Unselected Line Research Articles

Dual immunotherapy in advanced or metastatic non-small cell lung cancer: A network meta-analysis

Recently, there has been extensive research on dual immunotherapy for advanced or metastatic non-small cell lung cancer (NSCLC), yet a comprehensive evaluation is lacking. This study aimed to rank the available treatment options and assess the efficacy and safety of dual immunotherapy regimens through the implementation of a Bayesian network meta-analysis (NMA). A thorough search was conducted to recognize eligible randomized controlled trials (RCTs) on March 20, 2023. Overall survival (OS), progression-free survival (PFS), treatment-related adverse events (TRAEs) and grade ≥3 TRAEs were evaluated to identify the efficacy and safety of dual immunotherapy regimens. The surface under the cumulative ranking curve (SUCRA) and P score were employed to rank the treatments. Eleven clinical trials involving six different regimens were included in this study. The combination of anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) antibodies with anti-T-cell immunoglobulin and ITIM domain (TIGIT) antibodies emerged as the most promising regimen for improving OS and PFS, followed by anti-PD-1/PD-L1+anti-cytotoxic T lymphocyte antigen 4 (CTLA-4)+chemotherapy treatment and anti-PD-1/PD-L1+anti-CTLA-4 treatment. The forest plots demonstrated that these three regimens were all superior to chemotherapy. The above results were observed in both unselected treatment line and first-line settings. The least likely to be associated with TRAEs and grade ≥3 TRAEs were respectively anti-CTLA-4 treatment and anti-PD-1/PD-L1+anti-TIGIT treatment, with anti-PD-1/PD-L1+anti-CTLA-4+chemotherapy treatment to be the worst. This NMA validated the promising efficacy and safety of dual immunotherapy in advanced or metastatic NSCLC. Among them, anti-PD-1/PD-L1+anti-TIGIT regimen emerges as a highly potential therapeutic approach. Ongoing research efforts should focus on improving treatment regimens, identifying biomarkers, and managing TRAEs to optimize the patient benefits of dual immunotherapy.

The Optimization of Program Operation for Low Power Consumption in 3D Ferroelectric (Fe)-NAND Flash Memory

This paper proposes an optimized program operation method for ferroelectric NAND (FE-NAND) flash memory utilizing the gate-induced drain leakage (GIDL) program and validated through simulations. The program operation was performed by setting the time for the unselected cell to reach the pass voltage (Vpass) to 0.1 µs, 0.2 µs, and 0.3 µs, respectively. As the time for the unselected word line (WL) to reach Vpass increases, the channel potential increases due to a decrease in the electron–hole recombination rate. After the program operation, the threshold voltage (Vth) shift of the selected cell and the pass disturb of the unselected cells according to the Vpass condition were analyzed. Consequently, there was a more significant change in Vth among selected cells compared to the time for unselected cells to reach Vpass as 0.1 µs. The findings of this study suggest an optimal program operation that increases slowly and decreases rapidly through the variation of Vth according to the program operation. By performing the proposed program operation, we confirmed that low-power operation is achievable by reducing the WL voltage by 2 V and the bit line (BL) voltage by 1 V, in contrast to the conventional GIDL program.

Voltage scheme for string-select transistors to improve inhibition characteristics during 1-bit erase in vertical NAND flash

We propose a new voltage scheme for string-select (SS) transistors to improve inhibition characteristics of unselected cells during selective 1-bit erase in vertical NAND flash memory. Different from the reported schemes, we apply different control voltages to each of the three SS transistors of unselected drain select lines and all source select lines to lower the channel potential. The change in the channel potential depending on the voltage of the SS transistors and the resulting gate-induced drain leakage is explained via TCAD simulation. The proposed pulse method can reduce the Vth of the 1-bit cell selected for erase by 168% compared to the reported method while maintaining the same inhibition characteristics.

Alterations in gonadotropin, apoptotic and metabolic pathways in granulosa cells warrant superior fertility of the Dummerstorf high fertility mouse line 1

The development and maturation of ovarian follicles is a complex and highly regulated process, which is essential for successful ovulation. During recent decades, several mouse models provided insights into the regulation of folliculogenesis. In contrast to the commonly used transgenic or knockout mouse models, the Dummerstorf high-fertility mouse line 1 (FL1) is a worldwide unique selection experiment for increased female reproductive performance and extraordinary high fertility. Interactions of cycle-related alterations of parameters of the hypothalamic pituitary gonadal axis and molecular factors in the ovary lead to improved follicular development and therefore increased ovulation rates in FL1 mice. FL1 females almost doubled the number of ovulated oocytes compared to the unselected control mouse line. To gain insights into the cellular mechanisms leading to the high fertility phenotype we used granulosa cells isolated from antral follicles for mRNA sequencing. Based on the results of the transcriptome analysis we additionally measured hormones and growth factors associated with follicular development to complement the picture of how the signaling pathways are regulated. While IGF1 levels are decreased in FL1 mice in estrus, we found no differences in insulin, prolactin and oxytocin levels in FL1 mice compared to the control line. The results of the mRNA sequencing approach revealed that the actions of insulin, prolactin and oxytocin are restricted local to the granulosa cells, since hormonal receptor expression is differentially regulated in FL1 mice. Additionally, numerous genes, which are involved in important gonadotropin, apoptotic and metabolic signaling pathways in granulosa cells, are differentially regulated in granulosa cells of FL1 mice.We showed that an overlap of different signaling pathways reflects the crosstalk between gonadotropin and growth factor signaling pathways, follicular atresia in FL1 mice is decreased due to improved granulosa cell survival and by improving the efficiency of intracellular signaling, glucose metabolism and signal transduction, FL1 mice have several advantages in reproductive performance and therefore increased the ovulation rate. Therefore, this worldwide unique high fertility model can provide new insights into different factors leading to improved follicular development and has the potential to improve our understanding of high fertility.

Brain size, gut size and cognitive abilities: the energy trade-offs tested in artificial selection experiment.

The enlarged brains of homeotherms bring behavioural advantages, but also incur high energy expenditures. The ‘expensive brain’ (EB) hypothesis posits that the energetic costs of the enlarged brain and the resulting increased cognitive abilities (CA) were met by either increased energy turnover or reduced allocation to other expensive organs, such as the gut. We tested the EB hypothesis by analysing correlated responses to selection in an experimental evolution model system, which comprises line types of laboratory mice selected for high or low basal metabolic rate (BMR), maximum (VO2max) metabolic rates and random-bred (unselected) lines. The traits are implicated in the evolution of homeothermy, having been pre-requisites for the encephalization and exceptional CA of mammals, including humans. High-BMR mice had bigger guts, but not brains, than mice of other line types. Yet, they were superior in the cognitive tasks carried out in both reward and avoidance learning contexts and had higher neuronal plasticity (indexed as the long-term potentiation) than their counterparts. Our data indicate that the evolutionary increase of CA in mammals was initially associated with increased BMR and brain plasticity. It was also fuelled by an enlarged gut, which was not traded off for brain size.

Colony fitness increases in the honey bee at queen mating frequencies higher than genetic diversity asymptote

Across the eusocial Hymenoptera, a queen’s mating frequency is positively associated with her workers’ genetic diversity and colony’s fitness. Over 90% of a colony’s diversity potential is achieved by its mother’s tenth effective mating (me); however, many females mate at levels of me > 10, a zone we here call hyperpolyandry. We compared honey bee colony fitness at mating levels near and above this genetic diversity asymptote. We were interested in how hyperpolyandry affects colony phenotypes arising from both common tasks (brood care) and rare specialized tasks (parasite resistance). We used an unselected wild line of bees and a Varroa Sensitive Hygiene (VSH) line selected to resist the parasite Varroa destructor. Virgin queens were instrumentally inseminated to replicate the following queen/colony conditions: (1) VSH semen/low polyandry (observed mating number = mo = 9), (2) VSH semen/high polyandry (mo = 54), (3) wild type semen/low polyandry, or (4) wild semen/high polyandry. There was a positive effect of polyandry on brood survival, an outcome of common tasks, with highest values at mo = 54. There was an interaction between polyandry and genetics such that differences between genetic lines expressed only at mo = 54, with fewer mites in VSH colonies. These results are consistent with two hypotheses for the evolution of mating levels in excess of the genetic diversity asymptote: hyperpolyandry improves colony fitness by (1) optimizing genotype compositions for common tasks and (2) by capturing rare specialist allele combinations, resisting cliff-edge ecological catastrophes.Significance statementPolyandry is a female’s practice of mating with several males, storing their sperm, and using it to produce one or more clutches of genetically diverse offspring. In the social Hymenoptera, polyandry increases the genetic diversity and task efficiency of workers, leading to improved colony fitness. Over 90% of the increase in a colony’s diversity potential is achieved by its mother’s tenth mating; however, many females practice hyperpolyandry, a term we reserve here for mating levels above this genetic diversity asymptote. We show that a token of colony fitness arising from common tasks, brood survival, improves universally as one moves from sub- to hyperpolyandrous mating levels. However, a colony phenotype arising from a rare parasite resistance task is only expressed in the presence of the controlling alleles and under conditions of hyperpolyandry. These results suggest adaptive mechanisms by which hyperpolyandry could evolve.

Experimental validation of genetic selection for resistance against Streptococcus agalactiae via different routes of infection in the commercial Nile tilapia breeding programme.

The objective of this study was to validate the genetic selection for resistance to streptococcosis under experimental challenge conditions in a commercial population of Nile tilapia. Further, effects of using two different routes of infection of Streptococcus agalactiae; intraperitoneal injection (IP) and cohabitation with the shedder fish (cohab), on the genomic parameters, prediction accuracy and response to selection are compared. The comparison was made between two different lines of fish; one selected for S. agalactiae resistance for one generation and randomly mated for two generations (to mimic the multiplication activities occurring in distribution channels and hatcheries); and the other unselected. 1,500 fish, each from these two lines, were used for the experimental challenge test. Survival analysis using Kaplan-Meier estimators and Hazard's ratio was used to quantify differences in mortality between the two lines. Further genomic analysis was performed with 2,684 fish and 35,745 SNPs using both univariate and bivariate GBLUP models. Genetic selection for resistance to S. agalactiae led to the significant (p<.001) reduction in the risk of death by 65% in the selected line, compared to the unselected line. Similarly, the risk of death via cohabitation route of infection significantly (p<.01) decreased by 80%, compared to IP. The genetic correlation between these two routes of infection was ~0.9. Genetic selection changed the impact of the routes of infection, with the change in the distribution of estimated breeding values and the gain of 3.04±1.25days as selection response (p<.05).

Identification and validation of quantitative trait loci for ascites syndrome in broiler chickens using whole genome resequencing

BackgroundAscites syndrome is a hypertensive, multifactorial, multigene trait affecting meat-type chickens imposing significant economic losses on the broiler industry. A region containing the CPQ gene has been previously identified as significantly affecting ascites phenotype. The region was discovered through whole genome resequencing focused on chicken chromosome 2. The association was confirmed through further genotyping in multiple broiler populations.ResultsThe whole genome resequencing analyses have now been extended to the current chicken genome assembly. DNA samples were pooled according to gender and phenotype and the pools subjected to next generation sequencing. Loci were identified as clusters of single nucleotide polymorphisms where frequencies of the polymorphisms differed between resistant and susceptible chickens. The chickens are an unselected line descended from a commercial elite broiler line. Regions identified were specific to one or both genders. The data identify a total of 28 regions as potential quantitative trait loci for ascites. The genes from these regions have been associated with hypertensive-related traits in human association studies. One region on chicken chromosome 28 contains the LRRTM4 gene. Additional genotyping for the LRRTM4 region demonstrates an epistatic interaction with the CPQ region for ascites phenotype.ConclusionsThe 28 regions identified were not previously identified in a multi-generational genome wide association study using 60k Single Nucleotide Polymorphism panels. This work demonstrates the utility of whole genome resequencing as a cost effective, direct, and efficient method for identifying specific gene regions affecting complex traits. The approach is applicable to any organism with a genome assembly and requires no a priori assumptions.

Genome-wide estimates of genetic diversity, inbreeding and effective size of experimental and commercial rainbow trout lines undergoing selective breeding

BackgroundSelective breeding is a relatively recent practice in aquaculture species compared to terrestrial livestock. Nevertheless, the genetic variability of farmed salmonid lines, which have been selected for several generations, should be assessed. Indeed, a significant decrease in genetic variability due to high selection intensity could have occurred, potentially jeopardizing the long-term genetic progress as well as the adaptive capacities of populations facing change(s) in the environment. Thus, it is important to evaluate the impact of selection practices on genetic diversity to limit future inbreeding. The current study presents an analysis of genetic diversity within and between six French rainbow trout (Oncorhynchus mykiss) experimental or commercial lines based on a medium-density single nucleotide polymorphism (SNP) chip and various molecular genetic indicators: fixation index (FST), linkage disequilibrium (LD), effective population size (Ne) and inbreeding coefficient derived from runs of homozygosity (ROH).ResultsOur results showed a moderate level of genetic differentiation between selected lines (FST ranging from 0.08 to 0.15). LD declined rapidly over the first 100 kb, but then remained quite high at long distances, leading to low estimates of Ne in the last generation ranging from 24 to 68 depending on the line and methodology considered. These results were consistent with inbreeding estimates that varied from 10.0% in an unselected experimental line to 19.5% in a commercial line, and which are clearly higher than corresponding estimates in ruminants or pigs. In addition, strong variations in LD and inbreeding were observed along the genome that may be due to differences in local rates of recombination or due to key genes that tended to have fixed favorable alleles for domestication or production.ConclusionsThis is the first report on ROH for any aquaculture species. Inbreeding appeared to be moderate to high in the six French rainbow trout lines, due to founder effects at the start of the breeding programs, but also likely to sweepstakes reproductive success in addition to selection for the selected lines. Efficient management of inbreeding is a major goal in breeding programs to ensure that populations can adapt to future breeding objectives and SNP information can be used to manage the rate at which inbreeding builds up in the fish genome.

Evaluation of Intestinal Permeability and Liver Bacterial Translocation in Two Modern Broilers and Their Jungle Fowl Ancestor.

The objective of this study was to evaluate the of intestinal permeability and liver bacterial translocation (BT) across a modern commercial broiler, a commercial broiler of 1995 genetics, and an unselected Jungle Fowl line. Modern 2015 (MB2015) broiler chicken, random bred line initiated from 1995 (RB1995), and the Giant Jungle fowl (JF). Chickens were randomly allocated to four different dietary treatments. Dietary treatments were (1) a control corn-based diet throughout the trial [corn-corn (C-C)]; (2) an early phase malnutrition diet where chicks received a rye-based diet for 10 days, and then switched to the control diet [rye-corn (R-C)]; (3) a malnutrition rye-diet that was fed throughout the trial [rye-rye (R-R)]; and (4) a late phase malnutrition diet where chicks received the control diet for 10 days, and then switched to the rye diet for the last phase [corn-rye (C-R)]. Paracellular permeability was evaluated using fluorescein isothiocyanate dextran (FITC-D). Liver BT was also evaluated. MB2015 and RB1995 consuming the rye-based diet showed increase serum levels of FITC-D when compared to the corn-fed chickens (P < 0.05). Overall, MB2015 appeared to have higher enteric permeability than the JF. To our knowledge, this would be the first paper to evaluate the effect of compensatory growth on intestinal permeability and liver BT. Further studies to evaluate microbiome and inflammatory markers in these chicken models are currently being evaluated.

Targeted exome sequencing of unselected heavy-ion beam-irradiated populations reveals less-biased mutation characteristics in the rice genome.

SummaryHeavy‐ion beams have been widely utilized as a novel and effective mutagen for mutation breeding in diverse plant species, but the induced mutation spectrum is not fully understood at the genome scale. We describe the development of a multiplexed and cost‐efficient whole‐exome sequencing procedure in rice, and its application to characterize an unselected population of heavy‐ion beam‐induced mutations. The bioinformatics pipeline identified single‐nucleotide mutations as well as small and large (>63 kb) insertions and deletions, and showed good agreement with the results obtained with conventional polymerase chain reaction (PCR) and sequencing analyses. We applied the procedure to analyze the mutation spectrum induced by heavy‐ion beams at the population level. In total, 165 individual M2 lines derived from six irradiation conditions as well as eight pools from non‐irradiated ‘Nipponbare’ controls were sequenced using the newly established target exome sequencing procedure. The characteristics and distribution of carbon‐ion beam‐induced mutations were analyzed in the absence of bias introduced by visual mutant selections. The average (±SE) number of mutations within the target exon regions was 9.06 ± 0.37 induced by 150 Gy irradiation of dry seeds. The mutation frequency changed in parallel to the irradiation dose when dry seeds were irradiated. The total number of mutations detected by sequencing unselected M2 lines was correlated with the conventional mutation frequency determined by the occurrence of morphological mutants. Therefore, mutation frequency may be a good indicator for sequencing‐based determination of the optimal irradiation condition for induction of mutations.

Genome changes due to artificial selection in U.S. Holstein cattle

BackgroundThe availability of a unique unselected Holstein line since 1964 provided a direct comparison between selected and unselected Holstein genomes whereas large Holstein samples provided unprecedented statistical power for identifying high-confidence SNP effects. Utilizing these unique resources, we aimed to identify genome changes affected by selection since 1964.ResultsDirect comparison of genome-wide SNP markers between a Holstein line unselected since 1964 and contemporary Holsteins showed that the 40 years of artificial selection since 1964 resulted in genome landscape changes. Among the regions affected by selection, the regions containing 198 genes with fertility functions had a larger negative correlation than that of all SNPs between the SNP effects on milk yield and daughter pregnancy rate. These results supported the hypothesis that hitchhiking of genetic selection for milk production by negative effects of fertility genes contributed to the unintended declines in fertility since 1964. The genome regions subjected to selection also contained 67 immunity genes, the bovine MHC region of Chr23 with significantly decreased heterozygosity in contemporary Holsteins, and large gene clusters including T-cell receptor and immunoglobulin genes.ConclusionsThis study for the first time provided direct evidence that genetic selection for milk production affected fertility and immunity genes and that the hitchhiking of genetic selection for milk production by negative fertility effects contributed to the fertility declines since 1964, and identified a large number of candidate fertility and immunity genes affected by selection. The results provided novel understanding about genome changes due to artificial selection and their impact on fertility and immunity genes and could facilitate developing genetic methods to reverse the declines in fertility and immunity in Holstein cattle.

Thermal challenge alters the transcriptional profile of the breast muscle in turkey poults

Extremes in temperature represent environmental stressors that impact the well-being and economic value of poultry. As homeotherms, young poultry with immature thermoregulatory systems are especially susceptible to thermal extremes. Genetic variation and differences in gene expression resulting from selection for production traits, likely contribute to thermal stress response. This study was designed to investigate in vivo transcriptional changes in the breast muscle of young turkey poults from an unselected randombred line and one selected for 16 wk body weight under hot and cold thermal challenge. Newly hatched turkey poults were brooded for 3 d at one of 3 temperatures: control (35°C), cold (31°C), or hot (39°C). Samples of the pectoralis major were harvested and subjected to deep RNA sequencing. Significant differential gene expression was observed in both growth-selected and randombred birds at both temperature extremes when compared to control-brooded poults. Growth-selected birds responded to thermal stress through changes in genes predicted to have downstream transcriptional effects and that would result in reduced muscle growth. Slower growing randombred birds responded to thermal stress through modulation of lipid-related genes, suggesting reduction in lipid storage, transport, and synthesis, consistent with changes in energy metabolism required to maintain body temperature.

An atlas of genetic influences on osteoporosis in humans and mice.

Osteoporosis is a common aging-related disease diagnosed primarily using bone mineral density (BMD). We assessed genetic determinants of BMD as estimated by heel quantitative ultrasound (eBMD) in 426,824 individuals, identifying 518 genome-wide significant loci (301 novel), explaining 20% of its variance. We identified 13 bone fracture loci, all associated with eBMD, in ~1.2M individuals. We then identified target genes enriched for genes known to influence bone density and strength (maximum odds-ratio=58, p=10-75) from cell-specific features, including chromatin conformation and accessible chromatin sites. We next performed rapid-throughput skeletal phenotyping of 126 knockout mice lacking target genes and found an increased abnormal skeletal phenotype frequency compared to 526 unselected lines (p<0.0001). In-depth analysis of one gene, DAAM2, showed a disproportionate decrease in bone strength relative to mineralization. This genetic atlas provides evidence testing how to link associated-SNPs to causal genes, offers new insights into osteoporosis pathophysiology and highlights opportunities for drug development.

Predicting ascites incidence in a simulated altitude-challenge using single nucleotide polymorphisms identified in multi-generational genome wide association studies.

Assessing pedigreed broiler lines for ascites resistance in an industry setting is time consuming. Further, the use of sibling selection implies study subjects are not used in the breeding program, and instead, siblings take their place in pedigree systems, which reduces overall genetic accuracy. The purpose of this study is to evaluate the effectiveness of prediction models produced with SNP with the goal of predicting ascites incidence. Ascites is the manifestation of a series of adverse changes in a broiler beginning with hypoxia. Increased blood pressure, accumulation of fluid in the abdominal cavity, and death can result. Ascites results in losses estimated at $100 million/year in the USA. A multi-generational genome wide association study in an unselected line maintained at the University of Arkansas since the 1990s identified chromosomal regions associated with ascites incidence in males when challenged at high altitude. From the identified regions of significance 20 SNP were selected to construct a predictive model (8 SNP on chromosome 11, and 12 SNP on chromosome Z). Ascites phenotype and genotype data were obtained for 295 male and female individuals from the REL line. Five modeling techniques were compared for their ascites predictive ability using a 70/30 split between training and validation. For both males and females, the artificial neural network model was the best fit prediction model due to the large area under the curve value of 0.997 and 0.997, respectively, as well as a low misclassification ratio of 0.027 and 0.037, respectively. Using a parameter decreasing method, the total number of SNP inputs used to construct artificial neural network (ANN) models was reduced. A 13 SNP male ANN model and an 18 SNP female ANN model were constructed with equally high levels of prediction accuracy compared with the 20 SNP input models. The construction of predictive ANN models indicates that we have found the genetic predictors to ascites outcome in male and female broilers from an elite line of the 1990s with a high level of accuracy.

Selection Signatures Underlying Dramatic Male Inflorescence Transformation During Modern Hybrid Maize Breeding.

Inflorescence capacity plays a crucial role in reproductive fitness in plants, and in production of hybrid crops. Maize is a monoecious species bearing separate male and female flowers (tassel and ear, respectively). The switch from open-pollinated populations of maize to hybrid-based breeding schemes in the early 20th century was accompanied by a dramatic reduction in tassel size, and the trend has continued with modern breeding over the recent decades. The goal of this study was to identify selection signatures in genes that may underlie this dramatic transformation. Using a population of 942 diverse inbred maize accessions and a nested association mapping population comprising three 200-line biparental populations, we measured 15 tassel morphological characteristics by manual and image-based methods. Genome-wide association studies identified 242 single nucleotide polymorphisms significantly associated with measured traits. We compared 41 unselected lines from the Iowa Stiff Stalk Synthetic (BSSS) population to 21 highly selected lines developed by modern commercial breeding programs, and found that tassel size and weight were reduced significantly. We assayed genetic differences between the two groups using three selection statistics: cross population extended haplotype homozogysity, cross-population composite likelihood ratio, and fixation index. All three statistics show evidence of selection at genomic regions associated with tassel morphology relative to genome-wide null distributions. These results support the tremendous effect, both phenotypic and genotypic, that selection has had on maize male inflorescence morphology.

Low‐Power Monolithically Stacked Organic Photodiode‐Blocking Diode Imager by Turn‐On Voltage Engineering

AbstractMultiplexing the signal readout from the organic photodetector matrix is essential for high‐resolution and large‐area imaging applications. This endeavor can be realized by pixels containing photodiodes and switching elements, such as transistors or blocking diodes. The use of blocking diodes is beneficial for simpler fabrication and fewer wires than transistors. However, imagers with blocking diodes can always require additional voltage to turn off the unselected lines, which causes high standby power and increased complexity of the readout circuit. In this study, low standby power organic imagers are realized that are suitable for wearable optical imaging applications in which resources for power and readout circuits are limited. Pixels with a vertical stack of organic photodiodes and blocking diode layers are investigated. By increasing the built‐in potential of blocking diodes, the turn‐on voltage of the monolithically stacked photodiode‐blocking diode device can be adjusted to enable its turn‐off at 0 V. This leads to a three‐orders‐of‐magnitude reduction of the current of pixels at 0 V. With these pixels, imagers based on organic photodiode‐blocking diode stack devices are demonstrated with improved image quality and substantially reduced crosstalk current, while operating at zero standby power.

A Shift in the Thermoregulatory Curve as a Result of Selection for High Activity-Related Aerobic Metabolism.

According to the “aerobic capacity model,” endothermy in birds and mammals evolved as a result of natural selection favoring increased persistent locomotor activity, fuelled by aerobic metabolism. However, this also increased energy expenditure even during rest, with the lowest metabolic rates occurring in the thermoneutral zone (TNZ) and increasing at ambient temperatures (Ta) below and above this range, depicted by the thermoregulatory curve. In our experimental evolution system, four lines of bank voles (Myodes glareolus) have been selected for high swim-induced aerobic metabolism and four unselected lines have been maintained as a control. In addition to a 50% higher rate of oxygen consumption during swimming, the selected lines have also evolved a 7.3% higher mass-adjusted basal metabolic rate. Therefore, we asked whether voles from selected lines would also display a shift in the thermoregulatory curve and an increased body temperature (Tb) during exposure to high Ta. To test these hypotheses we measured the RMR and Tb of selected and control voles at Ta from 10 to 34°C. As expected, RMR within and around the TNZ was higher in selected lines. Further, the Tb of selected lines within the TNZ was greater than the Tb of control lines, particularly at the maximum measured Ta of 34°C, suggesting that selected voles are more prone to hyperthermia. Interestingly, our results revealed that while the slope of the thermoregulatory curve below the lower critical temperature (LCT) is significantly lower in the selected lines, the LCT (26.1°C) does not differ. Importantly, selected voles also evolved a higher maximum thermogenesis, but thermal conductance did not increase. As a consequence, the minimum tolerated temperature, calculated from an extrapolation of the thermoregulatory curve, is 8.4°C lower in selected (−28.6°C) than in control lines (−20.2°C). Thus, selection for high aerobic exercise performance, even though operating under thermally neutral conditions, has resulted in the evolution of increased cold tolerance, which, under natural conditions, could allow voles to inhabit colder environments. Further, the results of the current experiment support the assumptions of the aerobic capacity model of the evolution of endothermy.

Comparative intensity of infection and performance of lambs selected for resistance or susceptibility to Haemonchus contortus in semi-arid Rajasthan

The present study aimed to determine the variation in intensity of strongyle infection and performance in lambs of three divergent lines (selected for resistance or susceptibility to Haemonchus contortus and unselected) in semiarid Rajasthan. From the year 2004 to 2014, a total of 13,515 faecal samples from lambs (5-6 month of age) naturally infected with gastrointestinal nematodes (GINs) were evaluated for intensity of strongyle infection and estimated pasture contamination rate by them. The monthly mean intensity of strongyle infection remained significantly higher in susceptible line compared to other lines. In the month of peak parasitism (September), minimum proportion (34.54-45.61%) of animals possess higher FEC in resistant lambs followed by unselected (44.32-50.50%) and maximum (53.58-56.27%) by susceptible lambs. In majority of months, resistant lambs had lower contamination rate (&gt;30%) compared to susceptible lambs. The magnitude of average daily gain (ADG) in body weight exhibited significant variation among different lines only between 6-9 months of age in Malpura (31.1±1.2 g/day in unselected line to 38.5±2.3 g/day in resistant line) and Avikalin breed (27.1±1.8 g/day in unselected line to 35.6±1.7 g/day in resistant line). During peak wormy season, a significant and negative correlation was found between FEC and weight at 6 and 9 month of age in susceptible line only. The study suggested that management of gastrointestinal nematodosis in flock through selection of sheep for resistance to strongyle worms led to decreased pasture contamination, lower intensity of infection with better performance in resistant flock.

Population Growth of Varroa destructor (Acari: Varroidae) in Colonies of Russian and Unselected Honey Bee (Hymenoptera: Apidae) Stocks as Related to Numbers of Foragers With Mites.

Varroa (Varroa destructor Anderson and Trueman) is an external parasite of honey bees (Apis mellifera L.) and a leading cause of colony losses worldwide. Varroa populations can be controlled with miticides, but mite-resistant stocks such as the Russian honey bee (RHB) also are available. Russian honey bee and other mite-resistant stocks limit Varroa population growth by affecting factors that contribute to mite reproduction. However, mite population growth is not entirely due to reproduction. Numbers of foragers with mites (FWM) entering and leaving hives also affect the growth of mite populations. If FWM significantly contribute to Varroa population growth, mite numbers in RHB colonies might not differ from unselected lines (USL). Foragers with mites were monitored at the entrances of RHB and USL hives from August to November, 2015, at two apiary sites. At site 1, RHB colonies had fewer FWM than USL and smaller phoretic mite populations. Russian honey bee also had fewer infested brood cells and lower percentages with Varroa offspring than USL. At site 2, FWM did not differ between RHB and USL, and phoretic mite populations were not significantly different. At both sites, there were sharp increases in phoretic mite populations from September to November that corresponded with increasing numbers of FWM. Under conditions where FWM populations are similar between RHB and USL, attributes that contribute to mite resistance in RHB may not keep Varroa population levels below that of USL.