Janus kinase (JAK) 2 is activated by ANG II in vitro and in vivo, and chronic blockade of JAK2 by the JAK2 inhibitor AG-490 has been shown recently to attenuate ANG II hypertension in mice. In this study, AG-490 was infused intravenously in chronically instrumented rats to determine if the blunted hypertension was linked to attenuation of the renal actions of ANG II. In male Sprague-Dawley rats, after a control period, ANG II at 10 ng·kg(-1)·min(-1) was infused intravenously with or without AG-490 at 10 ng·kg(-1)·min(-1) iv for 11 days. ANG II infusion (18 h/day) increased mean arterial pressure from 91 ± 3 to 168 ± 7 mmHg by day 11. That response was attenuated significantly in the ANG II + AG-490 group, with mean arterial pressure increasing only from 92 ± 5 to 127 ± 3 mmHg. ANG II infusion markedly decreased urinary sodium excretion, caused a rapid and sustained decrease in glomerular filtration rate to ∼60% of control, and increased renal JAK2 phosphorylation; all these responses were blocked by AG-490. However, chronic AG-490 treatment had no effect on the ability of a separate group of normal rats to maintain normal blood pressure when they were switched rapidly to a low-sodium diet, whereas blood pressure fell dramatically in losartan-treated rats on a low-sodium diet. These data suggest that activation of the JAK/STAT pathway is critical for the development of ANG II-induced hypertension by mediating its effects on renal sodium excretory capability, but the physiological control of blood pressure by ANG II with a low-salt diet does not require JAK2 activation.

SUMMARY.In two centres urinary excretion ofHMMA was measured in a total of 359 children, aged from birth to 17 years, who were suspected of having a neuroblastoma; the diagnosis was subsequently confirmed in 39. Measurements were made on 24 h urine samples in 246 children, and on random samples in a further 113.The urinary excretion of HMMA relative to creatinine declined progressively with increasing age. After the age of four years the rate of decline was such that some age groups could be combined for statistical analysis. The range of values for each group was similar whether 24 h or random urine collections were used. It is concluded that the latter are adequate for the initial assessment of HMMA excretion.The measurement of 4-hydroxy-3-methoxy mandelic acid (HMMA) in urine is widely used to confirm the diagnosis of neuroblastoma. However, the interpretation of such measurements in children is difficult because excretion increases with age and varies widely between individuals of a given age and between the sexes. Relating the HMMA to creatinine excretion reduces the variation between individuals of the same agel and abolishes the sex difference.? but there remains a need for age-related reference ranges. The data so far published are, with a few exceptions (see Table 1), too sparse for age-related ranges to be determined under four years of age, or are not related to creatinine excretion.V We have analysed the data from 359 children, inpatients and outpatients, in whom HMMA measurements were requested by the attending paediatrician because their illness suggested the possibility of neuroblastoma. We have also compared the value of random and 24 h urine collections for the measurement of HMMA excretion. Children without neuroblastoma in this group provide a more appropriate reference range for use in the diagnosis of neuroblastoma than normal children. Patients and methodsUrine HMMA excretion was measured at clinical Correspondence: Dr G Walters, Department ofChemical Pathology, Bristol Royal Infirmary, Bristol BS2 8HW, UK. 44 presentation in a total of 359 children, aged from birth to 17 years, who were suspected at some stage of having a neuroblastoma. The studies were conducted in two centres, A and B. In 39 children, the diagnosis of neuroblastoma was subsequently confirmed; in the remaining 320 the diagnosis was eventually rejected and a neuroblastoma did not become evident during at least the next three years.Measurements were made on 24 h urine samples in 145 children at centre A and 101 children at centre B; random urine samples were analysed in a further 113 children at centre B. None of these children was on a vanillin exclusion diet as this is now considered unnecessary. 7In both centres the 24 h samples were collected into 20 mL of 5 M HCI, and the random samples were acidified with six drops of 12 M HCI within two hours of collection. HMMA was extracted and oxidised to vanillin by sodium periodate." Vanillin was estimated by spectrophotometry! in centre A and by gas liquid chromatography" in c...

Angiotensin II (ANG II) utilizes activation of JAK2 signaling pathways to cause hypertension. It is unknown if NE is dependent on JAK2 pathway activation to increase in blood pressure. We hypothesized that NE requires JAK2 activation to increase blood pressure. Male Sprague‐Dawley rats were catheterized via abdominal aorta and femoral vein to chronically measure blood pressure and infuse drugs. NE and ANG II were infused for 18 days and tissues harvested for western blot analysis. Mean arterial pressure (MAP) increased significantly in the ANG II and NE infused rats. There was a significant increase in phosphorylation levels of JAK2 as measured by Western blot analysis in the ANG II (10 ng/kg/min) and NE (2.8 mg/kg/day) treated rats than the saline controls. Infusion of JAK2 inhibitor AG490 (10 ng/kg/min) did not inhibit initial NE‐induced increases in blood pressure but did reduce NE's ability to maintain sustained increases in MAP. To determine if NE also requires a vascular component that involves JAK2 activation we utilized ex vivo myograph recordings. Using the thoracic aorta from naïve male rats we tested whether NE requires JAK2 activation for vascular contraction. We found that NE‐induced contraction was not significantly reduced by treatment with the JAK2 inhibitor AG490. These data suggest that NE and ANG II both increase and utilize JAK2 activation but via different mechanisms. (ABB NHLBI R00; MWB NHLBI R01).

We present an on-chip source of path-entangled photonic qudits by parallel excitation of 8 microring pair sources. The device is foundry-fabricated and uses advanced packaging techniques, a significant advance in generating high-dimensional quantum light on-chip.

Morphological and molecular analyses within the subtribe Gloxiniinae have led to the discovery of several previously undescribed genera. One of these genera comes from studies of the species Diastema vexans H.E. Moore, which has been identified from central to south Colombia. The nomenclatural history of the species has been very confused due to multiple species being designated under the same name. Morphological studies of the species and other closely related plants to confirm the species identification has provided evidence of a differing evolutionary lineage leading to the group. These studies have also revealed three new species that are distributed from Colombia southward through Peru. These taxa are identified by a suite of characters including axillary inflorescences, orbicular calyx base, and cup-shaped fruits. The traits are not seen among the other species of Diastema and this grouping represents a new genus in the tribe. Recent molecular studies have provided support to show that the flower shape and color of Diastema vexans and congeners is due to convergence through pollinator selection. Ongoing molecular and morphological research will be used to confirm the placement of the new genus Regeliantha within the subtribe Gloxiniinae.