Serotonin systems in three socially communicating teleost species, the grunting toadfish (Allenbatrachus grunniens), a South American marine catfish (Ariopsis seemanni), and the upside-down catfish (Synodontis nigriventris)

We investigated immunohistochemically the distribution of serotonergic cell populations in three teleost species (one toadfish, Allenbatrachus grunniens, and two catfishes, Synodontis nigriventris and Ariopsis seemanni). All three species exhibited large populations of 5-HT positive neurons in the paraventricular organ (PVO) and the dorsal (Hd) and caudal (Hc) periventricular hypothalamic zones, plus a smaller one in the periventricular pretectum, a few cells in the pineal stalk, and – only in catfishes – in the preoptic region. Furthermore, the rhombencephalic superior and inferior raphe always contained ample serotonergic cells. In each species, a neuronal mass extended into the hypothalamic lateral recess. Only in the toadfish, did this intraventricular structure contain serotonergic cells and arise from Hd, whereas in the catfishes it emerged from medially and represents the dorsal tuberal nucleus seen in other catfishes as well. Serotonergic cells in PVO, Hd and Hc were liquor-contacting. Those of the PVO extended into the midline area of the periventricular posterior tubercular nucleus in both catfishes. Dopaminergic, liquor-contacting neurons were additionally investigated using an antibody against tyrosine hydroxylase (TH) in S. nigriventris showing that TH was never co-localized with serotonin. Because TH antibodies are known to reveal mostly or only the TH1 enzyme, we hypothesize that th1-expressing dopamine cells (unlike th2-expressing ones) do not co-localize with serotonin. Since the three investigated species engage in social communication using swim bladder associated musculature, we investigated the serotonergic innervation of the hindbrain vocal or electromotor nuclei initiating the social signal. We found in all three species serotonergic fibers seemingly originating from close-by serotonergic neurons of inferior raphe or anterior spinal cord. Minor differences appear to be rather species-specific than dependent on the type of social communication

Prader–Willi syndrome and autism spectrum disorders: an evolving story

Prader–Willi syndrome (PWS) is well-known for its genetic and phenotypic complexities. Caused by a lack of paternally derived imprinted material on chromosome 15q11–q13, individuals with PWS have mild to moderate intellectual disabilities, repetitive and compulsive behaviors, skin picking, tantrums, irritability, hyperphagia, and increased risks of obesity. Many individuals also have co-occurring autism spectrum disorders (ASDs), psychosis, and mood disorders. Although the PWS 15q11–q13 region confers risks for autism, relatively few studies have assessed autism symptoms in PWS or directly compared social, behavioral, and cognitive functioning across groups with autism or PWS. This article identifies areas of phenotypic overlap and difference between PWS and ASD in core autism symptoms and in such comorbidities as psychiatric disorders, and dysregulated sleep and eating. Though future studies are needed, PWS provides a promising alternative lens into specific symptoms and comorbidities of autism

Thus Precum, In Nuptiis, quod Deus velit, Auspicatissimis Viri ... Dni. Jeremiae Michaelis Rosneri, Pastoris Substituti Weltwitzensium ... Sponsi, Cum Virgine ... Dorothea Elisabetha, Viri ... Domini Michaelis Hartmanni Dioecesios Neostadiensis ad Orlam Senioris maxime spectabilis, & per XLV. annos Pastoris Weltwicensis longe meritissimi, Filia Tertia, Eaque Ultima, Ipso Nuptiarum Festo d. 20. Octobris 1685.

THUS PRECUM, IN NUPTIIS, QUOD DEUS VELIT, AUSPICATISSIMIS VIRI ... DNI. JEREMIAE MICHAELIS ROSNERI, PASTORIS SUBSTITUTI WELTWITZENSIUM ... SPONSI, CUM VIRGINE ... DOROTHEA ELISABETHA, VIRI ... DOMINI MICHAELIS HARTMANNI DIOECESIOS NEOSTADIENSIS AD ORLAM SENIORIS MAXIME SPECTABILIS, & PER XLV. ANNOS PASTORIS WELTWICENSIS LONGE MERITISSIMI, FILIA TERTIA, EAQUE ULTIMA, IPSO NUPTIARUM FESTO D. 20. OCTOBRIS 1685. Thus Precum, In Nuptiis, quod Deus velit, Auspicatissimis Viri ... Dni. Jeremiae Michaelis Rosneri, Pastoris Substituti Weltwitzensium ... Sponsi, Cum Virgine ... Dorothea Elisabetha, Viri ... Domini Michaelis Hartmanni Dioecesios Neostadiensis ad Orlam Senioris maxime spectabilis, & per XLV. annos Pastoris Weltwicensis longe meritissimi, Filia Tertia, Eaque Ultima, Ipso Nuptiarum Festo d. 20. Octobris 1685. ([1]) Titelseite ([1]) Text ([1]

Co-aggregate formation of CADASIL-mutant NOTCH3: A single-particle analysis.

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is the most common monogenic cause of stroke and vascular dementia. Accumulation and deposition of the NOTCH3 (N3) extracellular domain in small blood vessels has been recognized as a central pathological feature of the disease. Recent experiments suggested enhanced formation of higher order multimers for mutant N3 compared with wild-type (WT). However, the mechanisms and consequences of N3 multimerization are still poorly understood, in part because of the lack of an appropriate in vitro aggregation assay. We therefore developed and validated a robust assay based on recombinant N3 fragments purified from cell culture supernatants. Using single-molecule analysis techniques such as scanning for intensely fluorescent targets and single-particle fluorescence resonance energy transfer, we show that spontaneous aggregation is limited to CADASIL-mutant N3, recapitulating a central aspect of CADASIL pathology in vitro. N3 aggregation requires no co-factor and is facilitated by sulfhydryl crosslinking. Although WT N3 does not exhibit multimerization itself, it can participate in aggregates of mutant N3. Furthermore, we demonstrate that thrombospondin-2, a known interaction partner of N3, co-aggregates with mutant N3. Sequestration of WT N3 and other proteins into aggregates represents a potentially important disease mechanism. These findings in combination with a new assay for single-molecule aggregation analysis provide novel opportunities for the development of therapeutic strategies