Regulated CPEB phosphorylation during meiotic progression suggests a mechanism for temporal control of maternal mRNA translation

CPEB is an mRNA-binding protein that stimulates polyadenylation-induced translation of maternal mRNA once it is phosphorylated on Ser 174 or Thr 171 (species-dependent). Disruption of the CPEB gene in mice causes an arrest of oogenesis at embryonic day 16.5 (E16.5), when most oocytes are in pachytene of prophase I. Here, we show that CPEB undergoes Thr 171 phosphorylation at E16.5, but dephosphorylation at the E18.5, when most oocytes are entering diplotene. Although phosphorylation is mediated by the kinase aurora, the dephosphorylation is due to the phosphatase PP1. The temporal control of CPEB phosphorylation suggests a mechanism in which CPE-containing mRNA translation is stimulated at pachytene and metaphase I.     

Adhesion activity of fetal gonadal cells to EGF and discoidin domains of milk fat globule-EGF factor 8 (MFG-E8), a secreted integrin-binding protein which is transiently expressed in mouse early gonadogenesis

MFG-E8, a secreted integrin-binding protein, consists of two EGF domains containing a RGD motif and two discoidin domains. In mouse embryogenesis, MFG-E8 is highly expressed in gonadal stromal cells near mesonephros at 11.5–12.5 dpc, but its function in gonadogenesis has not been characterized. To clarify a possible role of MFG-E8 in developing gonads, we analyzed the adhesion activity of 10.5–15.5 dpc gonadal cells to recombinant proteins of EGF or discoidin domains of MFG-E8. In EGF-coated wells, the gonadal cells at 11.5–12.5 dpc revealed a significantly higher adhesion activity as compared to those at 10.5 and 15.5 dpc, while discoidin domains showed a constant number of the adhered cells throughout these stages. To identify the adhesive cells of 11.5-dpc gonads, immunohistochemistry with anti-SF1/Ad4Bp antibody (a specific marker for supporting, steroidogenic, and coelomic epithelial cells) and staining for alkaline phosphatase (a germ cell marker) were carried out. As a result, EGF domains, as well as discoidin domains, were capable of binding to all three groups of SF1/Ad4Bp-positive and negative somatic cells, and germ cells of 11.5-dpc gonads. These findings therefore suggest that MFG-E8 mediates the cell-to-cell interaction among several somatic cell types and germ cells in mouse early gonadogenesis.     

The epidemiology of atopic dermatitis at a tertiary referral skin center in Singapore

Atopic dermatitis is a common chronic, relapsing, pruritic ecematous skin condition with a predilection for the flexural areas and occurs in patients with a personal or family history of atopy. The aim of this study is to describe the profile of atopic dermatitis seen at the National Skin Centre in Singapore. A retrospective chart review was conducted of all the patients with atopic dermatitis seen during the first six months of 1994. There were 492 patients whose ages ranged from one month to 74 years with an equal sex ratio. The prevalence was 2%. The onset of the disease occurred before the age of 10 years in 61.2% of patients. In 13.6% of the patients, the onset was after the age of 21 years. Two hundred and fifty-four patients (52%) had "pure" atopic dermatitis without concomitant respiratory allergies. Two hundred and thirty-eight patients (48%) suffered from a "mixed" type, with 23% having allergic rhinitis, 12% having asthma and 13% having both asthma and allergic rhinitis. Two hundred and thirty-one patients (47%) had at least one first-degree family member with atropy: atopic dermatitis (17%), asthma (15%) and allergic rhinitis (15%). Most of the patients, 416 (84.5%), had subacute eczema at presentation. Ichthyosis vulgaris was present in 38 patients (8%) and pityriasis alba in 13 patients (3%). The most common infective complication was bacterial infection (impetiginized eczema, folliculitis, cellullitis) present in 95 patients (19%) followed by viral infections (eczema herpeticum, viral warts and molluscum contagiosum) in 17 patients (3%). Allergies were noted in 43 patients (9%) based on the history given. The most common was drug allergies (penicillin and co-trimoxazole) in 28 patients followed by food allergies in 11 patients. Common aggravating factors reported include heat, sweating, stress, thick clothing and grass intolerance. Most patients could be controlled with a fairly simple regimen of moisturizers, topical steroids and antibiotics for acute flares. Short courses of systemic steroids were used in 78 patients (16%). Three patients were treated with phototherapy, Two on UVAB and one on PUVA. The pattern of atopic dermatitis in Singapore is similar to that reported in the Western literature except for a lower prevalence and a significant proportion of adult onset atopic dermatitis.     

Founder effect in spinal and bulbar muscular atrophy (SBMA)

We analyzed the polymorphic (CAG)n and (GGC)n repeats of the androgen receptor gene in 113 unrelated X-linked spinal and bulbar muscular atrophy (SBMA) X chromosomes and 173 control X chromosomes in Japanese males. The control chromosomes had an average CAG repeat number of 21 +/- 3 with a range from 14-32 repeat units, and SBMA chromosomes had a range from 40-55 with a median of 47 +/- 3 copies. The control chromosomes had seven different alleles of the (GGC)n repeat with the range of 11 to 17; the most frequent size of (GGC)n was 16 (79%), while (GGC)17 was very rare (1%). However, in SBMA chromosomes only two alleles were seen; the most frequent size of (GGC)n was 16 (61%) followed by 17 (39%). (GGC)n size distribution was significantly different between SBMA and control chromosomes (P < 0.0001), indicating the presence of linkage disequilibrium. There was no allelic association between the (CAG)n and (GGC)n microsatellites among control subjects as well as SBMA patients, which suggests that a founder effect makes a more significant contribution to generation of Japanese SBMA chromosomes than new mutations.      

Distal oblique osteotomy versus cheilectomy for moderate-advanced hallux rigidus: A 2-year propensity-score-matched study

BackgroundThe surgical treatment of moderate-advanced hallux rigidus is controversial. Cheilectomy is widely used but has recurrence rates of up to 30%. Dorsal oblique metatarsal osteotomy (DOO) has also shown good results, however, there is no study comparing outcomes of the DOO against cheilectomy.MethodsThis was a retrospective propensity score matched study based on registry data from a single tertiary institution. Between 2007 and 2017, all patients who had undergone dorsal cheilectomy or DOO for hallux rigidus were included. Patients with previous foot surgery, revision surgeries, and concomitant surgical procedures were excluded. Clinical outcomes, complication rates, revision rates and patient satisfaction were assessed at 2 years postoperatively.ResultsThere were 44 patients (34 cheilectomy, 10 DOO). After propensity score matching, 17 cheilectomy and all 10 DOO cases were selected for comparison. Patients in both groups had a significant improvement in visual analogue pain scores (VAS) and AOFAS 1st toe scores 2-years post-operatively (P < 0.001) with high levels of post-operative satisfaction (85.1%). Overall there were no statistically significant differences in post-operative scores, improvement in scores, complication rates, revision rates, and levels of patient satisfaction between groups.ConclusionsBoth the DOO and cheilectomy give similarly good outcomes for moderate-advanced hallux rigidus. Further studies are needed to elucidate differences in indications for each procedure.     

Ultrastructural study of the effects of 6-hydroxydopamine on the sinuatrial and atrioventricular nodes of the heart of the monkey (Macaca fascicularis)

The present study examined the ultrastructural changes in the sinuatrial and atrioventricular nodes of the heart of the monkey (Macaca fascicularis) after 6-hydroxydopamine (6-OHDA) at survival times of 1, 3, 5, 7 and 14 days. Changes ranged from dissolution of the cytoplasm to amorphous appearance and darkening of the nodal cells. Initially, the ultrastructural changes were quite similar in both sinuatrial (SA) and atrioventricular (AV) nodal cells but in the later stage, especially at fourteen days, affected SA nodal cells showed empty-looking appearance while affected AV nodal cells displayed a darkened appearance. The cardiac neurons also showed ultrastructural changes such as diffuse accumulation of glycogen particles, distended cisternae of the rough endoplasmic reticulum and increased lipofuscin granules. Some of the vacuolated axonal profiles containing large dense-cored vesicles were in close association with the somata of the cardiac neurons. There were also changes in the non-neuronal cells such as darkening and vacuolation of the cells capping the neurons. Macrophages and Schwann cells were activated to engulf the degenerating nodal cells and axonal profiles. The ultrastructural changes in the nodal cells and the cardiac neurons reflect a disturbance in the cell metabolism presumably brought about by the impairment of the sympathetic nervous system.     

Ultrastructural changes in the atrioventricular valves of streptozotocin-induced diabetic rats

The present study describes ultrastructural changes in the atrioventricular (AV) valves of diabetic rats at 3, 6, 9 and 12 months. At 3 and 6 months of diabetes, the interstitial cells were characterized by an accumulation of vacuoles, lysosomes, electron-dense vesicles, mitochondria and cisternae of rough endoplasmic reticulum in the cytoplasm. There were numerous collagen fibres in the interstitial space. Unmyelinated axons were ensheathed by Schwann cells. Infiltration of macrophages was observed near the interstitial cells. Each macrophage showed a large round or oval nucleus containing heterochromatin masses at the periphery of the cell nucleus. At 9 and 12 months of diabetes, the interstitial cells contained numerous vacuoles, dilated mitochondria, agranular vesicles and a prominent multivesicular body in the cytoplasm. Degenerating unmyelinated nerve fibres were encountered near the interstitial cells. Phagocytic macrophages contained numerous vacuoles of various sizes, which occupied most of the cytoplasmic area. Several vacuoles and degenerated electron-dense granules (some of them appeared to be fragmented) were present in the cytoplasm of interstitial cells and macrophages. It is concluded that interstitial cells in the AV valves contribute to valvular dysfunction in the streptozotocin-induced diabetic rats.