Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers

The emerging concept of psychobiotics—live microorganisms with a potential mental health benefit—represents a novel approach for the management of stress-related conditions. The majority of studies have focused on animal models. Recent preclinical studies have identified the B. longum 1714 strain as a putative psychobiotic with an impact on stress-related behaviors, physiology and cognitive performance. Whether such preclinical effects could be translated to healthy human volunteers remains unknown. We tested whether psychobiotic consumption could affect the stress response, cognition and brain activity patterns. In a within-participants design, healthy volunteers (N=22) completed cognitive assessments, resting electroencephalography and were exposed to a socially evaluated cold pressor test at baseline, post-placebo and post-psychobiotic. Increases in cortisol output and subjective anxiety in response to the socially evaluated cold pressor test were attenuated. Furthermore, daily reported stress was reduced by psychobiotic consumption. We also observed subtle improvements in hippocampus-dependent visuospatial memory performance, as well as enhanced frontal midline electroencephalographic mobility following psychobiotic consumption. These subtle but clear benefits are in line with the predicted impact from preclinical screening platforms. Our results indicate that consumption of B. longum 1714 is associated with reduced stress and improved memory. Further studies are warranted to evaluate the benefits of this putative psychobiotic in relevant stress-related conditions and to unravel the mechanisms underlying such effects.

Comparative survey of the relative impact of mRNA features on local ribosome profiling read density

Ribosome profiling (Ribo-seq), a promising technology for exploring ribosome decoding rates, is characterized by the presence of infrequent high peaks in ribosome footprint density and by long alignment gaps. Here, to reduce the impact of data heterogeneity we introduce a simple normalization method, Ribo-seq Unit Step Transformation (RUST). RUST is robust and outperforms other normalization techniques in the presence of heterogeneous noise. We illustrate how RUST can be used for identifying mRNA sequence features that affect ribosome footprint densities globally. We show that a few parameters extracted with RUST are sufficient for predicting experimental densities with high accuracy. Importantly the application of RUST to 30 publicly available Ribo-seq data sets revealed a substantial variation in sequence determinants of ribosome footprint frequencies, questioning the reliability of Ribo-seq as an accurate representation of local ribosome densities without prior quality control. This emphasizes our incomplete understanding of how protocol parameters affect ribosome footprint densities.

Functional and structural dissection of the tape measure protein of lactococcal phage TP901-1

The tail tape measure protein (TMP) of tailed bacteriophages (also called phages) dictates the tail length and facilitates DNA transit to the cell cytoplasm during infection. Here, a thorough mutational analysis of the TMP from lactococcal phage TP901-1 (TMPTP901-1) was undertaken. We generated 56 mutants aimed at defining TMPTP901-1 domains that are essential for tail assembly and successful infection. Through analysis of the derived mutants, we determined that TP901-1 infectivity requires the N-terminal 154 aa residues, the C-terminal 60 residues and the first predicted hydrophobic region of TMPTP901-1 as a minimum. Furthermore, the role of TMPTP901-1 in tail length determination was visualized by electron microscopic imaging of TMP-deletion mutants. The inverse linear correlation between the extent of TMPTP901-1-encoding gene deletions and tail length of the corresponding virion provides an estimate of TMPTP901-1 regions interacting with the connector or involved in initiator complex formation. This study represents the most thorough characterisation of a TMP from a Gram-positive host-infecting phage and provides essential advances to understanding its role in virion assembly, morphology and infection.

Influence of combined fundamental potentials in a nonlinear vibration energy harvester

Ambient mechanical vibrations have emerged as a viable energy source for low-power wireless sensor nodes aiming the upcoming era of the ‘Internet of Things’. Recently, purposefully induced dynamical nonlinearities have been exploited to widen the frequency spectrum of vibration energy harvesters. Here we investigate some critical inconsistencies between the theoretical formulation and applications of the bistable Duffing nonlinearity in vibration energy harvesting. A novel nonlinear vibration energy harvesting device with the capability to switch amidst individually tunable bistable-quadratic, monostable-quartic and bistable-quartic potentials has been designed and characterized. Our study highlights the fundamentally different large deflection behaviors of the theoretical bistable-quartic Duffing oscillator and the experimentally adapted bistable-quadratic systems, and underlines their implications in the respective spectral responses. The results suggest enhanced performance in the bistable-quartic potential in comparison to others, primarily due to lower potential barrier and higher restoring forces facilitating large amplitude inter-well motion at relatively lower accelerations.

A novel non-peptidic agonist of the ghrelin receptor with orexigenic activity in vivo

Loss of appetite in the medically ill and ageing populations is a major health problem and a significant symptom in cachexia syndromes, which is the loss of muscle and fat mass. Ghrelin is a gut-derived hormone which can stimulate appetite. Herein we describe a novel, simple, non-peptidic, 2-pyridone which acts as a selective agonist for the ghrelin receptor (GHS-R1a). The small 2-pyridone demonstrated clear agonistic activity in both transfected human cells and mouse hypothalamic cells with endogenous GHS-R1a receptor expression. In vivo tests with the hit compound showed significant increased food intake following peripheral administration, which highlights the potent orexigenic effect of this novel GHS-R1a receptor ligand.

Bifidobacterium breve UCC2003 metabolises the human milk oligosaccharides lacto-N-tetraose and lacto-N-neo-tetraose through overlapping, yet distinct pathways

In this study, we demonstrate that the prototype B. breve strain UCC2003 possesses specific metabolic pathways for the utilisation of lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT), which represent the central moieties of Type I and Type II human milk oligosaccharides (HMOs), respectively. Using a combination of experimental approaches, the enzymatic machinery involved in the metabolism of LNT and LNnT was identified and characterised. Homologs of the key genetic loci involved in the utilisation of these HMO substrates were identified in B. breve, B. bifidum, B. longum subsp. infantis and B. longum subsp. longum using bioinformatic analyses, and were shown to be variably present among other members of the Bifidobacterium genus, with a distinct pattern of conservation among human-associated bifidobacterial species.

Edge enhancement improves disruptive camouflage by emphasising false edges and creating pictorial relief

Disruptive colouration is a visual camouflage composed of false edges and boundaries. Many disruptively camouflaged animals feature enhanced edges; light patches are surrounded by a lighter outline and/or a dark patches are surrounded by a darker outline. This camouflage is particularly common in amphibians, reptiles and lepidopterans. We explored the role that this pattern has in creating effective camouflage. In a visual search task utilising an ultra-large display area mimicking search tasks that might be found in nature, edge enhanced disruptive camouflage increases crypsis, even on substrates that do not provide an obvious visual match. Specifically, edge enhanced camouflage is effective on backgrounds both with and without shadows; i.e. this is not solely due to background matching of the dark edge enhancement element with the shadows. Furthermore, when the dark component of the edge enhancement is omitted the camouflage still provided better crypsis than control patterns without edge enhancement. This kind of edge enhancement improved camouflage on all background types. Lastly, we show that edge enhancement can create a perception of multiple surfaces. We conclude that edge enhancement increases the effectiveness of disruptive camouflage through mechanisms that may include the improved disruption of the object outline by implying pictorial relief.

Atmospheric calibration for sub-millimeter radio astronomy

This thesis is focused on improving the calibration accuracy of sub-millimeter astronomical observations. The wavelength range covered by observational radio astronomy has been extended to sub-millimeter and far infrared with the advancement of receiver technology in recent years. Sub-millimeter observations carried out with airborne and ground-based telescopes typically suffer from 10% to 90% attenuation of the astronomical source signals by the terrestrial atmosphere. The amount of attenuation can be derived from the measured brightness of the atmospheric emission. In order to do this, the knowledge of the atmospheric temperature and chemical composition, as well as the frequency-dependent optical depth at each place along the line of sight is required. The altitude-dependent air temperature and composition are estimated using a parametrized static atmospheric model, which is described in Chapter 2, because direct measurements are technically and financially infeasible. The frequency dependent optical depth of the atmosphere is computed with a radiative transfer model based on the theories of quantum mechanics and, in addition, some empirical formulae. The choice, application, and improvement of third party radiative transfer models are discussed in Chapter 3. The application of the calibration procedure, which is described in Chapter 4, to the astronomical data observed with the SubMillimeter Array Receiver for Two Frequencies (SMART), and the German REceiver for Astronomy at Terahertz Frequencies (GREAT), is presented in Chapters 5 and 6. The brightnesses of atmospheric emission were fitted consistently to the simultaneous multi-band observation data from GREAT at 1.2 ∼ 1.4 and 1.8 ∼ 1.9 THz with a single set of parameters of the static atmospheric model. On the other hand, the cause of the inconsistency between the model parameters fitted from the 490 and 810 GHz data of SMART is found to be the lack of calibration of the effective cold load temperature. Besides the correctness of atmospheric modeling, the stability of the receiver is also important to achieving optimal calibration accuracy. The stabilities of SMART and GREAT are analyzed with a special calibration procedure, namely the “load calibration". The effects of the drift and fluctuation of the receiver gain and noise temperature on calibration accuracy are discussed in Chapters 5 and 6. Alternative observing strategies are proposed to combat receiver instability. The methods and conclusions presented in this thesis are applicable to the atmospheric calibration of sub-millimeter astronomical observations up to at least 4.7 THz (the H channel frequency of GREAT) for observations carried out from ∼ 4 to 14 km altitude. The procedures for receiver gain calibration and stability test are applicable to other instruments using the same calibration approach as that for SMART and GREAT. The structure of the high performance, modular, and extensible calibration program used and further developed for this thesis work is presented in the Appendix C.

Licenshantering inom webbprojekt : Hur medvetna är företag om tredjepartslicenser?

Teknikutvecklingen går snabbt framåt, och idag finns det ett stort behov av att använda andra utvecklares kod för att hänga med i det höga tempot. De kallas samlat för ramverk eller bibliotek, och hjälper utvecklaren att på ett effektivare sätt ta sig från start till mål utan att behöva skriva all programmeringskod själv. Dessa tredjepartslösningar är nästintill alltid bundna till ett licensavtal, vars restriktioner och tillåtelser utvecklaren måste följa vid nyttjandet. I denna studie har vi undersökt hur medvetenheten ser ut kring de licenser som är bundna till dessa tredjepartslösningar. Då det framkom i vår förstudie att vårt fall hade en relativt låg medvetenhet har vi även valt att titta på hur medvetenheten kan ökas. För att genomföra detta har vi valt att intervjua utvecklare och projektledare på ett konsultföretag. Vi undersökte även vilka faktorer som är viktiga för att höja medvetenheten samt vilka konsekvenser som kunde uppkomma vid bristfällande licenshantering. Vi upptäckte att det var en bristfällig kunskap om tredjepartslicenser på det studerade företaget, och hur de följde de licensrestriktioner som fanns för respektive licens. För att höja medvetenheten föreslår vi hjälpmedel i form av en automatiserad centraliserad lösning, lathundar för en enklare överblick av licensavtalen och hur användning av redan färdiga programvaror kan hjälpa till att öka medvetenheten och hanteringen av licenser.

Music copyright in the digital age: creators, commerce and copyright - an empirical study of the UK music copyright industries

Copyright markets, it is said, are ‘winner takes all’ markets favouring the interests of corporate investors over the interests of primary creators. However, little is known about popular music creators’ ‘lived experience’ of copyright. This thesis interrogates key aspects of copyright transactions between creators and investors operating in the UK music industries using analysis of various copyright related documents and semi-structured interviews with creators and investors. The research found considerable variety in the types of ‘deal’ creators enter into and considerable divergence in the potential rewards. It was observed that new-entrant creators have little comprehension of the basic tenets of copyright, but with experience they become more ‘copyright aware’. Documentary and interview evidence reveals creators routinely assign copyright to third party investors for the full term of copyright in sound recordings: the justification for this is questionable. An almost inevitable consequence of this asymmetry of understanding of copyright and asymmetry of bargaining power is that creators become alienated from their copyright works. The empirical evidence presented here supports historic and contemporary calls for a statutory mechanism limiting the maximum copyright assignment period to ten-years.

The effects of attractiveness and underlying components on the motivational salience and the memorability of face photographs

Facial attractiveness is a particularly salient social cue that influences many important social outcomes. Using a standard key-press task to measure motivational salience of faces and an old/new memory task to measure memory for face photographs, this thesis investigated both within-woman and between-women variations in response to facial attractiveness. The results indicated that within-woman variables, such as fluctuations in hormone levels, influenced the motivational salience of facial attractiveness. However, the between-women variable, romantic relationship status, did not appear to modulate women’s responses to facial attractiveness. In addition to attractiveness, dominance also contributed to both the motivational salience and memorability of faces. This latter result demonstrates that, although attractiveness is an important factor for the motivational salience of faces, other factors might also cause faces to hold motivational salience. In Chapter 2, I investigated the possible effects of women’s salivary hormone levels (estradiol, progesterone, testosterone, and estradiol-to-progesterone ratio) on the motivational salience of facial attractiveness. Physically attractive faces generally hold greater motivational salience, replicating results from previous studies. Importantly, however, the effect of attractiveness on the motivational salience of faces was greater in test sessions where women had high testosterone levels. Additionally, the motivational salience of attractive female faces was greater in test sessions where women had high estradiol-to-progesterone ratios. While results from Chapter 2 suggested that the motivational salience of faces was generally positively correlated with their physical attractiveness, Chapter 3 explored whether physical characteristics other than attractiveness contributed to the motivational salience of faces. To address this issue, I first had the faces rated on multiple traits. Principal component analysis of third-party ratings of faces for these traits revealed two orthogonal components that were highly correlated with trustworthiness and dominance ratings respectively. Both components were positively and independently related to the motivational salience of faces. While Chapter 2 and 3 did not examine the between-woman differences in response to facial attractiveness, Chapter 4 examined whether women’s responses to facial attractiveness differed as a function of their romantic partnership status. As several researchers have proposed that partnership status influences women’s perception of attractiveness, in Chapter 4 I compared the effects of men’s attractiveness on partnered and unpartnered women’s performance on two response measures: memory for face photographs and the motivational salience of faces. Consistent with previous research, women’s memory was poorer for face photographs of more attractive men and more attractive men’s faces held greater motivational salience. However, in neither study were the effects of attractiveness modulated by women’s partnership status or partnered women’s reported commitment to or happiness with their romantic relationship. A key result from Chapter 4 was that more attractive faces were harder to remember. Building on this result, Chapter 5 investigated the different characteristics that contributed to the memorability of face photographs. While some work emphasizes relationships with typicality, familiarity, and memorability ratings, more recent work suggests that ratings of social traits, such as attractiveness, intelligence, and responsibility, predict the memorability of face photographs independently of typicality, familiarity, and memorability ratings. However, what components underlie these traits remains unknown, as well as whether these components relate to the actual memorability of face photographs. Principal component analysis of all these face ratings produced three orthogonal components that were highly correlated with trustworthiness, dominance, and memorability ratings, respectively. Importantly, each of these components also predicted the actual memorability of face photographs.

El rol de la Unión Africana (UA) en el Cuerno de África a partir del caso de Somalia - AMISOM (2007-2013)

El propósito de esta monografía es comprender cuál ha sido el rol de la Unión Africana (UA), dentro de la misión de paz AMISOM en el periodo de 2007- 2013. Por ello, el trabajo abarca aspectos geopolíticos e históricos, que han influido en la configuración del conflicto armado de Somalía y que han llevado progresivamente a la creación, evolución e implementación de mecanismos como las misiones de paz. Además, se abarcan los planteamientos del neo-funcionalismo y el neo-regionalismo para comprender las estructuras y las dinámicas propias de la UA y así, comprender la naturaleza tanto de sus acciones, como de sus propósitos; propósitos que aclaman el fomento del panafricanismo. Desde aquí se puede entender como su rol ha contribuido con el crecimiento del mercado de la industria militar en la región, a costa de la responsabilidad de proteger. Por último, se concluye que dichas dinámicas han llevado a la creación de comunidades de inseguridad.

As imagens de vestir da Procissão dos Terceiros: história, conceitos, e tradições. Um legado patrimonial franciscano na ilha de S. Miguel, Açores, nos séculos XVII a XIX

A temática proposta como objeto de estudo na presente tese, é o resultado de uma investigação dedicada ao fenómeno de utilização da imaginária processional nos cortejos de penitência de pendor franciscano, nos séculos XVII a XX na ilha de S. Miguel, Açores. Este tipo de manifestações religiosas, particularmente característico no espaço Iberoamericano, evidencia-se pela originalidade cenográfica, na qual são utilizados vestuário e adereços cénicos como complementos dos respetivos conjuntos escultóricos, as denominadas imagens de vestir. No arquipélago dos Açores, a Venerável Ordem Terceira da Penitência teve um papel de grande importância na organização destes eventos processionais, sendo que as ilhas de S. Miguel e da Terceira representam atualmente um dos últimos redutos na organização de procissões penitenciais, com recurso à utilização de imagens de vestir. No caso especifíco de S. Miguel, este tipo de imaginária pode ser ainda observada nos acervos de algumas das antigas igrejas conventuais da Ordem dos Frades Menores existentes nesta ilha, bem como na única procissão oriunda do espírito penitencial da Ordem Terceira, que se realiza anualmente na cidade da Ribeira Grande. O estudo agora apresentado pretende compreender as diversas componentes da utilização deste tipo de imaginária, bem como o registo do legado patrimonial que os seculares franciscanos perpetuaram até à atualidade, materializado num processo de patrimonialização das suas imagens de vestir, expresso na dicotomia entre os objetos, enquanto matéria, e as suas realidades biográficas, ligadas às comunidades de Terceiros que estiveram por detrás do uso destas imagens processionais; ABSTRACT: Religious sculptures for dressing of the Third Procession: history, concepts, typologies and traditions - A Franciscan heritage legacy in the island of S. Miguel, Azores, between the 17th and 19th centuries. The theme proposed as object of study in this thesis is the result of a research dedicated to the custom of adorning religious sculptures and displaying them in Franciscan penitential processions between the seventeenth and twentieth centuries, in the island of S. Miguel, Azores. This type of religious expression, particularly characteristic in the Ibero-American space, featuring up by scenic originality, in which clothing and scenic props are used to complement the respective sculptural groups, called religious sculptures for dressing. In the Azores, the Venerable Third Order of Penance had a major role in organizing these processional events, and the islands of S. Miguel and Terceira currently represents one of the last holdouts in organizing penitential processions, with the use of religious sculptures for dressing. In the case of S. Miguel, this type of imaginary can still be seen in the collections of some of the ancient Order of the convent churches of the Friars Minor existing on this island, and the only procession coming from the penitential spirit of the Third Order, which is held annually in the city of Ribeira Grande. The study now being presented aims to understand the various components of the use of such imaginary, and the recording of heritage legacy that the Franciscan secular perpetuated to the present day, materialized in a patrimonialization process of their dress images, expressed in the dichotomy between objects, as matter, and their biographical realities, linked to third-party communities that were behind the use of these processional images.