Controlled Waterfowl Hunting At Lake Odessa, Louisa County, Iowa

The Lake Odessa Public Hunting Area supports two systems of regulated waterfowl hunting. Control Area A consists of 55 marked blind sites which are chosen randomly by hunters during a daily drawing. Hunters using the second area, Control Area B, are not restricted to blind sites and a daily fee is not required, but all parties must possess a valid permit. Hunter use of Control Area A was uniform throughout the 1972 and 1973 hunting seasons due to the better mallard (Anas platy rhynchos) shooting on that area. Control Area B hunter use decreased as the season progressed, reflecting the early migration of wood ducks (Aix sponsa) which were more prevalent. In 1973, a year of poor mallard production but good wood duck production, hunter use of Control Area B increased over the previous year as hunters sought wood ducks. Hunters using Control Area A belonged to higher income, education, and occupation brackets, spent more money on equipment, and drove further to hunt than hunters in Control Area B. Hunter success was positively related to increasing values of vegetation parameters, but the dominant influence was not apparent. A heavy zone of annual emergent vegetation appeared to influence hunter success, but a lack of this zone could be compensated for with a strong representation of buttonbush (Cephalanthus occidentalis). Sites on medium-sized water areas (14-20 ac.) with a strong zone of annual emergent vegetation produced the highest success rates in 1972, but the same or similar sites produced low success rates in 1973 after severe loss of vegetation. Because of reduced annual emergent vegetation on the area and the receding zones of bottonbush, a summer drawdown of water level was recommended

Neuromuscular Adaptations in Elderly Adults Are Task-Specific during Stepping and Obstacle Clearance Tasks.

Elderly adults have a diminished movement capacity due to physiological and neurological declines associated with advancing age. Previous research suggests that elderly adults use altered neuromuscular patterns to conduct activities of daily living (ADLs). Limited research has addressed these altered activation strategies in obstacle clearance, stair ascent and stair descent. The purpose of this study was to compare neuromuscular activation patterns in young and elderly adults during these tasks. Eleven young and 10 healthy elderly adults performed five downward stepping, upward stepping and obstacle clearance trials. Surface EMG was measured from the quadriceps, hamstrings, gastrocnemius and tibialis anterior muscles. A 2x3 (group x condition) repeated measures analysis of variance was used to determine significant differences in muscle activation intensity. An apriori alpha level was set at p\u3c0.05. The results showed that elderly adults exhibited greater activation intensity than the young adults in all movement conditions. The significant differences in muscle activation intensity in the elderly adults were limited to the musculature driving the tested movement. The findings of the current study support previous research that elderly adults perform ADLs at a greater relative intensity than young adults. Furthermore, the current study shows that the disproportionate increase in muscle activation intensity is limited to the muscles that functionally drive the required task

Dwarf koa (Desmanthus virgatus)

This is the final version. It was first published by BioMed Central at http://www.biomedcentral.com/1471-2164/16/473.Background: Mobile elements are active in the human genome, both in the germline and cancers, where they can\ud mutate driver genes.\ud Results: While analysing whole genome paired-end sequencing of oesophageal adenocarcinomas to find genomic\ud rearrangements, we identified three ways in which new mobile element insertions appear in the data, resembling\ud translocation or insertion junctions: inserts where unique sequence has been transduced by an L1 (Long interspersed\ud element 1) mobile element; novel inserts that are confidently, but often incorrectly, mapped by alignment software to\ud L1s or polyA tracts in the reference sequence; and a combination of these two ways, where different sequences within\ud one insert are mapped to different loci. We identified nine unique sequences that were transduced by neighbouring\ud L1s, both L1s in the reference genome and L1s not present in the reference. Many of the resulting inserts were small\ud fragments that include little or no recognisable mobile element sequence. We found 6 loci in the reference genome to\ud which sequence reads from inserts were frequently mapped, probably erroneously, by alignment software: these were\ud either L1 sequence or particularly long polyA runs. Inserts identified from such apparent rearrangement junctions\ud averaged 16 inserts/tumour, range 0?153 insertions in 43 tumours. However, many inserts would not be detected by\ud mapping the sequences to the reference genome, because they do not include sufficient mappable sequence. To\ud estimate total somatic inserts we searched for polyA sequences that were not present in the matched normal or other\ud normals from the same tumour batch, and were not associated with known polymorphisms. Samples of these candidate\ud inserts were verified by sequencing across them or manual inspection of surrounding reads: at least 85 % were somatic\ud and resembled L1-mediated events, most including L1Hs sequence. Approximately 100 such inserts were detected per\ud tumour on average (range zero to approximately 700).\ud Conclusions: Somatic mobile elements insertions are abundant in these tumours, with over 75 % of cases having a\ud number of novel inserts detected. The inserts create a variety of problems for the interpretation of paired-end\ud sequencing data.Funding\ud was primarily from Cancer Research UK program grants to RCF and ST\ud (C14478/A15874 and C14303/A17197), with additional support awarded to\ud RCF from UK Medical Research Council, NHS National Institute for Health\ud Research (NIHR), the Experimental Cancer Medicine Centre Network and\ud the NIHR Cambridge Biomedical Research Centre, and Cancer Research UK\ud Project grant C1023/A14545 to PAWE. JMJW was funded by a Wellcome\ud Trust Translational Medicine and Therapeutics grant

Rearrangement processes and structural variations show evidence of selection in oesophageal adenocarcinomas

Oesophageal adenocarcinoma (OAC) provides an ideal case study to characterize large-scale rearrangements. Using whole genome short-read sequencing of 383 cases, for which 214 had matched whole transcriptomes, we observed structural variations (SV) with a predominance of deletions, tandem duplications and inter-chromosome junctions that could be identified as LINE-1 mobile element (ME) insertions. Complex clusters of rearrangements resembling breakage-fusion-bridge cycles or extrachromosomal circular DNA accounted for 22% of complex SVs affecting known oncogenes. Counting SV events affecting known driver genes substantially increased the recurrence rates of these drivers. After excluding fragile sites, we identified 51 candidate new drivers in genomic regions disrupted by SVs, including ETV5, KAT6B and CLTC. RUNX1 was the most recurrently altered gene (24%), with many deletions inactivating the RUNT domain but preserved the reading frame, suggesting an altered protein product. These findings underscore the importance of identification of SV events in OAC with implications for targeted therapies.</p

Rearrangement processes and structural variations show evidence of selection in oesophageal adenocarcinomas

Oesophageal adenocarcinoma (OAC) provides an ideal case study to characterize large-scale rearrangements. Using whole genome short-read sequencing of 383 cases, for which 214 had matched whole transcriptomes, we observed structural variations (SV) with a predominance of deletions, tandem duplications and inter-chromosome junctions that could be identified as LINE-1 mobile element (ME) insertions. Complex clusters of rearrangements resembling breakage-fusion-bridge cycles or extrachromosomal circular DNA accounted for 22% of complex SVs affecting known oncogenes. Counting SV events affecting known driver genes substantially increased the recurrence rates of these drivers. After excluding fragile sites, we identified 51 candidate new drivers in genomic regions disrupted by SVs, including ETV5, KAT6B and CLTC. RUNX1 was the most recurrently altered gene (24%), with many deletions inactivating the RUNT domain but preserved the reading frame, suggesting an altered protein product. These findings underscore the importance of identification of SV events in OAC with implications for targeted therapies.</p

Systematic techniques for assisting recruitment to trials (START): study protocol for embedded, randomized controlled trials

BACKGROUND: Randomized controlled trials play a central role in evidence-based practice, but recruitment of participants, and retention of them once in the trial, is challenging. Moreover, there is a dearth of evidence that research teams can use to inform the development of their recruitment and retention strategies. As with other healthcare initiatives, the fairest test of the effectiveness of a recruitment strategy is a trial comparing alternatives, which for recruitment would mean embedding a recruitment trial within an ongoing host trial. Systematic reviews indicate that such studies are rare. Embedded trials are largely delivered in an ad hoc way, with interventions almost always developed in isolation and tested in the context of a single host trial, limiting their ability to contribute to a body of evidence with regard to a single recruitment intervention and to researchers working in different contexts. METHODS/DESIGN: The Systematic Techniques for Assisting Recruitment to Trials (START) program is funded by the United Kingdom Medical Research Council (MRC) Methodology Research Programme to support the routine adoption of embedded trials to test standardized recruitment interventions across ongoing host trials. To achieve this aim, the program involves three interrelated work packages: (1) methodology - to develop guidelines for the design, analysis and reporting of embedded recruitment studies; (2) interventions - to develop effective and useful recruitment interventions; and (3) implementation - to recruit host trials and test interventions through embedded studies. DISCUSSION: Successful completion of the START program will provide a model for a platform for the wider trials community to use to evaluate recruitment interventions or, potentially, other types of intervention linked to trial conduct. It will also increase the evidence base for two types of recruitment intervention. TRIAL REGISTRATION: The START protocol covers the methodology for embedded trials. Each embedded trial is registered separately or as a substudy of the host trial

Prophylactic evaluation of verubecestat on disease- and symptom-modifying effects in 5XFAD mice.

Introduction: Alzheimer\u27s disease (AD) is the most common form of dementia. Beta-secretase (BACE) inhibitors have been proposed as potential therapeutic interventions; however, initiating treatment once disease has significantly progressed has failed to effectively stop or treat disease. Whether BACE inhibition may have efficacy when administered prophylactically in the early stages of AD has been under-investigated. The present studies aimed to evaluate prophylactic treatment of the BACE inhibitor verubecestat in an AD mouse model using the National Institute on Aging (NIA) resources of the Model Organism Development for Late-Onset Alzheimer\u27s Disease (MODEL-AD) Preclinical Testing Core (PTC) Drug Screening Pipeline. Methods: 5XFAD mice were administered verubecestat ad libitum in chow from 3 to 6 months of age, prior to the onset of significant disease pathology. Following treatment (6 months of age), in vivo imaging was conducted with 18F-florbetapir (AV-45/Amyvid) (18F-AV45) and 18-FDG (fluorodeoxyglucose)-PET (positron emission tomography)/MRI (magnetic resonance imaging), brain and plasma amyloid beta (Aβ) were measured, and the clinical and behavioral characteristics of the mice were assessed and correlated with the pharmacokinetic data. Results: Prophylactic verubecestat treatment resulted in dose- and region-dependent attenuations of 18F-AV45 uptake in male and female 5XFAD mice. Plasma Aβ40 and Aβ42 were also dose-dependently attenuated with treatment. Across the dose range evaluated, side effects including coat color changes and motor alterations were reported, in the absence of cognitive improvement or changes in 18F-FDG uptake. Discussion: Prophylactic treatment with verubecestat resulted in attenuated amyloid plaque deposition when treatment was initiated prior to significant pathology in 5XFAD mice. At the same dose range effective at attenuating Aβ levels, verubecestat produced side effects in the absence of improvements in cognitive function. Taken together these data demonstrate the rigorous translational approaches of the MODEL-AD PTC for interrogating potential therapeutics and provide insight into the limitations of verubecestat as a prophylactic intervention for early-stage AD

Plcg2M28L Interacts With High Fat/High Sugar Diet to Accelerate Alzheimer\u27s Disease-Relevant Phenotypes in Mice.

Obesity is recognized as a significant risk factor for Alzheimer\u27s disease (AD). Studies have supported the notion that obesity accelerates AD-related pathophysiology in mouse models of AD. The majority of studies, to date, have focused on the use of early-onset AD models. Here, we evaluate the impact of genetic risk factors on late-onset AD (LOAD) in mice fed with a high fat/high sugar diet (HFD). We focused on three mouse models created through the IU/JAX/PITT MODEL-AD Center. These included a combined risk model wit

NRG1 fusions in breast cancer

Funder: Cancer Research UKFunder: Breast Cancer NowFunder: Addenbrookes Charitable TrustFunder: Mark Foundation For Cancer Research; doi: http://dx.doi.org/10.13039/100014599Funder: Addenbrooke's Charitable Trust, Cambridge University Hospitals (GB)Abstract: Background: NRG1 gene fusions may be clinically actionable, since cancers carrying the fusion transcripts can be sensitive to tyrosine kinase inhibitors. The NRG1 gene encodes ligands for the HER2(ERBB2)-ERBB3 heterodimeric receptor tyrosine kinase, and the gene fusions are thought to lead to autocrine stimulation of the receptor. The NRG1 fusion expressed in the breast cancer cell line MDA-MB-175 serves as a model example of such fusions, showing the proposed autocrine loop and exceptional drug sensitivity. However, its structure has not been properly characterised, its oncogenic activity has not been fully explained, and there is limited data on such fusions in breast cancer. Methods: We analysed genomic rearrangements and transcripts of NRG1 in MDA-MB-175 and a panel of 571 breast cancers. Results: We found that the MDA-MB-175 fusion—originally reported as a DOC4(TENM4)-NRG1 fusion, lacking the cytoplasmic tail of NRG1—is in reality a double fusion, PPP6R3-TENM4-NRG1, producing multiple transcripts, some of which include the cytoplasmic tail. We hypothesise that many NRG1 fusions may be oncogenic not for lacking the cytoplasmic domain but because they do not encode NRG1’s nuclear-localised form. The fusion in MDA-MB-175 is the result of a very complex genomic rearrangement, which we partially characterised, that creates additional expressed gene fusions, RSF1-TENM4, TPCN2-RSF1, and MRPL48-GAB2. We searched for NRG1 rearrangements in 571 breast cancers subjected to genome sequencing and transcriptome sequencing and found four cases (0.7%) with fusions, WRN-NRG1, FAM91A1-NRG1, ARHGEF39-NRG1, and ZNF704-NRG1, all splicing into NRG1 at the same exon as in MDA-MB-175. However, the WRN-NRG1 and ARHGEF39-NRG1 fusions were out of frame. We identified rearrangements of NRG1 in many more (8% of) cases that seemed more likely to inactivate than to create activating fusions, or whose outcome could not be predicted because they were complex, or both. This is not surprising because NRG1 can be pro-apoptotic and is inactivated in some breast cancers. Conclusions: Our results highlight the complexity of rearrangements of NRG1 in breast cancers and confirm that some do not activate but inactivate. Careful interpretation of NRG1 rearrangements will therefore be necessary for appropriate patient management

NRG1 fusions in breast cancer

Funder: Cancer Research UKFunder: Breast Cancer NowFunder: Addenbrookes Charitable TrustFunder: Mark Foundation For Cancer Research; doi: http://dx.doi.org/10.13039/100014599Funder: Addenbrooke's Charitable Trust, Cambridge University Hospitals (GB)Abstract: Background: NRG1 gene fusions may be clinically actionable, since cancers carrying the fusion transcripts can be sensitive to tyrosine kinase inhibitors. The NRG1 gene encodes ligands for the HER2(ERBB2)-ERBB3 heterodimeric receptor tyrosine kinase, and the gene fusions are thought to lead to autocrine stimulation of the receptor. The NRG1 fusion expressed in the breast cancer cell line MDA-MB-175 serves as a model example of such fusions, showing the proposed autocrine loop and exceptional drug sensitivity. However, its structure has not been properly characterised, its oncogenic activity has not been fully explained, and there is limited data on such fusions in breast cancer. Methods: We analysed genomic rearrangements and transcripts of NRG1 in MDA-MB-175 and a panel of 571 breast cancers. Results: We found that the MDA-MB-175 fusion—originally reported as a DOC4(TENM4)-NRG1 fusion, lacking the cytoplasmic tail of NRG1—is in reality a double fusion, PPP6R3-TENM4-NRG1, producing multiple transcripts, some of which include the cytoplasmic tail. We hypothesise that many NRG1 fusions may be oncogenic not for lacking the cytoplasmic domain but because they do not encode NRG1’s nuclear-localised form. The fusion in MDA-MB-175 is the result of a very complex genomic rearrangement, which we partially characterised, that creates additional expressed gene fusions, RSF1-TENM4, TPCN2-RSF1, and MRPL48-GAB2. We searched for NRG1 rearrangements in 571 breast cancers subjected to genome sequencing and transcriptome sequencing and found four cases (0.7%) with fusions, WRN-NRG1, FAM91A1-NRG1, ARHGEF39-NRG1, and ZNF704-NRG1, all splicing into NRG1 at the same exon as in MDA-MB-175. However, the WRN-NRG1 and ARHGEF39-NRG1 fusions were out of frame. We identified rearrangements of NRG1 in many more (8% of) cases that seemed more likely to inactivate than to create activating fusions, or whose outcome could not be predicted because they were complex, or both. This is not surprising because NRG1 can be pro-apoptotic and is inactivated in some breast cancers. Conclusions: Our results highlight the complexity of rearrangements of NRG1 in breast cancers and confirm that some do not activate but inactivate. Careful interpretation of NRG1 rearrangements will therefore be necessary for appropriate patient management