Genes important for survival or reproduction in Varroa destructor identified by RNAi

The Varroa mite,(Varroa destructor),is the worst threat to honey bee health worldwide.To explore the possibility of using RNA interference to control this pest, we determined the effects of knocking down various genes on Varroa mite survival and reproduction.Double-stranded RNA (dsRNA)of six candidate genes (Da,Pros26S,RpL8, RpL11,RpPO and RpS13)were synthesized and each injected into Varroa mites,then mite survival and reproduction were assessed.Injection of dsRNA for Da (Daughterless)and Pros26S (Gene for proteasome 26S subunit adenosine triphosphatase)caused a significant reduction in mite survival,with 3.57%±1.94% and 30.03%±11.43% mites surviving at 72 h post-inj ection (hpi),respectively.Control mites injected with green fluorescent protein (GFP)-dsRNA showed survival rates of 81.95%±5.03% and 82.36 ±2.81%,respectively. Injections of dsRNA for four other genes (RpL8,RpL11,RpPO and RpS13)did not affect survival significantly,enabling us to assess their effect on Varroa mite reproduction.The number of female offspring per mite was significantly reduced for mites injected with dsRNA of each of these four genes compared to their GFP-dsRNA controls.Knockdown of the target genes was verified by real-time polymerase chain reaction for two genes important for reproduction (RpL8,RpL11)and one gene important for survival (Pros26S). In conclusion,through RNA interference,we have discovered two genes important for mite survival and four genes important for mite reproduction.These genes could be explored as possible targets for the control of Varroa destructor in the future.     

MiR‐140 modulates the inflammatory responses of Mycobacterium tuberculosis‐infected macrophages by targeting TRAF6

This study aimed to examine miR‐140 expression in clinical samples from tuberculosis (TB) patients and to explore the molecular mechanisms of miR‐140 in host‐bacterial interactions during Mycobacterium tuberculosis (M tb) infections. The miR‐140 expression and relevant mRNA expression were detected by quantitative real‐time PCR (qRT‐PCR); the protein expression levels were analysed by ELISA and western blot; M tb survival was measured by colony formation unit assay; potential interactions between miR‐140 and the 3′ untranslated region (UTR) of tumour necrosis factor receptor‐associated factor 6 (TRAF6) was confirmed by luciferase reporter assay. MiR‐140 was up‐regulated in the human peripheral blood mononuclear cells (PBMCs) from TB patients and in THP‐1 and U937 cells with M tb infection. Overexpression of miR‐140 promoted M tb survival; on the other hand, miR‐140 knockdown attenuated M tb survival. The pro‐inflammatory cytokines including interleukin 6, tumour necrosis‐α, interleukin‐1β and interferon‐γ were enhanced by M tb infection in THP‐1 and U937 cells. MiR‐140 overexpression reduced these pro‐inflammatory cytokines levels in THP‐1 and U937 cells with M tb infection; while knockdown of miR‐140 exerted the opposite actions. TRAF6 was identified to be a downstream target of miR‐140 and was negatively modulated by miR‐140. TRAF6 overexpression increased the pro‐inflammatory cytokines levels and partially restored the suppressive effects of miR‐140 overexpression on pro‐inflammatory cytokines levels in THP‐1 and U937 cells with M tb infection. In conclusion, our results implied that miR‐140 promoted M tb survival and reduced the pro‐inflammatory cytokines levels in macrophages with M tb infection partially via modulating TRAF6 expression.     

Integrative analysis identifies potential DNA methylation biomarkers for pan-cancer diagnosis and prognosis

DNA methylation status is closely associated with diverse diseases, and is generally more stable than gene expression, thus abnormal DNA methylation could be important biomarkers for tumor diagnosis, treatment and prognosis. However, the signatures regarding DNA methylation changes for pan-cancer diagnosis and prognosis are less explored. Here we systematically analyzed the genome-wide DNA methylation patterns in diverse TCGA cancers with machine learning. We identified seven CpG sites that could effectively discriminate tumor samples from adjacent normal tissue samples for 12 main cancers of TCGA (1216 samples, AUC > 0.99). Those seven potential diagnostic biomarkers were further validated in the other 9 different TCGA cancers and 4 independent datasets (AUC > 0.92). Three out of the seven CpG sites were correlated with cell division, DNA replication and cell cycle. We also identified 12 CpG sites that can effectively distinguish 26 different cancers (7605 samples), and the result was repeatable in independent datasets as well as two disparate tumors with metastases (micro-average AUC > 0.89). Furthermore, a series of potential signatures that could significantly predict the prognosis of tumor patients for 7 different cancer were identified via survival analysis (p-value < 1e-4). Collectively, DNA methylation patterns vary greatly between tumor and adjacent normal tissues, as well as among different types of cancers. Our identified signatures may aid the decision of clinical diagnosis and prognosis for pan-cancer and the potential cancer-specific biomarkers could be used to predict the primary site of metastatic breast and prostate cancers.     

Systems Neuroprotective Mechanisms in Ischemic Stroke

Ischemic stroke, although causing brain infarction and neurological deficits, can activate innate neuroprotective mechanisms, including regional mechanisms within the ischemic brain and distant mechanisms from non-ischemic organs such as the liver, spleen, and pancreas, supporting neuronal survival, confining brain infarction, and alleviating neurological deficits. Both regional and distant mechanisms are defined as systems neuroprotective mechanisms. The regional neuroprotective mechanisms involve release and activation of neuroprotective factors such as adenosine and bradykinin, inflammatory responses, expression of growth factors such as nerve growth factors and neurotrophins, and activation and differentiation of resident neural stem cells to neurons and glial cells. The distant neuroprotective mechanisms are implemented by expression and release of endocrine neuroprotective factors such as fibroblast growth factor 21, resistin like molecule γ, and trefoil factor 3 from the liver; brain-derived neurotrophic factor and nerve growth factor from the spleen; and neurotrophin 3 and vascular endothelial growth factor C from the pancreas. Furthermore, ischemic stroke induces mobilization of bone marrow hematopoietic stem cells and endothelial progenitor cells into the circulatory system and brain, contributing to neuroprotection. The regional and distant mechanisms may act in coordination and synergy to protect the ischemic brain from injury and death. This paper addresses these mechanisms and associated signaling networks.     

Effects of low-level combined static and weak low-frequency alternating magnetic fields on cytokine production and tumor development in mice

We investigated the effects of weak combined magnetic fields (MFs) produced by superimposing a constant MF (in the range 30 - 150 µT) and an alternating MF (100 or 200 nT) on cytokine production in healthy Balb/C male mice exposed 2 h daily for 14 days. The alternating magnetic field was a sum of several frequencies (ranging from 2.5 - 17.5 Hz). The frequencies of the alternating magnetic field were calculated formally based on the cyclotron resonance of ions of free amino acids (glutamic and aspartic acids, arginine, lysine, histidine, and tyrosine). The selection of different intensity and frequency combinations of constant and alternating magnetic fields was performed to find the optimal characteristics for cytokine production stimulation in immune cells. MF with a constant component of 60 μT and an alternating component of 100 nT, which was a sum of six frequencies (from 5 to 7 Hz), was found to stimulate the production of tumor necrosis factor-α, interferon-gamma, interleukin-2, and interleukin-3 in healthy mouse cells and induce cytokine accumulation in blood plasma. Then, we studied the effect of this MF on tumor-bearing mice with solid tumors induced by Ehrlich ascite carcinoma cells by observing tumor development processes, including tumor size, mouse survival rate, and average lifespan. Tumor-bearing mice exposed to a combined constant magnetic field of 60 μT and an alternating magnetic field of 100 nT containing six frequencies showed a strong suppression of tumor growth with an increase in survival rate and enhancement of average lifespan.     

Population genomic evidence for plant glacial survival in Scandinavia

Quaternary glaciations have played a major role in shaping the genetic diversity and distribution of plant species. Strong palaeoecological and genetic evidence supports a postglacial recolonization of most plant species to northern Europe from southern, eastern and even western glacial refugia. Although highly controversial, the existence of small in situ glacial refugia in northern Europe has recently gained molecular support. We used genomic analyses to examine the phylogeography of a species that is critical in this debate. Carex scirpoidea Michx subsp. scirpoidea is a dioecious, amphi‐Atlantic arctic–alpine sedge that is widely distributed in North America, but absent from most of Eurasia, apart from three extremely disjunct populations in Norway, all well within the limits of the Weichselian ice sheet. Range‐wide population sampling and variation at 5,307 single nucleotide polymorphisms show that the three Norwegian populations comprise unique evolutionary lineages divergent from Greenland with high between‐population divergence. The Norwegian populations have low within‐population genetic diversity consistent with having experienced genetic bottlenecks in glacial refugia, and host private alleles that probably accumulated in long‐term isolated populations. Demographic analyses support a single, pre‐Weichselian colonization into Norway from East Greenland, and subsequent divergence of the three populations in separate refugia. Other refugial areas are identified in North‐east Greenland, Minnesota/Michigan, Colorado and Alaska. Admixed populations in British Columbia and West Greenland indicate postglacial contact. Taken together, evidence from this study strongly indicates in situ glacial survival in Scandinavia.     

Balancing competing life‐stage requirements in salmon habitat rehabilitation: between a rock and a hard place

Gravel augmentation is often applied to rivers and streams to rehabilitate salmonid spawning and incubation habitat. However, the effect of gravel size on salmon spawning utilization and embryo survival during incubation is not well understood. We conducted an experiment on a regulated and previously mined Northern California salmonid‐bearing stream in which different sized gravel (small, medium, and large) patches were placed into the stream's degraded spawning reach. We documented Oncorhynchus tshawytscha (Chinook salmon) spawning activity within the three gravel sizes for two seasons. In addition, we deployed Chinook salmon embryos into each gravel size patch and allowed them to incubate until estimated emergence time. Although all experimental gravel sizes were predicted to be within the spawning population's mobilization capabilities, model results indicated the probability of salmon building redds decreased as substrate size increased. Conversely, embryo survival increased as gravel size increased. A possible mechanism of disparate Chinook salmon embryo survival is provided by an observed decrease in embryo survival correlating with greater presence of embryo predators (leeches), which are associated with smaller gravel. Our results indicate a parent‐offspring conflict in optimal spawning gravel size for Chinook salmon, and suggest that an intermediate gravel size would maximize overall reproductive success across both spawning and incubation life stages.     

Early life of fathers affects offspring fitness in a wild rodent

Intergenerational fitness effects on offspring due to the early life of the parent are well studied from the standpoint of the maternal environment, but intergenerational effects owing to the paternal early life environment are often overlooked. Nonetheless, recent laboratory studies in mammals and ecologically relevant studies in invertebrates predict that paternal effects can have a major impact on the offspring's phenotype. These nongenetic, environment‐dependent paternal effects provide a mechanism for fathers to transmit environmental information to their offspring and could allow rapid adaptation. We used the bank vole Myodes glareolus, a wild rodent species with no paternal care, to test the hypothesis that a high population density environment in the early life of fathers can affect traits associated with offspring fitness. We show that the protein content in the diet and/or social environment experienced during the father's early life (prenatal and weaning) influence the phenotype and survival of his offspring and may indicate adaptation to density‐dependent costs. Furthermore, we show that experiencing multiple environmental factors during the paternal early life can lead to a different outcome on the offspring phenotype than stimulated by experience of a single environmental factor, highlighting the need to study developmental experiences in tandem rather than independent of each other.