In the Case of Protosemiosis: Indexicality vs. Iconicity of Proteins

The concept of protosemiosis or semiosis at the lower levels of the living goes back to Giorgio Prodi, Thomas A. Sebeok and others. More recently, a typology of proto-signs was introduced by Sharov and Vehkavaara. Kull uses the term of vegetative semiosis, defined by iconicity, when referring to plants and lower organism semiosis. The criteria for the typology of proto-signs by Sharov and Vehkavaara are mostly based on two important presuppositions: agency and a lack of representation in low-level semiosis. We would like to focus on an alternative approach to protosign classification. In particular, we aim to provide a sign-typological characteristic of proteins (in analogy to Maran’ s classification of environmental signs). Our approach is focused on representation, that is, we only consider the relation between a sign and its object. We are considering representation independently from the role of interpretant and interpretation (which is an epiphenomenon of agency). Two hypotheses are investigated and accordingly evaluated in this paper: (I) Proteins are indexical protosigns. (II) Proteins are iconic protosigns. The conclusion our argumentation leads to supports the hypothesis (II).

Global Role of Low Molecular Weight Nucleic Acids in Biological Systems

Some considerations and reports are made regarding personal scientific developments carried out by author V.M. Zemskov in partnership with colleagues team and my close colleague prof. Zemskov A.M. for many years, specifically, 50 years. This is a problem, to which almost entire life has been devoted. It relates to a completely new global consistent pattern that we managed to stumble upon in those distant years, and that is implemented in any biological systems -whether it’s a higher or a lower organism, a human being, or various microbial and cellular populations. Realized by low molecular weight RNA or oligonucleotides of RNA.

APOL1 and Kidney Disease: From Genetics to Biology

Genetic variants in the APOL1 gene, found only in individuals of recent African ancestry, greatly increase risk of multiple types of kidney disease. These APOL1 kidney risk alleles are a rare example of genetic variants that are common but also have a powerful effect on disease susceptibility. These alleles rose to high frequency in sub-Saharan Africa because they conferred protection against pathogenic trypanosomes that cause African sleeping sickness. We consider the genetic evidence supporting the association between APOL1 and kidney disease across the range of clinical phenotypes in the APOL1 nephropathy spectrum. We then explore the origins of the APOL1 risk variants and evolutionary struggle between humans and trypanosomes at both the molecular and population genetic level. Finally, we survey the rapidly growing literature investigating APOL1 biology as elucidated from experiments in cell-based systems, cell-free systems, mouse and lower organism models of disease, and through illuminating natural experiments in humans.

Repeated Chlamydia trachomatis infections are associated with lower bacterial loads

Chlamydia trachomatis (CT) infections remain highly prevalent. CT reinfection occurs frequently within months after treatment, likely contributing to sustaining the high CT infection prevalence. Sparse studies have suggested CT reinfection is associated with a lower organism load, but it is unclear whether CT load at the time of treatment influences CT reinfection risk. In this study, women presenting for treatment of a positive CT screening test were enrolled, treated and returned for 3- and 6-month follow-up visits. CT organism loads were quantified at each visit. We evaluated for an association of CT bacterial load at initial infection with reinfection risk and investigated factors influencing the CT load at baseline and follow-up in those with CT reinfection. We found no association of initial CT load with reinfection risk. We found a significant decrease in the median log10 CT load from baseline to follow-up in those with reinfection (5.6 CT/ml vs. 4.5 CT/ml; P = 0.015). Upon stratification of reinfected subjects based upon presence or absence of a history of CT infections prior to their infection at the baseline visit, we found a significant decline in the CT load from baseline to follow-up (5.7 CT/ml vs. 4.3 CT/ml; P = 0.021) exclusively in patients with a history of CT infections prior to our study. Our findings suggest repeated CT infections may lead to possible development of partial immunity against CT.

Drosophila SOCS36E negatively regulates JAK/STAT pathway signaling via two separable mechanisms

Conserved from humans to Drosophila, the Janus kinase/signal transducer and activators of transcription (JAK/STAT) signaling cascade is essential for multiple developmental and homeostatic processes, with regulatory molecules controlling pathway activity also highly conserved. We characterize the Drosophila JAK/STAT pathway regulator SOCS36E and show that it functions via two independent mechanisms. First, we show that Drosophila Elongin B/C and Cullin-5 act via the SOCS-box of SOCS36E to reduce pathway activity specifically in response to ligand stimulation—a process that involves endocytic trafficking and lysosomal degradation of the Domeless (Dome) receptor. Second, SOCS36E also suppresses both stimulated and basal pathway activity via an Elongin/Cullin-independent mechanism that is mediated by the N-terminus of SOCS36E, which is required for the physical interaction of SOCS36E with Dome. Although some human SOCS proteins contain N-terminal kinase-inhibitory domains, we do not identify such a region in SOCS36E and propose a model wherein the N-terminal of SOCS36E blocks access to tyrosine residues in Dome. Our biochemical analysis of a SOCS-family regulator from a lower organism highlights the fundamental conserved roles played by regulatory mechanisms in signal transduction.

Toxicity of As on Soil Neutral Phosphatase

Toxicity of As on soil neutral phosphatase was studied through a series indoor incubation experiments. Results showed that the activity of soil neutral phosphatase was significantly inhibited by As pollution, and the peak inhibiting ratio was appeared at the sixth incubation day. While the activity of soil neutral phosphatase was also decreased with concentration of As increasing in the same incubation day. The relationship between the concentration of as and soil neutral phosphatase was fit by model ①y=c/(1+bx)and ②y=c(1+ax)(1+bx).The model② was more suitable to describe the relationship between the concentration of As and soil enzyme. This means the effect mechanism of As on the soil neutral phosphatase was part of inhibition. The Km of neutral phosphatase was increase by As concentration adding, while the Vmax was lowered. This kind of inhibition belongs to mix competition inhibition. Phosphatase widely exists in the biological world, from lower organism Escherichia coli, yeast to higher animals and plant tissues, body fluid and human liver, prostate gland are found to have phosphatase exist. It can catalyze the phosphate hydrolysis of elemental and inorganic phosphate release, important enzymes of biological phosphorus metabolism [1-2]. Soil phosphatase is an enzyme that has a major impact on agricultural production, producing an important role in the cycle of soil phosphorus. Research show that phosphatase in soil and aquatic systems of phosphorus, organic phosphorus pesticide contaminated soil bioremediation is very important, so it can be used as material for ecosystem beneficial or deleterious effects of indicator. Therefore, some can be as the instructions of the beneficial or harmful effects of ecosystem biology. Arsenic is widespread nature of toxic heavy metals often pollute the environment with the waste material, pesticides, fertilizers and other. According to the statistics in early 1990s, each year around the world due to human activities the importation of soil arsenic content of 0.52-1.2 million tons, its impact on soil ecosystem is one of the important topics. This experiment which proposed indoor simulation method analysis different concentrations of arsenic contaminated soils of neutral phosphatase activity, to explore the effects of different concentrations of arsenic on soil phosphatase activity of short-term toxicity effect. Analysis of the influence degree and duration, further analysis between the two possible mechanism, provides the basis for environmental protection and monitoring.

Naturally Attenuated, Orally Administered Mycobacterium microti as a Tuberculosis Vaccine Is Better than Subcutaneous Mycobacterium bovis BCG

ABSTRACT Mycobacterium microti is phylogenetically closely related to Mycobacterium tuberculosis and is a member of that complex of organisms. It is a curved, acid-fast bacillus that is naturally attenuated with a narrow host range for Microtus species only. In this study, we confirm the unique susceptibility of voles to infection with M. microti and the relative resistance of mice with a significantly lower organism burden after 8 weeks of infection. In addition, histopathologic examination of lungs reveals a lack of cellular, granulomatous aggregates characteristically seen in murine M. tuberculosis infection. In the past, M. microti has been used successfully in humans as a vaccine against tuberculosis but was associated with cutaneous reactions. In an attempt to circumvent this adverse effect, we report the efficacy of aerosol and oral vaccination with M. microti. High-dose orogastric vaccination with M. microti resulted in a statistically significant improvement in protection against aerosol challenge with virulent M. tuberculosis in the murine model compared with subcutaneous M. bovis BCG Pasteur vaccination.