Differential susceptibility epidemic models

We formulate compartmental differential susceptibility (DS) susceptible-infective-removed (SIR) models by dividing the susceptible population into multiple subgroups according to the susceptibility of individuals in each group. We analyze the impact of disease-induced mortality in the situations where the number of contacts per individual is either constant or proportional to the total population. We derive an explicit formula for the reproductive number of infection for each model by investigating the local stability of the infection-free equilibrium. We further prove that the infection-free equilibrium of each model is globally asymptotically stable by qualitative analysis of the dynamics of the model system and by utilizing an appropriately chosen Liapunov function. We show that if the reproductive number is greater than one, then there exists a unique endemic equilibrium for all of the DS models studied in this paper. We prove that the endemic equilibrium is locally asymptotically stable for the models with no disease-induced mortality and the models with contact numbers proportional to the total population. We also provide sufficient conditions for the stability of the endemic equilibrium for other situations. We briefly discuss applications of the DS models to optimal vaccine strategies and the connections between the DS models and predator-prey models with multiple prey populations or host-parasitic interaction models with multiple hosts are also given.This research was partially supported by the Department of Energy under contracts W-7405-ENG-36 and the Applied Mathematical Sciences Program KC-07-01-01.     

Hypertrophy, increased ejection fraction, and reduced Na-K-ATPase activity in phospholemman-deficient mice

Phospholemman (FXYD1), a 72-amino acid transmembrane protein abundantly expressed in the heart and skeletal muscle, is a major substrate for phosphorylation in the cardiomyocyte sarcolemma. Biochemical, cellular, and electrophysiological studies have suggested a number of possible roles for this protein, including ion channel modulator, taurine-release channel, Na(+)/Ca(2+) exchanger modulator, and Na-K-ATPase-associated subunit. We have generated a phospholemman-deficient mouse. The adult null mice exhibited increased cardiac mass, larger cardiomyocytes, and ejection fractions that were 9% higher by magnetic resonance imaging compared with wild-type animals. Notably, this occurred in the absence of hypertension. Total Na-K-ATPase activity was 50% lower in the phospholemman-deficient hearts. Expression (per unit of membrane protein) of total Na-K-ATPase was only slightly diminished, but expression of the minor alpha(2)-isoform, which has been specifically implicated in the control of contractility, was reduced by 60%. The absence of phospholemman thus results in a complex response, including a surprisingly large reduction in intrinsic Na-K-ATPase activity, changes in Na-K-ATPase isoform expression, increase in ejection fraction, and increase in cardiac mass. We hypothesize that a primary effect of phospholemman is to modulate the Na-K-ATPase and that its reduced activity initiates compensatory responses.     

A biochemical and functional characterization of diet-induced brain insulin resistance

While considerable research has examined diminished insulin responses within peripheral tissues, comparatively little has been done to examine the effects of this metabolic disruption upon the CNS. The present study employed biochemical and electrophysiological assays of acutely prepared brain slices to determine whether neural insulin resistance is a component of the metabolic syndrome observed within the fructose-fed (FF) hamster. The tyrosine phosphorylation levels of the insulin receptor (IR) and insulin receptor substrate 1 (IRS-1) in response to insulin were significantly reduced within FF hamsters. Also, insulin-mediated phosphorylation of both residues necessary for activation of the serine-threonine kinase Akt/PKB, a key effector of insulin signaling, was markedly decreased. Elevated levels of the protein tyrosine phosphatase 1B, which dephosphorylates the IR and IRS-1, were also observed within the cerebral cortex and hippocampus of FF hamsters. Examination of whether a nutritionally induced compromise of neural insulin signaling altered synaptic function revealed a significant attenuation of insulin-induced long-term depression, but no effect upon either paired-pulse facilitation or electrically induced long-term potentiation. Collectively, our results demonstrate, for the first time, that nutritionally induced insulin resistance significantly affects the neural insulin signaling pathway, and suggest that brain insulin resistance may contribute to cognitive impairment.     

Murine gammaherpesvirus 68 open reading frame 45 plays an essential role during the immediate-early phase of viral replication

Murine gammaherpesvirus 68 (MHV-68) has been developed as a model for the human gammaherpesviruses Epstein-Barr virus and human herpesvirus 8/Kaposi's sarcoma-associated herpesvirus (HHV-8/KSHV), which are associated with several types of human diseases. Open reading frame 45 (ORF45) is conserved among the members of the Gammaherpesvirinae subfamily and has been suggested to be a virion tegument protein. The repression of ORF45 expression by small interfering RNAs inhibits MHV-68 viral replication. However, the gene product of MHV-68 ORF45 and its function have not yet been well characterized. In this report, we show that MHV-68 ORF45 is a phosphorylated nuclear protein. We constructed an ORF45-null MHV-68 mutant virus (45STOP) by the insertion of translation termination codons into the portion of the gene encoding the N terminus of ORF45. We demonstrated that the ORF45 protein is essential for viral gene expression immediately after the viral genome enters the nucleus. These defects in viral replication were rescued by providing ORF45 in trans or in an ORF45-null revertant (45STOP.R) virus. Using a transcomplementation assay, we showed that the function of ORF45 in viral replication is conserved with that of its KSHV homologue. Finally, we found that the C-terminal 23 amino acids that are highly conserved among the Gammaherpesvirinae subfamily are critical for the function of ORF45 in viral replication.     

Microsatellite mapping of a Triticum urartu Tum. derived powdery mildew resistance gene transferred to common wheat (Triticum aestivum L.)

A powdery mildew resistance gene from Triticum urartu Tum. accession UR206 was successfully transferred into hexaploid wheat (Triticum aestivum L.) through crossing and backcrossing. The F₁ plants, which had 28 chromosomes and an average of 5.32 bivalents and 17.36 univalents in meiotic pollen mother cells (PMC), were obtained through embryos rescued owing to shriveling of endosperm in hybrid seed of cross Chinese Spring (CS) × UR206. Hybrid seeds were produced through backcrossing F₁ with common wheat parents. The derivative lines had normal chromosome numbers and powdery mildew resistance similar to the donor UR206, indicating that the powdery mildew resistance gene originating from T. urartu accession UR206 was successfully transferred and expressed in a hexaploid wheat background. Genetic analysis indicated that a single dominant gene controlled the powdery mildew resistance at the seedling stage. To map and tag the powdery mildew resistance gene, 143 F₂ individuals derived from a cross UR206 × UR203 were used to construct a linkage map. The resistant gene was mapped on the chromosome 7AL based on the mapped microsatellite makers. The map spanned 52.1 cM and the order of these microsatellite loci agreed well with the established microsatellite map of chromosome arm 7AL. The resistance gene was flanked by the microsatellite loci Xwmc273 and Xpsp3003, with the genetic distances of 2.2 cM and 3.8 cM, respectively. On the basis of the origin and chromosomal location of the gene, it was temporarily designated PmU.     

社会行为发育的行为神经内分泌效应

发育过程中行为神经内分泌环境能够调节解剖和生理的长期变化,产生深远的行为效应,所以神经内分泌环境在幼体发育及其行为生理特征的形成中起重要作用。本文综述了神经垂体激素、类固醇激素及它们的受体在社会行为发育中的行为神经内分泌效应;指出该领域有待解决的问题和进一步研究的方向;希望能使人们重视人类发育过程中双亲行为和激素作用对儿童社会行为及其相关神经内分泌特征的影响。     

Synthesis and characterization of binuclear molybdenum-polycarboxylate complexes with sulfur bridges

A group of four binuclear sulfur-bridged molybdenum-polycarboxylato complexes with homocitrate, citrate, cysteine, ethylenediaminetetraacetate ligands, respectively, have been synthesized and characterized. These complexes were prepared in order to study the interaction of Mo and homocitrate in the FeMo-co of nitrogenases. In the structures of K4(NH4)2[Mo2O2S2(C6H4O7)2].10H2O (2), (NH4)2[Mo2O2S2(C3H5SNO2)2].5H2O (3) and (NH4)2[Mo2O2S2(C10H12N2O8)].3.5H2O (4), molybdenum (V) atom adopts a distorted octahedral arrangement through a terminal oxygen atom, two bridging sulfur atoms and three atoms from the ligand (hydroxyl, alpha-, beta-carboxylates, sulfide or amine). The coordination mode of homocitrate ligand in K5(NH4)[Mo2O2S2(C7H5O7)2].3H2O.CH3OH (1) has been proposed in a tridentate fashion via its hydroxyl and a pair of carboxylate groups (alpha-, beta-carboxylates). The electrochemical properties of these complexes have been discussed.     

DNA interaction of dioxycyclobutenedione-(1,2-cyclohexanediamine) platinum(II) complex with potential anticancer activity

Dioxycyclobutenedione-(1,2-cyclohexanediamine)platinum(II), (R,R-DC-Pt) was found to have stronger cytotoxicity against six cancer cell lines than cisplatin and its DNA interactions was studied by calorimetric measurements, (13)C NMR. The binding specificity study of DNA base with R,R-DC-Pt was conducted by HPLC. To understand the molecular mechanism of R,R-DC-Pt with stronger cytotoxicity than that of cisplatin, we studied R,R-DC-Pt interaction with an oligonucleotide, d(ACCACGTGGT)(2), which contained c-H-ras gene encoding GGT by NMR spectroscopy. The oligomer DNA double helix was destroyed almost completely upon the R,R-DC-Pt binding. However under the same condition, the cisplatin binding with DNA was not so affected, and instead another conformation was formed, which suggests that larger damage to DNA can be induced by R,R-DC-Pt complex than that by cisplatin.     

Dynamic distribution of Ser-10 phosphorylated histone H3 in cytoplasm of MCF-7 and CHO cells during mitosis

The dynamic distribution of phosphorylated Histone H3 on Serl 0 (phospho-H3) in cells was investigated to determine its function during mitosis. Human breast adenocarcinoma cells MCF-7, and Chinese hamster cells CHO were analyzed by indirect immunofluorescence staining with an antibody against phospho-H3. We found that the phosphorylation begins at early prophase, and spreads throughout the chromosomes at late prophase. At metaphase, most of the phospho-H3 aggregates at the end of the condensed entity of chromosomes at equatorial plate. During anaphase and telophase,the fluorescent signal of phospho-H3 is detached from chromosomes into cytoplasm. At early anaphase, phospho-H3 shows ladder bands between two sets of separated chromosome, and forms “sandwich-like structure” when the chromosomes condensed. With the cleavage progressing, the “ladders” of the histone contract into a bigger bright dot. Then the histone aggregates and some of compacted microtubules in the midbody region are composed into a “bar-like”complex to separate daughter cells. The daughter cells seal their plasma membrane along with the ends of the “bar”,inside which locates microtubules and modified histones, to finish the cytokinesis and keep the “bar complex” out of the cells. The specific distribution and kinetics of phospho-H3 in cytoplasm suggest that the modified histones may take part in the formation of midbody and play a crucial role in cytokinesis.