Diversity of Formyltetrahydrofolate Synthetases in the Guts of the Wood-Feeding Cockroach Cryptocercus punctulatus and the Omnivorous Cockroach Periplaneta americana

We examined the diversity of a marker gene for homoacetogens in two cockroach gut microbial communities. Formyltetrahydrofolate synthetase (FTHFS or fhs) libraries prepared from a wood-feeding cockroach, Cryptocercus punctulatus, were dominated by sequences that affiliated with termite gut treponemes. No spirochete-like sequences were recovered from the omnivorous roach Periplaneta americana, which was dominated by Firmicutes-like sequences

To DGC or not to DGC: oxygen guarding in the termite Zootermopsis nevadensis (Isoptera: Termopsidae)

The ability of some insects to engage in complex orchestrations of tracheal gas exchange has been well demonstrated, but its evolutionary origin remains obscure. According to a recently proposed hypothesis, insects may employ spiracular control of gas exchange to guard tissues against long-term oxidative damage by using the discontinuous gas-exchange cycle (DGC) to limit internal oxygen partial pressure (P_(O_2)). This manuscript describes a different approach to oxygen guarding in the lower termite Zootermopsis nevadensis. These insects do not display a DGC but respond to elevated oxygen concentrations by restricting spiracular area, resulting in a transient decline in CO_2 emission. High internal CO_2 concentrations are then maintained; restoring normoxia results in a transient reciprocal increase in CO_2 emission caused by release of excess endotracheal CO_2. These changes in spiracular area reflect active guarding of low internal O_2 concentrations and demonstrate that regulation of endotracheal hypoxia takes physiological priority over prevention of CO_2 build-up. This adaptation may reflect the need to protect oxygen-sensitive symbionts (or, gut bug guarding). Termites may eschew the DGC because periodic flushing of the tracheal system with air may harm the obligate anaerobes upon which the lower termites depend for survival on their native diet of chewed wood

BRCA1 promoter methylation: the influence on gene expression and the effect of long term drug treatment

Breast cancer is the most common type of cancer among woman all over the world, with over 1.67 million new cases in 2012. Heritable breast cancer is closely linked to mutations in the tumor suppressor gene BRCA1, with up to 80% lifetime risk for developing breast cancer among women harboring a mutation in this gene. However, most breast cancer cases are sporadic and somatic mutations of the BRCA1 gene are rare. Furthermore, some tumors show BRCAness, despite being BRCA1 wild-type. Thus, it is of great interest to assess alternative mechanisms for inactivation of the BRCA1 gene, and addressing the missing causality of many breast cancers. Furthermore, it is of great interest to assess the mechanisms of drug resistance, a major challenge in cancer treatment today, where BRCA1 may play an important role. The overall aim of this thesis is to increase the understanding of the biological role of BRCA1 promoter methylation in breast cancer. Three sub aims for the present project were outlined; 1) Quantify the BRCA1 α and β transcripts and the total BRCA1 protein levels and relate the expression data to the methylation pattern in the BRCA1 promoter region in a panel of breast cancer cell lines. 2) Investigate how the total expression levels, as well as the ratio between the α and β transcripts are affected by alterations in the α and β promoter region of BRCA1, including methylation of specific CpGs as well as the polymorphisms rs71361504 and rs799905. 3) Investigate the effect of long term treatment with the drugs olaparib and doxorubicin on the BRCA1 promoter methylation in SKBR3 breast cancer cells as a potential cause of drug resistance. The study showed a weak correlation between BRCA1 methylation pattern and BRCA1 mRNA expression. No correlation was observed between the methylation pattern and protein expressed or between mRNA levels and protein expression. Analysis of polymorphisms rs71361504 and rs799905 found in the BRCA1 promoter showed that the two variants seemed to counter-balance each other, giving equal luciferase expression levels when differing in two positions and lower expression levels when intermediate variants were studied. Finally, long term drug treatment of the cell line SKBR3 did not alter the methylation levels in the BRCA1 promoter, consequently demethylation seems not to be a mechanism for drug resistance in the experimental setup tested in this study.Masteroppgåve i molekylærbiologiMAMN-MOLMOL39

Styremedlemmers ansvar for forsvarlig egenkapital og likviditet etter utdeling av utbytte

Styremedlemmers ansvar for forsvarlig egenkapital og likviditet etter utdeling av utbytt

A Basic Theory of Everything

What are the basic building blocks of the world? This book presents a naturalistic theory saying that the universe and everything in it can be reduced to three fundamental entities: a field, a set of values that can be actualized at different places in the field, and an actualizer of the values. The theory is defended by using it to answer the main questions in metaphysics, such as: What is causality, existence, laws of nature, consciousness, thinking, free will, time, mathematical entities, ethical values, etc.? The theory is compared with the main alternatives and argued to solve problems better than the existing theories. Several new theories are suggested, such as how to understand mental causation, free will and the truth of ethics and mathematics

Etiology and Diagnosis of Major Depression - A Novel Quantitative Approach

Copyright © 2013 Johnny T. Ottesen. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Classical psychiatric opinions are relative uncertain and treatment results are not impressive when deal-ing with major depression. Depression is related to the endocrine system, but despite much effort a good quantitative measure for characterizing depression has not yet emerged. Methods: Based on ACTH and cortisol levels and using clustering analysis and mixture effect modeling we propose a novel and scientifically based quantitative index, denoted the O-index. The O-index combines a weighted and scaled deviation from normal values in both ACTH and cortisol. Results: Using ANOVA we compare the O-index with opinions reach by classical psychiatric diagnostic procedure (sensitivity 83%, specificity 59%, likelihood ratio positive 2.0, and likelihood ratio negative 0.29). The O-index nicely refines the etiology of depression: Combined with clinical data for 29 subjects earlier reported three categories emerge (p = 4.4 × 10−13): hypocortisolemic depressed, non-depressed, and hypercotisolemic depressed. The O-index also re-veals why it has been difficult to obtain good markers earlier. It explains that healthy subjects may have an elevated (suppressed) level of cortisol or ACTH, however, the healthy system is able to deal with such elevated (suppressed) lev-els by compensating through suppressing (stimulating) the other component. In contrast the O-index shows that de

ISS-N1 makes the first FDA-approved drug for spinal muscular atrophy

Spinal muscular atrophy (SMA) is one of the leading genetic diseases of children and infants. SMA is caused by deletions or mutations of Survival Motor Neuron 1 (SMN1) gene. SMN2, a nearly identical copy of SMN1, cannot compensate for the loss of SMN1 due to predominant skipping of exon 7. While various regulatory elements that modulate SMN2 exon 7 splicing have been proposed, intronic splicing silencer N1 (ISS-N1) has emerged as the most promising target thus far for antisense oligonucleotide-mediated splicing correction in SMA. Upon procuring exclusive license from the University of Massachussets Medical School in 2010, Ionis Pharmaceuticals (formerly ISIS Pharamaceuticals) began clinical development of Spinraza™ (synonyms: Nusinersen, IONIS-SMNRX, ISIS-SMNRX), an antisense drug based on ISS-N1 target. Spinraza™ showed very promising results at all steps of the clinical development and was approved by US Food and Drug Administration (FDA) on December 23, 2016. Spinraza™ is the first FDA-approved treatment for SMA and the first antisense drug to restore expression of a fully functional protein via splicing correction. The success of Spinraza™ underscores the potential of intronic sequences as promising therapeutic targets and sets the stage for further improvement of antisense drugs based on advanced oligonucleotide chemistries and delivery protocols

Transgenic Mice as Immunogenicity Model

The development of antibodies after administration of pharmaceutical proteins is not only of academic interest. Antibodies can be responsible for local and systemic allergic reactions, injection site lipoatrophy and have effect on the dose requirements.Tolerant transgenic mice are used to evaluate the potential immunogenicity of pharmaceutical proteins, e.g.. human insulin. human tissue plasminogen activator and human growth hormone. The results indicate that transgenic mice should be useful as an in vivo model to map immunogenic epitopes. Transgenic mice with tissue specific expression of human insulin that are tolerant to human insulin (in contrast to their nontransgenic littermates that produce antibodies)are able to respond with antibody formation against human insulin With substitution of single amino acids, if the substitutions results in immunogenic epitopes.Finally potential future immunogenicity models are discussed