Biomedical subjects

X Wang

Publications and source records attributed to X Wang.

At least 19 recordsLinked to original sources

PubMed2007

SHP-2 and PI3-kinase genes PTPN11 and PIK3R1 may influence serum apoB and LDL cholesterol levels in normal women.

Insulin regulates apoB metabolism via activation of PI3K or regulation of MTP via MAPK/ERK signalling. SHP-2 enhances both pathways through increased IRS-1 phosphorylation. We hypothesized that variants in the SHP-2 gene PTPN11 and PI3K p85alpha subunit gene PIK3R1 may influence fasting levels of plasma apoB and/or LDL cholesterol. We tested association of tagging SNPs (tSNPs) in each gene with serum lipids in a large sample of unselected population-based Caucasian female twins (n=2771, mean age 47.4+/-12.5 years) and then tested interaction between tSNPs in determining apoB and LDL levels. PTPN11 tSNP rs11066322 was associated with apoB (P=0.007) and rs11066320 was associated with LDL cholesterol (P=0.016). PIK3R1 tSNP rs251406 was associated with apoB (P=0.0003) and rs706713 was associated with LDL cholesterol (P=0.009). PTPN11 tSNP rs11066322 interacted with PIK3R1 tSNP rs251406 in determining serum apoB levels (P=0.012) and with PIK3R1 tSNP rs40318 in determining LDL cholesterol levels (P=0.009). Association of single tSNPs with both apoB and LDL cholesterol as well as interactions between the two genes suggest that variants influencing SHP-2 activity may modulate the acute pathway by which insulin regulates these lipids.

Adult↗

PubMed2006

Interleukin 3 and schizophrenia: the impact of sex and family history.

Chromosome 5q21-33 has been implicated in harboring risk genes for schizophrenia. In this paper, we report evidence that multiple single nucleotide polymorphisms in and around interleukin 3 (IL3) are associated with the disease in the Irish Study of High-Density Schizophrenia Families (ISHDSF), the Irish Case-Control Study of Schizophrenia (ICCSS) and the Irish Trio Study of Schizophrenia (ITRIO). The associations are sex-specific and depend on the family history (FH) of schizophrenia. In all three samples, rs31400 shows female-specific and FH-dependent associations (P=0.0062, 0.0647 and 0.0284 for the ISHDSF, ICCSS and ITRIO, respectively). Several markers have similar associations in one or two of the three samples. In haplotype analyses, identical risk and protective haplotypes are identified in the ISHDSF and ITRIO samples in several multimarker combinations. For ICCSS, the same haplotypes are implicated; however, the risk haplotypes observed in the family samples become protective. Several significant markers, rs440970, rs31400 and rs2069803, are located in and around known estrogen response elements, promoter and enhancer of the IL3 gene. They may explain the sex-specific associations and be functional for the expression of IL3 gene.

Case-Control Studies↗

PubMed2006

Thiamine deficiency induces endoplasmic reticulum stress in neurons.

Thiamine (vitamin B1) deficiency (TD) causes region selective neuronal loss in the brain; it has been used to model neurodegeneration that accompanies mild impairment of oxidative metabolism. The mechanisms for TD-induced neurodegeneration remain incompletely elucidated. Inhibition of protein glycosylation, perturbation of calcium homeostasis and reduction of disulfide bonds provoke the accumulation of unfolded proteins in the endoplasmic reticulum (ER), and cause ER stress. Recently, ER stress has been implicated in a number of neurodegenerative models. We demonstrated here that TD up-regulated several markers of ER stress, such as glucose-regulated protein (GRP) 78, growth arrest and DNA-damage inducible protein or C/EBP-homologus protein (GADD153/Chop), phosphorylation of eIF2alpha and cleavage of caspase-12 in the cerebellum and the thalamus of mice. Furthermore, ultrastructural analysis by electron microscopic study revealed an abnormality in ER structure. To establish an in vitro model of TD in neurons, we treated cultured cerebellar granule neurons (CGNs) with amprolium, a potent inhibitor of thiamine transport. Exposure to amprolium caused apoptosis and the generation of reactive oxygen species in CGNs. Similar to the observation in vivo, TD up-regulated markers for ER stress. Treatment of a selective inhibitor of caspase-12 significantly alleviated amprolium-induced death of CGNs. Thus, ER stress may play a role in TD-induced brain damage.

Amprolium↗

PubMed2006

Anisotropy and corotation of galactic cosmic rays.

The intensity of Galactic cosmic rays is nearly isotropic because of the influence of magnetic fields in the Milky Way. Here, we present two-dimensional high-precision anisotropy measurement for energies from a few to several hundred teraelectronvolts (TeV), using the large data sample of the Tibet Air Shower Arrays. Besides revealing finer details of the known anisotropies, a new component of Galactic cosmic ray anisotropy in sidereal time is uncovered around the Cygnus region direction. For cosmic-ray energies up to a few hundred TeV, all components of anisotropies fade away, showing a corotation of Galactic cosmic rays with the local Galactic magnetic environment. These results have broad implications for a comprehensive understanding of cosmic rays, supernovae, magnetic fields, and heliospheric and Galactic dynamic environments.

Journal Article↗

PubMed2006

Apoptosis-inducing factor is a major contributor to neuronal loss induced by neonatal cerebral hypoxia-ischemia.

Nine-day-old harlequin (Hq) mice carrying the hypomorphic apoptosis-inducing factor (AIF)(Hq) mutation expressed 60% less AIF, 18% less respiratory chain complex I and 30% less catalase than their wild-type (Wt) littermates. Compared with Wt, the infarct volume after hypoxia-ischemia (HI) was reduced by 53 and 43% in male (YX(Hq)) and female (X(Hq)X(Hq)) mice, respectively (P<0.001). The Hq mutation did not inhibit HI-induced mitochondrial release of cytochrome c or activation of calpain and caspase-3. The broad-spectrum caspase inhibitor quinoline-Val-Asp(OMe)-CH(2)-PH (Q-VD-OPh) decreased the activation of all detectable caspases after HI, both in Wt and Hq mice. Q-VD-OPh reduced the infarct volume equally in Hq and in Wt mice, and the combination of Hq mutation and Q-VD-OPh treatment showed an additive neuroprotective effect. Oxidative stress leading to nitrosylation and lipid peroxidation was more pronounced in ischemic brain areas from Hq than Wt mice. The antioxidant edaravone decreased oxidative stress in damaged brains, more pronounced in the Hq mice, and further reduced brain injury in Hq but not in Wt mice. Thus, two distinct strategies can enhance the neuroprotection conferred by the Hq mutation, antioxidants, presumably compensating for a defect in AIF-dependent redox detoxification, and caspase inhibitors, presumably interrupting a parallel pathway leading to cellular demise.

Amino Acid Chloromethyl Ketones↗

PubMed2006

Porcine reproductive and respiratory syndrome virus productively infects monocyte-derived dendritic cells and compromises their antigen-presenting ability.

Dendritic cells (DC) are potent antigen-presenting cells that play an important role in inducing primary antigen-specific immune responses. However, some viruses have evolved to specifically target DC to circumvent the host's immune responses for their persistence in the host. Porcine reproductive and respiratory syndrome virus (PRRSV) causes a persistent infection in susceptible animals. Although it is generally believed that the existence of PRRSV quasispecies is partly responsible for the virus persistence, other mechanisms of immune evasion or immune suppression may also exist. Here, we studied the role of DC in PRRSV persistence and immune suppression. Our results showed that PRRSV underwent a productive replication in pig monocyte-derived DC (Mo-DC) as measured by both immunofluorescence staining of viral nucleocapsid protein and virus titration assays, leading to cell death via both apoptosis and necrosis mechanisms. Additionally, PRRSV infection of Mo-DC resulted in reduced expression of MHC class I, MHC class II, CD14 and CD11b/c. This was in agreement with the impaired mixed lymphocyte reaction of PRRSV-infected Mo-DC compared to that of mock-infected Mo-DC. We also examined the cytokine profiles of PRRSV-infected Mo-DC using a quantitative ELISA method. Results indicated that no apparent change in the levels of IL-10, IL-12 and IFN-gamma was detected. Taken together, our data demonstrate that PRRSV productively infects Mo-DC and impairs the normal antigen presentation ability of Mo-DC by inducing cell death, down-regulating the expression of MHC class I, MHC class II, CD11b/c and CD14 and by inducing minimal Th1 cytokines.

Animals↗

PubMed2006

Sulfur-dioxide exposure increases TRPV1-mediated responses in nodose ganglia cells and augments cough in guinea pigs.

The objective of the present experiments was to study the effects of pulmonary inflammation induced by subacute Sulfur-dioxide (SO(2)) exposure on capsaicin-induced responses in isolated primary vagal sensory neurons and cough. Additionally, we examined the effects of SO(2) exposure on respiratory function and lung histology. All experiments were conducted 24 h after 4 days of subacute SO(2) (1000 ppm, 3 h/day for 4 days) exposure. In in vitro experiments, intracellular Ca(2+) concentrations were measured in single nodose ganglia cells isolated from SO(2) treated and control guinea pigs, using a fluorescence-based methodology. In nodose ganglia cells from SO(2)-exposed animals, intracellular Ca(2+) responses evoked by capsaicin (1 x 10(-7) and 1 x 10(-6) M) were significantly augmented (87% and 59%, respectively) compared to nodose ganglia from control animals. In vivo experiments, cough responses induced by a submaximal dose of aerosolized capsaicin (30 microM) were increased approximately 50% in SO(2) exposed animals compared to control animals. The enhanced cough response produced by SO(2) was inhibited by the corticosteroid, dexamethasone (10 mg/kg, p.o. b.i.d for 4 days and 10 mg/kg, p.o. once on day 5). In separate experiments, guinea pigs exposed to SO(2) displayed a decrease in respiratory frequency and minute ventilation and an increase in enhanced pause (PenH), a surrogate measure for pulmonary obstruction. Associated with the SO(2)-induced increase in cough and changes in respiratory parameters was an increase in BAL neutrophils. BAL neutrophil counts were 5+/-4 and 691+/-141 cells x 10(3)/ml for air and SO(2)-exposed animals, respectively. The neutrophillic inflammation induced by SO(2) was attenuated by dexamethasone treatment. Finally, staining for collagen, smooth muscle and goblet cells showed inflammation, remodeling and goblet cell metaphasia in the SO(2)-exposed animals. Our results demonstrate that SO(2) exposure enhances TRPV1 receptor function at the level of the nodose ganglia. This effect occurs in parallel with an increase sensitivity of the cough response to capsaicin.

Air Pollutants↗

PubMed2006

Genistein inhibits Brca1 mutant tumor growth through activation of DNA damage checkpoints, cell cycle arrest, and mitotic catastrophe.

Epidemiological studies revealed that amount of consumption of soy was inversely related to incidence of breast cancer. Genistein, the predominant isoflavone in soy, has been reported to reduce the incidence of breast cancer in animal models. To investigate whether genistein has a therapeutic effect on BRCA1-associated breast cancer, we treated Brca1 mutant mammary tumor cells with genistein. We showed that genistein treatment depleted the G1 population of cells, which was accompanied by an accumulation of cells at G2. Some genistein-treated cells entered mitosis; however, they exhibited chromosome abnormalities and maintained tetraploidy owing to abortive mitotic exit. A fraction of G2 cells underwent endoreduplication and became polyploid, which was accompanied by increased cell death through activating DNA damage response. Furthermore, our data indicated that Brca1 mutant cells were more sensitive to genistein than some other types of cancer cells, highlighting a good therapeutic potential of genistein for BRCA1-associated breast cancer.

Animals↗

PubMed2006

Highly efficient and specific modulation of cardiac calcium homeostasis by adenovector-derived short hairpin RNA targeting phospholamban.

Impaired function of the phospholamban (PLB)-regulated sarcoplasmic reticulum Ca(2+) pump (SERCA2a) contributes to cardiac dysfunction in heart failure (HF). PLB downregulation may increase SERCA2a activity and improve cardiac function. Small interfering (si)RNAs mediate efficient gene silencing by RNA interference (RNAi). However, their use for in vivo gene therapy is limited by siRNA instability in plasma and tissues, and by low siRNA transfer rates into target cells. To address these problems, we developed an adenoviral vector (AdV) transcribing short hairpin (sh)RNAs against rat PLB and evaluated its potential to silence the PLB gene and to modulate SERCA2a-mediated Ca(2+) sequestration in primary neonatal rat cardiomyocytes (PNCMs). Over a period of 13 days, vector transduction resulted in stable > 99.9% ablation of PLB-mRNA at a multiplicity of infection of 100. PLB protein gradually decreased until day 7 (7+/-2% left), whereas SERCA, Na(+)/Ca(2+) exchanger (NCX1), calsequestrin and troponin I protein remained unchanged. PLB silencing was associated with a marked increase in ATP-dependent oxalate-supported Ca(2+) uptake at 0.34 microM of free Ca(2+), and rapid loss of responsiveness to protein kinase A-dependent stimulation of Ca(2+) uptake was maintained until day 7. In summary, these results indicate that AdV-derived PLB-shRNA mediates highly efficient, specific and stable PLB gene silencing and modulation of active Ca(2+) sequestration in PNCMs. The availability of the new vector now enables employment of RNAi for the treatment of HF in vivo.

Animals↗

PubMed2006

Menstrual cycle lengths and bone mineral density: a cross-sectional, population-based study in rural Chinese women ages 30-49 years.

INTRODUCTION: The menstrual cycle involves periodic fluctuations in estrogen and progesterone levels. Longer cycles have been associated with longer follicular phase, delayed estrogen peak and a lower mean oestradiol level of the entire cycle. METHODS: We hypothesized that prolonged menstrual cycle length is associated with decreased bone mineral density (BMD) in a population of pre- and perimenopausal women. This population-based cross-sectional study was conducted in rural Anhui province, China. It includes 4,771 women, aged 30 to 49 years, who did not smoke or drink alcohol, and did not use oral contraceptives or breastfeed during the previous year. Dual-energy X-ray absorptionometry (DEXA) BMD measurements were taken at four skeletal sites: whole body, total hip, femoral neck and lumbar spine. Menstrual cycle characteristics (polymenorrhea, short normal, long normal, oligomenorrhea, 90-day amenorrhea, irregular cycle) in the prior year were assessed by questionnaire. RESULTS: Prolonged menstrual cycle was consistently associated with decreased BMD at whole body, total hip, and femoral neck in both age 30-39, and age 40-49 stratum (p(trend)<0.05). Prolonged menstrual cycle was also associated with decreased lumbar spine BMD for women aged 40-49 (p(trend)<0.05). Among women with normal cycles aged 30-39, menstrual cycle length in the previous year was inversely associated with whole-body BMD (p<0.05). Women with 90-day amenorrhea had significantly lower mean total hip and femoral neck BMD relative to women with short normal cycles in the 30-39 age group; and had significantly lower whole body and total hip BMD relative to short normal cycles in the 40-49 age group. BMD in polymenorrheic women did not differ from BMD in women with short normal cycles at any of the skeletal sites. CONCLUSIONS: We conclude that prolonged menstrual cycle length is associated with decreased BMD in pre- and perimenopausal women in this population.

Adult↗

PubMed2006

Phosphatidylinositol 3-kinase p85alpha regulatory subunit gene PIK3R1 haplotype is associated with body fat and serum leptin in a female twin population.

AIMS/HYPOTHESIS: Phosphatidylinositol 3-kinase (PI3K) couples the leptin and insulin signalling pathways via the insulin receptor substrates IRS1 and IRS2. Hence, defective activation of PI3K could be a novel mechanism of peripheral leptin or insulin resistance. We investigated associations of tagging single-nucleotide polymorphisms (tSNPs) in the PI3K p85alpha regulatory subunit gene PIK3R1 with anthropometry, leptin, body fat and insulin sensitivity in a female twin population of European extraction. MATERIALS AND METHODS: Eight tSNPs were genotyped in 2,778 women (mean age 47.4+/-12.5 years) from the St Thomas' UK Adult Twin Registry (Twins UK). RESULTS: SNP rs1550805 was associated with serum leptin (p=0.028), BMI (p=0.025), weight (p=0.019), total fat (p=0.004), total fat percentage (p=0.002), waist circumference (p=0.025), central fat (p=0.005) and central fat percentage (p=0.005). SNPs rs7713645 and rs7709243 were associated with BMI (p=0.020 and p=0.029, respectively), rs7709243 with weight, total and central fat (p=0.026, p=0.031 and p=0.023, respectively) and both SNPs with fasting glucose (p=0.003 and p=0.001, respectively) and glucose 2-h post OGTT (p=0.023 and p=0.007, respectively). Subjects with haplotype 222 (frequency 7.2%) showed higher serum leptin concentration (p=0.007) and body fat measures (p< or =0.001 for all), and those with haplotype 221 (frequency 38.7%) showed higher fasting and 2-h glucose (p=0.035 and p=0.021, respectively) compared with subjects with the most common haplotype, 111 (frequency 45.5%). CONCLUSIONS/INTERPRETATION: Association of the PIK3R1 SNP rs1550805 with serum leptin and body fat may reflect a diminished ability of PI3K to signal via IRS1 or IRS2 in response to leptin.

Adipose Tissue↗

PubMed2006

K isomers in 254No: probing single-particle energies and pairing strengths in the heaviest nuclei.

We have identified two isomers in 254No, built on two- and four-quasiparticle excitations, with quantum numbers K pi = 8- and (14+), as well as a low-energy 2-quasiparticle Kpi = 3+ state. The occurrence of isomers establishes that K is a good quantum number and therefore that the nucleus has an axial prolate shape. The 2-quasiparticle states probe the energies of the proton levels that govern the stability of superheavy nuclei, test 2-quasiparticle energies from theory, and thereby check their predictions of magic gaps.

Journal Article↗

PubMed2006

DNA-duplexes containing abasic sites: correlation between thermostability and acoustic wave properties.

Aldehydic apurinic or apyrimidinic sites that lack a nucleobase moiety are one of the most common forms of toxic lesions in DNA. In the present study, a close structural analog of such a site, the 2-(hydroxymethyl) tetrahydrofuranyl residue, was synthesized in order to act as a model for damaged nucleic acid probes. Prepared oligodeoxyribonucleotides containing one, two or three abasic sites were hybridized to complementary sequences immobilized on a gold surface using the neutravidin-biotin interaction for study by thickness shear mode acoustic wave detector. Measurement of the complex electrical impedance of an AT-cut quartz device with immobilized biotinylated nucleotide allowed the detection of changes of series resonance frequency, Deltafs, and motional resistance, Rm, associated with duplex formation. The changes as detected by the acoustic wave method correlated well with the thermostability of DNA duplexes in solution. With respect to the latter, UV-monitored melting curves indicate that both the number of sites and their localization in the double-stranded structure influence the amount by which a 19 b.p. duplex is destabilized. The presence of 3 abasic sites completely destabilized the DNA duplex.

Acoustics↗

PubMed2006

Cigarette smoke upregulates pulmonary vascular matrix metalloproteinases via TNF-alpha signaling.

Cigarette smoke exposure causes vascular remodeling and pulmonary hypertension by poorly understood mechanisms. To ascertain whether cigarette smoke exposure affects production of matrix metalloproteinases (MMPs) in the pulmonary vessels, we exposed C57Bl/6 (C57) mice or mice lacking TNF-alpha receptors (TNFRKO) to smoke daily for 2 wk or 6 mo. Using laser capture microdissection and RT-PCR analysis, we examined gene expression of MMP-2, MMP-9, MMP-12, MMP-13, and tissue inhibitor of metalloproteinase (TIMP-1) and examined protein production by immunohistochemistry for MMP-2, MMP-9, and MMP-12 in small intrapulmonary arteries. At 2 wk, mRNA levels of TIMP-1 and all MMPs were increased in the C57, but not TNFRKO, mice, and immunoreactive protein for MMP-2, MMP-9, and MMP-12 was also increased in the C57 mice. Increased gelatinase activity was identified by in situ and bulk tissue zymography. At 6 mo, only MMP-12 mRNA levels remained increased in the C57 mice, but at a much lower level; however, MMP-2 mRNA levels increased in the TNFRKO mice. We conclude that smoke exposure increases MMP production in the small intrapulmonary arteries but that, with the exception of MMP-12, increased MMP production is transient. MMPs probably play a role in smoke-induced vascular remodeling, as they do in other forms of pulmonary hypertension, implying that MMP inhibitors might be beneficial. MMP production is largely TNF-alpha dependent, further supporting the importance of TNF-alpha in the pathogenesis of cigarette smoke-induced lung disease.

Animals↗

PubMed2006

A novel scratching approach for measuring age-related changes in the in situ toughness of bone.

A scratch test using a nanoindentation system was proposed in this study to assess the age-related changes in the in situ toughness of bone matrix at ultrastructural levels. A tissue removal energy density (u(r)) was defined and estimated as the work done by the scratch (U(T)) divided by the total volume of the scratch groove (u(s)). The value of u(s) was used as a relative measure of the in situ toughness of the tissue. Human cortical bone specimens obtained from middle-aged (between 49 and 59 years old) and elderly groups (over 69 years old) were tested using this technique. A significant difference in the estimated removal energy density (u(s)) in the secondary osteons was found between the middle-aged and elderly groups (5.49+/-0.696 vs. 4.09+/-1.30 N/mm(2), respectively).

Aged↗

PubMed2006

Role of MEK/ERK pathway in the MAD2-mediated cisplatin sensitivity in testicular germ cell tumour cells.

Testicular germ cell tumour (TGCT) is the most common malignancy in young males. Although most TGCTs are sensitive to cisplatin-based chemotherapy, significant numbers of TGCT patients still relapse and die each year because of the development of resistance to cisplatin. Previously, we first reported that a key regulator of the mitotic checkpoint, mitotic arrest deficient-2 (MAD2), was a mediator of cisplatin sensitivity in human cancer cells. In this study, we investigated whether MAD2 played a role in cellular sensitivity to cisplatin in TGCT cells and the underlying molecular mechanisms responsible. Using 10 TGCT cell lines, we found that increased MAD2 expression was correlated with cellular sensitivity to cisplatin, which was associated with activation of the MEK pathway. Treatment of cells expressing high levels of MAD2 with an MEK inhibitor, U0126, led to cellular protection against cisplatin-induced apoptosis. Inactivation of MAD2 by transfecting a dominant-negative construct in TGCT cells with high levels of MAD2 resulted in the suppression of MEK pathway and resistance to cisplatin-induced cell death. These results support previous suggestion on the involvement of mitotic checkpoint in DNA damage response in human cancer cells and demonstrate a possible molecular mechanism responsible for the MAD2-mediated sensitivity to cisplatin in TGCT cells. Our results also suggest that downregulation of MAD2 may be an indicator for identification of TGCT cancer cells that are potentially resistant to cisplatin-based therapy.

Butadienes↗

PubMed2006

Prenatal cannabis exposure increases heroin seeking with allostatic changes in limbic enkephalin systems in adulthood.

BACKGROUND: Prenatal cannabis exposure is a growing concern with little known about the long-term consequences on behavior and neural systems relevant for reward and emotional processing. METHODS: We used an animal model to study the effects of prenatal exposure to Delta(9)-tetrahydrocannabinol (THC) on heroin self-administration behavior and opioid neural systems in adult males (postnatal day 62). Rats were exposed to THC (.15 mg/kg) or vehicle from gestational day 5 to postnatal day 2. RESULTS: Both pretreatment groups showed similar heroin intake, but THC-exposed rats exhibited shorter latency to the first active lever press, responded more for low heroin doses, and had higher heroin-seeking during mild stress and drug extinction. THC exposure reduced preproenkephalin (PENK) mRNA expression in the nucleus accumbens during early development, but was elevated in adulthood; no adult striatal changes on preprodynorphin mRNA or PENK in caudate-putamen. PENK mRNA was also increased in the central and medial amygdala in adult THC-exposed animals. THC animals had reduced heroin-induced locomotor activity and nucleus accumbens mu opioid receptor coupling. CONCLUSIONS: This study demonstrates enduring effects of prenatal THC exposure into adulthood that is evident on heroin-seeking behavior during extinction and allostatic changes in mesocorticolimbic PENK systems relevant to drug motivation/reward and stress response.

Analysis of Variance↗

PubMed2006

On the role of cross-immunity and vaccines on the survival of less fit flu-strains.

A pathogen's route to survival involves various mechanisms including its ability to invade (host's susceptibility) and its reproductive success within an invaded host ("infectiousness"). The immunological history of an individual often plays an important role in reducing host susceptibility or it helps the host mount a faster immunological response de facto reducing infectiousness. The cross-immunity generated by prior infections to influenza A strains from the same subtype provide a significant example. The results of this paper are based on the analytical study of a two-strain epidemic model that incorporates host isolation (during primary infection) and cross-immunity to study the role of invasion mediated cross-immunity in a population where a precursor related strain (within the same subtype, i.e. H3N2, H1N1) has already become established. An uncertainty and sensitivity analysis is carried out on the ability of the invading strain to survive for given cross-immunity levels. Our findings indicate that it is possible to support coexistence even in the case when invading strains are "unfit", that is, when the basic reproduction number of the invading strain is less than one. However, such scenarios are possible only in the presence of isolation. That is, appropriate increments in isolation rates and weak cross-immunity can facilitate the survival of less fit strains. The development of "flu" vaccines that minimally enhance herd cross-immunity levels may, by increasing genotype diversity, help facilitate the generation and survival of novel strains.

Animals↗