Identification of SPLUNC1's ENaC-inhibitory domain yields novel strategies to treat sodium hyperabsorption in cystic fibrosis airways.

The epithelial sodium channel (ENaC) is responsible for Na+ and fluid absorption across colon, kidney, and airway epithelia. We have previously identified SPLUNC1 as an autocrine inhibitor of ENaC. We have now located the ENaC inhibitory domain of SPLUNC1 to SPLUNC1's N terminus, and a peptide corresponding to this domain, G22-A39, inhibited ENaC activity to a similar degree as full-length SPLUNC1 (∼2.5 fold). However, G22-A39 had no effect on the structurally related acid-sensing ion channels, indicating specificity for ENaC. G22-A39 preferentially bound to the β-ENaC subunit in a glycosylation-dependent manner. ENaC hyperactivity is contributory to cystic fibrosis (CF) lung disease. Addition of G22-A39 to CF human bronchial epithelial cultures (HBECs) resulted in an increase in airway surface liquid height from 4.2±0.6 to 7.9±0.6 μm, comparable to heights seen in normal HBECs, even in the presence of neutrophil elastase. Our data also indicate that the ENaC inhibitory domain of SPLUNC1 may be cleaved away from the main molecule by neutrophil elastase, which suggests that it may still be active during inflammation or neutrophilia. Furthermore, the robust inhibition of ENaC by the G22-A39 peptide suggests that this peptide may be suitable for treating CF lung disease.

Prospects of doubling global wheat yields

While an adequate supply of food can be achieved at present for the current global population, sustaining this into the future will be difficult in the face of a steadily increasing population, increased wealth and a diminishing availability of fertile land and water for agriculture. This problem will be compounded by the new uses of agricultural products, for example, as biofuels. Wheat alone provides ≥20% of the calories and the protein for the world's population, and the value and need to increase the production is recognized widely. Currently, the world average wheat yield is around 3 t/ha but there is considerable variation between countries, with region-specific factors limiting yield, each requiring individual solutions. Delivering increased yields in any situation is a complex challenge that is unlikely to be solved by single approaches and a multidisciplinary integrated approach to crop improvement is required. There are three specific major challenges: increasing yield potential, protecting yield potential, and increasing resource use efficiency to ensure sustainability. Since the green revolution, yields at the farm gate have stagnated in many countries, or are increasing at less than half the rate required to meet the projected demand. In some countries, large gains can still be achieved by improvements in agronomy, but in many others the yield gains will only be achieved by further genetic improvement. In this overview, the problems and potential solutions for increased wheat yields are discussed, in the context of specific geographic regions, with a particular emphasis on China. The importance and the prospects for improvement of individual traits are presented. It is concluded that there are opportunities for yield increase but a major challenge will be avoiding a simultaneous increase in resource requirements.

Effect of annually repeated undersowing on cereal grain yields

Selostus: Aluskasveja voi käyttää toistuvasti viljan viljelyssä

Estimated metabolizable energy yields of perennial and annual grass swards compared with those of spring barley and oat

Selostus: Yksi- ja monivuotisen nurmen, ohran sekä kauran muuntokelpoisen energian sadot märehtijän rehutuksessa lajikekokeiden tuloksista estimoituina

International Society of Urological Pathology (ISUP) Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens. Working group 4: seminal vesicles and lymph nodes.

The 2009 International Society of Urological Pathology Consensus Conference in Boston made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to the infiltration of tumor into the seminal vesicles and regional lymph nodes were coordinated by working group 4. There was a consensus that complete blocking of the seminal vesicles was not necessary, although sampling of the junction of the seminal vesicles and prostate was mandatory. There was consensus that sampling of the vas deferens margins was not obligatory. There was also consensus that muscular wall invasion of the extraprostatic seminal vesicle only should be regarded as seminal vesicle invasion. Categorization into types of seminal vesicle spread was agreed by consensus to be not necessary. For examination of lymph nodes, there was consensus that special techniques such as frozen sectioning were of use only in high-risk cases. There was no consensus on the optimal sampling method for pelvic lymph node dissection specimens, although there was consensus that all lymph nodes should be completely blocked as a minimum. There was also a consensus that a count of the number of lymph nodes harvested should be attempted. In view of recent evidence, there was consensus that the diameter of the largest lymph node metastasis should be measured. These consensus decisions will hopefully clarify the difficult areas of pathological assessment in radical prostatectomy evaluation and improve the concordance of research series to allow more accurate assessment of patient prognosis.

Long-term impacts of forest harvesting related soil disturbance on log product yields and economic potential in a New Zealand forest

Abstract

The interplay between radiation and the immune system in the field of post-radical pneumonitis and fibrosis and why it is important to understand it.

A discussion on the importance and pathogenesis of radiation-induced pneumonitis and fibrosis is provided, with a special focus on the role of the immune system. The need to understand this interaction is highlighted in view of emerging therapeutic potential.

Altering α-dystroglycan receptor affinity of LCMV pseudotyped lentivirus yields unique cell and tissue tropism.

BACKGROUND: The envelope glycoprotein of lymphocytic choriomeningitis virus (LCMV) can efficiently pseudotype lentiviral vectors. Some strains of LCMV exploit high affinity interactions with α-dystroglycan (α-DG) to bind to cell surfaces and subsequently fuse in low pH endosomes. LCMV strains with low α-DG affinity utilize an unknown receptor and display unique tissue tropisms. We pseudotyped non-primate feline immunodeficiency virus (FIV) vectors using LCMV derived glycoproteins with high or low affinity to α-DG and evaluated their properties in vitro and in vivo. METHODS: We pseudotyped FIV with the LCMV WE54 strain envelope glycoprotein and also engineered a point mutation in the WE54 envelope glycoprotein (L260F) to diminish α-DG affinity and direct binding to alternate receptors. We hypothesized that this change would alter in vivo tissue tropism and enhance gene transfer to neonatal animals. RESULTS: In mice, hepatic α- and β-DG expression was greatest at the late gestational and neonatal time points. When displayed on the surface of the FIV lentivirus the WE54 L260F mutant glycoprotein bound weakly to immobilized α-DG. Additionally, LCMV WE54 pseudotyped FIV vector transduction was neutralized by pre-incubation with soluble α-DG, while the mutant glycoprotein pseudotyped vector was not. In vivo gene transfer in adult mice with either envelope yielded low transduction efficiencies in hepatocytes following intravenous delivery. In marked contrast, neonatal gene transfer with the LCMV envelopes, and notably with the FIV-L260F vector, conferred abundant liver and lower level cardiomyocyte transduction as detected by luciferase assays, bioluminescent imaging, and β-galactosidase staining. CONCLUSIONS: These results suggest that a developmentally regulated receptor for LCMV is expressed abundantly in neonatal mice. LCMV pseudotyped vectors may have applications for neonatal gene transfer. ABBREVIATIONS: Armstrong 53b (Arm53b); baculovirus Autographa californica GP64 (GP64); charge-coupled device (CCD); dystroglycan (DG); feline immunodeficiency virus (FIV); glycoprotein precursor (GP-C); firefly luciferase (Luc); lymphocytic choriomeningitis virus (LCMV); nuclear targeted β-galactosidase (ntLacZ); optical density (OD); PBS/0.1% (w/v) Tween-20 (PBST); relative light units (RLU); Rous sarcoma virus (RSV); transducing units per milliliter (TU/ml); vesicular stomatitis virus (VSV-G); wheat germ agglutinin (WGA); 50% reduction in binding (C50).

Hidradenitis suppurativa of the groin treated by radical excision and defect closure by medial thigh lift: aesthetic surgery meets reconstructive surgery.

INTRODUCTION: Hidradenitis suppurativa of the groin is a chronic, relapsing inflammatory disease of the skin and subcutaneous tissues. Radical surgical excision is the treatment of choice. Often split-skin grafting or wound healing by secondary intention are used for defect closure, sometimes with disfiguring results. We describe our experience with radical excision of localised inguinal hidradenitis suppurativa and immediate defect closure with a medial thigh lift. PATIENTS AND METHODS: Our hospital database was searched for all patients presenting to our institution for surgical treatment of hidradenitis suppurativa between 2001 and 2006. Only patients with hidradenitis confined to the groin were included. Exclusion criteria were simple abscess incisions, recurrence after previous grafting or flap surgery and extension of the disease outside the groin and presence of clinical signs of infection at the time of surgery. We documented patient demographics, sizes of defects, complications, time of follow-up, recurrences and patient satisfaction. RESULTS: A total of 8 patients with localised inguinal hidradenitis suppurativa were identified and 15 thigh lifts were performed. Defect size assessed on pathologic examination of the excised specimens averaged 15.9 cm x 4.3 cm x 1.3 cm (length x width x depth). All wounds but one healed primarily. Functional and aesthetic results were satisfactory. No major complications and no irritations of the genital area were observed. No recurrences were observed either. CONCLUSION: We propose the medial thigh lift to be considered for immediate defect closure after radical excision of localised inguinal hidradenitis suppurativa provided that no perifocal signs of infection are present after debridement.