Search

ABSTRACT Infection with pathogens can increase the fecundity and other fitness-related traits of insect vectors for their own advantage. Our previous research has reported the pivotal role of DcKr-h1 in the fecundity improvement of Diaphorina citri induced by the bacterium, “Candidatus Liberibacter asiaticus” (CLas), and the fungus, Cordyceps fumosorosea (Cf). However, the posttranscriptional regulation of this process remains poorly understood. Given the significance of miRNAs in gene regulation, we delved into their roles in shaping phenotypes and their underlying molecular mechanisms. Our results indicated that two miRNAs, miR-2 and novel-miR-109, jointly inhibited DcKr-h1 expression by binding to its 3′ untranslated region (UTR). In the D. citri-CLas interaction, the expression levels of miR-2 and novel-miR-109 in the ovaries of CLas-positive psyllids were lower compared to CLas-negative individuals. Overexpression of miR-2 or novel-miR-109 significantly decreased fecundity and CLas titer in ovaries and caused reproductive defects reminiscent of DcKr-h1 knockdown. Similarly, in the D. citri-Cf interaction, the levels of miR-2 and novel-miR-109 markedly decreased in the ovaries. Upregulation of miR-2 or novel-miR-109 also resulted in reduced fecundity and ovary defects similar to those caused by DcKr-h1 silencing. Moreover, feeding antagomir-2 or antagomir-109 partially rescued the defective phenotypes caused by DcKr-h1 silencing in both model systems, and miR-2 and novel-miR-109 were repressed by juvenile hormone (JH) and regulated the genes associated with egg development. This study shows a conserved regulatory mechanism, whereby JH suppresses the expression of miR-2 and novel-miR-109 which, together with JH-induced transcription of DcKr-h1, increases female fecundity induced by both symbiotic bacteria and pathogenic fungi.IMPORTANCEInfection with pathogens can increase the fecundity and other fitness-related traits of insect vectors for their own advantage. Our previous research has reported that DcKr-h1 plays a critical role in the increase in fecundity of Diaphorina citri induced by the bacterium, “Candidatus Liberibacter asiaticus” (CLas) and the fungus, Cordyceps fumosorosea (Cf). However, the posttranscriptional regulation of this process remains poorly understood. Given the significance of miRNAs in gene regulation, we delved into their roles in shaping phenotypes and their underlying molecular mechanisms. Our results indicated that two miRNAs, miR-2 and novel-miR-109, jointly inhibited DcKr-h1 expression by binding to its 3′ untranslated region (UTR). In both D. citri-CLas and D. citri-Cf interactions, the increased juvenile hormone (JH) titer and reduced abundance of miR-2 and novel-miR-109 ensure high levels of DcKr-h1 expression, consequently stimulating ovarian development and enhancing fecundity. These observations provide evidence that miR-2 and miR-109 are crucial players in the JH-dependent increase in fecundity in psyllids induced by infection with different pathogens.

Apoptosis is a form of programmed cell death that is mediated by intrinsic and extrinsic pathways. Dysregulation of and resistance to cell death are hallmarks of cancer. For over three decades, the development of therapies to promote treatment of cancer by inducing various cell death modalities, including apoptosis, has been a main goal of clinical oncology. Apoptosis pathways also interact with other signaling mechanisms, such as the p53 signaling pathway and the integrated stress response (ISR) pathway. In addition to agents directly targeting the intrinsic and extrinsic pathway components, anticancer drugs that target the p53 and ISR signaling pathways are actively being developed. In this Review, we discuss selected and promising anticancer therapies in various stages of development, including drug targets, mechanisms, and resistance to related treatments, focusing especially on B cell lymphoma 2 (BCL-2) inhibitors, TRAIL analogues, DR5 antibodies, and strategies that target p53, mutant p53, and the ISR., Introduction Apoptosis is a form of regulated cell death with a critical role in development and homeostasis (1). Activation of apoptotic pathways results in destruction of target cells with minimal [...]

Diaphorina citri serves as the primary vector for ‘Candidatus Liberibacter asiaticus (CLas),’ the bacterium associated with the severe Asian form of huanglongbing. CLas-positive D. citri are more fecund than their CLas-negative counterparts and require extra energy expenditure. Therefore, understanding the molecular mechanisms linking metabolism and reproduction is of particular importance. In this study, we found adipokinetic hormone (DcAKH) and its receptor (DcAKHR) were essential for increasing lipid metabolism and fecundity in response to CLas infection in D. citri. Knockdown of DcAKH and DcAKHR not only resulted in the accumulation of triacylglycerol and a decline of glycogen, but also significantly decreased fecundity and CLas titer in ovaries. Combined in vivo and in vitro experiments showed that miR-34 suppresses DcAKHR expression by binding to its 3’ untranslated region, whilst overexpression of miR-34 resulted in a decline of DcAKHR expression and CLas titer in ovaries and caused defects that mimicked DcAKHR knockdown phenotypes. Additionally, knockdown of DcAKH and DcAKHR significantly reduced juvenile hormone (JH) titer and JH signaling pathway genes in fat bodies and ovaries, including the JH receptor, methoprene-tolerant (DcMet), and the transcription factor, Krüppel homolog 1 (DcKr-h1), that acts downstream of it, as well as the egg development related genes vitellogenin 1-like (DcVg-1-like), vitellogenin A1-like (DcVg-A1-like) and the vitellogenin receptor (DcVgR). As a result, CLas hijacks AKH/AKHR-miR-34-JH signaling to improve D. citri lipid metabolism and fecundity, while simultaneously increasing the replication of CLas, suggesting a mutualistic interaction between CLas and D. citri ovaries.

ABSTRACT The ‘Tahiti’ acid lime and orange trees are hosts of ‘Candidatus Liberibacter asiaticus’ (CLas), the pathogen associated with the severe Asian form of huanglongbing (HLB), the most devasting citrus disease. They are also hosts of the vector of CLas, the Asian citrus psyllid (ACP) Diaphorina citri Kuwayama. Relatively small numbers of lime trees occur in gardens and small orchards near large commercial ‘Valencia’ sweet orange orchards in Brazil. Applications of insecticides to suppress populations of ACP on the lime trees are usually nil or less frequent than in the orange orchards. Abundance of the psyllid on lime trees may therefore increase the risk of CLas spreading to the orchards. Because the abundance of the psyllid is influenced by the suitability of the trees as hosts, we compared reproductive potential of the insect on the two hosts in a controlled environment chamber (CEC) and in a greenhouse (GH). Daily temperature and relative humidity averaged 22ºC and 60% inside the CEC and 24°C and 70% inside the GH. Two pairs of adult male and female psyllids were caged for 3 days on new shoots and the fecundity and durations of development and survival of eggs and nymphs evaluated. Overall, acid ‘Tahiti’ was 3.5 times less suitable to ACP than ‘Valencia’. Fecundity and survival of nymphs were 27% and 59% lower, and the life cycle 34% longer on ‘Tahiti’ than on ‘Valencia’. Potential impacts of the results on CLas spread and HLB control are discussed.

This evaluation assessed the effectiveness of graphic-based (i.e., pictorial) report-back materials in communicating the presence of toxic metals in private well water and soil samples. It also explored associations between recommendations in the report-back materials and appropriate actions to protect health taken by a subset of participants in an environmental monitoring pilot study. Overall, 39 residents of Stokes County, North Carolina, participated in the Well Empowered pilot study, which included water and soil testing and analysis. All participants received materials explaining the extent to which toxic metals were present in their well water and soil. A subset of participants (n = 14) responded to a follow-up evaluation, which showed that many found at least one component of their test results 'very easy to understand.' The existence of a federal standard for comparison appeared to influence participant recall of results, which was more accurate for contaminants with a federal maximum contaminant level. Our evaluation results suggest that a simple pictorial format, in combination with more detailed supporting text, can be useful in highlighting results that require action., Introduction More than 42.5 million people in the U.S. rely on private wells for household water use (Dieter et al., 2018); over 20% of those wells contain one or more [...]

Simpson‐Golabi‐Behmel syndrome (SGBS) is a rare congenital overgrowth condition characterized by macrosomia, macroglossia, coarse facial features, and development delays. It is caused by pathogenic variants in the GPC3 gene on chromosome Xq26.2. Here, we performed a comprehensive literature review and phenotyping of known patients with molecularly confirmed SGBS and reviewed a novel cohort of 22 patients. Using these data, we characterized the tumor risk for Wilms tumor and hepatoblastoma to suggest appropriate screening for this patient population. In addition, we discuss the phenotypic overlap between SGBS and Beckwith‐Wiedemann Spectrum. [ABSTRACT FROM AUTHOR]

Beckwith–Wiedemann spectrum (BWSp) is caused by genetic and epigenetic alterations on chromosome 11 that regulate cell growth and division. Considering the diverse phenotypic landscape in BWSp, the characterization of the CDKN1C molecular subtype remains relatively limited. Here, we investigate the role of CDKN1C in the broader BWSp phenotype. Notably, patients with CDKN1C variants appear to exhibit a different tumor risk than other BWSp molecular subtypes. We performed a comprehensive literature review using the search term "CDKN1C Beckwith" to identify 113 cases of patients with molecularly confirmed CDKN1C‐BWSp. We then assessed the genotype and phenotype in a novel cohort of patients with CDKN1C‐BWSp enrolled in the BWS Research Registry. Cardinal and suggestive features were evaluated for all patients reported, and tumor risk was established based on available reports. The most common phenotypes included macroglossia, omphalocele, and ear creases/pits. Tumor types reported from the literature included neuroblastoma, acute lymphocytic leukemia, superficial spreading melanoma, and intratubular germ cell neoplasia. Overall, this study identifies unique features associated with CDKN1C variants in BWSp, enabling more accurate clinical management. The absence of Wilms tumor and hepatoblastoma suggests that screening for these tumors may not be necessary, while the neuroblastoma risk warrants appropriate screening recommendations. [ABSTRACT FROM AUTHOR]

Populations of Diaphorina citri decline with elevation and, in a study in Bhutan, were rarely found above 1200 m ASL. The impact of ultraviolet (UV) radiation, particularly UV-B, on immature stages of the psyllid was proposed as limiting factor. As no studies have been undertaken on the influences of UV radiation on the development of D. citri, we examined the effects of UV-A and UV-B on different stadia of the psyllid. In addition, compliance with the Bunsen–Roscoe reciprocity law was examined. Irradiation with UV-A marginally reduced egg hatch and the survival times of emerging nymphs. Early instar nymphs were little affected by this waveband, but the survival of adults was reduced at the higher doses used. With UV-B, egg hatch and the survival times of early and late instar nymphs declined in proportion to UV-B dose. A dose of 57.6 kJ m−2 d−1 reduced the survival time of only adult females. Female fecundity was reduced at high UV-A and UV-B doses but increased at low doses. The Bunsen–Roscoe law held true for eggs and early instar nymphs for different durations and irradiances of UV-B. Eggs and nymphs had ED50 values for UV-B lower than the daily fluxes of this wavelength experienced worldwide. Thus, UV-B could be a factor causing the psyllid to be scarce at high elevations.

Background and Purpose: Oligomeric amyloid β 1‐42 (oAβ1‐42) exhibits agonist‐like action at human α7‐ and α7β2‐containing nicotinic receptors. The N‐terminal amyloid β1‐15 fragment (N‐Aβ fragment) modulates presynaptic calcium and enhances hippocampal‐based synaptic plasticity via α7‐containing nicotinic receptors. Further, the N‐Aβ fragment and its core sequence, the N‐amyloid‐beta core hexapeptide (N‐Aβcore), protect against oAβ1‐42‐associated synapto‐ and neurotoxicity. Here, we investigated how oAβ1‐42, the N‐Aβ fragment, and the N‐Aβcore regulate the single‐channel properties of α7‐ and α7β2‐nicotinic receptors. Experimental Approach: Single‐channel recordings measured the impact of acetylcholine, oAβ1‐42, the N‐Aβ fragment, and the N‐Aβcore on the unitary properties of human α7‐ and α7β2‐containing nicotinic receptors expressed in nicotinic‐null SH‐EP1 cells. Molecular dynamics simulations identified potential sites of interaction between the N‐Aβ fragment and orthosteric α7+/α7‐ and α7+/β2‐ nicotinic receptor binding interfaces. Key Results: The N‐Aβ fragment and N‐Aβcore induced α7‐ and α7β2‐nicotinic receptor single‐channel openings. Relative to acetylcholine, oAβ1‐42 preferentially enhanced α7β2‐nicotinic receptor single‐channel open probability and open‐dwell times. Co‐application with the N‐Aβcore neutralized these effects. Further, administration of the N‐Aβ fragment alone, or in combination with acetylcholine or oAβ1‐42, selectively enhanced α7‐nicotinic receptor open probability and open‐dwell times (compared to acetylcholine or oAβ1‐42). Conclusions and Implications: Amyloid‐beta peptides demonstrate functional diversity in regulating α7‐ and α7β2‐nicotinic receptor function, with implications for a wide range of nicotinic receptor‐mediated functions in Alzheimer's disease. The effects of these peptides on α7‐ and/or α7β2‐nicotinic receptors revealed complex interactions with these subtypes, providing novel insights into the neuroprotective actions of amyloid β‐derived fragments against the toxic effects of oAβ1‐42. [ABSTRACT FROM AUTHOR]

Ultraviolet radiation (UVR) has positive and negative impacts on organisms and affects entire ecosystems. It is currently receiving attention because of the interactions of UVR with changes in climate that are likely to affect agriculture and food security.A review is provided on the effects of different types of UVR on the survival, development and reproduction of insects, collembolans and mites. The foci are on how UVR is used in pest control and how it affects arthropod coloration and distribution.Direct exposure to UV‐A, UV‐B and UV‐C delays development and reduces survival and host‐seeking ability of arthropods; immature stages are more sensitive than the adults. Increased exposure of crops to UVR has indirect effects on herbivory, and regions with high UVR levels may permit crop production in the absence of certain pest insect species.The Bunsen‐Roscoe law of reciprocity was upheld for Diaphorina citri and Tetranychus urticae under the range of irradiances and durations of exposure used in two studies, which showed that, for a constant dose, the effects of low irradiances of long durations were equivalent to those of higher irradiances of shorter durations.DNA damage caused by UV‐C and UV‐B can be repaired by photoreactivation; both white light and UV‐A are effective. [ABSTRACT FROM AUTHOR]

Two novel cyclometalated ruthenium complexes, RC‐4 and RC‐5, featuring 1‐phenylisoquinoline and phenyl quinazoline as ancillary ligands, respectively, were synthesized to investigate their viability with the environmentally friendly copper (Cu) redox mediator, [Cu(bpye)2]2+/+. The modification of the ligand environment resulted in variations in the energetics, photophysical properties, and photovoltaic performance of RC‐4 and RC‐5 sensitizers. Despite RC‐5 sensitizer possessing a more positive ground state potential of 1.19 V versus the NHE, the RC‐4 sensitizer, with a lower HOMO level of 0.72 V versus NHE, exhibited superior photovoltaic performance along with the Cu electrolyte, attributed to its enhanced light harvesting ability, improved lifetime and reduced back electron transfer, contributing to higher Jsc, Voc, and PCE. [ABSTRACT FROM AUTHOR]