Phototriggered Complex Motion by Programmable Construction of Light-Driven Molecular Motors in Liquid Crystal Networks

Recent developments in artificial molecular machines have enabled precisely controlled molecular motion, which allows several distinct mechanical operations at the nanoscale. However, harnessing and amplifying molecular motion along multiple length scales to induce macroscopic motion are still major challenges and comprise an important next step toward future actuators and soft robotics. The key to addressing this challenge relies on effective integration of synthetic molecular machines in a hierarchically aligned structure so numerous individual molecular motions can be collected in a cooperative way and amplified to higher length scales and eventually lead to macroscopic motion. Here, we report the complex motion of liquid crystal networks embedded with molecular motors triggered by single-wavelength illumination. By design, both racemic and enantiomerically pure molecular motors are programmably integrated into liquid crystal networks with a defined orientation. The motors have multiple functions acting as cross-linkers, actuators, and chiral dopants inside the network. The collective rotary motion of motors resulted in multiple types of motion of the polymeric film, including bending, wavy motion, fast unidirectional movement on surfaces, and synchronized helical motion with different handedness, paving the way for the future design of responsive materials with enhanced complex functions

A Novel Endothelial L-Selectin Ligand Activity in Lymph Node Medulla That Is Regulated by α(1,3)-Fucosyltransferase-IV

Lymphocytes home to peripheral lymph nodes (PLNs) via high endothelial venules (HEVs) in the subcortex and incrementally larger collecting venules in the medulla. HEVs express ligands for L-selectin, which mediates lymphocyte rolling. L-selectin counterreceptors in HEVs are recognized by mAb MECA-79, a surrogate marker for molecularly heterogeneous glycans termed peripheral node addressin. By contrast, we find that medullary venules express L-selectin ligands not recognized by MECA-79. Both L-selectin ligands must be fucosylated by α(1,3)-fucosyltransferase (FucT)-IV or FucT-VII as rolling is absent in FucT-IV+VII−/− mice. Intravital microscopy experiments revealed that MECA-79–reactive ligands depend primarily on FucT-VII, whereas MECA-79–independent medullary L-selectin ligands are regulated by FucT-IV. Expression levels of both enzymes paralleled these anatomical distinctions. The relative mRNA level of FucT-IV was higher in medullary venules than in HEVs, whereas FucT-VII was most prominent in HEVs and weak in medullary venules. Thus, two distinct L-selectin ligands are segmentally confined to contiguous microvascular domains in PLNs. Although MECA-79–reactive species predominate in HEVs, medullary venules express another ligand that is spatially, antigenically, and biosynthetically unique. Physiologic relevance for this novel activity in medullary microvessels is suggested by the finding that L-selectin–dependent T cell homing to PLNs was partly insensitive to MECA-79 inhibition

The α(1,3)fucosyltransferases FucT-IV and FucT-VII Exert Collaborative Control over Selectin-Dependent Leukocyte Recruitment and Lymphocyte Homing

AbstractE-, P-, and L-selectin counterreceptor activities, leukocyte trafficking, and lymphocyte homing are controlled prominently but incompletely by α(1,3)fucosyltransferase FucT-VII-dependent fucosylation. Molecular determinants for FucT-VII-independent leukocyte trafficking are not defined, and evidence for contributions by or requirements for other FucTs in leukocyte recruitment is contradictory and incomplete. We show here that inflammation-dependent leukocyte recruitment retained in FucT-VII deficiency is extinguished in FucT-IV−/−/FucT-VII−/− mice. Double deficiency yields an extreme leukocytosis characterized by decreased neutrophil turnover and increased neutrophil production. FucT-IV also contributes to HEV-born L-selectin ligands, since lymphocyte homing retained in FucT-VII−/− mice is revoked in FucT-IV−/−/FucT-VII−/− mice. These observations reveal essential FucT-IV-dependent contributions to E-, P-, and L-selectin ligand synthesis and to the control of leukocyte recruitment and lymphocyte homing

MiR130b from Schlafen4+ MDSCs stimulates epithelial proliferation and correlates with preneoplastic changes prior to gastric cancer

The myeloid differentiation factor Schlafen4 (Slfn4) marks a subset of myeloid-derived suppressor cells (MDSCs) in the stomach during Helicobacter-induced spasmolytic polypeptide-expressing metaplasia (SPEM). OBJECTIVE: To identify the gene products expressed by Slfn4+-MDSCs and to determine how they promote SPEM. DESIGN: We performed transcriptome analyses for both coding genes (mRNA by RNA-Seq) and non-coding genes (microRNAs using NanoString nCounter) using flow-sorted SLFN4+ and SLFN4- cells from Helicobacter-infected mice exhibiting metaplasia at 6 months postinfection. Thioglycollate-elicited myeloid cells from the peritoneum were cultured and treated with IFNα to induce the T cell suppressor phenotype, expression of MIR130b and SLFN4. MIR130b expression in human gastric tissue including gastric cancer and patient sera was determined by qPCR and in situ hybridisation. Knockdown of MiR130b in vivo in Helicobacter-infected mice was performed using Invivofectamine. Organoids from primary gastric cancers were used to generate xenografts. ChIP assay and Western blots were performed to demonstrate NFκb p65 activation by MIR130b. RESULTS: MicroRNA analysis identified an increase in MiR130b in gastric SLFN4+ cells. Moreover, MIR130b colocalised with SLFN12L, a human homologue of SLFN4, in gastric cancers. MiR130b was required for the T-cell suppressor phenotype exhibited by the SLFN4+ cells and promoted Helicobacter-induced metaplasia. Treating gastric organoids with the MIR130b mimic induced epithelial cell proliferation and promoted xenograft tumour growth. CONCLUSION: Taken together, MiR130b plays an essential role in MDSC function and supports metaplastic transformation.Open access articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

The Mitochondrial Genome of Baylisascaris procyonis

BACKGROUND: Baylisascaris procyonis (Nematoda: Ascaridida), an intestinal nematode of raccoons, is emerging as an important helminthic zoonosis due to serious or fatal larval migrans in animals and humans. Despite its significant veterinary and public health impact, the epidemiology, molecular ecology and population genetics of this parasite remain largely unexplored. Mitochondrial (mt) genomes can provide a foundation for investigations in these areas and assist in the diagnosis and control of B. procyonis. In this study, the first complete mt genome sequence of B. procyonis was determined using a polymerase chain reaction (PCR)-based primer-walking strategy. METHODOLOGY/PRINCIPAL FINDINGS: The circular mt genome (14781 bp) of B. procyonis contained 12 protein-coding, 22 transfer RNA and 2 ribosomal RNA genes congruent with other chromadorean nematodes. Interestingly, the B. procyonis mtDNA featured an extremely long AT-rich region (1375 bp) and a high number of intergenic spacers (17), making it unique compared with other secernentean nematodes characterized to date. Additionally, the entire genome displayed notable levels of AT skew and GC skew. Based on pairwise comparisons and sliding window analysis of mt genes among the available 11 Ascaridida mtDNAs, new primer pairs were designed to amplify specific short fragments of the genes cytb (548 bp fragment) and rrnL (200 bp fragment) in the B. procyonis mtDNA, and tested as possible alternatives to existing mt molecular beacons for Ascaridida. Finally, phylogenetic analysis of mtDNAs provided novel estimates of the interrelationships of Baylisasaris and Ascaridida. CONCLUSIONS/SIGNIFICANCE: The complete mt genome sequence of B. procyonis sequenced here should contribute to molecular diagnostic methods, epidemiological investigations and ecological studies of B. procyonis and other related ascaridoids. The information will be important in refining the phylogenetic relationships within the order Ascaridida and enriching the resource of markers for systematic, population genetic and evolutionary biological studies of parasitic nematodes of socio-economic importance

Illegal births and legal abortions – the case of China

BACKGROUND: China has a national policy regulating the number of children that a woman is allowed to have. The central concept at the individual level application is "illegal pregnancy". The purpose of this article is to describe and problematicize the concept of illegal pregnancy and its use in practice. METHODS: Original texts and previous published and unpublished reports and statistics were used. RESULTS: By 1979 the Chinese population policy was clearly a policy of controlling population growth. For a pregnancy to be legal, it has to be defined as such according to the family-level eligibility rules, and in some places it has to be within the local quota. Enforcement of the policy has been pursued via the State Family Planning (FP) Commission and the Communist Party (CP), both of which have a functioning vertical structure down to the lowest administrative units. There are various incentives and disincentives for families to follow the policy. An extensive system has been created to keep the contraceptive use and pregnancy status of all married women at reproductive age under constant surveillance. In the early 1990s FP and CP officials were made personally responsible for meeting population targets. Since 1979, abortion has been available on request, and the ratio of legal abortions to birth increased in the 1980s and declined in the 1990s. Similar to what happens in other Asian countries with low fertility rates and higher esteem for boys, both national- and local-level data show that an unnaturally greater number of boys than girls are registered as having been born. CONCLUSION: Defining a pregnancy as "illegal" and carrying out the surveillance of individual women are phenomena unique in China, but this does not apply to other features of the policy. The moral judgment concerning the policy depends on the basic question of whether reproduction should be considered as an individual or social decision