Neurochemical effects of a 20 kHz magnetic field on the central nervous system in prenatally exposed mice

C57/B1 mice were exposed during pregnancy (gestation days 0–19) to a 20 kHz magnetic field (MF). The asymmetric sawtooth-wave form magnetic field in the exposed racks had a flux density of 15 μT (peak to peak). After 19 days, the exposure was terminated, and the mice were housed individually under normal laboratory conditions. On postnatal day (PD) 1, PD21, and PD308, various neurochemical markers in the brains of the offspring were investigated and the brains weighed. No significant difference was found in the whole brain weight at PD1 or PD21 between exposed offspring and control animals. However, on PD308, a significant decrease in weight of the whole brain was detected in exposed animals. No significant differences were found in the weight of cortex, hippocampus, septum, or cerebellum on any of the sampling occasions, nor were any significant differences detected in protein-, DNA-level, nerve growth factor (NGF), acetylcholine esterase- (AChE), or 2′,3′-cyclic nucle-otide 3′-phosphodiesterase- (CNP; marker for oligodendrocytes) activities on PD21 in cerebellum. Cortex showed a more complex pattern of response to MF: MF treatment resulted in a decrease in DNA level and increases in the activities of CNP, AChE, and NGF protein. On PD308, the amount of DNA was significantly reduced in MF-treated cerebellum and CNP activity was still enhanced in MF-treated cortex compared to controls. Most of the effects of MF treatment during the embryonic period were similar to those induced by ionizing radiation but much weaker. However, the duration of the exposure required to elucidate the response of different markers to MF seems to be greater and effects appear later during development compared to responses to ionizing radiation. © 1995 Wiley-Liss, Inc.     

New peptide alkaloids from Hovenia dulcis and H. tomentella

From the root bark of Hovenia dulcis Thunb. and H. tommentella (Makino) Nakai (Rhamnaceae), three peptide alkaloids, frangulanine, hovenins-A and -B have been isolated. Hovenin-A has been shown to be des-N-methylfrangulanine (II).     

Using,risking, and consent: Why risking harm to bystanders is morally different from risking harm to research subjects

Subjects in studies on humans are used as a means of conducting the research and achieving whatever good would justify putting them at risk. Accordingly, consent must normally be obtained before subjects are exposed to any substantial risks to their welfare. Bystanders are also often put at risk, but they are not used as a means. Accordingly—or so I argue—consent is more often unnecessary before bystanders are exposed to similar substantial risks to their welfare.     

The human–primate interface in the New Normal: Challenges and opportunities for primatologists in the COVID-19 era and beyond

The emergence of SARS-CoV-2 in late 2019 and human responses to the resulting COVID-19 pandemic in early 2020 have rapidly changed many aspects of human behavior, including our interactions with wildlife. In this commentary, we identify challenges and opportunities at human–primate interfaces in light of COVID-19, focusing on examples from Asia, and make recommendations for researchers working with wild primates to reduce zoonosis risk and leverage research opportunities. First, we briefly review the evidence for zoonotic origins of SARS-CoV-2 and discuss risks of zoonosis at the human–primate interface. We then identify challenges that the pandemic has caused for primates, including reduced nutrition, increased intraspecific competition, and increased poaching risk, as well as challenges facing primatologists, including lost research opportunities. Subsequently, we highlight opportunities arising from pandemic-related lockdowns and public health messaging, including opportunities to reduce the intensity of problematic human–primate interfaces, opportunities to reduce the risk of zoonosis between humans and primates, opportunities to reduce legal and illegal trade in primates, new opportunities for research on human–primate interfaces, and opportunities for community education. Finally, we recommend specific actions that primatologists should take to reduce contact and aggression between humans and primates, to reduce demand for primates as pets, to reduce risks of zoonosis in the context of field research, and to improve understanding of human–primate interfaces. Reducing the risk of zoonosis and promoting the well-being of humans and primates at our interfaces will require substantial changes from “business as usual.” We encourage primatologists to help lead the way.     

The Nuffield Council’s green light for genome editing human embryos defies fundamental human rights law

In July 2018, the Nuffield Council on Bioethics released the report Genome editing and human reproduction: Social and ethical issues, concluding that human germline modification of human embryos for implantation is not ‘morally unacceptable in itself’ and could be ethically permissible in certain circumstances once the risks of adverse outcomes have been assessed and the procedure appears ‘reasonably safe’. The Nuffield Council set forth two main principles governing anticipated uses and envisions applications that may include health enhancements as a public health measure. This essay provides a critique of three aspects in the Nuffield Council’s Report: its presumption of therapeutic efficacy, its inflation of parental rights to create a certain type of child, and its reliance on a specially commissioned report that appears to distort key definitions in international law.     

Improved design of peptides exhibiting angiogenic activities for clinical applications

Vascularization is one of the key steps for engraftment in regenerative medicine. Previously one of the authors had discovered peptides exhibiting significant angiogenic activities designated AGP and elucidated the active core. For neovascularization basic fibroblast growth factor is used although permeation can be envisaged. The original AGPs did not suffer from this although their half-life times are short because of decomposition by endogenous enzymes. Several new AGP-libraries have been constructed and their enzymatic resistance has been investigated by the use of human umbilical vein endothelial cells to find candidates for clinical applications.     

The protective effect of WKYMVm peptide on inflammatory osteolysis through regulating NF‐κB and CD9/gp130/STAT3 signalling pathway

The balance between bone formation and bone resorption is closely related to bone homeostasis. Osteoclasts, originating from the monocyte/macrophage lineage, are the only cell type possessing bone resorption ability. Osteoclast overactivity is thought to be the major reason underlying osteoclast‐related osteolytic problems, such as Paget's disease, aseptic loosening of prostheses and inflammatory osteolysis; therefore, disruption of osteoclastogenesis is considered a crucial treatment option for these issues. WKYMVm, a synthetic peptide, which is a potent FPR2 agonist, exerts an immunoregulatory effect. This peptide inhibits the production of inflammatory cytokines, such as (IL)‐1β and TNF‐α, thus regulating inflammation. However, there are only few reports on the role of WKYMVm and FPR2 in osteoclast cytology. In the current study, we found that WKYMVm negatively regulates RANKL‐ and lipopolysaccharide (LPS)‐induced osteoclast differentiation and maturation in vitro and alleviates LPS‐induced osteolysis in animal models. WKYMVm down‐regulated the expression of osteoclast marker genes and resorption activity. Furthermore, WKYMVm inhibited osteoclastogenesis directly through reducing the phosphorylation of STAT3 and NF‐kB and indirectly through the CD9/gp130/STAT3 pathway. In conclusion, our findings demonstrated the potential medicinal value of WKYMVm for the treatment of inflammatory osteolysis.     

Exosomes derived from umbilical cord mesenchymal stem cells alleviate viral myocarditis through activating AMPK/mTOR‐mediated autophagy flux pathway

Human umbilical cord mesenchymal stem cell‐derived exosomes (hucMSC‐exosomes) have been implicated as a novel therapeutic approach for tissue injury repair and regeneration, but the effects of hucMSC‐exosomes on coxsackievirus B3 (CVB3)‐induced myocarditis remain unknown. The object of the present study is to investigate whether hucMSC‐exosomes have therapeutic effects on CVB3‐induced myocarditis (VMC). HucMSC‐exosomes were identified using nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and Western blot. The purified hucMSC‐exosomes tagged with PKH26 were tail intravenously injected into VMC model mice in vivo and used to administrate CVB3‐infected human cardiomyocytes (HCMs) in vitro, respectively. The effects of hucMSC‐exosomes on myocardial pathology injury, proinflammatory cytokines and cardiac function were evaluated through haematoxylin and eosin (H&E) staining, quantitative polymerase chain reaction (qPCR) and Doppler echocardiography. The anti‐apoptosis role and potential mechanism of hucMSC‐exosomes were explored using TUNEL staining, flow cytometry, immunohistochemistry, Ad‐mRFP‐GFP‐LC3 transduction and Western blot. In vivo results showed that hucMSC‐exosomes (50 μg iv) significantly alleviated myocardium injury, shrank the production of proinflammatory cytokines and improved cardiac function. Moreover, in vitro data showed that hucMSC‐exosomes (50 μg/mL) inhibited the apoptosis of CVB3‐infected HCM through increasing pAMPK/AMPK ratio and up‐regulating autophagy proteins LC3II/I, BECLIN‐1 and anti‐apoptosis protein BCL‐2 as well as decreasing pmTOR/mTOR ratio, promoting the degradation of autophagy flux protein P62 and down‐regulating apoptosis protein BAX. In conclusion, hucMSC‐exosomes could alleviate CVB3‐induced myocarditis via activating AMPK/mTOR‐mediated autophagy flux pathway to attenuate cardiomyocyte apoptosis, which will be benefit for MSC‐exosome therapy of myocarditis in the future.     

AVPR1A variation is linked to gray matter covariation in the social brain network of chimpanzees

The vasopressin system has been implicated in the regulation of social behavior and cognition in humans, nonhuman primates and other social mammals. In chimpanzees, polymorphisms in the vasopressin V1a receptor gene (AVPR1A) have been associated with social dimensions of personality, as well as to responses to sociocommunicative cues and mirror self‐recognition. Despite evidence of this association with social cognition and behavior, there is little research on the neuroanatomical correlates of AVPR1A variation. In the current study, we tested the association between AVPR1A polymorphisms in the RS3 promotor region and gray matter covariation in chimpanzees using magnetic resonance imaging and source‐based morphometry. The analysis identified 13 independent brain components, three of which differed significantly in covariation between the two AVPR1A genotypes (DupB?/? and DupB+/?; P < .05). DupB+/? chimpanzees showed greater covariation in gray matter in the premotor and prefrontal cortex, basal forebrain, lunate and cingulate cortex, and lesser gray matter covariation in the superior temporal sulcus and postcentral sulcus. Some of these regions were previously found to differ in vasopressin and oxytocin neural fibers between nonhuman primates, and in AVPR1A gene expression in humans with different RS3 alleles. This is the first report of an association between AVPR1A and gray matter covariation in nonhuman primates, and specifically links an AVPR1A polymorphism to structural variation in the social brain network. These results further affirm the value of chimpanzees as a model species for investigating the relationship between genetic variation, brain structure and social cognition with relevance to psychiatric disorders, including autism.