Monosynaptic connections between pairs of spiny stellate cells in layer 4 and pyramidal cells in layer 5A indicate that lemniscal and paralemniscal afferent pathways converge in the infragranular somatosensory cortex.

Monosynaptic interlaminar connections between spiny stellate cells in layer 4 (L4), the main cortical recipient layer for thalamic projections, and pyramidal cells in layer 5A (L5A), one of the main cortical output layers, were examined anatomically and functionally by paired recordings in acute brain slices. The somata of pairs forming interlaminar L4-to-L5A connections were located predominantly close to or directly under the barrel-septum wall in layer 4. Superposition of spiny stellate axon arbors and L5A pyramidal cell dendritic arbors suggested an innervation domain underneath an L4 barrel wall. Functionally, the L4-to-L5A connections were of high reliability and relatively low efficacy, with a unitary EPSP amplitude of 0.6 mV, and the connectivity was moderately high (one in seven pairs tested was connected). The EPSP amplitude was weakly depressing (paired-pulse ratio of approximately 0.8) during repetitive presynaptic action potentials at 10 Hz. The existence of Monosynaptic L4-to-L5A connections indicates that the specific 'lemniscal' thalamic input from the ventro-basal nucleus of the thalamus to the cortex and the more unspecific 'paralemniscal' afferent thalamic projections from the posterior medial nucleus of the thalamus merge already at an initial stage of cortical signal processing. These Monosynaptic connections establish a Monosynaptic coupling of the input to the cortex and its output, thereby effectively bypassing the supragranular layers

Genomic basis of ecological niche divergence among cryptic sister species of non-biting midges

Background: There is a lack of understanding the evolutionary forces driving niche segregation of closely related organisms. In addition, pinpointing the genes driving ecological divergence is a key goal in molecular ecology. Here, larval transcriptome sequences obtained by next-generation-sequencing are used to address these issues in a morphologically cryptic sister species pair of non-biting midges (Chironomus riparius and C. piger). Results: More than eight thousand orthologous open reading frames were screened for interspecific divergence and intraspecific polymorphisms. Despite a small mean sequence divergence of 1.53% between the sister species, 25.1% of 18,115 observed amino acid substitutions were inferred by α statistics to be driven by positive selection. Applying McDonald-Kreitman tests to 715 alignments of gene orthologues identified eleven (1.5%) genes driven by positive selection. Conclusions: Three candidate genes were identified as potentially responsible for the observed niche segregation concerning nitrite concentration, habitat temperature and water conductivity. Additionally, signs of positive selection in the hydrogen sulfide detoxification pathway were detected, providing a new plausible hypothesis for the species’ ecological differentiation. Finally, a divergently selected, nuclear encoded mitochondrial ribosomal protein may contribute to reproductive isolation due to cytonuclear coevolution

Structure and function of neocortical layer 6b

Cortical layer 6b is considered by many to be a remnant of the subplate that forms during early stages of neocortical development, but its role in the adult is not well understood. Its neuronal complement has only recently become the subject of systematic studies, and its axonal projections and synaptic input structures have remained largely unexplored despite decades of research into neocortical function. In recent years, however, layer 6b (L6b) has attracted increasing attention and its functional role is beginning to be elucidated. In this review, I will attempt to provide an overview of what is currently known about the excitatory and inhibitory neurons in this layer, their pre- and postsynaptic connectivity, and their functional implications. Similarities and differences between different cortical areas will be highlighted. Finally, layer 6b neurons are highly responsive to several neuropeptides such as orexin/hypocretin, neurotensin and cholecystokinin, in some cases exclusively. They are also strongly controlled by neurotransmitters such as acetylcholine and norepinephrine. The interaction of these neuromodulators with L6b microcircuitry and its functional consequences will also be discussed

Shared and divergent principles of synaptic transmission between cortical excitatory neurons in rodent and human brain

Information transfer between principal neurons in neocortex occurs through (glutamatergic) synaptic transmission. In this focussed review, we provide a detailed overview on the strength of synaptic neurotransmission between pairs of excitatory neurons in human and laboratory animals with a specific focus on data obtained using patch clamp electrophysiology. We reach two major conclusions: (1) the synaptic strength, measured as unitary excitatory postsynaptic potential (or uEPSP), is remarkably consistent across species, cortical regions, layers and/or cell-types (median 0.5 mV, interquartile range 0.4–1.0 mV) with most variability associated with the cell-type specific connection studied (min 0.1–max 1.4 mV), (2) synaptic function cannot be generalized across human and rodent, which we exemplify by discussing the differences in anatomical and functional properties of pyramidal-to-pyramidal connections within human and rodent cortical layers 2 and 3. With only a handful of studies available on synaptic transmission in human, it is obvious that much remains unknown to date. Uncovering the shared and divergent principles of synaptic transmission across species however, will almost certainly be a pivotal step toward understanding human cognitive ability and brain function in health and disease

Secondary succession in a Swiss mire after a bog burst

Severe natural disturbances can lead to the recovery of the original vegetation or the shift to new vegetation types. While post-disturbance succession is well documented for regularly disturbed ecosystems, little is known about the pathways and rapidity of vegetation dynamics after rare events such as peat mass movements in bogs. We monitored the floristic changes in a mire subject to a bog burst in 1987 for two decades through the repeated sampling of permanent plots. The mean species number per plot increased continuously, while the evenness increased only in the first decade and then slightly decreased. Declining species were mostly mire species, while colonist species were mostly wet meadow species. Species turnover was higher in the first decade after the disturbance, and was also higher in the area of peat erosion than in the area of peat accumulation. Changes in plant species composition indicate a succession towards tall-forb vegetation (Filipendulion), acidic fen vegetation (Caricion fuscae) and swamp willow forest (Salicion). We conclude that the effects of the disturbance are still ongoing, and that the mire's potential for recovery is therefore difficult to predic

Appeasement versus fighting: a new slavemaker employs alternative raiding strategies

Trabalho final de mestrado integrado em Medicina (Urologia), apresentado á Faculdade de Medicina da Universidade de CoimbraA disfunção miccional que sucede ao traumatismo vertebro-medular, frequentemente designada de bexiga neurogénica, é uma das consequências mais importantes e limitativas para o indivíduo, após este tipo de lesão. A reorganização das vias de inervação da bexiga altera o controlo voluntário da micção e causa a emergência de reflexos não fisiológicos, de onde advêm os diferentes sintomas. Ainda que a incidência dos traumatismos tenha vindo a diminuir, as sequelas devastadoras impostas ao indivíduo, quer imediatas quer futuras, que condicionam a sua qualidade de vida e dificultam uma recuperação funcional completa, fazem com que estes nunca deixem de representar uma importante causa de morbilidade. Décadas de investigação na área e os conhecimentos adquiridos acerca dos mecanismos moleculares, organizacionais e neuroquímicos permitiram desenvolver estratégias de tratamento cada vez mais eficazes, particularmente na área da farmacologia. Actualmente, os objectivos passam pelo desenvolvimento de agentes que se revelem seguros e com um adequado perfil de reacções adversas, contra novos alvos terapêuticos. Este artigo de revisão pretende, assim, analisar e resumir a anatomia e a fisiologia do tracto urinário inferior e do processo miccional, bem como a fisiopatologia da sua disfunção de etiologia neurogénica. Pretende ainda abordar as manifestações clínicas que subjazem a esta patologia, os meios de diagnóstico disponíveis ao seu estudo e as estratégias terapêuticas recomendadas actualmente. Para a sua realização, foi pesquisada a literatura científica relevante através da base de dados PubMed, dando preferência aos estudos mais recentes, quando possível. Foram ainda consultados livros e publicações da especialidade.Voiding dysfunction following spinal cord injury, often referred to as neurogenic bladder, is one of the most important and limiting consequences for the individual, after this kind of injury. The reorganization of bladder innervation pathways alters the voluntary control of micturiton and causes the emergence of non-physiological reflexes, from which the different symptoms arise. Even though the incidence of spinal cord injuries has been declining, the devastating sequelae imposed upon the individual, either immediate or upcoming, which affect his quality of life and hinder a full functional recovery, make that these never cease to represent a major morbidity cause. Decades of research in the field and the acquired knowledge about the molecular, organizational and neurochemical mechanisms allowed developing increasingly effective treatment strategies, particularly in the area of pharmacology. Currently, the objective is the development of agents found to be safe and with a proper adverse event profile, against new therapeutic targets. This review thus aims to analyze and summarize the anatomy and physiology of the lower urinary tract and voiding process, as well as the pathophysiology of its dysfunction of neurogenic etiology. It also intends to address the clinical manifestations that underlie this pathology, the diagnostic procedures available for its study and the treatment strategies currently recommended. For accomplishing this, relevant scientific literature was searched via PubMed database and preference was given to the more recent studies, whenever possible. Books and publications of the specialty were also consulted

Untersuchungen zur Regulation der Aktivierung humaner T-Lymphozyten bei Arginindepletion

Die Verstoffwechslung der semiessentiellen Aminosäure Arginin ist entscheidend beteiligt an der Regulation der Immunantwort im Verlauf von Infektionen, entzündlichen Erkrankungen und bei Tumorwachstum. Arginin wird durch die Enzyme Arginase und Stickstoffmonoxid-Synthase abgebaut, wodurch die Verfügbarkeit der Aminosäure reguliert wird. Eine lokale Arginindepletion, welche z.B. durch Freisetzung von Arginase 1 aus myeloischen Zellen verursacht wird, führt zur völligen Hemmung der Proliferation und zahlreicher Effektor-Funktionen aktivierter humaner T-Lymphozyten. Hierbei waren die intrazellulären Mechanismen, welche zur Suppression zahlreicher T-Zell-Funktionen bei Argininmangel führen, bei Beginn dieser Promotionsarbeit, weitgehend unklar. In der vorliegenden Arbeit wurde der Einfluss von Argininmangel auf die intrazelluläre Signaltransduktion in aktivierten primären humanen T-Zellen gesunder Blutspender in vitro untersucht. Durch proteomische Analysen konnte gezeigt werden, dass das Fehlen der Aminosäure Arginin bei T-Zell-Aktivierung zu einer signifikant reduzierten Dephoshorylierung des Aktin-bindenden Proteins Cofilin führt. Normalerweise führt die Stimulation über den T-Zell-Rezeptor und kostimulatorische Moleküle via Dephosphorylierung zur Aktivierung von Cofilin, welches eine entscheidende Rolle bei der Reorganisation des Aktin-Zytoskeletts, der T-Zellproliferation und Zytokinsekretion spielt. Im Zusammenhang mit der Persistenz der phosphorylierten Form von Cofilin zeigte sich bei Argininabwesenheit ein veränderter F-Aktingehalt in aktivierten T-Zellen. Außerdem korrelierte die verminderte Ausbildung der Immunologischen Synapse, der Kontaktzone zwischen T-Zelle und antigenpräsentierende Zelle, mit der fehlenden Aktin-Bindefähigkeit von Cofilin. Im Gegensatz dazu ist ein weiterer Cofilin-abhängiger Prozess, die Migration, bei Argininabwesenheit unbeeinträchtigt. Ferner konnte erstmals eine dichotome Regulation der Zytokinsynthese und -sekretion in humanen T-Lymphozyten bei Arginindefizienz gezeigt werden. Während Arginindepletion zu einer signifikanten Inhibition von Produktion und Sekretion der Zytokine IFN-g, TNF-b und IL-10 führt, zeigte sich eine unbeeinträchtigte Synthese der Zytokine IL-2, IL-6 und IL-8. Weitere Untersuchungen zur frühen (1-30 min) Signaltransduktion bei T-Zell-Aktivierung zeigten, dass der Kalziumflux unabhängig von der extrazellulären Argininkonzentration induziert wird. Auch fanden sich keine argininabhängigen Unterschiede in der frühen Cofilin-Dephosphorylierung sowie bei Aktivierung der für die Cofilin-Dephosphorylierung verantwortlichen Ras-MEK-ERK- und Ras-PI3K-Akt-Signalwege. Im weiteren Verlauf zeigte sich dann bei Argininmangel in Assoziation mit der beeinträchtigten Cofilin- Dephosphorylierung eine reduzierte ERK-Phosphorylierung bei prolongierter Akt-Phosphorylierung. Diese Alterationen der T-Zell-Signaltransduktion fanden sich gleichartig auch bei Stimulation der Zellen in einem durch humane Granulozyten-Arginase (aus humanem Eiter ex vivo gewonnen) von Arginin depletierten Milieu und waren durch Zugabe eines Arginase-Inhibitors vollständig inhibierbar. Dieses Modell unterstreicht die Relevanz der beschriebenen T-Zell-Alterationen für die Situation granulozytär dominierter Inflammation in vivo. Das durch diese Arbeit gewonnene, bessere Verständnis intrazellulärer Regulationsmechanismen humaner T-Lymphozyten bei Arginindefizienz sollte dazu beitragen, in Zukunft in die unerwünschte Immunsuppression bei Tumorerkrankungen oder chronischer Inflammation kausal pharmakologisch eingreifen zu können

Post-Irradiation Morphea of the Breast in a Patient with Subacute Cutaneous Lupus Erythematosus: Case Report and a Literature Review.

The appearance of morphea after radiotherapy, especially in the context of breast cancer, is a rare but known phenomenon. The incidence of post-irradiation morphea (PIM) of the breast is approximately one in every 500 patients, a higher rate than morphea of any other etiology, which is three per 100,000 per year. PIM usually appears less than 1 year after irradiation (range 1 month to 32 years). The histological pattern of PIM is different from the one in post-irradiation fibrosis, which is a common side effect of radiotherapy and usually appears during the first 3 months after irradiation. Several theories have been proposed to explain the pathogenesis of PIM, probably caused by a disturbance of the cytokine pattern. The development of PIM in patients with autoimmune diseases has been described in the literature. To our knowledge, we report the first case of PIM in a patient with subacute cutaneous lupus erythematosus. We should therefore pay attention when looking at patients with PIM to search for an underlying autoimmune disease