A first genetic portrait of synaptonemal complex variation.

The synaptonemal complex (SC) is a proteinaceous scaffold required for synapsis and recombination between homologous chromosomes during meiosis. Although the SC has been linked to differences in genome-wide crossover rates, the genetic basis of standing variation in SC structure remains unknown. To investigate the possibility that recombination evolves through changes to the SC, we characterized the genetic architecture of SC divergence on two evolutionary timescales. Applying a novel digital image analysis technique to spermatocyte spreads, we measured total SC length in 9,532 spermatocytes from recombinant offspring of wild-derived mouse strains with differences in this fundamental meiotic trait. Using this large dataset, we identified the first known genomic regions involved in the evolution of SC length. Distinct loci affect total SC length divergence between and within subspecies, with the X chromosome contributing to both. Joint genetic analysis of MLH1 foci-immunofluorescent markers of crossovers-from the same spermatocytes revealed that two of the identified loci also confer differences in the genome-wide recombination rate. Causal mediation analysis suggested that one pleiotropic locus acts early in meiosis to designate crossovers prior to SC assembly, whereas a second locus primarily shapes crossover number through its effect on SC length. One genomic interval shapes the relationship between SC length and recombination rate, likely modulating the strength of crossover interference. Our findings pinpoint SC formation as a key step in the evolution of recombination and demonstrate the power of genetic mapping on standing variation in the context of the recombination pathway

Design and simulation of shear-tension spring-type quasi-zero stiffness isolator

By connecting the linear compression spring (positive stiffness mechanism) in parallel with the tension spring (negative stiffness mechanism) and using the shear lever mechanism to amplify the motion of the negative stiffness mechanism, a shear-tension spring type quasi-zero stiffness isolation system is constructed, which is suitable for low-frequency and ultra-low-frequency vibration isolation, especially for small-amplitude, low-frequency vibration isolation. In addition, the vibration isolation system has adjustable function. When the mass of the isolated object changes, it is needed to adjust the linear bearing at the bottom of the vertical spring to change the length of the spring, so as to keep the isolation system in the equilibrium position of the quasi-zero state. The results show that the isolator has excellent performance in isolation of low frequency vibration with small and micro amplitude

Effect of sodium stibogluconate in recruiting and awakening immune cells in the pleural fluid of pancreatic cancer: preparation for immunotherapy

Ascites and pleural effusion are recognized complications of pancreatic cancer. These diseases are accompanied by ascites and pleural effusion, and drug treatment is limited by high costs, long hospital stays, and failure rates. Immunotherapy may offer new option, but in most patients with late stages of cancer, immune cells may lose the ability to recognize tumor cells, how to activate their immune cells is a major problem, sodium glucosidate (SSG) is injected into ascites as a protein tyrosine phosphatase inhibitor to wake up immune cells and prepare for immunotherapy. We used single-cell RNA sequencing (scRNA-seq) to investigate whether and how SSG injected into ascites of pancreatic cancer elicits an immune response. Our study showed that the process of SSG fusion treatment of ascites and pleural effusion, the interaction between TandNK cells, MPs cells, monocytes and neutrophils was induced, and large numbers of genes were expressed, resulting in upregulation of immune response, which also approved that SSG is not only used as a protein tyrosine phosphatase inhibitor, but also it works as a protein tyrosine phosphatase inhibitor. It can also be used to regulate immune cell function, recruiting immune cells to the right place with the help of PD-1 or PD-L1 to fight cancer cells in ascites and pleural effusions in cancer patients

Chemical immune conization of precancerous cervical lesions awakens immune cells and restores normal HPV negative and abnormal proliferation

BackgroundCervical cancer is one of the most common and deadly cancers in women, which is closely linked to the persistent infection of high-risk human papillomavirus (HPV). Current treatment of cervical cancer involves radical hysterectomy, radiotherapy, and chemotherapy or a combination.ObjectiveWe investigated if hapten-enhanced intratumoral chemotherapy (HEIC) was effective in boosting immunity for effective treatment of precancerous cervical lesions and HPV infection.Study designWe used single-cell RNA sequencing (scRNA-Seq) to obtain transcriptome profiles of 40,239 cells from biopsies of precancerous cervical lesions from the cervix directly from one patient before the start of HEIC and approximately 1 week after HEIC. The blood samples were taken at the same time as biopsies. We compared the expression characteristics of malignant epithelial cells and immune cells, including epithelial cells, endothelial cells (ECs), fibroblasts, mural cells, T cells, B cells, T and NK neutrophils, mast cells, microparticles (MPs), and platelets, as well as the dynamic changes in cell percentage and cell subtype heterogeneity.ResultsIntratumoral injection of chemotherapy drug plus hapten induces an acute immune response in precancerous cervical lesions with HPV and further awakens immune cells to prevent the abnormal proliferation of the precancerous cells.ConclusionHEIC provides a potential treatment method for cervical cancer and HPV infection tailored to each patient’s condition

A first genetic portrait of synaptonemal complex variation.

The synaptonemal complex (SC) is a proteinaceous scaffold required for synapsis and recombination between homologous chromosomes during meiosis. Although the SC has been linked to differences in genome-wide crossover rates, the genetic basis of standing variation in SC structure remains unknown. To investigate the possibility that recombination evolves through changes to the SC, we characterized the genetic architecture of SC divergence on two evolutionary timescales. Applying a novel digital image analysis technique to spermatocyte spreads, we measured total SC length in 9,532 spermatocytes from recombinant offspring of wild-derived mouse strains with differences in this fundamental meiotic trait. Using this large dataset, we identified the first known genomic regions involved in the evolution of SC length. Distinct loci affect total SC length divergence between and within subspecies, with the X chromosome contributing to both. Joint genetic analysis of MLH1 foci-immunofluorescent markers of crossovers-from the same spermatocytes revealed that two of the identified loci also confer differences in the genome-wide recombination rate. Causal mediation analysis suggested that one pleiotropic locus acts early in meiosis to designate crossovers prior to SC assembly, whereas a second locus primarily shapes crossover number through its effect on SC length. One genomic interval shapes the relationship between SC length and recombination rate, likely modulating the strength of crossover interference. Our findings pinpoint SC formation as a key step in the evolution of recombination and demonstrate the power of genetic mapping on standing variation in the context of the recombination pathway

China’s engagement with development assistance for health in Africa

Abstract Background As an emerging donor in health related development across the world, particularly towards Africa, the People’s Republic of China (PRC) has been increasing its influence within the field of global public health over the past few decades. Yet between the period of 2000 and 2013, little is known about the scope, scale and priority of China’s grant-making programs. Methods Based on data sourced from the China Aid Database (version-1.2), descriptive analyses were applied to analyze the features of 531 health related projects that were undertaken between 2000 and 2013. Spearmen correlation was also performed to assess the relationship between China’s export and aid to recipient countries. Results The total value of China’s grant-making programs in the health related sector between 2000 and 2013 was 5.67 billion USD, with 531 projects undertaken. During the five year period between 2004 and 2008, China had a contribution of 1.54 billion USD, which increased to 3.8 billion USD during the five year period between 2009 and 2013 – an 146.26% increase. In terms of specific diseases, China is most concerned with building an African public health system through donations targeted towards general health (313 projects), combating Malaria (115 projects) and maternal, neonatal and child health (MNCH), (12 projects). When it comes to recipient countries, if counted in total value, Zimbabwe received the most financial assistance from China, totaling 1.08 billion USD and 19 projects, while Angola and Tanzania received more projects - 30 and 29 projects respectively. In terms of the channeling of aid funding, most projects were targeted towards infrastructure, equipment and medicine (304 projects in total), followed by medical teams (189 projects). Moreover, there is a statistically significant relationship between aid to Africa and Chinese exports to Africa. Conclusion During the past decade, Chinese aid projects played an important role in the African public health system through providing funding for infrastructure, equipment and medicine, training health professionals, as well as disease treatment. However, very limited attention was paid towards disease prevention, health promotion and awareness initiatives, and health education. Furthermore, serious questions were raised regarding the long-term financial sustainability and actual impact these projects have on health development

Successful targeting in situ of an oncogenic nuclear antigen by hapten induced tumor associated autoantibodies (iTAA)

Abstract The abscopal is a hypothesis for treating of non-irradiated tumors after localized radiation therapy. It is associated with the products of tumor-associated gene as autoantibodies (aTAAs) in reaction to the tumor-associated antigens (TAAs), with increasing of anti-MAGEA3 and an relationship between the abscopal effect and immune response. The hapten enhanced local chemotherapy (HELC) was studied to kills tumor and release tumor TAAs, then hapten modify the TAAs to neu-TAAs, to produce tumor autologous antibodies, called induced tumor-associated autoantibodies (iTAAs) that is different from natural TAAs. Since the iTAAs and complement (C) are associated with cancer therapy Immunofluorescence (IF) was applied to evaluate the expression of the iTAAs and C3, C5, C9. Traces resulted in a partial staining of the nucleus in C3’s perinuclear reaction. The iTTAs of Survivin, C-MYC, and IMP1 increased significantly in the tumor cells' intranuclear regions (P = 0.02, P = 0.00, P < 0.0001). Koc, zeta, RalA, and p53 had a similar trend in the perinuclear regions (P < 0.0001, P = 0.004, P < 0.0001, P = 0.003). Therefore, we can propose that tumor antigens inside the cancer cells’ nuclei are targeted by the iTAAs since the iTAAs binding levels are higher after HELC. The iTAA tagging oncogenic nuclear antigens may play a distinctive role in regulating tumor cell growth

Rapid and slow progressors differ by a single MHC class I haplotype in a family of MHC-defined rhesus macaques infected with SIV

Highly polymorphic HLA class I molecules may influence rates of disease progression of HIV-infected individuals. Recent evidence suggests that individuals who mount vigorous CTL responses to multiple HIV-1 epitopes have reduced viral loads, and survive longer than individuals that make a less robust or less diverse CTL response. It has been difficult, however, to define associations between particular HLA class I alleles and rates of disease progression. This may be due, in part, to the uncontrolled variables associated with naturally acquired HIV infections. Studies using MHC-defined, non-human primates infected with well characterized viral stocks should help to clarify this relationship. To explore the possibility that MHC class I polymorphism can influence disease progression, we infected four Mamu-DRB-identical individuals from a family of MHC-defined rhesus macaques intravenously with 40 TCID 50SIV mac239. Two of these macaques developed severe wasting and were euthanized within 80 days of infection, while the other two survived for more than 400 days without showing any symptoms of disease. Since all four of these macaques were Mamu-DRB-identical, we were able to exclude the MHC class II DRB loci as determinant of disease progression. Interestingly, both of the slow progressors made CTL responses to the same three SIV CTL epitopes, which were restricted by two molecules (Mamu-B*03 and B*04) encoded by their common maternal haplotype. The two rapid progressors did not share this haplotype with the slow progressors, and we were unable to detect CTL responses in these two siblings. These observations implicate products of the Mamu-B*03 and B*04 alleles in resistance to disease progression in this family of SIV-infected macaques, and provide additional evidence that certain MHC class I-restricted CTL responses may play a significant role in delaying the onset of AIDS

Novel Two-Step Process in Cellulose Depolymerization : Hematite-Mediated Photocatalysis by Lytic Polysaccharide Monooxygenase and Fenton Reaction

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