Effects of Thermocycles on Body Weight Gain and Gonadal Growth in the Goldfish, Carassius auratus

Goldfish subjected to increased temperatures at one of six different times of day had significant differences in weight gain and testicular growth depending on the time of treatment. Depending on the time of day the thermocycle was initiated, weight gain and testicular growth could be either stimulated, inhibited, or equal to that in fishes subjected to constant heat or constant cold. Heat applied during the last 4 h of darkness was particularly conducive to weight gain and testicular growth. The results of this study may have important implications for aquaculture

Clinical Implications of Mutations at Reverse Transcriptase Codon 135 on Response to NNRTI-Based Therapy

To evaluate the impact of mutations at reverse transcriptase codon 135 on treatment outcomes in patients receiving NNRTI-based antiretroviral therapy, a total of 68 patients (30 with and 38 without baseline mutations at codon 135) were evaluated. Median increases in CD4 counts were 135 and 90 cells/mm3 (p=0.32), virologic suppression (HIV RNA < 400 copies/mL) was achieved in 16 (53%) and 16 (42%) patients (p=0.50), while NNRTI resistance was detected in 10/14 (71%) and 16/22 (73%) in patients with and without mutations at codon 135, respectively. Patients who experienced a virologic breakthrough and had a baseline mutation at codon 135 were more likely to evolve a single NNRTI resistance mutation (8/14 vs 4/22, p=0.029) but less likely to evolve multiple NNRTI resistance mutations (2/14 vs 12/22, p = 0.033). Mutations at codon 135 do not affect response rates, but affect the pattern of development of NNRTI resistance mutations. This has important implications for the subsequent use of newer NNRTIs such as etravirine in salvage therapy

Temperature-Induced Phase Shift of Daily Rhythm of Serum Prolactin in Gulf Killifish

Daily variations in circulating levels of the pituitary hormone prolactin have been reported in several vertebrates, including fishes. In some animals, the 24-h rhythm changes seasonally with respect to the time of day that maximum and minimum prolactin levels occur. It has been hypothesised that this seasonal change in phase of prolactin rhythm is an important component of the mechanism controlling seasonality in vertebrates. Because water temperature is generally considered the principal environmental regulator of seasonal changes in reproduction and metabolism in many fishes, including the gulf killifish Fundulus grandis, we determined the daily rhythm of serum prolactin concentrations in fish held at temperatures that are stimulatory (20 °C) or inhibitory (28 °C) for reproductive development. We found that an increase in water temperature from 20° to 28 °C phase shifts the daily variation of serum prolactin with respect to the daily photoperiod in F. grandis

Mutations in DCHS1 Cause Mitral Valve Prolapse

SUMMARY Mitral valve prolapse (MVP) is a common cardiac valve disease that affects nearly 1 in 40 individuals1–3. It can manifest as mitral regurgitation and is the leading indication for mitral valve surgery4,5. Despite a clear heritable component, the genetic etiology leading to non-syndromic MVP has remained elusive. Four affected individuals from a large multigenerational family segregating non-syndromic MVP underwent capture sequencing of the linked interval on chromosome 11. We report a missense mutation in the DCHS1 gene, the human homologue of the Drosophila cell polarity gene dachsous (ds) that segregates with MVP in the family. Morpholino knockdown of the zebrafish homolog dachsous1b resulted in a cardiac atrioventricular canal defect that could be rescued by wild-type human DCHS1, but not by DCHS1 mRNA with the familial mutation. Further genetic studies identified two additional families in which a second deleterious DCHS1 mutation segregates with MVP. Both DCHS1 mutations reduce protein stability as demonstrated in zebrafish, cultured cells, and, notably, in mitral valve interstitial cells (MVICs) obtained during mitral valve repair surgery of a proband. Dchs1+/− mice had prolapse of thickened mitral leaflets, which could be traced back to developmental errors in valve morphogenesis. DCHS1 deficiency in MVP patient MVICs as well as in Dchs1+/− mouse MVICs result in altered migration and cellular patterning, supporting these processes as etiological underpinnings for the disease. Understanding the role of DCHS1 in mitral valve development and MVP pathogenesis holds potential for therapeutic insights for this very common disease