Probabilistic estimation of microarray data reliability and underlying gene expression

Background: The availability of high throughput methods for measurement of mRNA concentrations makes the reliability of conclusions drawn from the data and global quality control of samples and hybridization important issues. We address these issues by an information theoretic approach, applied to discretized expression values in replicated gene expression data. Results: Our approach yields a quantitative measure of two important parameter classes: First, the probability $P(\sigma | S)$ that a gene is in the biological state $\sigma$ in a certain variety, given its observed expression $S$ in the samples of that variety. Second, sample specific error probabilities which serve as consistency indicators of the measured samples of each variety. The method and its limitations are tested on gene expression data for developing murine B-cells and a $t$-test is used as reference. On a set of known genes it performs better than the $t$-test despite the crude discretization into only two expression levels. The consistency indicators, i.e. the error probabilities, correlate well with variations in the biological material and thus prove efficient. Conclusions: The proposed method is effective in determining differential gene expression and sample reliability in replicated microarray data. Already at two discrete expression levels in each sample, it gives a good explanation of the data and is comparable to standard techniques.Comment: 11 pages, 4 figure

The impact of land consolidation on a forest estates land value

The purpose of this study is to find out if there exist a linear relation between a forest estates abstract characteristics, such as its land consolidation, the degree of its cohesion, the amount of the estate that’s accessible by road and its land value. The study was based upon 525 forest estates that had been sold between the years 2012 and 2016 throughout Sweden. The data was made available by NAI Svefa, a concern whose main focus is on the brokerage of real estates. A multiple regression analyse was then based upon the results. The results show a high degree of chance which made it difficult to draw certain conclusions, though it seems to show a negative connection between road accessibility and its land value in southernmost Sweden. Furthermore the results show a positive connection between the forest estates cohesion and their land value in the same region. Beyond that the high risk of chance making an impac

How light affects sexual maturation and egglaying in hens (Gallus domesticus)

Det är sedan länge känt att om höns hålls i naturlig belysning varierar äggläggningen med årstiderna. Lägst antal ägg läggs när dagarna är som kortast och ljusstimuleringen är som lägst. Eftersom hönan reagerar även på artificiellt ljus kan ljusprogram användas för att styra antalet ljusa respektive mörka timmar per dygn för att därigenom undvika årstidsvariation. Syftet med denna litteraturstudie är att ta reda på hur ljuset styr hönans könsmognad och ägg-läggning. Ljus registreras av fotoreceptorceller i retina, hypotalamus och epifysen vilka omvandlar energin i fotonerna till en biologisk signal. Vid ljusstimulering stimuleras gonadotropinfrisät-tande hormon (GnRH) vilket ökar frisläppningen av gonadotropinerna follikelstimulerande hormon (FSH) och luteiniserande hormon (LH). Ljusstimulering aktiverar även inhibitoriska neuropeptider i hypotalamus som minskar GnRH-frisläppningen. Så länge ljusstimuleringen sker kommer ökningen av GnRH-frisläppning att radera effekten av de inhibitoriska neuro-peptiderna, men när stimuleringen minskar tar den inhibitoriska effekten över och reproduk-tionsförmågan minskar. Hönans reproduktionsorgan består av äggstock och äggledare. Äggstockens funktion styrs av hypofysen, hypotalamus, epifysen och äggstockens egna hormonproducerande celler. Gonad-utveckling stimuleras av GnRH. Endast den vänstra äggstocken utvecklas till ett funktionellt organ. Den könsmogna äggstocken innehåller en hierarki av folliklar i olika utvecklings-stadier. Folliklarna tillväxer kraftigt under den mognadsprocess som sker när de utvecklas och upptar ägguleprotein. I äggstocken omges äggcellen av två cellager, thecaceller respektive granulosaceller. Thecaceller producerar androstenedion, som granulosacellerna konverterar till östrogen. Östrogen stimulerar inlagringen av ägguleprotein från levern. Granulosacellerna producerar även progesteron, det hormon som initierar den kraftiga ökning av LH som föregår ovuleringen. Ljus påverkar både könsmognad och den fortsatta äggläggningen. Rätt ljus är viktigt under hela äggläggningsperioden. För att en ökad ljusstimulering ska ske vid en höjning av antalet ljustimmar måste antalet timmar överstiga en undre kritisk gräns. Det finns även en övre mättnadsgräns där en ytterligare höjning av antalet ljustimmar inte ger ytterligare stimulering. Höns har relativ ljusutmattning vilket innebär att deras känslighet för ljusstimuli minskar över tid. I litteraturstudien beskrivs hönans reproduktionsorgan, vilka hormoner som inverkar och hur ljusstimuli kan användas för att påverka könsmognad och äggproduktion. Min slutsats är att ljus har en stor inverkan på hönans äggläggning. Både antal ljustimmar per dygn, förändringar i ljusmönster över tid, ljusintensitet och ljusets våglängd har visat sig påverka äggläggningen. Även om det bedrivits intensiv forskning under lång tid på olika aspekter av hur ljuset påver-kar hönans äggläggning finns det ett behov av ytterligare forskning, exempelvis på hur låg-energibelysning bör vara utformad för att efterlikna dagsljuset på bästa möjliga sätt.It is general knowledge that if poultry is kept in natural light the egg-laying rate will vary throughout the year. Egg production will be at its lowest point during the seasons with short days, when the stimulation of light is low. Artificial light can be used to manipulate this varia-tion. The aim of this paper is to find out how light regulates sexual maturity and egg-laying in the hen. Light is perceived through photoreceptor cells in retina, hypothalamus and the pineal gland. The photoreceptors transduce energy from photons to a biological signal. The stimulation of light induces production and release of gonadotropin releasing hormone (GnRH), which en-hances the release of the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Light will also increase the inhibitory neuropeptides in hypothalamus that will decrease the release of GnRH. As long as light stimulation continues, the inhibitory neuro-peptides will be overruled by the effect of stimulatory peptides, but once the stimulation of light disappears the impact of the inhibitory neuropeptides increases and reproduction ceases. The reproduction system consists of the left ovary and the oviduct. Ovarian function in the hen is controlled by neuroendocrine information from pituitary gland, hypothalamus, pineal gland and from hormone producing cells in the ovarian tissue. GnRH stimulates the gonadal development. In the mature hen the ovary consists of a hierarchy of follicles in different states of development. During follicular maturation assembly of the yolk, development and the ab-ility to produce hormones increases. In the ovarian tissue the egg cell is surrounded by theca and granulosa cells. Theca cells produce androstenedione, which is converted to oestrogen by granulosa cells. Oestrogen stimulates assembly of yolk proteins from the liver. Granulosa cells also produce progesterone. Progesterone stimulates the increased level of plasma LH which initiates the ovulation. The duration of light exposure controls GnRH release, which affects both maturation and the egg-laying process. Appropriate light management is therefore important during the whole laying period. Two factors that are important to consider when designing a stimulatory photo schedule are critical and saturation day length. The critical day length must be reached to give a higher rate of gonadotropin secretion. The saturation limit occurs when maximum stimula-tion is reached and increasing day length over this limit does not further stimulate the endo-crine system. Photorefractoriness is the process when transduction of photon energy into a physiological stimulus is reduced over time. This literature study includes a description of the avian reproduction system, the hormones that have an effect on egg-laying and sexual maturity and how light management can be used to increase the egg production. The conclusion of this paper is that appropriate light has a strong effect on the hen reproduction system. Both the number of light hours per day, light intensity and wavelength affects the egg-laying process. More research on light and its effects is still needed for example on how new low energy light systems should be designed to imi-tate natural daylight

Development and validation of a mobile phone application developed for measuring dietary fiber intake

We have developed a mobile phone application for measuring the intake of dietary fiber and validated the ability of the application to accurately capture this intake against measurements registered by a dietary record. We also investigated what food groups contributed most to the total, soluble, and insoluble dietary fiber intake. Twenty-six randomly selected Swedish women aged 35–85 years were included and randomized to either start to register dietary intake in the application or by a dietary record, during three consecutive days. After a washout period of at least two weeks, the participants used the other method. We found that the difference in measured mean fiber intake between the dietary record and the application was two grams independent of the total intake per day. A statistically significant correlation between fiber intake as measured by the two methods was found (rho = 0.65, p < 0.001). Vegetables and roots were the predominantly contributing foods to total and soluble fiber intake. Bread and crackers contributed most to insoluble fiber intake. In conclusion, the application may be considered as a useful and easy-to-use method to measure dietary fiber intake

A Preparatory Study for a Randomized Controlled Trial of Dietary Fiber Intake During Adult Pelvic Radiotherapy

Background: Patients undergoing pelvic radiotherapy are often advised to omit fiber-rich foods from their diet to reduce the adverse effects of treatment. Scientific evidence supporting this recommendation is lacking, and recent studies on animals and humans have suggested that there is a beneficial effect of dietary fiber for the alleviation of symptoms. Randomized controlled studies on dietary fiber intake during pelvic radiotherapy of sufficient size and duration are needed. As preparation for such a large-scale study, we evaluated the feasibility, compliance, participation rate, and logistics and report our findings here in this preparatory study. Methods: In this preparatory study of a fiber intervention trial, Swedish gynecological cancer patients scheduled for radiotherapy were recruited between January 2019 and August 2020. During the intervention, the participants filled out questionnaires and used an application. They also consumed a fiber supplement at first in powder form, later in capsules. Blood- and fecal samples were collected. The study is registered in clinicaltrials.gov (https://clinicaltrials.gov/ct2/show/NCT04534075?cond=fidura&draw=2&rank=1). Results: Among 136 approached patients, 57 started the study and the participation rate for primary outcomes was 63% (third blood sample) and 65% (third questionnaire). Barely half of the participants provided fecal samples. Providing concise and relevant information to the patients at the right time was crucial in getting them to participate and stay in the study. The most common reasons for declining participation or dropping out were the expected burden of radiotherapy or acute side effects. Tailoring the ambition level to each patient concerning the collection of data beyond the primary endpoints was an important strategy to keep the dropout rate at an acceptable level. Using capsules rather than psyllium in powder form made it much easier to document intake and to create a control group. During the course of the preparatory study, we improved the logistics and for the last 12 participants included, the participation rate was 100% for the earliest primary outcome. Conclusion: A variety of adjustments in this preparatory study resulted in an improved participation rate, which allowed us to set a final protocol and proceed with the main study

Exit of pediatric pre-B acute lymphoblastic leukaemia cells from the bone marrow to the peripheral blood is not associated with cell maturation or alterations in gene expression

<p>Abstract</p> <p>Background</p> <p>Childhood pre-B acute lymphoblastic leukemia (ALL) is a bone marrow (BM) derived disease, which often disseminates out of the BM cavity, where malignant cells to a variable degree can be found circulating in the peripheral blood (PB). Normal pre-B cells are absolutely dependent on BM stroma for survival and differentiation. It is not known whether transformed pre-B ALL cells retain any of this dependence, which possibly could impact on drug sensitivity or MRD measurements.</p> <p>Results</p> <p>Pre-B ALL cells, highly purified by a novel method using surface expression of CD19 and immunoglobulin light chains, from BM and PB show a very high degree of similarity in gene expression patterns, with differential expression of vascular endothelial growth factor (VEGF) as a notable exception. In addition, the cell sorting procedure revealed that in 2 out of five investigated patients, a significant fraction of the malignant cells had matured beyond the pre-B cell stage.</p> <p>Conclusion</p> <p>The transition of ALL cells from the BM into the circulation does not demand, or result in, major changes of gene expression pattern. This might indicate an independence of BM stroma on the part of transformed pre-B cells, which contrasts with that of their normal counterparts.</p

EBF1 and PAX5 control pro-B cell expansion via opposing regulation of the Myc gene

Genes encoding B lineage restricted transcription factors are frequently mutated in B-lymphoid leukemias, suggesting a close link between normal and malignant B-cell development. One of these transcription factors is Early B cell Factor 1 (EBF1), a protein of critical importance for lineage specification and survival of B-lymphoid progenitors. Here, we report that impaired EBF1 function in mouse B-cell progenitors results in reduced expression of Myc. Ectopic expression of MYC partially rescued B-cell expansion in the absence of EBF1 both in vivo and in vitro. Using chromosome conformation analysis in combination with ATAC-seq, ChIP-seq and reporter gene assays, we identified six EBF responsive enhancer elements within the Myc locus. CRISPR-Cas9 mediated targeting of EBF1 binding sites identified one element of key importance for Myc expression and pro-B cell expansion. These data provide evidence that Myc is a direct target of EBF1. Furthermore, ChIP-seq analysis revealed that several regulatory elements in the Myc locus are targets of PAX5. However, ectopic expression of PAX5 in EBF1 deficient cells inhibits the cell cycle and reduces Myc expression, suggesting that EBF1 and PAX5 act in an opposing manner to regulate Myc levels. This hypothesis is further substantiated by the finding that Pax5 inactivation reduces requirements for EBF1 in pro-B cell expansion. The binding of EBF1 and PAX5 to regulatory elements in the human MYC gene in a B-ALL cell line indicate that the EBF1:PAX5:MYC regulatory loop is conserved and may control both normal and malignant B-cell development