Inflationary cosmology has been developed over the last twenty years to remedy serious shortcomings in the standard hot big bang model of the universe. This textbook, first published in 2005, explains the basis of modern cosmology and shows where the theoretical results come from. The book is divided into two parts; the first deals with the homogeneous and isotropic model of the Universe, the second part discusses how inhomogeneities can explain its structure. Established material such as the inflation and quantum cosmological perturbation are presented in great detail, however the reader is brought to the frontiers of current cosmological research by the discussion of more speculative ideas. An ideal textbook for both advanced students of physics and astrophysics, all of the necessary background material is included in every chapter and no prior knowledge of general relativity and quantum field theory is assumed.

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Physical Foundations of Cosmology

Cancer Invasion and the Microenvironment: Plasticity and Reciprocity

Climate change in the past has led to significant changes in species' distributions. However, how individual species respond to climate change depends largely on their adaptations and environmental tolerances. In the Quaternary, temperate-adapted taxa are in general confined to refugia during glacials while cold-adapted taxa are in refugia during interglacials. In the Northern Hemisphere, evidence appears to be mounting that in addition to traditional southern refugia for temperate species, cryptic refugia existed in the North during glacials. Equivalent cryptic southern refugia, to the south of the more conventional high-latitude polar refugia, exist in montane areas during periods of warm climate, such as the current interglacial. There is also a continental/oceanic longitudinal gradient, which should be included in a more complete consideration of the interaction between species ranges and climates. Overall, it seems clear that there is large variation in both the size of refugia and the duration during which species are confined to them. This has implications for the role of refugia in the evolution of species and their genetic diversity.

https://royalsocietypublishing.org/doi/pdf/10.1098/rspb.2009.1272

Refugia revisited: individualistic responses of species in space and time

Plant biologists have long recognized that host defence against parasites and pathogens can be divided into two conceptually different components: the ability to limit parasite burden (resistance) and the ability to limit the harm caused by a given burden (tolerance). Together these two components determine how well a host is protected against the effects of parasitism. This distinction is useful because it recognizes that hosts that are best at controlling parasite burdens are not necessarily the healthiest. Moreover, resistance and tolerance can be expected to have different effects on the epidemiology of infectious diseases and host–parasite coevolution. However, studies of defence in animals have to date focused on resistance, whereas the possibility of tolerance and its implications have been largely overlooked. The aim of our review is to (i) describe the statistical framework for analysis of tolerance developed in plant science and how this can be applied to animals, (ii) review evidence of genetic and environmental variation for tolerance in animals, and studies indicating which mechanisms could contribute to this variation, and (iii) outline avenues for future research on this topic.

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Decomposing health: tolerance and resistance to parasites in animals.

https://helda.helsinki.fi/bitstream/handle/10138/22049/gelatina.pdf?sequence=1

Gelatinase-mediated migration and invasion of cancer cells.

OBJECTIVE To establish an indirect immunofluorescent test so as to improve the sensitivity and specificity of examination of antibodies to beta(2)-glycoprotein METHODS Full-length beta(2)GP cDNA was obtained from human hepatocellular cancer cell line HepG2 by RT-PCR and cloned into the mammalian expression vector pEGFP-C1 The recombinant plasmid pEGFP-beta(2)GP was transfected into HEp-2 cells RT-PCR, immunoblotting (IBT), confocal fluorescence microscopy, and indirect immunofluorescent test (IIF) were used to confirm the expression, localization, and antigenicity of fusion protein of green fluorescent protein (GFP) Serum specimens from 19 patients suspected as with secondary antiphospholipid syndrome (APS), 1 patient diagnosed as with primary APS, and 10 normal persons were detected with IIF-IgG-beta(2)GP1, ELISA-IgG-ACL, and ELISA-IgG-beta(2)GP I simultaneously RESULTS (1) The HEp-beta(2)GP I cells thus obtained retained their ability of expression of beta(2)GP-I-GFP for more than ten generations This beta(2)GP-I-GFP showed the antigenicity of beta(2)GP-I with a characteristic feature (2) Seven of the 20 serum specimens from APS patients showed characteristic immunofluorescent pattern No serum specimen from normal persons showed immunofluorescent staining The comparison of results of the three methods showed that the concordance between IIF-IgG-beta(2)GP I and ELISA-IgG-beta(2)GP I was the most perfect (Kappa = 0886) (3) HEp-beta(2)GP I retained the immunofluorescent property of HEp-2 cell CONCLUSION As a new kind of substrate of IIF, beta(2)GP I transfectant can be used to detect anti-beta(2)GP-I antibodies Transfeted HEp-2 cells keep the immunofluorescent property of HEp-2 cells in IFANA test and can be used as substrate for routine IFANA detection

[Expression of fusion proteins in beta(2)GP I gene-transfected HEp-2 cells and its clinical application].

The purpose of this study is to describe the etiology, characteristics and outcomes of central nervous system (CNS) infections in patients with systemic lupus erythematosus (SLE), while also identifying prognostic and risk factors. Thirty-eight SLE patients with CNS infections were identified from review of all charts of patients with SLE hospitalized from January 1995 to June 2005. These patients were divided into 3 groups, i.e., Mycobacterium tuberculosis (TB), non-TB bacterial and fungal infection groups. Of the 38 SLE cases with CNS infections, TB was identified in 19 patients, Listeria monocytogenes in 3 patients, Klebsiella pneumoniae in 1 patient, Staphylococcus aureus in 1 patient, Gram's stain positive bacteria in 1 patient, Cryptococcus neoformans in 12 patients, and Aspergillus fumigatus in 1 patient. The rate of unfavorable outcome in patients with fungal infection was lower than in patients with TB (P=0.028) and non-TB bacterial CNS infections (P=0.046). SLE patients with TB or fungal CNS infections had a more insidious or atypical clinical presentation. Compared to SLE patients without CNS infections, those with CNS infections were more likely to have low serum albumin levels (P=0.048) and have been receiving higher doses of prednisolone at the onset of CNS infection (P=0.015) or higher mean doses of prednisolone within the previous year (P=0.039). In conclusion, low levels of serum albumin and higher doses of received prednisolone are important risk factors for the development of CNS infections in SLE patients.

Clinical features, prognostic and risk factors of central nervous system infections in patients with systemic lupus erythematosus.

The aim of the present study was to determine the levels of soluble fractalkine (sFKN) and expression of CX3CR1 in neuropsychiatric systemic lupus erythematosus (NPSLE). Disease activity of SLE was assessed using the SLE Disease Activity Index (SLEDAI). The mRNA expression levels of CX3CR1 and FKN were quantified using reverse transcription-quantitative polymerase chain reaction. Levels of sFKN in the serum and cerebrospinal fluid (CSF) were measured using enzyme-linked immunosorbent assays. The mRNA expression levels of CX3CR1 in peripheral blood mononuclear cells from patients with NPSLE, non-NPSLE and Behcet's disease were significantly higher than that of rheumatoid arthritis and healthy persons. Levels of sFKN in the serum and CSF of cells with diffuse NPSLE (DNPSLE) were significantly higher than those of focal NPSLE (FNPSLE) cells. Serum levels of sFKN were higher in patients with NPSLE or non-NPSLE than heathy persons. sFKN in CSF were significantly higher in DNPSLE than non-NPSLE cells, but there were no significant difference between FNPSLE and control. Treatment reduced sFKN in serum and CSF in patients with NPSLE. There was significant correlation between sFKN in the serum of patients with SLE and the SLEDAI. sFKN levels were correlated with IgG in CSF from patients with NPSLE. The mRNA expression levels of CX3CR1 in the brain tissue of lupus mice were significantly higher than normal mice; however, the mRNA expression of FKN was lower than normal mice. These results suggest that sFKN and CX3CR1 may be involved in vasculitis and SLE, particularly in DNPSLE, which may occur by damaging the blood-brain barrier or recruiting expression microglial cells of CX3CR1. Additionally, sFKN appears to be a serological marker in patients with SLE, and may be useful for the diagnosis and treatment of NPSLE.

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Elevated levels of soluble fractalkine and increased expression of CX3CR1 in neuropsychiatric systemic lupus erythematosus.

OBJECTIVE: To study the association between bcl-2 gene polymorphism and systemic lupus erythematosus (SLE) in Chinese and detect the synergism between IL-10 and bcl-2 genotypes in determining susceptibility to SLE METHODS: The peripheral white blood cells from 232 nuclear families of SLE and 106 ethnically matched normal controls were collected and the DNA extracted The allelic distribution of one microsatellite located in Bcl-2 gene was determined by using fluorescent-labeled primer and genotyping method RESULTS: (1) The distribution frequency of Bcl-2 alleles and its major genotypes were significantly different between SLE group and normal controls (P = 0001 and 00029 respectively) (2) Transmission disequilibrium existed in Bcl-2 alleles Bcl-2-195 bp allele was preferentially transmitted to affected offspring (t: non-t = 122:82, P = 00051) by TDT approach Individuals carrying specific genotypes with both Bcl-2-195 bp allele and IL-10G138 bp allele were at higher risk of developing SLE than those carrying only Bcl-2-195 bp allele or IL-10G138 bp allele (OR = 300, 177, 107 respectively) CONCLUSION: Bcl-2 gene polymorphism is associated with SLE and may be directly involved in the process of SLE or in linkage disequilibrium with some susceptibility loci nearby Synergistic effect may exist between IL-10 and bcl-2 genotypes in determining susceptibility to SLE

[Association between Bcl-2 gene polymorphism with systemic lupus erythematosus].

Objective To localize susceptibility loci in Chinese systemic lupus erythematosus (SLE) cohort by linkage disequilibrium mapping the genomic interval in human chromosome 16 so as to understand whether the pathogenesis of human SLE is related to chromosome 16. Methods Five microsatellite markers in chromosome 16 spanning from 57.79 cM to 65.1 cM were used for fluorescence based genotyping in 157 SLE families. Evidence for linkage disequilibrium was assessed using the extended transmission disequilibrium test (ETDT) program and Genehunter software. Susceptibility gene was searched in the positive locus, and real time PCR method was used to detect gene expression. Results With the ETDT, evidence for linkage disequilibrium of the marker D16S409 ( P =0.0278) and D16S517 ( P 0 0001) with SLE were found. It was observed that 271 bp allele of D16S517 was much in evidence for preferential transmission, while 277 bp allele was found to be transmitted less often than expected. Genehunter analysis is concordant with ETDT. By real time PCR, OAZ(OLF1/ EBF associated zinc finger protein)gene which is located in the positive locus showed higher expression in SLE patients than in normal controls. Conclusion Results reveal that 16q12 (58.46 cM) is associated with Chinese SLE. OAZ is a likely susceptibility gene in this locus for SLE.

Yuan Wang

Papers

[Expression of fusion proteins in beta(2)GP I gene-transfected HEp-2 cells and its clinical application].

Clinical features, prognostic and risk factors of central nervous system infections in patients with systemic lupus erythematosus.

Elevated levels of soluble fractalkine and increased expression of CX3CR1 in neuropsychiatric systemic lupus erythematosus.

[Association between Bcl-2 gene polymorphism with systemic lupus erythematosus].

Susceptibility gene of systemic lupus erythematosus in 16q12 in Chinese cohort