The evolutionary history and genomics of European blackcap migration

Seasonal migration is a taxonomically widespread behaviour that integrates across many traits. The European blackcap exhibits enormous variation in migration and is renowned for research on its evolution and genetic basis. We assembled a reference genome for blackcaps and obtained whole genome resequencing data from individuals across its breeding range. Analyses of population structure and demography suggested divergence began ~30,000 ya, with evidence for one admixture event between migrant and resident continent birds ~5000 ya. The propensity to migrate, orientation and distance of migration all map to a small number of genomic regions that do not overlap with results from other species, suggesting that there are multiple ways to generate variation in migration. Strongly associated single nucleotide polymorphisms (SNPs) were located in regulatory regions of candidate genes that may serve as major regulators of the migratory syndrome. Evidence for selection on shared variation was documented, providing a mechanism by which rapid changes may evolve

(Micro)evolutionary changes and the evolutionary potential of bird migration

Seasonal migration is the yearly long-distance movement of individuals between their breeding and wintering grounds. Individuals from nearly every animal group exhibit this behavior, but probably the most iconic migration is carried out by birds, from the classic V-shape formation of geese on migration to the amazing nonstop long-distance flights undertaken by Arctic Terns Sterna paradisaea. In this chapter, we discuss how seasonal migration has shaped the field of evolution. First, this behavior is known to turn on and off quite rapidly, but controversy remains concerning where this behavior first evolved geographically and whether the ancestral state was sedentary or migratory (Fig. 7.1d, e). We review recent work using new analytical techniques to provide insight into this topic. Second, it is widely accepted that there is a large genetic basis to this trait, especially in groups like songbirds that migrate alone and at night precluding any opportunity for learning. Key hypotheses on this topic include shared genetic variation used by different populations to migrate and only few genes being involved in its control. We summarize recent work using new techniques for both phenotype and genotype characterization to evaluate and challenge these hypotheses. Finally, one topic that has received less attention is the role these differences in migratory phenotype could play in the process of speciation. Specifically, many populations breed next to one another but take drastically different routes on migration (Fig. 7.2). This difference could play an important role in reducing gene flow between populations, but our inability to track most birds on migration has so far precluded evaluations of this hypothesis. The advent of new tracking techniques means we can track many more birds with increasing accuracy on migration, and this work has provided important insight into migration's role in speciation that we will review here

Population-specific association of Clock gene polymorphism with annual cycle timing in stonechats

Timing is essential for survival and reproduction of organisms across the tree of life. The core circadian clock gene Clk has been implicated in annual timing and shows highly conserved sequence homology across vertebrates except for one variable region of poly Glutamine repeats. Clk genotype varies in some species with latitude, seasonal timing and migration. However, findings are inconsistent, difficult to disentangle from environmental responses, and biased towards high latitudes. Here we combine field data with a common-garden set up to study associations of Clk with latitude, migration and annual-cycle timing within the stonechat species complex with trans-equatorial distribution range. Including 950 individuals from nine populations with diverse migratory strategies. Gene diversity was lowest in resident African and Canary Island populations and increased with latitude, independently of migration distance. Repeat length and annual-cycle timing was linked in a population-specific way. Specifically, equatorial African stonechats showed delayed timing with longer repeat length for all annual-cycle stages. Our data suggest that at low latitudes with constant photoperiod, Clk genotype might orchestrate a range of consistent, individual chronotypes. In contrast, the influence of Clk on annual-cycle timing at higher latitudes might be mediated by its interactions with genes involved in (circadian) photoperiodic pathways

Molecular beam surface analysis. 1993 Summary report

The Molecular Beam Surface Analysis (MBSA) program is developing both laboratory-based and potentially field-portable chemical analyses systems taking advantage of new surface analysis technology developed at the Idaho National Engineering Laboratory (INEL). The objective is to develop the means to rapidly detect and identify, with high specificity and high sensitivity, nonvolatile and low volatile organics found in Chemical Weapons (CW) and High Explosives (HE) feedstocks, agents, and decomposition products on surfaces of plants, rocks, paint chips, filters, smears of buildings, vehicles, equipment, etc.. Ideally, the method would involve no sample preparation and no waste generation, and would have the potential for being implemented as a field-portable instrument. In contrast to existing analytical methods that rely on sample volatility, MBSA is optimized for nonvolatile and low volatile compounds. This makes it amenable for rapidly screening field samples for CW agent decomposition products and feedstock chemicals and perhaps actual agents. In its final configuration (benchtop size) it could be operated in a non-laboratory environment (such as an office building) requiring no sample preparation chemistry or chemical supplies. It could also be included in a mobile laboratory used in on-site, ore remote site cooperative surveys, or in a standard laboratory, where it would provide fast screening of samples at minimal cost

Investigating the Etiology of Sour Knuckles in Postchilled Beef Carcasses

Development of sourness in beef round muscle cuts, such as knuckles, has been a long-standing issue in the beef industry with little characterization. Therefore, the objective of this study was to investigate and characterize the sour odor associated with beef knuckles using sensory, analytical (gas chromatography-mass spectrometry [GC-MS]), and microbiological approaches. Knuckles (n = 10) with no sour odor (control), a slight sour odor, or severe sour odor were collected during fabrication from a commercial beef processing plant. In addition, the synovial fluid from the femur joint, and the femur surface associated with the collected knuckles, were sponge-sampled. Knuckles were separated into 2 halves, with one half subjected to an odor panel, GC-MS, and microbial analyses on the day of collection (day 0). The remaining half was analyzed for odor and microbial populations following 35 d of vacuum-packaged storage at 0°C ± 2°C (day 35). Odor panelists identified differences (P < 0.05) between control and sour knuckles (slight sour odor and severe sour odor) for all attributes tested (off-odor, oxidation, putrid, and sour notes) regardless of storage day. GC-MS analysis found no statistical difference (P > 0.05) in volatiles between control and severe-sour-odor samples. Microbial analysis (aerobic plate counts and lactic acid bacteria counts) of muscle tissue on day 0 and day 35 of storage revealed no (P > 0.05) differences between the 3 treatment groups. Similarly, no (P > 0.05) differences between the treatment groups were obtained following analysis of synovial fluid and femur surface sponge samples for psychrotrophic anaerobic sporeformer counts. The findings of the study indicated that the souring condition in knuckles exists at identifiable intensities with no volatile acid or microbial population differences; therefore, further investigation is needed to determine the etiology

A phase II evaluation of cediranib in the treatment of recurrent or persistent endometrial cancer: An NRG Oncology/Gynecologic Oncology Group study

PURPOSE: Cediranib is a multi-tyrosine kinase inhibitor targeting vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF) receptors. This phase II study was conducted to assess activity and tolerability of single-agent cediranib in recurrent/persistent endometrial cancer. PATIENTS AND METHODS: Eligible patients had recurrent or persistent endometrial cancer after receiving one or two prior cytotoxic regimens, measurable disease, and Gynecologic Oncology Group (GOG) performance status of ≤2 (≤1 if two prior cytotoxic regimens given). Cediranib 30mg orally daily for a 28daycycle was administered until disease progression or prohibitive toxicity. Microvessel density (MVD) was measured in tumor tissue from initial hysterectomy specimens and correlated with clinical outcome. Primary endpoints were tumor response and surviving progression-free for six months without subsequent therapy (6-month event-free survival [EFS]). RESULTS: Of 53 patients enrolled, 48 were evaluable for cediranib efficacy and toxicity. Median age was 65.5 years, 52% of patients had received prior radiation, and 73% of patients received only one prior chemotherapy regimen. A partial response was observed in 12.5%. Fourteen patients (29%) had six-month EFS. Median progression-free survival (PFS) was 3.65 months and median overall survival (OS) 12.5 months. No grade 4 or 5 toxicities were observed. A trend towards improved PFS was found in patients whose tumors expressed high MVD. CONCLUSION: Cediranib as a monotherapy treatment for recurrent or persistent endometrial cancer is well tolerated and met protocol set objectives for sufficient activity to warrant further investigation. MVD may be a useful biomarker for activity

Individual variability and versatility in an eco-evolutionary model of avian migration

Seasonal migration is a complex and variable behaviour with the potential to promote reproductive isolation. In Eurasian blackcaps (Sylvia atricapilla), a migratory divide in central Europe separating populations with southwest (SW) and southeast (SE) autumn routes may facilitate isolation, and individuals using new wintering areas in Britain show divergence from Mediterranean winterers. We tracked 100 blackcaps in the wild to characterize these strategies. Blackcaps to the west and east of the divide used predominantly SW and SE directions, respectively, but close to the contact zone many individuals took intermediate (S) routes. At 14.0° E, we documented a sharp transition from SW to SE migratory directions across only 27 (10–86) km, implying a strong selection gradient across the divide. Blackcaps wintering in Britain took northwesterly migration routes from continental European breeding grounds. They originated from a surprisingly extensive area, spanning 2000 km of the breeding range. British winterers bred in sympatry with SW-bound migrants but arrived 9.8 days earlier on the breeding grounds, suggesting some potential for assortative mating by timing. Overall, our data reveal complex variation in songbird migration and suggest that selection can maintain variation in migration direction across short distances while enabling the spread of a novel strategy across a wide range

Understanding the Impact of Oven Temperature and Relative Humidity on the Beef Cooking Process

The objective of this study was to evaluate the roles that cooking rate and relative humidity has on the sensory development of beef strip steaks. Thirty USDA Choice beef strip loins were collected from a commercial packing facility. Each strip loin was cut into steaks and randomly assigned to 1 of 6 cooking methods utilizing 2 oven temperatures (80°C and 204°C) and 3 levels of relative humidity [zero (ZH), mid (MH), and high (HH)]. Cooked steaks were used to evaluate internal and external color, Warner-Bratzler and slice shear force, total collagen content, protein denaturation, and trained sensory ratings. Relative humidity greatly reduced cooking rate, especially at 80°C. Steaks cooked at 80°C-ZH had the greatest (P 0.05). Steaks cooked at 80°C-ZH appeared the most (P 0.01) surface color. Total collagen was greatest (P 0.05) by treatment. Increased (P = 0.02) sarcoplasmic protein denaturation was observed with ZH and MH, while increased (P = 0.02) actin denaturation was observed only with ZH. Oven temperature did not influence (P > 0.05) protein denaturation. Trained panelists rated steaks the most tender (P 0.05) juiciness at 204°C; however, MH and HH produced a juicier (P < 0.01) steak when cooked at 80°C. Humidity hindered (P < 0.01) the development of beefy/brothy and brown/grilled flavors but increased (P = 0.01) metallic/bloody intensity. Lower oven temperatures and moderate levels of humidity could be utilized to maximize tenderness, while minimally affecting flavor development

Selective small molecule induced degradation of the BET bromodomain protein BRD4

The Bromo- and Extra-Terminal (BET) proteins BRD2, BRD3, and BRD4 play important roles in transcriptional regulation, epigenetics, and cancer and are the targets of pan-BET selective bromodomain inhibitor JQ1. However, the lack of intra-BET selectivity limits the scope of current inhibitors as probes for target validation and could lead to unwanted side effects or toxicity in a therapeutic setting. We designed Proteolysis Targeted Chimeras (PROTACs) that tether JQ1 to a ligand for the E3 ubiquitin ligase VHL, aimed at triggering the intracellular destruction of BET proteins. Compound MZ1 potently and rapidly induces reversible, long-lasting, and unexpectedly selective removal of BRD4 over BRD2 and BRD3. The activity of MZ1 is dependent on binding to VHL but is achieved at a sufficiently low concentration not to induce stabilization of HIF-1α. Gene expression profiles of selected cancer-related genes responsive to JQ1 reveal distinct and more limited transcriptional responses induced by MZ1, consistent with selective suppression of BRD4. Our discovery opens up new opportunities to elucidate the cellular phenotypes and therapeutic implications associated with selective targeting of BRD4