Mature and immature synaptosomal membranes have a different lipid composition

Subfractionation of the optic tectum in chick embryos results in the isolation of two fractions enriched in synaptosomes (fraction A and fraction B). In chicks after hatching, this fractionation results in the isolation of a single synaptosomal fraction (fraction B) and of a fraction enriched in myelin membranes devoid of synaptosomes (fraction A). The lipid composition of synaptosomal fractions (A and B) and corresponding synaptosomal plasma membranes has been analyzed and compared to the lipid composition of similar fractions isolated from 2–3 day-old chicks. The phospholipid composition of fraction A in embryos was mainly represented by phosphatidylcholine (PC) and phosphatidylethanolamine (PE). The PE content was significantly lower than that of PC, which accounted for by approximately 50%. Sphingomyelin (SP) and phosphatidylinositol (PI) accounted for by only 6% of the total membrane phopsholipids. Fraction A isolated from the young chicks showed many significant changes. PC accounted for by approximately 40% and PE made up 35%. The amount of phosphatidylserine (PS) and SP increased. These data parallel our previous morphological observations, which showed that fraction A contains immature synaptosomes in embryos but myelin membranes and no synaptosomes in the young chicks. Fraction B has been shown to contain synaptosomes at all stages considered. It possessed in embryos a lipid composition similar to fraction A, except that PC content was higher in young embryos. The analyses on membrane fractions confirmed these results. On the contrary, this fraction showed many significant changes after hatching. The content of PC was significantly reduced, PE/PC ratio was significantly increased as well as ethanolamine plasmalogen (PLE) content. The percentage of PS, PI and SP were increased. The composition of fatty acids of the total fraction of phospholipids was also examined. The results parallel the observations on phospholipid classes.     

Galectin-1 in cartilage: Expression, influence on chondrocyte growth and interaction with ECM components

Galectin-1 is a 14 kDa beta-galactoside binding protein, capable of forming lattice-like structures with glycans of cellular glycoconjugates and inducing intracellular signaling. The expression of Galectin-1 in porcine cartilage is described in this work for the first time. Immunocytochemical methods revealed distinct distribution patterns for both articular and growth plate cartilage. In articular cartilage, the highest reactivity for Galectin-1 was found in all chondrocytes at the superficial zone and in most of those at the lower layer of the middle zone. In the growth plate, marked reactivity was seen in chondrocytes at the proliferative zone and reached a maximum level for the column-forming cells at the hypertrophic zone. In addition, different Galectin-1 distribution patterns were observed at the subcellular level. With regards to the metabolic effects of Galectin-1, the results in vitro seem to indicate an inhibitory effect of Galectin-1 on articular chondrocyte anabolism (i.e. inhibition of cell proliferation and anabolic gene expression) and a stimulation of catabolic processes (i.e. induction of matrix degradation and hypertrophy marker expression). These data represent a starting point for the understanding the molecular mechanisms underlining ECM-Galectin-1 interaction and the subsequent signaling-cell transduction processes involving cartilage formation and maturation.     

Three-dimensional reconstruction of tarantula myosin filaments suggests how phosphorylation may regulate myosin activity

Muscle contraction involves the interaction of the myosin heads of the thick filaments with actin subunits of the thin filaments. Relaxation occurs when this interaction is blocked by molecular switches on these filaments. In many muscles, myosin-linked regulation involves phosphorylation of the myosin regulatory light chains (RLCs). Electron microscopy of vertebrate smooth muscle myosin molecules (regulated by phosphorylation) has provided insight into the relaxed structure, revealing that myosin is switched off by intramolecular interactions between its two heads, the free head and the blocked head. Three-dimensional reconstruction of frozen-hydrated specimens revealed that this asymmetric head interaction is also present in native thick filaments of tarantula striated muscle. Our goal in this study was to elucidate the structural features of the tarantula filament involved in phosphorylation-based regulation. A new reconstruction revealed intra- and intermolecular myosin interactions in addition to those seen previously. To help interpret the interactions, we sequenced the tarantula RLC and fitted an atomic model of the myosin head that included the predicted RLC atomic structure and an S2 (subfragment 2) crystal structure to the reconstruction. The fitting suggests one intramolecular interaction, between the cardiomyopathy loop of the free head and its own S2, and two intermolecular interactions, between the cardiac loop of the free head and the essential light chain of the blocked head and between the Leu305-Gln327 interaction loop of the free head and the N-terminal fragment of the RLC of the blocked head. These interactions, added to those previously described, would help switch off the thick filament. Molecular dynamics simulations suggest how phosphorylation could increase the helical content of the RLC N-terminus, weakening these interactions, thus releasing both heads and activating the thick filament.     

Assessing amendment properties of digestate by studying the organic matter composition and the degree of biological stability during the anaerobic digestion of the organic fraction of MSW

The transformation of organic matter during anaerobic digestion of mixtures of energetic crops, cow slurry, agro-industrial waste and organic fraction of municipal solid waste (OFMSW) was studied by analysing different samples at diverse points during the anaerobic digestion process in a full-scale plant. Both chemical (fiber analysis) and spectroscopic approaches (¹³C CPMAS NMR) indicated the anaerobic digestion process proceeded by degradation of more labile fraction (e.g. carbohydrate-like molecules) and concentration of more recalcitrant molecules (lignin and non-hydrolysable lipids). These modifications determined a higher degree of biological stability of digestate with respect to the starting mixture, as suggested, also, by the good correlations found between the cumulative oxygen uptake (OD₂₀), and the sum of (cellulose + hemicellulose + cell soluble) contents of biomasses detected by fiber analysis (r = 0.99; P < 0.05), and both O–alkyl-C (r = 0.98; P < 0.05) and alkyl-C (r = −0.99; P < 0.05) measured by ¹³C CPMAS NMR.     

Are spontaneous fractures possible? An example of clinical application for personalised,multiscale neuro-musculo-skeletal modelling

Elderly frequently present variable degrees of osteopenia, sarcopenia, and neuromotor control degradation. Severely osteoporotic patients sometime fracture their femoral neck when falling. Is it possible that such fractures might occur without any fall, but rather spontaneously while the patient is performing normal movements such as level walking? The aim of this study was to verify if such spontaneous fractures are biomechanically possible, and in such case, which conditions of osteoporosis, sarcopenia, and neuromotor degradation could produce them. To the purpose, a probabilistic multiscale body-organ model validated against controlled experiments was used to predict the risk of spontaneous fractures in a population of 80-years old women, with normal weight and musculoskeletal anatomy, and variable degree of osteopenia, sarcopenia, and neuromotor control degradation. A multi-body inverse dynamics sub-model, coupled to a probabilistic neuromuscular sub-model, and to a femur finite element sub-model, formed the multiscale model, which was run within a Monte Carlo stochastic scheme, where the various parameters were varied randomly according to well defined distributions. The model predicted that neither extreme osteoporosis, nor extreme neuromotor degradation alone are sufficient to predict spontaneous fractures. However, when the two factors are combined an incidence of 0.4% of spontaneous fractures is predicted for the simulated population, which is consistent with clinical reports. When the model represented only severely osteoporotic patients, the incidence of spontaneous fractures increased to 29%. Thus, is biomechanically possible that spontaneous femoral neck fractures occur during level walking, due to a combination of severe osteoporosis and severe neuromotor degradation.     

Hospital Admission of Cancer Patients: Avoidable Practice or Necessary Care?

Background

Cancer patients are frequently admitted to hospital due to acute conditions or refractory symptoms. This occurs through the emergency departments and requires medical oncologists to take an active role. The use of acute-care hospital increases in the last months of life.

Patients and methods

We aimed to describe the admissions to a medical oncology inpatient service within a 16-month period with respect to patients and tumor characteristics, and the outcome of the hospital stay.

Results

672 admissions of 454 patients were analysed. The majority of admissions were urgent (74.1%), and were due to uncontrolled symptoms (79.6%). Among the chief complaints, dyspnoea occurred in 15.7%, pain in 15.2%, and neurological symptoms in 14.5%. The majority of the hospitalizations resulted in discharge to home (60.6%); in 26.5% the patient died and in 11.0% was transferred to a hospice. Admissions due to symptoms correlated with a longer hospital stay and a higher incidence of in-hospital death.

Conclusion

We suggest that hospital use is not necessarily a sign of inappropriately aggressive care: inpatient care is probably an unavoidable step in the cancer trajectory. Optimization of inpatient supportive procedures should be a specific task of modern medical oncology.