Marker chromosome genomic structure and temporal origin implicate a chromoanasynthesis event in a family with pleiotropic psychiatric phenotypes

Small supernumerary marker chromosomes (sSMC) are chromosomal fragments difficult to characterize genomically. Here, we detail a proband with schizoaffective disorder and a mother with bipolar disorder with psychotic features who present with a marker chromosome that segregates with disease. We explored the architecture of this marker and investigated its temporal origin. Array comparative genomic hybridization (aCGH) analysis revealed three duplications and three triplications that spanned the short arm of chromosome 9, suggestive of a chromoanasynthesis‐like event. Segregation of marker genotypes, phased using sSMC mosaicism in the mother, provided evidence that it was generated during a germline‐level event in the proband's maternal grandmother. Whole‐genome sequencing (WGS) was performed to resolve the structure and junctions of the chromosomal fragments, revealing further complexities. While structural variations have been previously associated with neuropsychiatric disorders and marker chromosomes, here we detail the precise architecture, human life‐cycle genesis, and propose a DNA replicative/repair mechanism underlying formation.     

Binding of host collectins to the pathogenic yeast Cryptococcus neoformans: human surfactant protein D acts as an agglutinin for acapsular yeast cells.

Cryptococcus neoformans is an opportunistic pathogen in AIDS patients causing disseminated disease and lethal meningitis after inhalation of acapsular or sparsely encapsulated yeast cells. In this study we have investigated whether a recently described family of primitive opsonins, termed collectins, contribute to innate resistance against C. neoformans. The pulmonary surfactant proteins SP-A and SP-D as well as the serum collectins mannose-binding protein and CL-43 bound in a calcium-dependent manner to acapsular C. neoformans in vitro. Binding was concentration dependent and abolished by competition with defined mono- and oligosaccharides. In contrast, no binding of the collectins was observed with the encapsulated form of the yeast. Furthermore, binding of purified collectin SP-D, but not SP-A, mannose-binding protein, or CL-43, led to a concentration-dependent agglutination of acapsular C. neoformans. These data indicate that collectins recognize carbohydrate structures in the cell wall of an initial infectious form of C. neoformans and may play a role in early antifungal defenses in the lung.     

The Ontogeny of Masticatory Muscle Architecture in Microcebus murinus

The masticatory apparatus has been the focus of many studies in comparative anatomy—especially analyses of skulls and teeth, but also of the mandibular adductor muscles which are responsible for the production of bite force and the movements of the mandible during food processing and transport. The fiber architecture of these muscles has been correlated to specific diets (e.g., prey size in felids) and modes of foraging (e.g., tree gouging in marmosets). Despite the well-elucidated functional implications of this architecture, little is known about its ontogeny. To characterize age-related myological changes, we studied the masticatory muscles in a large (n = 33) intraspecific sample of a small, Malagasy primate, Microcebus murinus including neonatal through geriatric individuals. We removed each of the mandibular adductors and recorded its mass as well as other linear measurements. We then chemically dissected each muscle to study its architecture—fascicle length and physiological cross-sectional area (PCSA) which relate to stretch (gape) and force capabilities, respectively. We observed PCSA and muscle mass to increase rapidly and plateau in adulthood through senescence. Fascicle lengths remained relatively constant once maximal length was reached, which occurred early in life, suggesting that subsequent changes in PCSA are driven by changes in muscle mass. Quadratic curvilinear models of each of the architectural variables of all adductors combined as well as individual muscles regressed against age were all significant. Anat Rec, 303:1364–1373, 2020. © 2019 American Association for Anatomy     

Ovarian recovery after stem cell transplantation

Autologous or allogeneic SCT with conventional conditioning (chemotherapy with or without irradiation) has emerged as an effective and potentially curative therapy in patients with hematologic malignancies and in other selected solid tumors; however, several patients experience significant early and delayed side effects, including long-term endocrine imbalance and infertility. In spite of several reproductive recovery and pregnancy reports published in the oncology literature, review of medical literature reveals a paucity of comparable information in the SCT field. We report here four cases of ovarian recovery in patients who received hormonal replacement therapy after diagnosis of primary ovarian failure due to high-dose chemotherapy and SCT.     

Older person behavioral and psychological symptoms (BPS) and functional limitations mediate the association between older person cognitive impairment and depressive symptoms in the caregiver

We assess for the mediation of the association between older person cognitive impairment and caregiver depressive symptoms through older person BPS and functional limitations, and whether the mediation varies by caregiver–older person relationship (spouse/adult child). Data for 1111 older person (aged 75+ with activity of daily living (ADL) limitation)–caregiver dyads from Singapore were used. The outcome variable was dichotomous (caregiver clinically significant depressive symptoms [CSDS]: yes/no) in the primary analysis and continuous (caregiver depressive symptoms score) in the sensitivity analysis. The causal steps approach assessed for the mediation of the association between older person cognitive impairment (yes/no) and the outcome variable through the two potential mediators. A bootstrapping approach calculated point estimates and confidence intervals (CIs) of the indirect (∼mediated) effects. Variation of the indirect effects by caregiver–older person relationship was also assessed. In the primary analysis, the causal steps approach supported older person BPS and functional limitations as mediators. The bootstrapping approach confirmed both as significant mediators, though BPS (indirect effect odds ratio (OR) 1.32 [95% bootstrap CI 1.19,1.48]; %mediation: 70.6%) was a stronger mediator than functional limitations (1.04 [1.01,1.11]; %mediation: 11.5%). Variation of the indirect effects by caregiver–older person relationship was not supported. Results of the sensitivity analysis confirmed these results. We conclude that while caring for an older person with cognitive impairment is detrimental for the caregiver's mood, management of associated BPS and functional limitations, especially the former, among such older persons may reduce depressive symptoms among their caregivers. Spouse as well as adult child caregivers benefit.     

Prospective evaluation of 68Ga-DOTA-NOC PET-CT in phaeochromocytoma and paraganglioma: preliminary results from a single centre study

Objective  

To evaluate the role of ⁶⁸Ga-labelled [1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid]-1-NaI³-Octreotide (⁶⁸Ga-DOTA-NOC) whole body positron emission tomography-computed tomography (PET-CT) as a functional imaging approach for phaeochromocytoma and paraganglioma.     

Priming of color and position during visual search in unilateral spatial neglect

We examined priming of visual search by repeated target location or color in two patients with left visual neglect and extinction, following strokes centered on the right inferior parietal lobe. Both patients, like the healthy controls we tested, showed intact priming, with performance speeded when either the location or color of a singleton target was repeated over successive trials in a standard search condition (Experiment 1). This was observed both from and to targets on the contralesional (left) side. Moreover, priming of search was still observed even when a return of fixation back to display-center was required between successive trials (Experiment 2). When briefer displays were used (Experiment 3), the patients often failed to detect left targets. This situation revealed an important dissociation: Whereas location priming only arose from preceding left targets that had been consciously detected, color priming (possibly arising within the intact ventral stream) did not depend on awareness of the preceding target. There was considerable color priming from missed targets. These findings demonstrate relatively intact priming of visual search by color and location in patients with right parietal damage, and also reveal that location priming may differ from color priming in requiring awareness.