Apoptotic gene expression in neuropathic pain

Pain initiated or caused by a primary lesion or dysfunction in the nervous system is defined as neuropathic pain. It results from direct injury to nerves in the peripheral or central nervous system and is associated with several clinical symptoms. Neuropathic pain treatment is extremely difficult, as it is a very complex disease, involving several molecular pathways. Excitatory or inhibitory pathways controlling neuropathic pain development show altered gene expression, caused by peripheral nerve injury.
This study used several experimental pain models to demonstrate the occurrence of programmed cell death in the centers controlling pain induction and maintenance, such as spinal cord and pre-frontal cortex. We combined behavioural, molecular and morphological approaches to assess the involvement of bcl-2 gene family and caspases in neuropathic pain. Chronic constriction injury (CCI) and spared nerve injury (SNI) of rodent sciatic nerve induced the appearance of pain-like behaviours, such as hyperalgesia and allodynia. An early (2-3 days post-CCI) apoptosis appeared in the spinal cord neurons as the pro-apoptotic bax gene increased (320±19%). The incidence of apoptosis appeared to be limited to the first few days following nerve injury. Subsequently, increased expression of anti-apoptotic bcl-2 family genes may inhibit further neuron loss. SNI triggered apoptotic pathway and caspases activation in pre-frontal cortex 7, 14, and 21 days post-injury. Among the time-points analyzed, RT-PCR analysis showed increased expression of the bax/bcl-2 ratio (40±2%), bid (16±2%), caspase-1 (84±3%), caspase-8 (53±6%), caspase-9 (25±6%), caspase-12 (58±2%), TNF (32±2%) genes in the cortex by 7 days post-injury. Western blot analysis showed increased active Caspase-3 protein levels in the cortex at 3, 7, 14, and 21 post-surgery. This study shows that apoptotic genes could be an useful pharmacological target in neuropathic pain controlling.
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Productivity and organization in Portuguese firms

The productivity of firms is, at least partly, determined by a firm's actions and decisions. One of these decisions involves the organization of production in terms of the number of layers of management the firm decides to employ. Using detailed employer-employee matched data and firm production quantity and input data for Portuguese firms, we study the endogenous response of revenue-based and quantity based productivity to a change in layers: a firm reorganization. We show that as a result of an exogenous demand or productivity shock that makes the firm reorganize and add a management layer, quantity based productivity increases by about 4%, while revenue-based productivity drops by more than 4%. Such a reorganization makes the firm more productive, but also increases the quantity produced to an extent that lowers the price charged by the firm and, as a result, its revenue-based productivity

Colorimetric and electrophoretic evaluation of lipoprotein fractions in healthy neonatal calves: Comparison with results from adult cows and from calves with inflammatory conditions

High density lipoproteins (HDLs) are pivotal in innate immunity and decrease in serum during inflammation. Several studies have been done about lipoprotein changes in transition cows but little is known about their changes in newborn calves. The aim of this study is to provide information about HDLs in newborn calves, by defining the possible age-related changes in healthy calves compared with adults and by assessing the possible differences in calves with inflammation. Lipoprotein electrophoretic separation (reported as percentages) and colorimetric measurement of HDL (HDL-C) were performed on healthy cows and calves in order to identify possible differences in the lipoprotein profile due to the age. Then, age-matched calves with inflammatory conditions were also evaluated. Results showed that in calves HDL% and VLDL% were lower (mean values ± SD: 77.6% ± 8.6% and 2.6% ± 2.5%, respectively) and LDL% was higher (19.7% ± 7.4%) than in adults (89.0% ± 3.9%; 5.2 ± 2.1% and 5.8% ± 3.1%, respectively). Sick calves revealed a decrease of both HDL% (mean values ± SD: 61.0% ± 22.1%) and HDL-C (22.8 ± 11.6 mg/dL) and an increase of VLDL% (12.1% ± 13.1%) compared with controls (77.6% ± 8.6%; 41.5 ± 11.2 mg/dL and 2.6% ± 2.5%, respectively). Paraoxonase-1 activity, influenced by inflammation and oxidation, was measured, and it appeared correlated with HDL% and HDL-C in sick calves. In conclusion, this study revealed that HDLs concentration in healthy calves is lower than in adults, and further decreases in calves with inflammation, likely due to oxidation

Tracking deformable objects with WISARD networks

In this paper, we investigate a new approach based on WISARD Neural Network for the tracking of non-rigid deformable object. The proposed approach allows deploying an on–line training on the texture and shape features of the object, to adapt in real–time to changes, and to partially cope with occlusions. Moreover, the use of parallel classificatory trained on the same set of images allows tracking the movements of the objects. We evaluate our tracking abilities in the scenario of pizza making that represents a very challenging benchmark to test the approach since in this context the shape of the object to track completely changes during the manipulation

Role of Neurotrophins in Neuropathic Pain

Neurotrophins (NTs) belong to a family of structurally and functionally related proteins, they are the subsets of neurotrophic factors. Neurotrophins are responsible for diverse actions in the developing peripheral and central nervous systems. They are important regulators of neuronal function, affecting neuronal survival and growth. They are able to regulate cell death and survival in development as well as in pathophysiologic states. NTs and their receptors are expressed in areas of the brain that undergo plasticity, indicating that they are able to modulate synaptic plasticity

On the properties of human mobility

The current age of increased people mobility calls for a better understanding of how people move: how many places does an individual commonly visit, what are the semantics of these places, and how do people get from one place to another. We show that the number of places visited by each person (Points of Interest - PoIs) is regulated by some properties that are statistically similar among individuals. Subsequently, we present a PoIs classification in terms of their relevance on a per-user basis. In addition to the PoIs relevance, we also investigate the variables that describe the travel rules among PoIs in particular, the spatial and temporal distance. As regards the latter, existing works on mobility are mainly based on spatial distance. Here we argue, rather, that for human mobility the temporal distance and the PoIs relevance are the major driving factors. Moreover, we study the semantic of PoIs. This is useful for deriving statistics on people's habits without breaking their privacy. With the support of different datasets, our paper provides an in-depth analysis of PoIs distribution and semantics; it also shows that our results hold independently of the nature of the dataset in use. We illustrate that our approach is able to effectively extract a rich set of features describing human mobility and we argue that this can be seminal to novel mobility research

Sviluppo di una micro CT con sorgente Quasi-Monocromatica Multi-Energy per lo studio in vivo della crescita e della metastasi tumorale

Un innovativo micro scanner CT per piccolo animali – basato su di una sorgente che genera una coppia di fasci X Quasi-Monocromatici paralleli con diverse energie selezionabili – è in corso di installazione e caratterizzazione al Dipartimento di Fisica dell’Università di Bologna. Lo scopo della ricerca è quello di effettuare l’imaging radiologico in vivo del tessuto tumorale e/o dei pattern di neo-angiogenesi in una fase diagnostica precoce realizzando la separazione del tessuto patologico da quello sano per mezzo della tecnica multi-energy che consiste nell’utilizzo di due o più fasci di raggi X quasi-monocromatici in sostituzione dell’unico fascio policromatico utilizzato nella radiologia convenzionale. Lo strumento consentirà inoltre lo studio, sui topi, della crescita tumorale e della formazione delle metastasi per differenti tipologie di tumore. Per la diagnosi precoce del tumore è essenziale essere in grado di rivelare i cambiamenti tissutali precancerosi, come la neo-angiogenesi. Si tratta di un meccanismo che si verifica in una fase iniziale dello sviluppo della patologia ed è dovuto alla produzione di molecole che stimolano la creazione di nuovi vasi sanguigni per alimentare la crescita delle cellule cancerose. Come dimostrato in precedenti studi di fattibilità [1], un sistema di imaging basato su due fasci di raggi X quasi-monocromatici di differenti energie fornisce maggiore sensibilità nella rivelazione di basse concentrazioni di mezzo di contrasto iodato rispetto ai tradizionali apparati RX con fascio policromatico. La K-edge dual energy radiology è una tecnologia potenzialmente in grado di rivelare il processo di neo-angiogenesi tumorale in uno stadio precoce quando la strumentazione convenzionale non dispone di sufficiente sensibilità. Inoltre, la possibilità di selezionare le energie dei fasci quasi-monocromatici consente l’applicazione della Multi-Energy Quasi-MonochromaticRadiology: selezionando opportunamente le energie è possibile esaltare le differenze fra i coefficienti di attenuazione lineare del tessuto patologico rispetto a quello sano aumentando il contrasto della patologia. Infatti, la tecnica multi-energy consente di ricostruire il numero atomico efficace e persino la composizione chimica del tessuto irradiato. Tuttavia, per ottenere questo risultato, si dovrebbero conoscere le bande di energia in cui l’assorbimento dei raggi X da parte del tessuto tumorale eventualmente differisce significativamente da quello dei tessuti sani. Per questo motivo è stata iniziata una sistematica caratterizzazione radiologica di molti tipi di tessuti sani e neoplastici, murini e umani allo scopo di costituire un catalogo delle finestre di energia in cui sarà possibile applicare la metodica multi-energy

Long-Lasting Effects of Human Mesenchymal Stem Cell Systemic Administration on Pain-Like Behaviors, Cellular, and Biomolecular Modifications in Neuropathic Mice

Background: Neuropathic pain (NP) is an incurable disease caused by a primary lesion in the nervous system. NP is a progressive nervous system disease that results from poorly defined neurophysiological and neurochemical changes. Its treatment is very difficult. Current available therapeutic drugs have a generalized nature, sometime acting only on the temporal pain properties rather than targeting the several mechanisms underlying the generation and propagation of pain. Methods: Using biomolecular and immunohistochemical methods, we investigated the effect of the systemic injection of human mesenchymal stem cells (hMSCs) on NP relief. We used the spared nerve injury (SNI) model of NP in the mouse. hMSCs were injected into the tail vein of the mouse. Stem cell injection was performed 4 days after sciatic nerve surgery. Neuropathic mice were monitored every 10 days starting from day 11 until 90 days after surgery. Results: hMSCs were able to reduce pain-like behaviors, such as mechanical allodynia and thermal hyperalgesia, once injected into the tail vein. An anti-nociceptive effect was detectable from day 11 post surgery (7 days post cell injection). hMSCs were mainly able to home in the spinal cord and pre-frontal cortex of neuropathic mice. Injected hMSCs reduced the protein levels of the mouse pro-inflammatory interleukin IL-1β and IL-17 and increased protein levels of the mouse anti-inflammatory interleukin IL-10, and the marker of alternatively activated macrophages CD106 in the spinal cord of SNI mice. Conclusion: As a potential mechanism of action of hMSCs in reducing pain, we suggest that they could exert their beneficial action through a restorative mechanism involving: (i) a cell-to-cell contact activation mechanism, through which spinal cord homed hMSCs are responsible for switching pro-inflammatory macrophages to anti-inflammatory macrophages; (ii) secretion of a broad spectrum of molecules to communicate with other cell types. This study could provide novel findings in MSC pre-clinical biology and their therapeutic potential in regenerative medicine

From the earth to the universe : a teaching proposal about basic concepts in Earth Sciences and Astronomy for Compulsory School

We will present an innovative way of teaching about Earth and the Universe in compulsory school, based on a phenomenological approach and on the development of transversal and intertwisted pathways between Physics, Astronomy and Earth Sciences. The main aim is to familiarize the students with the idea of a systemic and a dynamic planet interacting with the other celestial bodies. Depending on age, the history of interacting systems is described and interpreted in terms of stories, models, variables and correlations among variables. Students are stimulated to participate through active cooperative work to field observations, data analysis, construction of interpretative models and theories at different levels of formalization. Results of first testing of this teaching proposal in some selected classes (students 6-11 and 11-14 years old) will be discussed