Genome-wide scan for runs of homozygosity in South American Camelids

Background: Alpaca (Vicugna pacos), llama (Lama glama), vicugna (Vicugna vicugna) and guanaco (Lama guanicoe), are the camelid species distributed over the Andean high-altitude grasslands, the Altiplano, and the Patagonian arid steppes. Despite the wide interest on these animals, most of the loci under selection are still unknown. Using whole-genome sequencing (WGS) data we investigated the occurrence and the distribution of Runs Of Homozygosity (ROHs) across the South American Camelids (SACs) genome to identify the genetic relationship between the four species and the potential signatures of selection. Results: A total of 37 WGS samples covering the four species was included in the final analysis. The multi-dimensional scaling approach showed a clear separation between the four species; however, admixture analysis suggested a strong genetic introgression from vicugna and llama to alpaca. Conversely, very low genetic admixture of the guanaco with the other SACs was found. The four species did not show significant differences in the number, length of ROHs (100-500 kb) and genomic inbreeding values. Longer ROHs (> 500 kb) were found almost exclusively in alpaca. Seven overlapping ROHs were shared by alpacas, encompassing nine loci (FGF5, LOC107034918, PRDM8, ANTXR2, LOC102534792, BSN, LOC116284892, DAG1 and RIC8B) while nine overlapping ROHs were found in llama with twenty-five loci annotated (ERC2, FZD9, BAZ1B, BCL7B, LOC116284208, TBL2, MLXIPL, PHF20, TRNAD-AUC, LOC116284365, RBM39, ARFGEF2, DCAF5, EXD2, HSPB11, LRRC42, LDLRAD1, TMEM59, LOC107033213, TCEANC2, LOC102545169, LOC116278408, SMIM15, NDUFAF2 and RCOR1). Four overlapping ROHs, with three annotated loci (DLG1, KAT6B and PDE4D) and three overlapping ROHs, with seven annotated genes (ATP6V1E1, BCL2L13, LOC116276952, BID, KAT6B, LOC116282667 and LOC107034552), were detected for vicugna and guanaco, respectively. Conclusions: The signatures of selection revealed genomic areas potentially selected for production traits as well as for natural adaptation to harsh environment. Alpaca and llama hint a selection driven by environment as well as by farming purpose while vicugna and guanaco showed selection signals for adaptation to harsh environment. Interesting, signatures of selection on KAT6B gene were identified for both vicugna and guanaco, suggesting a positive effect on wild populations fitness. Such information may be of interest to further ecological and animal production studies

Factors associated with dog behavioral problems referred to a behavior clinic

Undesirable behaviors are common in the domestic dog population. This study aimed to identify similarities and differences in characteristics underlying 2 major groups of behavioral problems, and their treatment outcome. The study focused on 335 dogs that visited a Behavioral Clinic in northern Italy between 2013 and 2016. These cases were categorized into 2 broad groups based on the diagnosis: an \u201caggressive\u201d group (behavioral pathologies involving aggression) and an \u201canxious\u201d group (behavioral pathologies not primarily involving aggression). Each dog underwent a behavior consultation made by a veterinary specialist who used a basic history questionnaire focused on all aspects of dog's behavior, management, and health issue. Several variables were selected from the questionnaires collected. We found a statistical association of the behavioral problem with factors such as size, sex, age, time of onset, dogs' resting place, family composition, and mounting behaviors involving people (P 64 0.05). Small- and medium-sized dogs were mainly \u201canxious\u201d instead of \u201caggressive\u201d; male dogs were mostly \u201caggressive\u201d and female dogs (neutered and intact) were mainly \u201canxious\u201d; dogs adopted from pet shops were all anxious. On average, \u201caggressive\u201d dogs exhibited the problem 4 months after adoption. \u201cAnxious\u201d dogs exhibited the problem within 1 week of adoption. The resting place and diagnosis were statistically related (P 64 0.05): the 20% of dogs that slept on owners' bed were mainly \u201canxious\u201d dogs (78% of these). Sixty-five percent of \u201canxious\u201d dogs and 33% of \u201caggressive\u201d dogs showed mounting behaviors toward people. Most (72.3%) (N = 242/335) of the dogs improved after behavior treatment. \u201cAggressive\u201d dogs (96%, N = 232/242) improved more than \u201canxious\u201d ones (4%; N = 10/242) (P 64 0.05). Moreover, owners of dogs with anxiety problems were significantly more prone to surrender the dog to a shelter or other people (P 64 0.05). Our work supports some previous findings and suggests some new information regarding factors associated with broad scale aggression and anxiety in domestic dogs. Anxiety problems appear more difficult and demanding for dog owners. A referral population is not likely representative of the entire population of dogs. To understand patterns of behavioral problems, we need more complete population data and we need data from dogs across their lifetime

The functional polymorphism rs73598374:G>A (p.Asp8Asn) of the ADA gene is associated with telomerase activity and leukocyte telomere length

Recent evidence demonstrated a relevant role of adenosine deaminase (ADA) in replicative senescence of T cells through its capacity to modulate telomerase activity (TA). Herein, we tested the impact of the functional polymorphism ADA rs73598374:G>A (c.22G>A, p.Asp8Asn) on telomere biology, by measuring TA and leukocyte telomere length (LTL) in healthy subjects selected according to rs73598374 genotype. rs73598374-A carriers showed lower TA (P=0.019) and shorter LTL (P=0.003), respectively, compared to G/G carriers. rs73598374-A carriers showed a stronger cross-sectional age reduction of LTL (r=-0.314, P=0.005) compared to G/G carriers (r=-0.243, P=0.022). The reduced ADA activity associated to rs73598374-A variant predisposes those carriers to display higher levels of adenosine compared to G/G carriers. Consequently, it may lead to an accelerated process of replicative senescence, causing a stronger reduction of TA and in turn shorter LTL. In conclusion, the crucial role played by replicative senescence of the immune system in several human diseases and in the aging process underscores the relevance of the present findings and also spurs interest into the possible involvement of rs73598374 in shaping the susceptibility to several age-related diseases

SNPchiMp: a database to disentangle the SNPchip jungle in bovine livestock

BACKGROUND: Currently, six commercial whole-genome SNP chips are available for cattle genotyping, produced by two different genotyping platforms. Technical issues need to be addressed to combine data that originates from the different platforms, or different versions of the same array generated by the manufacturer. For example: i) genome coordinates for SNPs may refer to different genome assemblies; ii) reference genome sequences are updated over time changing the positions, or even removing sequences which contain SNPs; iii) not all commercial SNP ID’s are searchable within public databases; iv) SNPs can be coded using different formats and referencing different strands (e.g. A/B or A/C/T/G alleles, referencing forward/reverse, top/bottom or plus/minus strand); v) Due to new information being discovered, higher density chips do not necessarily include all the SNPs present in the lower density chips; and, vi) SNP IDs may not be consistent across chips and platforms. Most researchers and breed associations manage SNP data in real-time and thus require tools to standardise data in a user-friendly manner. DESCRIPTION: Here we present SNPchiMp, a MySQL database linked to an open access web-based interface. Features of this interface include, but are not limited to, the following functions: 1) referencing the SNP mapping information to the latest genome assembly, 2) extraction of information contained in dbSNP for SNPs present in all commercially available bovine chips, and 3) identification of SNPs in common between two or more bovine chips (e.g. for SNP imputation from lower to higher density). In addition, SNPchiMp can retrieve this information on subsets of SNPs, accessing such data either via physical position on a supported assembly, or by a list of SNP IDs, rs or ss identifiers. CONCLUSIONS: This tool combines many different sources of information, that otherwise are time consuming to obtain and difficult to integrate. The SNPchiMp not only provides the information in a user-friendly format, but also enables researchers to perform a large number of operations with a few clicks of the mouse. This significantly reduces the time needed to execute the large number of operations required to manage SNP data

Mind‐mindedness and parenting stress in mothers of preterm and full‐term infants: The moderating role of perceived social support

The goal of this study was to examine the effects of preterm birth and maternal childbirth‐related posttraumatic stress and parenting stress on maternal mind‐mindedness (MM). The study also investigated the effects of perceived social support on parenting stress and MM. Sixty‐five preterm (N = 32) and full‐term (N = 33) mother–infant dyads were observed at 6 months. Measures of maternal MM were obtained from observations of mother–infant interaction. Mothers also provided ratings of their posttraumatic stress disorder (PTSD) symptoms, parenting stress, and perceived social support via an online survey. Experiencing a preterm birth did not affect mothers’ use of mental state descriptors during mother–infant interaction. Neither childbirth‐related posttraumatic stress nor parenting stress directly affected maternal ability to comment on the child's mental states appropriately. However, at medium and high levels of perceived social support, a negative association between parenting stress and MM was observed. Maternal perception of being emotionally supported by significant others promoted MM in mothers showing low or mild levels of parenting stress, but not in mothers experiencing high stress in parenting their infants. Results suggest that a proclivity to MM might be affected by the interaction between parenting stress and social support, rather than by childbirth‐related variables, such as prematurity

Recent Advances on Surface-Modified GBM Targeted Nanoparticles: Targeting Strategies and Surface Characterization

Glioblastoma multiforme (GBM) is the most common malignant brain tumor, associated with low long-term survival. Nanoparticles (NPs) developed against GBM are a promising strategy to improve current therapies, by enhancing the brain delivery of active molecules and reducing off-target effects. In particular, NPs hold high potential for the targeted delivery of chemotherapeutics both across the blood-brain barrier (BBB) and specifically to GBM cell receptors, pathways, or the tumor microenvironment (TME). In this review, the most recent strategies to deliver drugs to GBM are explored. The main focus is on how surface functionalizations are essential for BBB crossing and for tumor specific targeting. We give a critical analysis of the various ligand-based approaches that have been used to target specific cancer cell receptors and the TME, or to interfere with the signaling pathways of GBM. Despite the increasing application of NPs in the clinical setting, new methods for ligand and surface characterization are needed to optimize the synthesis, as well as to predict their in vivo behavior. An expert opinion is given on the future of this research and what is still missing to create and characterize a functional NP system for improved GBM targeting

La percezione della disabilità con il questionario ICF-CY : il punto di vista del sanitario e del caregiver. Dati preliminari in una popolazione di bambini con ritardo mentale

Riassunto Introduzione e background: l\u2019ICF-CY (International Classification of Functioning, Disability and Health Children and Young), costituisce uno strumento importante per la valutazione olistica della salute. L\u2019ICF consente di indagare aspetti relativi alle Funzioni e alle Strutture Corporee, ad Attivit\ue0 e Partecipazione e ai Fattori Ambientali implicati nello stato di salute del soggetto. Studi precedentemente condotti hanno mirato ad indagare la coerenza tra questo nuovo strumento e quelli valutativi gi\ue0 in uso, al fine di evidenziarne eventuali punti di forza. Obiettivo: verificare l\u2019adeguatezza dell\u2019ICF come mezzo per creare un linguaggio comune tra differenti professionisti che interagiscono con il paziente, ricercando il livello di concordanza, mediante la somministrazione del questionario a sanitari, genitori ed insegnanti in una popolazione di minori con ritardo mentale. Materiali e Metodi: lo studio ha coinvolto 9 sanitari, Medici e professionisti dell\u2019area della riabilitazione, 40 genitori e 35 educatori che hanno compilato il questionario ICF-CY di 20 soggetti con ritardo mentale di et\ue0 compresa tra 3 e 11 anni seguiti presso un Servizio di NPIA per trattamenti o controlli periodici e iscritti in strutture formative del territorio. Per ciascun soggetto sono stati compilati 3 questionari ICF-CY e la compilazione \ue8 stata effettuata separatamente al fine di confrontare le risposte fornite. Analisi statistica: si \ue8 proceduto ad effettuare una comparazione dei punteggi assegnati a ciascuna voce dei questionari dello stesso bambino nelle quattro parti di cui l\u2019ICF si compone. Il confronto \ue8 stato effettuato tra tutti e tre i gruppi di valutatori (Kappa di Fleiss) nonch\ue9 a coppie: sanitari Vs genitori, genitori Vs insegnanti, sanitari Vs insegnanti (Kappa di Cohen). Risultati: si \ue8 riscontrata una diversit\ue0 nei risultati ottenuti dai due metodi di analisi utilizzati: il confronto tra i tre gruppi di esaminatori ha evidenziato una concordanza tra moderata e buona in tutte le parti del questionario; l\u2019analisi a coppie ha invece consentito di rilevare una concordanza moderata-buona nelle parti Funzioni corporee e Attivit\ue0 e partecipazione, un confronto impossibile nel 50% dei casi della parte Strutture Corporee, una discordanza nella parte Fattori ambientali per le coppie sanitari-insegnanti e genitori-insegnanti. Discussione: dai dati emersi, sembra che la discordanza rilevata nella parte Fattori Ambientali possa essere riferibile a carenza di linguaggio comune e deficit di comunicazione tra scuola e famiglia e tra professionisti e genitori; l\u2019incongruenza rilevata sulle Strutture Corporee \ue8 probabilmente legata alla tipologia del campione con disabilit\ue0 cognitiva e non funzionale, ma anche al dominio che per il suo contenuto si presta maggiormente ad essere compilato da sanitari. Conclusioni: l\u2019ICF si \ue8 dimostrato strumento adeguato per la rilevazione della differente percezione dello stato di salute e per il confronto tra differenti figure. Tuttavia, il ridotto campione a cui si fa riferimento non consente di trarre conclusioni definitive circa la significativit\ue0 dei livelli di concordanza rilevati e il reale accordo tra le differenti figure. Prospettive future di studio potrebbero dunque essere legate all\u2019incremento del campione oggetto di studio nonch\ue9 alla selezione di un campione con patologie differenti dal ritardo mentale. Abstract Introduction and background: ICF-CY is a comprehensive tool for holistic assessment of health that allows to investigate aspects of Functions and Body Structures, of Activities and Participation and of Environmental Factors involved in the health status of the subject. Previous studies about ICF had the purpose to investigate the consistency between this new instrument and assessment tools already in use, in order to highlight possible differences. Purpose: Verifying the effective usability of the ICF as tool for creating a common language between different figures that interact with the patient researching the level of correlation between the assessments made by sanitary staff, parents and teachers of children with mental retardation using ICF-CY check list. Materials and Methods: the study involved the use of the ICF-CY check list, 9 members of sanitary staff, including physicians and rehabilitators, 40 parents and 35 teachers filled in ICF-CY check list of 20 children with mental retardation, aged 3-11, followed by NPIA service for therapy or periodic controls, attending various educational institutions. For each subject of the sample were filled in three ICF-CY checklists and the compilation was carried out separately in order to compare the answers. Statistical Analysis: it was made by a comparison of the scores assigned to each item of the check lists of the same child. The comparison was made between all three groups of examiners (Kappa Fleiss) and in pairs: sanitary staff Vs parents, parents Vs teachers, sanitary staff Vs teachers (Cohen's Kappa). Results: there was a discrepancy in the results from the two methods of analysis used: the comparison between the three groups of examiners showed a correlation moderate-good in all parts of the check list; the analysis in pairs, allowed to observe the impossibility of calculate the correlation of scoring in Part 1.b (Body Structures) and a discordance in pairs sanitary staff-teacher and parent-teacher in Part 3 (Environmental Factors). Discussion: it seems that the discrepancy found in the Environmental Factors is attributable to a lack of communication between teachers and parents; the inconsistency detected on Body Structures is probably related to the reduced presence of malformations in the sample which did not allow to detect possible discrepancies. Conclusions: as documented in literature, the ICF is an appropriate tool for the detection of different perception of health status and the comparison of different opinions. However, the small sample of the study can't draw conclusions about the significance of the correlation levels detected and the real agreement between the different people. Prospects for the future study could be linked to the increase of the sample and the selection of a sample with different diseases

Membrane-binding peptides for extracellular vesicles on-chip analysis

Small extracellular vesicles (sEVs) present fairly distinctive lipid membrane features in the extracellular environment. These include high curvature, lipid-packing defects and a relative abundance in lipids such as phosphatidylserine and ceramide. sEV membrane could be then considered as a "universal" marker, alternative or complementary to traditional, characteristic, surface-associated proteins. Here, we introduce the use of membrane-sensing peptides as new, highly efficient ligands to directly integrate sEV capturing and analysis on a microarray platform. Samples were analysed by label-free, single-particle counting and sizing, and by fluorescence co-localisation immune staining with fluorescent anti-CD9/anti-CD63/anti-CD81 antibodies. Peptides performed as selective yet general sEV baits and showed a binding capacity higher than anti-tetraspanins antibodies. Insights into surface chemistry for optimal peptide performances are also discussed, as capturing efficiency is strictly bound to probes surface orientation effects. We anticipate that this new class of ligands, also due to the versatility and limited costs of synthetic peptides, may greatly enrich the molecular toolbox for EV analysis