Melatonin concentrations were determined in serum and 10 segments of the gastrointestinal tract (GIT) of 48 pigs (100 kg weight). The animals were fasted for 30 hr and then sacrificed 0, 1, 2, 5, 10, and 20 hr after refeeding. Peak amount of gastric digesta (2,428 g) and ileum digesta (850 g) were observed 1 hr and 5 hr, after refeeding, respectively. Conversely, colon content reached a minimal weight (726 g) at 2 hr after refeeding. Serum levels of melatonin increased from 3.4 pg/ml to 15.5 pg/ml (peak 5 hr after refeeding). Melatonin levels in GIT tissues before refeeding varied from 23.8 pg/g (stomach-fundus) to 62.1 pg/g (rectum). Increasingly higher levels of melatonin were detected in the distal segments of the GIT. Higher melatonin levels after refeeding were observed in most GIT tissues except the rectum. In most tissues, peak melatonin values were detected 5 hr after refeeding. A significant change in weight of digesta across time (P < 0.05) was detected in the stomach, ileum, and cecum. Similar changes in melatonin levels across time were found in most tissues except the esophagus, stomach (cardia and pylorus), and rectum. Adjacent GIT tissues exhibited similar (P < 0.05) melatonin levels. The GIT melatonin levels correlated best with the variation of digesta weight in the ileum. In addition, the increase of serum melatonin levels correlated best with the increase of GIT melatonin levels in the distal part of the GIT. Our results suggest that melatonin produced in the ileum, cecum, and colon may contribute significantly to the short-term increase of serum melatonin levels observed after refeeding.

Circadian levels of melatonin were determined in the hepatic portal vein, cranial vena cava, and the lower aorta of ten juvenile pigs. Blood was sampled every hour for a total of 24 hr via temporary cannulas introduced into blood vessels under anesthesia. No peak levels of melatonin were found in the mid-scotophase, but hepatic portal concentrations peaked at 06.00 hr. Overall levels of melatonin were highest in the hepatic portal vein (range 35-65 pg/mL), followed by an artery (range 30-55 pg/mL) and the vena cava (range 25-35 pg/mL). Levels of melatonin exhibit strong variation between individual pigs, but generally the average levels from all three sources follow each other's time course. However, on occasion, melatonin levels in the hepatic portal vein varied independently from the levels in the vena cava. Large portal peaks were usually preceded by a feeding period and were associated with a subsequent period of sleep. The data indicate that: 1) there is no clear circadian rhythm of melatonin in the peripheral blood of pigs, 2) relatively little melatonin is metabolized during the first liver passage, 3) food intake may elevate melatonin levels in the hepatic portal vein, and 4) increased levels of melatonin originated in the gastrointestinal tract may induce sleep.

Phosphorus deficiencies are limiting crop production in agricultural soils worldwide. Locally available sources of raw phosphate rock (PR) are being recognized for their potential role in soil fertility improvement. Phosphorus bioavailability is essential for the efficiency of PRs and can be increased by acid treatments. The utilization of organic acid producing micro‐organisms, notably Aspergillus niger, presents a sustainable alternative to the use of strong inorganic acids, but acid production of A. niger strongly depends on the mineral content of the growth media. This study compared the phosphorus mobilization efficiency of two biological treatments, namely addition of acidic cell‐free supernatants from A. niger cultivations to PRs and the direct cultivation of A. niger with PRs. The results show that addition of PR to cultivations leads to significant differences in the profile of organic acids produced by A. niger. Additions of PR, especially igneous rocks containing high amounts of iron and manganese, lead to reduced citric acid concentrations. In spite of these differences, phosphorus mobilization was similar between treatments, suggesting that the simpler direct cultivation method was not inferior. In addition to citric acid, it is suggested that oxalic acid contributes to PR solubilization in direct cultivations with A. niger, which would benefit farmers in developing countries where conventional fertilizers are not adequately accessible.

ABSTRACT1. Detailed knowledge of habitat requirements is particularly relevant to the conservation of rare and threatened fish species because habitat fragmentation and loss are usually the major threats to species with limited distributions and restricted habitat requirements, and habitat restoration is typically the first step in species' recovery plans. This paper documents the macro-, meso-and microhabitat habitat associations of a small threatened percichthyid, the Oxleyan pygmy perch, Nannoperca oxleyana, in south-eastern Queensland and north-eastern New South Wales (NSW), Australia.2. The species' range encompasses approximately 530 km of coastline from Coongul Creek on Fraser Island, Queensland (258 16 0 S, 1538 09 0 E) south to Tick Gate Swamp near the township of Wooli, NSW (298 54 0 S, 1538 15 0 E). It is confined primarily to dystrophic, acidic, freshwater systems draining through sandy coastal lowlands and Banksia -dominated heath ecosystems.3. Both lentic and lotic environments provide habitat for N. oxleyana but the species is found only in slowflowing pools and backwaters of river channels and tributaries as well as in swampy drainages, lakes, ponds and dams.4. Trapping studies found that an abundance of structural aquatic habitat was a defining microhabitat feature either in the form of beds of emergent or submerged plants or the presence of steep/undercut banks fringed with the semi-submerged branches and fine rootlets of riparian vegetation. When present, leaf litter and snags also provided cover.5. Recent and historical survey data suggest that human activities have had a significant influence on contemporary species presence/absence patterns and may have been responsible for the prominent gaps within the Queensland-NSW distribution of N. oxleyana.6. The distinctive relationships of N. oxleyana with features of aquatic habitat at the macro-, meso-and microhabitat scale demonstrate principles applicable to any study focused on the conservation of an endangered fish species.

Single-agent sunitinib, an oral small molecule inhibitor of multiple tyrosine kinase receptors, was evaluated for treatment of patients with recurrent glioblastoma (GB) and anaplastic astrocytoma (AA). Fourteen AA and 16 GB patients, all previously treated with surgery, radiotherapy, and temozolomide, were enrolled in a prospective phase II study at either first or second relapse. Patients were treated with daily sunitinib for 4 consecutive weeks, followed by a 2-week break. For AA patients, the most common side effects were fatigue (86 %), diarrhea (43 %), hand-foot syndrome (36 %), neutropenia (36 %), thrombocytopenia (36 %), and nausea (29 %). In the GB cohort, the most common side effects were fatigue (56 %), diarrhea (44 %), neutropenia (31 %), and thrombocytopenia (25 %). Six of 14 (43 %) AA and 5 of 16 (31 %) GB patients experienced grade 3 or greater toxicities. Five patients discontinued study due to drug toxicities. There were no partial or complete responses in either cohort; 8/14 (57 %) AA and 5/16 (31 %) GB patients had stable disease at the first planned assessment. Progression-free survival at 6 months was 21.5 % (AA) and 16.7 % (GB). Median overall survival was 12.1 months (AA) and 12.6 months (GB). These results are comparable to those reported in the literature in patients treated with standard cytotoxic therapies. This is the largest reported trial of sunitinib in recurrent malignant astrocytic gliomas to date, as well as contains the largest AA cohort. Nonetheless, sunitinib did not demonstrate significant anti-glioma activity in patients with recurrent malignant astrocytic gliomas.

No abstract

X-linked hypophosphatemia (XLH), the most prevalent heritable renal phosphate (Pi) wasting disorder, is caused by deactivating mutations of PHEX. Consequently, circulating phosphatonin FGF23 becomes elevated and hypophosphatemia in affected children leads to rickets with skeletal deformity and reduced linear growth while affected adults suffer from osteomalacia and forms of ectopic mineralization. In 2015, we reported uniquely mild XLH in six children and four of their mothers carrying the non-coding PHEX 3 0 -UTR mutation c.*231A>G. Herein, we characterize this mild XLH variant by comparing its features in 30 individuals to 30 age-and sexmatched patients with XLH but without the 3 0 -UTR mutation. The "UTR" and "XLH" groups, both comprising 17 children (2 to 17 years, 3 girls) and 13 adults (23 to 63 years, 10 women), had mean ages of 23 years. Only 43% of the UTR group versus 90% of the XLH group had received medical treatment for their disorder, including 0% versus 85% of the females, respectively (ps < .0001). The UTR group was taller: mean AE SD height Z-score (HZ) −1.0 AE 1.0 versus −2.0 AE 1.4 (p = .0034), with significantly greater height for females (−0.9 AE 0.7 versus −2.3 AE 1.4; p = .0050) but not males (−1.2 AE 1.1 versus −1.9 AE 1.5; p = .1541), respectively. Mean AE SD "arm span Z-score" (AZ) did not differ between the UTR −0.8 AE 1.3 versus XLH −1.3 AE 1.8 groups (p = .2269). Consequently, the UTR group was more proportionate with a mean ΔZ (AZ -HZ) of 0.1 AE 0.6 versus 0.7 AE 1.0 (p = .0158), respectively. Compared to the XLH group, the UTR group had significantly higher fasting serum Pi and renal tubular threshold maximum for phosphorus per glomerular filtration rate (TmP/GFR) (ps ≤ .0060), serum FGF23 concentrations within the reference range (p = .0068), and similar serum alkaline phosphatase levels (p = .6513). UTR lumbar spine bone mineral density Z-score was higher (p = .0343). Thus, the 3 0 -UTR variant of XLH is distinctly mild, especially in girls and women, posing challenges for its recognition and management.

Five milligrams of melatonin (M) per day was administered orally to four male white-tailed deer on a schedule that mimicked first decreasing and then increasing lengths of natural photoperiod. The following seasonal phenotypic and hormonal responses were observed: Pelage exchange, antler mineralization, velvet shedding, and rutting behavior of experimental animals were advanced by 50-55 days. Prolactin (PRL) levels exhibited a bimodal curve with peaks in May and August, as compared to a monomodal curve of controls (peak in June). Peak FSH levels of M-fed deer were advanced 2 months as compared to controls (June vs August). LH concentrations of both groups reached maxima in July; however, in the experimental group, LH levels declined much faster than in controls and then rose again in October-November. Testosterone (T) concentrations of M-fed bucks were elevated 2 months ahead of controls. Melatonin treatment had no significant effect on seasonal variation of T3, or T4. No seasonal rhythm of cortisol was seen in either group and no detectable effect of M was evident. No statistical differences in levels of alkaline phosphatase were seen between groups, although concentrations in experimental bucks sharply dropped to basal levels two months ahead of controls.