Biomedical subjects

Peter L Chang

Publications and source records attributed to Peter L Chang.

7 recordsLinked to original sources

PubMed2015

Evolutionary genomics of Culex pipiens: global and local adaptations associated with climate, life-history traits and anthropogenic factors.

We present the first genome-wide study of recent evolution in Culex pipiens species complex focusing on the genomic extent, functional targets and likely causes of global and local adaptations. We resequenced pooled samples of six populations of C. pipiens and two populations of the outgroup Culex torrentium. We used principal component analysis to systematically study differential natural selection across populations and developed a phylogenetic scanning method to analyse admixture without haplotype data. We found evidence for the prominent role of geographical distribution in shaping population structure and specifying patterns of genomic selection. Multiple adaptive events, involving genes implicated with autogeny, diapause and insecticide resistance were limited to specific populations. We estimate that about 5-20% of the genes (including several histone genes) and almost half of the annotated pathways were undergoing selective sweeps in each population. The high occurrence of sweeps in non-genic regions and in chromatin remodelling genes indicated the adaptive importance of gene expression changes. We hypothesize that global adaptive processes in the C. pipiens complex are potentially associated with South to North range expansion, requiring adjustments in chromatin conformation. Strong local signature of adaptation and emergence of hybrid bridge vectors necessitate genomic assessment of populations before specifying control agents.

Adaptation, Biological↗

PubMed2006

Structure alignment based on coding of local geometric measures.

BACKGROUND: A structure alignment method based on a local geometric property is presented and its performance is tested in pairwise and multiple structure alignments. In this approach, the writhing number, a quantity originating from integral formulas of Vassiliev knot invariants, is used as a local geometric measure. This measure is used in a sliding window to calculate the local writhe down the length of the protein chain. By encoding the distribution of writhing numbers across all the structures in the protein databank (PDB), protein geometries are represented in a 20-letter alphabet. This encoding transforms the structure alignment problem into a sequence alignment problem and allows the well-established algorithms of sequence alignment to be employed. Such geometric alignments offer distinct advantages over structural alignments in Cartesian coordinates as it better handles structural subtleties associated with slight twists and bends that distort one structure relative to another. RESULTS: The performance of programs for pairwise local alignment (TLOCAL) and multiple alignment (TCLUSTALW) are readily adapted from existing code for Smith-Waterman pairwise alignment and for multiple sequence alignment using CLUSTALW. The alignment algorithms employed a blocked scoring matrix (TBLOSUM) generated using the frequency of changes in the geometric alphabet of a block of protein structures. TLOCAL was tested on a set of 10 difficult proteins and found to give high quality alignments that compare favorably to those generated by existing pairwise alignment programs. A set of protein comparison involving hinged structures was also analyzed and TLOCAL was seen to compare favorably to other alignment methods. TCLUSTALW was tested on a family of protein kinases and reveal conserved regions similar to those previously identified by a hand alignment. CONCLUSION: These results show that the encoding of the writhing number as a geometric measure allow high quality structure alignments to be generated using standard algorithms of sequence alignment. This approach provides computationally efficient algorithms that allow fast database searching and multiple structure alignment. Because the geometric measure can employ different window sizes, the method allows the exploration of alignments on different, well-defined length scales.

Algorithms↗

PubMed2002

Successive pregnancies with delivery of two healthy infants in a couple who was discordant for human immunodeficiency virus infection.

OBJECTIVE: To describe two successive pregnancies resulting in two healthy infants in an HIV-discordant couple who underwent IVF-ICSI. DESIGN: Case report. SETTING: University-based infertility clinic. PATIENT(S): A couple seeking fertility treatment in which the male partner was seropositive for HIV-1. INTERVENTION(S): Controlled ovarian hyperstimulation and IVF-ET with ICSI. MAIN OUTCOME MEASURE(S): Pregnancy outcome and HIV-1 seroconversion. RESULT(S): The couple delivered two healthy infants on successive pregnancies with use of IVF-ET with ICSI. CONCLUSION(S): For HIV-discordant couples in which the male partner is seropositive for HIV-1, IVF with ICSI is a viable option.

Adult↗

PubMed2002

Establishing a clinical program for human immunodeficiency virus 1-seropositive men to father seronegative children by means of in vitro fertilization with intracytoplasmic sperm injection.

OBJECTIVE: We assessed the safety and efficacy of providing assisted reproduction to men who are seropositive for human immunodeficiency virus type 1 (HIV-1). STUDY DESIGN: HIV-1-serodiscordant couples underwent in vitro fertilization with intracytoplasmic sperm injection (IVF-ICSI). Patients were screened for HIV-1 3 and 6 months after embryo transfer to determine safety. Infants and mothers were tested at delivery and at 3 months after delivery. Clinical outcomes were compared with those of matched control couples who had undergone IVF-ICSI to measure efficacy. RESULTS: There were no seroconversions in women (n = 34) or offspring (n = 25) after 55 embryo transfers. Treatment efficacy was similar to that for control couples: retrieved eggs (15.8 +/- 1.3 vs 12.3 +/- 0.8); fertilization rate (64.9% vs 68.0%); embryos cryopreserved (1.1 +/- 0.3 vs 0.3 +/- 0.1, P <.05); clinical pregnancies per embryo transfer (45.5% vs 35.4%); ongoing or delivered pregnancies per embryo transfer (30.9% vs 25.0%). CONCLUSION: Although findings are preliminary, IVF-ICSI provides HIV-1-serodiscordant couples with a reasonably safe means of having children because their assisted reproduction performance is similar to that of conventional patients.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Supraphysiological estradiol levels do not affect oocyte and embryo quality in oocyte donation cycles.

BACKGROUND: The study aim was to determine whether supraphysiological estradiol (E(2)) levels reduce oocyte/embryo quality in oocyte donation cycles. METHODS: A retrospective analysis of 330 consecutive fresh oocyte donation cycles was performed in an assisted reproductive treatment programme between January 1996 and December 2000. Throughout the study period, oocyte donors and recipients followed a standard synchronization regimen that did not vary. A serum E(2) level (peak E(2)) was obtained from all oocyte donors on the morning of HCG administration. Peak E(2) values were grouped by 33rd percentile (group I, <1500 pg/ml; group II, 1500-3000 pg/ml; and group III, >3000 pg/ml). All embryo transfers were performed on day 3 after oocyte recovery. RESULTS: Comparisons between groups revealed no significant differences in the quality of oocytes retrieved, and in fertilization rates. Higher peak E(2) levels were directly correlated with a greater number of oocytes retrieved, embryos available for transfer and cryopreservation, and higher average embryo quality scores (P < 0.005). Compared with group I, group III had significantly higher embryo implantation rates (P < 0.05). CONCLUSIONS: Sustained supraphysiological E(2) levels do not adversely affect the quality of developing oocytes and embryos. On the contrary, elevated E(2) levels are associated with a larger number of oocytes and embryos and high-grade embryos for transfer/cryopreservation and, consequently, improved implantation rates.

Adult↗

PubMed2002

Serum estradiol levels after 4 days of ovarian hyperstimulation in oocyte donors are predictive of embryo quality and clinical outcomes.

OBJECTIVE: To determine whether estradiol (E(2)) levels after 4 days of ovarian hyperstimulation in leuprolide-downregulated cycles are predictive of embryo quality and pregnancy outcome in oocyte donation. MATERIAL AND METHODS: Retrospective analysis of 287 consecutive oocyte donation cycles performed at a university assisted reproduction therapy program between January 1996 and December 2000. Oocyte donors and recipients followed a non-varied standard synchronization regimen. A serum E(2) (day-5 E(2)) was obtained from egg donors the morning after leuprolide acetate downregulation and 4 days after hMG/FSH administration. Day-5 E(2) was categorized into 3 groups: group I <75 pg/ml; group II 75-350 pg/ml, and group III > or =350 pg/ml. All embryo transfers were performed 3 days after oocyte recovery. RESULTS: Elevated day-5 E(2) levels were directly correlated with higher average embryo scores, greater number of oocytes retrieved, and greater number of embryos available for transfer and cryopreservation. Improved pregnancy outcomes were also noted for group III (day-5 E(2) level >350 pg/ml). CONCLUSION: After 4 days of gonadotropin stimulation, an E(2) level of >350 pg/ml is most predictive of higher embryo grade and pregnancy outcome in oocyte donation.

Adult↗

PubMed2002

GnRH antagonist in older IVF patients. Retrieval rates and clinical outcome.

OBJECTIVE: To determine if the use of a midcycle GnRH antagonist provides better clinical outcomes and lower cancellation rates in in vitro fertilization (IVF). STUDY DESIGN: We examined all patients older than 40 years undergoing IVF-embryo transfer cycles between January 1999 and December 2000. Prior to June 2000, controlled ovarian stimulation in women > or = 40 years was performed with follicle stimulating hormone (FSH)/human menopausal gonadotropin (hMG) only and no GnRH agonist or antagonist (group I). After June 2000, following the release of Ganirelix in the U.S., all women > or = 40 years were stimulated with FSH/hMG + Ganirelix (group II). Outcomes of IVF cycles prior to Ganirelix were compared to results after its introduction. RESULTS: Cancellation rates were significantly lower in group II (16%) as compared to group I (67%) (P < .05). In patients with oocytes retrieved, group II had a significantly higher number of recovered oocytes (7.7 +/- 0.8 vs. 5.3 +/- 0.7, P < .05). However, the number of embryos transferred, cumulative embryo scores, implantation rates and ongoing pregnancy rates did not differ significantly between groups. CONCLUSION: Although our results are preliminary, the addition of GnRH antagonist avoids ovarian suppression at the start of controlled ovarian hyperstimulation and prevents the premature LH surge at midcycle. Thus, more patients attempting IVF undergo oocyte retrieval, although clinical outcomes may not necessarily be improved.

Adult↗