17β-estradiol inhibits the production of infectious particles of hepatitis C virus

Persistent infection with hepatitis C virus causes serious liver diseases, such as chronic hepatitis, hepatic cirrhosis and hepatocellular carcinoma. The male gender is one of the critical factors in progression of hepatic fibrosis due to chronic HCV infection; thus female hormones may play a role in delaying the progression of hepatic fibrosis. It has also been reported that women are more likely than men to clear HCV in the acute phase of infection. These observations lead the present authors to the question: do female hormones inhibit HCV infection? In this study using HCV J6/JFH1 and Huh‐7.5 cells, the possible inhibitory effect(s) of female hormones such as 17β‐estradiol (the most potent physiological estrogen) and progesterone on HCV RNA replication, HCV protein synthesis and production of HCV infectious particles (virions) were analyzed. It was found that E₂, but not P₄, significantly inhibited production of the HCV virion without inhibiting HCV RNA replication or HCV protein synthesis. E₂–mediated inhibition of HCV virion production was abolished by a nuclear estrogen receptor (ER) antagonist ICI182780. Moreover, treatment with the ERα‐selective agonist 4, 4′, 4″‐ (4‐propyl‐[1H]‐pyrazole‐1, 3, 5‐triyl)trisphenol (PPT), but not with the ERβ‐selective agonist 2, 3‐bis (4‐hydroxyphenyl)‐propionitrile (DPN) or the G protein‐coupled receptor 30 (GPR30)‐selective agonist 1‐(4‐[6‐bromobenzo 1, 3 dioxol‐5‐yl]‐3a, 4, 5, 9b‐tetrahydro‐3H‐cyclopenta [c] quinolin‐8‐yl)‐ethanone (G‐1), significantly inhibited HCV virion production. Taken together, the present results suggest that the most potent physiological estrogen, E₂, inhibits the production of HCV infectious particles in an ERα–dependent manner.     

Changes in age at menarche in Spain (1909–1965)

The data used in this work have been collected from clinical histories of women who have been examined at the Ginecology and Obstetritian Service of the Santa cruz y San Pablo Hospital of Barcelona. The sample consisted of 12,803 Spanish women, born between 1909 and 1965, by regions of birth. The method used is retrospective. The maximum menarcheal age in Spain (13.91±0.049 years) is found among those women born between 1925 and 1929 and the minimum menarcheal age (12.92±0.036 years) among women born between 1955 and 1959; so in an interval of 30 years, a reduction of almost a year (11.88 months) has taken place in age at first menstruation. This means a reduction of almost four months per decade. These differences are significant (p=.0000). The higher menarcheal age appears in the Northern Zone, due to the influence of Galicia in the sample (Galicia being a depressed zone with a great emigration rate). The earliest menarcheal age appears in the Mediterranean Zone due to the great percentage of catalan women (Catalonia being a region with a higher socioeconomical level). It is also to be observed that although the menarcheal age has decreased in all the zones, it has done so more dramatically in those zones which had higher values at the beginning. Although the secular trend of reduction in the age at menarche varies greatly from region to region, it may be considered that, in general, the socieconomic conditions have been the decisive factor in the change in physical maturation of Spanish women.     

A centuries-long epidemic of scrapie in British sheep?

The apparent persistence of scrapie in British sheep for more than 250 years is difficult to explain. Susceptibility to scrapie is associated with particular alleles at a single locus, the PrP gene. As the only known effect of these alleles is to confer susceptibility to a fatal disease, natural selection is expected to reduce their frequency, as has been observed in practice during scrapie outbreaks in single sheep flocks. Susceptibility alleles, and hence scrapie itself, are therefore expected to become rare, yet the disease remains widespread. We suggest that the paradox of scrapie's persistence can be explained by the exceptionally long time-scales inherent in the epidemiology of the disease. It is proposed that scrapie should be regarded as epidemic in British sheep but, unlike more familiar epidemics, which have time-scales of months or years, the scrapie epidemic has a time-scale of centuries. This interpretation implies that scrapie should eventually disappear from the sheep population.     

Divide and conquer? Persistence of infectious agents in spatial metapopulations of hosts

Persistence of an infectious agent in a population is an important issue in epidemiology. It is assumed that spatially fragmenting a population of hosts increases the probability of persistence of an infectious agent and that movement of hosts between the patches is vital for that. The influence of migration on persistence is however often studied in mean-field models, whereas in reality the actual distance travelled can be limited and influence the movement dynamics. We use a stochastic model, where within- and between-patch dynamics are coupled and movement is modelled explicitly, to show that explicit consideration of movement distance makes the relation between persistence of infectious agents and the metapopulation structure of its hosts less straightforward than previously thought. We show that the probability of persistence is largest at an intermediate movement distance of the host and that spatially fragmenting a population of hosts is not necessarily beneficial for persistence.     

Neanderthal mobility and technological change in the northeastern of the Iberian Peninsula: The patterns of chert exploitation at the Abric Romaní rock-shelter

Understanding the changes in the technological organization of prehistoric hunter–gatherers is important to research into hominin foraging activities. During the Middle Paleolithic, the coexistence or the replacement between Levallois and discoid technologies has frequently been recorded, but there is still no clear understanding of the reasons for their alternating and fragmented use in the archaeological record. This paper aims to contribute with new data to the current debate, by exploring the chert assemblages from levels O and M of the Abric Romaní rock-shelter. The results reveal that the change from Levallois in level O to discoid in level M is accompanied by the use of different axes of mobility, a reduction in the foraging radius and a more careful management of raw materials. A cross comparison with other archaeological evidences indicates the general pattern in the Northeast of the Iberian Peninsula during the late Middle Paleolithic, in which the use of Levallois technology is associated with chert and high mobility patterns whereas discoid technology is more closely linked to the use of local raw materials and a lower degree of mobility. The modifications to the mountainous environments and to the distribution of preferred prey animals may have influenced the Neanderthals’ mobility patterns and contributed to modifying their technical behaviours in order to obtain better foraging incomes.     

The role of the P2X₇ receptor in infectious diseases

ATP is an extracellular signal for the immune system, particularly during an inflammatory response. It is sensed by the P2X₇ receptor, the expression of which is upregulated by pro-inflammatory cytokines. Activation of the P2X₇ receptor opens a cation-specific channel that alters the ionic environment of the cell, activating several pathways, including (i) the inflammasome, leading to production of IL-1β and IL-18; (ii) the stress-activated protein kinase pathway, resulting in apoptosis; (iii) the mitogen-activated protein kinase pathway, leading to generation of reactive oxygen and nitrogen intermediates; and (iv) phospholipase D, stimulating phagosome-lysosome fusion. The P2X₇ receptor can initiate host mechanisms to remove pathogens, most particularly those that parasitise macrophages. At the same time, the P2X₇ receptor may be subverted by pathogens to modulate host responses. Moreover, recent genetic studies have demonstrated significant associations between susceptibility or resistance to parasites and bacteria, and loss-of-function or gain-of-function polymorphisms in the P2X₇ receptor, underscoring its importance in infectious disease.     

An infectious agent causing “spontaneous” degeneration of swine cells in vitro

Summary “Spontaneous” cell degeneration occurred in clone C-19 of the IB-RS-2 swine kidney cell line at around the 20th passage after each cloning. An infectious cytopathogenic agent designated AgC-19 was isolated from such degenerating cultures; the agent was studied through its inoculation into cultures of the cell clone C-12 derived from the same line. AgC-19 was identified as a medium size ribonucleic acid lipovirus belonging to the Togavirus group, and it was shown to be closely related to hog cholera virus (HCV). The evidence indicated that, most likely, AgC-19 is a cytopathogenic mutant of an attenuated HCV that persistently infects the IB-RS-2 cell cultures. After extensive destruction of the cell monolayers, a few viable cells were able to restore the cultures. Such recuperated cultures were resistant to a reinfection with AgC-19. Therefore, the persistent non-cytopathogenic infection is not able to interfere with AgC-19. On the other hand, in relation to the resistant cell cultures, either AgC-19 had selected genetically resistant cells or it had induced resistance through homologous interference.     

Pesticides and birds—A review of the situation in Great Britain in 1965

Capsule Arrival date strongly influenced date of breeding and breeding success.

Aim To check our hypothesis that in years with low April temperatures, i.e. when storks started to breed, the relationship between timing of breeding and success would be absent, meaning that migrants would have no advantage by returning early to their breeding area.

Methods We collected data in Poznań province, western Poland during the period 1983–2002. Based on local climatological data we selected eight cold spring years and compared them with the 12 ‘normal’ years. We analysed how weather affected the timing and arrival pattern of White Stork.

Results The two groups of years did not differ significantly in population size, but in normal years the arrival date of both parents was earlier. Arrival date strongly influenced (was positively correlated with) date of breeding and (negatively correlated with) breeding success.

Conclusion The slopes describing the above relationships did not differ significantly between the two groups of years. Therefore, we speculate that natural selection strongly favours birds that return early from the wintering grounds.     

Who was the infector—probabilities in the presence of variability in latent and infectious times

The probability that an observed infection has been transmitted from a particular member of a set of potential infectors is calculated. The calculations only use knowledge of the times of infection. It is shown that the probabilities depend on individual variability in latent and infectious times. The analysis are based on different background information and different assumptions on the progress of infectivity. The results are illustrated by numerical calculations and simulations.     

Detection of Mycobacterium tuberculosis in sputum from Suruí Indian subjects, Brazilian Amazon

This investigation aimed at the detection of Mycobacterium tuberculosis (MTB) in the sputum of Suruí Indian subjects from Amazonia, Brazil. Polymerase chain reaction analyses were positive for 12 samples, five of which were also culture-positive (N = 147). Four MTB genotypes were identified, one of which showed resistance to rifampicin and isoniazid. The study also highlighted one village complex as of particular importance, considering the relatively high number of tuberculosis cases reported and of MTB isolates obtained.     

Detection of an internal translation activity in the 5′ region of Bombyx mori infectious flacherie virus

The 5′ untranslated region plays an important role in positive-sense single-stranded RNA virus translation initiation, as it contains an internal ribosome entry site (IRES) that mediates cap-independent translation and is applied to simultaneously express several proteins. Infectious flacherie virus (IFV) is a positive-sense single-stranded RNA virus; however, the IRES function is still not proved. To investigate whether the sequences of IFV contain IRES activity, a series of bicistronic reporter (DsRed and enhanced green fluorescent protein) recombinant baculoviruses were constructed to infect the insect cells and silkworm using the Bombyx mori baculovirus expression system. Results showed that the upstream 311, 323, 383, 551, and 599 nt have IRES activity except for the 155-nt region in BmN cells. More importantly, the tetraloop structure containing region between 551 and 599 nt appeared to be responsible for the enhanced IRES activity in different insect cell lines and silkworm. These results indicated that the IRES activity is not species specific and tissue specific. Therefore, our findings may provide the basis for the simultaneous expression of two or various different genes under the same promoter in baculovirus expression system.     

Village division in lowland South America: The case of the Bakairí Indians of central Brazil

A Brazilian Indian village divided into several settlements during the 1980s. In this article, the political ecology approach is used to account for the process whereby this occurred. Data on ecology, subsistence practices, demography, and regional dynamics are presented. Analysis of results explores the articulation between shifts in population levels both in the region and in the Indian reservation, on one hand, with environmental stresses on reservation resources. The effects on national economic development programs on the regional and local levels are also discussed. The relationship between these policies and programs, on one hand, and alterations in local production systems are made explicit.