Uterine adenomyosis in an orang-utan (Pongo abelii/pygmaeus)

A 48-year-old, multiparous, female hybrid orang-utan ( Pongo abelii/pygmaeus ) was investigated after a 3-year history of irregular and excessively heavy menstrual bleeding. Opportunistic pelvic examinations over a 2.5-year period were non-diagnostic. Medical therapy was not effective. A subtotal hysterectomy with bilateral salpingo-ovariectomy was performed. A pedunculated mass spanning 90% of the uterine lumen was seen grossly, and histopathology confirmed uterine adenomyosis. Adenomyosis is defined as the ectopic occurrence or diffuse implantation of endometrial tissue, including glands and stroma, into the myometrium. It is common in older, usually premenopausal, multiparous women and is frequently associated with other uterine pathology, including endometrial hyperplasia and leiomyomas. The most common clinical signs are dysmenorrhoea and heavy menstrual bleeding; however, up to 35% of women are asymptomatic. Diagnosis is difficult and requires myometrial sampling and an experienced pathologist. A hysterectomy in this case was diagnostic and curative. There have been few reports of uterine adenomyosis in non-human primates and none reported in an orang-utan. Uterine adenomyosis should be considered in the differential diagnosis in any multiparous, aged, non-human female primate with irregular and excessively heavy menstrual bleeding, and hysterectomy with bilateral salpingo-ovariectomy is recommended as a diagnostic and therapeutic solution.     

Structure of an intermediate state in protein folding and aggregation

Protein-folding intermediates have been implicated in amyloid fibril formation involved in neurodegenerative disorders. However, the structural mechanisms by which intermediates initiate fibrillar aggregation have remained largely elusive. To gain insight, we used relaxation dispersion nuclear magnetic resonance spectroscopy to determine the structure of a low-populated, on-pathway folding intermediate of the A39V/N53P/V55L (A, Ala; V, Val; N, Asn; P, Pro; L, Leu) Fyn SH3 domain. The carboxyl terminus remains disordered in this intermediate, thereby exposing the aggregation-prone amino-terminal β strand. Accordingly, mutants lacking the carboxyl terminus and thus mimicking the intermediate fail to safeguard the folding route and spontaneously form fibrillar aggregates. The structure provides a detailed characterization of the non-native interactions stabilizing an aggregation-prone intermediate under native conditions and insight into how such an intermediate can derail folding and initiate fibrillation.     

Synaptic transmission at single glomeruli in the turtle cerebellum

We have recorded from the granular layer of the turtle cerebellum extracellular unitary potentials that appear to reflect pre- and postsynaptic events at the synapse between a single swelling of a mossy fiber and the dendritic tips of several granule cells. The presynaptic component is an all-or-none potential. It can be directly activated by spinal stimulation and is unaltered by repetitive activity or by high concentrations of magnesium. The postsynaptic component is a graded potential. It follows the presynaptic component by approximately 1 millisecond and is depressed by repetitive activity and by high concentrations of magnesium. The recording of large potentials produced by the flow of postsynaptic current within a single glomerulus suggests powerful transmission. Electron micrographs demonstrate large cerebellar glomeruli in the turtle and a substantial accumulation of mitochondria in the dendritic tips of granule cells.