Reassessing the role of grazing lands in carbon-balance estimations: Meta-analysis and review.

Assuming a steady state between carbon (C) gains and losses, greenhouse gases (GHG) inventories that follow a widely used simplified procedure (IPCC Tier 1) tend to underestimate the capacity of soils in grazing-land to sequester C. In this study we compared the C balance reported by (i) national inventories that followed the simplified method (Tier 1) of IPCC (1996/2006), with (ii) an alternative estimation derived from the meta-analysis of science-based, peer-reviewed data. We used the global databases (i) EDGAR 4.2 to get data on GHG emissions due to land conversion and livestock/crop production, and (ii) HYDE 3.1 to obtain historical series on land-use/land cover (LULC). In terms of sequestration, our study was focused on C storage as soil organic carbon (SOC) in rural lands of four countries (Argentina, Brazil, Paraguay and Uruguay) within the so-called MERCOSUR region. Supported by a large body of scientific evidence, we hypothesized that C gains and losses in grazing lands are not in balance and that C gains tend to be higher than C losses at low livestock densities. We applied a two-way procedure to test our hypothesis: i) a theoretical one based on the annual conversion of belowground biomass into SOC; and ii) an empirical one supported by peer-reviewed data on SOC sequestration. Average figures from both methods were combined with LULC data to reassess the net C balance in the study countries. Our results show that grazing lands generate C surpluses that could not only offset rural emissions, but could also partially or totally offset the emissions of non-rural sectors. The potential of grazing lands to sequester and store soil C should be reconsidered in order to improve assessments in future GHG inventory reports.

Multiple sclerosis: getting personal with induced pluripotent stem cells.

Human induced pluripotent stem (iPS) cells can be derived from lineage-restricted cells and represent an important tool to develop novel patient-specific cell therapies and research models for inherited and acquired diseases. Recently, patient-derived iPS cells, containing donor genetic background, have offered a breakthrough approach to study human genetics of neurodegenerative diseases. By offering an unlimited source of patient-specific disease-relevant cells, iPS cells hold great promise for understanding disease mechanisms, identifying molecular targets and developing phenotypic screens for drug discovery. This review will discuss the potential impact of using iPS cell-derived models in multiple sclerosis (MS) research and highlight some of the current challenges and prospective for generating novel therapeutic treatments for MS patients.

Induced pluripotent stem cells in hematology: current and future applications.

Reprogramming somatic cells into induced pluripotent stem (iPS) cells is nowadays approaching effectiveness and clinical grade. Potential uses of this technology include predictive toxicology, drug screening, pathogenetic studies and transplantation. Here, we review the basis of current iPS cell technology and potential applications in hematology, ranging from disease modeling of congenital and acquired hemopathies to hematopoietic stem and other blood cell transplantation.

The Aurora B kinase activity is required for the maintenance of the differentiated state of murine myoblasts.

Reversine is a synthetic molecule capable of inducing dedifferentiation of C2C12, a murine myoblast cell line, into multipotent progenitor cells, which can be redirected to differentiate in nonmuscle cell types under appropriate conditions. Reversine is also a potent inhibitor of Aurora B, a protein kinase required for mitotic chromosome segregation, spindle checkpoint function, cytokinesis and histone H3 phosphorylation, raising the possibility that the dedifferentiation capability of reversine is mediated through the inhibition of Aurora B. Indeed, here we show that several other well-characterized Aurora B inhibitors are capable of dedifferentiating C2C12 myoblasts. Significantly, expressing drug-resistant Aurora B mutants, which are insensitive to reversine block the dedifferentiation process, indicating that Aurora B kinase activity is required to maintain the differentiated state. We show that the inhibition of the spindle checkpoint or cytokinesis per se is not sufficient for dedifferentiation. Rather, our data support a model whereby changes in histone H3 phosphorylation result in chromatin remodeling, which in turn restores the multipotent state.

Psychophysiological aspects of voluntary skilled movement after stroke: a follow-up study.

OBJECTIVES: The aim of the study was to follow the psychophysiological evolution of a self-paced voluntary skilled movement in hemiparetic subjects after ischemic stroke by means of a skilled performance task (SPT). The task consisted in starting a sweep of an oscilloscope trace by pushing one button with the left index finger (trigger point), and in stopping it within a central area on the oscilloscope screen, between 40 and 60 ms (correct performance) after the start of the sweep, by pushing the other button with the right index finger. A SPT yields a considerable amount of information on the electrophysiological components, which reflect pre-programming activity (Bereitschaftspotential--BP), control strategies (Skilled Performance Positivity--SPP) and behavioural response (Correct Performances). The study was also aimed at detecting any longitudinal changes in the psychophysiological pattern, as evaluated by the clinical examination and specific motility scales, that parallel motor recovery. METHODS: Movement related potentials (MRPs) were recorded in 12 control subjects and 9 patients in the acute phase, before the start of neurorehabilitation (time 0), when the patients were able to execute an index finger press with the affected hand. The patients (mean age = 62.33 years, SD = 8.17) presented a mild to moderate central arm paresis caused by a first-ever unilateral supratentorial and subcortical ischemic lesion. The subsequent recordings were carried out respectively 3, 9 and 12 months later. RESULTS: At the first recording, hemiparetic patients achieved a significantly lower percentage of correct performances and had a lower BP amplitude than controls (p < 0.001); SPP was absent. The number of correct performances did not improve significantly during the subsequent recordings. BP amplitude showed a mild increase in the second, third and fourth recordings (p < 0.05), while SPP amplitude revealed a slight improvement at the second and a marked improvement at the third and fourth recordings, when there was no longer a statistically significant difference from controls. CONCLUSIONS: Our findings point to an early recovery of pre-programming activity and a delayed improvement in control activity. The delayed development of control activity in the absence of procedural learning, i.e. skill learning through practice, forces patients to exploit attentional strategies to compensate for their procedural learning impairment. SPT shows that the efficacy of physical therapy aimed at motor ability recovery in hemiparetic patients does not keep up with the slow recovery process of an automatic motor level.

Modern psychophysical tests to assess olfactory function.

The sense of smell significantly contributes to quality of life. In recent years much progress has been made in understanding the biochemistry, physiology and pathology of the human olfactory system. Olfactory disorders may arise not only from upper airway phlogosis but also from neurodegenerative disease. Hyposmia may precede motor signs in Parkinson's disease and cognitive deficit in Alzheimer's disease. These findings suggest the complementary role of olfactory tests in the diagnosis and management of neurodegenerative diseases. In this report we present a review of modern olfactory tests and their clinical applications. Although rarely employed in routine clinical practice, the olfactory test evaluates the ability of odour identification and is a useful diagnostic tool for olfaction evaluation. Olfactory screening tests are also available. In this work we strongly recommend the importance of an ENT evaluation before the test administration and dissuade from a self-administration of an olfactory test.

Olfactory screening test in mild cognitive impairment.

Mild cognitive impairment (MCI) is a transient status between physiologic ageing and dementia. Each year more than 12% of subjects with MCI develop Alzheimer's disease. This study evaluated the presence of an olfactory deficit in amnesic MCI (aMCI) patients. Twenty-nine patients diagnosed with aMCI and a homogeneous control group of 29 subjects were enrolled in the study. Olfactory function was assessed by the Sniffin' Sticks Screening Test (SSST) and the Mini Mental State Examination, the Clinical Dementia Rating, the Geriatric Depression Scale and the Mental Deterioration Battery were used to evaluate the neurocognitive status. aMCI patients showed a significant impairment of their olfactory identification compared to controls (SSST score: 8.3+/-2.1 vs. 10.8+/-0.9; p<0.001). These results suggest that olfactory tests should be part of the diagnostic armamentarium of pre-clinical dementia. A long-term follow up might confirm the olfactory identification function as an early and reliable marker in the diagnosis of pre-clinical dementia.

Abnormal head nociceptive withdrawal reaction to facial nociceptive stimuli in Parkinson's disease.

INTRODUCTION: Trigemino-cervical-spinal reflexes (TCSRs) are complex brainstem stereotyped nociceptive responses involved in a defensive withdrawal reaction of the head from facial nociceptive stimuli. OBJECTIVE: The present study was undertaken to collect data on possible TCSR abnormalities in idiopathic Parkinson's disease (PD) and investigate any correlation with motor signs and L-DOPA administration. METHODS: TCSRs were registered from the semispinalis capitis and biceps brachii muscles after electrical stimulation of the supraorbital nerve in 18 patients with PD and 24 controls. The latency (L) and area (A), as well as the sensory (ST), painful (PT) and reflex (RT) thresholds were measured during the 'off' and 'on' state, and possible correlations with the UPDRS III total score, selected subscores (tremor, neck rigidity, upper limb rigidity, akinesia, rising from a chair, posture and posture instability) and duration of illness were investigated. RESULTS: Significant changes between controls and PD patients were found in the L, A, PT and RT of TCSRs. These results were not significantly influenced by L-DOPA treatment. A significant correlation was found between neck rigidity, postural instability scores and duration of illness and the TCSR L and A values in PD patients in the 'off' state. CONCLUSIONS: TCSRs abnormalities, combined with dopamine resistance, are consistent with a primary loss of brainstem neurons mediating a complex sensory-motor integration including neck muscle tone and postural control as well as the head withdrawal reaction to the nociceptive stimuli. SIGNIFICANCE: TCSRs may represent a useful tool for the assessment of brainstem sensory-motor function in PD as well as other movement and degenerative disorders.

Sporadic Creutzfeldt-Jakob disease without dementia at onset: clinical features, laboratory tests and sequential diffusion MRI (in an autopsy-proven case).

A rapidly progressing dementia, followed by focal neurological signs, and evidence of periodic sharp wave complexes (PSWC) in the EEG may lead to the clinical suspicion of Creutzfeldt-Jakob disease (CJD). Different clinical variants of CJD have been described in the past, with prominent extrapyramidal or occipital lobe involvement, all included in the sporadic form of CJD (sCJD). Familiar and iatrogenic forms of CJD are also known. More recently a new variant has been described, vCJD, casually linked to bovine spongiform encephalopathy (BSE) and it has attracted increasing attention toward each form of rapidly progressing dementia; likewise the differential diagnosis between sCJD vs. vCJD is not always easy. Magnetic resonance imaging (MRI) too seems to have a peculiar role in differentiating sCJD from vCJD, even if the role of MRI in the diagnosis of CJD is still debated. Diffusion MRI is expected to play an important role in the clinical setting of CJD, contributing to formulation of an early diagnosis, especially in cases with unusual clinical presentation. In fact, the sensitivity of diffusion MRI is superior to that of conventional MRI (T1, T2, FLAIR) in detecting specific basal ganglia and cortical abnormalities early in the course of CJD and these abnormalities correlate well with areas of the most severe and characteristic neuropathological changes. We describe a case of autopsy-proven sCJD, with an unusual clinical course without dementia as a presenting symptom and discuss the role of diffusion MRI and laboratory tests in making an early diagnosis.

Clinical and genetic studies in hereditary spastic paraplegia with thin corpus callosum.

BACKGROUND: A complicated form of recessive hereditary spastic paraplegias (HSPs) with thin corpus callosum (TCC) was first described in Japan, and most of the Japanese families showed linkage to chromosome 15q13-15. A recessive HSP locus (SPG11) has also been mapped to chromosome 15q13-15 in Italian and North American families with and without TCC, and it overlaps the region identified in the Japanese families. OBJECTIVE: To study clinically and genetically 12 Italian families with HSP and TCC. METHODS: The authors investigated 18 affected and 30 healthy individuals from 12 unrelated Italian families with recessive HSP-TCC. Clinical, neurophysiologic, and neuroradiologic studies were undertaken. All patients were negative for SPG7 mutations. Genetic linkage analyses were carried out with polymorphic DNA markers on 15q13-15. RESULTS: Five families were consistent with linkage, thus defining a 19.8-cM region between markers D15S1007 and D15S978, encompassing the SPG11 interval. In one consanguineous family, linkage could be firmly excluded, confirming genetic heterogeneity. Two families appeared not linked to the region, but this could not be firmly proved because of the small family size. The remaining four families were uninformative for linkage purposes. CONCLUSION: HSP-TCC is common in Italy. The phenotype is fairly homogeneous and is associated with impaired cognition. There are at least two loci for HSP-TCC, one of which is on chromosome 15q13-15.

Growth retardation, developmental delay, distinctive face, multiple endocrine abnormalities, and adenylyl cyclase dysfunction: a new syndrome?

We report on a 17-year-old male with severe pre- and postnatal growth retardation, craniosynostosis, distinctive facial features, acanthosis nigricans, deafness, mental retardation and progressive multi-organ involvement, particularly of the endocrine system, including hypothyroidism, hypogonadism, transitory hypoparathyroidism, and insulin resistance. In order to find a common mechanism explaining these multiple abnormalities, we searched for a possible defect in the signal transduction pathways from membrane to nucleus involving G-protein coupled receptors (GPCR). Adenylyl cyclase activity was evaluated by assaying c-AMP in the patient's cultured fibroblasts stimulated with several drugs and toxins acting on different effectors upstream of adenylyl cyclase. The preliminary results indicate a reduced cAMP accumulation in the patient, neither caused by constitutive activation of Gi nor inhibition of Gs signaling, and probably resulting from an alteration in the adenylyl cyclase system. The differential diagnosis with syndromes showing common clinical features with our patient is discussed.

Muscular cramps: proposals for a new classification.

Muscle cramps are involuntary, painful, sudden contractions of the skeletal muscles. They are present in normal subjects under certain conditions (during a strong voluntary contraction, sleep, sports, pregnancy) and in several pathologies such as myopathies, neuropathies, motoneuron diseases, metabolic disorders, hydroelectrolyte imbalances or endocrine pathologies. There has been considerable uncertainty in the literature regarding the classification and nomenclature of muscle cramps, both because the term "cramp" is used to indicate a variety of clinical features of muscles, leading to its use as an imprecise "umbrella" term that includes stiffness, contractures and local pain, and because the spectrum of the diseases in which it appears is wide. The purpose of the present study is to propose a simple classification to provide a framework to better recognize the full spectrum of phenomenology of muscle cramps.

SPG3A: An additional family carrying a new atlastin mutation.

The authors report on a novel frameshift mutation (c.1688insA) in the SPG3A gene resulting in premature translation termination of the gene product atlastin. These data add a new variant to the second disease gene in autosomal dominant hereditary spastic paraplegia (ADHSP) and lend definitive support to its causative role. By combining direct testing of SPAST and SPG3A, at least 50% of ADHSP families can now receive appropriate genetic diagnosis.

L-dopa effects on preprogramming and control activity in a skilled motor act in Parkinson's disease.

OBJECTIVES: The authors investigated whether preprogramming (Bereitschaftspotential, BP) and control activity (skilled performance positivity, SPP) in a bimanual, sequential skilled performance task (SPT) is sensitive to L-dopa administration in non-demented Parkinson's disease (PD) patients. METHODS: Movement related potentials (MRPs) were recorded in 12 non-demented parkinsonian patients before and after acute L-dopa administration, and in 17 control subjects, all of whom were performing SPT for the first time. BP, SPP and correct performances were evaluated both as a grand average and in sequential blocks in order to verify the learning effect. RESULTS: After L-dopa administration the PD patients scored a significantly higher percentage of correct performances (P<0.05), linked to a decreased BP amplitude (P<0.001) and an increased SPP amplitude (P<0.005), than before therapy. Dynamic evaluation through the block analysis did not show any learning effect in off-therapy patients but showed that L-dopa intake improved learning, linked to a BP amplitude decrease (P<0.005) and a SPP amplitude increase (P<0.05). Furthermore, L-dopa minimized differences in the learning trend between off-therapy PD patients and controls. CONCLUSIONS: Our findings suggest that skilled motor learning is impaired in non-demented untreated PD patients. Dopaminergic drug administration seems to restore the ability of PD patients to use more automatic motor strategies, as demonstrated by the electrophysiological and behavioural pattern, which became more similar to that of normal subjects.

Psychophysiological approach in Parkinson's disease: L-dopa effects on preprogramming and control activity.

To investigate whether preprogramming (Bereitschaftspotential, BP) and control activity (skilled performance positivity, SPP) in a complex task are sensitive to L-dopa, movement related potentials (MRPs) were recorded in 12 non-demented Parkinson's disease (PD) patients before and after acute L-dopa administration, and in 17 control subjects. After L-dopa administration, the PD patients scored a significantly higher percentage of correct performances ( p<0.05), linked to a decreased BP amplitude ( p<0.001) and an increased SPP amplitude ( p<0.005), than before therapy. Our findings suggest that preprogramming activity is impaired in untreated PD patients. Dopaminergic drug administration seems to restore their ability to use more automatic motor strategies which become more similar to that of normal subjects.

Respiratory chain defects in hereditary spastic paraplegias.

Hereditary Spastic Paraplegias (HSPs) are heterogeneous neurodegenerative disorders whose etiopathogenesis is still unclear. The identification of pathogenic mutations in a gene (SPG7) encoding a mitochondrial metalloprotease suggested that oxidative phosphorylation (OXPHOS) alterations might underlie HSP in a subgroup of patients. We performed clinical, morphological, biochemical, and molecular genetic studies in six HSP patients and in six sporadic patients to investigate OXPHOS in muscle biopsies. Complicated and pure forms were included in our study. Morphological alterations of the type seen in OXPHOS-related disorders were found in three patients. Five patients showed an isolated defect of complex I activity. No mutations in the SPG7 gene were detected. Our results suggest that OXPHOS defects in HSP patients are more common than previously believed.

Mitochondrial myopathy, parkinsonism, and multiple mtDNA deletions in a Sephardic Jewish family.

The authors describe a family of Sephardic Jews with progressive external ophthalmoparesis, skeletal muscle weakness, and parkinsonism. Autosomal recessive inheritance was suggested by many consanguineous marriages, although a dominant disorder could not be excluded. No linkage to known progressive external ophthalmoparesis locus was found. The presence of cytochrome c oxidase-negative ragged-red fibers, biochemically reduced respiratory chain complexes, and multiple mitochondrial DNA deletions in muscle biopsies from four patients suggested a new mitochondrial disorder of intergenomic communication.