Female‐producing parthenogenesis can be induced by endosymbionts that increase their transmission by manipulating host reproduction. Our literature survey indicates that such endosymbiont‐induced ...parthenogenesis is known or suspected in 124 host species from seven different arthropod taxa, with Wolbachia as the most frequent endosymbiont (in 56–75% of host species). Most host species (81%, 100 out of 124) are characterized by haplo‐diploid sex determination, but a strong ascertainment bias likely underestimates the frequency of endosymbiont‐induced parthenogenesis in hosts with other sex determination systems. In at least one taxon, hymenopterans, endosymbionts are a significant driver of transitions from sexual to parthenogenetic reproduction, with one‐third of lineages being parthenogenetic as a consequence of endosymbiont infection. Endosymbiont‐induced parthenogenesis appears to facilitate the maintenance of reproductive polymorphism: at least 50% of species comprise both sexual (uninfected) and parthenogenetic (infected) strains. These strains feature distribution differences similar to the ones documented for lineages with genetically determined parthenogenesis, with endosymbiont‐induced parthenogens occurring at higher latitudes than their sexual relatives. Finally, although gamete duplication is often considered as the main mechanism for endosymbiont‐induced parthenogenesis, it underlies parthenogenesis in only half of the host species studied thus far. We point out caveats in the methods used to test for endosymbiont‐induced parthenogenesis and suggest specific approaches that allow for firm conclusions about the involvement of endosymbionts in the origin of parthenogenesis.
Summary Kashin-Beck disease (KBD) is an endemic chronic osteochondral disease, which has a high prevalence and morbidity in the Eastern Siberia of Russia, and in the broad diagonal, northern-east to ...southern-west belt in China and North Korea. In 1990's, it was estimated that in China 1–3 million people had some degree of symptoms of the disease, although even higher estimates have been presented. In China, the extensive prevalence peaked in the late 1950's, but since then, in contrast to the global trend of the osteoarthritis (OA), the number of cases has been dramatically falling. Up to 2013, there are 0.64 millions patients with the KBD and 1.16 millions at risk in 377 counties of 13 provinces or autonomous regions. This is obviously thanks to the preventive efforts carried out, which include providing millions of people with dietary supplements and clean water, as well as relocation of whole villages in China. However, relatively little is known about the molecular mechanisms behind the cartilage damage, the genetic and the environmental risk factors, and the rationale of the preventive effects. During the last decade, new data on a cellular and molecular level has begun to accumulate, which hopefully will uncover the grounds of the disease.
Colorectal cancer (CRC) is highly heterogeneous at the genetic and molecular level, which has major repercussions on the efficacy of immunotherapy. A small subset of CRCs exhibit microsatellite ...instability (MSI), a molecular indicator of defective DNA mismatch repair (MMR), but the majority are microsatellite-stable (MSS). The high tumor mutational burden (TMB) and neoantigen load in MSI tumors favors the infiltration of immune effector cells, and antitumor immune responses within these tumors are strong relative to their MSS counterparts. MSI has emerged as a major predictive marker for the efficacy of immune checkpoint blockade over the last few years and nivolumab or pembrolizumab targeting PD-1 has been approved for patients with MSI refractory or metastatic CRC. However, some MSS tumors show DNA polymerase epsilon (POLE) mutations that also confer a very high TMB and may also be heavily infiltrated by immune cells making them amenable to respond to immune checkpoint inhibitors (ICI). In this review we discuss the role of the different immune landscapes in CRC and their relationships with defined CRC genetic subtypes. We discuss potential reasons why immune checkpoint blockade has met with limited success for the majority of CRC patients, despite the finding that immune cell infiltration of primary non-metastatic tumors is a strong predictive, and prognostic factor for relapse and survival. We then consider in which ways CRC cells develop mechanisms to resist ICI. Finally, we address the latest advances in CRC vaccination and how a personalized neoantigen vaccine strategy might overcome the resistance of MSI and MSS tumors in patients for whom immune checkpoint blockade is not a treatment option.
Circulating fatty acids (FA) are associated with a multitude of chronic diseases. However, a major gap in establishing such relationships is the lack of accepted fatty acid reference ranges ...representing healthy individuals. Data on validated FA reference ranges would provide a better understanding of study baseline measures and aid in the evaluation and interpretation of pharmaceutical or dietary interventions. Reference ranges for plasma FA levels have been reported in a few small studies and on a limited number of FA. Therefore, we determined the average and percentiles of a broad set of 61 FA (C14 - C24:1) from plasma total lipids from an ethnically diverse population of healthy young Canadian males and females (Total n = 826). Plasma concentrations of some of the major FA ranged from 0.3 to 4.1 mmol/L for palmitic acid, 0.1 to 1.0 mmol/L for stearic acid, 0.03 to 3.2 mmol/L for oleic acid, 0.2 to 5.0 mmol/L for linoleic acid (LA), 12.0 to 186.9 μmol/L for α-linolenic acid, and 7.2 to 237.5 μmol/L for docosahexaenoic acid (DHA). Males had significantly higher plasma concentrations of γ-linolenic acid (GLA) and n-3 docosapentaenoic acid and lower concentrations of palmitoleic acid, LA and DHA than females. Comparison of FA concentrations between Caucasians, East Asians and South Asians revealed that South Asians had significantly lower levels of palmitoleic acid (p < 0.01) and oleic acid (p = 0.01) while East Asians had lower levels of GLA (p = 0.02) and dihomo-γ-linolenic acid (p = 0.03). Overall, these data provide a comprehensive set of quantitative values that profiles a small cohort of Canadians which highlights the utility of establishing validated FA reference ranges that may be used to understand how deficient, suboptimal, or excess amounts of a given FA may be associated with chronic disease.
Paclitaxel (PTX) is an effective drug against diseases such as lung cancer, ovarian cancer, and breast cancer. However, multidrug resistance limits the clinical applications of this drug. Tetrahedral ...DNA nanostructures (TDNs) offer great promise as a drug delivery candidate. In our study, we prepared TDNs that were subsequently loaded with PTX (PTX/TDNs). The cytotoxicity of PTX/TDNs and PTX alone on non-small cell lung cancer (NSCLC) cells (A549) and the PTX-resistant cell line (A549/T) was determined using a cell count kit-8 (CCK-8) assay. PTX/TDNs exerted strong lethality on both cell lines. Moreover, drug resistance was overcome. Furthermore, the mechanisms used by PTX/TDNs to overcome drug resistance were studied. The expression of mdr 1 gene and P-glycoprotein (P-gp) in A549/T was found to be downregulated, thus indicating that TDNs serve as a P-gp inhibitor. We also showed that PTX/TDNs killed cancer cells via apoptosis. Thus, PTX/TDNs have great potential for use as a nanodelivery system for the treatment of PTX-resistant NSCLC.
Supersymmetry (SUSY) relating bosons and fermions plays an important role in unifying different fundamental interactions in particle physics. Since no superpartners of elementary particles have been ...observed, SUSY, if present, must be broken at low-energy. This makes it important to understand how SUSY is realized and broken, and study their consequences. We show that an N = (1, 0) SUSY, arguably the simplest type, can be realized at the edge of the Moore-Read quantum Hall state. Depending on the absence or presence of edge reconstruction, both SUSY-preserving and SUSY broken phases can be realized in the same system, allowing for their unified description. The significance of the gapless fermionic Goldstino mode in the SUSY broken phase is discussed.
Transparent conductive carbon nanotube (CNT) films were fabricated by dip-coating solutions of pristine CNTs dissolved in chlorosulfonic acid (CSA) and then removing the CSA. The film performance and ...morphology (including alignment) were controlled by the CNT length, solution concentration, coating speed, and level of doping. Using long CNTs (∼10 μm), uniform films were produced with excellent optoelectrical performance (∼100 Ω/sq sheet resistance at ∼90% transmittance in the visible), in the range of applied interest for touch screens and flexible electronics. This technique has potential for commercialization because it preserves the length and quality of the CNTs (leading to enhanced film performance) and operates at high CNT concentration and coating speed without using surfactants (decreasing production costs).
Abstract
Massive contact binaries contain two early-type stars that have filled their respective critical Roche lobes and share a common envelope. Their formation and evolution are still unknown. ...Searching for massive binaries in special evolutionary stages is required to solve this problem. Many massive binaries in the Andromeda galaxy (M31) have been found out and they provide an ideal laboratory to explore the formation of massive contact binaries and to test evolutionary models in massive binaries. By analyzing the light curves of two massive binaries containing twin components, M31V J00452011+4145037 (hereafter J004520) and M31V J00450522+4138462 (hereafter J004505), observed by Vilardell et al., we found that J004520 is a semidetached binary with a mass ratio of 0.924 and a lobe-filling secondary, while J004505 is a deep-contact binary with a mass ratio of 0.974 and a fill-out factor of 88%. Both of them evolved from originally detached binaries via case A mass transfer and are at a critical evolutionary state with the shortest possible period and the highest possible mass ratio (
q
= 1). The evolution of J004520 has passed the critical state and cannot evolve into a contact binary, while J004505 is just close to the key state. The asymmetric light curve of J004505 is explained by the presence of a hot spot on the less-massive component caused by mass transfer from the more-massive one; the same conclusion can be obtained from the
O
−
C
curve. These results support the conclusion that massive contact binaries are formed from mass transfer between the two components and only some systems can evolve into the contact stage.
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