Interactions between the neuromodulatory systems and the amygdala: exploratory survey using the Allen Mouse Brain Atlas.

Neuromodulatory systems originate in nuclei localized in the subcortical region of the brain and control fundamental behaviors by interacting with many areas of the central nervous system. An exploratory survey of the cholinergic, dopaminergic, noradrenergic, and serotonergic receptor expression energy in the amygdala, and in the neuromodulatory areas themselves was undertaken using the Allen Mouse Brain Atlas. The amygdala was chosen because of its importance in cognitive behavior and its bidirectional interaction with the neuromodulatory systems. The gene expression data of 38 neuromodulatory receptor subtypes were examined across 13 brain regions. The substantia innominata of the basal forebrain and regions of the amygdala had the highest amount of receptor expression energy for all four neuromodulatory systems examined. The ventral tegmental area also displayed high receptor expression of all four neuromodulators. In contrast, the locus coeruleus displayed low receptor expression energy overall. In general, cholinergic receptor expression was an order of magnitude greater than other neuromodulatory receptors. Since the nuclei of these neuromodulatory systems are thought to be the source of specific neurotransmitters, the projections from these nuclei to target regions may be inferred by receptor expression energy. The comprehensive analysis revealed many connectivity relations and receptor localization that had not been previously reported. The methodology presented here may be applied to other neural systems with similar characteristics, and to other animal models as these brain atlases become available

Analysis of nifH-RNA reveals phylotypes related to Geobacter and Cyanobacteria as important functional components of the N2-fixing community depending on depth and agricultural use of soil

In this survey, a total of 80 787 reads and 28 171 unique NifH protein sequences were retrieved from soil RNA. This dataset extends our knowledge about the structure and diversity of the functional diazotrophic communities in agricultural soils from Argentinean Pampas. Operational taxonomic unit (OTU)-based analyses showed that nifH phylotypes related to Geobacter and Anaeromyxobacter (44.8%), Rhizobiales (29%), Cyanobacteria (16.7%), and Verrucomicrobiales (8%) are key microbial components of N2 fixation in soils associated with no-till management and soil depth. In addition, quantification of nifH gene copies related to Geobacter and Cyanobacteria revealed that these groups are abundant in soils under maize-soybean rotation and soybean monoculture, respectively. The correlation of physicochemical soil parameters with the diazotrophic diversity and composition showed that soil stability and organic carbon might contribute to the functional signatures of particular nifH phylotypes in fields under no-till management. Because crop production relies on soil-borne microorganism´s activities, such as free N2 fixation, the information provided by our study on the diazotrophic population dynamics, associated with the edaphic properties and land-use practices, represents a major contribution to gain insight into soil biology, in which functionally active components are identified.Fil: Calderoli, Priscila Anabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; ArgentinaFil: Collavino, Mónica Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Botánica del Nordeste. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botánica del Nordeste; ArgentinaFil: Behrends Kraemer, Filipe. Universidad de Buenos Aires. Facultad de Agronomía; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación de Recursos Naturales. Instituto de Suelos; ArgentinaFil: Morrás, Héctor José María. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación de Recursos Naturales. Instituto de Suelos; ArgentinaFil: Aguilar, Orlando Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; Argentin

Male breast cancer

Male breast cancer (MBC) is a rare disease representing less than 1% of all breast cancers (BC) and less than 1% of cancers in men. Age at presentation is mostly in the late 60s. MBC is recognized as an estrogen-driven disease, specifically related to hyperestrogenism. About 20% of MBC patients have family history for BC. Mutations in BRCA1 and, predominantly, BRCA2, account for approximately 10% of MBC cases. Because of its rarity, MBC is often compared with female BC (FBC). Based on age-frequency distribution, age-specific incidence rate patterns and prognostic factors profiles, MBC is considered similar to late-onset, postmenopausal estrogen/progesterone receptor positive (ER+/PR+) FBC. However, clinical and pathological characteristics of MBC do not exactly overlap FBC. Compared with FBC, MBC has been reported to occur later in life, present at a higher stage, and display lower histologic grade, with a higher proportion of ER+ and PR+ tumors. Although rare, MBC remains a substantial cause for morbidity and mortality in men, probably because of its occurrence in advanced age and delayed diagnosis. Diagnosis and treatment of MBC generally is similar to that of FBC. Men tend to be treated with mastectomy rather than breast-conserving surgery. The backbone of adjuvant therapy or palliative treatment for advanced disease is endocrine, mostly tamoxifen. Use of FBC-based therapy led to the observation that treatment outcomes for MBC are worse and that survival rates for MBC do not improve like FBC. These different outcomes may suggest a non-appropriate utilization of treatments and that different underlying pathogenetic mechanisms may exist between male and female BC

Ohustatud Euroopa naaritsa (Mustela lutreola) sigimine ja käitumine tehiskeskkonnas

Väitekirja elektrooniline versioon ei sisalda publikatsiooneEuroopa naarits on kriitiliselt ohustatud imetaja, mis on loodusest kadumas. Päästmaks liiki väljasuremisest hakati naaritsaid pidama loomaaedades. Vangistuses on loomade paljundamine keeruline, kuna sealne keskkond erineb looma looduslikust elupaigast. Loomaaias elavatel naaritsatel on täheldatud probleeme sigimisega. Paljud ei saa järglasi, mis võib saada saatuslikuks asurkonna jätkusuutlikkusele. Käesolevas doktoritöös uurisin, miks on naaritsa sigimine loomaaias ebaedukas ja kuidas leida probleemile lahendus. Olukorrast parema ülevaate saamiseks uurisime, mis mõjutab pesakonna suurust ja poegade tõenäosust ellu jääda. Leidsime, et olulised on ema vanus ja kaal, kuid muidu oli emaste sigimisedu sarnane. Lisaks uurisime emase hormonaaltsüklit indlemise ja tiinuse ajal. Tulemused olid ootuspärased, hormonaaltsükkel järgis liigile tüüpilist rada. Me ei leidnud tõendeid, et paaritamiskatsete ebaõnnestumise põhjust tuleks otsida emastest. Leidsime, et ebaedu sigimisel on seotud vangistuses sündinud isastega. Mõni isane on paaritamiskatses emase vastu agressiivne või siis neil puudub indleva emase vastu huvi. Mõistmaks isaste käitumist vaatlesime naaritsate lapsepõlve – uurisime poegade vahelisi suhteid pesakonnas kasvamise ajal. Paljudel imetajatel on tõendatud, et varajane keskkond mõjutab isendi käitumist täiskasvanueas. Me ei leidnud, et naaritsatel oleks pesakonnaperioodil ebanormaalset käitumist. Nagu igati kohane, kulus poegade põhiaeg mängule. Agressiivsust ei olnud palju ja see ei tõusnud ajas. Pesakonnad ei erinenud käitumismustrilt üksteisest, seega ei leidnud me hälbiva poegade käitumisega pesakondi, mis oleksid võinud ebasobiva sigimiskäitumise tekkimist seletada. Töötasime välja metoodika naartisate iseloomutüüpide määramiseks, sest üha enam soovitatakse, et loomadesse tuleks loomaaias suhtuda neist igaühe iseloomu arvestades. Leidsime, et naaritsaid saab eristada julguse, uurivuse ja sotsiaalsuse alusel . Meie töös ilmnes, et probleemid sigimishooajal on seotud eelkõige vangistuses sündinud isastega, nende põhjuseid peaks otsima mujalt kui pesakonnaperioodist, abi võiks olla iga looma iseloomu tundmisest. Saadud tulemused on oluliseks alusteadmisteks töös, mis on suunatud naaritsate tehiskeskkonnas pidamise edukuse tõstmisele.European mink is a critically endangered carnivore which has almost disappeared from nature. To save the species from extinction a captive population was established. Unfortunately, keeping wild animals in captivity always causes problems, just because in a zoo everything is different from the species’ natural habitat. In the case of the European mink, there are problems with breeding in captive conditions. Some animals will fail to produce offspring which may threaten the persistence of the captive population. In this doctorial thesis, I addressed the reasons of breeding failures and how to find solutions to this problem. At first we studied what affects the size and survival of the litter. We found that the weight and age of the mother are most significant. Additionally we studied the hormonal cycle of the females during the mating season and gestation. Results were expectable: the hormonal cycle followed a profile typical of the species. Analysing the diaries kept at Tallinn zoo for 20 years, we did not find that something is wrong on the females’ side. Instead, we found that the breeding problems are caused by males which have been born in captivity. Some males are aggressive toward the female during the mating attempt or remain passive. To understand the reasons for kind of behaviour, we focused on the childhood of the mink: we studied the interactions between the cubs during the litter period. It has often been found that, in mammals, the early environment affects the development of the behaviour of an animal. In our study, however, we did not find abnormalities in cubs’ behaviour during the litter period. As it should be, the most frequent type of behaviour was play. Aggression was low, it did not rise in time and did not differ between the litters. We developed tests to identify personality types in European mink. We found that it is possible to distinguish individual mink in boldness, sociability and exploration. In summary, we found that the main reason why breeding fails in the European mink is in the behaviour of captive born males. The causes of behavioural distortion may not be related to the litter period, an analysis of personality types may help here. The knowledge obtained forms important basis information for the work aimed at improving keeping condition of captive European mink

Comparison of the Effects of Early Pregnancy with Human Interferon, Alpha 2 (IFNA2), on Gene Expression in Bovine Endometrium

Interferon tau (IFNT), a type I IFN similar to alpha IFNs (IFNA), is the pregnancy recognition signal produced by the ruminant conceptus. To elucidate specific effects of bovine IFNT and of other conceptus-derived factors, endometrial gene expression changes during early pregnancy were compared to gene expression changes after intrauterine application of human IFNA2. In experiment 1, endometrial tissue samples were obtained on Day (D) 12, D15, and D18 postmating from nonpregnant or pregnant heifers. In experiment 2, heifers were treated from D14 to D16 of the estrous cycle with an intrauterine device releasing IFNA2 or, as controls, placebo lipid extrudates or PBS only. Endometrial biopsies were performed after flushing the uterus. All samples from both experiments were analyzed with an Affymetrix Bovine Genome Array. Experiment 1 revealed differential gene expression between pregnant and nonpregnant endometria on D15 and D18. In experiment 2, IFNA2 treatment resulted in differential gene expression in the bovine endometrium. Comparison of the data sets from both studies identified genes that were differentially expressed in response to IFNA2 but not in response to pregnancy on D15 or D18. In addition, genes were found that were differentially expressed during pregnancy but not after IFNA2 treatment. In experiment 3, spatiotemporal alterations in expression of selected genes were determined in uteri from nonpregnant and early pregnant heifers using in situ hybridization. The overall findings of this study suggest differential effects of bovine IFNT compared to human IFNA2 and that some pregnancy-specific changes in the endometrium are elicited by conceptus-derived factors other than IFNT

A conceptual approach to gene expression analysis enhanced by visual analytics

The analysis of gene expression data is a complex task for biologists wishing to understand the role of genes in the formation of diseases such as cancer. Biologists need greater support when trying to discover, and comprehend, new relationships within their data. In this paper, we describe an approach to the analysis of gene expression data where overlapping groupings are generated by Formal Concept Analysis and interactively analyzed in a tool called CUBIST. The CUBIST workflow involves querying a semantic database and converting the result into a formal context, which can be simplified to make it manageable, before it is visualized as a concept lattice and associated charts

De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development

Bosma arhinia microphthalmia syndrome (BAMS) is an extremely rare and striking condition characterized by complete absence of the nose with or without ocular defects. We report here that missense mutations in the epigenetic regulator SMCHD1 mapping to the extended ATPase domain of the encoded protein cause BAMS in all 14 cases studied. All mutations were de novo where parental DNA was available. Biochemical tests and in vivo assays in Xenopus laevis embryos suggest that these mutations may behave as gain-of-function alleles. This finding is in contrast to the loss-of-function mutations in SMCHD1 that have been associated with facioscapulohumeral muscular dystrophy (FSHD) type 2. Our results establish SMCHD1 as a key player in nasal development and provide biochemical insight into its enzymatic function that may be exploited for development of therapeutics for FSHD