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African trypanosomes proliferate as bloodstream forms (BSFs) and procyclic forms in the mammal and tsetse fly midgut, respectively. This allows them to colonise the host environment upon infection and ensure life cycle progression. Yet, understanding of the mechanisms that regulate and drive the cell replication cycle of these forms is limited. Using single-cell transcriptomics on unsynchronised cell populations, we have obtained high resolution cell cycle regulated (CCR) transcriptomes of both procyclic and slender BSF Trypanosoma brucei without prior cell sorting or synchronisation. Additionally, we describe an efficient freeze-thawing protocol that allows single-cell transcriptomic analysis of cryopreserved T. brucei. Computational reconstruction of the cell cycle using periodic pseudotime inference allowed the dynamic expression patterns of cycling genes to be profiled for both life cycle forms. Comparative analyses identify a core cycling transcriptome highly conserved between forms, as well as several genes where transcript levels dynamics are form specific. Comparing transcript expression patterns with protein abundance revealed that the majority of genes with periodic cycling transcript and protein levels exhibit a relative delay between peak transcript and protein expression. This work reveals novel detail of the CCR transcriptomes of both forms, which are available for further interrogation via an interactive webtool. [ABSTRACT FROM AUTHOR]

Simple Summary: Oesophago-gastric cancer is one of the commonest cancers worldwide, yet it can be particularly difficult to diagnose given that initial symptoms are often non-specific and routine screening is not available. Cancer risk-assessment tools, which calculate cancer risk based on symptoms and other risk factors present in the primary care record, can aid decisions on referrals for cancer investigations, facilitating earlier diagnosis. Diagnosing common cancers earlier could help improve survival rates. Using UK primary care electronic health record data, we compared five different machine learning techniques for probabilistic classification of cancer patients against a current widely used UK primary care cancer risk-assessment tool. The machine learning algorithms outperformed the current risk-assessment tool, with a higher overall accuracy and an ability to reasonably identify 11–25% more cancer patients. We conclude that machine-learning-based risk-assessment tools could help better identify suitable patients for further investigation and support earlier diagnosis. Oesophago-gastric cancer is difficult to diagnose in the early stages given its typical non-specific initial manifestation. We hypothesise that machine learning can improve upon the diagnostic performance of current primary care risk-assessment tools by using advanced analytical techniques to exploit the wealth of evidence available in the electronic health record. We used a primary care electronic health record dataset derived from the UK General Practice Research Database (7471 cases; 32,877 controls) and developed five probabilistic machine learning classifiers: Support Vector Machine, Random Forest, Logistic Regression, Naïve Bayes, and Extreme Gradient Boosted Decision Trees. Features included basic demographics, symptoms, and lab test results. The Logistic Regression, Support Vector Machine, and Extreme Gradient Boosted Decision Tree models achieved the highest performance in terms of accuracy and AUROC (0.89 accuracy, 0.87 AUROC), outperforming a current UK oesophago-gastric cancer risk-assessment tool (ogRAT). Machine learning also identified more cancer patients than the ogRAT: 11.0% more with little to no effect on false positives, or up to 25.0% more with a slight increase in false positives (for Logistic Regression, results threshold-dependent). Feature contribution estimates and individual prediction explanations indicated clinical relevance. We conclude that machine learning could improve primary care cancer risk-assessment tools, potentially helping clinicians to identify additional cancer cases earlier. This could, in turn, improve survival outcomes. [ABSTRACT FROM AUTHOR]

Genomic testing is a commercially available tool that has the potential to be beneficial in selecting cattle for retained ownership, as well as making management and marketing decisions after finishing. The objectives of this study were to determine if commercially available genomic tests are predictive of differences in finishing performance of steers from sires selected based on divergent growth and milk EPDs. The commercial genomic testing of milk and average daily gain (ADG) scores used in the current experiment were based on Neogen Igenity Beef test results. Two trials were conducted at the OSU Willard Sparks Beef Research Center in Stillwater, Oklahoma. These experiments used two sets of steers from the OSU Range Cow Research Center (400 ± 13 kg, n = 154) from a spring calving cowherd (South Range Unit) and a fall calving cowherd (North Range Unit) of primarily Angus ancestry. Following preconditioning and a wheat pasture stocker program (South Range) or dry lot growing period (North Range), steers were allocated into pens (n = 5 animals/pen) by Igenity ADG Score: low growth (LG) had scores ranging from 1 to 4, medium growth (MG) had scores from 5 to 6, and high (HG) had scores from 7 to 10. Steers were blocked by initial BW and fed a step-up diet for 30 d before being switched to a finishing ration diet (8% prairie hay, 20% Sweet Bran, 62% dry-rolled corn, 5% liquid supplement, and 5% dry supplement [DM basis]). Cattle were fed ractopamine hydrochloride for 30 d before slaughter. The heavy block was on feed for an average of 136 d, while the light block was on feed for an average of 160 d. Data were analyzed as a randomized complete block design using the mixed procedure of SAS (SAS Inst. Inc., Cary NC) with pen as the experimental unit and finishing pen within block as the random statement. During the feeding period, HG steers gained more rapidly than MG or LG steers, with ADG of 2.08, 1.94, and 1.90 kg/d, respectively (P = 0.04). Because gains were greater, BW at slaughter for the HG steers was greater than MG and LG, averaging 690, 669, and 660 kg, respectively (P = 0.04) and hot carcass weights were greater for HG than MG and LG, averaging 438, 426 and 418 kg, respectively (P = 0.02). There were no other differences (P > 0.19) in carcass characteristics among steers. These data suggests that the genomic testing is accurate predictor of performance and can be used by producers can make better marketing decisions in selecting cattle for the retained. Genomic testing could be very beneficial for producers looking to minimize risk and maximize performance in their herd. [ABSTRACT FROM AUTHOR]

Wild bees can be essential pollinators in natural, agricultural, and urban systems, but populations of some species have declined. Efforts to assess the status of wild bees are hindered by uncertainty in common sampling methods, such as pan traps and aerial netting, which may or may not provide a valid index of abundance across species and habitats. Mark-recapture methods are a common and effective means of estimating population size, widely used in vertebrates but rarely applied to bees. Here we review existing mark-recapture studies of wild bees and present a new case study comparing mark-recapture population estimates to pan trap and net capture for four taxa in a wild bee community. Net, but not trap, capture was correlated with abundance estimates across sites and taxa. Logistical limitations ensure that mark-recapture studies will not fully replace other bee sampling methods, but they do provide a feasible way to monitor selected species and measure the performance of other sampling methods. [ABSTRACT FROM AUTHOR]

In recent years, substantial progress has been made in understanding the sources of biological variation and genetic components of feed efficiency in growing animals consuming energy-dense mixed diets during the post-weaning phase. Much less is known about within-animal variation of feed efficiency for beef cows consuming moderate to low-quality forage diets common to most cow/calf production systems. Considerable evidence indicates the existence of a genetic by environment interaction for feed efficiency. Phenotype for feed intake and feed efficiency are most practically and cost effectively determined during the post-weaning growing stage. However, due to the additional nutrient sinks associated with gestation and lactation, and the cost, labor and technology required to measure economically relevant traits in mature cows, little is known about forage utilization efficiency in beef cows. The beef cow/calf segment of the industry represents, by far, the greatest opportunity to reduce beef production input costs and reduce the industry's carbon footprint. We reason that selection tools for feed intake and feed efficiency developed over the last 20 years are effective for the post-weaning growing and finishing phases, although only marginally effective for beef cows consuming unprocessed, moderate to low-quality forage. In this session, we will discuss challenges, opportunities, and experiences associated with measuring forage intake and recovered energy in beef cows. [ABSTRACT FROM AUTHOR]

The objective of this experiment was to determine the relationships among enteric gas production, body weight (BW) gain, and feed intake for growing heifers consuming two energy divergent diets. Fifty-five fall born yearling Angus and Angus cross heifers were used in a 157-d experiment. Heifers were fed two consecutive diets at the Oklahoma State University Range Cow Research Center. Heifers were sorted into one of two drylot pens based on BW. Each drylot pen was equipped with individual intake monitoring system (C-Lock Inc., Rapid City, SD) with a stocking rate of 3.3 heifers per feeder. The first intake segment (HAY) was initiated with a 21 d of adaptation followed by 70 d of data collection. Heifers were offered ad libitum access to long stem unprocessed bermudagrass hay and a salt/mineral/vitamin supplement. After the HAY period, heifers were adapted to a 50% forage, 50% concentrate diet (TMR) during a 14-d adaptation period, followed by 52-d of data collection. Means and standard deviations for phenotypic traits of DMI, ADG, RFI, and CH4 were 6.7 ± 0.7 kg, 0.44 ± 0.13kg, and 194.6 ± 17.56 g/d respectively for HAY and 14.3 ± 1.34 kg, 1.72 ± 0.20 kg, and 280 ± 24.69 g/d respectively for TMR. Pearson correlations between diets for DMI, ADG, and CH4 were 0.32, -0.16, and 0.29, respectively. Coefficient of variation for DMI was 10.8% for HAY and 9.4% for TMR. Coefficient of variation for ADG was 29.9% for HAY and 11.6% for TMR. Methane intensity was calculated as CH4, g/day divided by DMI, kg/d resulting in 29.6 ± 3.5 and 19.9 ± 2.2 g CH4/kg DMI for HAY and TMR, respectively. In summary, HAY DMI was moderately and positively correlated with TMR DMI while ADG was not correlated among the two diet types. The HAY diet generated less total daily CH4, although more CH4 per unit of feed intake. [ABSTRACT FROM AUTHOR]

Switching of the Variant Surface Glycoprotein (VSG) in Trypanosoma brucei provides a crucial host immune evasion strategy that is catalysed both by transcription and recombination reactions, each operating within specialised telomeric VSG expression sites (ES). VSG switching is likely triggered by events focused on the single actively transcribed ES, from a repertoire of around 15, but the nature of such events is unclear. Here we show that RNA-DNA hybrids, called R-loops, form preferentially within sequences termed the 70 bp repeats in the actively transcribed ES, but spread throughout the active and inactive ES, in the absence of RNase H1, which degrades R-loops. Loss of RNase H1 also leads to increased levels of VSG coat switching and replication-associated genome damage, some of which accumulates within the active ES. This work indicates VSG ES architecture elicits R-loop formation, and that these RNA-DNA hybrids connect T. brucei immune evasion by transcription and recombination. [ABSTRACT FROM AUTHOR]

Background: Cancer-related pain is a complex multidimensional experience that affects all aspects of life. To support those impacted by cancer-related pain it is essential that health professionals have adequate knowledge in its assessment and management. Aims: To explore the knowledge of health professionals regarding cancer-related pain. Methods: A scoping review methodology was used to systematically search the literature published between 2010 and 2020. Databases CINAHL, Medline and PsycINFO were searched using terms 'cancer pain', 'healthcare professional', 'knowledge', 'attitudes' and 'barriers'. Findings: The search identified 38 articles. They focused on nursing knowledge with minimal involvement of allied health professionals. Knowledge levels were variable with the majority demonstrating poor knowledge. Common knowledge gaps included around fear of addiction, principles of cancer-related pain assessment and management, and interventional techniques. Conclusion: Knowledge of cancer-related pain is variable with several knowledge gaps. More work is needed to ensure health professionals have adequate knowledge regarding the complexity of cancer-related pain. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate weight gain, feed intake, and feed efficiency in beef heifers while consuming two diets divergent in energy density. Fifty-four yearling Angus and Angus cross heifers (initial body weight = 307.5 ± 30.35 kg) were subject to sequential intake trials using SmartFeed individual intake measuring technology (C-Lock Inc., Rapid City, SD) in drylot pens at the Oklahoma State University Range Cow Research Center. The first intake period (HAY) was initiated on July 15 (d -21) with a 21-d adaptation period and a 70-d intake period. Bermudagrass hay (10.3% CP, 2.0 Mcal ME, and 56% TDN) and a salt/mineral/vitamin supplement was offered on an ad libitum basis throughout the experiment. The second intake period was initiated on d-92 and included 14 d of adaption with 42 d of data collection. A mixed diet (12.4% CP, 45% NDF, and 65% TDN) consisting of 50% chopped bermudagrass hay, concentrate feeds, and a liquid supplement containing minerals and vitamins (TMR) was offered on an ad libitum basis. In both periods, weights were recorded every 14 days, and ADG was calculated by regressing body weight over time. Dry matter intake (DMI) and residual feed intake (RFI) were calculated at the end of each feeding period. Statistical regression equations were used to predict RFI for both HAY and TMR, including average metabolic body weight and average daily gain for each of their respective trials. For RFI, cattle were classified as inefficient, average, or efficient based on 0.5 SD away from the mean RFI score. Descriptive statistics for HAY evaluated traits of DMI, ADG, and RFI (means ± SD) were 5.49 ± 0.84 kg, 0.15 ± 0.16 kg, and 0.0 ± 1.01 kg, respectively. Means ± SD for DMI, ADG, and RFI for TMR were 9.54 ±1.26 kg, 1.45 ± 0.38 kg, and 0.0 ± 0.15 kg. Spearman rank correlations for DMI, ADG, and RFI were 0.35 (P = 0.0089), 0.16 (P = 0.2367), and 0.52 (P < 0.0001), respectively. This initial study suggests that intake of hay and a mixed diet may be modestly correlated, while there is no relationship of weight gain when consuming forage and weight gain consuming a mixed, processed diet. [ABSTRACT FROM AUTHOR]

The objective of this study was to compare residual feed intake (RFI) and greenhouse gas exchange in mature beef cows during gestation and lactation when consuming an unprocessed, grass hay diet. Twenty-six mature Angus and Angus x Hereford cows (4.5 ± 0.0 yr) were used in two voluntary intake studies. Cows were evaluated during mid-gestation (GEST) and late lactation (LACT). Unprocessed grass hay (GEST = 8.73% CP and 59.25% TDN; LACT = 8.31% CP and 54.50% TDN) and a mineral mix were provided for ad libitum consumption. Individual animal feed intake data was collected for 52 d and 71 d for GEST and LACT respectively using SmartFeed intake units (C-Lock Inc., Rapid City, SD) and a stocking rate of 3 cows per feeder. An open-circuit, gas-quantification system (GreenFeed, C-Lock Inc., Rapid City, SD) was used to collect CH4 production for 9 days per pen for a minimum of 20 visits per cow. Hay intake averaged 13.8 ± 2.3 kg and 16.6 ± 2.0 kg during GEST and LACT, respectively. The Pearson correlation coefficient for hay intake among the two stages of production was 0.65 (P < 0.01). Metabolic body weight, average daily gain, and ultrasound ribeye area explained 46% of the variation in GEST DMI (P < 0.01), and milk yield, metabolic body weight, and average daily gain explained 64% of the variation in LACT DMI (P < 0.01). Each one kg additional milk production resulted in 0.7 kg greater hay intake during LACT (P < 0.01). There was a moderate correlation between GEST and LACT CH4 (r = 0.64) and a moderate correlation between CH4 production within each stage of production and DMI for that same stage of production (r = 0.58 and 0.63 for GEST and LACT, respectively). Hay intake was moderately correlated between stages of production although highly sensitive to milk yield. [ABSTRACT FROM AUTHOR]

Forage and supplemental feed costs remain the overriding factors driving profitability in U.S. cow/calf operations. The cow/calf sector uses 74% of the total feed energy required to produce one pound of carcass weight. Methane is the second most abundant anthropogenic greenhouse gas after carbon dioxide. The cow/calf sector of beef production accounts for 77 to 81% of enteric methane emissions per unit of carcass weight produced. Reducing feed energy required and methane emissions by the cow/calf segment of the beef production system will improve economic, environmental, and social sustainability. Most of the beef production cycle occurs on land not suitable for raising crops. Of the 2.3 billion acres available in the United States, about 655 million acres (29%) are classified as grassland pasture and rangeland, and 316 million acres (14%) are identified as parks and wildlife areas, some of which are grazed. Therefore, improving forage utilization efficiency would have a wide-reaching impact on U.S. food security and profitability of cow/calf enterprises. Beef production is a critical component in U.S. and global food security because cattle upcycle poorly digestible plant components and food waste products into high-quality human edible protein. In recent years, substantial progress has been made in understanding biological variation and genetic components of feed efficiency in growing animals consuming energy-dense mixed diets during the post-weaning phase. Much less is known about within-animal variation of forage utilization efficiency for beef cows consuming moderate to low-quality forage diets common to most cow/calf production systems. Considerable evidence indicates the existence of an environment by genetic interaction for feed efficiency. More rapid progress in forage utilization efficiency and reduction in greenhouse gas emissions could be made by studying forage utilization efficiency directly. [ABSTRACT FROM AUTHOR]

Survival of the African trypanosome within its mammalian hosts, and hence transmission between hosts, relies upon antigenic variation, where stochastic changes in the composition of their protective variant-surface glycoprotein (VSG) coat thwart effective removal of the pathogen by adaptive immunity. Antigenic variation has evolved remarkable mechanistic complexity in Trypanosoma brucei , with switching of the VSG coat executed by either transcriptional or recombination reactions. In the former, a single T. brucei cell selectively transcribes one telomeric VSG transcription site, termed the expression site (ES), from a pool of around 15. Silencing of the active ES and activation of one previously silent ES can lead to a co-ordinated VSG coat switch. Outside the ESs, the T. brucei genome contains an enormous archive of silent VSG genes and pseudogenes, which can be recombined into the ES to execute a coat switch. Most such recombination involves gene conversion, including copying of a complete VSG and more complex reactions where novel 'mosaic' VSG s are formed as patchworks of sequences from several silent (pseudo)genes. Understanding of the cellular machinery that directs transcriptional and recombination VSG switching is growing rapidly and the emerging picture is of the use of proteins, complexes and pathways that are not limited to trypanosomes, but are shared across the wider grouping of kinetoplastids and beyond, suggesting co-option of widely used, core cellular reactions. We will review what is known about the machinery of antigenic variation and discuss if there remains the possibility of trypanosome adaptations, or even trypanosome-specific machineries, that might offer opportunities to impair this crucial parasite-survival process. • African trypanosomes evade host immune defences by stochastically switching the Variant Surface Glycoprotein (VSG) expressed on their surface, a process called antigenic variation. • African trypanosomes co-opt widely conserved factors and processes to coordinate switching events, and possibly monogenic antigen expression. • The wide conservation of these reactions may hinder the development of anti-trypanocidal drugs targeting antigenic variation. • VSG switching by recombination potentially involves a number of DNA break repair reactions, initiated by lesions within the telomeric sites of VSG transcription. • The spatial integration of transcription and splicing shapes a specific and critical nuclear organisation to sustain VSG monogenic expression and boost RNA processing. [ABSTRACT FROM AUTHOR]

Four years of feedlot performance and carcass characteristics were pooled on spring-(SPRING) and fall-(FALL) born steers (n=460) into a mixed model to evaluate the effects of calving season, sire breed (Angus [AN], Charolais [CHAR] or Hereford [HER]) and their interaction on feedlot performance and carcass traits. Initial and final BW, DOF, ADG, DMI, and G:F were evaluated as performance measures and HCW, YG, FT, REA, and MS were collected at harvest. There was no season by breed interaction for entry or final BW (P >0.05). SPRING steers (400.2 kg, 686.4 kg) weighed more than FALL (350.9 kg, 668.3 kg) upon entering and leaving the feedyard (P< 0.001). CHAR weighed 14.3 kg less than AN upon feedlot entry (P=0.01) although final BW did not differ by breed (P >0.05). SPRING steers (21.8 kg/d) consumed more feed than FALL steers (18.8 kg/d; P=0.002), but there was no difference in gain:feed due to calving season nor sire breed (P=0.575). A calving season by sire breed interaction was present for ADG and DOF (P=0.014). FALL AN (1.70 kg/d) and FALL HER (1.80 kg/d) gained more than FALL CHAR (1.55 kg/d;P< 0.001) and FALL AN were fed over a shorter period than FALL CHAR and FALL HER (P=0.006). However, average daily gain of SPRING calves did not differ by breed (P >0.05). There was a tendency for FALL (400.9 kg) steers to have lighter carcasses than SPRING steers (407.9 kg; P=0.068). HER carcasses were 18.0 kg heavier than AN carcasses (P< 0.001), but did not differ from CHAR (P=0.13). CHAR had larger REA (93.5 cm2) than both AN (87.7 cm2) and HER steers (88.5 cm2;P=0.001). Fall-born steers had less YG than spring-born steers (P< 0.042). Feedlot performance was generally less for fall-born steers finished during the winter months. Under these conditions, numerous performance and carcass traits were influenced by the interaction of breed and season. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the relationship between beef heifer feed efficiency and subsequent greenhouse gas emissions using an unprocessed hay diet. Fifty-four Angus and Angus Herford cross heifers were subject to a 71-day hay intake test using individual intake technology (C-Lock Inc., Rapid City, SD) with a stocking rate of 3.6 heifers per feeder. Heifers were blocked by BW into 2 drylot pens (HEAVY, n=21; LIGHT, n=33) at the Oklahoma State University Range Cow Research Center located near Stillwater, OK. Throughout the study, heifers were fed a long-stem, unprocessed, grass hay diet (10.8% CP, 2.0 Mcal ME, and 56% TDN) with 21-d adaptation. A subset of 39 heifers were used for the collection of gas flux data using an open-circuit, portable, gas-quantification system (GreenFeed, C-Lock Inc., Rapid City, SD) to measure (means±SD) oxygen consumption (3,118±330.9 g/d), carbon dioxide production (4,664±467.9 g/d), and methane production (169±23.4 g/d). Phenotypic measures (means±SD) for dry matter intake (DMI), average daily gain (ADG), average body weight (BW), and residual feed intake (RFI) were 6.75±1.12 kg, 0.15±0.2 kg, 312.7±30.5 kg, and 0.08±0.84 kg, respectively. Predicted DMI was calculated using a multiple regression equation (-3.11 + 0.13*BW0.75+0.76*ADG; P< 0.05; R2=0.43) in R. To further evaluate forage efficiency, heifers were segregated by 0.5 SD into three RFI categories of efficient (n=13), average (n=31), and inefficient (n=10) resulting in means of 5.8, 6.76, and 7.94 kg DMI and 0.16, 0.16, and 0.15 kg ADG, respectively. There was no significant difference (p< 0.05) between RFI categories for ADG, CO2, CH4, and O2. Phenotypic correlations of DMI with CO2, CH4, and O2 were 0.59, 0.45, and 0.61, respectively. Efficient heifers consumed 21% less forage compared with inefficient heifers, suggesting that improvement in forage utilization can be achieved when efficiency is evaluated using an unprocessed grass hay diet. [ABSTRACT FROM AUTHOR]

The objective of this study was to compare high and low residual feed intake (RFI) beef cows when consuming an unprocessed, grass hay diet (93% DM, 8.73% CP, 2.11 Mcal ME, and 59.25% TDN). Relationships of hay intake to carbon dioxide (CO2) and methane (CH4) production were also evaluated. Thirty-six mature Angus and Angus x Hereford cows were assigned randomly to five pens (n = 6 or 9) and individual feed intakes were collected for 52-d using SmartFeed intake units (C-Lock Inc. Rapid City, SD) at a stocking rate of 3 cows per feeder. An open-circuit, gas-quantification system (GreenFeed, C-Lock Inc. Rapid City, SD) was used to collect CO2 (7611.63±714.09 g) and CH4 (283.64±37.10 g) production for 9 days of collection per pen for a minimum of 20 visits per cow (n = 22 cows, 36.18±14.24 visits). Data collection on cows included (means ± SD) dry matter intake (DMI; 13.86±2.16 kg), metabolic body weight (MBW, 111.65±9.28 kg), average daily gain (ADG, 0.77±0.29 kg), and rib eye area by ultrasound (REA, 46.62±6.34 cm).To calculate RFI (0.03±1.71), a multiple regression model was used to predict DMI (PDMI = ADG + REA + MBW; R2=0.50, P = 0.001). Cows were categorized into three RFI classes: low (n = 7), moderate (n = 6), and high (n = 9). Differences between RFI and RFI class and DMI and RFI class were analyzed using PROC MIXED in SAS (SAS, Cary, NC). Low RFI cows (-1.81 kg) consumed 12.08 kg hay DM daily and high RFI cows (1.59 kg) consumed 15.27 kg hay DM daily (P < 0.001). Correlations between DMI and daily gas exchange were estimated using PROC CORR in SAS (SAS, Cary, NC). Pearson Correlation Coefficients were significant between DMI and CO2 (r=0.58, P = 0.004), and CH4 (r=0.70, P < 0.001) production. Differences in feed intake for high and low RFI rankings were similar to previously reported literature when growing cattle consumed energy-dense diets. [ABSTRACT FROM AUTHOR]

The objective of this study was to rank beef heifers for residual feed intake and greenhouse gas emissions using an unprocessed, grass hay diet. Fifty yearling Angus heifers were monitored for 62 days using the SmartFeed individual intake measuring technology (C-Lock Inc. Rapid City, SD) in drylot pens at the Oklahoma State University Range Cow Research Center located in Stillwater, OK. Means ± SD for dry matter intake (DMI; 6.76 ± 1.20 kg), average daily gain (ADG; 0.51 ± 0.21 kg), body weight (BW; 338.67 ± 55.24 kg), and residual feed intake (RFI; -0.04 ± 0.80 kg) were recorded while the heifers were fed unprocessed long-stem grass hay (10.3% CP, 2.0 Mcal ME, and 56% TDN). Additionally, a subset of 29 heifers were subjected to the collection of gas flux data using an open-circuit, portable, gas-quantification system (GreenFeed, C-Lock Inc. Rapid City, SD) to measure (means ± SD) oxygen consumption (O2; 3979.51 ± 510.32 g), carbon dioxide production (CO2; 5299.65 ± 610.89 g), and methane production (CH4; 202.656 ± 28.30 g). Using R, RFI was calculated using a multiple regression equation to predict DMI using BW0.75 and ADG (P > 0.05; R2 = 0.37). To analyze forage utilization efficiency, heifers were classified into three RFI categories consisting of efficient (n = 16), average (n = 16), and inefficient (n =18). The ADG was low for all RFI classifications and similar for all three categories (P < 0.05). Heifers classified in the top third of RFI rank consumed 22% less forage per day compared to the inefficient heifers. The phenotypic correlation between DMI with CO2, CH4, and O2 was 0.66, 0.18, and 0.49, respectively. These data suggest that progress in feed efficiency can be achieved when cattle are tested using a moderate-quality, unprocessed forage diet. [ABSTRACT FROM AUTHOR]

This study's objective was to determine the relationship between retained energy, lactation maintenance energy requirement (MER), and dry period voluntary feed intake (VOL) in beef cows. Twenty-four mature fallcalving Angus cows were used in an 82-d study during lactation to establish maintenance energy requirements followed by a voluntary feed intake study after weaning. During the lactation MER experiment, cows were housed in 2 drylot pens and limit-fed a mixed hay/concentrate diet (17.8% CP, 2.6 Mcal/kg ME, DM basis) individually once per d in a stall barn. Cows were adapted to the diet and feeding management for the first 16 d. Subsequently, cows were weighed and feed allowance adjusted at 14-d intervals to achieve BW and BCS stasis. Milk yield and composition were determined on d - 10, 49, and 77 using a milking machine. Retained energy was calculated as average daily maternal tissue energy change plus average daily milk energy yield. During the post-weaning VOL experiment, cows were provided ad libitum access to a grass hay diet for 41 d (8.15% CP, 1.8 Mcal/kg ME, DM basis) using five individual feed intake monitoring units (SmartFeed, C-Lock, Inc). Each one unit increase in metabolizable energy intake, kcal/kg BW0.75 was associated with a 0.86 ± 0.28 kcal/kg BW0.75 increase in total retained energy (P = 0.005). Using this partial efficiency coefficient, ME required for maintenance declined by 0.80 ± 0.11 kcal ME/kg BW0.75 for each additional kcal net energy retained/kg BW0.75 (P < 0.0001). There was no relationship between lactation-period retained energy and post-weaning VOL forage dry matter intake. The present study results contradict previous reports suggesting that maintenance requirements increase with increasing productivity. [ABSTRACT FROM AUTHOR]

Abstract: A novel series of pyridothieno-1,2,3-triazines with potent antifungal activity against Erysiphe graminis f. sp. tritici has been discovered. Two complementary synthetic routes to compounds of this type have been developed and used to efficiently explore the structure–activity relationships around the lead compound. The incorporation of oxygen atoms into the side chains of the molecules has allowed the solubility of the compounds to be increased 10-fold whilst retaining biological activity. [Copyright &y& Elsevier]

The article discusses the results of a survey of psychiatrists and trainees in Western Australia to determine their level of familiarity with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Topics covered include the increasing reporting of the disorder in the literature in recent years, a comparison of the survey results with a similar Japanese survey, and the findings which show the need for improving training in the area.

In this article, we present a secondary analysis of a descriptive phenomenological study that we conducted in the United Kingdom exploring nurses' experiences of working with patients with substance dependence and pain. Our aim was to focus upon the ethical issues that emerged in the empirical data and so we used the Four Principles of Biomedical Ethics plus attention to scope to guide and inform our analysis. We present six key themes: trust, paternalism, coercion, failure to respect autonomy, advocacy and withholding. We discuss how these themes intersect with the four principles plus scope to illuminate practice and the ethical issues that emerge when managing this patient population's pain. We recommend that clinicians adopt a collaborative approach to managing pain for patients with substance dependence that they remain aware of the power differentials inherent within the clinical setting and ensure that communication and teamwork remain at the forefront of decisions. Clinicians need access to ethical guidance to inform their practice decisions and clinical ethics support services could provide one solution. [ABSTRACT FROM AUTHOR]

RNA-DNA hybrids are epigenetic features of all genomes that intersect with many processes, including transcription, telomere homeostasis, and centromere function. Increasing evidence suggests that RNA-DNA hybrids can provide two conflicting roles in the maintenance and transmission of genomes: They can be the triggers of DNA damage, leading to genome change, or can aid the DNA repair processes needed to respond to DNA lesions. Evasion of host immunity by African trypanosomes, such as Trypanosoma brucei, relies on targeted recombination of silent Variant Surface Glycoprotein (VSG) genes into a specialized telomeric locus that directs transcription of just one VSG from thousands. How such VSG recombination is targeted and initiated is unclear. Here, we show that a key enzyme of T. brucei homologous recombination, RAD51, interacts with RNA-DNA hybrids. In addition, we show that RNA-DNA hybrids display a genome-wide colocalization with DNA breaks and that this relationship is impaired by mutation of RAD51. Finally, we show that RAD51 acts to repair highly abundant, localised DNA breaks at the single transcribed VSG and that mutation of RAD51 alters RNA-DNA hybrid abundance at 70 bp repeats both around the transcribed VSG and across the silent VSG archive. This work reveals a widespread, generalised role for RNA-DNA hybrids in directing RAD51 activity during recombination and uncovers a specialised application of this interplay during targeted DNA break repair needed for the critical T. brucei immune evasion reaction of antigenic variation. [ABSTRACT FROM AUTHOR]

Antigenic variation by variant surface glycoprotein (VSG) coat switching in African trypanosomes is one of the most elaborate immune evasion strategies found among pathogens. Changes in the identity of the transcribed VSG gene, which is always flanked by 70-bp and telomeric repeats, can be achieved either by transcriptional or DNA recombination mechanisms. The major route of VSG switching is DNA recombination, which occurs in the bloodstream VSG expression site (ES), a multigenic site transcribed by RNA polymerase I. Recombinogenic VSG switching is frequently catalyzed by homologous recombination (HR), a reaction normally triggered by DNA breaks. However, a clear understanding of how such breaks arise—including whether there is a dedicated and ES-focused mechanism—is lacking. Here, we synthesize data emerging from recent studies that have proposed a range of mechanisms that could generate these breaks: action of a nuclease or nucleases; repetitive DNA, most notably the 70-bp repeats, providing an intra-ES source of instability; DNA breaks derived from the VSG-adjacent telomere; DNA breaks arising from high transcription levels at the active ES; and DNA lesions arising from replication–transcription conflicts in the ES. We discuss the evidence that underpins these switch-initiation models and consider what features and mechanisms might be shared or might allow the models to be tested further. Evaluation of all these models highlights that we still have much to learn about the earliest acting step in VSG switching, which may have the greatest potential for therapeutic intervention in order to undermine the key reaction used by trypanosomes for their survival and propagation in the mammalian host. [ABSTRACT FROM AUTHOR]

The article explores the survey for planning patient-centered intervention of pain relief strategies used by older people with chronic pain. The authors emphasize the need for both pharmacological and non-pharmacological approaches to ensure effective pain management. A partnership is also required between health professionals or carers and older people to conduct an adequate pain assessment and negotiate a pain management strategy.

Background Glioblastoma (GBM) is a devastating form of brain cancer, with a short life expectancy. In addition to this poor prognosis, people with GBM often experience symptoms that may have a profound impact on their subjective well-being (SWB). The aim of this study was to investigate the lived experiences and perceptions of people with GBM regarding their SWB. Methods The study adopted a longitudinal, hermeneutical phenomenological approach. Twenty-seven interviews were conducted with 15 patients over a period of two years. Most participants were interviewed twice on a face-to-face basis (during combined chemotherapy and radiotherapy, and again during adjuvant chemotherapy). The hermeneutic circle was used to guide data analysis. Results Data analysis identified four key themes that depicted the lived experiences and perceptions of SWB of people with GBM. "Experience of the disease" focuses on the impact of diagnosis, symptoms and side effects. "Daily life" relates to daily activities, family roles, work and social lives. "Coping" includes the importance of normality and goal-setting. "Experiences of care" focuses on the impact of the treatment schedule, experiences of care and impressions of the monitoring of QoL. Conclusion SWB is affected by a variety of factors throughout the GBM disease and treatment journey. The findings of this study suggest that healthcare professionals can enhance the SWB of people with GBM by providing personalized care that supports people to set themselves goals for the future and retain a degree of normality wherever possible. [ABSTRACT FROM AUTHOR]

The genomes of all organisms are read throughout their growth and development, generating new copies during cell division and encoding the cellular activities dictated by the genome's content. However, genomes are not invariant information stores but are purposefully altered in minor and major ways, adapting cellular behaviour and driving evolution. Kinetoplastids are eukaryotic microbes that display a wide range of such read–write genome activities, in many cases affecting critical aspects of their biology, such as host adaptation. Here we discuss the range of read–write genome changes found in two well-studied kinetoplastid parasites, Trypanosoma brucei and Leishmania , focusing on recent work that suggests such adaptive genome variation is linked to novel strategies the parasites use to replicate their unconventional genomes. Polycistronic transcription dominates and shapes kinetoplastid genomes, inevitably leading to clashes with DNA replication. By harnessing the resultant DNA damage for adaptation, kinetoplastids have huge potential for dynamic read–write genome variation. Major origins of DNA replication are confined to the boundaries of polycistronic transcription units in the Trypanosoma brucei and Leishmania genomes, putatively limiting DNA damage. Subtelomeres may lack this arrangement, generating read–write hotspots. In T. brucei , early replication of the highly transcribed subtelomeric variant surface glycoprotein (VSG) expression site may ensure replication-transcription clashes within this site to trigger DNA recombination, an event critical for antigenic variation. Leishmania genomes show extensive aneuploidy and copy number variation. Notably, DNA replication requires recombination factors and relies on post-S phase replication of subtelomeres. Evolution of compartmentalised DNA replication programmes underpin important aspects of genome biology in kinetoplastids, illustrating the consolidation of genome maintenance strategies to promote genome plasticity. [ABSTRACT FROM AUTHOR]

Genomic testing of feeder cattle is reported to be beneficial in selecting cattle for the feedlot, as well as making management and marketing decisions. The objective of this study was to determine differences in performance and efficiency of finishing steers with a range of Neogen Igenity Beef scores for average daily gain (ADG) and milk. Spring born steer calves from the Oklahoma State University Range Cow Research Center (n = 83, BW = 419 ± 31.9) of Angus ancestry were placed on feed at the Willard Sparks Beef Research Center on May 5, 2022, after grazing wheat pasture for 155 d. The steers were grouped based on Igenity ADG Score [low (1-4), medium (5-6), or high (7-10)] and Milk Score [low (1-5) or high (6-10)] based on the Igenity results. Steers were allocated into pens (n = 5 steers/pen) in heavy and light BW blocks. Steers were fed a step-up diet for 30 d before being switched to a finishing ration diet (8% prairie hay, 20% Sweet Bran and 62% dry-rolled corn). Cattle were fed ractopamine for 30 d before slaughter. The heavy block were on feed for 119 d, while the light block were on feed for 148 d. Data were analyzed as a randomized complete block design using the mixed procedure of SAS (SAS Inst. Inc., Cary NC) with pen as the experimental unit. Steers with high growth (HG) scores gained weight more rapidly during finishing and weighed more at slaughter than medium growth (MG) and low growth (LG; P < 0.01); while steers with high milk (HM) gained faster (P < 0.01) and tended (P = 0.06) to be heavier at slaughter than low milk (LM). Growth score was shown to have an effect on dry matter intake (P < 0.01) with HG consuming more feed than MG or LG. Cattle with HM scores were less efficient than LM scores (P = 0.01), but there was no difference (P = 0.37) in feed efficiency due to ADG score. Those with high growth and milk scores had a higher average daily gain (P < 0.01). These data indicate that Igenity ADG scores can be used to select cattle with higher performance and bodyweight at slaughter with no adverse effect on feed efficiency. Steers with higher Igenity Milk scores were less efficient than those with LM scores. Igenity Milk scores can be used to predict efficiency, according to these data. [ABSTRACT FROM AUTHOR]

All cells are subject to structural damage that must be addressed for continued growth. A wide range of damage affects the genome, meaning multiple pathways have evolved to repair or bypass the resulting DNA lesions. Though many repair pathways are conserved, their presence or function can reflect the life style of individual organisms. To identify genome maintenance pathways in a divergent eukaryote and important parasite, Trypanosoma brucei, we performed RNAi screens to identify genes important for survival following exposure to the alkylating agent methyl methanesulphonate. Amongst a cohort of broadly conserved and, therefore, early evolved repair pathways, we reveal multiple activities not so far examined functionally in T. brucei, including DNA polymerases, DNA helicases and chromatin factors. In addition, the screens reveal Trypanosoma- or kinetoplastid-specific repair-associated activities. We also provide focused analyses of repair-associated protein kinases and show that loss of at least nine, and potentially as many as 30 protein kinases, including a nuclear aurora kinase, sensitises T. brucei to alkylation damage. Our results demonstrate the potential for synthetic lethal genome-wide screening of gene function in T. brucei and provide an evolutionary perspective on the repair pathways that underpin effective responses to damage, with particular relevance for related kinetoplastid pathogens. By revealing that a large number of diverse T. brucei protein kinases act in the response to damage, we expand the range of eukaryotic signalling factors implicated in genome maintenance activities. [ABSTRACT FROM AUTHOR]