The RNA-binding protein HuR contributes to neuroinflammation by promoting C-C chemokine receptor 6 (CCR6) expression on Th17 cells.

In both multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), the C-C chemokine receptor 6 (CCR6) is critical for pathogenic T helper 17 (Th17) cell migration to the central nervous system (CNS). Whereas many cytokines and their receptors are potently regulated via post-transcriptional mechanisms in response to various stimuli, how CCR6 expression is post-transcriptionally regulated in Th17 cells is unknown. Here, using RNA-binding protein HuR conditional knock-out (KO) and wild-type (WT) mice, we present evidence that HuR post-transcriptionally regulates CCR6 expression by binding to and stabilizing Ccr6 mRNA and by promoting CCR6 translation. We also found that HuR down-regulates several microRNA expressions, which could target the 3\u27-UTR of Ccr6 mRNA for decay. Accordingly, knock-out of HuR reduced CCR6 expression on Th17 cells and impaired their migration to CNS compared with the response of WT Th17 cells and thereby ameliorated EAE. Together, these findings highlight how HuR contributes to Th17 cell-mediated autoimmune neuroinflammation and support the notion that targeting HuR might be a potential therapeutic intervention for managing autoimmune disorders of the CNS

Nurse staffing and workload drivers in small rural hospitals: An imperative for evidence

Purpose: The aim of this study was to explore staffing issues and the workload drivers influencing nursing activities in designated small rural hospitals of Western Australia. A problem for small rural hospitals is an imbalance between nurse staffing resources and work activity. Sample: A purposive sample of 17 nurse leaders employed at designated small rural hospitals in Western Australia. Method: A qualitative research design was used. Data were collected by focus group and semi-structured interviews and review of Western Australian Country Health Service records. Thematic analysis was used to interpret data. Findings: A minimum nurse staffing model is in use. Staff workload is generated from multiple activities involving 24-hour emergency services, inpatient care, and other duties associated with a lack of clinical and administrative services. These factors together impact on nursing staff resources and the skill mix required to ensure the safety and quality of patient care. Conclusion: Nurse staffing for small rural hospitals needs site-specific recording techniques for workload measurement, staff utilisation and patient outcomes. It is imperative that evidence guide nurse staffing decisions and that the workload driving nursing activity is reviewed

Implementing a Film Series for Community Engagement

This paper will review the experiences of the LSU Libraries with its film series, which has been running to this point for two years. The authors will investigate the nuts and bolts of an academic library initiating a film series, some of the pitfalls and opportunities such a series entails, and how those pitfalls can be managed and opportunities capitalized upon, as well as touching on some theoretical issues related to these matters, such as collaboration between libraries and faculty, the academic library as place, and engagement vs. outreach

Transcriptional Regulation of Chemical Diversity in Aspergillus fumigatus by LaeA

Secondary metabolites, including toxins and melanins, have been implicated as virulence attributes in invasive aspergillosis. Although not definitively proved, this supposition is supported by the decreased virulence of an Aspergillus fumigatus strain, ΔlaeA, that is crippled in the production of numerous secondary metabolites. However, loss of a single LaeA-regulated toxin, gliotoxin, did not recapitulate the hypovirulent ΔlaeA pathotype, thus implicating other toxins whose production is governed by LaeA. Toward this end, a whole-genome comparison of the transcriptional profile of wild-type, ΔlaeA, and complemented control strains showed that genes in 13 of 22 secondary metabolite gene clusters, including several A. fumigatus–specific mycotoxin clusters, were expressed at significantly lower levels in the ΔlaeA mutant. LaeA influences the expression of at least 9.5% of the genome (943 of 9,626 genes in A. fumigatus) but positively controls expression of 20% to 40% of major classes of secondary metabolite biosynthesis genes such as nonribosomal peptide synthetases (NRPSs), polyketide synthases, and P450 monooxygenases. Tight regulation of NRPS-encoding genes was highlighted by quantitative real-time reverse-transcription PCR analysis. In addition, expression of a putative siderophore biosynthesis NRPS (NRPS2/sidE) was greatly reduced in the ΔlaeA mutant in comparison to controls under inducing iron-deficient conditions. Comparative genomic analysis showed that A. fumigatus secondary metabolite gene clusters constitute evolutionarily diverse regions that may be important for niche adaptation and virulence attributes. Our findings suggest that LaeA is a novel target for comprehensive modification of chemical diversity and pathogenicity

Perspectives on conservation impacts of the global primate trade

MFH and DRKN are grateful to Animal Protection Denmark and MFH to the Carlsberg Foundation (grant number CF21-0473). AMM thanks the Whitley Fund for Nature, The Rufford Small Grants, The International Primate Protection League, and Mr. Martin Stanley for their long-term financial support toward night monkey conservation.The global trade in nonhuman primates represents a substantial threat to ecosystem health, human health, and primate conservation worldwide. Most of the primate trade involves trade for pet-keeping, consumption, or biomedical experimentation. We present an overview of international primate trade through five case studies; each describes a different facet of this trade. We draw on published scientific literature, media outlets, and open access datasets, including the CITES Trade Database to build these case studies. Case study 1 describes the role of introduced island populations of Macaca and Chlorocebus in trade for biomedical experimentation; case study 2 covers the global health threats posed by the primate trade, including zoonotic disease transmission once animals enter the trade pipeline; case study 3 addresses the ways that changing patterns of primate trade, from local markets to online, have increased the demand for primates as pets; case study 4 recognizes the role that local environmental activism can play in mitigating trade; and case study 5 shows variation between global regions in their contribution to the primate trade. We recommend greater oversight of primate trade, especially domestic trade within primate range countries, and real-time reporting to CITES to accurately track primate trade. Effective conservation-focused regulations that can minimise the negative effects of primate trade must be tailored to specific regions and species and require transparency, careful regulation, field research, and an understanding of the magnitude of this trade.Peer reviewe

Genomic diversity of Escherichia coli isolates from non-human primates in the Gambia

Increasing contact between humans and non-human primates provides an opportunity for the transfer of potential pathogens or antimicrobial resistance between host species. We have investigated genomic diversity and antimicrobial resistance in Escherichia coli isolates from four species of non-human primates in the Gambia: Papio papio (n=22), Chlorocebus sabaeus (n=14), Piliocolobus badius (n=6) and Erythrocebus patas (n=1). We performed Illumina whole-genome sequencing on 101 isolates from 43 stools, followed by nanopore long-read sequencing on 11 isolates. We identified 43 sequence types (STs) by the Achtman scheme (ten of which are novel), spanning five of the eight known phylogroups of E. coli. The majority of simian isolates belong to phylogroup B2 - characterized by strains that cause human extraintestinal infections - and encode factors associated with extraintestinal disease. A subset of the B2 strains (ST73, ST681 and ST127) carry the pks genomic island, which encodes colibactin, a genotoxin associated with colorectal cancer. We found little antimicrobial resistance and only one example of multi-drug resistance among the simian isolates. Hierarchical clustering showed that simian isolates from ST442 and ST349 are closely related to isolates recovered from human clinical cases (differences in 50 and 7 alleles, respectively), suggesting recent exchange between the two host species. Conversely, simian isolates from ST73, ST681 and ST127 were distinct from human isolates, while five simian isolates belong to unique core-genome ST complexes - indicating novel diversity specific to the primate niche. Our results are of planetary health importance, considering the increasing contact between humans and wild non-human primates

Fibroid explants reveal a higher sensitivity against MDM2-inhibitor nutlin-3 than matching myometrium

<p>Abstract</p> <p>Background</p> <p>Spontaneous cessation of growth is a frequent finding in uterine fibroids. Increasing evidence suggests an important role of cellular senescence in this growth control. Deciphering the underlying mechanisms of growth control that can be expected not only to shed light on the biology of the tumors but also to identify novel therapeutic targets.</p> <p>Methods</p> <p>We have analyzed uterine leiomyomas and matching normal tissue for the expression of p14^Arfand used explants to see if reducing the MDM2 activity using the small-molecule inhibitor nutlin-3 can induce p53 and activate genes involved in senescence and/or apoptosis. For these studies quantitative real-time RT-PCR, Western blots, and immunohistochemistry were used. Statistical analyses were performed using the student's <it>t </it>test.</p> <p>Results</p> <p>An in depth analysis of 52 fibroids along with matching myometrium from 31 patients revealed in almost all cases a higher expression of p14^Arfin the tumors than in the matching normal tissue. In tissue explants, treatment with the MDM2 inhibitor nutlin-3 induced apoptosis as well as senescence as revealed by a dose-dependent increase of the expression of <it>BAX </it>as well as of <it>p21</it>, respectively. Simultaneously, the expression of the proliferation marker Ki-67 drastically decreased. Western-blot analysis identified an increase of the p53 level as the most likely reason for the increased activity of its downstream markers <it>BAX </it>and <it>p21</it>. Because as a rule fibroids express much higher levels of p14^Arf, a major negative regulator of MDM2, than matching myometrium it was then analyzed if fibroids are more sensitive against nutlin-3 treatment than matching myometrium. We were able to show that in most fibroids analyzed a higher sensibility than that of matching myometrium was noted with a corresponding increase of the p53 immunopositivity of the fibroid samples compared to those from myometrium.</p> <p>Conclusions</p> <p>The results show that uterine fibroids represent a cell population of advanced cellular age compared to matching myometrium. Moreover, the data point to members of the p53-network as to potential novel therapeutic targets for the treatment of uterine fibroids.</p

Practice patterns of naturopathic physicians: results from a random survey of licensed practitioners in two US States

BACKGROUND: Despite the growing use of complementary and alternative medicine (CAM) by consumers in the U.S., little is known about the practice of CAM providers. The objective of this study was to describe and compare the practice patterns of naturopathic physicians in Washington State and Connecticut. METHODS: Telephone interviews were conducted with state-wide random samples of licensed naturopathic physicians and data were collected on consecutive patient visits in 1998 and 1999. The main outcome measures were: Sociodemographic, training and practice characteristics of naturopathic physicians; and demographics, reasons for visit, types of treatments, payment source and visit duration for patients. RESULT: One hundred and seventy practitioners were interviewed and 99 recorded data on a total of 1817 patient visits. Naturopathic physicians in Washington and Connecticut had similar demographic and practice characteristics. Both the practitioners and their patients were primarily White and female. Almost 75% of all naturopathic visits were for chronic complaints, most frequently fatigue, headache, and back symptoms. Complete blood counts, serum chemistries, lipids panels and stool analyses were ordered for 4% to 10% of visits. All other diagnostic tests were ordered less frequently. The most commonly prescribed naturopathic therapeutics were: botanical medicines (51% of visits in Connecticut, 43% in Washington), vitamins (41% and 43%), minerals (35% and 39%), homeopathy (29% and 19%) and allergy treatments (11% and 13%). The mean visit length was about 40 minutes. Approximately half the visits were paid directly by the patient. CONCLUSION: This study provides information that will help other health care providers, patients and policy makers better understand the nature of naturopathic care