Loss of CHSY1, a secreted FRINGE enzyme, causes syndromic brachydactyly in humans via increased NOTCH signaling

We delineated a syndromic recessive preaxial brachydactyly with partial duplication of proximal phalanges to 16.8 Mb over 4 chromosomes. High-throughput sequencing of all 177 candidate genes detected a truncating frameshift mutation in the gene CHSY1 encoding a chondroitin synthase with a Fringe domain. CHSY1 was secreted from patients' fibroblasts and was required for synthesis of chondroitin sulfate moieties. Noticeably, its absence triggered massive production of JAG1 and subsequent NOTCH activation, which could only be reversed with a wild-type but not a Fringe catalytically dead CHSY1 construct. In vitro, depletion of CHSY1 by RNAi knockdown resulted in enhanced osteogenesis in fetal osteoblasts and remarkable upregulation of JAG2 in glioblastoma cells. In vivo, chsy1 knockdown in zebrafish embryos partially phenocopied the human disorder; it increased NOTCH output and impaired skeletal, pectoral-fin, and retinal development. We conclude that CHSY1 is a secreted FRINGE enzyme required for adjustment of NOTCH signaling throughout human and fish embryogenesis and particularly during limb patterning.     

Taxonomic Review of the Genus Mycterothrips (TEREBRANTIA: THYSANOPTERA) and its Species from Pakistan

ABSTRACT Genus Mycterothrips and one species M. nilgiriensis with both male and female specimens has been recorded for the first time from Pakistan. The genus and the species have been described in detail, measurements of body parts along with illustrations have also been provided for future references. Thus adding to the list of Thysanoptera fauna from Pakistan.     

Effect of periovulatory prostaglandin F2alpha on pregnancy rates and luteal function in the mare.

The objective of this study was to determine whether periovulatory treatments with PGF2alpha affects the development of the CL, and whether the treatment was detrimental to the establishment of pregnancy. Reproductively sound mares were assigned randomly to one of the following treatment groups during consecutive estrus cycles: 1. 3,000 IU hCG within 24 hours before artificial insemination and 500 microg cloprostenol (PGF2alpha analogue) on Days 0, 1, and 2 after ovulation (n=8), 2. 2 mL sterile water injection within 24 hours before artificial insemination and 500 microg cloprostenol on Days 0, 1, and 2 after ovulation (n=8); 3. 3,000 IU hCG within 24 hours before artificial insemination and 500 microg cloprostenol on Day 2 after ovulation (n=8); or 4. 3,000 IU hCG within 24 hours before artificial insemination and 2 mL of sterile water on Days 0, 1, and 2 after ovulation (controls; n=8). Blood samples were collected from the jugular vein on Days 0, 1, 2, 5, 8, 11, and 14 after ovulation. Plasma progesterone concentrations were determined by the use of a solid phase 125I radioimmunoassay. All mares were examined for pregnancy by the use of transrectal ultrasonography at 14 days after ovulation. Mares in Group 1 and 2 had lower plasma progesterone concentrations at Day 2 and 5, compared to mares in the control group (P < 0.001). No difference was detected between group 1 and 2. Plasma progesterone concentrations in group 3 were similar to the control group until the day of treatment, but decreased after treatment and were significantly lower than the control group at Day 5 (P < 0.001). Plasma progesterone concentrations increased in all treatment groups after Day 5, and were comparable among all groups at Day 14 after ovulation. Cloprostenol treatment had a significant effect on pregnancy rates (P < 0.01). The pregnancy rate was 12.5% in Group 1, 25% in Group 2, 38% in Group 3, and 62.5% in Group 4. It was concluded that periovulatory treatment with PGF2alpha has a detrimental effect on early luteal function and pregnancy.     

Prevalence of factor V G1691A (Leiden) and prothrombin G20210A polymorphisms among apparently healthy Jordanians

Factor V Leiden and prothrombin G20210A are related genetic risk factors for venous thromboembolism (VTE). Analysis for both mutations is increasingly being performed on patients exhibiting hypercoagulability. The objective of this study was to determine the prevalence of factor V Leiden (FVL), prothrombin-G20210A (PT-G20210A) polymorphisms and their coexistence among apparently healthy Jordanians. One thousand apparently healthy individuals from representative regions of Jordan with no previous history of VTE participated in this study. The mean age of participants was 28.5+/-6.4 years (age range 18-45 years). Two hundred and eighteen subjects were APC resistant with an APC-R mean of 85.52+/-15.35 seconds; the non-resistant subjects had an APC-R mean of 159.90+/-26.96 seconds. A multiplex polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the simultaneous detection of FVL and prothrombin G20210A was used to analyze the 218 DNA samples that were APC-R resistant. Both mutations generate HindIII RFLPs and the prothrombin amplicon contains an invariant HindIII recognition sites. The multiplex PCR-RFLP of Factor V for those 218-samples was: 41 wild-type, 169 heterozygous mutant, and eight homozygous mutant individuals. For prothrombin G20210A, the multiplex PCR-RFLP identified 215 wild-type and three heterozygous mutant individuals. Factor V positive individuals (n=50) had a mean F-V activity of 78.04%+/-25.81. F-V activity among wild type (n=41), F-V Leiden heterozygous (n=169) and F-V Leiden homozygous (n=8) were 92.93%+/-16.17, 87.02%+/-15.21 and 96.14%+/-12.32, respectively. Factor II positive subjects (n=47) had a mean factor II activity of 127.96%+/-21.37. F-II activity among carriers (heterozygous, n=3) and non-carriers (normal, n=215) of PT-G20210A mutation were 107.67%+/-9.29 and 105.00%+/-17.79, respectively. The prevalence of FVL was 21.8% and there is a little likelihood of the co-inheritance of the FVL and PT-G20210A among healthy young adults, since only few cases were found to be carriers for the two alleles.     

A new strategy for superior reproductive performance of ewes bred out-of-season utilizing progestagen supplement prior to withdrawal of intravaginal pessaries

Two experiments were conducted to examine the effect of progestagen supplement 24h prior to intravaginal pessary withdrawal on reproductive performance of seasonal anestrous ewes. Ewes in each experiment were allocated to treatment and control and all were induced to estrus using either intravaginal MAP (Exp. 1; n=24) or CIDR-G (Exp. 2; n=28) pessaries for 12 days. Half of the ewes in each experiment were supplemented 24h before withdrawal of pessaries with either 10mg oral MAP tablets (Exp. 1) or 25mg i.m. progesterone (P(4)) administration (Exp. 2; P(4)-supplement-treated group). Fertile rams were allowed with the ewes at sponge removal (Day 0, 0h) and estrus was monitored at 6-h intervals for 3 days. Blood samples were collected for measurements of P(4) (Exp. 1 and Exp. 2) and LH (Exp. 2). In both experiments, the percent of ewes in estrus was greater (P<0.05) and intervals to estrus were longer (P<0.05) in progestagen-supplement-treated than control ewes. In Exp. 2, the occurrence and magnitude of LH surges were greater (P<0.01) and intervals to onset of LH surge were longer (P<0.01) in P(4)-supplement-treated than control ewes. In Exp. 2, P(4) supplement elevated P(4) levels from 1.8+/-0.1ng/mL on Day -1 to 4.2+/-0.3 on Day 0 (P<0.001). Following pessaries removal, P(4) concentrations fell to basal values on Day 1 in both groups and remained low until Day 5. Then, P(4) concentrations increased and remained elevated through Day 19 in all (100%) progestagen-supplement-treated in Exp. 1 (12/12) and Exp. 2 (14/14) and in only 5/12 (41.7%) and 6/14 (42.9%) control ewes, respectively. These ewes were confirmed pregnant by ultrasonography and lambed on Day 149.2+/-0.2 following Day 0. In conclusion, progestagen supplement 24h prior to removal of pessary can be used successfully to improve reproductive performance of ewes bred out-of-season.     

Pygo基因的细胞定位及其在果蝇发育过程中的表达(英文)

Wingless信号传导是果蝇胚胎和幼虫发育过程中的一个关键性的信号传导通路。已鉴定出来许多参与Wg Wnt信号传导的Wg或其脊椎动物同源基因Wnt下游传导通路的基因。Wg下游的Wg信号传导是由核TCF LEF 1通过Armadillo (Arm) β catenin介导的。pygopus (pygo)是一个最近发现的Wg Wnt信号传导通路新成员。通过细胞定位实验发现pygo专一性的表达在细胞核中。运用反义mRNA作探针的原位杂交技术 ,观察到了pygo基因在果蝇胚胎中的表达特性。虽然pygo普遍表达于果蝇胚胎发生全过程 ,但pygo在前囊胚层 (pre blastoderm)中的表达水平相对较高 ,这说明胚胎发生过程中来自母方的贡献较高。在幼虫组织 (包括翅成虫盘 ,眼成虫盘和腿成虫盘 )的发育过程中 ,pygo的表达水平总的来说比较低。然而 ,比较翅成虫盘 ,眼成虫盘和腿成虫盘的pygo表达水平 ,则在翅成虫盘和腿成虫盘pygo的表达水平相对较高。     

云南茶树上的附生地衣

对云南茶叶农场中的附生地衣进行调查发现: 附生在茶树上的地衣有25 属, 51 种; 其中, 45 种是首次报道附生在茶树上, 包括2 个中国新记录种: 癞屑衣( Lepraria lobificans) 和阿曼原胚衣( Protoblastenia amagiensis) , 以及20 个云南新分布种。壳状地衣的共生菌丝侵入茶叶树干外皮层组织, 在生长过程中产生地衣酸, 一定程度的加速了农场中茶树的老化; 靠近茶树发芽点生长的壳状地衣和叶状地衣, 造成芽体发育不良, 对茶叶的产量和品质有一定影响。     

宁夏沙坡头地区中国新记录地衣（英文）

报道了宁夏沙坡头沙漠地区地衣3个中国新记录种:Fulgensia desertorum,Rinodina bischoffii和Seirophora orientalis,描述了3种地衣的表型特征,生态学特征及分布情况。