Overcoming super‐knock down resistance (super‐kdr) mediated resistance: multi‐halogenated benzyl pyrethroids are more toxic to super‐kdr than kdr house flies

Target site insensitivity because of mutations in the voltage‐sensitive sodium channel gene (Vssc) is a major mechanism of resistance to pyrethroid insecticides in the house fly, Musca domestica. There are three known Vssc alleles that confer resistance to pyrethroids in the house fly: knock down resistance (kdr; L1014F), super‐kdr (M918T + L1014F) and kdr‐his (L1014H), but there has been no side‐by‐side comparison of the resistance levels that they confer. We compared the levels of resistance conferred by the three Vssc alleles in congenic strains to 19 structurally diverse pyrethroids, and compared the full‐length Vssc cDNA sequences from each strain. Generally, the levels of resistance conferred were kdr‐his < kdr < super‐kdr. However, there was significant variation in this pattern, especially for super‐kdr, for which both high and low resistance ratios were observed for several pyrethroids. We also examined the levels of resistance in heterozygotes. Resistance in each of the hybrids was generally inherited as an incompletely recessive trait, except for the kdr‐his/kdr hybrids, which showed incompletely to completely dominant resistance (ie had resistance levels comparable to kdr homozygotes). The importance of these results to understanding the frequencies of these resistance alleles in natural populations, the evolution of insecticide resistance and resistance management strategies are discussed.     

An Aminopropyl Carbazole Derivative Induces Neurogenesis by Increasing Final Cell Division in Neural Stem Cells

P7C3 and its derivatives, 1-(3,6-dibromo-9H-carbazol-9-yl)-3-(p-tolylamino)propan-2-ol (1) and N-(3-(3,6-dibromo-9H-carbazol-9-yl)-2-hydroxypropyl)-N-(3-methoxyphenyl)-4-methylbenzenesulfonamide (2), were previously reported to increase neurogenesis in rat neural stem cells (NSCs). Although P7C3 is known to increase neurogenesis by protecting newborn neurons, it is not known whether its derivatives also have protective effects to increase neurogenesis. In the current study, we examined how 1 induces neurogenesis. The treatment of 1 in NSCs increased numbers of cells in the absence of epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2), while not affecting those in the presence of growth factors. Compound 1 did not induce astrocytogenesis during NSC differentiation. 5-Bromo-2′-deoxyuridine (BrdU) pulsing experiments showed that 1 significantly enhanced BrdU-positive neurons. Taken together, our data suggest that 1 promotes neurogenesis by the induction of final cell division during NSC differentiation.     

Editorial: Let's talk about sex – the gender binary revisited

Sex refers to biological differences and gender to socioculturally delineated masculine and feminine roles. Sex or gender are included as a covariate or effect modifier in the majority of child psychology and psychiatry studies, and differences found between boys and girls have inspired many researchers to postulate underlying mechanisms. Empirical tests of whether including these proposed explanatory variables actually reduces the variance explained by gender are lagging behind somewhat. That is a pity, because a lot can be gained from a greater focus on the active agents of specific gender differences. As opposed to biological sex as such, some of the processes explaining why a specific outcome shows gender differences may be changeable and so possible prevention targets. Moreover, while the sex binary may be reasonable adequate as a classification variable, the gender binary is far from perfect. Gender is a multidimensional, partly context-dependent factor, and the dichotomy generally used in research does not do justice to the diversity existing within boys and girls.     

Purine and Its Analogues and Radiation Damage in Bacillus Megaterium Spores

Summary

As an extension of results obtained from radiation studies on caffeine both in other laboratories and more recently in this laboratory using the bacterial spore as the test system, six compounds with chemical structures closely resembling that of caffeine were tested as radiation modifiers. Of these compounds, purine, adenine and hypoxanthine resembled caffeine in sensitizing spores to radiation, while theobromine, xanthine and theophylline did not. These responses are discussed in relation to the electron sequestration hypothesis of cellular sensitization to high-energy radiation.     

Structural design and mechanical behavior of alligator (Alligator mississippiensis) osteoderms

Alligator is a well-adapted living fossil covered with dorsal armor. This dermal shield consists of bony plates, called osteoderms, interconnected by sutures and non-mineralized collagen fibers, providing a dual function of protection and flexibility. Osteoderm features a sandwich structure, combining an inner porous core and an outer dense cortex, to offer enhancements for stiffness and energy absorbance. In this study, we investigated the multi-scale structure and mechanical behaviors of the American alligator (Alligator mississippiensis) osteoderm. Microcomputed tomography was applied to reveal the complex neurovascular network. Through the observation under optical and scanning electron microscopes, the osteoderm was found to consist of woven bone in the dorsal region and lamellar-zonal bone in the ventral region. Nanoindentation and compressive tests were performed to evaluate the mechanical properties of osteoderms. The varying mineral contents and porosity result in a graded mechanical property: a hard and stiff dorsal cortex gradually transform to a more compliant ventral base. Three protective mechanisms optimized for alligator osteoderms were proposed and elucidated.     

TH1/TH2 CYTOKINES IN THE CENTRAL NERVOUS SYSTEM

For the past 20 years it has become increasingly evident that cytokines play an important role in both the normal development of the brain, acting as neurotrophic factors, and in brain injuries. Although cytokines and their receptors are synthesized and expressed in the brain (normally at low levels), increased cytokine production levels are now associated with various neurological disorders. T lymphocytes are the cells responsible for coordinating the immune response and a major source of cytokines. Different cytokines induce different subsets of T cells or have different effects on proliferation within a particular subset. Recent studies suggest that the immune response is in fact regulated by the balance between Th1 and Th2 cytokines. These two pathways are often mutually exclusive, the one resulting in protection and the other in progression of disease. Various studies describe the function and production of proinflammatory cytokines in the central nervous system (CNS) and their role in health and disease. Inflammation is upregulated following activation of Th1 cells, whereas Th2 cells may play a significant role in downregualting Th1 proinflammatory responses in those instances in which there is overproduction of Th2 cytokines. Although both Th1 and Th2 cytokines may influence CNS functioning, most studies have so far dealt with proinflammatory cytokines, probably because they directly affect CNS cells and are thought to be implicated in CNS pathology. It is of interest that endogenous glucocorticoids also control Th1-Th2 balance, favoring Th2 cell development. This review presents the evidence that cytokines have important functions in the CNS, both during development and as a part of brain pathology. In particular, the author highlighted recent work that supports a major role for the so-called inflammatory cytokines, Th1, and the anti-inflammatory Th2 cytokines.     

Alexithymia in neurodegenerative disease

We investigated alexithymia, a deficit in the ability to identify and describe one's emotions, in a sample that included patients with neurodegenerative disease and healthy controls. In addition, we investigated the relationship that alexithymia has with behavioral disturbance and with regional gray matter volumes. Alexithymia was examined with the Toronto Alexithymia Scale-20, behavioral disturbance was assessed with the Neuropsychiatric Inventory, and regional gray matter volumes were obtained from structural magnetic resonance images. Group analyses revealed higher levels of alexithymia in patients than controls. Alexithymia scores were positively correlated with behavioral disturbance (apathy and informant distress, in particular) and negatively correlated with the gray matter volume of the right pregenual anterior cingulate cortex, a region of the brain that is thought to play an important role in self and emotion processing.     

微塑料生殖和胚胎发育毒性的研究进展

目的 研究发现微塑料（粒径小于5 μm的塑料颗粒）在低等生物和哺乳动物中均可诱导生殖毒性和胚胎发育毒性。本文对微塑料在生殖和胚胎中的毒性效应和作用机制进行综述，可为预防和控制微塑料所致生殖毒性提供理论基础和科学依据。方法 以微塑料、暴露途径、毒性机制、生殖毒性、胚胎毒性为关键词在中国知网、PubMed 等数据库检索相关文献，并对国内外相关文献进行归纳与总结。结果 综述微塑料暴露途径及其转运和代谢分布、全面系统地概述微塑料生殖和胚胎发育毒性效应及毒性机制。结论 研究发现微塑料在低等生物和哺乳动物中均可诱导生殖毒性和胚胎发育毒性，但微塑料所致生殖毒性主要局限在表型研究，目前仍缺乏针对微塑料生殖毒性作用机制的系统研究，同时需在人群层面进一步研究。