Search Results (22)

Five major antimicrobial peptides (AMPs) in Drosophila are induced in multiple sex combs (mxc) mutant larvae harboring lymph gland (LG) tumors, and they exhibit anti-tumor effects. The effects of other well-known AMPs, Cecropin A and Drosocin, remain unexplored. We investigated the tumor-elimination mechanism of these AMPs. A half-dose reduction in either the Toll or Imd gene reduced the induction of these AMPs and enhanced tumor growth in mxc^mbn1 mutant larvae, indicating that their anti-tumor effects depend on the innate immune pathway. Overexpression of these AMPs in the fat body suppressed tumor growth without affecting cell proliferation. Apoptosis was promoted in the mutant but not in normal LGs. Conversely, knockdown of them inhibited apoptosis and enhanced tumor growth; therefore, they inhibit LG tumor growth by inducing apoptosis. The AMPs from the fat body were incorporated into the hemocytes of mutant but not normal larvae. Another AMP, Drosomycin, was taken up via phagocytosis factors. Enhanced phosphatidylserine signals were observed on the tumor surface. Inhibition of the signals exposed on the cell surface enhanced tumor growth. AMPs may target phosphatidylserine in tumors to induce apoptosis and execute their tumor-specific effects. AMPs could be beneficial anti-cancer drugs with minimal side effects for clinical development. Full article

The additional sex combs-like (ASXL) family, a mammalian homolog of the additional sex combs (Asx) of Drosophila, has been implicated in transcriptional regulation via chromatin modifications. Abnormal expression of ASXL family genes leads to myelodysplastic syndromes and various types of leukemia. De novo mutation of these genes also causes developmental disorders. Genes in this family and their neighbor genes are evolutionary conserved in humans and mice. This review provides a comprehensive summary of epigenetic regulations associated with ASXL family genes. Their expression is commonly regulated by DNA methylation at CpG islands preceding transcription starting sites. Their proteins primarily engage in histone tail modifications through interactions with chromatin regulators (PRC2, TrxG, PR-DUB, SRC1, HP1α, and BET proteins) and with transcription factors, including nuclear hormone receptors (RAR, PPAR, ER, and LXR). Histone modifications associated with these factors include histone H3K9 acetylation and methylation, H3K4 methylation, H3K27 methylation, and H2AK119 deubiquitination. Recently, non-coding RNAs have been identified following mutations in the ASXL1 or ASXL3 gene, along with circular ASXLs and microRNAs that regulate ASXL1 expression. The diverse epigenetic regulations linked to ASXL family genes collectively contribute to tumor suppression and developmental processes. Our understanding of ASXL-regulated epigenetics may provide insights into the development of therapeutic epigenetic drugs. Full article

Several antimicrobial peptides suppress the growth of lymph gland (LG) tumors in Drosophila multi sex comb (mxc) mutant larvae. The activity of another family of polypeptides, called Turandots, is also induced via the JAK/STAT pathway after bacterial infection; however, their influence on Drosophila tumors remains unclear. The JAK/STAT pathway was activated in LG tumors, fat body, and circulating hemocytes of mutant larvae. The mRNA levels of Turandot (Tot) genes increased markedly in the mutant fat body and declined upon silencing Stat92E in the fat body, indicating the involvement of the JAK/STAT pathway. Furthermore, significantly enhanced tumor growth upon a fat-body-specific silencing of the mRNAs demonstrated the antitumor effects of these proteins. The proteins were found to be incorporated into small vesicles in mutant circulating hemocytes (as previously reported for several antimicrobial peptides) but not normal cells. In addition, more hemocytes containing these proteins were found to be associated with tumors. The mutant LGs contained activated effector caspases, and a fat-body-specific silencing of Tots inhibited apoptosis and increased the number of mitotic cells in the LG, thereby suggesting that the proteins inhibited tumor cell proliferation. Thus, Tot proteins possibly exhibit antitumor effects via the induction of apoptosis and inhibition of cell proliferation. Full article

Mites, the second largest arthropod group, exhibit rich phenotypic diversity in the development of appendages (legs). For example, the fourth pair of legs (L4) does not form until the second postembryonic developmental stage, namely the protonymph stage. These leg developmental diversities drive body plan diversity in mites. However, little is known about the mechanisms of leg development in mites. Hox genes, homeotic genes, can regulate the development of appendages in arthropods. Three Hox genes, Sex combs reduced (Scr), Fushi tarazu (Ftz) and Antennapedia (Antp), have previously been shown to be expressed in the leg segments of mites. Here, the quantitative real-time reverse transcription PCR shows that three Hox genes are significantly increased in the first molt stage. RNA interference results in a set of abnormalities, including L3 curl and L4 loss. These results suggest that these Hox genes are required for normal leg development. Furthermore, the loss of single Hox genes results in downregulating the expression of the appendage marker Distal-less (Dll), suggesting that the three Hox genes can work together with Dll to maintain leg development in Tetranychus urticae. This study will be essential to understanding the diversity of leg development in mites and changes in Hox gene function. Full article

Sex trafficking victims are often advertised through online escort sites. These ads can be publicly accessed, but law enforcement lacks the resources to comb through hundreds of ads to identify those that may feature sex-trafficked individuals. The purpose of this study was to implement and test multi-input, deep learning (DL) binary classification models to predict the probability of an online escort ad being associated with sex trafficking (ST) activity and aid in the detection and investigation of ST. Data from 12,350 scraped and classified ads were split into training and test sets (80% and 20%, respectively). Multi-input models that included recurrent neural networks (RNN) for text classification, convolutional neural networks (CNN, specifically EfficientNetB6 or ENET) for image/emoji classification, and neural networks (NN) for feature classification were trained and used to classify the 20% test set. The best-performing DL model included text and imagery inputs, resulting in an accuracy of 0.82 and an F1 score of 0.70. More importantly, the best classifier (RNN + ENET) correctly identified 14 of 14 sites that had classification probability estimates of 0.845 or greater (1.0 precision); precision was 96% for the multi-input model (NN + RNN + ENET) when only the ads associated with the highest positive classification probabilities (>0.90) were considered (n = 202 ads). The models developed could be productionalized and piloted with criminal investigators, as they could potentially increase their efficiency in identifying potential ST victims. Full article

Two marine halacarids, Copidognathus levicostatus n. sp. and C. vicinus Bartsch, 1997, belonging to the C. gibbus group, have been recorded based on both sexes from the microhabitat of intertidal and sublittoral rocks on the coast of South Korea. Copidognathus levicostatus n. sp. Is characterized by a combination of features, as follows: the absence of areolae with rosette pores on all dorsal and ventral plates, the presence of a short frontal process, a pair of costae with raised narrow ribs on the posterior dorsal plate, the partial fusion of the anterior epimeral plate and genitoanal plate in both sexes, and three pairs of perigenital setae in the male. The Korean specimens of C. vicinus Bartsch, 1997 agree well with the original description from Hong Kong, except for the lateral claws bearing a comb. This study provides detailed (re)descriptions of the morphological characteristics of the two Korean halacarid species, C. levicostatus n. sp. and C. vicinus, based on illustrations and scanning electron microscope photomicrographs. Additionally, we present a dichotomous key for known Copidognathus species in Korean waters, accompanied by a brief comment on their occurrence in various microhabitats, especially their habitat preferences for geniculate and non-geniculate red coralline algae. Full article

Androgenic alopecia (AGA) is a genetically predetermined condition that occurs as a result of stepwise miniaturization of the dermal papilla. During this process, the hair follicle suffers from increasing malnutrition and eventually dies, causing progressive hair loss. We recently highlighted that HIF-1α modulation may counteract hair loss. Here, we aim to demonstrate the positive influence of Tomorrowlabs HIF strengthening factor [HSF] hair restoration technology on hair biology in a monocentric blinded clinical trial over a total period of 9 months. A trial with 20 subjects (4 female and 16 male) and once-daily application of [HSF] hair restoration technology to the scalp was conducted. To assess the tolerability and efficacy of [HSF], testing included dermatological assessment, determination of hair loss by counting after combing, macro images of the head and TrichoScan evaluation of hair density as well as the proportion of anagen hair versus telogen hair. The clinical data show Tomorrowlabs [HSF] hair restoration to be safe and effective to counteract AGA. The use of Tomorrowlabs [HSF] hair restoration resulted in improvements in the clinical parameters of hair quality such as thickness (+7.2%), hair density (+14.3%) and shine and elasticity (+20.3%) during the test period. The effectiveness of the test product was further determined by a significant reduction in hair loss of an average of 66.8% in treatment-responsive subjects after 6 months and an increase in hair growth reaching up to 32.5%, with an average percentage change of 8.4% in all participants and 10.8% in the responsive patients (85% of the study cohort) after 9 months on TrichoScan evaluation. The hair growth cycle was harmonized with the result of an average anagen hair percentage increase of +8.0% and telogen hair percentage reduction of −14.0% shown in the test area. Applicable for both sexes in an alcohol-free formulation, beneficial to scalp health and free of complications or side effects, this novel product provides objectively measurable results counteracting hair loss paired with an improved look and feel of the hair. Full article

Dual-energy computed tomography (DECT) is an imaging technique that detects monosodium urate (MSU) deposits. This study aimed to assess the clinical utility of DECT in the diagnosis of gout. A total of 120 patients with clinical suspicion of gout who underwent DECT were retrospectively enrolled. The sensitivity and specificity of DECT alone, American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria without DECT, and ACR/EULAR criteria with DECT were assessed. Additionally, an analysis of gout risk factors was performed. When artifacts were excluded, any MSU volume provided the best diagnostic value of DECT (AUC = 0.872, 95% CI 0.806–0.938). DECT alone had a sensitivity of 90.4% and specificity of 74.5%. Although ACR/EULAR criteria without DECT provided better diagnostic accuracy than DECT alone (AUC = 0.926, 95% CI 0.878–0.974), the best value was obtained when combing both (AUC = 0.957, 95% CI 0.924–0.991), with 100% sensitivity and 76.6% specificity. In univariate analysis, risk factors for gout were male sex, presence of tophi, presence of MSU deposits on DECT, increased uric acid in serum (each p < 0.001), and decreased glomerular filtration rate (GFR) (p = 0.029). After logistic regression, only increased serum uric acid (p = 0.034) and decreased GFR (p = 0.018) remained independent risk factors for gout. Our results suggest that DECT significantly increases the sensitivity of the ACR/EULAR criteria in the diagnosis of gout. Full article

Novel coronavirus disease 2019 (COVID-19) pandemic restrictions have negatively impacted physical activity (PA) and sedentary time/behaviour. This integrative review systematically explored the socioecological factors that impacted and influenced these movement behaviours in children and adolescents during the pandemic. Five electronic databases were systematically searched in January 2021, with data extracted from 16 articles (n = 18,352; 5–17 years; 12 countries). Risk-of-bias was assessed using the Mixed Methods Assessment Tool (MMAT), with correlates identified, coded, and themed via thematic analysis. A socioecological model of during-pandemic PA and sedentary time/behaviour was conceptualised and mapped to the Capability, Opportunity, Motivation, and Behaviour (COM-B) model of behaviour-change mechanisms, illustrating influences over five levels: Individual (biological)—age and sex; Individual (psychological)—mental health, and cognition, motivation, and behaviour; Social—family factors, and structured support; Environmental—area of residence and resources; and Policy—COVID-19-related rules. For sedentary time/behaviour, individual-(age and sex), social-(family factors) and policy-(COVID-19-related rules) level factors may be important correlates. There were no age or sex associations with PA levels, though there was some indication that sedentary time/behaviour increased with age. Interventions seeking to enhance young people’s movement behaviours during periods of enforced restrictions should focus on enhancing opportunities on a social and environmental level. Full article

Population-level physical activity (PA) and sedentary time/behaviour estimates represent a significant public health issue exacerbated by restrictions enforced to control COVID-19. This integrative review interrogated available literature to explore the pandemic’s impact on correlates of such behaviours in adults (≥18 years). Five electronic databases were systematically searched in January 2021. Data extracted from 64 articles were assessed for risk-of-bias using the Mixed Methods Assessment Tool, with correlates identified, coded, and themed via thematic analysis. A socioecological model of during-pandemic PA was conceptualized and mapped to the Capability, Opportunity, Motivation, and Behaviour (COM-B) model of behaviour change mechanisms, which illustrates influences over five levels: Individual (biological)—general health; Individual (psychological)—mental health, cognition, motivation, and behaviour; Social—domestic situation, sociodemographic factors, support, and lifestyle choices; Environmental—resources and area of residence; and Policy—COVID-19-related rules. For sedentary time/behaviour, individual level factors, namely general and mental health, may be important correlates. Neither age or sex were clearly correlated with either behaviour. As we transition into a new normal, understanding which behaviour mechanisms could effectively challenge physical inactivity is essential. Targeting capability on a psychological level may facilitate PA and limit sedentary time/behaviour, whereas, on a physical level, maximizing PA opportunities could be crucial. Full article

Scorpions have elaborate chemo-tactile organs called pectines on their ventral mesosoma. The teeth of the comb-like pectines support thousands of minute projections called peg sensilla (a.k.a. “pegs”), each containing approximately 10 chemosensory neurons. Males use pectines to detect pheromones released by females, and both sexes apparently use pectines to find prey and navigate to home retreats. Electrophysiological recordings from pegs of Paruroctonus utahensis reveal three spontaneously active cells (A₁, A₂, and B), which appear to interact synaptically. We made long-term extracellular recordings from the bases of peg sensilla and used a combination of conditional cross-interval and conditional interspike-interval analyses to assess the temporal dynamics of the A and B spike trains. Like previous studies, we found that A cells are inhibited by B cells for tens of milliseconds. However, after normalizing our records, we also found clear evidence that the A cells excite the B cells. This simple local circuit appears to maintain the A cells in a dynamic firing range and may have important implications for tracking pheromonal trails and sensing substrate chemistry for navigation. Full article

Clinical evidence suggests that conventional cardiovascular disease (CVD) risk factors cannot explain all CVD incidences. Recent studies have shown that telomere attrition, clonal hematopoiesis of indeterminate potential (CHIP), and atherosclerosis (telomere–CHIP–atherosclerosis, TCA) evolve to play a crucial role in CVD. Telomere dynamics and telomerase have an important relationship with age-related CVD. Telomere attrition is associated with CHIP. CHIP is commonly observed in elderly patients. It is characterized by an increase in blood cell clones with somatic mutations, resulting in an increased risk of hematological cancer and atherosclerotic CVD. The most common gene mutations are DNA methyltransferase 3 alpha (DNMT3A), Tet methylcytosine dioxygenase 2 (TET2), and additional sex combs-like 1 (ASXL1). Telomeres, CHIP, and atherosclerosis increase chronic inflammation and proinflammatory cytokine expression. Currently, their epidemiology and detailed mechanisms related to the TCA axis remain incompletely understood. In this article, we reviewed recent research results regarding the development of telomeres and CHIP and their relationship with atherosclerotic CVD. Full article

Monstrilloid copepods are protelean parasites with a complex life cycle that includes an endoparasitic juvenile phase and free-living early naupliar and adult phases. The monstrilloid copepod genus Caromiobenella Jeon, Lee and Soh, 2018 is known to contain nine species, each one with a limited distribution; except for two species, members of this widespread genus are known exclusively from males. Hitherto, members of Caromiobenella have not been recorded from tropical waters of the South Western Atlantic (SWA). The nominal species Monstrilla brasiliensis Dias and Suárez-Morales, 2000 was originally described from female specimens collected in coastal waters of Espírito Santo and Rio de Janeiro (Brazil), but the male remained unknown. The failure to reliably link both sexes of monstrilloid species is one of the main problems in the current taxonomy of the group, thus leading to a separate treatment for each sex. New zooplankton collections in coastal waters and intertidal rocky pools of the SWA yielded several male and female monstrilloid copepods tentatively identified as Monstrilla brasiliensis. Our results of both morphologic and molecular (mtCOI) analyses allowed us to confirm that these males and females were conspecific. We also found evidence suggesting that Caromiobenella is not a monophyletic taxon. Our male specimens are morphologically assignable to Caromiobenella, therefore, females of the nominal species Monstrilla brasiliensis, are matched here with the aforementioned males and, thus, the species should be known as C. brasiliensis comb. nov. (Dias and Suárez-Morales, 2000). This finding represents the third documented discovery of a female of Caromiobenella, the first record of the genus in the Southwestern Atlantic, and the first documented record of monstrilloids from coastal tidepools. With the addition of C. brasiliensis, Caromiobenella now includes 10 valid species worldwide. This work represents the second successful use of molecular methods to link both sexes of a monstrilloid copepod. The male of C. brasiliensis is herein described, and a key to the known species of Caromiobenella and data on the habitat and local abundance of C. brasiliensis are also provided. Full article

Myeloid malignancy is a broad term encapsulating myeloproliferative neoplasms (MPN), myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). Initial studies into genomic profiles of these diseases have shown 2000 somatic mutations prevalent across the spectrum of myeloid blood disorders. Epigenetic mutations are emerging as critical components of disease progression, with mutations in genes controlling chromatin regulation and methylation/acetylation status. Genes such as DNA methyltransferase 3A (DNMT3A), ten eleven translocation methylcytosine dioxygenase 2 (TET2), additional sex combs-like 1 (ASXL1), enhancer of zeste homolog 2 (EZH2) and isocitrate dehydrogenase 1/2 (IDH1/2) show functional impact in disease pathogenesis. In this review we discuss how current knowledge relating to disease progression, mutational profile and therapeutic potential is progressing and increasing understanding of myeloid malignancies. Full article

Background: The early non-invasive discrimination of Type 2 versus Type 1 Myocardial Infarction (T2MI, T1MI) is a major unmet clinical need. We aimed to externally validate a recently derived clinical score (Neumann) combing female sex, no radiating chest pain, and high-sensitivity cardiac troponin I (hs-cTnI) concentration ≤40.8 ng/L. Methods: Patients presenting with acute chest discomfort to the emergency department were prospectively enrolled into an international multicenter diagnostic study. The final diagnoses of T2MI and T1MI were centrally adjudicated by two independent cardiologists using all information including cardiac imaging and serial measurements of hs-cTnT/I according to the fourth universal definition of MI. Model performance for T2MI diagnosis was assessed by formal tests and graphical means of discrimination and calibration. Results: Among 6684 enrolled patients, MI was the adjudicated final diagnosis in 1079 (19%) patients, of which 242 (22%) had T2MI. External validation of the Neumann Score showed a moderate discrimination (C-statistic 0.67 (95%CI 0.64–0.71)). Model calibration showed underestimation of the predicted probabilities of having T2MI for low point scores. Model extension by adding the binary variable heart rate >120/min significantly improved model performance (C-statistic 0.73 (95% CI 0.70–0.76, p < 0.001) and had good calibration. Patients with the highest score values of 3 (Neumann Score, 9.9%) and 5 (Extended Neumann Score, 3.3%) had a 53% and 91% predicted probability of T2MI, respectively. Conclusion: The Neumann Score provided moderate discrimination and suboptimal calibration. Extending the Neumann Score by adding heart rate >120/min improved the model’s performance. Full article