Interaction between TGF-β1 (869C/T) polymorphism and biochemical risk factor for prediction of disease progression in rheumatoid arthritis

Objectives

Rheumatoid arthritis (RA) is a chronic inflammatory disease. Transforming growth factor-β1 (TGF-β1) may be a promising candidate gene for susceptibility and severity in RA. We aimed to determine whether TGF-β1 polymorphism is associated with susceptibility to RA and progression of joint destruction, as well as to identify the interaction between TGF-β1 polymorphism and biochemical risk factor.

Methods

A total of 160 RA patients and 168 healthy unrelated controls were tested for the TGF-β1 (869C/T) polymorphism using polymerase chain reaction.

Results

The TGF-β1 T allele was associated with susceptibility to RA. Within the RA group, TGF-β1 T allele carriers had a significant increased risk to develop osteoporosis (OR = 4.4, 95% CI = - 2. 4 – 8.1, P < 0.001), as well as more likely to develop bone erosion (OR = 1.7, 95% CI = 0. 99–2.7, P = 0. 034). Better prediction was achieved when the TGF-β1 TT genotype was used in combination with either elevated, rheumatoid factor (RF) or C-reactive protein (CRP) (OR = 6.8, 3.7 respectively). Also, they increased the risk to develop bone erosion in patients with rheumatoid arthritis (OR = 3.3, 9.8, P = 0.017, 0.001 respectively).

Conclusion

Our results suggest that TGF-β1 TT genotype may determine the development of osteoporosis and bone erosion in RA. Also, our results points to a synergism between TGF-β1 TT genotype and elevated serum RF or elevated CRP that lead to the development of osteoporosis and bone erosion in patients with rheumatoid arthritis.     

Floral sex ratios, disease and seed set in dioecious Silene dioica

1 In the dioecious, perennial herb Silene dioica , the density of pollen donors in a population is determined by overall plant density, the sex ratio and the proportion of plants infected with the anther-smut fungus Microbotryum violaceum , which results in permanent sterility of both male and female plants.
2 Pollinators ( Bombus spp.) were found to prefer male flowers and to avoid diseased flowers. This may result in an overall lower visitation frequency and increased risk for pollen limitation in populations with a low density of males or a high incidence of disease.
3 Compared with open-pollinated flowers, hand pollination resulted in a significant increase in the number of seeds produced per fruit in populations with an experimentally reduced proportion of males (25% and 50% male flowers) but not in a naturally male-dominated population (75% male flowers). Seed production per plant was increased by hand pollination only in the most female-dominated population. Because the floral sex ratio is often male-biased, resources rather than pollen availability are likely to set the upper limit for total seed production per individual in most healthy populations of S. dioica.
4 There was a negative relationship between seed set and incidence of disease across 22 populations in both years of a field study. However, there was no consistent difference between the responses of highly diseased populations (incidence 30–56%) and populations with a low disease incidence (incidence 0–8%) to hand pollination.
5 In a greenhouse experiment with cloned hand-pollinated females, the presence of spores on healthy flowers was found to reduce seed set significantly. In highly diseased populations, therefore, the frequent deposition of spores by flower visitors onto remaining healthy plants may decrease seed production below the potential level determined by resources or pollen availability.     

Influence of hydrocarbon-stapling on membrane interactions of synthetic antimicrobial peptides

Cyclization has been recognized as a valuable technique for increasing the efficacy of small molecule and peptide therapeutics. Here we report the application of a hydrocarbon staple to a rationally-designed cationic antimicrobial peptide (CAP) that acquires increased membrane targeting and interaction vs. its linear counterpart. The previously-described CAP, 6K-F17 (KKKKKK-AAFAAWAAFAA-NH₂) was used as the backbone for incorporation of an i to i?+?4 helical hydrocarbon staple through olefin ring closing metathesis. Stapled versions of 6K-F17 showed an increase in non-selective membrane interaction, where the staple itself enhances the degree of membrane interaction and rate of cell death while maintaining high potency against bacterial membranes. However, the higher averaged hydrophobicity imparted by the staple also significantly increases toxicity to mammalian cells. This deleterious effect is countered through stepwise reduction of the stapled 6K-F17’s backbone hydrophobicity through polar amino acid substitutions. Circular dichroism assessment of secondary structure in various bacterial membrane mimetics reveals that a helical structure may improve – but is not an absolute requirement for – antimicrobial activity of 6K-F17. Further, phosphorus-31 static solid state NMR spectra revealed that both non-toxic stapled and linear peptides bind bacterial membranes in a similar manner that does not involve a detergent-like mechanism of lipid removal. The overall results suggest that the technique of hydrocarbon stapling can be readily applied to membrane-interactive CAPs to modulate how they interact and target biological membranes.     

An analytical study of the factors that influence COVID-19 spread

The outbreak of the coronavirus disease 2019 (COVID-19) continues to constitute an international public health emergency. Seasonality is a long-recognized attribute of many viral infections of humans. Nevertheless, the relationship between environmental factors and the spread of infection, particularly for person-to-person communicable diseases, remains poorly understood. This study explores the relationship between environmental factors and the incidence of COVID-19 in 188 countries with reported COVID-19 cases as of April 13, 2020. Here we show that COVID-19 growth rates peaked in temperate zones in the Northern Hemisphere during the outbreak period, while they were lower in tropical zones. The relationships between COVID-19 and environmental factors were resistant to the potentially confounding effects of air pollution, sea level, and population. To prove the effect of those factors, study, and analysis of the prevalence of COVID-19 in Italy, Spain, and China was undertaken. A fuzzy logic system was designed to predict the effects of that variables on the rate of viral spread of COVID-19.     

Oviposition in an eruptive moth species, Yponomeuta evonymellus, is insensitive to the population density experienced during the larval period

We studied if the population density experienced during larval development affects the reproductive schedule of Yponomeuta evonymellus L. (Lepidoptera, Yponomeutidae), a moth species characterized by outbreak population dynamics. More specifically, we predicted that reproduction would be delayed to facilitate emigration from sites with suboptimally high densities of conspecifics. We manipulated larval densities in the laboratory, as well as in those pupae collected from the extremes of natural densities. As the response, we also recorded the timing and sizes of egg clutches laid. The results did not support our initial predictions: the timing of oviposition was not dependent on larval growth conditions. This apparent lack of adaptation might be related to the loss of ‘memory’ during metamorphosis in holometabolous insects. However, oviposition schedules were also only minimally sensitive to elevated adult density. An inability to respond to high larval densities may contribute to the outbreak dynamics in this species.     

Estimating abundance and spatial distribution patterns of the bubble crab Dotilla fenestrata (Crustacea: Brachyura)

Abstract The bubble crab Dotilla fenestrata forms very dense populations on the sand flats of the eastern coast of Inhaca Island, Mozambique, making it an interesting biological model to examine spatial distribution patterns and test the relative efficiency of common sampling methods. Due to its apparent ecological importance within the sandy intertidal community, understanding the factors ruling the dynamics of Dotilla populations is also a key issue. In this study, different techniques of estimating crab density are described, and the trends of spatial distribution of the different population categories are shown. The studied populations are arranged in discrete patches located at the well‐drained crests of nearly parallel mega sand ripples. For a given sample size, there was an obvious gain in precision by using a stratified random sampling technique, considering discrete patches as strata, compared to the simple random design. Density average and variance differed considerably among patches since juveniles and ovigerous females were found clumped, with higher densities at the lower and upper shore levels, respectively. Burrow counting was found to be an adequate method for large‐scale sampling, although consistently underestimating actual crab density by nearly half. Regression analyses suggested that crabs smaller than 2.9 mm carapace width tend to be undetected in visual burrow counts. A visual survey of sampling plots over several patches of a large Dotilla population showed that crab density varied in an interesting oscillating pattern, apparently following the topography of the sand flat. Patches extending to the lower shore contained higher densities than those mostly covering the higher shore. Within‐patch density variability also pointed to the same trend, but the density increment towards the lowest shore level varied greatly among the patches compared.     

Recent advances in lactic acid production by microbial fermentation processes

Fermentative production of optically pure lactic acid has roused interest among researchers in recent years due to its high potential for applications in a wide range of fields. More specifically, the sharp increase in manufacturing of biodegradable polylactic acid (PLA) materials, green alternatives to petroleum-derived plastics, has significantly increased the global interest in lactic acid production. However, higher production costs have hindered the large-scale application of PLA because of the high price of lactic acid. Therefore, reduction of lactic acid production cost through utilization of inexpensive substrates and improvement of lactic acid production and productivity has become an important goal. Various methods have been employed for enhanced lactic acid production, including several bioprocess techniques facilitated by wild-type and/or engineered microbes. In this review, we will discuss lactic acid producers with relation to their fermentation characteristics and metabolism. Inexpensive fermentative substrates, such as dairy products, food and agro-industrial wastes, glycerol, and algal biomass alternatives to costly pure sugars and food crops are introduced. The operational modes and fermentation methods that have been recently reported to improve lactic acid production in terms of concentrations, yields, and productivities are summarized and compared. High cell density fermentation through immobilization and cell-recycling techniques are also addressed. Finally, advances in recovery processes and concluding remarks on the future outlook of lactic acid production are presented.