Indel and single nucleotide variations of zeins generate unique 2D-zein patterns and molecular markers useful in maize (Zea mays) genotyping

In this study, we investigated the inter- and intra-genomic sequence variation of alpha-zein genes and their polypeptide expression in different maize genotypes, i.e. inbreds and a set of Lombardy open pollinated varieties, by analyzing their RFLP, coding nucleotides and 2-dimensional (2D) protein fractionation profiles. An extensive analysis of coding capacity of alpha-zein sequences in various genotypes and in the B73 reference inbred allowed us to assign 2D-spots to specific zein sequences. Moreover, we found that some genes reported to contain in frame stop codons are very likely expressed. Collectively these data allowed us to constitute two barcodes respectively based on nucleotide variation and on 2-D protein patterns that identify univocally each genotype

Risk of classical Kaposi sarcoma by plasma levels of Epstein-Barr virus antibodies, sCD26, sCD23 and sCD30

<p>Abstract</p> <p>Background</p> <p>To clarify the immunological alterations leading to classical Kaposi sarcoma (cKS) among people infected with KS-associated herpesvirus (KSHV).</p> <p>Methods</p> <p>In a population-based study of 119 cKS cases, 105 KSHV-seropositive controls, and 155 KSHV-seronegative controls, we quantified plasma soluble cluster of differentiation (sCD) levels and antibodies against Epstein-Barr virus nuclear antigen-1 (anti-EBNA-1) and viral capsid antigen (anti-VCA). Differences between groups in prevalence of low-tertile anti-EBNA-1 and high-tertile anti-VCA were compared by logistic regression. Continuous levels between groups and by presence of cKS co-factors among controls were compared by linear regression and Mann-Whitney-Wilcoxon methods.</p> <p>Results</p> <p>Comparisons of cKS cases to seropositive controls and of seropositive to seronegative controls revealed no significant differences. However, controls with known cKS cofactors (male sex, nonsmoking, diabetes and cortisone use) had significantly lower levels of anti-EBNA (<it>P </it>= 0.0001 - 0.07) and anti-VCA (<it>P </it>= 0.0001 - 0.03). Levels of sCD26 were significantly lower for male and non-smoking controls (<it>P</it>_adj≤ 0.03), and they were marginally lower with older age and cortisone use (<it>P</it>_adj≤ 0.09).</p> <p>Conclusions</p> <p>Anti-EBV and sCD26 levels were associated with cofactors for cKS, but they did not differ between cKS cases and matched controls. Novel approaches and broader panels of assays are needed to investigate immunological contributions to cKS.</p

Glycemic Variability Assessed by Continuous Glucose Monitoring and Short-Term Outcome in Diabetic Patients Undergoing Percutaneous Coronary Intervention: An Observational Pilot Study

Poor glycemic control is associated with unfavorable outcome in patients undergoing percutaneous coronary intervention (PCI), irrespective of diabetes mellitus. However a complete assessment of glycemic status may not be fully described by glycated hemoglobin or fasting blood glucose levels, whereas daily glycemic fluctuations may influence cardiovascular risk and have even more deleterious effects than sustained hyperglycemia. Thus, this paper investigated the effectiveness of a continuous glucose monitoring (CGM), registering the mean level of glycemic values but also the extent of glucose excursions during coronary revascularization, in detecting periprocedural outcome such as renal or myocardial damage, assessed by serum creatinine, neutrophil gelatinase-associated lipocalin (NGAL), and troponin I levels. High glycemic variability (GV) has been associated with worse postprocedural creatinine and NGAL variations. Moreover, GV, and predominantly hypoglycemic variations, has been observed to increase in patients with periprocedural myocardial infarction. Thus, our study investigated the usefulness of CGM in the setting of PCI where an optimal glycemic control should be achieved in order to prevent complications and improve outcome

Glycemic Variability Assessed by Continuous Glucose Monitoring and Short-Term Outcome in Diabetic Patients Undergoing Percutaneous Coronary Intervention: An Observational Pilot Study

Poor glycemic control is associated with unfavorable outcome in patients undergoing percutaneous coronary intervention (PCI), irrespective of diabetes mellitus. However a complete assessment of glycemic status may not be fully described by glycated hemoglobin or fasting blood glucose levels, whereas daily glycemic fluctuations may influence cardiovascular risk and have even more deleterious effects than sustained hyperglycemia. Thus, this paper investigated the effectiveness of a continuous glucose monitoring (CGM), registering the mean level of glycemic values but also the extent of glucose excursions during coronary revascularization, in detecting periprocedural outcome such as renal or myocardial damage, assessed by serum creatinine, neutrophil gelatinase-associated lipocalin (NGAL), and troponin I levels. High glycemic variability (GV) has been associated with worse postprocedural creatinine and NGAL variations. Moreover, GV, and predominantly hypoglycemic variations, has been observed to increase in patients with periprocedural myocardial infarction. Thus, our study investigated the usefulness of CGM in the setting of PCI where an optimal glycemic control should be achieved in order to prevent complications and improve outcome

Two functional different mitochondrial phosphate carriers support Drosophila melanogaster OXPHOS throughout distinct developmental stages.

The mitochondrial oxidative phosphorylation system (OXPHOS) plays a central role in cellular energy metabolism by producing ATP. In this study, an in silico analysis conducted on nuclear somatically expressed Drosophila melanogaster OXPHOS genes, revealed shared features including widespread expression, presence of Nuclear Respiratory Gene (NRG) elements, and coordinated developmental-dependent expression, with two distinct peaks of expression during late embryonic and pupal stages. In contrast, OXPHOS paralog genes showed a unique pupal peak and were primarily expressed in adult testes. Furthermore, we conducted an extensive characterization of D. melanogaster mitochondrial phosphate carrier (Mpcp), a key player of OXPHOS. In Drosophila two genes, CG9090 and CG4994, encode putative Mpcp known as Mpcp1 and Mpcp2. Intriguingly, the expression patterns of Mpcps during development exhibited significant differences from each other and from those of other OXPHOS genes. This suggests that both isoforms contribute to ATP synthesis and are essential for the full organism development, with CG9090 also showing a connection with lifespan and aging processes. Functional complementation assays, swelling experiments carried out in the yeast mir1∆ strain and an extensive kinetic characterization of recombinant mature Mpcp2 confirmed that both isoforms transport phosphate. However, Mpcp1 displays a three folds lower activity compared to Mpcp2. Collectively, these findings suggest that mMpcp1 and mMpcp2 operate similarly to mammalian PiC-A and PiC-B, respectively. This provides a basis for exploring functional differences in mammals and gaining new insights into the mechanisms underlying OXPHOS-related diseases associated to deficiencies in human PiC transporters

Impact of 2021 European Academy of Neurology/Peripheral Nerve Society diagnostic criteria on diagnosis and therapy of chronic inflammatory demyelinating polyradiculoneuropathy variants

Background and purpose: there are different criteria for the diagnosis of different variants of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The 2021 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) guidelines provide specific clinical criteria for each CIDP variant even if their therapeutical impact has not been investigated. Methods: we applied the clinical criteria for CIDP variants of the 2021 EAN/PNS guidelines to 369 patients included in the Italian CIDP database who fulfilled the 2021 EAN/PNS electrodiagnostic criteria for CIDP. Results: according to the 2021 EAN/PNS clinical criteria, 245 patients achieved a clinical diagnosis of typical CIDP or CIDP variant (66%). We identified 106 patients with typical CIDP (29%), 62 distal CIDP (17%), 28 multifocal or focal CIDP (7%), four sensory CIDP (1%), 27 sensory-predominant CIDP (7%), 10 motor CIDP (3%), and eight motor-predominant CIDP (2%). Patients with multifocal, distal, and sensory CIDP had milder impairment and symptoms. Patients with multifocal CIDP had less frequently reduced conduction velocity and prolonged F-wave latency and had lower levels of cerebrospinal fluid protein. Patients with distal CIDP more frequently had reduced distal compound muscle action potentials. Patients with motor CIDP did not improve after steroid therapy, whereas those with motor-predominant CIDP did. None of the patients with sensory CIDP responded to steroids, whereas most of those with sensory-predominant CIDP did. Conclusions: the 2021 EAN/PNS criteria for CIDP allow a better characterization of CIDP variants, permitting their distinction from typical CIDP and more appropriate treatment for patients

Risk of classic Kaposi sarcoma with exposures to plants and soils in Sicily

<p>Abstract</p> <p>Background</p> <p>Ecologic and in vitro studies suggest that exposures to plants or soil may influence risk of Kaposi sarcoma (KS).</p> <p>Methods</p> <p>In a population-based study of Sicily, we analyzed data on contact with 20 plants and residential exposure to 17 soils reported by 122 classic KS cases and 840 sex- and age-matched controls. With 88 KS-associated herpesvirus (KSHV) seropositive controls as the referent group, novel correlates of KS risk were sought, along with factors distinguishing seronegatives, in multinomial logistic regression models that included matching variables and known KS cofactors - smoking, cortisone use, and diabetes history. All plants were summed for cumulative exposure. Factor and cluster analyses were used to obtain scores and groups, respectively. Individual plants and soils in three levels of exposure with <it>P</it>_trend≤ 0.15 were retained in a backward elimination regression model.</p> <p>Results</p> <p>Adjusted for known cofactors, KS was not related to cumulative exposures to 20 plants [per quartile adjusted odds ratio (OR_adj) 0.96, 95% confidence interval (CI) 0.73 - 1.25, <it>P</it>_trend= 0.87], nor was it related to any factor scores or cluster of plants (<it>P </it>= 0.11 to 0.81). In the elimination regression model, KS risk was associated with five plants (<it>P</it>_trend= 0.02 to 0.10) and with residential exposure to six soils (<it>P</it>_trend= 0.01 to 0.13), including three soils (eutric regosol, chromic/pellic vertisol) used to cultivate durum wheat. None of the KS-associated plants and only one soil was also associated with KSHV serostatus. Diabetes was associated with KSHV seronegativity (OR_adj4.69, 95% CI 1.97 - 11.17), but the plant and soil associations had little effect on previous findings that KS risk was elevated for diabetics (OR_adj7.47, 95% CI 3.04 - 18.35) and lower for current and former smokers (OR_adj0.26 and 0.47, respectively, <it>P</it>_trend= 0.05).</p> <p>Conclusions</p> <p>KS risk was associated with exposure to a few plants and soils, but these may merely be due to chance. Study of the effects of durum wheat, which was previously associated with cKS, may be warranted.</p

Colchicine treatment in amyotrophic lateral sclerosis: safety, biological and clinical effects in a randomized clinical trial

: In preclinical studies, the anti-inflammatory drug colchicine, which has never been tested in amyotrophic lateral sclerosis, enhanced the expression of autophagy factors and inhibited accumulation of transactive response DNA-binding protein 43 kDa, a known histopathological marker of amyotrophic lateral sclerosis. This multicentre, randomized, double-blind trial enrolled patients with probable or definite amyotrophic lateral sclerosis who experienced symptom onset within the past 18 months. Patients were randomly assigned in a 1:1:1 ratio to receive colchicine at a dose of 0.005 mg/kg/day, 0.01 mg/kg/day or placebo for a treatment period of 30 weeks. The number of positive responders, defined as patients with a decrease lesser than 4 points in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised total score during the 30-week treatment period, was the primary outcome. Disease progression, survival, safety and quality of life at the end of treatment were the secondary clinical outcomes. Secondary biological outcomes included changes from baseline to treatment end of stress granule and autophagy responses, transactive response DNA-binding protein 43 kDa, neurofilament accumulation and extracellular vesicle secretion, between the colchicine and placebo groups. Fifty-four patients were randomized to receive colchicine (n = 18 for each colchicine arm) or placebo (n = 18). The number of positive responders did not differ between the placebo and colchicine groups: 2 out of 18 patients (11.1%) in the placebo group, 5 out of 18 patients (27.8%) in the colchicine 0.005 mg/kg/day group (odds ratio = 3.1, 97.5% confidence interval 0.4-37.2, P = 0.22) and 1 out of 18 patients (5.6%) in the colchicine 0.01 mg/kg/day group (odds ratio = 0.5, 97.5% confidence interval 0.01-10.2, P = 0.55). During treatment, a slower Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised decline was detected in patients receiving colchicine 0.005 mg/kg/day (mean difference = 0.53, 97.5% confidence interval 0.07-0.99, P = 0.011). Eight patients experienced adverse events in placebo arm (44.4%), three in colchicine 0.005 mg/kg/day (16.7%) and seven in colchicine 0.01 mg/kg/day arm (35.9%). The differences in adverse events were not statistically significant. In conclusion, colchicine treatment was safe for amyotrophic lateral sclerosis patients. Further studies are required to better understand mechanisms of action and clinical effects of colchicine in this condition

Neuronal models of TDP-43 proteinopathy display reduced axonal translation, increased oxidative stress, and defective exocytosis

Amyotrophic lateral sclerosis (ALS) is a progressive, lethal neurodegenerative disease mostly affecting people around 50–60 years of age. TDP-43, an RNA-binding protein involved in pre-mRNA splicing and controlling mRNA stability and translation, forms neuronal cytoplasmic inclusions in an overwhelming majority of ALS patients, a phenomenon referred to as TDP-43 proteinopathy. These cytoplasmic aggregates disrupt mRNA transport and localization. The axon, like dendrites, is a site of mRNA translation, permitting the local synthesis of selected proteins. This is especially relevant in upper and lower motor neurons, whose axon spans long distances, likely accentuating their susceptibility to ALS-related noxae. In this work we have generated and characterized two cellular models, consisting of virtually pure populations of primary mouse cortical neurons expressing a human TDP-43 fusion protein, wt or carrying an ALS mutation. Both forms facilitate cytoplasmic aggregate formation, unlike the corresponding native proteins, giving rise to bona fide primary culture models of TDP-43 proteinopathy. Neurons expressing TDP-43 fusion proteins exhibit a global impairment in axonal protein synthesis, an increase in oxidative stress, and defects in presynaptic function and electrical activity. These changes correlate with deregulation of axonal levels of polysome-engaged mRNAs playing relevant roles in the same processes. Our data support the emerging notion that deregulation of mRNA metabolism and of axonal mRNA transport may trigger the dying-back neuropathy that initiates motor neuron degeneration in ALS