Linear time complexity de novo long read genome assembly with GoldRush.

Current state-of-the-art de novo long read genome assemblers follow the Overlap-Layout-Consensus paradigm. While read-to-read overlap - its most costly step - was improved in modern long read genome assemblers, these tools still often require excessive RAM when assembling a typical human dataset. Our work departs from this paradigm, foregoing all-vs-all sequence alignments in favor of a dynamic data structure implemented in GoldRush, a de novo long read genome assembly algorithm with linear time complexity. We tested GoldRush on Oxford Nanopore Technologies long sequencing read datasets with different base error profiles sourced from three human cell lines, rice, and tomato. Here, we show that GoldRush achieves assembly scaffold NGA50 lengths of 18.3-22.2, 0.3 and 2.6 Mbp, for the genomes of human, rice, and tomato, respectively, and assembles each genome within a day, using at most 54.5 GB of random-access memory, demonstrating the scalability of our genome assembly paradigm and its implementation.

Are testicular cortisol and WISP2 involved in estrogen-regulated Sertoli cell proliferation?

The number of Sertoli cells has a major effect on adult testis size and sperm production capacity. Mechanisms that regulate the number of Sertoli cells in livestock are at best nebulously understood; however, with lesser testicular estrogen production, proliferation of Sertoli cells is prolonged compared with vehicle-treated littermates. Decreased WISP2 gene expression in testes as a result of less endogenous estrogen is similar to altered WISP2 gene expression following corticosteroid treatment of some cultured cells. Taken together, these findings indicate decreased testicular cortisol might be in the signaling pathway between reduced endogenous estrogens and the prolonged interval of Sertoli cell proliferation. Hence, in these studies, potential actions of testicular corticosteroid on Sertoli cell numbers were evaluated. Testicular cortisol concentrations were reduced at 6.5 weeks of age (P < 0.05) in littermates treated with the aromatase inhibitor, letrozole, compared with littermates treated with vehicle. Letrozole treatment leads to reduced testicular estradiol and greater Sertoli cell numbers during the early juvenile interval in pigs. The inverse relationship between testicular glucocorticoid and Sertoli cell proliferation was also tested by increasing local testicular glucocorticoids using the synthetic compound, dexamethasone. Local administration beginning at 1.5 weeks of age (osmotic pump and catheter (n = 3) or a silastic implant (n = 5)) reduced Sertoli cell numbers at 6.5 weeks of age compared with littermates that received the vehicle treatment (P< 0.05). In summary, testicular glucocorticoid concentration was inversely correlated with Sertoli cell numbers during the first wave of Sertoli cell proliferation.

Effect of enhanced external counterpulsation on clinical symptoms, quality of life, 6-minute walking distance, and echocardiographic measurements of left ventricular systolic and diastolic function after 35 days of treatment and at 1-year follow up in 47 patients with chronic refractory angina pectoris.

In a prospective study, enhanced external counterpulsation (EECP) was performed for 1 hour each day for 35 days in 47 patients, mean age 61 +/- 8 years, with prior coronary revascularization who had chronic refractory angina pectoris despite antianginal drugs and who were not candidates for further coronary revascularization. Compared with baseline values, EECP significantly improved anginal symptoms, dyspnea on exertion, and quality of life after 35 days of treatment (P < 0.001) and at 1-year follow up (P < 0.001). Compared with the baseline value of 653 +/- 249 feet, EECP significantly improved the 6-minute walking distance to 1025 +/- 234 feet after 35 days of treatment (P < 0.001) and to 1040 +/- 221 feet at 1-year follow up (P < 0.001). However, EECP did not significantly affect left ventricular ejection fraction, left ventricular end-diastolic and end-systolic dimensions, left ventricular end-diastolic and end-systolic volumes, E/A ratio, isovolumic relaxation time, and deceleration time measured by two2-dimensional and Doppler echocardiography.

Waardenburg syndrome.

Waardenburg syndrome is a rare inherited and genetically heterogenous disorder of neural crest cell development. Four distinct subtypes showing marked interfamilial and intrafamilial variability have been described. We report a girl showing constellation of congenital hearing impairment with 110 dB and 105 dB loss in right and left ear respectively, hypoplastic blue iridis, white forelock, dystopia canthorum and broad nasal root. Other affected relatives of the family, with variable features of the syndrome, have been depicted in the pedigree.