The cysteine-histidine-rich region of the movement protein of Cucumber mosaic virus contributes to plasmodesmal targeting, zinc binding and pathogenesis

Viral movement proteins (MPs) are central to the establishment of viral pathogenesis, and yet relatively little is understood about the structural and functional aspects of MPs or about the host factors on which they depend. Through chemical mutagenesis of transgenic Arabidopsis expressing Cucumber mosaic virus (CMV) MP fused with the green fluorescent protein, we have studied the function of a central region of the MP, defined by a number of conserved cysteine and histidine residues (Cys-His-rich region), which potentially functions as a zinc-binding domain. Transient expression of mutant MPs identified through an in planta screen for altered MP function or constructed with altered putative zinc ligands through site-directed mutagenesis showed that mutations in the Cys-His-rich region affected localization to and trafficking through plasmodesmata. In vitro zinc-binding analysis revealed that wild type (wt) CMV MP had the ability to bind zinc and that movement-defective mutants bound zinc with less affinity than wt MP. Furthermore, a correlation between the association of the MP with plasmodesmata and virus pathogenesis was shown. We discuss roles of the Cys-His region in biochemical and biological functions of the MP during virus movement.     

Recommendations for the use of cardiovascular tests in diagnosing diabetic autonomic neuropathy

Despite its prevalence, clinical and prognostic impact, diabetic autonomic neuropathy, is widely under-diagnosed. The need for training and expertise to perform the cardiovascular tests (usually the task of diabetologists) is one possible reason. The availability of computer-assisted systems has allowed a wider diffusion of testing, but has also highlighted the need for an adequate knowledge of physiopathological backgrounds for their correct application and interpretation. The recommendations presented here were developed by the Neuropathy Study Group of the Italian Society of Diabetology and then endorsed by the Italian Association for the Study of Neurovegetative System, to promote the widespread adoption of good clinical practice in diabetic cardiovascular autonomic testing by outlining main evidence-based aspects, i.e. which tests, how to perform them, adequate interpretation of the results and their diagnostic use, confounding conditions that can impact on tests reliability. Therefore, these recommendations include the essential aspects of the physiopathological substrate of the tests, the controversial points in their analysis, their diagnostic characteristics, as well as safety. Detailed information is given on the physiological (age, weight, body position, resting heart rate and blood pressure, respiratory pattern, exercise, meals, acute blood glucose changes) and pathophysiological confounding factors, with emphasis on the effects of drugs. Instructions on how to perform the tests and interpret their results are also considered together with indications of candidate patients and periodicity of testing. A patient instruction sheet on why and how to perform the tests is included. Finally, the specific requirements for computerized systems to perform and evaluate cardiovascular tests are provided.     

Health-related quality of life of long-term childhood cancer survivors: a population-based study from the Childhood Cancer Registry of Piedmont, Italy

Aim of the studyTo determine the Health Related Quality of Life (HRQL) in a population-based cohort of long-term survivors of childhood cancer in Piedmont, northwestern Italy.Patients and methodsDuring 2003, a 15-item Health Utilities Index questionnaire was mailed to 1005 5-year survivors, identified from the population-based Childhood Cancer Registry of Piedmont, to derive scores for overall HRQL and for eight single attributes of health. Score differences were estimated as adjusted prevalence odds ratios.ResultsA large majority of long-term survivors had moderately high scores for overall HRQL and for each of the single attributes. Males reported better overall HRQL and less morbidity with respect to dexterity, emotion and pain than females. Survivors diagnosed when they were 10–14 years of age had better overall HRQL and less morbidity with respect to emotion, cognition and pain than younger persons. Long-term survivors of central nervous system (CNS) tumours, retinoblastoma and bone tumours had greater impairment of overall HRQL, vision, ambulation, dexterity, cognition and pain than survivors of other forms of cancer.ConclusionMany survivors of childhood cancer in Piedmont had fairly good overall HRQL. Greater probability of impaired HRQL was seen for females, survivors of CNS tumours, retinoblastoma and bone tumours, and persons diagnosed before 10 years of age.     

Adaptation of visual tracking synchronization after one night of sleep deprivation

The temporal delay between sensory input and motor execution is a fundamental constraint in interactions with the environment. Predicting the temporal course of a stimulus and dynamically synchronizing the required action with the stimulus are critical for offsetting this constraint, and this prediction–synchronization capacity can be tested using visual tracking of a target with predictable motion. Although the role of temporal prediction in visual tracking is assumed, little is known of how internal predictions interact with the behavioral outcome or how changes in the cognitive state influence such interaction. We quantified and compared the predictive visual tracking performance of military volunteers before and after one night of sleep deprivation. The moment-to-moment synchronization of visual tracking during sleep deprivation deteriorated with sensitivity changes greater than 40 %. However, increased anticipatory saccades maintained the overall temporal accuracy with near zero phase error. Results suggest that acute sleep deprivation induces instability in visuomotor prediction, but there is compensatory visuomotor adaptation. Detection of these visual tracking features may aid in the identification of insufficient sleep.     

Sympathetic hyperactivity in patients with ulcerative colitis

Hypo and hyperactivity of the autonomic nervous system have been associated with chronic bowel inflammation diseases. We investigated the autonomic function in 11 patients with chronic ulcerative colitis (UC) and 17 healthy controls by means of cardiovascular autonomic tests and heart rate variability. Autonomic responses were normal in patients and controls. At rest, LF/HF ratios were significantly (P < 0.05) higher in chronic UC patients (2.4 ± 1.6) compared to controls (1.2 ± 1.0). Our results suggest a higher sympathetic tone at rest in patients with chronic UC.     

Arrhythmic syncope in neurogenic orthostatic hypotension: two case reports

Patients with autonomic failure experience orthostatic hypotension (OH) often leading to syncope. Arrhythmias may cause severe syncope, characterized by an increased risk of mortality. We report two cases of patients with primary autonomic neuropathy suffering from both severe OH and arrhythmic syncope.     

Tissue-specific molecular immune response to lipopolysaccharide challenge in emaciated anadromous Arctic charr

Anadromous Arctic charr (Salvelinus alpinus) undergo voluntary winter fasting for months in the Arctic. We tested the hypothesis that extended fasting will compromise the ability of this species to evoke an immune response. Charr were either fed or fasted for 85 days and challenged with lipopolysaccharide (LPS), and the molecular immune response in the liver and spleen assessed at 8 and 96 h post-injection. LPS increased IL-1β, IL-8, and serum amyloid protein A (SAA) mRNA levels in both groups, but the liver IL-1β and IL-8, and spleen IL-8 responses were reduced in the fasted group. Fasting upregulated SOCS-1 and SOCS-2 mRNA abundance, while LPS stimulated SOCS-3 mRNA abundance and this response was higher in the fasted liver. Collectively, extended fasting and emaciation does not curtail the capacity of charr to evoke an immune response, whereas upregulation of SOCS may be a key adaptation to conserve energy by restricting the inflammatory response.     

Kinematic but not clinical measures predict falls in Parkinson-related orthostatic hypotension

Journal of Neurology - We sought to test the hypothesis that technology could predict the risk of falls in Parkinson’s disease (PD) patients with orthostatic hypotension (OH) with greater...     

Burden of caregiving for cardiovascular dysautonomia in Parkinson’s disease

Purpose

We sought to estimate the impact of cardiovascular autonomic neuropathy (cAN) on informal caregivers of patients with Parkinson’s disease (PD), defined as individuals providing regular care to a friend, partner, or family member with PD, and to evaluate the mutual relationship between caregiver burden and patient health-related quality of life (HRQoL).

Methods

We enrolled 36 consecutive patients with PD and their informal caregivers. Patients underwent a detailed motor, autonomic, cognitive, and functional assessment. Caregivers were assessed using the Zarit Burden Interview (ZBI). Differences in caregiver burden, expressed by the ZBI score, and strength of association between caregiver burden, cAN, and HRQoL were assessed using analysis of covariance (ANCOVA), logistic regression, and linear regression analyses. Analyses were adjusted for patients’ age, PD duration, and motor and cognitive disability, as well as caregivers’ age.

Results

Moderate-severe caregiver burden was reported in 41.7% of PDcAN⁺ versus 8.7% of PDcAN⁻ (p < 0.001). The ZBI score was increased in PDcAN⁺ versus PDcAN⁻ (31.5 ± 3.4 versus 15.2 ± 2.3; p < 0.001), with tenfold higher odds (p = 0.012) of moderate-severe caregiver burden in PDcAN⁺, even after adjusting for potential confounders. The ZBI score correlated with cAN severity (p = 0.005), global autonomic impairment (p = 0.012), and HRQoL impairment (p < 0.001).

Conclusion

These results highlight the significant impact of cAN on PD caregivers and the need for targeted interventions addressing this frequently overlooked and insufficiently treated source of nonmotor disability in PD.