Phase Diagram Detection via Gaussian Fitting of Number Probability Distribution

We investigate the number probability density function that characterizes sub-portions of a quantum many-body system with globally conserved number of particles. We put forward a linear fitting protocol capable of mapping out the ground-state phase diagram of the rich one-dimensional extended Bose-Hubbard model: The results are quantitatively comparable with more sophisticated traditional and machine learning techniques. We argue that the studied quantity should be considered among the most informative bipartite properties, being moreover readily accessible in atomic gases experiments

Diverse reductive dehalogenases are associated with Clostridiales-enriched microcosms dechlorinating 1,2-dichloroethane

The achievement of successful biostimulation of active microbiomes for the cleanup of a polluted site is strictly dependent on the knowledge of the key microorganisms equipped with the relevant catabolic genes responsible for the degradation process. In this work, we present the characterization of the bacterial community developed in anaerobic microcosms after biostimulation with the electron donor lactate of groundwater polluted with 1,2-dichloroethane (1,2-DCA). Through a multilevel analysis, we have assessed (i) the structural analysis of the bacterial community; (ii) the identification of putative dehalorespiring bacteria; (iii) the characterization of functional genes encoding for putative 1,2-DCA reductive dehalogenases (RDs). Following the biostimulation treatment, the structure of the bacterial community underwent a notable change of the main phylotypes, with the enrichment of representatives of the order Clostridiales. Through PCR targeting conserved regions within known RD genes, four novel variants of RDs previously associated with the reductive dechlorination of 1,2-DCA were identified in the metagenome of the Clostridiales-dominated bacterial community

A Novel Family with Demyelinating Charcot–Marie–Tooth Disease Caused by a Mutation in the PMP2 Gene: A Case Series of Nine Patients and a Brief Review of the Literature

Introduction: Charcot-Marie-Tooth (CMT) is a group of inherited peripheral neuropathies characterized by wide genotypic and phenotypic variability. The onset is typically in childhood, and the most frequent clinical manifestations are predominantly distal muscle weakness, hypoesthesia, foot deformity (pes cavus) and areflexia. In the long term, complications such as muscle-tendon retractions, extremity deformities, muscle atrophy and pain may occur. Among CMT1, demyelinating and autosomal dominant forms, CMT1G is determined by mutations in the PMP2 myelin protein. Results: Starting from the index case, we performed a clinical, electrophysiological, neuroradiological and genetic evaluation of all family members for three generations; we identified p.Ile50del in PMP2 in all the nine affected members. They presented a typical clinical phenotype, with childhood-onset variable severity between generations and a chronic demyelinating sensory-motor polyneuropathy on the electrophysiologic examination; the progression was slow to very slow and predominant in the lower limbs. Our study reports a relatively large sample of patients, members of the same family, with CMT1G by PMP2, which is a rare form of demyelinating CMT, highlighting the genetic variability of the CMT family instead of the overlapping clinical phenotypes within demyelinating forms. To date, only supportive and preventive measures for the most severe complications are available; therefore, we believe that early diagnosis (clinical, electrophysiological and genetic) allows access to specialist follow-up and therapies, thereby improving the quality of life of patients

Horizontal transmission of the symbiotic bacterium Asaia sp. in the leafhopper Scaphoideus titanus Ball (Hemiptera: Cicadellidae)

<p>Abstract</p> <p>Background</p> <p>Bacteria of the genus <it>Asaia</it> have been recently recognized as secondary symbionts of different sugar-feeding insects, including the leafhopper <it>Scaphoideus titanus</it>, vector of Flavescence dorée phytoplasmas. <it>Asaia</it> has been shown to be localized in <it>S. titanus</it> gut, salivary glands and gonoducts and to be maternally transmitted to the progeny by an egg smearing mechanism. It is currently not known whether <it>Asaia</it> in <it>S. titanus</it> is transmitted by additional routes. We performed a study to evaluate if <it>Asaia</it> infection is capable of horizontal transmission <it>via</it> co-feeding and venereal routes.</p> <p>Results</p> <p>A Gfp-tagged strain of <it>Asaia</it> was provided to <it>S. titanus</it> individuals to trace the transmission pathways of the symbiotic bacterium. Co-feeding trials showed a regular transfer of bacterial cells from donors to recipients, with a peak of frequency after 72 hours of exposure, and with concentrations of the administrated strain growing over time. Venereal transmission experiments were first carried out using infected males paired with uninfected females. In this case, female individuals acquired Gfp-labelled <it>Asaia</it>, with highest infection rates 72-96 hours after mating and with increasing abundance of the tagged symbiont over time. When crosses between infected females and uninfected males were conducted, the occurrence of “female to male” transmission was observed, even though the transfer occurred unevenly.</p> <p>Conclusions</p> <p>The data presented demonstrate that the acetic acid bacterial symbiont <it>Asaia</it> is horizontally transmitted among <it>S</it>. <it>titanus</it> individuals both by co-feeding and venereal transmission, providing one of the few direct demonstrations of such a symbiotic transfer in Hemiptera. This study contributes to the understanding of the bacterial ecology in the insect host, and indicates that <it>Asaia</it> evolved multiple pathways for the colonization of <it>S</it>. <it>titanus</it> body.</p

Metadynamics Simulations Distinguish Short- and Long-Residence-Time Inhibitors of Cyclin-Dependent Kinase 8.

The duration of drug efficacy in vivo is a key aspect primarily addressed during the lead optimization phase of drug discovery. Hence, the availability of robust computational approaches that can predict the residence time of a compound at its target would accelerate candidate selection. Nowadays the theoretical prediction of this parameter is still very challenging. Starting from methods reported in the literature, we set up and validated a new metadynamics (META-D)-based protocol that was used to rank the experimental residence times of 10 arylpyrazole cyclin-dependent kinase 8 (CDK8) inhibitors for which target-bound X-ray structures are available. The application of reported methods based on the detection of the escape from the first free energy well gave a poor correlation with the experimental values. Our protocol evaluates the energetics of the whole unbinding process, accounting for multiple intermediates and transition states. Using seven collective variables (CVs) encoding both roto-translational and conformational motions of the ligand, a history-dependent biasing potential is deposited as a sum of constant-height Gaussian functions until the ligand reaches an unbound state. The time required to achieve this state is proportional to the integral of the deposited potential over the CV hyperspace. Average values of this time, for replicated META-D simulations, provided an accurate classification of CDK8 inhibitors spanning short, medium, and long residence times

Genuine Memory Deficits as Assessed by the Free and Cued Selective Reminding Test (FCSRT) in the Behavioural Variant of Frontotemporal Dementia. A Systematic Review and Meta-analysis Study

The current diagnostic criteria for the behavioural variant of frontotemporal dementia (bvFTD) foresee a relative sparing of long-term memory. Although bvFTD patients were thought to report secondary memory deficits associated with prefrontal dysfunctions, some studies indicated the presence of a "genuine memory deficit" related to mesial temporal lobe dysfunctions. Among various neuropsychological tests, the Free and Cue Selective Reminding Test (FCSRT) has been recommended to distinguish genuine from apparent amnesia. We conducted a systematic review and a random effect Bayesian meta-analysis to evaluate the nature and severity of memory deficit in bvFTD. Our objective was to determine whether the existing literature offers evidence of genuine or apparent amnesia in patients with bvFTD, as assessed via the FCSRT. On 06/19/2021, we conducted a search across four databases (PMC, Scopus, Web of Science, and PubMed). We included all studies that evaluated memory performance using the FCSRT in patients with bvFTD, as long as they also included either cognitively unimpaired participants or AD groups. We tested publication bias through the Funnel plot and Egger's test. To assess the quality of studies, we used the Newcastle-Ottawa quality assessment scale adapted for cross-sectional studies. We included 16 studies in the meta-analysis. The results showed that bvFTD patients perform better than AD patients (pooled effects between 0.95 and 1.14), as their memory performance stands between AD and control groups (pooled effects between - 2.19 and - 1.25). Moreover, patients with bvFTD present both genuine and secondary memory disorders. As a major limitation of this study, due to our adoption of a rigorous methodology and stringent inclusion criteria, we ended up with just 16 studies. Nonetheless, our robust findings can contribute to the ongoing discussion on international consensus criteria for bvFTD and the selection of appropriate neuropsychological tools to facilitate the differential diagnosis between AD and bvFTD

Infantile-Onset Charcot–Marie–Tooth Disease With Pyramidal Features and White Matter Abnormalities Due to a De novo MORC2 Gene Variant: A Case Report and Brief Review of the Literature

Background: Charcot–Marie–Tooth (CMT) is the most frequent group of inherited neuropathies and includes several heterogeneous phenotypes. Over 80 causative genes have been described so far. Variants in the microrchidia family CW-type zinc finger 2 (MORC2) gene have been described in several axonal polyneuropathy (CMT2) patients with childhood or adult onset. Occasionally more complex phenotypes with delayed milestones, severe hypotonia, intellectual disability, dystonic postures, pyramidal signs, and neuroimaging abnormalities have been reported. Case Presentation: We report on a patient with a de novo MORC2 gene variant (c.1181A&gt;G p.Tyr394Cys) with a history of developmental delay, axial hypotonia, progressive gait disorder with dystonic features, and intentional tremor. At the age of 8 years, he showed bilateral pyramidal signs (clonus, increased tendon reflexes, and Babinski sign) and bilateral pes cavus. The first neuroimaging performed at the age of 3 years demonstrated white matter abnormalities in the posterior periventricular zone, in the frontal lobes bilaterally and at the midbrain, stable during childhood and adolescence. Nerve conduction studies (NCS) were negative until the age of 15 years, when a sensory axonal neuropathy appeared. The association between pyramidal signs and neuropathy due to the MORC2 gene variant is increasingly being highlighted, although a neuroradiological correlate is evident only in about half of the cases. Longitudinal nerve conduction velocity (NCV) are helpful to identify late-onset features and provide useful information for diagnosis in patients with rare neurogenetic disorders. Conclusions: Characterization of complex neurological disorders is important to delineate the expanding phenotypic spectrum of MORC2-related disease, to confirm if possible the pathogenicity of the variants and to deepen the genotype–phenotype correlation

Association of Tricuspid Regurgitation With Outcome in Acute Heart Failure

Background: Tricuspid regurgitation (TR) is common in chronic heart failure (HF) and is associated with negative prognosis. However, evidence on prognostic implications of TR in acute HF is lacking. We sought to investigate the association between TR and mortality and the interaction with pulmonary hypertension (PH) in patients admitted for acute HF. Methods: We enrolled 1176 consecutive patients with a primary diagnosis of acute HF and with available noninvasive estimation of TR and pulmonary arterial systolic pressure. Results: Moderate-severe TR was present in 352 patients (29.9%) and was associated with older age and more comorbidities. The prevalence of PH (ie, pulmonary arterial systolic pressure >40 mm Hg), right ventricular dysfunction, and mitral regurgitation was higher in moderate-severe TR. At 1 year, 184 (15.6%) patients died. Moderate-severe TR was associated with higher 1-year mortality risk after adjustment for other echocardiographic parameters (pulmonary arterial systolic pressure, left ventricle ejection fraction, right ventricular dysfunction, mitral regurgitation, left and right atrial indexed volumes; hazard ratio, 1.718; P=0.009), and the association with outcome was maintained when clinical variables (eg, natriuretic peptides, serum creatinine and urea, systolic blood pressure, atrial fibrillation) were added to the multivariable model (hazard ratio, 1.761; P=0.024). The association between moderate-severe TR and outcome was consistent in patients with versus without PH, with versus without right ventricular dysfunction, and with versus without left ventricle ejection fraction <50%. Patients with coexistent moderate-severe TR and PH had 3-fold higher 1-year mortality risk compared with patients with no TR or PH (hazard ratio, 3.024; P<0.001). Conclusions: In patients hospitalized for acute HF, the severity of TR is associated with 1-year survival, regardless of the presence of PH. The coexistence of moderate-severe TR and estimated PH was associated with a further increase in mortality risk. Our data must be interpreted in the context of potential underestimation of pulmonary arterial systolic pressure in patients with severe TR