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Diploids derived from polyploids: genetic characteristics of four novel interspecific Sorghum populations.

Polyploidy has repeatedly shaped grass evolution, yet direct observations of how polyploid-derived chromosomes behave when returned to diploidy remain rare. Interspecific crosses between diploid Sorghum bicolor and tetraploid hybrids derived from Sorghum halepense generate mixed-ploidy progeny, providing an opportunity to examine chromosome transmission during the early stages of diploidization. Using genome-wide SNP markers, we characterized chromosomal inheritance patterns in 2 diploid and 2 tetraploid families derived from these crosses. Genotype-dosage profiles alone distinguished diploids from tetraploids with complete accuracy, reflecting strong ploidy-dependent differences in dosage-class distributions. Although diploid progeny retained much of the halepense-derived genomic background, several genomic intervals exhibited extended, nonrandom runs of S. bicolor homozygosity that remained polymorphic in corresponding tetraploid populations. These patterns, together with recurrent segregation distortion across independent families, suggest that the transition from tetraploidy to diploidy can expose allelic combinations that differ in transmission or viability. Analyses of flowering time further indicated that diploid and tetraploid derivatives possess distinct genomic architectures, with major association peaks occurring in different chromosomal regions across ploidy levels. Collectively, these results indicate that early diploidization involves nonrandom retention and loss of parental haplotypes shaped by both selective and structural constraints. The diploid extractions characterized here provide a rare empirical system for investigating the early stages of diploidization and a practical framework for studying and eventually mobilizing polyploid-derived variation for sorghum germplasm development. However, broader integration into elite breeding programs will require additional evaluation of cross-fertility, meiotic behavior, and chromosomal stability across diverse breeding backgrounds.

Sorghum

Newly Developed Structure-Based Methods Do Not Outperform Standard Sequence-Based Methods for Large-Scale Phylogenomics.

Recent developments in protein structure prediction have allowed the use of this previously limited source of information at genome-wide scales. It has been proposed that the use of structural information may offer advantages over sequences in phylogenetic reconstruction, due to their slower rate of evolution and direct correlation to function. Here, we examined how recently developed methods for structure-based homology search and tree reconstruction compare with current state-of-the-art sequence-based methods in reconstructing genome-wide collections of gene phylogenies (i.e. phylomes). While structure-based methods can be useful in specific scenarios, we found that their current performance does not justify using the newly developed structure-based methods as a default choice in large-scale phylogenetic studies. On the one hand, the best performing sequence-based tree reconstruction methods still outperform structure-based methods for this task. On the other hand, structure-based homology detection methods provide larger lists of candidate homologs, as previously reported. However, this comes at the expense of missing hits identified by sequence-based methods, as well as providing sets of homolog candidates with higher fractions of false positives. These insights help to guide the use of structural data in comparative genomics and highlight the need to continue improving structure-based approaches. Our pipeline is fully reproducible and has been implemented in a Snakemake workflow. This will facilitate a continuous assessment of future improvements of structure-based tools in the AlphaFold era.

Phylogeny

Darwinism and the expansion of evolutionary theory.

The essence of Darwinism lies in the claim that natural selection is a creative force, and in the reductionist assertion that selection upon individual organisms is the locus of evolutionary change. Critiques of adaptationism and gradualism call into doubt the traditional consequences of the argument for creativity, while a concept of hierarchy, with selection acting upon such higher-level "individuals" as demes and species, challenges the reductionist claim. An expanded hierarchical theory would not be Darwinism, has strictly defined, but it would capture, in abstract form, the fundamental feature of Darwin's vision--direction of evolution by selection at each level.

Biological Evolution

Growth and metabolism of live vaccine strain of Pasteurella tularensis.

The growth and metabolism of the live vaccine strain of Pasteurella tularensis in different media were investigated. Maximal growth was observed in a medium containing a sulfuric acid digest of casein as amino acid source. Amino acid metabolism produced considerable ammonia, and the rate of ammonia evolution was directly proportional to the growth rate. The most likely route for amino acid breakdown is nonspecific oxidative deamination.

Amino Acids

Heterogeneity of genome rearrangements in rotaviruses isolated from a chronically infected immunodeficient child.

Rotaviruses with genome rearrangements, isolated from a chronically infected immunodeficient child, were adapted to growth in BSC-1 cells. Preparations of viral RNA from fecal extracts showed a mixed atypical rotavirus RNA profile, which was due to the presence of at least 12 subpopulations of viruses grossly differing in genotype. Besides various forms of genome rearrangements involving segment 8-, 10-, and 11-specific sequences, reassortment in vivo was likely to have occurred during the emergence of these viruses. The protein products of viral genomes with various forms of segmental rearrangements seemed to be largely unaltered. Genome rearrangement is proposed to be a third mechanism directing the evolution of rotaviruses.

Animals

Adeno-Associated Virus Engineering and Load Strategy for Tropism Modification, Immune Evasion and Enhanced Transgene Expression.

Gene therapy aims to add, replace or turn off genes to help treat disease. To date, the US Food and Drug Administration (FDA) has approved 14 gene therapy products. With the increasing interest in gene therapy, feasible gene delivery vectors are necessary for inserting new genes into cells. There are different kinds of gene delivery vectors including viral vectors like lentivirus, adenovirus, retrovirus, adeno-associated virus et al, and non-viral vectors like naked DNA, lipid vectors, polymer nanoparticles, exosomes et al, with viruses being the most commonly used. Among them, the most concerned vector is adeno-associated virus (AAV) because of its safety, natural ability to efficiently deliver gene into cells and sustained transgene expression in multiple tissues. In addition, the AAV genome can be engineered to generate recombinant AAV (rAAV) containing transgene sequences of interest and has been proven to be a safe gene vector. Recently, rAAV vectors have been approved for the treatment of various rare diseases. Despite these approvals, some major limitations of rAAV remain, namely nonspecific tissue targeting and host immune response. Additional problems include neutralizing antibodies that block transgene delivery, a finite transgene packaging capacity, high viral titer used for per dose and high cost. To deal with these challenges, several techniques have been developed. Based on differences in engineering methods, this review proposes three strategies: gene engineering-based capsid modification (capsid modification), capsid surface tethering through chemical conjugation (surface tethering), and other formulations loaded with AAV (virus load). In addition, the major advantages and limitations encountered in rAAV engineering strategies are summarized.

Dependovirus

[Acquisition of masticatory structures in mammalian reptiles (preliminary study].

Possession of the masticatory function and apparatus appears as essential for the passage from Reptiles to Mammals. The present study, based on material of the Museum of d'Histoire Naturelle of Paris and on the literature, tries to distinguish the different stages of modification and specialization of feeding device in the cynodont theriodonts, leading to the mammalian stomatognathic system. The relationship between bone components (lateral skull and lower jaw), teeth and muscles are discussed. Induction of these changes comes from the external adductor muscular system in which the transformation from a primitive mass to mammalianlike masticatory muscles, directs this evolution. The conditions of feeding specialization of the Gomphodonts are discussed, as well as their evolutionary failure. Lastly, without taking up the quarrel about the double jaw-joint, it seems for the authors that the jaw-joint transformation appears as the most determinative element for assigning mammalian origins to the Cynodonts.

Animals

Converting catabolic ornithine carbamoyltransferase to an anabolic enzyme.

Pseudomonas aeruginosa has an anabolic and a catabolic ornithine carbamoyltransferase (OTCase). In vitro, these homologous enzymes catalyze the same reaction (ornithine + carbamoyl phosphate (CP) in equilibrium citrulline + Pi), yet in vivo they function unidirectionally owing to specific kinetic properties. The catabolic OTC-ase cannot promote the anabolic reaction (citrulline formation) in vivo because of a sigmoidal CP saturation curve and a high CP concentration for half-maximal velocity. The structural basis for this kinetic specialization was examined. The catabolic OTCase lost most of its homotropic cooperativity and gained anabolic activity when an amino acid residue near the CP binding site, Glu-106, was replaced by alanine or glycine. In the anabolic OTCase of Escherichia coli the glutamine residue corresponding to Glu-106 was exchanged for glutamate; however, in this case no CP cooperativity was acquired. Thus, in catabolic OTCase, sequence features in addition to Glu-106 are important for sigmoidal CP saturation, and such a sequence was identified in the C-terminal part. By an in vivo gene fusion technique the 9 C-terminal amino acids of catabolic OTCase were replaced by the homologous 8 amino acids from anabolic OTCase of E. coli; the hybrid enzyme had a markedly reduced homotropic cooperativity. This gene fusion method should be generally useful for directed enzyme evolution.

Amino Acid Sequence

[The direction and motivation for an evolution in methods of antiulcer surgery].

A 23-year retroactive analysis of a heterogeneous series of observations with unfavourable tardy results after antiulcer surgeries showed that the most failures requiring a second surgery appear after large resections with gastrojejunal or gastroduodenal anastomosis and after vagotomies associated with gastric drainage. The most favourable tardy results followed the vagotomy associated with limited gastric resection (hemigastrectomy). This kind of intervention prevents the appearance of the ulcerous relapses and lowers significantly the incidence of the other type of post-surgical iatrogenic complications. The optimal protection against the ulcerous relapse given by vagotomy associated with hemigastrectomy permits a tactical adaptation of the intervention to the lesional and physiopathological characteristics of each case.

Anastomosis, Surgical

Effects of 2,4-dinitrophenol and other metabolic inhibitors on the thermograms of Ehrlich ascites carcinoma cells registered with a microcalorimeter.

The heat produced by Ehrlich ascites carcinoma cells was measured microcalorimetrically to investigate the characteristics of the energetics of these cells. 2,4-Dinitrophenol and other inhibitors were used to obtain the standard thermograms. The heat level of starved Ehrlich ascites carcinoma cells (endogenous) was almost constant and linear and depended on the cell number used in the experiments (about 1 cal/1 X 10(8) cells/hr). The endogenous heat generation was suppressed strongly by potassium cyanide but not by iodoacetic acid or 2,4-dinitrophenol. On the other hand, heat evolution was directly related to the amount of glucose added to the medium but not to the number of cells (19 cal/mmol of glucose). The addition of iodoacetic acid markedly suppressed heat generation, but potassium cyanide did not. In contrast, glucose with dinitrophenol increased heat production markedly to about 10% higher than that of the control, possibly due to the uncoupled energy from oxidative phosphorylation. Malonic acid (1 mM) suppressed slightly the endogenous heat but caused a 15% reduction in exogenous heat. The amount of heat produced by the addition of glucose (19 cal/mmol) was equivalent to 40% of the theoretical value of energy released through glycolysis (47 cal/mmol). Thus, the heat produced by exogenous glucose appears to be mainly dependent on glycolysis.

2,4-Dinitrophenol

Ureteric hemorrhage in hemophilia with rapid healing.

A rapidly regressing ureteric hemorrhage, probably intramural, in a 14-year-old hemophiliac, is demonstrated by two closely sequential intravenous urograms. In the presence of hematuria, the intravenous urogrom outlines both the complications of hemophilia and their evolution, often directing therapy, and identifies concurrent disease.

Adolescent

Directional fixation of mutations in vertebrate evolution.

We have made pairwise comparisons between the coding sequences of 21 genes from cold-blooded vertebrates and 41 homologous sequences from warm-blooded vertebrates. In the case of 12 genes, GC levels were higher, especially in third codon positions, in warm-blooded vertebrates compared to cold-blooded vertebrates. Six genes showed no remarkable difference in GC level and three showed a lower level. In the first case, higher GC levels appear to be due to a directional fixation of mutations, presumably under the influence of body temperature (see Bernardi and Bernardi 1986b). These GC-richer genes of warm-blooded vertebrates were located, in all cases studied, in isochores higher in GC than those comprising the homologous genes of cold-blooded vertebrates. In the third case, increases appear to be due to a limited formation of GC-rich isochores which took place in some cold-blooded vertebrates after the divergence of warm-blooded vertebrates. The directional changes in the GC content of coding sequences and the evolutionary conservation of both increased and unchanged GC levels are in keeping with the existence of compositional constraints on the genome.

Animals

Turnover of mouse intestinal brush border membrane proteins and enzymes in organ culture. A direct evaluation from studies on the evolution of enzyme activities during the culture.

The turnover of mouse intestinal brush border membrane enzymes has been studied by kinetic analysis of the evolution of enzyme activities during organ culture. By comparing the results obtained in these studies with the predictions from a mathematical model of enzyme synthesis and degradation in organ cultures, it has been possible to reach the following conclusions: (1) There is no degradation of brush border membrane enzymes during culture and the rate of synthesis of each enzyme is directly measurable from the kinetics of total enzyme accumulation (tissue + media). (2) Brush border membrane enzymes are released in culture media by two complementary processes. The first one involves a differential solubilization of enzymes but its exact nature cannot be exactly stated. The second one involves a microvesiculation of brush border membranes, the importance of which in vivo is seen in the possible conciliation between urinary membrane synthesis and heterogeneous turnover of membrane components.

Alkaline Phosphatase

[Evolution of the locomotor-sensory systems].

Among directing physical factors of evolution of the locomotor-sensory system (LSS) gravitation, photons energy, oscillations of water and air media, ligands play the main role. At the molecular level the LSS elements are formed on the base of synthesizing genes that bring about development of protein molecules of tubulin and specific protonizing proteins in composition of the locomotor apparatus in Procariota flagellas. Tubulin and dinein with ATPh-ase activity are included in the flagella composition of LSS in Eukaryota, actin and miozin--with a high ATPh-ase activity--in composition of LSS myofilaments in ameboid Eukaryota and locomotor musculature in Metazoa. Simultaneously, in Pro- and Eukaryota in the same cell sensory molecules of rhodopsin, mechanoreceptors, chemoreceptors and so on can be synthesized. As a rule they localize in the flagellar membranes. In Metazoa single receptory flagellar cells are differentiated; they realize conservatively some receptive molecules that are already prepared by their ancessors--Eukaryota. The molecules also preserve their localization in the flagellar membranes. In Metazoa two types of locomotion take place according to the function of regulatory genes: initial flagellar and muscular definitive apparatus. Both types of locomotion are directed and regulated by the organs of sense and CNS; they form a strict spatial model of fixated synaptic connections of LSS. For the first time it was discovered in Ctenophora. This model, despite a complicated organization, is conservatively preserved in its general form in all Proto- and Denterostomia.

Animals

A theory of evolution above the species level.

Gradual evolutionary change by natural selection operates so slowly within established species that it cannot account for the major features of evolution. Evolutionary change tends to be concentrated within speciation events. The direction of transpecific evolution is determined by the process of species selection, which is analogous to natural selection but acts upon species within higher taxa rather than upon individuals within populations. Species selection operates on variation provided by the largely random process of speciation and favors species that speciate at high rates or survive for long periods and therefore tend to leave many daughter species. Rates of speciation can be estimated for living taxa by means of the equation for exponential increase, and are clearly higher for mammals than for bivalve mollusks.

Adaptation, Biological