Endocrine regulation of dynamic communication signals in gymnotiform fish

Communication signals are shaped by the opposing selection pressures imposed by predators and mates. A dynamic signal might serve as an adaptive compromise between an inconspicuous signal that evades predators and an extravagant signal preferred by females. Such a signal has been described in the gymnotiform electric fish, Brachyhypopomus gauderio, which produces a sexually dimorphic electric organ discharge (EOD). The EOD varies on a circadian rhythm and in response to social cues. This signal plasticity is mediated by the slow action of androgens and rapid action of melanocortins. My dissertation research tested the hypotheses that (1) signal plasticity is related to sociality levels in gymnotiform species, and (2) differences in signal plasticity are regulated by differential sensitivity to androgen and melanocortin hormones. To assess the breadth of dynamic signaling within the order Gymnotiformes, I sampled 13 species from the five gymnotiform families. I recorded EODs to observe spontaneous signal oscillations after which I injected melanocortin hormones, saline control, or presented the fish with a conspecific. I showed that through the co-option of the ancient melanocortin pathway, gymnotiforms dynamically regulate EOD amplitude, spectral frequency, both, or neither. To investigate whether observed EOD plasticities are related to species-specific sociality I tested four species; two territorial, highly aggressive species, Gymnotus carapo and Apteronotus leptorhynchus, a highly gregarious species, Eigenmannia cf. virescens , and an intermediate short-lived species with a fluid social system, Brachyhypopomus gauderio. I examined the relationship between the androgens testosterone and 11-ketotestosterone, the melanocortin α-MSH, and their roles in regulating EOD waveform. I implanted all fish with androgen and blank silicone implants, and injected with α-MSH before and at the peak of implant effect. I found that waveforms of the most territorial and aggressive species were insensitive to hormone treatments; maintaining a static, stereotyped signal that preserves encoding of individual identity. Species with a fluid social system were most responsive to hormone treatments, exhibiting signals that reflect immediate condition and reproductive state. In conclusion, variation in gymnotiform signal plasticity is hormonally regulated and seems to reflect species-specific sociality.

Transcriptome Analysis Reveals New Insights into the Modulation of Endometrial Stromal Cell Receptive Phenotype by Embryo-Derived Signals Interleukin-1 and Human Chorionic Gonadotropin: Possible Involvement in Early Embryo Implantation

The presence of the conceptus in uterine cavity necessitates an elaborate network of interactions between the implanting embryo and a receptive endometrial tissue. We believe that embryo-derived signals play an important role in the remodeling and the extension of endometrial receptivity period. Our previous studies provided original evidence that human Chorionic Gonadotropin (hCG) modulates and potentiates endometrial epithelial as well as stromal cell responsiveness to interleukin 1 (IL1), one of the earliest embryonic signals, which may represent a novel pathway by which the embryo favors its own implantation and growth within the maternal endometrial host. The present study was designed to gain a broader understanding of hCG impact on the modulation of endometrial cell receptivity, and in particular, cell responsiveness to IL1 and the acquisition of growth-promoting phenotype capable of receiving, sustaining, and promoting early and crucial steps of embryonic development. Our results showed significant changes in the expression of genes involved in cell proliferation, immune modulation, tissue remodeling, apoptotic and angiogenic processes. This points to a relevant impact of these embryonic signals on the receptivity of the maternal endometrium, its adaptation to the implanting embryo and the creation of an environment that is favorable for the implantation and the growth of this latter within a new and likely hostile host tissue. Interestingly our data further identified a complex interaction between IL1 and hCG, which, despite a synergistic action on several significant endometrial target genes, may encompass a tight control of endogenous IL1 and extends to other IL1 family members.

Paleoenvironments and geochemical signals from the late Barremian to the middle Aptian in a Tethyan marginal basin, northeast Spain: Implications for carbon sequestration in restricted basins

The hallmark of oceanic anoxic event 1a (OAE1a) (early Aptian ~125 Ma) corresponds to worldwide deposition of black shales with total organic carbon (TOC) content > 2% and a δ13C positive excursion up to ~5‰. OAE1a has been related to large igneous province volcanism and dissociation of methane hydrates during the Lower Cretaceous. However, the occurrence of atypical, coeval and diachronous organic-rich deposits associated with OAE1a, which are also characterized by positive spikes of the δ 13C in epicontinental to restricted marine environments of the Tethys Ocean, indicates localized responses decoupled from complex global forcing factors. ^ The present research is a high-resolution, multiproxy approach to assess the paleoenvironmental conditions that led to enhanced carbon sequestration from the late Barremian to the middle Aptian in a restricted, Tethyan marginal basin prior to and during OAE1a. I studied the lower 240 m of the El Pui section, Organyà Basin, Spanish Pyrenees. The basin developed as the result of extensional tectonism linked to the opening of the Atlantic Ocean. At the field scale the section consists of a sequence of alternating beds of cm – m-scale, medium-gray to grayish-black limestones and marlstones with TOC up to ~4%. ^ The results indicate that the lowest 85 m of the section, from latest Barremian -earliest Aptian, characterize a deepening phase of the basin concomitant with sustained riverine flux and intensified primary productivity. These changes induced a shift in the sedimentation pattern and decreased the oxygen levels in the water column through organic matter respiration and limited ventilation of the basin. ^ The upper 155 m comprising the earliest – late-early Aptian document the occurrence of OAE1a and its associated geochemical signatures (TOC up to 3% and a positive shift in δ13C of ~5‰). However, a low enrichment of redox-sensitive trace elements indicates that the basin did not achieve anoxic conditions. The results also suggest that a shallower-phase of the basin, coeval with platform progradation, may have increased ventilation of the basin at the same time that heightened sedimentation rates and additional input of organic matter from terrestrial sources increased the burial and preservation rate of TOC in the sediment.^

Corpus annotation of causal relations and their signals in English and Spanish

El estudio de las relaciones causales y su expresión lingüística ha sido comúnmente estudiado desde diferentes perspectivas en los años recientes. Sin embargo, pocos estudios han intentado combinar diferentes enfoques para establecer el significado de estas relaciones, y han investigado de manera contrastiva las señales usadas para expresarlas. Este trabajo de fin de master es un proyecto para avanzar el conocimiento en este área mediante la investigación de: a) la posibilidad de caracterizar las relaciones causales en diferentes tipos, usando características que combinan un enfoque funcional y cognitivo; b) los tipos de relaciones causales preferidas en los textos expositivos en inglés y sus traducciones al español; c) las expresiones lingüísticas preferidas para expresar dichas relaciones causales en los textos originales en inglés y sus traducciones al español. La metodología usada en esta investigación se basa en la anotación manual de un corpus bilingüe compuesto de un total de 37 textos expositivos (incluyendo los textos originales en inglés y sus traducciones al español) extraídos del corpus MULTINOT, un corpus de alta calidad, con registros diversificados y multifuncional bilingüe inglésespañol, actualmente compilado y anotado multidimensionalmente por los miembros del grupo de investigación FUNCAP con el proyecto MULTINOT (véase Lavid et al.2015) El estudio se llevó a cabo en cuatro pasos principales: primero, un esquema de anotación para las relaciones causales en inglés y español fue diseñado constando de tres sistemas interrelacionados y sus correspondientes características; tras ello, se compiló un inventario de señales para las relaciones causales en inglés y español, y una categorización en diferentes tipos; seguidamente, el esquema de anotación fue implementado en la herramienta UAM Corpus Tool y el conjunto de textos bilingües fue anotado por el autor de este estudio; finalmente, los datos extraídos de la anotación fueron analizados estadísticamente para comprobar las posibles diferencias entre los textos originales en inglés y sus traducciones al español respecto a la selección del tipo de relación de causa y sus señales. El análisis estadístico de los datos anotados sugiere que los tipos de relaciones de causa preferidos en los textos originales en inglés y son los tipos de contenido y no volitivos, que el orden de aparición de estos tipos de señales preferido es la segunda posición, y las señales más recurrentes usadas para expresar dichas relaciones son las conjunciones, seguidas de los sintagmas verbales. El análisis de las traducciones al español revela un alto grado de similitud con los datos de los textos originales en inglés, lo que sugiere que en las traducciones al español se conservan las preferencias de los textos originales en la mayoría de los casos y que estas elecciones pueden considerarse un indicativo de los textos expositivos en inglés. Proyectos futuros se centraran en el análisis de los textos originales en español para comprobar si las tendencias observadas en los textos originales en inglés y sus traducciones al español son también validas en textos originales en español, y en la especificación de patrones que puede ayudar al análisis automático de estas relaciones

Regulatory factors controlling muscle mass : competition between innate immune function and anabolic signals in regulation of atrogin-1 in Atlantic salmon

The research was supported by an industrial PhD studentship between University of Aberdeen and by BioMar Ltd., for Z. Heidari.

Regulatory factors controlling muscle mass : competition between innate immune function and anabolic signals in regulation of atrogin-1 in Atlantic salmon

The research was supported by an industrial PhD studentship between University of Aberdeen and by BioMar Ltd., for Z. Heidari.

Beak colour dynamically signals changes in fasting status and parasite loads in king penguins

Peer reviewed

Regulatory factors controlling muscle mass : competition between innate immune function and anabolic signals in regulation of atrogin-1 in Atlantic salmon

The research was supported by an industrial PhD studentship between University of Aberdeen and by BioMar Ltd., for Z. Heidari.

Characterisation of cascaded Raman-assisted fibre optical parametric amplifiers using WDM QPSK signals

We report the first WDM numerical characterisation of crosstalk growth in cascaded Raman-Assisted Fibre Optical Parametric Amplifiers (RA-FOPAs). A cascade of ten RA-FOPAs results in ∼13dB lower crosstalk than the equivalent cascade of conventional FOPAs.

Calcium/Calmodulin-Dependent Protein Kinase II Serves as a Biochemical Integrator of Calcium Signals for the Induction of Synaptic Plasticity

Repetitive Ca2+ transients in dendritic spines induce various forms of synaptic plasticity by transmitting information encoded in their frequency and amplitude. CaMKII plays a critical role in decoding these Ca2+ signals to initiate long-lasting synaptic plasticity. However, the properties of CaMKII that mediate Ca2+ decoding in spines remain elusive. Here, I measured CaMKII activity in spines using fast-framing two-photon fluorescence lifetime imaging. Following each repetitive Ca2+ elevations, CaMKII activity increased in a stepwise manner. This signal integration, at the time scale of seconds, critically depended on Thr286 phosphorylation. In the absence of Thr286 phosphorylation, only by increasing the frequency of repetitive Ca2+ elevations could high peak CaMKII activity or plasticity be induced. In addition, I measured the association between CaMKII and Ca2+/CaM during spine plasticity induction. Unlike CaMKII activity, association of Ca2+/CaM to CaMKII plateaued at the first Ca2+ elevation event. This result indicated that integration of Ca2+ signals was initiated by the binding of Ca2+/CaM and amplified by the subsequent increases in Thr286-phosphorylated form of CaMKII. Together, these findings demonstrate that CaMKII functions as a leaky integrator of repetitive Ca2+ signals during the induction of synaptic plasticity, and that Thr286 phosphorylation is critical for defining the frequencies of such integration.

Degradation rates and productivity signals of organic-walled dinoflagellate cyst species in surface sediment samples

To understand the role of the ocean within the global carbon cycle, detailed information is required on key-processes within the marine carbon cycle; bio-production in the upper ocean, export of the produced material to the deep ocean and the storage of carbon in oceanic sediments. Quantification of these processes requires the separation of signals of net primary production and the rate of organic matter decay as reflected in fossil sediments. This study examines the large differences in degradation rates of organic-walled dinoflagellate cyst species to separate these degradation and productivity signals. For this, accumulation rates of cyst species known to be resistant (R-cysts) or sensitive (S-cysts) to aerobic degradation of 62 sites are compared to mean annual chlorophyll-a, sea-surface temperature, sea-surface salinity, nitrate and phosphate concentrations of the upper waters and deep-water oxygen concentrations. Furthermore, the degradation of sensitive cysts, as expressed by the degradation constant k and reaction time t, has been related to bottom water [O2]. The studied sediments were taken from the Arabian Sea, north-western African Margin (North Atlantic), western-equatorial Atlantic Ocean/Caraibic, south-western African margin (South Atlantic) and Southern Ocean (Atlantic sector). Significant relationships are observed between (a) accumulation rates of R-cysts and upper water chlorophyll-a concentrations, (b) accumulation rates of S-cysts and bottom water [O2] and (c) degradation rates of S-cysts (kt) and bottom water [O2]. Relationships that are extremely weak or are clearly insignificant on all confidence intervals are between (1) S-cyst accumulation rates and chlorophyll-a concentrations, sea-surface temperature (SST), sea-surface salinity (SSS), phosphate concentrations (P) and nitrate concentrations (N), (2) between R-cyst accumulation rates and bottom water [O2], SST, SSS, P and N, and between (3) kt and water depth. Co-variance is present between the parameters N and P, N, P and chlorophyll-a, oxygen and water depth. Correcting for this co-variance does not influence the significance of the relationship given above. The possible applicability of dinoflagellate cyst degradation to estimate past net primary production and deep ocean ventilation is discussed.

Subfornical organ neurons integrate cardiovascular and metabolic signals

The subfornical organ (SFO) is a critical circumventricular organ involved in the control of cardiovascular and metabolic homeostasis. Despite the abundant literature clearly demonstrating the ability of SFO neurons to sense and respond to a plethora of circulating signals that influence various physiological systems, investigation of how simultaneously sensed signals interact and are integrated in the SFO is lacking. In this study, we use patch clamp techniques to investigate how the traditionally classified ‘cardiovascular’ hormone angiotensin II (ANG), ‘metabolic’ hormone cholecystokinin (CCK) and ‘metabolic’ signal glucose interact and are integrated in the SFO. Sequential bath-application of CCK (10nM) and ANG (10nM) onto dissociated SFO neurons revealed that: 63% of responsive SFO neurons depolarized to both CCK & ANG; 25% depolarized to ANG only; and 12% hyperpolarized to CCK only. We next investigated the effects of glucose by incubating and recording neurons in either hypo-, normo- or hyperglycemic conditions for a minimum of 24 hours and comparing the proportions of responses to ANG (n=55) or CCK (n=83) application in each condition. A hyperglycemic environment was associated with a larger proportion of depolarizing responses to ANG (X2, p<0.05), and a smaller proportion of depolarizing responses along with a larger proportion of hyperpolarizing responses to CCK (X2, p<0.01). These data demonstrate that SFO neurons excited by CCK are also excited by ANG, suggesting that CCK may influence fluid intake or blood pressure via the SFO, complementary to the well-understood actions of ANG at this site. Additionally, the demonstration that glucose environment affects the responsiveness of neurons to both these hormones highlights the ability of SFO neurons to integrate multiple metabolic and cardiovascular signals to affect transmission of information from the circulation to the brain, which has important implications for this structure’s critical role regulation of autonomic function.

Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. CONCLUSION: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk

A Reliable Downscaling of ECG Signals for the Detection of T wave Heterogeneity Features

In cardiovascular disease the definition and the detection of the ECG parameters related to repolarization dynamics in post MI patients is still a crucial unmet need. In addition, the use of a 3D sensor in the implantable medical devices would be a crucial mean in the assessment or prediction of Heart Failure status, but the inclusion of such feature is limited by hardware and firmware constraints. The aim of this thesis is the definition of a reliable surrogate of the 500 Hz ECG signal to reach the aforementioned objective. To evaluate the worsening of reliability due to sampling frequency reduction on delineation performance, the signals have been consecutively down sampled by a factor 2, 4, 8 thus obtaining the ECG signals sampled at 250, 125 and 62.5 Hz, respectively. The final goal is the feasibility assessment of the detection of the fiducial points in order to translate those parameters into meaningful clinical parameter for Heart Failure prediction, such as T waves intervals heterogeneity and variability of areas under T waves. An experimental setting for data collection on healthy volunteers has been set up at the Bakken Research Center in Maastricht. A 16 – channel ambulatory system, provided by TMSI, has recorded the standard 12 – Leads ECG, two 3D accelerometers and a respiration sensor. The collection platform has been set up by the TMSI property software Polybench, the data analysis of such signals has been performed with Matlab. The main results of this study show that the 125 Hz sampling rate has demonstrated to be a good candidate for a reliable detection of fiducial points. T wave intervals proved to be consistently stable, even at 62.5 Hz. Further studies would be needed to provide a better comparison between sampling at 250 Hz and 125 Hz for areas under the T waves.