Early CSF Biomarkers and Late Functional Outcomes in Spinal Cord Injury. A Pilot Study

Although, biomarkers are regarded as an important tool for monitoring injury severity and treatment efficacy, and for predicting clinical evolution in many neurological diseases and disorders including spinal cord injury, there is still a lack of reliable biomarkers for the assessment of clinical course and patient outcome. In this study, a biological dataset of 60 cytokines/chemokines, growth factorsm and intracellular and extracellular matrix proteins, analyzed in CSF within 24 h of injury, was used for correlation analysis with the clinical dataset of the same patients. A heat map was generated of positive and negative correlations between biomarkers and clinical rating scale scores at discharge, and between biomarkers and changes in clinical scores during the observation period. Using very stringent statistical criteria, we found 10 molecules which correlated with clinical scores at discharge, and five molecules, which correlated with changes in clinical scores. The proposed methodology may be useful for generating hypotheses regarding “predictive” and “treatment effectiveness” biomarkers, thereby suggesting potential candidates for disease-modifying therapies using a “bed-to-bench” approach.     

Anti-Inflammatory Treatment with FTY720 Starting after Onset of Symptoms Reverses Synaptic Deficits in an AD Mouse Model

Therapeutic approaches providing effective medication for Alzheimer’s disease (AD) patients after disease onset are urgently needed. Previous studies in AD mouse models suggested that physical exercise or changed lifestyle can delay AD-related synaptic and memory dysfunctions when treatment started in juvenile animals long before onset of disease symptoms, while a pharmacological treatment that can reverse synaptic and memory deficits in AD mice was thus far not identified. Repurposing food and drug administration (FDA)-approved drugs for treatment of AD is a promising way to reduce the time to bring such medication into clinical practice. The sphingosine-1 phosphate analog fingolimod (FTY720) was approved recently for treatment of multiple sclerosis patients. Here, we addressed whether fingolimod rescues AD-related synaptic deficits and memory dysfunction in an amyloid precursor protein/presenilin-1 (APP/PS1) AD mouse model when medication starts after onset of symptoms (at five months). Male mice received intraperitoneal injections of fingolimod for one to two months starting at five to six months. This treatment rescued spine density as well as long-term potentiation in hippocampal cornu ammonis-1 (CA1) pyramidal neurons, that were both impaired in untreated APP/PS1 animals at six to seven months of age. Immunohistochemical analysis with markers of microgliosis (ionized calcium-binding adapter molecule 1; Iba1) and astrogliosis (glial fibrillary acid protein; GFAP) revealed that our fingolimod treatment regime strongly down regulated neuroinflammation in the hippocampus and neocortex of this AD model. These effects were accompanied by a moderate reduction of Aβ accumulation in hippocampus and neocortex. Our results suggest that fingolimod, when applied after onset of disease symptoms in an APP/PS1 mouse model, rescues synaptic pathology that is believed to underlie memory deficits in AD mice, and that this beneficial effect is mediated via anti-neuroinflammatory actions of the drug on microglia and astrocytes.     

Extracellular Vesicles in CNS Developmental Disorders

The central nervous system (CNS) is the most complex structure in the body, consisting of multiple cell types with distinct morphology and function. Development of the neuronal circuit and its function rely on a continuous crosstalk between neurons and non-neural cells. It has been widely accepted that extracellular vesicles (EVs), mainly exosomes, are effective entities responsible for intercellular CNS communication. They contain membrane and cytoplasmic proteins, lipids, non-coding RNAs, microRNAs and mRNAs. Their cargo modulates gene and protein expression in recipient cells. Several lines of evidence indicate that EVs play a role in modifying signal transduction with subsequent physiological changes in neurogenesis, gliogenesis, synaptogenesis and network circuit formation and activity, as well as synaptic pruning and myelination. Several studies demonstrate that neural and non-neural EVs play an important role in physiological and pathological neurodevelopment. The present review discusses the role of EVs in various neurodevelopmental disorders and the prospects of using EVs as disease biomarkers and therapeutics.     

Substrate Flexibility of the Flavin-Dependent Dihydropyrrole Oxidases PigB and HapB Involved in Antibiotic Prodigiosin Biosynthesis

In the biosynthesis of the tripyrrolic pigment prodigiosin, PigB is a predicted flavin-dependent oxidase responsible for the formation of 2-methyl-3-amylpyrrole (MAP) from a dihydropyrrole. To prove which dihydropyrrole is the true intermediate, both possibilities, 5-methyl-4-pentyl-3,4-dihydro-2H-pyrrole ( 5 a , resulting from transamination of the aldehyde of 3-acetyloctanal) and 2-methyl-3-pentyl-3,4-dihydro-2H-pyrrole ( 6 , resulting from transamination of the ketone), were synthesised. Only 5 a restored pigment production in a strain of Serratia sp. ATCC 39006 blocked earlier in MAP biosynthesis. PigB is membrane-associated and inactive when its transmembrane domain was deleted, but HapB, its homologue in Hahella chejuensis, lacks the transmembrane domain and is active in solution. Two colourimetric assays for PigB and HapB were developed, and the HapB-catalysed reaction was kinetically characterised. Ten analogues of 5 a were synthesised, varying in the C2 and C3 side chains, and tested as substrates of HapB in vitro and for restoration of pigment production in Serratia ΔpigD in vivo. All lengths of side chain tested at C3 were accepted, but only short side chains at C2 were accepted. The knowledge that 5 a is an intermediate in prodigiosin biosynthesis and the ease of synthesis of analogues of 5 a makes a range of prodigiosin analogues readily available by mutasynthesis.     

An efficient routing protocol for cognitive radio networks of energy-limited devices

Telecommunication Systems - In the era of Internet-of-things (IoT), the future 5G networks are supposed to provide ubiquitous connectivity, high speed, as well as low latency and energy efficiency...     

The influence of brewing method on bioactive compounds residues in spent coffee grounds of different roasting degree and geographical origin

The content of bioactive compounds in spent coffee grounds (SGC) was studied. SGC were obtained from Coffea arabica beans of different roasting degrees (light and dark) and different geographical origins (Nicaragua, Columbia and Mexico) processed using four brewing methods (mocha, filtered, drip and infusion). The highest caffeine and chlorogenic acid contents were determined in filtered spent coffee extracts. All extracts of light roasted spent coffee grounds showed lower browning index levels in comparison to that from dark roasted spent coffee grounds. Generally, the highest content of total polyphenolic compounds and highest antioxidant capacity were determined in extracts prepared in drip. In conclusion, the results obtained in this study indicate that the spent coffee grounds produced of domestic levels, especially those obtained from filter coffeemaker, could be considered as a good source of natural antioxidants.     

Selected Physicochemical Properties of Starch Isolated from Fermented Sorghum Flour

Starch was isolated from fermented sorghum flour (24 h natural lactic acid fermentation), and water retention, starch solubility, clarity of starch pastes and freeze‐thaw stability were measured. In comparison with starch isolated from unfermented sorghum flour, fermentation increased the solubility of the starch and decreased the water retention, but it had no effect on the freeze‐thaw stability of the starch. There was no substantial difference in the starch paste clarity between the two samples. Storage of starch pastes at lower temperature (4°C) resulted in a very low clarity of starch.     

Effects of Tomato and Soy Germ on Lipid Bioaccumulation and Atherosclerosis in ApoE−/− Mice

Dietary patterns with cardiovascular benefits have been recommended, but the relative contributions of individual foods and food components, alone or in combination, remain undefined. Male ApoE^?/? mice were fed either a purified AIN‐93G control diet, a Western diet (WD), or a WD with 10% tomato powder (TP), 2% soy germ (SG), or the combination, for 4 wk (n = 10 per group). Plasma total cholesterol and triglycerides were measured with enzymatic colorimetric kits, and serum amyloid A (SAA) was measured by ELISA. Liver lipids were extracted with chloroform:methanol, and triglycerides, free and esterified cholesterol measured with enzymatic colorimetric kits. Expression of Cyp27a1, Cyp7a1, Abcg5, and Abcg8 in the liver was determined by quantitative polymerase chain reaction. Sections of the aortic root and aorta were cut and stained with hematoxylin and eosin (H&E) to assess extent of atherosclerotic lesions. WD‐fed animals had greater liver and adipose weights, plasma cholesterol and SAA, hepatic lipids, and atherosclerosis than AIN‐93G animals. TP and SG did not decrease atherosclerosis as measured by H&E‐stained sections of the aortic root, aortic arch, and descending aorta. The TP diets further increased plasma cholesterol, but also led to increased expression of the Abcg5/8 transporters involved in cholesterol efflux. Addition of SG alone to the WD attenuated WD‐induced increases in plasma cholesterol, liver lipids, and gonadal adipose weight. The results of this study do not support the use of either TP or SG for reduction of atherosclerosis, but suggest some beneficial effects of SG on lipid metabolism in this model of cardiovascular disease.