Serial founder effects slow range expansion in an invasive social insect.

Invasive populations often experience founder effects: a loss of genetic diversity relative to the source population, due to a small number of founders. Even where these founder effects do not impact colonization success, theory predicts they might affect the rate at which invasive populations expand. This is because secondary founder effects are generated at advancing population edges, further reducing local genetic diversity and elevating genetic load. We show that in an expanding invasive population of the Asian honey bee (Apis cerana), genetic diversity is indeed lowest at range edges, including at the complementary sex determiner, csd, a locus that is homozygous-lethal. Consistent with lower local csd diversity, range edge colonies had lower brood viability than colonies in the range centre. Further, simulations of a newly-founded and expanding honey bee population corroborate the spatial patterns in mean colony fitness observed in our empirical data and show that such genetic load at range edges will slow the rate of population expansion.

A postmeiotically bifurcated roadmap of honeybee spermatogenesis marked by phylogenetically restricted genes.

Haploid males of hymenopteran species produce gametes through an abortive meiosis I followed by meiosis II that can either be symmetric or asymmetric in different species. Thus, one spermatocyte could give rise to two spermatids with either equal or unequal amounts of cytoplasm. It is currently unknown what molecular features accompany these postmeiotic sperm cells especially in species with asymmetric meiosis II such as bees. Here we present testis single-cell RNA sequencing datasets from the honeybee (Apis mellifera) drones of 3 and 14 days after emergence (3d and 14d). We show that, while 3d testes exhibit active, ongoing spermatogenesis, 14d testes only have late-stage spermatids. We identify a postmeiotic bifurcation in the transcriptional roadmap during spermatogenesis, with cells progressing toward the annotated spermatids (SPT) and small spermatids (sSPT), respectively. Despite an overall similarity in their transcriptomic profiles, sSPTs express the fewest genes and the least RNA content among all the sperm cell types. Intriguingly, sSPTs exhibit a relatively high expression level for Hymenoptera-restricted genes and a high mutation load, suggesting that the special meiosis II during spermatogenesis in the honeybee is accompanied by phylogenetically young gene activities.

Interspecific Host Variation and Biotic Interactions Drive Pathogen Community Assembly in Chinese Bumblebees.

Bumblebees have been considered one of the most important pollinators on the planet. However, recent reports of bumblebee decline have raised concern about a significant threat to ecosystem stability. Infectious diseases caused by multiple pathogen infections have been increasingly recognized as an important mechanism behind this decline worldwide. Understanding the determining factors that influence the assembly and composition of pathogen communities among bumblebees can provide important implications for predicting infectious disease dynamics and making effective conservation policies. Here, we study the relative importance of biotic interactions versus interspecific host resistance in shaping the pathogen community composition of bumblebees in China. We first conducted a comprehensive survey of 13 pathogens from 22 bumblebee species across China. We then applied joint species distribution modeling to assess the determinants of pathogen community composition and examine the presence and strength of pathogen-pathogen associations. We found that host species explained most of the variations in pathogen occurrences and composition, suggesting that host specificity was the most important variable in predicting pathogen occurrences and community composition in bumblebees. Moreover, we detected both positive and negative associations among pathogens, indicating the role of competition and facilitation among pathogens in determining pathogen community assembly. Our research demonstrates the power of a pluralistic framework integrating field survey of bumblebee pathogens with community ecology frameworks to understand the underlying mechanisms of pathogen community assembly.

Gut microbiota is a potential factor in shaping phenotypic variation in larvae and adults of female bumble bees.

Host symbionts are often considered an essential part of the host phenotype, influencing host growth and development. Bumble bee is an ideal model for investigating the relationship between microbiota and phenotypes. Variations in life history across bumble bees may influence the community composition of gut microbiota, which in turn influences phenotypes. In this study, we explored gut microbiota from four development stages (early-instar larvae, 1st instar; mid-instar larvae, 5th instar; late-instar larvae, 9th instar; and adults) of workers and queens in the bumble bee Bombus terrestris using the full-length 16S rRNA sequencing technology. The results showed that morphological indices (weight and head capsule) were significantly different between workers and queens from 5th instar larvae (p < 0.01). The alpha and beta diversities of gut microbiota were similar between workers and queens in two groups: early instar and mid instar larvae. However, the alpha diversity was significantly different in late instar larvae or adults. The relative abundance of three main phyla of bacteria (Cyanobacteria, Proteobacteria, and Firmicutes) and two genera (Snodgrassella and Lactobacillus) were significantly different (p < 0.01) between workers and queens in late instar larvae or adults. Also, we found that age significantly affected the microbial alpha diversity as the Shannon and ASVs indices differed significantly among the four development stages. Our study suggests that the 5th instar larval stage can be used to judge the morphology of workers or queens in bumble bees. The key microbes differing in phenotypes may be involved in regulating phenotypic variations.

Sex-Biased Expression of Olfaction-Related Genes in the Antennae of Apis cerana (Hymenoptera: Apidae).

The olfactory system is essential for honeybees to adapt to complex and ever-changing environments and maintain cohesiveness. The Eastern honeybee Apis cerana is native to Asia and has a long history of managed beekeeping in China. In this study, we analysed the antennal transcriptomes of A. cerana workers and drones using Illumina sequencing. A total of 5262 differentially expressed genes (DEGs) (fold change > 2) were identified between these two castes, with 2359 upregulated and 2903 downregulated in drones compared with workers. We identified 242 candidate olfaction-related genes, including 15 odourant-binding proteins (OBPs), 5 chemosensory proteins (CSPs), 110 odourant receptors (ORs), 9 gustatory receptors (GRs), 8 ionotropic receptors (IRs), 2 sensory neuron membrane proteins (SNMPs) and 93 putative odourant-degrading enzymes (ODEs). More olfaction-related genes have worker-biased expression than drone-biased expression, with 26 genes being highly expressed in workers' antennae and only 8 genes being highly expressed in drones' antennae (FPKM > 30). Using real-time quantitative PCR (RT-qPCR), we verified the reliability of differential genes inferred by transcriptomics and compared the expression profiles of 6 ORs (AcOR10, AcOR11, AcOR13, AcOR18, AcOR79 and AcOR170) between workers and drones. These ORs were expressed at significantly higher levels in the antennae than in other tissues (p < 0.01). There were clear variations in the expression levels of all 6 ORs between differently aged workers and drones. The relative expression levels of AcOR10, AcOR11, AcOR13, AcOR18 and AcOR79 reached a high peak in 15-day-old drones. These results will contribute to future research on the olfaction mechanism of A. cerana and will help to better reveal the odourant reception variations between different biological castes of honeybees.

Hemolymph Metabolism Analysis of Honey Bee (Apis mellifera L.) Response to Different Bee Pollens.

Pollen is essential to the development of honey bees. The nutrients in bee pollen vary greatly among plant species. Here, we analyzed the differences in the amino acid compositions of pear (Pyrus bretschneideri), rape (Brassica napus), and apricot (Armeniaca sibirica) pollens and investigated the variation in hemolymph metabolites and metabolic pathways through untargeted metabolomics in caged adult bees at days 7 and 14. The results showed that the levels of five essential amino acids (isoleucine, phenylalanine, lysine, methionine, and histidine) were the highest in pear pollen, and the levels of four amino acids (isoleucine: 50.75 ± 1.93 mg/kg, phenylalanine: 87.25 ± 2.66 mg/kg, methionine: 16.00 ± 0.71 mg/kg and histidine: 647.50 ± 24.80 mg/kg) were significantly higher in pear pollen than in the other two kinds of bee pollen (p < 0.05). The number of metabolites in bee hemolymph on day 14 (615) was significantly lower than that on day 7 (1466). The key metabolic pathways of bees, namely, "sphingolipid metabolism (p = 0.0091)", "tryptophan metabolism (p = 0.0245)", and "cysteine and methionine metabolism (p = 0.0277)", were significantly affected on day 7. There was no meaningful pathway enrichment on day 14. In conclusion, pear pollen had higher nutritional value among the three bee pollens in terms of amino acid level, followed by rape and apricot pollen, and the difference in amino acid composition among bee pollens was reflected in the lipid and amino acid metabolism pathways of early adult honey bee hemolymph. This study provides new insights into the physiological and metabolic functions of different bee pollens in bees.

Large-Section Histopathology Can Better Indicate the Immune Microenvironment and Predict the Prognosis of Pancreatic Ductal Adenocarcinoma Than Small-Section Histopathology.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor and is insensitive to radiotherapy and chemotherapy, as it is highly correlated with its complex tumor microenvironment (TME). A comprehensive description of PDAC's immune microenvironment at the pathological level has not been reported, thus limiting its treatment. Previous studies have shown that large-section histopathology (LSH) can reveal the complete structure and margin of the tumor on a single slice and effectively reflect intratumoral heterogeneity. LSH, as opposed to classic small-section histopathology (SSH), can also be used to explore the infiltration state of immune cells in different regions. In the current study, EnVision immunohistochemical staining was used to explore the panoramic distribution of CD4-, CD8-, CD15-, CD20-, and CD56 (surface markers of helper T cells, cytotoxic T cells, neutrophils, B cells, and NK cells, respectively)-positive cells in 102 pairs of paraffin wax-embedded PDAC samples (LSH vs SSH) for the first time. These indicators were then analyzed, and correlations of clinicopathological characteristics with clinical prognoses were analyzed. The findings of this study show that LSH can effectively indicate more immune cells than SSH. Upregulated CD4, CD8, CD20, and CD56 or downregulated CD15 was correlated with a good prognosis in PDAC patients. However, analysis of SSH showed that only upregulated CD4 and CD8 can be used as indicators of a good prognosis. Multivariate Cox regression analysis showed that 7 variables, namely, pTNM stage (P=0.002), PDL1 expression (P=0.001), CDX2 expression (P=0.008), DPC4 expression (P=0.004), CD4 expression in LSH (P<0.001), CD8 expression in LSH (P=0.010) and CD15 expression in LSH (P=0.031), were significantly correlated with the prognosis of PDAC patients. The findings of this study indicate that LSH is an effective tool for a panoramic assessment of the immune microenvironment in pancreatic cancer patients.

Sites of Distant Metastases and Cancer-Specific Survival in Intraductal Papillary Mucinous Neoplasm With Associated Invasive Carcinoma: A Study of 1,178 Patients.

BACKGROUND: To explore the impact of distant metastases on cancer-specific survival in patients with intraductal papillary mucinous neoplasm (IPMN) with associated invasive carcinoma and identify the risk factor of distant metastases in IPMN with associated invasive carcinoma. METHODS: Patients with IPMN with associated invasive carcinoma between 2010 and 2015 were retrospectively selected from the Surveillance, Epidemiology, and End Results (SEER) database. The survival analyses were assessed by Kaplan-Meier analyses and log-rank test. The impact of distant metastases was evaluated by Cox regression model and the risk factors of distant metastases were identified by logistic regression analyses, respectively. RESULTS: The median cancer-specific survival time of patients with no metastases, isolated liver, isolated lung, and multiple site metastases were 19 months, 4 months, 7 months, and 3 months, respectively. In patients with isolated liver metastases, multivariate analysis after adjustment indicated that chemotherapy (Hazard Ratio [HR]=0.351, 95% confidence interval [CI]=0.256-0.481, P<0.001) was a protective prognostic factor for cancer-specific survival (CSS) in patients with isolated liver metastases. In isolated lung metastases subgroup, old age (HR=1.715, 95% CI=1.037-2.838, P=0.036) and chemotherapy (HR=0.242, 95% CI=0.134-0.435, P<0.001) were related to CSS in multivariable Cox regression analysis(P<0.05). Tumor located in the pancreatic body/tail (HR=2.239, 95% CI=1.140-4.400, P=0.019) and chemotherapy (HR=0.191, 95% CI=0.108-0.340, P<0.001) were independent prognostic factors for CSS in patients with multiple metastases. Finally, a nomogram was constructed for cancer-specific survival and the predicted C-index was 0.780 (95% CI=0.762-0.798). CONCLUSION: The liver is the most common site of distant metastases in IPMN with associated invasive carcinoma. Tumor located in the pancreatic body/tail and chemotherapy are independent prognostic factors for CSS in patients with multiple metastases. Further, tumor located in body/tail is identified as a risk factor of distant metastases.

Pollen Source Affects Development and Behavioral Preferences in Honey Bees.

With the availability of various plants in bloom simultaneously, honey bees prefer to collect some pollen types over others. To better understand pollen's role as a reward for workers, we compared the digestibility and nutritional value of two pollen diets, namely, pear (Pyrus bretschneideri Rehd.) and apricot (Armeniaca sibirica L.). We investigated the visits, pollen consumption, and pollen extraction efficiency of caged Apis mellifera workers. Newly emerged workers were reared, and the effects of two pollen diets on their physiological status (the development of hypopharyngeal glands and ovaries) were compared. The choice-test experiments indicated a significant preference of A. mellifera workers for apricot pollen diets over pear pollen diets (number of bees landing, 29.5 ± 8.11 and 9.25 ± 5.10, p < 0.001 and pollen consumption, 0.052 ± 0.026 g/day and 0.033 ± 0.013 g/day, p < 0.05). Both pollen diets had comparable extraction efficiencies (67.63% for pear pollen and 67.73% for apricot pollen). Caged workers fed different pollen diets also exhibited similar ovarian development (p > 0.05). However, workers fed apricot pollen had significantly larger hypopharyngeal glands than those fed pear pollen (p < 0.001). Our results indicated that the benefits conferred to honey bees by different pollen diets may influence their foraging preference.

Global allele polymorphism indicates a high rate of allele genesis at a locus under balancing selection.

When selection favours rare alleles over common ones (balancing selection in the form of negative frequency-dependent selection), a locus may maintain a large number of alleles, each at similar frequency. To better understand how allelic richness is generated and maintained at such loci, we assessed 201 sequences of the complementary sex determiner (csd) of the Asian honeybee (Apis cerana), sampled from across its range. Honeybees are haplodiploid; hemizygotes at csd develop as males and heterozygotes as females, while homozygosity is lethal. Thus, csd is under strong negative frequency-dependent selection because rare alleles are less likely to end up in the lethal homozygous form. We find that in A. cerana, as in other Apis, just a few amino acid differences between csd alleles in the hypervariable region are sufficient to trigger female development. We then show that while allelic lineages are spread across geographical regions, allelic differentiation is high between populations, with most csd alleles (86.3%) detected in only one sample location. Furthermore, nucleotide diversity in the hypervariable region indicates an excess of recently arisen alleles, possibly associated with population expansion across Asia since the last glacial maximum. Only the newly invasive populations of the Austral-Pacific share most of their csd alleles. In all, the geographic patterns of csd diversity in A. cerana indicate that high mutation rates and balancing selection act together to produce high rates of allele genesis and turnover at the honeybee sex locus, which in turn leads to its exceptionally high local and global polymorphism.

The complete mitochondrial genome of the Xinyuan honey bee, Apis mellifera sinisxinyuan (Insecta: Hymenoptera: Apidae).

We analyzed the complete mitochondrial genome of the recently discovered Xinyuan honey bee, Apis mellifera sinisxinyuan using single molecule real-time sequencing. The mitochondrial genome of A. m. sinisxinyuan is a circular molecule of 16,886 bp, comprising 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes and a control region rich in A + T. Phylogenetic analysis using 13 protein-coding genes supports a close relationship to another M-lineage honey bee, A. m. mellifera.

Characteristics of the Two Asian Bumblebee Species Bombus friseanus and Bombus breviceps (Hymenoptera: Apidae).

This study compared the food plants, life cycle, colony development, and mating behaviour of the two Asian bumblebee species Bombus friseanus and B. breviceps, which are very important pollinators for many wild flowers and crops in local ecosystems. Both species were shown to be highly polylectic. Differences were observed in their life cycles and colony development patterns. The colony foundation rate of the field-collected queens was high in both species, 95.5% in B. friseanus and 86.5% in B. breviceps. The intervals from colony initiation to colony sizes of 30, 60, and 80 workers and to the first male and gyne emergence were significantly shorter in B. friseanus than in B. breviceps (p < 0.01). The development period of the first batch of workers showed no significant difference between the two species (p > 0.05). Compared with B. friseanus, B. breviceps produced remarkably higher numbers of workers (135 ± 30 workers/colony in B. friseanus and 318 ± 123 workers/colony in B. breviceps) and males (199 ± 46 males/colony in B. friseanus and 355 ± 166 males/colony in B. breviceps) (p < 0.01), with notable variation was found among the colonies in both species. With no significant difference in the mating rate between these two species, the copulation duration of B. breviceps (1.54 ± 0.63 min) was strikingly shorter than that of B. friseanus (27.44 ± 11.16 min) (p < 0.001). This study highlights the characteristics of the two Asian bumblebee species and will aid further studies on their conservation and agricultural pollination use.

Diagnostic indicators of wild pollinators for biodiversity monitoring in long-term conservation.

For the conservation of wild pollinators, instead of surveying the whole community, one or more indicator species can be used as monitoring targets for long-term conservation. China, the richest country in terms of bumblebee species with 125 species, was selected here to investigate the indicator species of the different biogeographic regions of bumblebees. Four principal biogeographic regions of bumblebee species, i.e., South China, North-Northeast China (North China), the Mongolian Plateau and surrounding mountains (Mongolian Plateau) and the Tibetan Plateau and surrounding mountains (Tibetan Plateau), were revealed by Ward's agglomerative cluster analysis. The role of climatic factors in defining the biogeographic regions was found to be greater than those of topographical factors and their joint effects. We found that 14, 13, 12 and 12 species were associated with the regions of South China, North China, the Mongolian Plateau and the Tibetan Plateau, respectively. In addition, among these species, seven (Bombus atripes, B. bicoloratus, B. breviceps, B. eximius, B. flavescens, B. montivagus and B. trifasciatus), five (B. deuteronymus, B. patagiatus, B. pseudobaicalensis, B. tricornis and B. ussurensis), ten (B. armeniacus, B. confusus, B. cryptarum, B. cullumanus, B. hortorum, B. muscorum, B. ruderarius, B. soroeensis, B. subterraneus and B. terrestris) and four species (B. kashmirensis, B. personatus, B. rufofasciatus and B. waltoni) were identified as important indicator species for South China, North China, the Mongolian Plateau and the Tibetan Plateau, respectively. Furthermore, we identified specific areas for targeted bumblebee diversity monitoring in each region. This study highlights the bioregionalization and the identification of indicator species of bumblebee pollinators for long-term monitoring in conservation.

First Record of the Velvet Ant Mutilla europaea (Hymenoptera: Mutillidae) Parasitizing the Bumblebee Bombus breviceps (Hymenoptera: Apidae).

Mutillid wasps are ectoparasitic insects that parasitize the enclosed developmental stages of their hosts. Adults are sexually dimorphic, with brilliantly colored and hardened cuticles. The biology of parasitic mutillid wasps has rarely been addressed. Here, we investigated the parasitization by Mutilla europaea on an important pollinator, Bombus breviceps. The parasitic biology and dispersal ability of M. europaea were observed and tested under experimental conditions. We provide the first record of M. europaea parasitizing B. breviceps in southwestern China. As is the case with other bumblebee species, M. europaea mainly parasitized the puparia of males. The dispersal and invasion ability of this parasite under experimental conditions indicates that it spreads rapidly, as far as 20 m in one week, and invades different hosts (B. breviceps and Bombus haemorrhoidalis). This report not only clarifies the parasitic relationship between M. europaea and B. breviceps, but also has important ecological implications for the conservation of bumblebees in China.

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Bees, wasps, and ants are among the most highly invasive social insects. Theoretically, the single-locus complementary sex determination (sl-CSD) would hinder the establishment of invasive population with limited founders. Apis cerana has colonized many regions with anthropogenic movement, with devastating effects on the commercial A. mellifera. Here, we summarized the distribution and sex determination mechanism of A. cerana, the recent research results about the invasive A. cerana in Australia, and analyzed how they counteracted the handicap of their sex determination system by the queen's extreme polyandry, worker's reproduction, balancing selection and thelytoky. The knowledge reviewed here could be used as the reference to reveal the establishment mechanism of invasive populations of related social insects.

Workers' sons rescue genetic diversity at the sex locus in an invasive honey bee population.

The hallmark of eusociality is the division of labour between reproductive (queen) and nonreproductive (worker) females. Yet in many eusocial insects, workers retain the ability to produce haploid male offspring from unfertilized eggs. The reproductive potential of workers has well-documented consequences for the structure and function of insect colonies, but its implications at the population level are less often considered. We show that worker reproduction in honey bees can have an important role in maintaining genetic diversity at the sex locus in invasive populations. The honey bee sex locus is homozygous-lethal, and, all else being equal, a higher allele number in the population lead to higher mean brood survival. In an invasive population of the honey bee Apis cerana in Australia, workers contribute significantly to male production: 38% of male-producing colonies are queenless, and these contribute one-third of all males at mating congregations. Using a model, we show that such male production by queenless workers will increase the number of sex alleles retained in nascent invasive populations following founder events, relative to a scenario in which only queens reproduce. We conclude that by rescuing sex locus diversity that would otherwise be lost, workers' sons help honey bee populations to minimize the negative effects of inbreeding after founder events and so contribute to their success as invaders.

Characterization of Sphingomyelin Phosphodiesterase Expression in Bumblebee (Bombus lantschouensis).

Sphingomyelin phosphodiesterase (SMPD) is a hydrolase that plays a major role in metabolic reactions involving sphingomyelin. Here, we describe an analysis of the cDNA sequence and gene structure of SMPD in bumblebee (Bombus lantschouensis). The expression of SMPD in different tissues and at different developmental stages and reproductive statuses was examined by real-time polymerase chain reaction (PCR). The results showed that the SMPD cDNA has a length of 2000 bp and contains an open reading frame (ORF) of 1,801 nucleotides that encodes a polypeptide of 599 amino acids. The full-length SMPD gene is 4228 bp and contains eight exons and seven introns. A comparative analysis revealed that the SMPD gene sequence in B. lantschouensis shares high sequence identity with those in other Bombus species. The SMPD gene is expressed broadly in various tissues and presents higher transcript levels in the ovary, midgut, and epidermis and thoracic tissues. Among the different developmental stages, the highest expression of SMPD was detected at the Pw pupal stage (pupae with an unpigmented body cuticle and white eyes), and the expression of this gene decreased from the Pp (pupae with pink eyes) to the Pdd (dark-eye pupae with a dark-pigmented cuticle) stages. In addition, SMPD expression was significantly upregulated after female egg laying. In conclusion, our results show that the bumblebee SMPD gene might play a key role at the Pw developmental stage and in female oviposition.

Safety and Efficacy of a New Smartphone-controlled Vibrating Capsule on Defecation in Beagles.

Constipation, mainly manifesting as abdominal discomfort and painful defecation, is considered as a chronic disorder. Due to a lack of effective therapy, it imposes a significant economic burden and greatly impacts patients' quality of life which prompt searches for new, original approaches. Based on the research of vibrating capsule (VC) carried out by Ron et al., we investigated the safety and efficacy of an innovative, multi-mode VC in terms of its effect on defecation in animal studies. The parameters associated with different operation modes of VCs can be detected and adjusted by smartphone controlled external configuration device (ECD). The results of blood tests, physiological parameters, CT scan and pathological examination showed no significant abnormality, which undoubtedly confirmed the safety of VCs. For efficacy studies, defecation frequency of beagles increased after administration of these capsules without influence on stool characters. Meanwhile, the mean time of capsule evacuation tended to be reduced while showing no significant difference between different modes. In summary, this study elucidates the safety and effectiveness of VC in prompting the passage of gastrointestinal walls thus greatly increasing the defecation frequency. This study innovatively displays the promising application of VC in the treatment of constipation.

CD13hi Neutrophil-like myeloid-derived suppressor cells exert immune suppression through Arginase 1 expression in pancreatic ductal adenocarcinoma.

Perineural invasion and immunosuppressive tumor microenvironment are the distinct features of pancreatic ductal adenocarcinoma (PDAC). Heterogeneous myeloid-derived suppressor cells (MDSCs) are potent suppressors of antitumor immunity, posing obstacles for cancer immunotherapy. Increasing evidences have demonstrated the accumulation of MDSCs in PDAC patients. However, the role of MDSCs in perineural invasion of PDAC and the existence of novel MDSC subsets during PDAC remain unclear. This study found that lymphocytic perineural cuffs were frequently present in chronic pancreatitis (CP) tissues and adjacent non-neoplastic pancreatic tissues (ANPTs), but not in PDAC with perineural invasion. Meanwhile, we found that neutrophil-like MDSCs (nMDSCs), but not monocyte-like MDSCs (mMDSCs), were significantly increased in PBMCs and tumor tissues of PDAC patients. Further observation identified two distinct subsets of nMDSCs, CD13hi and CD13low nMDSCs in PDAC patients, which have not been reported previously. Despite a similar morphology, CD13hi nMDSCs expressed higher levels of CD11b, CD33, CD16 and arginase 1 but lower levels of CD66b than CD13low nMDSCs. Importantly, CD13hi MDSCs, compared with CD13low nMDSCs, more effectively suppressed alloreactive T cell responses via an arginase-1-related mechanism. After tumor resection, the circulating CD13hi nMDSCs were decreased markedly. PDAC patients with more CD13hi nMDSCs had a shorter overall survival than those with less CD13hi nMDSCs. To conclude, we identified two novel MDSC subsets with different characteristics and functions in PDAC, demonstrated the association of the two MDSC subsets with cancer progression, and explored their roles in perineural invasion and immune escape of PDAC.

An invasive social insect overcomes genetic load at the sex locus.

Some invasive hymenopteran social insects found new populations with very few reproductive individuals. This is despite the high cost of founder effects for such insects, which generally require heterozygosity at a single locus-the complementary sex determiner, csd-to develop as females. Individuals that are homozygous at csd develop as either infertile or subfertile diploid males or not at all. Furthermore, diploid males replace the female workers that are essential for colony function. Here we document how the Asian honey bee (Apis cerana) overcame the diploid male problem during its invasion of Australia. Natural selection prevented the loss of rare csd alleles due to genetic drift and corrected the skew in allele frequencies caused by founder effects to restore high average heterozygosity. Thus, balancing selection can alleviate the genetic load at csd imposed by severe bottlenecks, and so facilitate invasiveness.