Autism spectrum disorder (ASD) is a group of developmental pathologies that impair social communication and cause repetitive behaviors. The suggested roles of noncoding RNAs in pathology led us to perform a comparative analysis of the microRNAs expressed in the serum of human ASD patients. The analysis of a cohort of 45 children with ASD revealed that six microRNAs (miR-19a-3p, miR-361-5p, miR-3613-3p, miR-150-5p, miR-126-3p, and miR-499a-5p) were expressed at low to very low levels compared to those in healthy controls. A similar but less pronounced decrease was registered in the clinically unaffected parents of the sick children and in their siblings but never in any genetically unrelated control. Results consistent with these observations were obtained in the blood, hypothalamus and sperm of two of the established mouse models of ASD: valproic acid-treated animals and Cc2d1a +/− heterozygotes. In both instances, the same characteristic miRNA profile was evidenced in the affected individuals and inherited together with disease symptoms in the progeny of crosses with healthy animals. The consistent association of these genetic regulatory changes with the disease provides a starting point for evaluating the changes in the activity of the target genes and, thus, the underlying mechanism(s). From the applied societal and medical perspectives, once properly confirmed in large cohorts, these observations provide tools for the very early identification of affected children and progenitors. Autism spectrum disorders (ASDs) encompass a range of disorders characterized by impaired social interactions and communications, together with repetitive stereotypic behaviors (refs. 1-5 for recent reviews). The genetic architecture underlying the range of ASD symptoms has been investigated (reviewed by Iakoucheva et al. 1). Mutations in more than 100 genes involved in brain development and neural activity have been identified in patients and are thought to confer a risk for ASD 2,3 , but a constant association that would suggest a causal relationship has not been observed. The same conclusion was recently reached from a large-scale exon sequencing analysis 4. Hence, mouse models that reproduce characteristic elements of the disease have been developed 5. As in other instances, attention has recently been focused on a peculiar class of regulatory alterations that modifies noncoding (nc) RNAs 6 with putative regulatory functions in the synthesis of proteins. One class of these alterations comprises the genes encoding 22 nt-long RNA (often abbreviated miRNAs) that regulate the expression of homologous target genes by blocking translation and inducing the degradation of the mRNAs 7. Among the miRNA genes in the mammalian genome (several hundred in the human genome), a large subset is expressed in the brain 8 , and dysfunctions of particular miRNAs have been tentatively associated with neuropathological conditions, including ASD 9,10 , with however diverging patterns of expression. They may reflect still unknown complexities of the dis...

Five adult donkeys of both sexes, used in applied anatomy classes, and perfused with formalin for teaching purposes, constituted the study material. Ganglion cervicale caudale of the examined materials has observed to exhibit individually variable situation as to extend on the left side of the median line, at the alignment of the first and second intercostal spaces and on the right side between the level of the first and third costa. The ganglion extended more caudally on the right side of median line. The lateral surface of the ganglion was determined to be covered with the m. scalenus medius. On the both sides of the median plane, the ganglion cervicale caudale was seen to be situated on the lateral surface of the m. longus colli. On the left side, the ganglion overlapped the oesophagus in two cadavers and on the right side it was situated within a groove between the m. longus colli and trachea in three cadavers. The rami communicantes received by the ganglion cervicale caudale originated from the eighth cervical and first thoracic spinal segments. The ganglion cervicale caudale was formed by the coalescence of the last cervical and first three thoracic sympathetic ganglia. The ganglion cervicale caudale gave off branches that formed the rami communicantes, plexus cardiacus, n. vertebralis and ansa subclavia. One branch extended from the ganglion to the plexus brachialis. in one specimen, two sympathetic-parasympathetic communicating branches were observed to extend from the ansa subclavia and near by the origin of the truncus sympathicus to the n. vagus. In one of the donkeys examined, a branch originating from the ganglion cervicale caudale on the left side of the median plane was determined to end on the ligamentum arteriosum. A microscopic ganglion structure suggesting the existence of the ganglion cervicale medium was determined in a donkey.

The development of the ileal Peyer's patches (ilPP) and follicle associated epithelium (FAE) was examined in 30 bovine foetuses ranging from 73 to 271 days of gestation by light and transmission electron microscopic methods. The first primordial ilPP was encountered in the foetus at 164 days of gestation The ilPP were found to have been formed from the aggregation of lymph follicles in the foetus at 227 days of gestation whereas in the foetus at 271 days of gestation the follicular development was observed to have been completed. While the cells in the FAE in the foetus at 164 days of gestation and those older were cuboidal, those of the foetus at 271 days of gestation were columnar. As from the foetus at 227 days of gestation, however, the FAE was found to be composed of uniform lymphoepithelial cells with an increase in the number of intraepithelial leukocytes. In the early stages, whereas the apical surfaces of the FAE cells appeared shorter with microfolds, with advancing age the apical surfaces of the FAE cells were observed to be heterogeneous. Our results suggest that bovine ilPP and FAE cells are histologically and functionally mature before birth.

Few studies exist regarding the distribution of intestinal mucins in fetuses of mammalians such as cattle and sheep. In this study, we aimed to describe the changes in the mucin production by ileal epithelium of bovine fetuses during their prenatal development. The goblet cells showed heterogeneity in mucins and the apical cytoplasm of the enterocytes demonstrated Periodic acid Schiff-positive reaction which declined gradually towards the birth. Moreover, the number of the goblet cells containing acidic and mixed mucins augmented, whereas those containing neutral mucins decreased with advancing gestational age. After sixth month of gestation, with the initiation of the ileal Peyer patches and follicle-associated epithelium development, a gradual increase in the number of goblet cells containing sulfomucins was also noticed towards the birth. The presence of different mucins in the ileum of bovine fetuses throughout prenatal development might play a role in the protection of the intestinal mucosa against urinary waste products in swallowed amniotic fluid and bile. Furthermore, mucins can also contribute for the formation of meconium in intra-uterine life and building of strong intestinal barrier with predominating sulfomucins, protecting the intestine against potential pathogens and digestive enzymes after birth.

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The present study was aimed at the immunohistochemical demonstration of M cells, found in the follicle-associated epithelium (FAE) of the sacculus rotundus (SR) and appendix of the Angora rabbit, using anti-vimentin primary antibodies, and at the determination of certain fine structural characteristics. Ten adult Angora rabbits constituted the material of the study. Immunohistochemical staining revealed that many cells composing the FAE, which covered the dome regions of the SR and appendix, reacted positively with vimentin. FAE contained two different types of vimentin-positive cells. The first type surrounded intraepithelial lymphocytes (IEL) with a basolateral invagination in the apex and periphery of the dome epithelium, whilst the second type consisted of columnar cells found in the FAE near crypts. The immunoreactivity of the cells found in the FAE covering the apex and periphery of the domes was observed particularly in the perinuclear cytoplasm and the cytoplasm surrounding the IEL. Electron microscopic examination demonstrated that the M cells found in the FAE covering the apex and periphery of the dome regions of the SR and appendix did not exhibit any microvilli on their apical surface. The FAE near crypts contained columnar cells, which resembled enterocytes. The apical membrane of these cells exhibited shorter and irregular microvilli, in contrast to neighbouring enterocytes. It was determined that M cells, found in the FAE of the SR and appendix in the Angora rabbit, displayed similarities in terms of localization and fine structure. This situation may be indicative of the two lymphoid structures with different localization having similar functional properties.

The presence, distribution, and localization of M cells in isolated lymphoid follicles (ILF) and in follicle-associated epithelia (FAE) covering Peyer's patches (PP) in Angora rabbits were investigated by immunohistochemistry and electron microscopy. Although PP could macroscopically be identified along the length of the mucosal and serosal surfaces of jejunum and ileum, the presence of ILF could only be located microscopically. Typical M cells in FAE were detected within the periphery of the dome regions of the PP, and immature columnar M cells in the FAE resided in the vicinity of the crypts. M cells in the FAE of both ILF and PP showed vimentin-positive reaction. M cells in the FAE of ILF were morphologically similar to the immature M cells found in the FAE of PP. Typical mature M cells were also observed in the FAE of a few ILF. In contrast to FAE of PP, numerous goblet cells were observed in the FAE of many ILF. Moreover, among intestinal villi, we noticed villi-like solitary lymphoid structures that showed abundant lymphocytes in their lamina propria and that were surrounded with vimentin-positive cells and goblet cells. Thus, the occurrence of copious immature M cells and goblet cells, in addition to the detection of villi-like solitary lymphoid structures full of lymphocytes in the FAE of many ILF, indicate that ILF do not complete their immunological maturation in contrast to PP. Various antigenic stimulations conceivably induce the formation and maturation of ILF along the length of the small intestine. The morphological resemblance between ILF M cells and PP M cells suggests that these two types of cells perform similar or the same immunological functions.