Clinical Implications of Intestinal Stem Cell Markers in Colorectal Cancer

AbstractColorectal cancer (CRC) still has one of the highest incidence and mortality rate among cancers. Therefore, improved differential diagnostics and personalized treatment are still needed. Several intestinal stem cell markers have been found to be associated with CRC and might have a prognostic and predictive significance in CRC patients. This review provides an overview of the intestinal stem cell markers leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), B cell–specific Moloney murine leukemia virus insertion site 1 (BMI1), Musashi1 (MSI1), and sex-determining region y-box 9 (SOX9) and their implications in human CRC. The exact roles of the intestinal stem cell markers in CRC development and progression remain unclear; however, high expression of these stem cell markers have a potential prognostic significance and might be implicated in chemotherapy resistance

Genome size and phenotypic plasticity in the seed beetle, Callosobruchus maculatus

It has long been evident that genome size is not an accurate measure of organismal complexity. This paradox was “solved” with the discovery of nonfunctional and selfish DNA in the 1970s. However, emerging from this explanation was an enigma of complexity. Neither neutral nor adaptive models can account for all genome size variation across the tree of life. An organism with intraspecific variation is needed to investigate the functional role of genome size differences. Here I use different populations of the seed beetle, Callosobruchus maculatus, with a known intraspecific genome size variation of ~4%. It has previously been shown that a larger genome is associated with higher scores in fitness-related traits for this species. In this study, genome size is regressed with phenotypic plasticity along three different environmental gradients. Genome size did not correlate with plasticity in mass and development time along environmental gradients of temperature and host types. However, the results show that larger genomes are consistent with higher canalization of fitness under different food regimes. This further supports the idea that natural selection acts on genome size variation in this species.

Genome size and phenotypic plasticity in the seed beetle, Callosobruchus maculatus

It has long been evident that genome size is not an accurate measure of organismal complexity. This paradox was “solved” with the discovery of nonfunctional and selfish DNA in the 1970s. However, emerging from this explanation was an enigma of complexity. Neither neutral nor adaptive models can account for all genome size variation across the tree of life. An organism with intraspecific variation is needed to investigate the functional role of genome size differences. Here I use different populations of the seed beetle, Callosobruchus maculatus, with a known intraspecific genome size variation of ~4%. It has previously been shown that a larger genome is associated with higher scores in fitness-related traits for this species. In this study, genome size is regressed with phenotypic plasticity along three different environmental gradients. Genome size did not correlate with plasticity in mass and development time along environmental gradients of temperature and host types. However, the results show that larger genomes are consistent with higher canalization of fitness under different food regimes. This further supports the idea that natural selection acts on genome size variation in this species.

Genome size and phenotypic plasticity in the seed beetle, Callosobruchus maculatus

It has long been evident that genome size is not an accurate measure of organismal complexity. This paradox was “solved” with the discovery of nonfunctional and selfish DNA in the 1970s. However, emerging from this explanation was an enigma of complexity. Neither neutral nor adaptive models can account for all genome size variation across the tree of life. An organism with intraspecific variation is needed to investigate the functional role of genome size differences. Here I use different populations of the seed beetle, Callosobruchus maculatus, with a known intraspecific genome size variation of ~4%. It has previously been shown that a larger genome is associated with higher scores in fitness-related traits for this species. In this study, genome size is regressed with phenotypic plasticity along three different environmental gradients. Genome size did not correlate with plasticity in mass and development time along environmental gradients of temperature and host types. However, the results show that larger genomes are consistent with higher canalization of fitness under different food regimes. This further supports the idea that natural selection acts on genome size variation in this species.

Customer Satisfaction – A Cash Issue : the impact of banks´ degree of cash management on customer satisfaction

Kontanter har en avtagande trend som betalningsmedel i samhället. Banksektorn har också påverkats av kontanternas minskande genom att allt fler banker avvecklar sin kontanthantering. Detta påverkar i sin tur bankkunderna som inte längre har samma tillgång till fysiska betalningsmedel. Kundnöjdhet är ett väl utforskat ämne, men tidigare forskning har inte fokuserat på den påverkan bankernas kontanthantering har på kundnöjdheten. Det är vad denna studie undersöker genom syftet att tydliggöra den påverkan som kundnöjdheten får av bankernas olika grader av kontanthantering samt hur ålder, kön, relationstid och personlig kontakts inverkan på sambandet utspelar sig. Studiens utförande överensstämmer med den positivistiska forskningsfilosofin, deduktiva ansatsen och kvantitativa metoden. Det empiriska material som uppsatsen baseras på samlades in genom två olika internetenkäter, där en riktade sig till banker och en var ställd till bankkunderna. Totalt brukades 8 svar från banker och 106 av kundenkätens respondenter till resultatet av studien. Den befintliga forskningen har påvisat att ålder, kön, relationstid och personlig kontakt påverkar kundnöjdheten hos banker. Av den anledningen undersöktes de fyra variablernas, tillsammans med bankernas grad av kontanthantering, påverkan på kundnöjdheten. Resultatet visar att bankernas kontanthantering påverkar kundnöjdheten genom att en lägre grad av kontanthantering ger en lägre kundnöjdhet. Dessutom beror förhållandet även på åldern då en äldre kund är mindre nöjd när bankens kontanthantering avvecklas. Studiens resultat belyser ett aktuellt ämne och bör beaktas ur bankens synvinkel när ett beslut om kontanthanteringen ska tas. I ett samhälle där allt fler banker minskar sin kontanthantering innebär därför uppsatsens resultat en viktig parameter i utvecklingen.Cash is a declining trend as a means of payment in society. The banking sector has also been affected by the decline of the accounts as more and more banks are dismantling their cash management. This affects the bank customers who no longer have the same access to cash. Customer satisfaction is a well-researched subject, but previous research hasn’t focused on the impact banks’ cash management has on customer satisfaction. That’s what this study examines through the purpose of clarifying the impact of banks’ different degree of cash management on customer satisfaction as well as age, gender, relationship time and personal contact´s impact on the relationship. The study’s execution complies with the positivistic research philosophy, deductive approach and quantitative method. The empirical material the study was based on was collected through two internet surveys, where one addressed the banks and one the bank customers. In total, 8 survey responses from the banks and 106 from the customers were used for the study’s outcome. Current research shows that age, gender, relationship time and personal contact affect the customer satisfaction at banks. Therefore, the impact of the four variables, along with the banks’ degree of cash management, was examined. The result shows that banks’ cash management affects customer satisfaction through the example that a lower degree of cash management results in lower customer satisfaction. In addition, the relationship is also dependent on age, since an elderly customer is less satisfied if the bank’s cash management is being dismantled. The result of the study highlights a current topic and should be considered from the bank’s point of view when a decision regarding cash management is taken. Therefore, in a society where more and more banks are reducing their cash management, the essay’s result is an important parameter in the development

Larger genomes show improved buffering of adult fitness against environmental stress in seed beetles

Our general understanding of the evolution of genome size (GS) is incomplete, and it has long been clear that GS does not reflect organismal complexity. Here, we assess the hypothesis that larger genomes may allow organisms to better cope with environmental variation. It is, for example, possible that genome expansion due to proliferation of transposable elements or gene duplications may affect the ability to regulate and fine-tune transcriptional profiles. We used 18 populations of the seed beetle Callosobruchus maculatus, which differ in GS by up to 4.5%, and exposed adults and juveniles to environmental stress in a series of experiments where stage-specific fitness was assayed. We found that populations with larger genomes were indeed better buffered against environmental stress for adult, but not for juvenile, fitness. The genetic correlation across populations between GS and canalization of adult fitness is consistent with a role for natural selection in the evolution of GS

Supplementary Methods, Figures and Table. from Larger genomes show improved buffering of adult fitness against environmental stress in seed beetles

Our general understanding of the evolution of genome size (GS) is incomplete, and it has long been clear that GS does not reflect organismal complexity. Here, we assess the hypothesis that larger genomes may allow organisms to better cope with environmental variation. It is, for example, possible that genome expansion due to proliferation of transposable elements or gene duplications may affect the ability to regulate and fine-tune transcriptional profiles. We used 18 populations of the seed beetle Callosobruchus maculatus, which differ in GS by up to 4.5%, and exposed adults and juveniles to environmental stress in a series of experiments where stage-specific fitness was assayed. We found that populations with larger genomes were indeed better buffered against environmental stress for adult, but not for juvenile, fitness. The genetic correlation across populations between GS and canalization of adult fitness is consistent with role for natural selection in the evolution of GS

The Effects of GC-Biased Gene Conversion on Patterns of Genetic Diversity among and across Butterfly Genomes

Recombination reshuffles the alleles of a population through crossover and gene conversion. These mechanisms have considerable consequences on the evolution and maintenance of genetic diversity. Crossover, for example, can increase genetic diversity by breaking the linkage between selected and nearby neutral variants. Bias in favor of G or C alleles during gene conversion may instead promote the fixation of one allele over the other, thus decreasing diversity. Mutation bias from G or C to A and T opposes GC-biased gene conversion (gBGC). Less recognized is that these two processes may-when balanced-promote genetic diversity. Here, we investigate how gBGC and mutation bias shape genetic diversity patterns in wood white butterflies (Leptidea sp.). This constitutes the first in-depth investigation of gBGC in butterflies. Using 60 resequenced genomes from six populations of three species, we find substantial variation in the strength of gBGC across lineages. When modeling the balance of gBGC and mutation bias and comparing analytical results with empirical data, we reject gBGC as the main determinant of genetic diversity in these butterfly species. As alternatives, we consider linked selection and GC content. We find evidence that high values of both reduce diversity. We also show that the joint effects of gBGC and mutation bias can give rise to a diversity pattern which resembles the signature of linked selection. Consequently, gBGC should be considered when interpreting the effects of linked selection on levels of genetic diversity

Base composition, codon usage and patterns of gene sequence evolution in butterflies.

Coding sequence evolution is influenced by both natural selection and neutral evolutionary forces. In many species, the effects of mutation bias, codon usage and GC-biased gene conversion (gBGC) on gene sequence evolution have not been detailed. Quantification of how these forces shape substitution patterns is therefore necessary to understand the strength and direction of natural selection. Here, we used comparative genomics to investigate the association between base composition and codon usage bias on gene sequence evolution in butterflies and moths (Lepidoptera), including an in-depth analysis of underlying patterns and processes in one species, Leptidea sinapis. The data revealed significant G/C to A/T substitution bias at third codon position with some variation in the strength among different butterfly lineages. However, the substitution bias was lower than expected from previously estimated mutation rate ratios, partly due to the influence of gBGC. We found that A/T-ending codons were overrepresented in most species and there was a negative association between the magnitude of codon usage bias and GC-content in third codon positions. In contrast, the tRNA-gene population in L. sinapis showed higher GC-content at third codon positions compared to coding sequences in general and less overrepresentation of A/T-ending codons. There was an inverse relationship between synonymous substitutions and codon usage bias indicating selection on synonymous sites. We conclude that the evolutionary rate in Lepidoptera is affected by a complex interaction between underlying G/C -> A/T mutation bias and partly counteracting fixation biases, predominantly conferred by overall purifying selection, gBGC and selection on codon usage

Nascent evolution of recombination rate differences as a consequence of chromosomal rearrangements

© 2023 Näsvall et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Reshuffling of genetic variation occurs both by independent assortment of chromosomes and by homologous recombination. Such reshuffling can generate novel allele combinations and break linkage between advantageous and deleterious variants which increases both the potential and the efficacy of natural selection. Here we used high-density linkage maps to characterize global and regional recombination rate variation in two populations of the wood white butterfly (Leptidea sinapis) that differ considerably in their karyotype as a consequence of at least 27 chromosome fissions and fusions. The recombination data were compared to estimates of genetic diversity and measures of selection to assess the relationship between chromosomal rearrangements, crossing over, maintenance of genetic diversity and adaptation. Our data show that the recombination rate is influenced by both chromosome size and number, but that the difference in the number of crossovers between karyotypes is reduced as a consequence of a higher frequency of double crossovers in larger chromosomes. As expected from effects of selection on linked sites, we observed an overall positive association between recombination rate and genetic diversity in both populations. Our results also revealed a significant effect of chromosomal rearrangements on the rate of intergenic diversity change between populations, but limited effects on polymorphisms in coding sequence. We conclude that chromosomal rearrangements can have considerable effects on the recombination landscape and consequently influence both maintenance of genetic diversity and efficiency of selection in natural populations.This work was funded by the Swedish Research Council (VR research grant #019-04791 to N.B.). The authors acknowledge support from the National Genomics Infrastructure in Stockholm funded by Science for Life Laboratory, the Knut and Alice Wallenberg Foundation and the Swedish Research Council, and SNIC/Uppsala Multidisciplinary Center for Advanced Computational Science for assistance with massively parallel sequencing and access to the UPPMAX computational infrastructure. The project was also supported by NBIS/SciLifeLab long-term bioinformatics support (WABI; to N.B.). R.V. was supported by the Spanish government (Agencia Estatal de Investigación) through grant PID2019-107078GB-I00/MCIN/AEI/10.13039/501100011033.Peer reviewe