Molecular correlates of axonal and synaptic pathology in mouse models of Batten disease

Neuronal ceroid lipofuscinoses (NCLs; Batten disease) are collectively the most frequent autosomal-recessive neurodegenerative disease of childhood, but the underlying cellular and molecular mechanisms remain unclear. Several lines of evidence have highlighted the important role that non-somatic compartments of neurons (axons and synapses) play in the instigation and progression of NCL pathogenesis. Here, we report a progressive breakdown of axons and synapses in the brains of two different mouse models of NCL: Ppt1−/− model of infantile NCL and Cln6nclf model of variant late-infantile NCL. Synaptic pathology was evident in the thalamus and cortex of these mice, but occurred much earlier within the thalamus. Quantitative comparisons of expression levels for a subset of proteins previously implicated in regulation of axonal and synaptic vulnerability revealed changes in proteins involved with synaptic function/stability and cell-cycle regulation in both strains of NCL mice. Protein expression changes were present at pre/early-symptomatic stages, occurring in advance of morphologically detectable synaptic or axonal pathology and again displayed regional selectivity, occurring first within the thalamus and only later in the cortex. Although significant differences in individual protein expression profiles existed between the two NCL models studied, 2 of the 15 proteins examined (VDAC1 and Pttg1) displayed robust and significant changes at pre/early-symptomatic time-points in both models. Our study demonstrates that synapses and axons are important early pathological targets in the NCLs and has identified two proteins, VDAC1 and Pttg1, with the potential for use as in vivo biomarkers of pre/early-symptomatic axonal and synaptic vulnerability in the NCLs

Agricultura e biodiversidade nas ciências sociais brasileiras: alimentando a comunicação entre ciência e políticas públicas.

O presente artigo decorre de uma reflexão sustentada em dois pressupostos: a) que as ciências e, em particular, as sociais, podem contribuir para informar as tomadas de decisão e a formulação de políticas públicas visando a melhoria da vida das pessoas no planeta e b) que o papel da agricultura na conservação da biodiversidade é uma questão atual de extrema relevância e que merece ser aprofundada. A relação entre a agricultura e a biodiversidade tem sido objeto de questionamentos recentes na sociedade e no campo das políticas públicas. Contudo, se os estudos relacionados à biodiversidade e à agricultura, separadamente, têm observado um considerável crescimento no Brasil, poucos são os investimentos de pesquisa sobre a relação entre esses dois grandes temas. A partir dessas considerações, seguimos dois objetivos principais: 1) investigar como o papel da agricultura familiar na preservação da biodiversidade tem sido abordado pelas Ciências Sociais no Brasil, particularmente nos artigos publicados em periódicos brasileiros nos últimos 20 anos; 2) testar uma metodologia de revisão bibliográfica, criteriosa, que possa ser útil aos tomadores de decisão em políticas públicas e demais interessados

Breeding systems in Tolpis (Asteraceae) in the Macaronesian islands: the Azores, Madeira and the Canaries

Plants on oceanic islands often originate from self-compatible (SC) colonizers capable of seed set by self fertilization. This fact is supported by empirical studies, and is rooted in the hypothesis that one (or few) individuals could find a sexual population, whereas two or more would be required if the colonizers were self-incompatible (SI). However, a SC colonizer would have lower heterozygosity than SI colonizers, which could limit radiation and diver sification of lineages following establishment. Limited evidence suggests that several species-rich island lineages in the family Asteraceae originated from SI colonizers with some ‘‘leakiness’’ (pseudo-self-compatibility, PSC) such that some self-seed could be produced. This study of Tolpis (Asteraceae) in Macaronesia provides first reports of the breeding system in species from the Azores and Madeira, and additional insights into variation in Canary Islands. Tolpis from the Azores and Madeira are predominately SI but with PSC. This study suggests that the breeding sys tems of the ancestors were either PSC, possibly from a single colonizer, or from SI colonizers by multiple dis seminules either from a single or multiple dispersals. Long distance colonists capable of PSC combine the advantages of reproductive assurance (via selfing) in the establishment of sexual populations from even a single colonizer with the higher heterozygosity resulting from its origin from an outcrossed source population. Evolution of Tolpis on the Canaries and Madeira has generated diversity in breeding systems, including the origin of SC. Macaronesian Tolpis is an excellent system for studying breeding system evolution in a small, diverse lineage.info:eu-repo/semantics/publishedVersio

Right ventricular volume measurement by conductance catheter

Continuous ventricular volume measurement by the conductance method assumes a homogeneous electrical field dispersed throughout and contained within the ventricle. Because of dense trabeculation and complex geometry, right ventricular (RV) volume description by this method may be seriously compromised. This study sought to determine the accuracy and limitations of RV volume measurement by conductance, with magnetic resonance (MR) imaging (MRI) used as a reference, in the porcine RV. Anesthetized pigs (n = 5, 45-55 kg) were placed in a 1.5-T magnet, and ECG-gated transverse MR images (5-mm slices) were acquired during the complete cardiac cycle. RV cavity volumes were subsequently determined by Simpson's technique. Animals were then instrumented with an RV conductance catheter and an ultrasonic pulmonary artery flow probe. Conductance catheter signals were recorded using single- and dual-field (SF and DF) excitation, and the saline-dilution technique was used to correct volumes for parallel conductance. The gain factor (α) was calculated as the ratio of conductance- to MRI-derived stroke volume (α sv). Variation of α during the cardiac cycle was computed by comparing RV conductance volumes with 1) MRI volumes at isochronal time points within the cardiac cycle [α(t)] and 2) the pulmonary flow integral during ejection. After calibration, the conductance-MRI volume relation was modeled lin-early with good correlation [r = 0.96 (SF) and r = 0.94 (DF)], close to the line of identity. Individual conductance-MRI plots displayed a slight curvilinear relation that was concave toward the MRI axis. Consistent with this finding, α(t) varied significantly during the cardiac cycle (0.49 and 0.39 by SF for end systole and end diastole, respectively, P = 0.011). DF excitation resulted in improved volume measurement [α sv = 0.41 (SF) and 0.96 (DF)], with less variation in α(t) (1.0 and 0.92 by DF for end systole and end diastole, respectively, P = 0.66). These results indicate that, with calibration, the conductance method can measure absolute RV volume under steady-state conditions. However, the curvilinearity and α(t) variation would indicate the potential for nonlinearity when RV volumes are varied over a wider range.link_to_subscribed_fulltex

Acute B-type natriuretic peptide response and early postoperative right ventricular physiology following tetralogy of Fallot's repair

B-type natriuretic peptide (BNP) response early after a tetralogy of Fallot's repair remains unclear. BNP was measured pre- and post-operatively (immediately, day 1) in 18 children undergoing corrective repair with concurrent echocardiography (pre-, post-op day 1) to assess right ventricular (RV) systolic dysfunction, restrictive physiology, wall motion and pulmonary regurgitation (PR). In the first 24 h postoperatively, BNP rose acutely in all patients (mean 34.9 vs 144.4 vs 716.9 pg/ml at pre-op, days 0 and 1; P < 0.001). Immediate postoperative BNP correlated with preoperative haematocrit (rho = 0.52, P = 0.03) and inversely with preoperative oxygen saturation (rho = −0.63, P = 0.007). All patients showed reduced RV systolic function and abnormal wall motion with at least moderate PR in six patients (33.3%) and restrictive physiology in four (24%). Subsequent BNP expression (post-op day 1) correlated with a low RV fractional area change (rho = −0.51, P = 0.04), high oxygen extraction ratio (rho = 0.56, P = 0.02) and high central venous pressure (rho = 0.79, P < 0.001). The LV function and wall motion remained preserved in all patients. The mechanism of BNP expression is likely to be multi-factorial in the presence of a complex postoperative RV physiology in tetralogy of Fallot. An acute BNP response in the early postoperative period reflects an important physiological role and may be used as an adjunct biomarker to assess the RV function