Makorin 1 is required for Drosophila oogenesis by regulating insulin/Tor signaling.

Reproduction is a process that is extremely sensitive to changes in nutritional status. The nutritional control of oogenesis via insulin signaling has been reported; however, the mechanism underlying its sensitivity and tissue specificity has not been elucidated. Here, we determined that Drosophila Makorin RING finger protein 1 gene (Mkrn1) functions in the metabolic regulation of oogenesis. Mkrn1 was endogenously expressed at high levels in ovaries and Mkrn1 knockout resulted in female sterility. Mkrn1-null egg chambers were previtellogenic without egg production. FLP-FRT mosaic analysis revealed that Mkrn1 is essential in germline cells, but not follicle cells, for ovarian function. As well, AKT phosphorylation via insulin signaling was greatly reduced in the germline cells, but not the follicle cells, of the mutant clones in the ovaries. Furthermore, protein-rich diet elevated Mkrn1 protein levels, without increased mRNA levels. The p-AKT and p-S6K levels, downstream targets of insulin/Tor signaling, were significantly increased by a nutrient-rich diet in wild-type ovaries whereas those were low in Mkrn1exS compared to wild-type ovaries. Taken together, our results suggest that nutrient availability upregulates the Mkrn1 protein, which acts as a positive regulator of insulin signaling to confer sensitivity and tissue specificity in the ovaries for proper oogenesis based on nutritional status.

Makorin 1 Regulates Developmental Timing in Drosophila.

The central mechanisms coordinating growth and sexual maturation are well conserved across invertebrates and vertebrates. Although mutations in the gene encoding makorin RING finger protein 3 (mkrn3 ) are associated with central precocious puberty in humans, a causal relationship has not been elucidated. Here, we examined the role of mkrn1, a Drosophila ortholog of mammalian makorin genes, in the regulation of developmental timing. Loss of MKRN1 in mkrn1 exS prolonged the 3rd instar stage and delayed the onset of pupariation, resulting in bigger size pupae. MKRN1 was expressed in the prothoracic gland, where the steroid hormone ecdysone is produced. Furthermore, mkrn1 exS larvae exhibited reduced mRNA levels of phantom, which encodes ecdysone-synthesizing enzyme and E74, which is a downstream target of ecdysone. Collectively, these results indicate that MKRN1 fine-tunes developmental timing and sexual maturation by affecting ecdysone synthesis in Drosophila. Moreover, our study supports the notion that malfunction of makorin gene family member, mkrn3 dysregulates the timing of puberty in mammals.

[Natural Transition Of Endemicity Of Malayan Flariasis In Inland Korea: Pattern Of Change In Microfilaria Rate Among Inhabitants Of Yongpung (Former Yongju) Area During The Period Of The Last Seven Years]

With a purpose to find out natural transition of endemicity of Malayan filariasis in inland Korea, a survey was conducted in June 1980 in Isan-Myeon of Yongpung-Gun (former Yongju-Gun) where an epidemiological investigation had been carried out in 1973 without any control activities such as chemotherapy. Five sample villages were surveyed for microfilaremia by 20 microliter night blood examination among inhabitants and the results of the surveys conducted in 1973 and 1980 were compared to determine natural transition of the endemicity of malayan filariasis during the period of the last 7 years. 1. The current microfilaria rate among inhabitants in the 5 villages was 2.2 % on the average (male: 1.6 %, female: 2.8 %) from 370 persons examined. By village, the rates were 5.9 % (number of persons examined: 34) in Baranggol, 0 % (30) in Guitonggl, 4.2 % (72) in Alseonggol, 0 %(65) in Jangjagol and 1.8 % (169) in Saehae. 2. Extremely low microfilaria rate was noted in young age groups. By age group, no positive case was found in those age groups below 30~39 years except 10~14 age group in which 2 positives (4.4 %) were found. Two positives each were found in the respective age groups of 40~49(3.2 %), 50~59 (4.4 %) and over 60 (3.4 %). 3. In evaluation of the natural transition of the endemicity during the period of the last 7 years, the microfilaria rate turned out from 13.1 % in 1973 to 2.2 % in 1980. The difference in the microfilaria rate was 10.9 % and the natural reduction rate per year was 1.6 % on the average. 4. From the examination of 35 cases which had revealed microfilaremia 7 years ago, 85.7 %(30) of them were found to have converted to microfilaria negatives. On the other hand, from the 151 cases which had revealed no microfilaria in 1973, only 0.7 % (1) of them was found to have converted to microfilaria positive. 5. In the intensity of microfilaremia, the number of microfilaria/20 microliter blood per positive case was 11.0 in 1973 and 9.1 in 1980. The number of microfilaria/20 microliter per examinee was 1.4 in 1973 and 0.2 in 1980, thus reduced to 1/7 during the period of the 7 years. 6. The retarding endemicity of malayan filariasis in inland Korea was considered to be resulted in by the gradual increase of environmental factors in relation to ecology of vector mosquitoes, which adversely affect to the transmission of malayan filariasis. Followings are suggested to be the factors which control the transmission of the malayan filariasis in this area: 1) Inhabitants are the only natural final host of Brugia malayi infection in this area, 2) Gradual elevation of living standards of the inhabitants, 3) Gradual awakening of consciousness and behavior among inhabitants to protect themselves from mosquito biting using such as mosquito nets and insecticide sprays, 4) Preference of animal bait of vector mosquitoes, Anopheles sinensis, 5) Increase in number of domestic animals and fowls being raised in the village areas which play a major part of blood donors to vector mosquitoes, and 6) Relatively short (3~4 months) period of mosquito season in a year.

[Epidemiological conditions of Metagonimus yokogawai infection in Hadong Gun, Gyeongsang Nam Do]

An epidemiological investigation was conducted on Metagonimus yokogawai infection in Hadong Gun (County), Gyeongsang Nam Do, Korea, and following findings were obtained. 1. Overall prevalence rate of Metagonimus yokogawai infection was 29.1% from a total of 1,163 inhabitants examined. By area of river and stream, Seomjin-gang R.: 9.5% (out of 95 inhabitants examined) in Jeondo Ri in the lower river, 19.9% (156) at Dugog Ri near Hadong town, and 90.8% (65) in Tab Ri of Hwagae Myeon where Hwagae-cheon Stream joins; Hwagae-Cheon Stream: 42.2% (45) in Yonggang Ri of the middle stream and 27.5% (72) in Daeseong Ri of the upper stream; Hoengcheon-gang R.: 54.7% (161) in Gojeol Ri of the lower river, 40.6% (128) in Hoengcheon Ri of the middle stream, and 5.4% (93) in Jungi Ri of the upper stream, and 43.8% (89) in Uge Ri located along a tributary of the Hoengcheon-gang R. and 4.0% (101) in Jangam Ri which is located about 4 km away from the river; Deogcheon-gang R.: 18.5% (54) in Munam Ri; Gwangog-cheon Stream: 2.8% (107) in Gwangog Ri. 2. The difference in prevalence rate of the infection by area was correlated with the opportunity and amount of raw eating of sweetfish by the inhabitants in the respective areas. 3. By age and sex, the overall prevalence rate increased from young age group and reached a peak at 20-29 age group and then the rate decreased gradually. In high endemic areas, however, a peak level of the rate lasted up to 40-49 age group in male. On the other hand, in low endemic areas, the rate was significantly lower in female, though moderate level of the infection was seen in male. The overall prevalence rate was higher in male than in female and the difference was greater in middle age groups. 4. The most significant mode of infection by the inhabitants was the raw eating of sweetfish which commonly harbour metacercariae of M. yokogawai during summer through autumn. Besides, it was noted that the infection can be acquired through contamination with the metacercariae on food of various side-dish and kitchen utensils as well as on hands of a cook when such fish are prepared or handled. 5. The inhabitants usually begin to acquire infection from early June of a year when fishing of sweetfish opens and acquire infection more frequently in July and August when fish are caught more productively and favored for raw consumption by inhabitants. From September, sweetfish are no more favored for raw consumption and accordingly are dried and cooked in this season. 6. The infection in the sweetfish Plecoglossus altivelis as the second intermediate host was first observed from May with low level of infection and the intensity of infection in a fish rapidly increased until reaching a peak in October when sweetfish season normally ends. 7. The first intermediate host snail of M. yokogawai in this area was Semisulcospira coreana (Martens) which is widely distributed in the streams and rivers in this locality.