Age-Characteristic Changes of Glucose Metabolism, Pancreatic Morphology and Function in Male Offspring Rats Induced by Prenatal Ethanol Exposure

Intrauterine growth restricted offspring suffer from abnormal glucose homeostasis and β cell dysfunction. In this study, we observed the dynamic changes of glucose metabolic phenotype, pancreatic morphology, and insulin synthesis in prenatal ethanol exposure (PEE) male offspring rats, and to explore the potential intrauterine programming mechanism of the glucocorticoid-insulin-like growth factor 1 (GC-IGF1) axis. Ethanol (4 g/kg·d) was administered through oral gavage during gestational day (GD) 9–20. Serum glucose and insulin levels, pancreatic β cell mass, and expression of glucocorticoid receptor (GR), IGF1 and insulin were determined on GD20, postnatal week (PW) 6, PW12 with/without chronic stress (CS), and PW24, respectively. Both intraperitoneal glucose and insulin tolerance tests were conducted at PW12 and PW24. Results showed that the serum glucose and insulin levels as well as pancreatic β cell mass were reduced on GD20 in PEE males compared with the controls, while pancreatic GR expression was enhanced but IGF1 and INS1/2 expression were suppressed. After birth, compared with the controls, β cell mass in the PEE males was initially decreased at PW6 and gradually recovered from PW12 to PW24, which was accompanied by increased serum glucose/insulin levels and insulin resistance index (IRI) at PW6 and decreased serum glucose contents at PW12, as well as unchanged serum glucose/insulin concentrations at PW24. In addition, both improved glucose tolerance and impaired insulin sensitivity of the PEE males at PW12 were inversed at PW24. Moreover, at PW6 and PW12, pancreatic GR expression in the PEE group was decreased, while IGF1 expression was reversely increased, resulting in a compensatory increase of insulin expression. Moreover, CS induced pancreatic GR activation and inhibited IGF1 expression, resulting in impaired insulin biosynthesis. Conclusively, the above changes were associated with age and the intrauterine programming alteration of GC-IGF1 axis may be involved in prenatal and postnatal pancreatic dysplasia and impaired insulin biosynthesis in PEE male offspring

Efficacious Intermittent Dosing of a Novel JAK2 Inhibitor in Mouse Models of Polycythemia Vera

A high percentage of patients with the myeloproliferative disorder polycythemia vera (PV) harbor a Val617→Phe activating mutation in the Janus kinase 2 (JAK2) gene, and both cell culture and mouse models have established a functional role for this mutation in the development of this disease. We describe the properties of MRLB-11055, a highly potent inhibitor of both the WT and V617F forms of JAK2, that has therapeutic efficacy in erythropoietin (EPO)-driven and JAK2V617F-driven mouse models of PV. In cultured cells, MRLB-11055 blocked proliferation and induced apoptosis in a manner consistent with JAK2 pathway inhibition. MRLB-11055 effectively prevented EPO-induced STAT5 activation in the peripheral blood of acutely dosed mice, and could prevent EPO-induced splenomegaly and erythrocytosis in chronically dosed mice. In a bone marrow reconstituted JAK2V617F-luciferase murine PV model, MRLB-11055 rapidly reduced the burden of JAK2V617F-expressing cells from both the spleen and the bone marrow. Using real-time in vivo imaging, we examined the kinetics of disease regression and resurgence, enabling the development of an intermittent dosing schedule that achieved significant reductions in both erythroid and myeloid populations with minimal impact on lymphoid cells. Our studies provide a rationale for the use of non-continuous treatment to provide optimal therapy for PV patients

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Species of Periacma, Irepacma and Epiracma from Taiwan (Lepidoptera: Oecophoridae)

Yin, Aihui, Wang, Shuxia (2014): Species of Periacma, Irepacma and Epiracma from Taiwan (Lepidoptera: Oecophoridae). Zootaxa 3835 (2): 283-291, DOI: 10.11646/zootaxa.3835.2.

Three new species of the genus Ripeacma (Lepidoptera: Oecophoridae) from China

Yin, Aihui, Wang, Shuxia (2013): Three new species of the genus Ripeacma (Lepidoptera: Oecophoridae) from China. Zootaxa 3718 (6): 591-595, DOI: http://dx.doi.org/10.11646/zootaxa.3718.6.

Periacma aduncata Wang, sp. nov.

Periacma aduncata Wang, sp. nov. (Figs. 1, 7, 12) Type material. Holotype: &male;, Taiwan: Taihoku, 10 May 1935, coll. S. Issiki, genitalia slide No. 142393 (USNM). Paratype: 1 &female;, same data as holotype except dated 7 May 1935 (USNM). Diagnosis. Periacma aduncata is similar to P. sinica Wang, Li et Liu, 2001 both in appearance and in genitalia. It can be distinguished from the latter by the forewing having a discontinuous fascia; the uncus with distal 2 / 5 expanded in a fan shape, the gnathos with widest part 1.1 times its length, and the valva with widest part about twice the width of the narrowest part at base in the male genitalia; and the apophysis anterioris that is less than 1 / 3 length of the apophysis posterioris in the female genitalia. In P. sinica, the forewing has a continuous brown fascia; the uncus is expanded roundly in distal 1 / 3, the widest part of the gnathos is 1.3 times its length, and the widest part of the valva is about 1.5 times width of the narrowest part at base; and the apophysis anterioris is more than 1 / 3 length of the apophysis posterioris. Description. Imago (Fig. 1). Wingspan 15.0−17.0 mm. Body orange yellow. Antenna with flagellum annulated with pale brown streaks on dorsal surface. Forewing with costal margin gently arched, dorsum almost straight, apex bluntly rounded; discontinuous brown fascia extending from beyond middle of costal margin to end of fold; brown spot at basal 1 / 3 and 3 / 5 of cell and at distal 2 / 5 of fold, respectively; cilia pale yellow. Hindwing and cilia pale gray. Fore- and midlegs orange yellow, speckled with brown on tarsi; hindlegs tinged with brown scales on tarsi. Male genitalia (Fig. 7). Uncus with basal 3 / 5 narrow, nearly parallel laterally, distal 2 / 5 expanded in a fan shape. Gnathos with basal half trapezoid, slightly widened from base to middle; distal half triangular, gradually narrowed to bluntly rounded apex, with long dense spines. Tegumen broad, inverted V shape. Valva elongate elliptical; basal 1 / 3 narrow, about same width; distal 2 / 3 gradually widened to before a slightly narrowed apex; widest part about twice width of narrowest part at base; dorsal-proximal process rod-like, setose, slightly dilated distally. Sacculus broad basally, distinctly narrowed to 3 / 5, distal 2 / 5 finger-like; with triangular process at ventral 1 / 4 and 3 / 4, respectively, the former distinctly larger than the latter. Saccus nearly semicircular. Aedeagus with basal 1 / 3 rod-like, gradually widened from basal 1 / 3 to 1 / 2, with a hooked process medially; distal 1 / 2 gradually narrowed to pointed apex, with teeth. Female genitalia (Fig. 12). Papilla analis setose, broad basally, gradually narrowed distally, forming an acute apex. Apophysis anterioris less than 1 / 3 length of apophysis posterioris. Lamella postvaginalis weakly sclerotized, with dense spinules, sinuate along posterior margin; lamella antevaginalis band-like, curved, with triangular plate laterally. Ductus bursae with posterior 1 / 3 sclerotized, anterior 2 / 3 membranous, widened. Corpus bursae rounded, longer than ductus bursae; sigmum thorn-like, curved, rounded at base. Distribution. China (Taiwan). Etymology. The specific name is from the Latin aduncatus, referring to the hooked process of the aedeagus.Published as part of Yin, Aihui & Wang, Shuxia, 2014, Species of Periacma, Irepacma and Epiracma from Taiwan (Lepidoptera: Oecophoridae), pp. 283-291 in Zootaxa 3835 (2) on pages 284-285, DOI: 10.11646/zootaxa.3835.2.8, http://zenodo.org/record/22628

Periacma Meyrick 1894

Genus Periacma Meyrick, 1894 Periacma Meyrick, 1894: 21. Type species: Periacma ferialis Meyrick, 1894, by original designation.Published as part of Yin, Aihui & Wang, Shuxia, 2014, Species of Periacma, Irepacma and Epiracma from Taiwan (Lepidoptera: Oecophoridae), pp. 283-291 in Zootaxa 3835 (2) on page 284, DOI: 10.11646/zootaxa.3835.2.8, http://zenodo.org/record/22628

Periacma

Key to species of Periacma, Irepacma and Epiracma from Taiwan 1 Valva in male with a dorso-proximal process.............................................................. 2 - Valva in male without dorso-proximal process.............................................................. 3 2 Aedeagus with a hooked process medially........................................... Periacma aduncata sp. nov. - Aedeagus without a hooked process....................................................... Periacma delegata 3 Apophysis anterioris in female absent.................................................................... 4 - Apophysis anterioris in female present................................................................... 5 4 Gnathos weakly sclerotized, nearly membranous........................................... Irepacma conioxantha - Gnathos heavily sclerotized....................................................... Irepacma flagellata sp. nov. 5 Gnathos broadly subtriangular................................................. Epiracma longicaudata sp. nov. - Gnathos annular................................................................. Epiracma annularis sp. nov.Published as part of Yin, Aihui & Wang, Shuxia, 2014, Species of Periacma, Irepacma and Epiracma from Taiwan (Lepidoptera: Oecophoridae), pp. 283-291 in Zootaxa 3835 (2) on page 283, DOI: 10.11646/zootaxa.3835.2.8, http://zenodo.org/record/22628

Taxonomic study of the genus Meleonoma Meyrick from Thailand (Lepidoptera, Gelechioidea)

Five species of the genus Meleonoma Meyrick are reported from Thailand. Meleonoma triangula Wang, sp. n., M. dorsolobulata Wang, sp. n., M. elongata Wang, sp. n., and M. bilobata Wang, sp. n. are described as new; M. facialis Li & Wang, 2002 is redescribed and recorded for the first time from Thailand