The Dynamics of Sex Ratio Evolution: From the Gene Perspective to Multilevel Selection

The new dynamical game theoretic model of sex ratio evolution emphasizes the role of males as passive carriers of sex ratio genes. This shows inconsistency between population genetic models of sex ratio evolution and classical strategic models. In this work a novel technique of change of coordinates will be applied to the new model. This will reveal new aspects of the modelled phenomenon which cannot be shown or proven in the original formulation. The underlying goal is to describe the dynamics of selection of particular genes in the entire population, instead of in the same sex subpopulation, as in the previous paper and earlier population genetics approaches. This allows for analytical derivation of the unbiased strategic model from the model with rigorous non-simplified genetics. In effect, an alternative system of replicator equations is derived. It contains two subsystems: the first describes changes in gene frequencies (this is an alternative unbiased formalization of the Fisher-Dusing argument), whereas the second describes changes in the sex ratios in subpopulations of carriers of genes for each strategy. An intriguing analytical result of this work is that the fitness of a gene depends on the current sex ratio in the subpopulation of its carriers, not on the encoded individual strategy. Thus, the argument of the gene fitness function is not constant but is determined by the trajectory of the sex ratio among carriers of that gene. This aspect of the modelled phenomenon cannot be revealed by the static analysis. Dynamics of the sex ratio among gene carriers is driven by a dynamic “tug of war” between female carriers expressing the encoded strategic trait value and random partners of male carriers expressing the average population strategy (a primary sex ratio). This mechanism can be called “double-level selection”. Therefore, gene interest perspective leads to multi-level selection.     

Effects of genetically modified human skin fibroblasts,stably overexpressing hepatocyte growth factor,on hepatic functions of cocultured C3A cells

Diseases leading to terminal hepatic failure are among the most common causes of death worldwide. Transplant of the whole organ is the only effective method to cure liver failure. Unfortunately, this treatment option is not available universally due to the serious shortage of donors. Thus, alternative methods have been developed that are aimed at prolonging the life of patients, including hepatic cells transplantation and bridging therapy based on hybrid bioartificial liver devices. Parenchymal liver cells are highly differentiated and perform many complex functions, such as detoxification and protein synthesis. Unfortunately, isolated hepatocytes display a rapid decline in viability and liver‐specific functions. A number of methods have been developed to maintain hepatocytes in their highly differentiated state in vitro, amongst them the most promising being 3D growth scaffolds and decellularized tissues or coculture with other cell types required for the heterotypic cell‐cell interactions. Here we present a novel approach to the hepatic cells culture based on the feeder layer cells genetically modified using lentiviral vector to stably produce additional amounts of hepatocyte growth factor and show the positive influence of these coculture conditions on the preservation of the hepatic functions of the liver parenchymal cells' model—C3A cells.     

Synthesis of 2,2′-Anhydro-2-Hydroxy- and 6,2′-Anhydro-6-Hydroxy-1-β-D-Arabindfuranosylnicotinamide as Conformationally Restricted Nicotinamide Nucleoside Analogs1

Abstract

1-(β-D-Ribofuranosy1)-2(1H)-pyridone-3-carboxamide (6a) and the 6(1H)-pyridone derivative (6b) were prepared by condensation of 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose (3) with 2- and 6-hydroxynicotinic acid, respectively, to 4a and 4b, followed by conversion of the carboxylic acid function of 4a,b into their corresponding carboxamides 5, and then deprotection of 5. Bath 6a and 6b were then treated with 1,3-dichlom-1,1,3,3-tetraisopropyldisiloxane to give the corresponding 3′,5′-O-TPDS derivatives, 7a and 7b. Mesylation of 7a,b with mesyl chloride in pyridine afforded the stable, protected mesylates 8a,b. Upon de-O-silylation of 8a,b with ET₃NHF gave a mixture of unprotectd mesylates 9a,b and 2,2-anhydro- and 6,2′-anhydronucleosides, 1a and 1b. Upon storage of 9a,b at man temperature, they are quantitatively converted into 1a,b. Mild alkaline hydrolysis of 1a,b afforded their corresponding arabino nucleosides 10a,b.     

Derivatives of 1-(2-Deoxy-2-fluoro-β-D-arabinofuranosyl)-5-phenyluracil and 5-Benzyluracil. Synthesis and Biological Properties

Abstract

A number of 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)uracil and -cytosine nucleosides substituted at the 5 position with a nitrophenyl or nitrobenzyl group were synthesized from 5-phenyl- and 5-benzyluracil via condensation of the fluorinated sugar, followed by nitration. The corresponding amino analogues were also prepared by reduction of the nitro nucleosides. The uracil nucleosides were converted into the corresponding cytosine nucleosides by way of the triazole intermediates. None of these nucleosides exhibited significant activity against herpes simplex virus type 1 in Vero cells. However, cytosine nucleosides containing the o-nitrophenyl, p-nitrophenyl, p-nitrobenzyl or p-aminobenzyl substituent were found to be toxic (even at 1 μM) to uninfected Vero cells, although they were essentially nontoxic in HL-60 cells. The 5′-monophosphates of the uracil nucleosides were inhibitors of the reaction catalyzed by purified Ehrlich ascites carcinoma thymidylate synthase, the 5-phenyluracil nucleotides causing a strong inhibition, competitive vs dUMP, described by the K_i value of 0.01 μM.     

C-Nucleoside Analogues of Nicotinamide Mononucleotide (NMN)

Abstract

5-(β-D-Ribofuranosyl)nicotinamide (lie) and 6-(β-D-ribo-furanosyDpicolinamide (IId) and their corresponding o-isomers (III) were synthesized from ribonolactone. The C-nucleoside lie was further converted to its 5′-monophosphate Up which is isosteric to NMN Ip).     

Pneumococcal immune evasion: ZmpC inhibits neutrophil influx

Neutrophil recruitment is essential in clearing pneumococcal infections. The first step in neutrophil extravasation involves the interaction between P‐selectin on activated endothelium and P‐Selectin Glycoprotein 1 (PSGL‐1) on neutrophils. Here, we identify pneumococcal Zinc metalloproteinase C as a potent inhibitor of PSGL‐1. ZmpC degrades the N‐terminal domain of PSGL‐1, thereby disrupting the initial rolling of neutrophils on activated human umbilical vein endothelial cells. Furthermore, mice infected with wild‐type strain in the model of pneumococcal pneumonia showed lower lungs neutrophil infiltration compare to animals infected with ZmpC mutant. In addition, we confirmed the association of zmpC with serotype 8 and 11A and found it to be associated with serotype 33F as well. In conclusion, wereport PSGL‐1 as a novel target for ZmpC and show that ZmpC inhibits neutrophil extravasation during pneumococcal pneumonia.     

Back from the Brink: The Holocene History of the Carpathian Barbel Barbus carpathicus

As a result of specific adaptations and habitat preferences strongly rheophilic fish species may show high levels of endemism. Many temperate rheophilic fish species were subjected to a series of range contractions during the Pleistocene, and then successfully expanded during the Holocene, colonising previously abandoned areas. The Carpathian barbel (Barbus carpathicus Kotlík, Tsigenopoulos, Ráb et Berrebi 2002) occurs in the montane streams in three basins of the main Central European rivers in the northern part of the Carpathian range. We used genetic variation within 3 mitochondrial and 9 microsatellite loci to determine a pattern of postglacial expansion in B. carpathicus. We found that overall genetic variation within the species is relatively low. Estimate of time to the most recent common ancestor (tMRCA) of mitochondrial sequences falls within the Holocene. The highest levels of genetic variation found in upper reaches of the Tisa river in the Danube basin suggest that glacial refugia were located in the south-eastern part of the species range. Our data suggest that the species crossed different watersheds at least six times as three genetically distinct groups (probably established in different expansion episodes) were found in northern part of the species range. Clines of genetic variation were observed in both the Danube and Vistula basins, which probably resulted from subsequent bottlenecks while colonizing successive habitats (south eastern populations) or due to the admixture of genetically diverse individuals to a previously uniform population (Vistula basin). Therefore, B. carpathicus underwent both demographic breakdowns and expansions during the Holocene, showing its distribution and demography are sensitive to environmental change. Our findings are important in the light of the current human-induced habitats alterations.     

Telocytes: new insight into the pathogenesis of gallstone disease

The major mechanisms of gallstone formation include biliary cholesterol hypersecretion, supersaturation and crystallization, mucus hypersecretion, gel formation and bile stasis. Gallbladder hypomotility seems to be a key event that triggers the precipitation of cholesterol microcrystals from supersaturated lithogenic bile. Telocytes, a new type of interstitial cells, have been recently identified in many organs, including gallbladder. Considering telocyte functions, it is presumed that these cells might be involved in the signalling processes. The purpose of this study was to correlate the quantity of telocytes in the gallbladder with the lithogenicity of bile. Gallbladder specimens were collected from 24 patients who underwent elective laparoscopic cholecystectomy for symptomatic gallstone disease. The control group consisted of 25 consecutive patients who received elective treatment for pancreatic head tumours. Telocytes were visualized in paraffin sections of gallbladders with double immunofluorescence using primary antibodies against c‐Kit (anti‐CD117) and anti‐mast cell tryptase. Cholesterol, phospholipid and bile acid levels were measured in gallbladder bile. The number of telocytes in the gallbladder wall was significantly lower in the study group than that in the control group (3.03 ± 1.43 versus 6.34 ± 1.66 cell/field of view in the muscularis propria, P < 0.001) and correlated with a significant increase in the cholesterol saturation index. The glycocholic and taurocholic acid levels were significantly elevated in the control subjects compared with the study group. The results suggest that bile composition may play an important role in the reduction in telocytes density in the gallbladder.