens. In China also another type, tartary buckwheat (Fagopyrum tartaricum) is grown and consumed. Three groups of individuals in Shanxi province, China, were investigated for buckwheat allergy using skin prick test. The groups were: agricultural researchers with occupational exposure to buckwheat (N = 16); workers in a food industry producing buckwheat noodles (N = 25), and patients with diabetes or cardiovascular disease consuming buckwheat as functional food (N = 20). Information on atopic disorders and adverse food reactions were collected by a doctors-administered questionnaire. One male industrial worker had a positive skin prick test to buckwheat, but no symptoms while eating or handling buckwheat products. In total, 34% consumed buckwheat food at least every week, and 23% had a weekly consumption of tartary buckwheat. The prevalence of doctor's diagnosed asthma was low (1.6%). Four subjects (6.6%) reported a history of allergic rhinitis, with allergy to cedar pollen, carnation and peach.

Adult↗
PubMed2000

[Areas of brain involved in immunoregulation].

OBJECTIVE: To study the location of brain areas involved in immunoregulation. METHODS: Immunohistochemistry and immunofluorescence were used to detect the different distribution of cytokines immunopositive cells in the brain of rats immunized via both intraperitoneal and subcutaneous injections. RESULTS: The cytokines immunopositive cells were distributed in the supraoptic (SO) and paraventricular (PV) nuclei of the hypothalamus, the anterior hypothalamic (AH) nucleus, arcuate and median eminence, the lateral hypothalamic nucleus (LH) and the amygdaloid nuclear complex while only the appearance of the cytokines immunopositive cells in LH and amygdaloid nuclear complex in hypothalamus was related with immunization status of the animals. Double-labelling results showed that the cytokines immunopositive cells were neurons. CONCLUSIONS: We have observed that neurons of the LH and amygdaloid nuclear complex in hypothalamus as a main source of the neuroimmunoregulation played a key role in neuroimmunoregulation and they participated in the neuroimmunoregulation at an early stage of the immune response.

Amygdala↗
PubMed1999

Bacteremia in HIV-infected patients: short-term predictors of mortality.

To identify characteristics associated with mortality in HIV-infected patients with bacteremia, 88 bacteremic episodes in 80 HIV-infected patients were prospectively identified over a 5-month period and observed for 30 days. Demographic, clinical, laboratory, and radiologic data were collected. Mean and median age was 41 years. Most study subjects were homosexual men. Median CD4 count was 20 cells/mm3. Gram-positive organisms predominated (65%). The most common source of bacteremia was intravascular catheters (45%). Overall mortality was 30%. A history of malignancy, three or more opportunistic infections, shock, low hemoglobin, source of bacteremia other than an intravascular catheter, resistance to therapy, and a second bacteremic episode during the study period, were all found to be independent predictors of mortality. In this cohort of HIV-infected patients, most of whom were severely immunosuppressed, several factors were found to be significantly and independently associated with mortality.

Adult↗
PubMed1999

Identification of the secretory leukocyte protease inhibitor (SLPI) as a target of IRF-1 regulation.

Interferon Regulatory Factor (IRF)-1 is a multifunctional transcription factor, involved in cell growth regulation, pathogen response and immune activation. To identify novel gene targets that may contribute to IRF-1 mediated activities, RNA fingerprinting was performed using NIH3T3 cells that inducibly express a hybrid form of IRF-1 under tetracycline regulated control. Secretory leukocyte protease inhibitor (SLPI) - a regulator of inflammation and an inhibitor of the LPS response - was identified as a gene repressed after doxycycline induced IRF-1 expression. Preliminary analysis of the human SLPI promoter identified an ISRE-like site located within the -221 to -200 region to which IRF-1 binds and a second, putative IRF-1 binding site upstream of the TATA box. Furthermore, co-transfection studies demonstrated that SLPI expression was inhibited by IRF-1 co-expression. The identification of SLPI as a target of IRF-1 regulation reveals a unique involvement of IRF-1 in repression of gene transcription and assigns a novel role for IRF-1 in inflammation.

3T3 Cells↗
PubMed1999

Interferon regulatory factors: the next generation.

Interferons are a large family of multifunctional secreted proteins involved in antiviral defense, cell growth regulation and immune activation. Viral infection induces transcription of multiple IFN genes, a response that is in part mediated by the interferon regulatory factors (IRFs). The initially characterized members IRF-1 and IRF-2 are now part of a growing family of transcriptional regulators that has expanded to nine members. The functions of the IRFs have also expanded to include distinct roles in biological processes such as pathogen response, cytokine signaling, cell growth regulation and hematopoietic development. The aim of this review is to provide an update on the novel discoveries in the area of IRF transcription factors and the important roles of the new generation of IRFs--particularly IRF-3, IRF-4 and IRF-7.

Amino Acid Sequence↗
PubMed1999

Specific contributions of the small GTPases Rho, Rac, and Cdc42 to Dbl transformation.

Dbl is a representative prototype of a growing family of oncogene products that contain the Dbl homology/pleckstrin homology elements in their primary structures and are associated with a variety of neoplastic pathologies. Members of the Dbl family have been shown to function as physiological activators (guanine nucleotide exchange factors) of the Rho-like small GTPases. Although the expression of GTPase-defective versions of Rho proteins has been shown to induce a transformed phenotype under different conditions, their transformation capacity has been typically weak and incomplete relative to that exhibited by dbl-like oncogenes. Moreover, in some cases (e.g. NIH3T3 fibroblasts), expression of GTPase-defective Cdc42 results in growth inhibition. Thus, in attempting to reconstitute dbl-induced transformation of NIH3T3 fibroblasts, we have generated spontaneously activated ("fast-cycling") mutants of Cdc42, Rac1, and RhoA that mimic the functional effects of activation by the Dbl oncoprotein. When stably expressed in NIH3T3 cells, all three mutants caused the loss of serum dependence and showed increased saturation density. Furthermore, all three stable cell lines were tumorigenic when injected into nude mice. Our data demonstrate that all three Dbl targets need to be activated to promote the full complement of Dbl effects. More importantly, activation of each of these GTP-binding proteins contributes to a different and distinct facet of cellular transformation.

3T3 Cells↗
PubMed1999

WRM-1 activates the LIT-1 protein kinase to transduce anterior/posterior polarity signals in C. elegans.

During C. elegans development, Wnt/WG signaling is required for differences in cell fate between sister cells born from anterior/posterior divisions. A beta-catenin-related gene, wrm-1, and the lit-1 gene are effectors of this signaling pathway and appear to downregulate the activity of POP-1, a TCF/LEF-related protein, in posterior daughter cells. We show here that lit-1 encodes a serine/threonine protein kinase homolog related to the Drosophila tissue polarity protein Nemo. We demonstrate that the WRM-1 protein binds to LIT-1 in vivo and that WRM-1 can activate the LIT-1 protein kinase when coexpressed in vertebrate tissue culture cells. This activation leads to phosphorylation of POP-1 and to apparent changes in its subcellular localization. Our findings provide evidence for novel regulatory avenues for an evolutionarily conserved Wnt/WG signaling pathway.

Amino Acid Sequence↗
PubMed1999

[Long-term follow-up of combined therapy with large-dose zinc sulfate and low-dose penicillamine in children with hepatolenticular degeneration].

OBJECTIVE: To summarize the long-term effect of combined treatment with large-dose zinc sulfate and low-dose penicillamine in children with hepatolenticular degeneration (HLD). METHODS: The patients who had symptoms were treated with large-dose zinc sulfate (100-150mg, <6yr; 150-200mg, 6-8yr; 200-300mg, 9-10yr; 300mg,>10yr; 3 times a day) in addition to low-dose penicillamine(8-10mg/kg/d) at the beginning of treatment. Zinc sulfate alone was given to the presymptomatic patients and it was used as maintenance therapy when clinical improvement was obtained. 31 children were followed up for 4-11 years. RESULTS: In 3 presymptomatic patients, no clinical abnormalities were found. Among 28 patients with symptoms, 23 patients (82%) had their symptoms and signs subsided or much improved, 2 patients(7%) remained unchanged, and 3(11%) died. Blood concentrations of copper were persistently lower than normal. Urine copper excretion of 24 hours was significantly lower than that before the combined therapy in all patients, and it became normal in 5 cases(16%) after 6 months of treatment, and in 26 cases(84%) after 1-2 years of treatment. Higher blood concentrations of zinc were found in 20 cases(65%), and higher urine zinc excretion was noted in 25 cases(81%) once or more times during the therapy. CONCLUSION: Combined therapy of large-dose zinc sulfate and low-dose penicillamine is an effective, safe and cheap treatment for children with HLD.

Adolescent↗