Adaptive response of reproduction to high-altitude hypoxic stress by altering mRNA expression of hypoxia-inducible factors in female yaks (Bos grunniens).

Hypoxia-inducible factors (HIFs) are oxygen-dependent transcriptional activators, but there is little information about their role in yak (Bos grunniens) reproduction. The present study, for the first time, investigated the adaptive mechanism of yak reproduction to high-altitude hypoxic stress by comparing the expression of HIF mRNAs between female yaks at high-altitude and cattle at low-altitude. Hypothalamus, anterior pituitary, oviduct, ovary and uterus tissue samples were collected from five adult female yaks and cattle. mRNA expression was determined by the quantitative real-time polymerase chain reaction. Both HIF-1α and HIF-2α were expressed in all five tissues examined from both species, albeit at different levels. In yaks, the highest mRNA levels of HIF-1α and HIF-2α occurred in the oviduct and anterior pituitary, respectively. Both HIF-1α and HIF-2α mRNA levels were higher in yaks than in cattle (p < 0.01). These data provide evidence that adaptation of reproduction to hypoxic conditions is associated with a greater expression of HIF-1α and HIF-2α in the reproductive axis of female yaks than cattle.

De Novo Mutations Contributes Approximately 7% of Pathogenicity in Inherited Eye Diseases.

Purpose: The purpose of this study was to describe genotype-phenotype associations and novel insights into genetic characteristics in a trio-based cohort of inherited eye diseases (IEDs). Methods: To determine the etiological role of de novo mutations (DNMs) and genetic profile in IEDs, we retrospectively reviewed a large cohort of proband-parent trios of Chinese origin. The patients underwent a detailed examination and was clinically diagnosed by an ophthalmologist. Panel-based targeted exome sequencing was performed on DNA extracted from blood samples, containing coding regions of 792 IED-causative genes and their flanking exons. All participants underwent genetic testing. Results: All proband-parent trios were divided into 22 subgroups, the overall diagnostic yield was 48.67% (605/1243), ranging from 4% to 94.44% for each of the subgroups. A total of 108 IED-causative genes were identified, with the top 24 genes explaining 67% of the 605 genetically solved trios. The genetic etiology of 6.76% (84/1243) of the trio was attributed to disease-causative DNMs, and the top 3 subgroups with the highest incidence of DNM were aniridia (n = 40%), Marfan syndrome/ectopia lentis (n = 38.78%), and retinoblastoma (n = 37.04%). The top 10 genes have a diagnostic yield of DNM greater than 3.5% in their subgroups, including PAX6 (40.00%), FBN1 (38.78%), RB1 (37.04%), CRX (10.34%), CHM (9.09%), WFS1 (8.00%), RP1L1 (5.88%), RS1 (5.26%), PCDH15 (4.00%), and ABCA4 (3.51%). Additionally, the incidence of DNM in offspring showed a trend of correlation with paternal age at reproduction, but not statistically significant with paternal (P = 0.154) and maternal (P = 0.959) age at reproduction. Conclusions: Trios-based genetic analysis has high accuracy and validity. Our study helps to quantify the burden of the full spectrum IED caused by each gene, offers novel potential for elucidating etiology, and plays a crucial role in genetic counseling and patient management.

Construction of urothelium-specific recombinant adenovirus and its inhibition in bladder cancer cell.

AIM: To construct urothelium-specific recombinant adenovirus and investigate its inhibition in bladder cancer cell. METHODS: RT-PCR analysis was used to determine expression patterns of hUPII and coxsackie adenovirus receptor on multiple cell lines. Transient transfection and luciferase detecting assay were used to detect tissue specificity of the hUPII promoter. Recombinant adenovirus Ad-UPII-E1A and Ad-UPII-Null were constructed. Restrictive enzyme digestion assay and PCR confirmed the correct construction. The adenovirus E1A protein expressed in BIU-87 was tested by Western blot after cells were infected with recombinant adenovirus. Recombinant adenovirus Ad-UPII-E1A was tested for its inhibition in bladder cancer cell line BIU-87. RESULTS: HUPII and CAR were expressed and the hUPII promoter is highly active in bladder cancer cell line BIU-87. Using homologous recombination in bacteria technology, the hUPII promoter and E1A gene were inserted into the genome of type 5 recombinant adenovirus. The E1A protein was markedly positive in the samples of BIU-87 cells infected with recombinant adenovirus Ad-UPII-E1A. MTT assay demonstrated recombinant adenovirus Ad-UPII-E1A inhibited bladder cancer cell BIU-87 growth. CONCLUSION: The hUPII promoter shows high tissue specificity. Recombinant adenovirus Ad-UPII-E1A and Ad-UPII-Null were constructed and confirmed. Recombinant adenovirus Ad-UPII-E1A is effective in inhibition in bladder cancer cell line BIU-87.

Traditional uses and pharmacological properties of Clerodendrum phytochemicals.

Clerodendrum is a genus of ca. 500 species in the family Lamiaceae and widely distributed throughout the whole world. Up to now, many species of this genus have been described in various indigenous systems of medicine and are used in preparation of folklore medicines for the treatment of various life-threatening diseases, and more than eleven species of the Clerodendrum genus have been very well studied for their chemical constituents and biological activities, and 283 compounds, including monoterpene and its derivatives, sesquiterpene, diterpenoids, triterpenoids, flavonoid and flavonoid glycosides, phenylethanoid glycosides, steroids and steroid glycosides, cyclohexylethanoids, anthraquinones, cyanogenic glycosides, and others have been isolated and identified. Pharmacological studies have shown that these compounds and extracts from the Clerodendrum genus have extensive activities, such as anti-inflammatory and anti-nociceptive, anti-oxidant, anti-hypertensive, anticancer, antimicrobial, anti-diarrheal, hepatoprotective, hypoglycemic and hypolipidemic, memory enhancing and neuroprotective, and other activities. In this review, we attempt to highlight over phytochemical progress and list the phytoconstituents isolated from the genus Clerodendrum reported so far. The biological activities of this genus are also covered.

Effects of CF(0) Proton Flow on the Distribution of Light Energy Between PSI and PSII.

The Influence of energy transfer inhibitors of ATP synthase on the chlorophyll fluorescence quenching of thylakoids was studied by the saturation pulse method. Triphenyltin chloride (TPT) treatment could result in an increase of q(Q) and a decrease of q(E) of the thylakoids, but DCCD could not. This increase could be abolished when the deltapH across the thylakoid membrane was dissipated by uncouplers (1O mM NH(4)Cl plus 1&mgr;M nigericin) or in higher salt medium which could relieve localized protons on the thylakoid membrane. In the electron transport system of H(2)O right curved arrow PD(0X) or H(2)O right curved arrow PBQ coupled with PSII. The stimulatory effect of TPT on q(Q) also diminished. By the methods of modulated fluorescence and low temperature fluorescence measurement we observed that TPT markedly increased the imbalance of the distribution of light energy between PSI and PSII in favor of PSII. These results suggest that the CF(0) proton flow could influence the light energy distribution between the two photosystems. This might be materialized by the regulation of the membrane-localized protons on the photochemical efficiency of photosystem II.