Proteomic changes in serum of first onset, antidepressant drug-naïve major depression patients

Major depressive disorder (MDD) is a complex and multi-factorial disorder. Although genetic factors and other molecular aspects of MDD have been widely studied, the underlying pathological mechanisms are still mostly unknown. We sought to investigate the pathophysiology of MDD by identifying and characterising serum molecular differences and their correlation to symptom severity in first onset, antidepressant drug-naïve MDD patients. We performed an exploratory molecular profiling study on serum samples of MDD patients and controls using multiplex immunoassay and label-free liquid chromatography mass spectrometry in data independent mode (LC-MSE). We included two independent cohorts of first onset, antidepressant drug-naïve MDD patients (n = 23 and 15) and matched controls (n = 42 and 21) in our study in order to validate the results. The main outcome included the following list of circulatory molecules changing and/or correlating to symptom severity: angiotensin-converting enzyme, acute phase proteins (e.g. ferritin and serotransferrin), brain-derived neurotrophic factor, complement component C4-B, cortisol, cytokines (e.g. macrophage migration inhibitory factor and interleukin-16), extracellular newly identified receptor for advanced glycosylation end products-binding protein, growth hormone and superoxide dismutase-1. This study provides evidence of an increased pro-inflammatory and oxidative stress response, followed by a hyperactivation of the HPA-axis in the acute stages of first onset MDD, as well as a dysregulation in growth factor pathways. These findings help to elucidate MDD related pathways in more detail and further studies may lead to identification of novel drug targets, inc

Auger electron wave packet interferometry on extreme timescales with coherent soft x rays

Wave packet interferometry provides benchmark information on light-induced electronic quantum states by monitoring their relative amplitudes and phases during coherent excitation, propagation,and decay. The relative phase control of soft x-ray pulse replicas on the single-digit attosecond timescale achieved in our experiments makes this method a powerful tool to probe ultrafast quantum phenomena such as the excitation of Auger shake-up states with sub-cycle precision. In this contribution we present first results obtained for different Auger decay channels upon generating L-shell vacancies in argon atoms using Michelson-type all-reflective interferometric autocorrelation at a central free-electron laser photon energy of 274.7 eV

Charge induced chemical dynamics in glycine probed with time resolved Auger electron spectroscopy

In the present contribution, we use x rays to monitor charge induced chemical dynamics in the photoionized amino acid glycine with femtosecond time resolution. The outgoing photoelectron leaves behind the cation in a coherent superposition of quantum mechanical eigenstates. Delayed x ray pulses track the induced coherence through resonant x ray absorption that induces Auger decay. Temporal modulation of the Auger electron signal correlated with specific ions is observed, which is governed by the initial electronic coherence and subsequent vibronic coupling to nuclear degrees of freedom. In the time resolved x ray absorption measurement, we monitor the time frequency spectra of the resulting many body quantum wave packets for a period of 175 fs along different reaction coordinates. Our experiment proves that by measuring specific fragments associated with the glycine dication as a function of the pump probe delay, one can selectively probe electronic coherences at early times associated with a few distinguishable components of the broad electronic wave packet created initially by the pump pulse in the cation. The corresponding coherent superpositions formed by subsets of electronic eigenstates and evolving along parallel dynamical pathways show different phases and time periods in the range of amp; 8722;0.3 0.1 amp; 120587; amp; 8804; amp; 120601; amp; 8804; 0.1 0.2 amp; 120587; and 18.2 1.7 amp; 8722;1.4 amp; 8804; amp; 119879; amp; 8804;23.9 1.2 amp; 8722;1.1 fs. Furthermore, for long delays, the data allow us to pinpoint the driving vibrational modes of chemical dynamics mediating charge induced bond cleavage along different reaction coordinate

A Bacia do Algarve: Estratigrafia, Paleogeografia e Tectónica

A “Bacia do Algarve” corresponde, segundo a literatura científica tradicional, aos terrenos mesocenozóicos que orlam o Sul de Portugal, desde o Cabo de São Vicente ao rio Guadiana (~140km), penetrando irregularmente para o interior entre 3 km a 25 km, sobre terrenos de idade carbónica da Zona Sul Portuguesa. O hiato, de aproximadamente 70 milhões de anos, materializado pela discordância angular entre as rochas sedimentares de tipo flysch do Carbónico, metamorfizadas e deformadas durante a orogenia varisca, e as rochas sedimentares continentais do Triásico inferior provável, separa dois ciclos de Wilson. Os sedimentos carbónicos metamorfizados resultam do empilhamento orogénico de um possível prisma de acrecção associado à orogenia varisca e ao fecho de um oceano paleozóico e formação da Pangeia, enquanto que os sedimentos continentais triásicos resultam do fim do colapso e do arrasamento do orógeno varisco e início do estiramento continental que viriam a culminar com a separação das placas litosféricas África, Eurásia e América.Os sedimentos mais recentes do Mesozóico e os mais antigos bem datados do Cenozóico encontram-se separados por um outro hiato que ultrapassa ligeiramente os 70 milhões de anos na área emersa. Este hiato resulta duma alteração tectónica radical no contexto onde nessa época geológica se inseria a Bacia do Algarve. Esta mudança, que ocorreu no fim do Cenomaniano, resultou da rotação do vector de deslocamento da trajectória de África em relação à Eurásia, de aproximadamente NW-SE para SW-NE (segundo as coordenadas actuais, e.g. Dewey et al, 1989), poria termo ao regime distensivo e de bacia de tipo rifte na Bacia do Algarve, com o fim do regime transtensivo entre a região noroeste da placa África e sudoeste da placa Eurásia e início da colisão

Electronic quantum coherence in glycine molecules probed with ultrashort x ray pulses in real time

Here, we use x rays to create and probe quantum coherence in the photoionized amino acid glycine. The outgoing photoelectron leaves behind the cation in a coherent superposition of quantum mechanical eigenstates. Delayed x ray pulses track the induced coherence through resonant x ray absorption that induces Auger decay and by photoelectron emission from sequential double photoionization. Sinusoidal temporal modulation of the detected signal at early times 0 to 25 fs is observed in both measurements. Advanced ab initio many electron simulations allow us to explain the first 25 fs of the detected coherent quantum evolution in terms of the electronic coherence. In the kinematically complete x ray absorption measurement, we monitor its dynamics for a period of 175 fs and observe an evolving modulation that may implicate the coupling of electronic to vibronic coherence at longer time scales. Our experiment provides a direct support for the existence of long lived electronic coherence in photoionized biomolecule