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Bees are critical for crop pollination, but there is limited information on levels and sources of pesticide exposure in commercial agriculture. We collected pollen from foraging honey bees and bumble bees returning to colonies placed in blooming blueberry fields with different management approaches (conventional, organic, unmanaged) and located across different landscape settings to determine how these factors affect pesticide exposure. We also identified the pollen and analyzed whether pesticide exposure was correlated with corbicular load composition. Across 188 samples collected in 2 years, we detected 80 of the 259 pesticide active ingredients (AIs) screened for using a modified QuEChERS method. Detections included 28 fungicides, 26 insecticides, and 21 herbicides. All samples contained pesticides (mean = 22 AIs per pollen sample), with pollen collected from bees on conventional fields having significantly higher average concentrations (2019 mean = 882.0 ppb) than those on unmanaged fields (2019 mean = 279.6 ppb). Pollen collected by honey bees had more AIs than pollen collected by bumble bees (mean = 35 vs. 19 AIs detected at each farm, respectively), whereas samples from bumble bees had higher average concentrations, likely reflecting differences in foraging behavior. Blueberry pollen was more common in pollen samples collected by bumble bees (25.9% per sample) than honey bees (1.8%), though pesticide concentrations were only correlated with blueberry pollen for honey bees. Pollen collected at farms with more blueberry in the surrounding landscape had higher pesticide concentrations, mostly AIs applied for control of blueberry pathogens and pests during bloom. However, for honey bees, the majority of AIs detected at each farm are not registered for use on blueberry at any time (55.2% of AIs detected), including several highly toxic insecticides. These AIs therefore came from outside the fields and farms they are expected to pollinate. For bumble bees, the majority of AIs detected in their pollen are registered for use on blueberry during bloom (56.9% of AIs detected), though far fewer AIs were sprayed at the focal farm (16.7%). Our results highlight the need for integrated farm and landscape-scale stewardship of pesticides to reduce exposure to pollinators during crop pollination.

Anaplasma species, which are distributed worldwide, are gram-negative obligate intracellular tick-borne bacteria that pose a threat to human and animal health. Haemaphysalis longicornis ticks play a vital role as vectors in the transmission of Anaplasma pathogens. However, the Anaplasma species carried by H. longicornis in China are yet to be characterized. In this study, 1074 H. longicornis specimens were collected from goats in four provinces of China from 2018 to 2019 and divided into 371 sample pools. All tick sample pools were examined for the presence of Anaplasma species via nested PCR amplification of 16S ribosomal RNA, major surface protein 4 (msp4), or citric acid synthase (gltA) genes, which were sequenced to determine the molecular and phylogenetic characteristics of the isolates. The overall Anaplasma spp-positive rate of H. longicornis was determined to be 26.68% (99/371). The percentage prevalence of A. phagocytophilum-like1, A. bovis, A. ovis, A. marginale, and A. capra were 1.08% (4/371), 13.21% (49/371), 13.21% (49/371), 1.35% (5/371), and 10.24% (38/371), respectively, and the co-infection rate of two or more types of Anaplasma was 6.47% (24/371). Phylogenetic analyses led to the classification of A. phagocytophilum into an A. phagocytophilum-like1 (Anaplasma sp. Japan) group. Anaplasma bovis sequences obtained in this study were 99.8–100% identical to those of an earlier strain isolated from a Chinese tick (GenBank accession no. KP314251). Anaplasma ovis sequences showed 99.3–99.6% identity to an A. ovis human strain identified from a Cypriot patient (GenBank accession no. FJ460443). Only one msp4 sequence of A. marginale was detected and was grouped with those of other A. marginale isolates, and these A. capra isolates obtained in this present study may be zoonotic. The detection and characterization of four Anaplasma species in H. longicornis in this study have added to the current knowledge of the parasite and provided data on multiple Anaplasma species with veterinary and medical significance from four provinces of China.

Deficiencies in DNA repair and DNA degrading nucleases lead to accumulation of cytosolic DNA. cGAS is a critical DNA sensor for the detection of cytosolic DNA and subsequent activation of the STING signaling pathway. Here, we show that the cGAS-STING pathway was unresponsive to STING agonists and failed to induce type I interferon (IFN) expression in many tested human tumor cells including DU145 prostate cancer cells. Inhibition of IL-6 or the downstream JAK2/STAT3 signaling restored responsiveness to STING agonists in DU145 cells. STING activity in murine TRAMP-C2 prostate cancer cells was critical for tumor rejection and immune cell infiltration. Endogenous STING agonists including double-stranded DNA and RNA:DNA hybrids present in TRAMP-C2 cells contribute to tumor rejection, but tumor growth was further suppressed by administration of cGAMP. Intratumoral co-injections of IL-6 significantly reduced the anti-tumor effects of cGAMP. In summary, STING in tumor cells contributes to tumor rejection in prostate cancer cells, but its functions are frequently suppressed in tumor cells in part via JAK2 and STAT3 pathways.

The leading cause of death in diabetic patients is diabetic cardiomyopathy, in which alteration of Akt signal plays an important role. Inpp5f is recently found to be a negative regulator of Akt signaling, while its expression and function in diabetic heart is largely unknown. In this study, we found that in both the streptozotocin (STZ) and high fat diet (HFD) induced diabetic mouse models, Inpp5f expression was coordinately regulated by insulin, blood glucose and lipid levels. Increased Inpp5f was inversely correlated with the cardiac function. Further studies revealed that Insulin transcriptionally activated Inpp5f in an Sp1 dependent manner and increased Inpp5f in turn reduced the phosphorylation of Akt, forming a negative feedback loop. The negative feedback plays a protective role under diabetic condition. However, high blood glucose and lipid, which are characteristics of uncontrolled diabetes and type 2 diabetes, increased Inpp5f expression through activation of NF-κB, blunts the protective feedback. Thus, our study has revealed that Inpp5f provides as a negative feedback regulator of insulin signaling and downregulation of Inpp5f in diabetes is cardioprotective. Increased Inpp5f by hyperglycemia and hyperlipidemia is an important mediator of diabetic cardiomyopathy and is a promising therapeutic target for the disease.

Nucleolar and spindle-associated protein (NuSAP) is a microtubule-associated protein that functions as a microtubule stabiliser. Depletion of NuSAP leads to severe mitotic defects, however the mechanism by which NuSAP regulates mitosis remains elusive. In this study, we identify the microtubule depolymeriser, mitotic centromere-associated kinesin (MCAK), as a novel binding partner of NuSAP. We show that NuSAP regulates the dynamics and depolymerisation activity of MCAK. Phosphorylation of MCAK by Aurora B kinase, a component of the chromosomal passenger complex, significantly enhances the interaction of NuSAP with MCAK and modulates the effects of NuSAP on the depolymerisation activity of MCAK. Our results reveal an underlying mechanism by which NuSAP controls kinetochore microtubule dynamics spatially and temporally by modulating the depolymerisation function of MCAK in an Aurora B kinase-dependent manner. Hence, this study provides new insights into the function of NuSAP in spindle formation during mitosis.

Multiferroic heterostructures combining ferromagnetic and ferroelectric layers are promising for applications in novel spintronic devices, such as memories with electrical writing and magnetic reading, assuming their magnetoelectric coupling (MEC) is strong enough. For conventional magnetic metal/ferroelectric heterostructures, however, the change of interfacial magnetic moment upon reversal of the electric polarization is often very weak. Here, by using first principles calculations, we demonstrate a new pathway towards a strong MEC at the interface between the semi-hydrogenated graphene (also called graphone) and ferroelectric PbTiO3. By reversing the polarization of PbTiO3, the magnetization of graphone can be electrically switched on and off through the change of carbon-oxygen bonding at the interface. Furthermore, a ferroelectric polarization can be preserved down to ultrathin PbTiO3 layers less than one nanometer due to an enhancement of the polarization at the interface. The predicted strong magnetoelectric effect in the ultimately thin graphone/ferroelectric layers opens a new opportunity for the electric control of magnetism in high-density devices.