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  • 1
    Online Resource
    Online Resource
    The Complexity of the Human–Animal Bond: Empathy, Attachment and Anthropomorphism in Human–Animal Relationships and Animal Hoarding
    MDPI AG ; 2022
    In:  Animals Vol. 12, No. 20 ( 2022-10-19), p. 2835-
    Details
    In: Animals, MDPI AG, Vol. 12, No. 20 ( 2022-10-19), p. 2835-
    Abstract: The human–animal relationship is ancient, complex and multifaceted. It may have either positive effects on humans and animals or poor or even negative and detrimental effects on animals or both humans and animals. A large body of literature has investigated the beneficial effects of this relationship in which both human and animals appear to gain physical and psychological benefits from living together in a reciprocated interaction. However, analyzing the literature with a different perspective it clearly emerges that not rarely are human–animal relationships characterized by different forms and levels of discomfort and suffering for animals and, in some cases, also for people. The negative physical and psychological consequences on animals’ well-being may be very nuanced and concealed, but there are situations in which the negative consequences are clear and striking, as in the case of animal violence, abuse or neglect. Empathy, attachment and anthropomorphism are human psychological mechanisms that are considered relevant for positive and healthy relationships with animals, but when dysfunctional or pathological determine physical or psychological suffering, or both, in animals as occurs in animal hoarding. The current work reviews some of the literature on the multifaceted nature of the human–animal relationship; describes the key role of empathy, attachment and anthropomorphism in human–animal relationships; seeks to depict how these psychological processes are distorted and dysfunctional in animal hoarding, with highly detrimental effects on both animal and human well-being.
    Type of Medium: Online Resource
    ISSN: 2076-2615
    URL: Article
    DOI: 10.3390/ani12202835
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2606558-7
    SSG: 23
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  • 2
    Online Resource
    Online Resource
    KMT2A: Umbrella Gene for Multiple Diseases
    MDPI AG ; 2022
    In:  Genes Vol. 13, No. 3 ( 2022-03-15), p. 514-
    Details
    In: Genes, MDPI AG, Vol. 13, No. 3 ( 2022-03-15), p. 514-
    Abstract: KMT2A (Lysine methyltransferase 2A) is a member of the epigenetic machinery, encoding a lysine methyltransferase responsible for the transcriptional activation through lysine 4 of histone 3 (H3K4) methylation. KMT2A has a crucial role in gene expression, thus it is associated to pathological conditions when found mutated. KMT2A germinal mutations are associated to Wiedemann–Steiner syndrome and also in patients with initial clinical diagnosis of several other chromatinopathies (i.e., Coffin–Siris syndromes, Kabuki syndrome, Cornelia De Lange syndrome, Rubinstein–Taybi syndrome), sharing an overlapping phenotype. On the other hand, KMT2A somatic mutations have been reported in several tumors, mainly blood malignancies. Due to its evolutionary conservation, the role of KMT2A in embryonic development, hematopoiesis and neurodevelopment has been explored in different animal models, and in recent decades, epigenetic treatments for disorders linked to KMT2A dysfunction have been extensively investigated. To note, pharmaceutical compounds acting on tumors characterized by KMT2A mutations have been formulated, and even nutritional interventions for chromatinopathies have become the object of study due to the role of microbiota in epigenetic regulation.
    Type of Medium: Online Resource
    ISSN: 2073-4425
    URL: Article
    DOI: 10.3390/genes13030514
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527218-4
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  • 3
    Online Resource
    Online Resource
    Single-Cell RNA Sequencing for the Detection of Clonotypic V(D)J Rearrangements in Multiple Myeloma
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 24 ( 2022-12-10), p. 15691-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 24 ( 2022-12-10), p. 15691-
    Abstract: Multiple myeloma (MM) has a highly heterogeneous genetic background, which complicates its molecular tracking over time. Nevertheless, each MM patient’s malignant plasma cells (PCs) share unique V(D)J rearranged sequences at immunoglobulin loci, which represent ideal disease biomarkers. Because the tumor-specific V(D)J sequence is highly expressed in bulk RNA in MM patients, we wondered whether it can be identified by single-cell RNA sequencing (scRNA-seq). To this end we analyzed CD138+ cells purified from bone marrow aspirates of 19 samples with PC dyscrasias by both a standard method based on bulk DNA and by an implementation of the standard 10x Genomics protocol to detect expressed V(D)J sequences. A dominant clonotype was easily identified in each sample, accounting on average for 83.65% of V(D)J-rearranged cells. Compared with standard methods, scRNA-seq analysis proved highly concordant and even more effective in identifying clonal productive rearrangements, by-passing limitations related to the misannealing of consensus primers in hypermutated regions. We next validated its accuracy to track 5 clonal cells with absolute sensitivity in a virtual sample containing 3180 polyclonal cells. This shows that single-cell V(D)J analysis may be used to find rare clonal cells, laying the foundations for functional single-cell dissection of minimal residual disease.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms232415691
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Insights into the Role of the Microbiota and of Short-Chain Fatty Acids in Rubinstein–Taybi Syndrome
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 7 ( 2021-03-31), p. 3621-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 7 ( 2021-03-31), p. 3621-
    Abstract: The short-chain fatty acid butyrate, produced by the gut microbiota, acts as a potent histone deacetylase (HDAC) inhibitor. We assessed possible ameliorative effects of butyrate, relative to other HDAC inhibitors, in in vitro and in vivo models of Rubinstein–Taybi syndrome (RSTS), a severe neurodevelopmental disorder caused by variants in the genes encoding the histone acetyltransferases CBP and p300. In RSTS cell lines, butyrate led to the patient-specific rescue of acetylation defects at subtoxic concentrations. Remarkably, we observed that the commensal gut microbiota composition in a cohort of RSTS patients is significantly depleted in butyrate-producing bacteria compared to healthy siblings. We demonstrate that the effects of butyrate and the differences in microbiota composition are conserved in a Drosophila melanogaster mutant for CBP, enabling future dissection of the gut–host interactions in an in vivo RSTS model. This study sheds light on microbiota composition in a chromatinopathy, paving the way for novel therapeutic interventions.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22073621
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 5
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    Online Resource
    Candida albicans Biofilm Inhibition by Two Vaccinium macrocarpon (Cranberry) Urinary Metabolites: 5-(3′,4′-DihydroxyPhenyl)-γ-Valerolactone and 4-Hydroxybenzoic Acid
    MDPI AG ; 2021
    In:  Microorganisms Vol. 9, No. 7 ( 2021-07-13), p. 1492-
    Details
    In: Microorganisms, MDPI AG, Vol. 9, No. 7 ( 2021-07-13), p. 1492-
    Abstract: Candida spp. are pathobionts, as they can switch from commensals to pathogens, responsible for a variety of pathological processes. Adhesion to surfaces, morphological switch and biofilm-forming ability are the recognized virulence factors promoting yeast virulence. Sessile lifestyle also favors fungal persistence and antifungal tolerance. In this study, we investigated, in vitro, the efficacy of two urinary cranberry metabolites, 5-(3′,4′-dihydroxy phenyl)-γ-valerolactone (VAL) and 4-hydroxybenzoic acid (4-HBA), in inhibiting C. albicans adhesion and biofilm formation. Both the reference strain SC5314 and clinical isolates were used. We evaluated biomass reduction, by confocal microscopy and crystal violet assay, and the possible mechanisms mediating their inhibitory effects. Both VAL and 4-HBA were able to interfere with the yeast adhesion, by modulating the expression of key genes, HWP1 and ALS3. A significant dose-dependent reduction in biofilm biomass and metabolic activity was also recorded. Our data showed that the two cranberry metabolites VAL and 4-HBA could pave the way for drug development, for targeting the very early phases of biofilm formation and for preventing genitourinary Candida infections.
    Type of Medium: Online Resource
    ISSN: 2076-2607
    URL: Article
    DOI: 10.3390/microorganisms9071492
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2720891-6
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  • 6
    Online Resource
    Online Resource
    NEAT1 Long Isoform Is Highly Expressed in Chronic Lymphocytic Leukemia Irrespectively of Cytogenetic Groups or Clinical Outcome
    MDPI AG ; 2020
    In:  Non-Coding RNA Vol. 6, No. 1 ( 2020-03-13), p. 11-
    Details
    In: Non-Coding RNA, MDPI AG, Vol. 6, No. 1 ( 2020-03-13), p. 11-
    Abstract: The biological role and therapeutic potential of long non-coding RNAs (lncRNAs) in chronic lymphocytic leukemia (CLL) are still open questions. Herein, we investigated the significance of the lncRNA NEAT1 in CLL. We examined NEAT1 expression in 310 newly diagnosed Binet A patients, in normal CD19+ B-cells, and other types of B-cell malignancies. Although global NEAT1 expression level was not statistically different in CLL cells compared to normal B cells, the median ratio of NEAT1_2 long isoform and global NEAT1 expression in CLL samples was significantly higher than in other groups. NEAT1_2 was more expressed in patients carrying mutated IGHV genes. Concerning cytogenetic aberrations, NEAT1_2 expression in CLL with trisomy 12 was lower with respect to patients without alterations. Although global NEAT1 expression appeared not to be associated with clinical outcome, patients with the lowest NEAT1_2 expression displayed the shortest time to first treatment; however, a multivariate regression analysis showed that the NEAT1_2 risk model was not independent from other known prognostic factors, particularly the IGHV mutational status. Overall, our data prompt future studies to investigate whether the increased amount of the long NEAT1_2 isoform detected in CLL cells may have a specific role in the pathology of the disease.
    Type of Medium: Online Resource
    ISSN: 2311-553X
    URL: Article
    DOI: 10.3390/ncrna6010011
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2813993-8
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  • 7
    Online Resource
    Online Resource
    Germline NUP98 Variants in Two Siblings with a Rothmund–Thomson-Like Spectrum: Protein Functional Changes Predicted by Molecular Modeling
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 4 ( 2023-02-16), p. 4028-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 4 ( 2023-02-16), p. 4028-
    Abstract: Two adult siblings born to first-cousin parents presented a clinical phenotype reminiscent of Rothmund–Thomson syndrome (RTS), implying fragile hair, absent eyelashes/eyebrows, bilateral cataracts, mottled pigmentation, dental decay, hypogonadism, and osteoporosis. As the clinical suspicion was not supported by the sequencing of RECQL4, the RTS2-causative gene, whole exome sequencing was applied and disclosed the homozygous variants c.83G 〉 A (p.Gly28Asp) and c.2624A 〉 C (p.Glu875Ala) in the nucleoporin 98 (NUP98) gene. Though both variants affect highly conserved amino acids, the c.83G 〉 A looked more intriguing due to its higher pathogenicity score and location of the replaced amino acid between phenylalanine-glycine (FG) repeats within the first NUP98 intrinsically disordered region. Molecular modeling studies of the mutated NUP98 FG domain evidenced a dispersion of the intramolecular cohesion elements and a more elongated conformational state compared to the wild type. This different dynamic behavior may affect the NUP98 functions as the minor plasticity of the mutated FG domain undermines its role as a multi-docking station for RNA and proteins, and the impaired folding can lead to the weakening or the loss of specific interactions. The clinical overlap of NUP98-mutated and RTS2/RTS1 patients, accounted by converging dysregulated gene networks, supports this first-described constitutional NUP98 disorder, expanding the well-known role of NUP98 in cancer.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms24044028
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 8
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    Online Resource
    The Potential Role of SARS-CoV-2 Infection and Vaccines in Multiple Sclerosis Onset and Reactivation: A Case Series and Literature Review
    MDPI AG ; 2023
    In:  Viruses Vol. 15, No. 7 ( 2023-07-18), p. 1569-
    Details
    In: Viruses, MDPI AG, Vol. 15, No. 7 ( 2023-07-18), p. 1569-
    Abstract: The recent SARS-CoV-2 pandemic and related vaccines have raised several issues. Among them, the potential role of the viral infection (COVID-19) or anti-SARS-CoV-2 vaccines as causal factors of dysimmune CNS disorders, as well as the safety and efficacy of vaccines in patients affected by such diseases and on immune-active treatments have been analyzed. The aim is to better understand the relationship between SARS-CoV-2 infection/vaccines with dysimmune CNS diseases by describing 12 cases of multiple sclerosis/myelitis onset or reactivation after exposure to SARS-CoV-2 infection/vaccines and reviewing all published case reports or case series in which MS onset or reactivation was temporally associated with either COVID-19 (8 case reports, 3 case series) or anti-SARS-CoV-2 vaccines (13 case reports, 6 case series). All the cases share a temporal association between viral/vaccine exposure and symptoms onset. This finding, together with direct or immune-based mechanisms described both during COVID-19 and MS, claims in favor of a role for SARS-CoV-2 infection/vaccines in unmasking dysimmune CNS disorders. The most common clinical presentations involve the optic nerve, brainstem and spinal cord. The preferential tropism of the virus together with the presence of some host-related genetic/immune factors might predispose to the involvement of specific CNS districts.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v15071569
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2516098-9
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  • 9
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    Online Resource
    From Shunt to Recovery: A Multidisciplinary Approach to Hydrocephalus Treatment in Severe Acquired Brain Injury Rehabilitation
    MDPI AG ; 2021
    In:  Brain Sciences Vol. 12, No. 1 ( 2021-12-21), p. 3-
    Details
    In: Brain Sciences, MDPI AG, Vol. 12, No. 1 ( 2021-12-21), p. 3-
    Abstract: Background: Hydrocephalus among Severe Acquired Brain Injury (SABI) patients remains overlooked during rehabilitation. Methods: A retrospective cohort study was carried out of traumatic and non-traumatic SABI patients with hydrocephalus, consecutively admitted over 9 years in a tertiary referral specialized rehabilitation hospital. Patients were treated with ventriculoperitoneal shunt before or during inpatient rehabilitation and assessed using the Level of Cognitive Functioning Scale and Disability Rating Scale. Logistic regression models were used to identify predictors of post-surgical complications. Linear regression models were used to investigate predictors of hospital length of stay (LOS), disability, and cognitive function. Results: Of the 82 patients, 15 had post-surgical complications and 16 underwent cranioplasty. Shunt placement complication risk was higher when fixed vs. when programmable pressure valves were used. A total of 56.3% achieved functional improvement at discharge and 88.7% improved in cognitive function; of the 82 patients, 56% were discharged home. In multiple regression analyses, higher disability at discharge was related to cranioplasty and longer LOS, while poorer cognitive function was associated with cranioplasty. Increase in LOS was associated with increasing time to shunt and decreasing age. Conclusions: A significant improvement in cognitive and functional outcomes can be achieved. Cranioplasty increased LOS, and fixed pressure valves were related to poorer outcomes.
    Type of Medium: Online Resource
    ISSN: 2076-3425
    URL: Article
    DOI: 10.3390/brainsci12010003
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2651993-8
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  • 10
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    Online Resource
    A New Clinical Protocol for a Timely Diagnosis and Treatment of Hydrocephalus in Patients with Severe Acquired Brain Injury
    MDPI AG ; 2023
    In:  Brain Sciences Vol. 13, No. 7 ( 2023-07-13), p. 1067-
    Details
    In: Brain Sciences, MDPI AG, Vol. 13, No. 7 ( 2023-07-13), p. 1067-
    Abstract: Background: Secondary hydrocephalus is a well-known complication of severe acquired brain injuries (sABIs) often diagnosed during inpatient rehabilitation. Currently, there is no gold standard for its detection. Therefore, we designed a novel clinical diagnostic protocol that integrates clinical, functional, biochemical and neuroradiological assessments to improve the accuracy of its diagnosis in patients with sABIs. Methods: This prospective cohort study will be conducted in a tertiary referral rehabilitation center in Italy. A historical cohort of patients will be compared with a prospective cohort undergoing the new clinical diagnostic protocol. Expected Results: The expected results include an increase in the proportion of diagnosed cases, a reduced incidence of clinical complications, an increase in the rehabilitative outcomes at discharge, a significant reduction in the length of hospital stay, and useful information about the diagnostic and prognostic value of the neuroradiological characteristics. Conclusion: We expect that this clinical diagnostic protocol will result in a more appropriate assessment and timely treatment of secondary hydrocephalus in patients with sABIs, with the ultimate goal of improving their prognosis. In addition, it could be adopted by other rehabilitation centers to improve hydrocephalus diagnosis and treatment, thereby reducing the length of hospital stay and accelerating recovery with benefits for both patients and hospitals.
    Type of Medium: Online Resource
    ISSN: 2076-3425
    URL: Article
    DOI: 10.3390/brainsci13071067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2651993-8
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