Who is going to walk? A review of the factors influencing walking recovery after spinal cord injury

The recovery of walking function is considered of extreme relevance both by patients and physicians. Consequently, in the recent years, recovery of locomotion become a major objective of new pharmacological and rehabilitative interventions. In the last decade, several pharmacological treatment and rehabilitative approaches have been initiated to enhance locomotion capacity of SCI patients. Basic science advances in regeneration of the central nervous system hold promise of further neurological and functional recovery to be studied in clinical trials. Therefore, a precise knowledge of the natural course of walking recovery after SCI and of the factors affecting the prognosis for recovery has become mandatory. In the present work we reviewed the prognostic factors for walking recovery, with particular attention paid to the clinical ones (neurological examination at admission, age, etiology gender, time course of recovery). The prognostic value of some instrumental examinations has also been reviewed. Based on these factors we suggest that a reliable prognosis for walking recovery is possible. Instrumental examinations, in particular evoked potentials could be useful to improve the prognosis

Stem cell plasticity and dormancy in the development of cancer therapy resistance

Cancer treatment with either standard chemotherapy or targeted agents often results in the emergence of drug-refractory cell populations, ultimately leading to therapy failure. The biological features of drug resistant cells are largely overlapping with those of cancer stem cells and include heterogeneity, plasticity, self-renewal ability, and tumor-initiating capacity. Moreover, drug resistance is usually characterized by a suppression of proliferation that can manifest as quiescence, dormancy, senescence, or proliferative slowdown. Alterations in key cellular pathways such as autophagy, unfolded protein response or redox signaling, as well as metabolic adaptations also contribute to the establishment of drug resistance, thus representing attractive therapeutic targets. Moreover, a complex interplay of drug resistant cells with the micro/macroenvironment and with the immune system plays a key role in dictating and maintaining the resistant phenotype. Recent studies have challenged traditional views of cancer drug resistance providing innovative perspectives, establishing new connections between drug resistant cells and their environment and indicating unexpected therapeutic strategies. In this review we discuss recent advancements in understanding the mechanisms underlying drug resistance and we report novel targeting agents able to overcome the drug resistant status, with particular focus on strategies directed against dormant cells. Research on drug resistant cancer cells will take us one step forward toward the development of novel treatment approaches and the improvement of relapse-free survival in solid and hematological cancer patients

Insertion polymorphisms of SINE200 retrotransposons within speciation islands of Anopheles gambiae molecular forms

<p>Abstract</p> <p>Background</p> <p>SINEs (Short INterspersed Elements) are homoplasy-free and co-dominant genetic markers which are considered to represent useful tools for population genetic studies, and could help clarifying the speciation processes ongoing within the major malaria vector in Africa, <it>Anopheles gambiae </it>s.s. Here, we report the results of the analysis of the insertion polymorphism of a nearly 200 bp-long SINE (<it>SINE200</it>) within genome areas of high differentiation (i.e. "speciation islands") of M and S <it>A. gambiae </it>molecular forms.</p> <p>Methods</p> <p>A <it>SINE</it>-PCR approach was carried out on thirteen <it>SINE200 </it>insertions in M and S females collected along the whole range of distribution of <it>A. gambiae </it>s.s. in sub-Saharan Africa. Ten specimens each for <it>Anopheles arabiensis</it>, <it>Anopheles melas, Anopheles quadriannulatus </it>A and 15 M/S hybrids from laboratory crosses were also analysed.</p> <p>Results</p> <p>Eight loci were successfully amplified and were found to be specific for <it>A. gambiae </it>s.s.: 5 on 2L chromosome and one on X chromosome resulted monomorphic, while two loci positioned respectively on 2R (i.e. <it>S200 </it>2R12D) and X (i.e. <it>S200 </it>X6.1) chromosomes were found to be polymorphic. <it>S200 </it>2R12D was homozygote for the insertion in most S-form samples, while intermediate levels of polymorphism were shown in M-form, resulting in an overall high degree of genetic differentiation between molecular forms (Fst = 0.46 p < 0.001) and within M-form (Fst = 0.46 p < 0.001). The insertion of <it>S200 </it>X6.1 was found to be fixed in all M- and absent in all S-specimens. This led to develop a novel easy-to-use PCR approach to straightforwardly identify <it>A. gambiae </it>molecular forms. This novel approach allows to overcome the constraints associated with markers on the rDNA region commonly used for M and S identification. In fact, it is based on a single copy and irreversible <it>SINE200 </it>insertion and, thus, is not subjected to peculiar evolutionary patterns affecting rDNA markers, e.g. incomplete homogenization of the arrays through concerted evolution and/or mixtures of M and S IGS-sequences among the arrays of single chromatids.</p> <p>Conclusion</p> <p>The approach utilized allowed to develop new easy-to-use co-dominant markers for the analysis of genetic differentiation between M and S-forms and opens new perspectives in the study of the speciation process ongoing within <it>A. gambiae</it>.</p

Principles to Design Smart Physical Objects as Adaptive Recommenders

Recommenders have proven to be useful means to support people in their activities and in making decisions. They evolved from online recommenders to context-aware and ubiquitous recommenders. Moving forward along this line, this paper introduces the new emerging class of smart physical recommenders: context-aware recommender systems that are embedded into physical everyday objects. This paper describes the features of these systems and presents a conceptual model to design them, by analyzing a number of issues that have to be addressed by a designer and discussing the consequences of different design choices with their impact on the smartness of the designed object. The model is structured in a number of layers corresponding to different conceptual design phases in which different requirements are analyzed. The contribution of this paper is to discuss and provide design guidelines for a new rising class of recommenders that combine the features of intelligent agents, cyber-physical objects, and recommender-support systems. The description of the model is complemented by an exemplary analysis of its application

The telomeric protein AKTIP interacts with A- and B-type lamins and is involved in regulation of cellular senescence

AKTIP is a shelterin-interacting protein required for replication of telomeric DNA. Here, we show that AKTIP biochemically interacts with A- and B-type lamins and affects lamin A, but not lamin C or B, expression. In interphase cells, AKTIP localizes at the nuclear rim and in discrete regions of the nucleoplasm just like lamins. Double immunostaining revealed that AKTIP partially co-localizes with lamin B1 and lamin A/C in interphase cells, and that proper AKTIP localization requires functional lamin A. In mitotic cells, AKTIP is enriched at the spindle poles and at the midbody of late telophase cells similar to lamin B1. AKTIP-depleted cells show senescence-associated markers and recapitulate several aspects of the progeroid phenotype. Collectively, our results indicate that AKTIP is a new player in lamin-related processes, including those that govern nuclear architecture, telomere homeostasis and cellular senescence

Comparative analyses reveal discrepancies among results of commonly used methods for Anopheles gambiaemolecular form identification

<p>Abstract</p> <p>Background</p> <p><it>Anopheles gambiae </it>M and S molecular forms, the major malaria vectors in the Afro-tropical region, are ongoing a process of ecological diversification and adaptive lineage splitting, which is affecting malaria transmission and vector control strategies in West Africa. These two incipient species are defined on the basis of single nucleotide differences in the IGS and ITS regions of multicopy rDNA located on the X-chromosome. A number of PCR and PCR-RFLP approaches based on form-specific SNPs in the IGS region are used for M and S identification. Moreover, a PCR-method to detect the M-specific insertion of a short interspersed transposable element (<it>SINE200</it>) has recently been introduced as an alternative identification approach. However, a large-scale comparative analysis of four widely used PCR or PCR-RFLP genotyping methods for M and S identification was never carried out to evaluate whether they could be used interchangeably, as commonly assumed.</p> <p>Results</p> <p>The genotyping of more than 400 <it>A. gambiae </it>specimens from nine African countries, and the sequencing of the IGS-amplicon of 115 of them, highlighted discrepancies among results obtained by the different approaches due to different kinds of biases, which may result in an overestimation of MS putative hybrids, as follows: i) incorrect match of M and S specific primers used in the allele specific-PCR approach; ii) presence of polymorphisms in the recognition sequence of restriction enzymes used in the PCR-RFLP approaches; iii) incomplete cleavage during the restriction reactions; iv) presence of different copy numbers of M and S-specific IGS-arrays in single individuals in areas of secondary contact between the two forms.</p> <p>Conclusions</p> <p>The results reveal that the PCR and PCR-RFLP approaches most commonly utilized to identify <it>A. gambiae </it>M and S forms are not fully interchangeable as usually assumed, and highlight limits of the actual definition of the two molecular forms, which might not fully correspond to the two <it>A. gambiae </it>incipient species in their entire geographical range. These limits are discussed and operational suggestions on the choice of the most convenient method for large-scale M- and S-form identification are provided, also taking into consideration technical aspects related to the epidemiological characteristics of different study areas.</p

High-intensity exercise training induces morphological and biochemical changes in skeletal muscles

IN THE PRESENT STUDY WE INVESTIGATED THE EFFECT OF TWO DIFFERENT EXERCISE PROTOCOLS ON FIBRE COMPOSITION AND METABOLISM OF TWO SPECIFIC MUSCLES OF MICE: the quadriceps and the gastrocnemius. Mice were run daily on a motorized treadmill, at a velocity corresponding to 60% or 90% of the maximal running velocity. Blood lactate and body weight were measured during exercise training. We found that at the end of training the body weight significantly increased in high-intensity exercise mice compared to the control group (P=0.0268), whereas it decreased in low-intensity exercise mice compared to controls (P=0.30). In contrast, the food intake was greater in both trained mice compared to controls (P &lt; 0.0001 and P &lt; 0.0001 for low-intensity and high-intensity exercise mice, respectively). These effects were accompanied by a progressive reduction in blood lactate levels at the end of training in both the exercised mice compared with controls (P=0.03 and P &lt; 0.0001 for low-intensity and high-intensity exercise mice, respectively); in particular, blood lactate levels after high-intensity exercise were significantly lower than those measured in low-intensity exercise mice (P=0.0044). Immunoblotting analysis demonstrated that high-intensity exercise training produced a significant increase in the expression of mitochondrial enzymes contained within gastrocnemius and quadriceps muscles. These changes were associated with an increase in the amount of slow fibres in both these muscles of high-intensity exercise mice, as revealed by the counts of slow fibres stained with specific antibodies (P &lt; 0.0001 for the gastrocnemius; P=0.0002 for the quadriceps). Our results demonstrate that high-intensity exercise, in addition to metabolic changes consisting of a decrease in blood lactate and body weight, induces an increase in the mitochondrial enzymes and slow fibres in different skeletal muscles of mice, which indicates an exercise-induced increase in the aerobic metabolism