The UV RESISTANCE LOCUS 8-Mediated UV-B Response Is Required Alongside CRYPTOCHROME 1 For Plant Survival Under Sunlight In Field Conditions

As sessile, photoautotrophic organisms, plants are subjected to fluctuating sunlight that includes potentially detrimental ultraviolet-B radiation (UV-B). Experiments under controlled conditions have shown that the UV-B photoreceptor UV RESISTANCE LOCUS 8 (UVR8) controls acclimation and tolerance to UV-B in Arabidopsis thaliana; however, its long-term impacts on plant fitness remain poorly understood in naturally fluctuating environments. Here we quantified the survival and reproduction of different Arabidopsis mutant genotypes in diverse field and laboratory conditions. We found that uvr8 mutants produced more fruits than wild type when grown in growth chambers under artificial low UV-B conditions but not in natural field conditions, indicating a fitness cost in absence of UV-B stress. Importantly, independent double mutants of UVR8 and the blue-light photoreceptor gene CRYPTOCHROME 1 (CRY1) in two genetic backgrounds showed a drastic reduction in fitness in the field. Experiments with UV-B attenuation experiments in field and with supplemental UV-B in growth chambers demonstrated that UV-B caused the conditional cry1 uvr8 lethality phenotype. Using RNA-seq data of field-grown single and double mutants, we explicitly identified genes showing statistical interaction of UVR8 and CRY1 mutations in the presence of UV-B in the field. They were enriched in Gene Ontology categories related to oxidative stress, photoprotection, and DNA damage repair in addition to UV-B response. Our study demonstrates the functional importance of the UVR8-mediated response across life stages in natura, which is partially redundant with that of cry1. Moreover, these data provide an integral picture of gene expression associated with plant responses under field conditions

Early Weight Bearing of Calcaneal Fractures Treated by Intraoperative 3D-Fluoroscopy and Locked-Screw Plate Fixation

Operative therapy of intraarticular fractures of the calcaneus is an established surgical standard. The aim is an accurate reduction of the fracture with reconstruction of Boehler’s angle, length, axis and subtalar joint surface. Intraoperative 3D-fluoroscopy with the Siremobil Iso-C 3D® mobile C-arm system is a valuable assistant for accurate reconstruction of these anatomical structures. Remaining incongruities can be recognized and corrected intraoperatively. The achieved reduction can be fixed by the advantages of an internal fixator (locked-screw plate interface). In the period of October 2002 until April 2007 we operated 136 patients with intraarticular fractures of the calcaneus by means of anatomical reduction, and internal plate fixator under intraoperative control of 3D-fluoroscopy. All patients were supplied with an orthesis after the operation which allowed weight bearing of 10 kg for 12 weeks for the patients operated between October 2002 and October 2004 (Group A). Transient local osteoporosis was observed in all X-Rays at follow-up after an average of 8,6 months. Therefore we changed our postoperative treatment plan for the patients operated between November 2004 and April 2007 (Group B). Weight bearing started with 20 KG after 6 weeks, was increased to 40 KG after 8 weeks and full weight bearing was allowed after 10 weeks for these patients. In no case a secondary dislocation of the fracture was seen. No bone graft was used. At follow up the average American Foot and Ankle Society Score (AOFAS) were 81 for Group_A, compared to 84 for Group B, treated with earlier weight bearing. Autologous bone graft was not necessary even if weight bearing was started after a period of six weeks postoperatively. The combination of 3D-fluoroscopy with locked internal fixation showed promising results. If the rate of patients developing subtalar arthrosis will decrease by this management will have to be shown in long term follow up

Chronic Activation of γ2 AMPK Induces Obesity and Reduces β Cell Function.

Despite significant advances in our understanding of the biology determining systemic energy homeostasis, the treatment of obesity remains a medical challenge. Activation of AMP-activated protein kinase (AMPK) has been proposed as an attractive strategy for the treatment of obesity and its complications. AMPK is a conserved, ubiquitously expressed, heterotrimeric serine/threonine kinase whose short-term activation has multiple beneficial metabolic effects. Whether these translate into long-term benefits for obesity and its complications is unknown. Here, we observe that mice with chronic AMPK activation, resulting from mutation of the AMPK γ2 subunit, exhibit ghrelin signaling-dependent hyperphagia, obesity, and impaired pancreatic islet insulin secretion. Humans bearing the homologous mutation manifest a congruent phenotype. Our studies highlight that long-term AMPK activation throughout all tissues can have adverse metabolic consequences, with implications for pharmacological strategies seeking to chronically activate AMPK systemically to treat metabolic disease

Colorectal cancer: prevention and early diagnosis

Colorectal cancer (CRC) is one of the leading causes of cancer deaths worldwide. This article reviews the aetiology and risk factors for CRC and focuses on strategies for prevention and early diagnosis. Prevention involves identifying and optimizing modifiable risk factors through public health awareness as well as population screening, for example using detection of occult blood in stool. Endoscopic surveillance in the UK is currently performed on a population basis with the bowel scope programme and faecal immunochemical testing, with colonoscopy reserved for patients known to be at higher risk of developing CRC. These include individuals with genetic predisposition or long-standing inflammatory bowel disease. Population screening for CRC is well established in clinical practice as an effective method for early cancer detection and prevention through polypectomy. It is effective at improving disease stage at diagnosis and thus reducing CRC-specific mortality. Recent changes to the NHS screening programmes and advances in the understanding of the serrated pathway for CRC development are highlighted and their respective roles for cancer prevention discussed. Finally, future directions in technology and research for prevention and early diagnosis of CRC, including computer-aided diagnosis (deep learning), are explored

Colorectal cancer: prevention and early diagnosis

Colorectal cancer (CRC) is one of the leading causes of cancer deaths worldwide. This article reviews the aetiology and risk factors for CRC and focuses on strategies for prevention and early diagnosis. Prevention involves identifying and optimizing modifiable risk factors through public health awareness as well as population screening, for example using detection of occult blood in stool. Endoscopic surveillance in the UK is currently performed on a population basis with the bowel scope programme and faecal immunochemical testing, with colonoscopy reserved for patients known to be at higher risk of developing CRC. These include individuals with genetic predisposition or long-standing inflammatory bowel disease. Population screening for CRC is well established in clinical practice as an effective method for early cancer detection and prevention through polypectomy. It is effective at improving disease stage at diagnosis and thus reducing CRC-specific mortality. Recent changes to the NHS screening programmes and advances in the understanding of the serrated pathway for CRC development are highlighted and their respective roles for cancer prevention discussed. Finally, future directions in technology and research for prevention and early diagnosis of CRC, including computer-aided diagnosis (deep learning), are explored