Microarray gene expression profiling of neural tissues in bovine spastic paresis

Abstract: Background: Bovine Spastic Paresis (BSP) is a neuromuscular disorder which affects both male and female cattle. BSP is characterized by spastic contraction and overextension of the gastrocnemious muscle of one or both limbs and is associated with a scarce increase in body weight. This disease seems to be caused by an autosomal and recessive gene, with incomplete penetration, although no genes clearly involved with its onset have been so far identified. We employed cDNA microarrays to identify metabolic pathways affected by BSP in Romagnola cattle breed. Investigation of those pathways at the genome level can help to understand this disease. Results: Microarray analysis of control and affected individuals resulted in 268 differentially expressed genes. These genes were subjected to KEGG pathway functional clustering analysis, revealing that they are predominantly involved in Cell Communication, Signalling Molecules and Interaction and Signal Transduction, Diseases and Nervous System classes. Significantly enriched KEGG pathway's classes for the differentially expressed genes were calculated; interestingly, all those significantly under-expressed in the affected samples are included in Neurodegenerative Diseases. To identify genome locations possibly harbouring gene(s) involved in the disease, the chromosome distribution of the differentially expressed genes was also investigated. Conclusions: The cDNA microarray we used in this study contains a brain library and, even if carrying an incomplete transcriptome representation, it has proven to be a valuable tool allowing us to add useful and new information to a poorly studied disease. By using this tool, we examined nearly 15000 transcripts and analysed gene pathways affected by the disease. Particularly, our data suggest also a defective glycinergic synaptic transmission in the development of the disease and an alteration of calcium signalling proteins. We provide data to acquire knowledge of a genetic disease for which literature still presents poor results and that could be further and specifically analysed in the next future. Moreover this study, performed in livestock, may also harbour molecular information useful for understanding human diseases

A Tool for Sheep Product Quality: Custom Microarrays from Public Databases

Milk and dairy products are an essential food and an economic resource in many countries. Milk component synthesis and secretion by the mammary gland involve expression of a large number of genes whose nutritional regulation remains poorly defined. The purpose of this study was to gain an understanding of the genomic influence on milk quality and synthesis by comparing two sheep breeds with different milking attitude (Sarda and Gentile di Puglia) using sheep-specific microarray technology. From sheep ESTs deposited at NCBI, we have generated the first annotated microarray developed for sheep with a coverage of most of the genome

A dual cis-regulatory code links IRF8 to constitutive and inducible gene expression in macrophages

The transcription factor (TF) interferon regulatory factor 8 (IRF8) controls both developmental and inflammatory stimulus-inducible genes in macrophages, but the mechanisms underlying these two different functions are largely unknown. One possibility is that these different roles are linked to the ability of IRF8 to bind alternative DNA sequences. We found that IRF8 is recruited to distinct sets of DNA consensus sequences before and after lipopolysaccharide (LPS) stimulation. In resting cells, IRF8 was mainly bound to composite sites together with the master regulator of myeloid development PU.1. Basal IRF8-PU.1 binding maintained the expression of a broad panel of genes essential for macrophage functions (such as microbial recognition and response to purines) and contributed to basal expression of many LPS-inducible genes. After LPS stimulation, increased expression of IRF8, other IRFs, and AP-1 family TFs enabled IRF8 binding to thousands of additional regions containing low-affinity multimerized IRF sites and composite IRF-AP-1 sites, which were not premarked by PU. 1 and did not contribute to the basal IRF8 cistrome. While constitutively expressed IRF8-dependent genes contained only sites mediating basal IRF8/PU.1 recruitment, inducible IRF8-dependent genes contained variable combinations of constitutive and inducible sites. Overall, these data show at the genome scale how the same TF can be linked to constitutive and inducible gene regulation via distinct combinations of alternative DNA-binding sites

Schizophrenia spectrum disorders: Focus on social cognition and empathy

Background Schizophrenic patients show deficits in social cognition, functioning and in interpreting facial expressions. These disabilities contribute to global impairment in social and relational skills. Data started being collected in the context of the Italian Network of Research on Psychosis headed by Prof. Maj and Prof. Galderisi (Galderisi S et al. The influence of illness-related variables, personal resources and context-related factors on real-life functioning of people with schizophrenia. World Psychiatry 2014:275\u201387. Mucci A et al. The Specific Level of Functioning Scale: Construct validity, internal consistency and factor structure in a large Italian sample of people with schizophrenia living in the community. Schizophr Res 2014;159(1):144-50); collection in our centre went on also after the conclusion of the national project. Aims To identify the correlations among social inference, facial emotion identification and clinical history and therapies in schizophrenic patients. Material and methods We recruited patients with Schizophrenia referring to our Psychiatry Ward, AOU Maggiore della Carit\ue0, Novara, Italy. Socio-demographic characteristics were gathered; assessment of patients included The Awareness of Social Inference Test (TASIT), the Facial Emotion Identification Test (FEIT), the Positive and Negative Syndrome Scale (PANSS) and the Brief Negative Symptom Scale (BNSS). Results Data collection is still ongoing. In a previous study we pointed out that schizophrenic patients showed social skills deficits and difficulties in identifying facial emotions. These features underlie poor and limited social relationships proper to schizophrenia. Our preliminary results revealed thatidentification of facial emotions is influenced by psychopathological symptoms especially by avolition, blunted affect and alogia. Implication will be discussed

A first exon termination checkpoint preferentially suppresses extragenic transcription

Interactions between the splicing machinery and RNA polymerase II increase protein-coding gene transcription. Similarly, exons and splicing signals of enhancer-generated long noncoding RNAs (elncRNAs) augment enhancer activity. However, elncRNAs are inefficiently spliced, suggesting that, compared with protein-coding genes, they contain qualitatively different exons with a limited ability to drive splicing. We show here that the inefficiently spliced first exons of elncRNAs as well as promoter-antisense long noncoding RNAs (pa-lncRNAs) in human and mouse cells trigger a transcription termination checkpoint that requires WDR82, an RNA polymerase II–binding protein, and its RNA-binding partner of previously unknown function, ZC3H4. We propose that the first exons of elncRNAs and pa-lncRNAs are an intrinsic component of a regulatory mechanism that, on the one hand, maximizes the activity of these cis-regulatory elements by recruiting the splicing machinery and, on the other, contains elements that suppress pervasive extragenic transcription

Bell's palsy: Symptoms preceding and accompanying the facial paresis

This individual prospective cohort study aims to report and analyze the symptoms preceding and accompanying the facial paresis in Bell's palsy (BP). Two hundred sixty-nine patients affected by BP with a maximum delay of 48 hours from the onset were enrolled in the study. The evolution of the facial paresis expressed as House-Brackmann grade in the first 10 days and its correlation with symptoms were analyzed. At the onset, 136 patients presented postauricular pain, 114 were affected by dry eye, and 94 reported dysgeusia. Dry mouth was present in 54 patients (19.7%), facial pain, hyperlacrimation, aural fullness, and hyperacusis represented a smaller percentage of the reported symptoms. After 10 days, 39.9% of the group had a severe paresis while 10.2% reached a complete recovery. Dry mouth at the onset was correlated with severe grade of palsy and was prognostic for poor recovery in the early period. These outcomes lead to the deduction that the nervus intermedius plays an important role in the presentation of the BP and it might be responsible for most of the accompanying symptomatology of the paresis. Our findings could be of important interest to early address a BP patient to further examinations and subsequent therapy

High constitutive activity of a broad panel of housekeeping and tissue-specific cis-regulatory elements depends on a subset of ETS proteins

Enhancers and promoters that control the transcriptional output of terminally differentiated cells include cell type-specific and broadly active housekeeping elements. Whether the high constitutive activity of these two groups of cis-regulatory elements relies on entirely distinct or instead also on shared regulators is unknown. By dissecting the cis-regulatory repertoire of macrophages, we found that the ELF subfamily of ETS proteins selectively bound within 60 base pairs (bp) from the transcription start sites of highly active housekeeping genes. ELFs also bound constitutively active, but not poised, macrophage-specific enhancers and promoters. The role of ELFs in promoting high-level constitutive transcription was suggested by multiple evidence: ELF sites enabled robust transcriptional activation by endogenous and minimal synthetic promoters, ELF recruitment was stabilized by the transcriptional machinery, and ELF proteins mediated recruitment of transcriptional and chromatin regulators to core promoters. These data suggest that the co-optation of a limited number of highly active transcription factors represents a broadly adopted strategy to equip both cell type-specific and housekeeping cis-regulatory elements with the ability to efficiently promote transcription

The Importance of Cooperation and Relative's Involvement in Combined Treatment for Eating Disorders: a Case Report

Introduction: The importance of combined treatment of EDs is widely acknowledged. We describe the good outcome of a combined treatment in a 43 year old woman, affected by severe Anorexia Nervosa \u2013 Binge Purging (BMI 9.1), since early adolescence. She sought treatment only after giving birth to her second-born when she became aware of her illness. Despite intensive treatment (as an inpatient in hospitals and specialized rehabilitation centres, and in Day Hospital facilities), her condition gradually worsened, and her personal, social, working and family functioning was severely compromised (Global Assessment of Functioning Scale 35), Methods: A multidisciplinary team including psychiatrist, psychotherapist, family psychotherapist, nutritionist, dietician, nurses was involved in treatment, working together to a common treatment strategy. The Psychiatrists role (psicopharmacology, therapeutic process, helping acknowledging and avoiding manipulation) and the nurses role (establishing a therapeutic relationship with the patient, assisting her during meals and supporting the overall therapeutic process), are discussed. Results: A gradual psychopathologic and somatic improvement occurred across a 12-months period: she spent two months in a Psychiatry ward, four more months in a rehab centre and six months in an ED therapeutic community. She gained weight (BMI 21.4) and regained an excellent personal, social and family functioning. She returned to her husband (they previously separated), and the relationship with her daughters, who previously rejected her, improved (GAF 90). Conclusions: The cooperation of the multidisciplinary equipe and the involvement of the patient\u2019s relatives succeeded in reducing anxiety, depression, dysmorphophobia and interrupting the manipulating attitudes typical of the illness