Lack of nuclear clusters in dwarf spheroidal galaxies: implications for massive black holes formation and the cusp/core problem

One of the leading scenarios for the formation of nuclear star clusters in galaxies is related to the orbital decay of globular clusters (GCs) and their subsequent merging, though alternative theories are currently debated. The availability of high-quality data for structural and orbital parameters of GCs allows us to test different nuclear star cluster formation scenarios. The Fornax dwarf spheroidal (dSph) galaxy is the heaviest satellite of the Milky Way and it is the only known dSph hosting five GCs, whereas there are no clear signatures for the presence of a central massive black hole. For this reason, it represents a suited place to study the orbital decay process in dwarf galaxies. In this paper, we model the future evolution of the Fornax GCs simulating them and the host galaxy by means of direct N-body simulations. Our simulations also take into account the gravitational field generated by the MilkyWay. We found that if the Fornax galaxy is embedded in a standard cold dark matter halo, the nuclear cluster formation would be significantly hampered by the high central galactic mass density. In this context, we discuss the possibility that infalling GCs drive the flattening of the galactic density profile, giving a possible alternative explanation to the so-called cusp/core problem. Moreover, we briefly discuss the link between GC infall process and the absence of massive black holes in the centre of dSphs

The interaction between supermassive black holes and globular clusters

Almost all galaxies along the Hubble sequence host a compact massive object (CMO) in their center. The CMO can be either a supermassive black hole (SMBH) or a very dense stellar cluster, also known as nuclear star cluster (NSC). Generally, heavier galaxies (mass ≳ 1011M⊙) host a central SMBH while lighter show a central NSC. Intermediate mass hosts, instead, contain both a NSC and a SMBH. One possible formation mechanisms of a NSC relies on the dry-merger (migratory) scenario, in which globular clusters (GCs) decay toward the center of the host galaxy and merge. In this framework, the absence of NSCs in high-mass galaxies can be imputed to destruction of the infalling GCs by the intense tidal field of the central SMBH. In this work, we report preliminary results of N-body simulations performed using our high-resolution, direct, code HiGPUs, to investigate the effects of a central SMBH on a single GC orbiting around it. By varying either the mass of the SMBH and the mass of the host galaxy, we derived an upper limit to the mass of the central SMBH, and thus to the mass of the host, above which the formation of a NSC is suppressed

Applicazione del laser scanner terrestre per la valutazione della condizione delle chiome in Quercus suber L.

The objective of this paper is to show the first results on the evaluation of the possible use of this technique for the estimation of crown condition in cork oak stands (Quercus suber L.). The results show that the TLS (Terrestrial laser Scanner) technology has good potential applications for the deciduous woodlands. The next objective will be to evaluate the performance of this approach in the estimation of the damage caused by insects

Using terrestrial LiDAR for monitoring canopy structure in cork oak trees

The main aim of this work was to assess the capabilities of terrestrial laser scanner in measuring both changes by the time and differences among trees of canopy characteristics of Quercus suber L. (cork oak) plants

Characterisation of patients with familial chylomicronaemia syndrome (FCS) and multifactorial chylomicronaemia syndrome (MCS): establishment of an FCS clinical diagnostic score

Data presented in this article are supplementary material to our article entitled "Identification and diagnosis of patients with familial chylomicronaemia syndrome (FCS): expert panel recom mendations and proposal of an "FCS Score" (Moulin et al., 2018, in press). The data describe the genotypes of patients with familial chylomicronaemia syndrome (FCS) and multifactorial chylomicro naemia syndrome (MCS), from the validation and replication cohorts

The effect of mission duration on LISA science objectives

The science objectives of the LISA mission have been defined under the implicit assumption of a 4-years continuous data stream. Based on the performance of LISA Pathfinder, it is now expected that LISA will have a duty cycle of ≈0.75 , which would reduce the effective span of usable data to 3 years. This paper reports the results of a study by the LISA Science Group, which was charged with assessing the additional science return of increasing the mission lifetime. We explore various observational scenarios to assess the impact of mission duration on the main science objectives of the mission. We find that the science investigations most affected by mission duration concern the search for seed black holes at cosmic dawn, as well as the study of stellar-origin black holes and of their formation channels via multi-band and multi-messenger observations. We conclude that an extension to 6 years of mission operations is recommended.publishedVersio

Spectrum of mutations in Italian patients with familial hypercholesterolemia: New results from the LIPIGEN study

Background Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by elevated plasma levels of LDL-cholesterol that confers an increased risk of premature atherosclerotic cardiovascular disease. Early identification and treatment of FH patients can improve prognosis and reduce the burden of cardiovascular mortality. Aim of this study was to perform the mutational analysis of FH patients identified through a collaboration of 20 Lipid Clinics in Italy (LIPIGEN Study). Methods We recruited 1592 individuals with a clinical diagnosis of definite or probable FH according to the Dutch Lipid Clinic Network criteria. We performed a parallel sequencing of the major candidate genes for monogenic hypercholesterolemia (LDLR, APOB, PCSK9, APOE, LDLRAP1, STAP1). Results A total of 213 variants were detected in 1076 subjects. About 90% of them had a pathogenic or likely pathogenic variants. More than 94% of patients carried pathogenic variants in LDLR gene, 27 of which were novel. Pathogenic variants in APOB and PCSK9 were exceedingly rare. We found 4 true homozygotes and 5 putative compound heterozygotes for pathogenic variants in LDLR gene, as well as 5 double heterozygotes for LDLR/APOB pathogenic variants. Two patients were homozygous for pathogenic variants in LDLRAP1 gene resulting in autosomal recessive hypercholesterolemia. One patient was found to be heterozygous for the ApoE variant p.(Leu167del), known to confer an FH phenotype. Conclusions This study shows the molecular characteristics of the FH patients identified in Italy over the last two years. Full phenotypic characterization of these patients and cascade screening of family members is now in progress

Lipoprotein(a) Genotype Influences the Clinical Diagnosis of Familial Hypercholesterolemia

: Background Evidence suggests that LPA risk genotypes are a possible contributor to the clinical diagnosis of familial hypercholesterolemia (FH). This study aimed at determining the prevalence of LPA risk variants in adult individuals with FH enrolled in the Italian LIPIGEN (Lipid Transport Disorders Italian Genetic Network) study, with (FH/M+) or without (FH/M-) a causative genetic variant. Methods and Results An lp(a) [lipoprotein(a)] genetic score was calculated by summing the number risk-increasing alleles inherited at rs3798220 and rs10455872 variants. Overall, in the 4.6% of 1695 patients with clinically diagnosed FH, the phenotype was not explained by a monogenic or polygenic cause but by genotype associated with high lp(a) levels. Among 765 subjects with FH/M- and 930 subjects with FH/M+, 133 (17.4%) and 95 (10.2%) were characterized by 1 copy of either rs10455872 or rs3798220 or 2 copies of either rs10455872 or rs3798220 (lp(a) score ≥1). Subjects with FH/M- also had lower mean levels of pretreatment low-density lipoprotein cholesterol than individuals with FH/M+ (t test for difference in means between FH/M- and FH/M+ groups <0.0001); however, subjects with FH/M- and lp(a) score ≥1 had higher mean (SD) pretreatment low-density lipoprotein cholesterol levels (223.47 [50.40] mg/dL) compared with subjects with FH/M- and lp(a) score=0 (219.38 [54.54] mg/dL for), although not statistically significant. The adjustment of low-density lipoprotein cholesterol levels based on lp(a) concentration reduced from 68% to 42% the proportion of subjects with low-density lipoprotein cholesterol level ≥190 mg/dL (or from 68% to 50%, considering a more conservative formula). Conclusions Our study supports the importance of measuring lp(a) to perform the diagnosis of FH appropriately and to exclude that the observed phenotype is driven by elevated levels of lp(a) before performing the genetic test for FH

Refinement of the diagnostic approach for the identification of children and adolescents affected by familial hypercholesterolemia: Evidence from the LIPIGEN study

Background and aims: We aimed to describe the limitations of familiar hypercholesterolemia (FH) diagnosis in childhood based on the presence of the typical features of FH, such as physical sings of cholesterol accumulation and personal or family history of premature cardiovascular disease or hypercholesterolemia, comparing their prevalence in the adult and paediatric FH population, and to illustrate how additional information can lead to a more effective diagnosis of FH at a younger age.Methods: From the Italian LIPIGEN cohort, we selected 1188 (>= 18 years) and 708 (<18 years) genetically-confirmed heterozygous FH, with no missing personal FH features. The prevalence of personal and familial FH features was compared between the two groups. For a sub-group of the paediatric cohort (N = 374), data about premature coronary heart disease (CHD) in second-degree family members were also included in the evaluation.Results: The lower prevalence of typical FH features in children/adolescents vs adults was confirmed: the prevalence of tendon xanthoma was 2.1% vs 13.1%, and arcus cornealis was present in 1.6% vs 11.2% of the cohorts, respectively. No children presented clinical history of premature CHD or cerebral/peripheral vascular disease compared to 8.8% and 5.6% of adults, respectively. The prevalence of premature CHD in first-degree relatives was significantly higher in adults compared to children/adolescents (38.9% vs 19.7%). In the sub-cohort analysis, a premature CHD event in parents was reported in 63 out of 374 subjects (16.8%), but the percentage increased to 54.0% extending the evaluation also to second-degree relatives.Conclusions: In children, the typical FH features are clearly less informative than in adults. A more thorough data collection, adding information about second-degree relatives, could improve the diagnosis of FH at younger age

Twelve Variants Polygenic Score for Low-Density Lipoprotein Cholesterol Distribution in a Large Cohort of Patients With Clinically Diagnosed Familial Hypercholesterolemia With or Without Causative Mutations

: Background A significant proportion of individuals clinically diagnosed with familial hypercholesterolemia (FH), but without any disease-causing mutation, are likely to have polygenic hypercholesterolemia. We evaluated the distribution of a polygenic risk score, consisting of 12 low-density lipoprotein cholesterol (LDL-C)-raising variants (polygenic LDL-C risk score), in subjects with a clinical diagnosis of FH. Methods and Results Within the Lipid Transport Disorders Italian Genetic Network (LIPIGEN) study, 875 patients who were FH-mutation positive (women, 54.75%; mean age, 42.47±15.00 years) and 644 patients who were FH-mutation negative (women, 54.21%; mean age, 49.73±13.54 years) were evaluated. Patients who were FH-mutation negative had lower mean levels of pretreatment LDL-C than patients who were FH-mutation positive (217.14±55.49 versus 270.52±68.59 mg/dL, P<0.0001). The mean value (±SD) of the polygenic LDL-C risk score was 1.00 (±0.18) in patients who were FH-mutation negative and 0.94 (±0.20) in patients who were FH-mutation positive (P<0.0001). In the receiver operating characteristic analysis, the area under the curve for recognizing subjects characterized by polygenic hypercholesterolemia was 0.59 (95% CI, 0.56-0.62), with sensitivity and specificity being 78% and 36%, respectively, at 0.905 as a cutoff value. Higher mean polygenic LDL-C risk score levels were observed among patients who were FH-mutation negative having pretreatment LDL-C levels in the range of 150 to 350 mg/dL (150-249 mg/dL: 1.01 versus 0.91, P<0.0001; 250-349 mg/dL: 1.02 versus 0.95, P=0.0001). A positive correlation between polygenic LDL-C risk score and pretreatment LDL-C levels was observed among patients with FH independently of the presence of causative mutations. Conclusions This analysis confirms the role of polymorphisms in modulating LDL-C levels, even in patients with genetically confirmed FH. More data are needed to support the use of the polygenic score in routine clinical practice