Un enfoque fisiológico para los procesos oceánicos y los cambios glaciares-interglaciares del CO2 atmosférico

18 pages, 6 figures, 1 table[EN] One possible path for exploring the Earth’s far-from-equilibrium homeostasis is to assume that it results from the organisation of optimal pulsating systems, analogous to that in complex living beings. Under this premise it becomes natural to examine the Earth’s organisation using physiological-like variables. Here we identify some of these main variables for the ocean’s circulatory system: pump rate, stroke volume, carbon and nutrient arterial-venous differences, inorganic nutrients and carbon supply, and metabolic rate. The stroke volume is proportional to the water transported into the thermocline and deep oceans, and the arterial-venous differences occur between recently-upwelled deep waters and very productive high-latitudes waters, with atmospheric CO2 being an indicator of the arterial-venous inorganic carbon difference. The metabolic rate is the internal-energy flux (here expressed as flux of inorganic carbon in the upper ocean) required by the system’s machinery, i.e. community respiration. We propose that the pump rate is set externally by the annual cycle, at one beat per year per hemisphere, and that the autotrophic ocean adjusts its stroke volume and arterial-venous differences to modify the internal-energy demand, triggered by long-period astronomical insolation cycles (external-energy supply). With this perspective we may conceive that the Earth’s interglacial-glacial cycle responds to an internal organisation analogous to that occurring in living beings during an exercise-recovery cycle. We use an idealised double-state metabolic model of the upper ocean (with the inorganic carbon/nutrients supply specified through the overturning rate and the steady-state inorganic carbon/nutrients concentrations) to obtain the temporal evolution of its inorganic carbon concentration, which mimics the glacial-interglacial atmospheric CO2 pattern[ES] Un posible camino para el estudio de la homeóstasis fuera-de-equilibrio de la tierra es suponer que resulta de la organización de sistemas pulsátiles optimizados, análoga a aquélla en seres vivos complejos. Bajo esta premisa parece natural examinar la organización de la tierra utilizando variables de tipo fisiológico. Aquí identificamos algunas de las principales variables del sistema circulatorio oceánico: tasa de bombeo del corazón, volumen de latido, diferencias arteriovenosas de carbono y nutrientes, suministro de carbono y nutrientes inorgánicos, y tasa metabólica. El volumen de latido es proporcional al transporte de agua hacia la termoclina y océano profundo, y las diferencias arterio-venosas ocurren entre las aguas profundas recientemente afloradas y aquellas altamente productivas de altas latitudes, con el CO2 atmosférico siendo un indicador de la diferencia arterio-venosa de carbono inorgánico. La tasa metabólica es el flujo de energía interna (aquí expresado como flujo de carbono inorgánico en el océano superior) requerido por la maquinaria que sostiene el sistema, i.e. respiración total de la comunidad. Se propone que la tasa de latido está impuesta externamente, un latido por año por hemisferio, y que el océano autotrófico ajusta su volumen de latido y las diferencias arteriovenosas a cambios en la demanda de energía interna, inducido por ciclos de insolación astronómica de largo período (suministro de energía externa). Bajo esta perspectiva podemos concebir que el ciclo interglacial-glacial de la tierra responde a una organización interna análoga a la que ocurre en seres vivos durante un ciclo de ejercicio-recuperación. Se utiliza un modelo metabólico idealizado de dos estados para el océano superior (con el suministro de carbono/nutrientes inorgánicos especificado mediante la tasa de recirculación de aguas profundas y las concentraciones de carbono/nutrientes inorgánicos en estado estacionario) para obtener la evolución temporal de su concentración de carbono inorgánico, la cual mimetiza el patrón glacial-interglacial del CO2 atmosféricoThis work was supported by the Spanish government through the CANOA project (CTM2005-00444/MAR)Peer reviewe

Cytotoxic CD8+ T cell-neuron interactions: perforin-dependent electrical silencing precedes but is not causally linked to neuronal cell death

Cytotoxic CD8(+) T cells are considered important effector cells contributing to neuronal damage in inflammatory and degenerative CNS disorders. Using time-lapse video microscopy and two-photon imaging in combination with whole-cell patch-clamp recordings, we here show that major histocompatibility class I (MHC I)-restricted neuronal antigen presentation and T cell receptor specificity determine CD8(+) T-cell locomotion and neuronal damage in culture and hippocampal brain slices. Two separate functional consequences result from a direct cell-cell contact between antigen-presenting neurons and antigen-specific CD8(+) T cells. (1) An immediate impairment of electrical signaling in single neurons and neuronal networks occurs as a result of massive shunting of the membrane capacitance after insertion of channel-forming perforin (and probably activation of other transmembrane conductances), which is paralleled by an increase of intracellular Ca(2+) levels (within <10 min). (2) Antigen-dependent neuronal apoptosis may occur independently of perforin and members of the granzyme B cluster (within approximately 1 h), suggesting that extracellular effects can substitute for intracellular delivery of granzymes by perforin. Thus, electrical silencing is an immediate consequence of MHC I-restricted interaction of CD8(+) T cells with neurons. This mechanism is clearly perforin-dependent and precedes, but is not causally linked, to neuronal cell death

Hippocampal CA3 Transcriptome Signature Correlates with Initial Precipitating Injury in Refractory Mesial Temporal Lobe Epilepsy

Background: Prolonged febrile seizures constitute an initial precipitating injury (IPI) commonly associated with refractory mesial temporal lobe epilepsy (RMTLE). in order to investigate IPI influence on the transcriptional phenotype underlying RMTLE we comparatively analyzed the transcriptomic signatures of CA3 explants surgically obtained from RMTLE patients with (FS) or without (NFS) febrile seizure history. Texture analyses on MRI images of dentate gyrus were conducted in a subset of surgically removed sclerotic hippocampi for identifying IPI-associated histo-radiological alterations.Methodology/Principal Findings: DNA microarray analysis revealed that CA3 global gene expression differed significantly between FS and NFS subgroups. An integrative functional genomics methodology was used for characterizing the relations between GO biological processes themes and constructing transcriptional interaction networks defining the FS and NFS transcriptomic signatures and its major gene-gene links (hubs). Co-expression network analysis showed that: i) CA3 transcriptomic profiles differ according to the IPI; ii) FS distinctive hubs are mostly linked to glutamatergic signalization while NFS hubs predominantly involve GABAergic pathways and neurotransmission modulation. Both networks have relevant hubs related to nervous system development, what is consistent with cell genesis activity in the hippocampus of RMTLE patients. Moreover, two candidate genes for therapeutic targeting came out from this analysis: SSTR1, a relevant common hub in febrile and afebrile transcriptomes, and CHRM3, due to its putative role in epilepsy susceptibility development. MRI texture analysis allowed an overall accuracy of 90% for pixels correctly classified as belonging to FS or NFS groups. Histological examination revealed that granule cell loss was significantly higher in FS hippocampi.Conclusions/Significance: CA3 transcriptional signatures and dentate gyrus morphology fairly correlate with IPI in RMTLE, indicating that FS-RMTLE represents a distinct phenotype. These findings may shed light on the molecular mechanisms underlying refractory epilepsy phenotypes and contribute to the discovery of novel specific drug targets for therapeutic interventions

Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

Ultrafast action potentials mediate Kilohertz signaling at a central synapse

SummaryFast synaptic transmission is important for rapid information processing. To explore the maximal rate of neuronal signaling and to analyze the presynaptic mechanisms, we focused on the input layer of the cerebellar cortex, where exceptionally high action potential (AP) frequencies have been reported in vivo. With paired recordings between presynaptic cerebellar mossy fiber boutons and postsynaptic granule cells, we demonstrate reliable neurotransmission up to ∼1 kHz. Presynaptic APs are ultrafast, with ∼100 μs half-duration. Both Kv1 and Kv3 potassium channels mediate the fast repolarization, rapidly inactivating sodium channels ensure metabolic efficiency, and little AP broadening occurs during bursts of up to 1.5 kHz. Presynaptic Cav2.1 (P/Q-type) calcium channels open efficiently during ultrafast APs. Furthermore, a subset of synaptic vesicles is tightly coupled to Ca2+ channels, and vesicles are rapidly recruited to the release site. These data reveal mechanisms of presynaptic AP generation and transmitter release underlying neuronal kHz signaling