Trends in Economic Science: Discussions of the Paths of Russian Modernization in the 19th-20th Centuries.

The article analyzes the evolution of economic thought in Russia throughout the 19th-20th centuries. The global context that shaped Russian economic science and the goals that it has faced are considered. The processes of the formation of different views on the country's development, economic policy, and the role of the state in the economy are described. It is shown that at the beginning of the 19th century the dominant ideas were those of classical economic liberalism. The issue of the emergence of the problem of catch-up development and its impact on the economic thought in Russia is discussed. The main directions of the development of views on regulation of the economy in the conditions of its increasing complexity in the process of industrial development-in particular, the strengthening role of the state and the selection of priorities of economic policy-are discussed. It is emphasized that by the end of the 20th century methods of government control of the economy had experienced a severe crisis, associated, among other reasons, with the collapse of the Eastern bloc. However, at the beginning of the 21st century, due to a number of objective and subjective reasons, the role of the state in economic management began to increase again.

Profiles of exposure to potentially traumatic events in refugees living in Australia.

AIMS: Refugees and asylum-seekers are typically exposed to multiple potentially traumatic events (PTEs) in the context of war, persecution and displacement, which confer elevated risk for psychopathology. There are significant limitations, however, in extant approaches to measuring these experiences in refugees. The current study aimed to identify profiles of PTE exposure, and the associations between these profiles and key demographics, contextual factors (including ongoing stressors, method of travel to Australia and separation from family), mental health and social outcomes, in a large sample of refugees resettled in Australia. METHODS: Participants were 1085 from Arabic, Farsi, Tamil and English-speaking refugee backgrounds who completed an online or pen-and-paper survey in their own language. Constructs measured included PTE exposure, demographics, pre-displacement factors, ongoing stressors, post-traumatic stress disorder symptoms, depression symptoms, anger reactions, plans of suicide and social engagement. RESULTS: Latent class analysis identified four profiles of PTE exposure, including the torture and pervasive trauma class, the violence exposure class, the deprivation exposure class and the low exposure class. Compared to the low exposure class, participants in the trauma-exposed classes were more likely to be male, highly educated, from Farsi and Tamil-speaking backgrounds, have travelled to Australia by boat, experience more ongoing stressors and report both greater psychological symptoms and social engagement. CONCLUSIONS: This study found evidence for four distinct profiles of PTE exposure in a large sample of resettled refugees, and that these were associated with different demographic, psychological and social characteristics. These findings suggest that person-centred approaches represent an important potential avenue for investigation of PTE exposure in refugees, particularly with respect to identifying subgroups of refugees who may benefit from different types or levels of intervention according to their pre-migration PTE experiences.

IL-12 receptor ß1 deficiency alters in vivo T follicular helper cell response in humans.

Antibody responses represent a key immune protection mechanism. T follicular helper (Tfh) cells are the major CD4(+) T-cell subset that provides help to B cells to generate an antibody response. Tfh cells together with B cells form germinal centers (GCs), the site where high-affinity B cells are selected and differentiate into either memory B cells or long-lived plasma cells. We show here that interleukin-12 receptor ß1 (IL-12Rß1)-mediated signaling is important for in vivo Tfh response in humans. Although not prone to B cell-deficient-associated infections, subjects lacking functional IL-12Rß1, a receptor for IL-12 and IL-23, displayed substantially less circulating memory Tfh and memory B cells than control subjects. GC formation in lymph nodes was also impaired in IL-12Rß1-deficient subjects. Consistently, the avidity of tetanus toxoid-specific serum antibodies was substantially lower in these subjects than in age-matched controls. Tfh cells in tonsils from control individuals displayed the active form of signal transducer and activator of transcription 4 (STAT4), demonstrating that IL-12 is also acting on Tfh cells in GCs. Thus, our study shows that the IL-12-STAT4 axis is associated with the development and the functions of Tfh cells in vivo in humans.

Rhythmic expression of clock and clock-controlled genes in the rat oviduct.

The rhythmic expression of clock and clock-controlled genes in the rat oviduct was investigated by real time RT-PCR. per1, per2, Clock, Bmal1, cry1 and cry2 were all expressed in the oviduct. With 4-hourly sampling over 24 h in a normal photoperiod, analysis of variance indicated that per2 and Bmal1 had highly significant sinusoidal-like changes with an amplitude of 3- and 10-fold respectively. Of the other clock genes, per1 and cry1 had non-significant rhythm amplitudes of 2.5- and 1.8-fold respectively. Using the same experimental approach the rhythmic expression of Bmal1, per1 and per2 mRNA in the liver was found to be highly significant with amplitudes of approximately 20-, 10- and 5-fold respectively. The expression of the clock-controlled transcription factors DBP and Rev-erb alpha showed significant rhythmicity in the oviduct with 5-fold changes in amplitude for both genes. Plasminogen activator inhibitor-1 (PAI-1), which has been implicated in oviduct function during the preimplantation period, also had a significant rhythm of expression (2.5-fold amplitude), peaking at the same time as the other clock-controlled genes, DBP and Rev-erb alpha. These results show for the first time that the female reproductive tract is inherently rhythmic and suggests that the developing embryo may be subjected to rhythmic changes in the environment created by the oviduct during transition to the uterus.

Uterine eosinophils and reproductive performance in interleukin 5-deficient mice.

Interleukin 5 is expressed in type 2 T lymphocytes and has a key role in driving the differentiation, recruitment and activation of eosinophils. Mice with a null mutation in the interleukin 5 gene (IL-5 -/- mice) have altered type 2 immune responses and severely depleted eosinophil populations. In the present study, the effect of interleukin 5 deficiency on the abundant population of eosinophils present in the female reproductive tract was investigated, and the reproductive performance in C57Bl/6 IL-5 -/- mice was measured. Endometrial eosinophils, detected on the basis of their endogenous peroxidase activity, were reduced in number by four-sevenfold during the oestrous cycle and in early pregnancy in IL-5 -/- mice. Eosinophils present in the cervix and decidual tissues at the time of parturition were similarly diminished. The temporal fluctuations in eosinophil recruitment and localization within these tissues were otherwise unchanged, indicating that interleukin 5 is not a necessary chemotactic agent in the female reproductive tract. Oestrous cycles were moderately greater in duration in IL-5 -/- mice (mean +/- SD = 5.6 +/- 1.0 days in IL-5 -/- mice versus 5.0 +/- 0.8 days in IL-5 +/+ mice), owing to an extended period in oestrus (2.7 +/- 0.9 days per cycle in IL-5 -/- mice versus 1.8 +/- 0.7 in IL-5 +/+ mice). The interval between placing females with males and the finding of copulatory plugs was reduced significantly in interleukin 5-deficient mice. Implantation rates and subsequent fetal development were comparable in IL-5 -/- and IL-5 +/+ mice, irrespective of whether pregnancies were sired by syngeneic (C57Bl/6) or allogeneic (CBA or Balb/c) males, apart from a 10% increase in placental size and a 6.5% decrease in placental∶fetal ratio seen on day 17 in pregnancies sired by CBA males. Parturition and post-partum uterine repair were not compromised in interleukin 5-deficient mice, as judged by the length of gestation, and the outcomes of pregnancies initiated at post-partum oestrus. The birth weights and growth trajectories of pups were significantly influenced by interleukin 5 status, with small but significant increases in the weights of IL-5 -/- pups, particularly C57Bl/6 and CBA F(1) animals, remaining evident until adulthood. These data are consistent with the view that eosinophils have a role in endometrial tissue remodelling associated with the oestrous cycle, but indicate that the events of pregnancy and parturition proceed quite normally in the absence of maternal and fetal interleukin 5. However, strain-dependent effects of interleukin 5 deficiency on placental growth and function and subsequent weight gain in the newborn indicate that this cytokine may act through the maternal or fetal immune axis to exert subtle influences on reproductive outcome.

Cytokine-leukocyte networks and the establishment of pregnancy.

PROBLEM: Factors in seminal plasma stimulate an intense but transient inflammatory response in the murine endometrium at mating. The aim of our current studies is to delineate the cytokine-leukocyte interactions comprising this response and to elucidate the significance of these events in changes in the maternal immune system and as determinants of pregnancy outcome. METHOD: We have reviewed our recent findings. RESULTS: Transforming growth factor (TGF)-beta1 has been identified as the inflammation-inducing moiety in seminal plasma. Seminal TGFbeta1 initiates endometrial leukocyte infiltration by up-regulating epithelial cell expression of granulocyte-macrophage colony-stimulating factor. Other cytokines and chemokines including regulated and normal T-cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and monocyte chemotactic protein-1 are also implicated as mediators of macrophage and granulocyte recruitment and activation. One consequence of this inflammatory response is the induction of a transient state of hyporesponsiveness to paternal major histocompatibility class I antigens. CONCLUSION: Our studies suggest that semen may play a critical role in providing the antigenic and environmental signals necessary to initiate an appropriate maternal immune response to the conceptus during pregnancy.

Role of high molecular weight seminal vesicle proteins in eliciting the uterine inflammatory response to semen in mice.

Mating evokes a characteristic pattern of molecular and cellular events in the rodent reproductive tract, including an infiltration of the endometrial stroma and uterine lumen with activated macrophages and granulocytes, which closely resembles a classic inflammatory response. Previous studies in mice indicate that these cellular changes are associated with, and are largely a consequence of, an upregulated synthesis and release of granulocyte-macrophage colony-stimulating factor (GM-CSF) from the uterine epithelium in response to seminal fluid. The aim of this study was to investigate further the origin and nature of the factors present in seminal fluid that trigger the GM-CSF response. It was found that the characteristic increase in uterine expression of mRNA encoding GM-CSF and release of GM-CSF bioactivity from uterine epithelial cells into the luminal cavity seen after mating with intact or vasectomized males was no longer evident in matings with male mice from whom the seminal vesicles had been surgically removed. The extent of inflammatory leucocyte infiltration into the endometrium was also reduced; the most notable effect was a complete absence of the exocytosis of neutrophils into the luminal cavity normally seen after matings with intact or vasectomized males. Bioassay of the GM-CSF output of oestrous endometrial cells after culture with crude or Sephacryl S-400 chromatographed fractions of seminal vesicle fluid showed that the GM-CSF stimulating activity was predominantly associated with protein moieties in seminal vesicle fluid of approximately 650,000 M(r) and 100,000-400,000 M(r). These data confirm the presence in seminal vesicle fluid of specific factors that initiate an inflammatory response in the uterus after mating through upregulating GM-CSF synthesis in the uterine epithelium. The significance of the cytokine release and cellular changes induced by seminal plasma for implantation of the conceptus and pregnancy outcome remain to be determined.

Cytokine secretion by macrophages in the rat testis.

The rat testis contains a large population of resident macrophages, the physiological roles of which are yet to be established. To investigate the functional capacity of these cells, we have analyzed the secretion of the cytokines interleukin (IL)-1, IL-6, tumor necrosis factor alpha (TNF alpha), and granulocyte macrophage-colony stimulating factor (GM-CSF) by isolated testicular macrophages (TMs) and, for comparison, by isolated rat peritoneal macrophages (PMs). Cells were cultured for 48 h in serum-free medium alone or with lipopolysaccharide (LPS, 10 micrograms/ml) and/or recombinant interferon-gamma (rIFN gamma, 200 U/ml). Specific bioassays were used to measure cytokines in the media collected from cultures. Basal production of IL-1, TNF alpha, and IL-6 by TMs and PMs were similar, but TMs produced 8-fold greater levels of GM-CSF than did PMs. LPS, alone or in combination with IFN gamma, significantly enhanced the secretion of all cytokines by PMs (340-840% increase). LPS alone had little effect on TM secretion except to reduce GM-CSF levels some 4-fold. The addition of LPS and IFN gamma increased IL-1, IL-6, and TNF alpha levels (200-750% increase) and reduced GM-CSF levels to 45% of basal levels. Treatment of cultures with indomethacin to minimize prostaglandin production enhanced the LPS-induced effects in both cell types. Expression of the mRNA for each cytokine in cultures of testicular and peritoneal macrophages, as well as in intact testis, was confirmed by reverse transcription polymerase chain reaction. These studies indicate that macrophages resident within the rat testis have a novel cytokine secretion profile and an altered responsiveness to inflammatory activators compared with macrophages from the peritoneal cavity. This may be important in physiological processes in the testis and may contribute to the dysfunctional afferent immune activity thought to underlie the immunologically privileged status of the testes.