Synthetic control of living cells by intracellular polymerization

An emerging cellular engineering method creates synthetic polymer matrices inside cells. By contrast with classical genetic, enzymatic, or radioactive techniques, this materials-based approach introduces non-natural polymers inside cells, thus modifying cellular states and functionalities. Here, we cover various materials and chemistries that have been exploited to create intracellular polymer matrices. In addition, we discuss emergent cellular properties due to the intracellular polymerization, including nonreplicating but active metabolism, maintenance of membrane integrity, and resistance to environmental stressors. We also discuss past work and future opportunities for developing and applying synthetic cells that contain intracellular polymers. The materials-based approach will usher in new applications of synthetic cells for broad biotechnological applications

Sex- and age-dependent association of SLC11A1 polymorphisms with tuberculosis in Chinese: a case control study

BACKGROUND: Host genetic factors are important determinants in tuberculosis (TB). The SLC11A1 (or NRAMP1) gene has been studied extensively for genetic association with TB, but with inconsistent findings. In addition, no study has yet looked into the effect of sex and age on the relationship between SLC11A1 polymorphisms and TB. METHODS: A case-control study was conducted. In total, 278 pulmonary TB patients and 282 sex- and age-matched controls without TB were recruited. All subjects were ethnic Chinese. On the basis of linkage disequilibrium pattern, three genetic markers from SLC11A1 and one from the nearby IL8RB locus were selected and examined for association with TB susceptibility. These markers were genotyped using single strand conformation polymorphism analysis or fragment analysis of amplified products. RESULTS: Statistically significant differences in allele (P = 0.0165, OR = 1.51) and genotype (P = 0.0163, OR = 1.59) frequencies of the linked markers SLC6a/b (classically called D543N and 3'UTR) of the SLC11A1 locus were found between patients and controls. With stratification by sex, positive associations were identified in the female group for both allele (P = 0.0049, OR = 2.54) and genotype (P = 0.0075, OR = 2.74) frequencies. With stratification by age, positive associations were demonstrated in the young age group (age ≤65 years) for both allele (P = 0.0047, OR = 2.52) and genotype (P = 0.0031, OR = 2.92) frequencies. All positive findings remained significant even after correction for multiple comparisons. No significant differences were noted in either the male group or the older age group. No significant differences were found for the other markers (one SLC11A1 marker and one IL8RB marker) either. CONCLUSION: This study confirmed the association between SLC11A1 and TB susceptibility and demonstrated for the first time that the association was restricted to females and the young age group

Agents of May Fourth. Jing Yinyu, Xu Zhongnian, and the Early Introduction of Modern Chinese Literature in France

Jing Yinyu (1901-1931?) and Xu Zhongnian (1904-1981) played a pivotal role in the dissemination of modern Chinese literature in France at the turn of the 1930s. Best known as Lu Xun’s first translator into a Western language and a friend of Romain Rolland’s, Jing compiled the Anthologie des conteurs chinois modernes in 1929. In his Anthologie de la littérature chinoise. Des origines à nos jours, published in 1932, Xu also devoted a section to recent literary developments. By analyzing the nature of the two projects, the translated corpora, and their paratexts, I will describe the features of Jing’s and Xu’s dissemination of May Fourth literature in France and scrutinize their artistic and ideological stance vis-à-vis the new literary scene. Ultimately, I will attempt to pinpoint in what terms the two scholars-cum-translators’ agency contributed to foreign readers’ awareness of the cultural, social and political experience of the May Fourth Movement

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Intracranial pressure monitoring alone: Not an absolutely reliable tool after decompressive craniectomy for traumatic acute subdural hematoma

Introduction: The monitoring of intracranial pressure (ICP) in traumatic brain injury (TBI) is important for postoperative care. In our clinical practice, we have found that neurological deterioration because of contralateral epidural hematoma (EDH) occurs despite normal ICP in patients who have undergone decompressive craniectomy (DC). This study was performed to elucidate the dilemmas associated with ICP monitoring after DC and the possible complementary role of intraoperative and immediate postoperative imaging studies. Methods: Patients who had received DC due to TBI during a 7-year period were retrospectively identified from our database and evaluated. Logistic regression analyses were used to evaluate the associations between patients. Results: Twenty patients had contralateral skull fractures. Five patients (5 of 10, 50%) who developed EDH on the ipsilateral side of the skull fracture underwent operations for EDH evacuation due to the deterioration of their clinical condition. The ICP was significantly lower (P = 0.016) in these patients compared with patients who did not undergo secondary surgery due to EDH. Conclusions: ICP monitoring alone cannot absolutely ensure early detection of contralateral space-occupying lesion after DC due to improvement in cerebral compliance. Imaging studies using brain computed tomography is beneficial for early detection of delayed EDH after DC in a high-risk skull fracture with contralateral acute subdural hematoma patients

Supplementary_Table_2_and_3_pancreatic_cancer_herbs_tonic_20181219_final – Supplemental material for Chinese Herbal Medicine Effectively Prolongs the Overall Survival of Pancreatic Cancer Patients: A Case Series

Supplemental material, Supplementary_Table_2_and_3_pancreatic_cancer_herbs_tonic_20181219_final for Chinese Herbal Medicine Effectively Prolongs the Overall Survival of Pancreatic Cancer Patients: A Case Series by Wendy Wong, Bing Zhong Chen, Allyson Kin Yan Lee, Adrian Ho Cheung Chan, Justin Che Yuen Wu and Zhixiu Lin in Integrative Cancer Therapies</p