The ClpP protease homologue is required for the transmission traits and cell division of the pathogen Legionella pneumophila

<p>Abstract</p> <p>Background</p> <p><it>Legionella pneumophila</it>, the intracellular bacterial pathogen that causes Legionnaires' disease, exhibit characteristic transmission traits such as elevated stress tolerance, shortened length and virulence during the transition from the replication phase to the transmission phase. ClpP, the catalytic core of the Clp proteolytic complex, is widely involved in many cellular processes via the regulation of intracellular protein quality.</p> <p>Results</p> <p>In this study, we showed that ClpP was required for optimal growth of <it>L. pneumophila </it>at high temperatures and under several other stress conditions. We also observed that cells devoid of <it>clpP </it>exhibited cell elongation, incomplete cell division and compromised colony formation. Furthermore, we found that the <it>clpP</it>-deleted mutant was more resistant to sodium stress and failed to proliferate in the amoebae host <it>Acanthamoeba castellanii</it>.</p> <p>Conclusions</p> <p>The data present in this study illustrate that the ClpP protease homologue plays an important role in the expression of transmission traits and cell division of <it>L. pneumophila</it>, and further suggest a putative role of ClpP in virulence regulation.</p

Profiling Caenorhabditis elegans non-coding RNA expression with a combined microarray

Small non-coding RNAs (ncRNAs) are encoded by genes that function at the RNA level, and several hundred ncRNAs have been identified in various organisms. Here we describe an analysis of the small non-coding transcriptome of Caenorhabditis elegans, microRNAs excepted. As a substantial fraction of the ncRNAs is located in introns of protein-coding genes in C.elegans, we also analysed the relationship between ncRNA and host gene expression. To this end, we designed a combined microarray, which included probes against ncRNA as well as host gene mRNA transcripts. The microarray revealed pronounced differences in expression profiles, even among ncRNAs with housekeeping functions (e.g. snRNAs and snoRNAs), indicating distinct developmental regulation and stage-specific functions of a number of novel transcripts. Analysis of ncRNA–host mRNA relations showed that the expression of intronic ncRNA loci with conserved upstream motifs was not correlated to (and much higher than) expression levels of their host genes. Even promoter-less intronic ncRNA loci, though showing a clear correlation to host gene expression, appeared to have a surprising amount of ‘expressional freedom’, depending on host gene function. Taken together, our microarray analysis presents a more complete and detailed picture of a non-coding transcriptome than hitherto has been presented for any other multicellular organism

Acupuncture for menstruation-related migraine prophylaxis:A multicenter randomized controlled trial

OBJECTIVE: The aim of this study was to evaluate the efficacy of acupuncture, an alternative medicine therapy, as a preventive treatment for menstruation-related migraine (MRM). PATIENTS AND METHODS: This was a prospective, multicenter, double-dummy, participant-blinded, randomized controlled clinical trial conducted in China between 1 April 2013, and 30 April 2014. The participants were enrolled from four study centers and randomized to into either the acupuncture group, which received 24 sessions of acupuncture at traditional acupoints plus placebo, or the medication group, which received sham acupuncture plus naproxen. The primary endpoint was change from the baseline average number of migraine days per perimenstrual period over cycles 1−3. The secondary endpoints included changes from the baseline average number of migraine days outside the perimenstrual period, mean number of migraine hours during and outside the perimenstrual period, mean visual analog scale score during and outside the perimenstrual period, ≥50% migraine responder rate, and the proportion of participants who used acute pain medication over cycles 1−3 and 4−6. RESULTS: A total of 172 women with MRM were enrolled; 170 in the intention-to-treat analyses. Our primary outcome reported a significant between-group difference that favored the acupuncture group (95% CI, 0.17–0.50; P < 0.001), with the average reduction of migraine days per perimenstrual period from the baseline was 0.94 (95% CI, 0.82–1.07) in the acupuncture group and 0.61 (95% CI, 0.50–0.71) in the medication group over cycles 1−3. CONCLUSION: This study showed that compared to medication, acupuncture reduces the number of migraine days experienced by patients with MRM. For patients who received the acupuncture treatment over three cycles, the preventive effect of the therapy was sustained for six cycles. CLINICAL TRIAL REGISTRATION: [https://www.isrctn.com/ISRCTN57133712], identifier [ISRCTN15663606]

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Additional file 1: Figure S1. of ClpP-deletion impairs the virulence of Legionella pneumophila and the optimal translocation of effector proteins

Immunoblots of whole-cell bacterial extracts expressing indicated Cya hybrid proteins from the wild type (Lp02) and the clpP mutant (Xp02) probed with monoclonal antibody specific to the CyaA epitope (Santa Cruz Biotechnology sc-13582) and ICDH with anti-ICDH antibody (a kind gift with Dr. Vogel JP). (TIF 3783 kb

Two Synthetic Peptides Corresponding to the Human Follicle-Stimulating Hormone β-Subunit Promoted Reproductive Functions in Mice

A follicle stimulating hormone (FSH) is widely used in the assisted reproduction and a synthetic peptide corresponding to a receptor binding region of the human (h) FSH-β-(34–37) (TRDL) modulated reproduction. Furthermore, a 13-amino acid sequence corresponding to hFSH-β-(37–49) (LVYKDPARPKIQK) was recently identified as the receptor binding site. We hypothesized that the synthetic peptides corresponding to hFSH-β-(37–49) and hFSH-β-(34–49), created by merging hFSH-β-(34–37) and hFSH-β-(37–49), modulate the reproductive functions, with the longer peptide being more biologically active. In male or female prepubertal mice, a single injection of 200 μg/g BW ip of hFSH-β-(37–49) or hFSH-β-(34–49) hastened (p p p Ccnd2 and Cyp19a1, respectively. In adult female mice, 200 μg/g BW ip of either peptide during diestrus antagonized the FSH-stimulated estradiol increase and uterine weight gain during proestrus. Furthermore, hFSH-β-(34–49) was a more potent (p < 0.05) reproductive modulator than hFSH-β-(37–49), both in vivo and in vitro. We concluded that hFSH-β-(37–49) and especially hFSH-β-(34–49), have the potential for reproductive modulation