ABSTRACT
Fragile X syndrome (FXS) is the leading inherited cause of intellectual disability, resulting from the lack of functional fragile X mental retardation protein (FMRP), an mRNA binding protein mainly serving as a translational regulator. Loss of FMRP leads to dysregulation of target mRNAs. The Drosophila model of FXS show an abnormal circadian rhythm with disruption of the output pathway downstream of the clock network. Yet the FMRP targets involved in circadian regulation have not been identified. Here, we identified collapsing response mediator protein (CRMP) mRNA as a target of FMRP. Knockdown of pan-neuronal CRMP expression ameliorated the circadian defects and abnormal axonal structures of clock neurons (ventral lateral neurons) in dfmr1 mutant flies. Furthermore, specific reduction of CRMP in the downstream output insulin-producing cells attenuated the aberrant circadian behaviors. Molecular analyses revealed that FMRP binds with CRMP mRNA and negatively regulates its translation. Our results indicate that CRMP is an FMRP target and establish an essential role for CRMP in the circadian output in FXS Drosophila.
ABSTRACT
Listeria monocytogenes (Lm) is zoonotic pathogen that can cause listeriosis, and vaccine is one of the effective methods to prevent this pathogen infection. In this study, we developed a novel vaccine that is a mixture of inactivated bacteria and Montanide™ ISA 61 VG, a mineral oil adjuvant, and evaluated the safety and immune response characteristics of this vaccine. The mice immunized with the ISA 61 VG adjuvant had high safety, and it could induce significantly higher titer of anti-listeriolysin O (LLO) antibody and higher value of IgG2a/IgG1 ratio compared with the group without the adjuvant. In particular, it could provide 100% immune protection against lethal doses of Lm challenge in mice. In summary, ISA 61VG adjuvant significantly enhanced the ability of inactivated listeria vaccine to induce humoral and cellular immune responses, thereby enhanced the protective immune response in the host, and it is a potential vaccine candidate for the prevention of Lm infection in humans and animals.
Subject(s)
Animals , Mice , Adjuvants, Immunologic , Pharmacology , Hemolysin Proteins , Allergy and Immunology , Pharmacology , Immunity, Cellular , Listeria monocytogenes , Allergy and Immunology , Listeriosis , Mice, Inbred BALB C , Vaccines, Inactivated , Allergy and ImmunologyABSTRACT
Objective To analyze the clinical characteristics of patients with metastatic carcinoma of bone. Methods The clinical data of 217 patients with metastatic carcinoma of bone was retrospectively analyzed. The clinical features were summarized,including primary tumor,age distribution,first symptom,time of onset and bone metastatic site. Visual analogue scale(VAS)was used to evaluate the difference of pain in patients with bone metastases before and after zoledronic acid treatment. Results The bone metastasis occurred more frequently in men(male:female = 1.28:1). The majority of primary tumors were lung cancer(51.61％)and breast cancer (15.67％),respectively. The peak ages of the patients with metastatic carcinoma of bone were between 50 and 70 years old. Most of the patients with metastatic carcinoma of bone initially showed varying degrees of pain ,some of the patients with dysfunction,pathological fracture,or local lumps as the initial symptoms,only a tiny minority of patients were inadvertently found. Onset time was often within 3 months ,which accountings for 54.84％. Bone metastases were mostly in the spine,pelvis,femur and ribs,and most of the bone metastases were multiple. The VAS score of 108 patients who with bone metastases pain treated by zoledronic acid was 0～4(1.31 ± 1.07),with statistically significant differences compared with pretherapy(P<0.01). Conclusion In order to reduce the pain of patients,and to improve the quality of life and prolong the survival time,bone metastases should be diagnosed early and given comprehensive treatment.
ABSTRACT
Objective To analyze the clinical characteristics of patients with metastatic carcinoma of bone. Methods The clinical data of 217 patients with metastatic carcinoma of bone was retrospectively analyzed. The clinical features were summarized,including primary tumor,age distribution,first symptom,time of onset and bone metastatic site. Visual analogue scale(VAS)was used to evaluate the difference of pain in patients with bone metastases before and after zoledronic acid treatment. Results The bone metastasis occurred more frequently in men(male:female = 1.28:1). The majority of primary tumors were lung cancer(51.61％)and breast cancer (15.67％),respectively. The peak ages of the patients with metastatic carcinoma of bone were between 50 and 70 years old. Most of the patients with metastatic carcinoma of bone initially showed varying degrees of pain ,some of the patients with dysfunction,pathological fracture,or local lumps as the initial symptoms,only a tiny minority of patients were inadvertently found. Onset time was often within 3 months ,which accountings for 54.84％. Bone metastases were mostly in the spine,pelvis,femur and ribs,and most of the bone metastases were multiple. The VAS score of 108 patients who with bone metastases pain treated by zoledronic acid was 0～4(1.31 ± 1.07),with statistically significant differences compared with pretherapy(P<0.01). Conclusion In order to reduce the pain of patients,and to improve the quality of life and prolong the survival time,bone metastases should be diagnosed early and given comprehensive treatment.
ABSTRACT
Ebola virus (EBOV) harbors an RNA genome encapsidated by nucleoprotein (NP) along with other viral proteins to form a nucleocapsid complex. Previous Cryo-eletron tomography and biochemical studies have shown the helical structure of EBOV nucleocapsid at nanometer resolution and the first 450 amino-acid of NP (NPΔ451-739) alone is capable of forming a helical nucleocapsid-like complex (NLC). However, the structural basis for NP-NP interaction and the dynamic procedure of the nucleocapsid assembly is yet poorly understood. In this work, we, by using an E. coli expression system, captured a series of images of NPΔ451-739 conformers at different stages of NLC assembly by negative-stain electron microscopy, which allowed us to picture the dynamic procedure of EBOV nucleocapsid assembly. Along with further biochemical studies, we showed the assembly of NLC is salt-sensitive, and also established an indispensible role of RNA in this process. We propose the diverse modes of NLC elongation might be the key determinants shaping the plasticity of EBOV virions. Our findings provide a new model for characterizing the self-oligomerization of viral nucleoproteins and studying the dynamic assembly process of viral nucleocapsid in vitro.