Ion channel function of aquaporin-1 natively expressed in choroid plexus

Aquaporins are known as water channels; however, an additional ion channel function has been observed for several including aquaporin-1 (AQP1). Using primary cultures of rat choroid plexus, a brain tissue that secretes CSF and abundantly expresses AQP1, we confirmed the ion channel function of AQP1 and assessed its functional relevance. The cGMP-gated cationic conductance associated with AQP1 is activated by an endogenous receptor guanylate cyclase for atrial natriuretic peptide (ANP). Fluid transport assays with confluent polarized choroid plexus cultures showed that AQP1 current activation by 4.5 μM ANP decreases the normal basal-to-apical fluid transport in the choroid plexus; conversely, AQP1 block with 500 μM Cd²⁺ restores fluid transport. The cGMP-gated conductance in the choroid plexus is lost with targeted knockdown of AQP1 by small interfering RNA (siRNA), as confirmed by immunocytochemistry and whole-cell patch electrophysiology of transiently transfected cells identified by enhanced green fluorescent protein. The properties of the current (permeability to Na⁺, K⁺, TEA⁺, and Cs⁺; voltage insensitivity; and dependence on cGMP) matched properties characterized previously in AQP1-expressing oocytes. Background K⁺ and Cl⁻ currents in the choroid plexus were dissected from AQP1 currents using Cs-methanesulfonate recording salines; the background currents recorded in physiological salines were not affected by AQP1–siRNA treatment. These results confirm that AQP1 can function as both a water channel and a gated ion channel. The conclusion that the AQP1-associated cation current contributes to modulating CSF production resolves a lingering concern as to whether an aquaporin ionic conductance can have a physiologically relevant function.Daniela Boassa, W. Daniel Stamer and Andrea J. Yoo

Ethical procedures and patient consent differ in Europe

BACKGROUND: Research ethics approvals, procedures and requirements for institutional research ethics committees vary considerably by country and by type of organisation. OBJECTIVE: To evaluate the requirements and procedures of research ethics committees, details of patient information and informed consent based on a multicentre European trial. DESIGN: Survey of European hospitals participating in the prospective observational study on chronic postsurgical pain (euCPSP) using electronic questionnaires. SETTING: Twenty-four hospitals in 11 European countries. PARTICIPANTS: From the 24 hospitals, 23 local investigators responded; 23 answers were analysed. OUTCOME MEASURES: Comparison of research ethics procedures and committee requirements from the perspective of clinical researchers. Comparison of the institutions' procedures regarding patient information and consent. Description of further details such as costs and the duration of the approval process. RESULTS: The approval process lasted from less than 2 weeks up to more than 2 months with financial fees varying between 0 and 575 €. In 20 hospitals, a patient information sheet of variable length (half page up to two pages) was provided. Requirements for patients' informed consent differed. Written informed consent was mandatory at 12, oral at 10 and no form of consent at one hospital. Details such as enough time for consideration, possibility for withdrawal and risks/benefits of participation were provided in 25 to 30% of the institutions. CONCLUSION: There is a considerable variation in the administrative requirements for approval procedures by research ethics committees in Europe. This results in variation of the extent of information and consent procedures for the patients involved

Pain Management in Patients with Cancer: Focus on Opioid Analgesics

Cancer pain is generally treated with pharmacological measures, relying on using opioids alone or in combination with adjuvant analgesics. Weak opioids are used for mild-to-moderate pain as monotherapy or in a combination with nonopioids. For patients with moderate-to-severe pain, strong opioids are recommended as initial therapy rather than beginning treatment with weak opioids. Adjunctive therapy plays an important role in the treatment of cancer pain not fully responsive to opioids administered alone (ie, neuropathic, bone, and visceral colicky pain). Supportive drugs should be used wisely to prevent and treat opioids’ adverse effects. Understanding the pharmacokinetics, pharmacodynamics, interactions, and cautions with commonly used opioids can help determine appropriate opioid selection for individual cancer patients

A Search for Jet Handedness in Hadronic Z0Z^0 Decays

We have searched for signatures of polarization in hadronic jets from $Z^0 \to q \bar{q}$ decays using the ``jet handedness'' method. The polar angle asymmetry induced by the high SLC electron-beam polarization was used to separate quark jets from antiquark jets, expected to be left- and right-polarized, respectively. We find no evidence for jet handedness in our global sample or in a sample of light quark jets and we set upper limits at the 95% C.L. of 0.063 and 0.099 respectively on the magnitude of the analyzing power of the method proposed by Efremov {\it et al.}Comment: Revtex, 8 pages, 2 figure

Different pathways of molecular pathophysiology underlie cognitive and motor tauopathy phenotypes in transgenic models for Alzheimer’s disease and frontotemporal lobar degeneration

Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. Acknowledgments From the Berlin Laboratory, we thank Ingo Voigt for performing the injections of the two constructs into the oocytes, Bettina Seelhorst for her extensive technical assistance, Anna Thoma for taking specific care of the animals, and John Horn, Charite Core Facility for electron microscopy for performing expert analyses in ultra-cryosections with immunogold technique. Expert comments on the manuscript from Silke Frahm-Barske (Berlin) are also acknowledged. Special thanks to Bob Switzer at NeuroScience Associates Inc. for embedding, sectioning and staining mouse brains. This work was funded by TauRx Therapeutics, Singapore. C.R.H. and C.M.W. declare that they are officers in TauRx Therapeutics Ltd.Peer reviewedPublisher PD

Measurement of the branching ratios of the Z0 into heavy quarks

We measure the hadronic branching ratios of the Z0 boson into heavy quarks: Rb=Gamma(Z0->bb)/Gamma(Z0->hadrons) and Rc=Gamma(Z0->cc/Gamma(Z0->hadrons) using a multi-tag technique. The measurement was performed using about 400,000 hadronic Z0 events recorded in the SLD experiment at SLAC between 1996 and 1998. The small and stable SLC beam spot and the CCD-based vertex detector were used to reconstruct bottom and charm hadron decay vertices with high efficiency and purity, which enables us to measure most efficiencies from data. We obtain, Rb=0.21604 +- 0.00098(stat.) +- 0.00073(syst.) -+ 0.00012(Rc) and, Rc= 0.1744 +- 0.0031(stat.) +- 0.0020(syst.) -+ 0.0006(Rb)Comment: 37 pages, 8 figures, to be submitted to Phys. Rev. D version 2: changed title to ratios, used common D production fractions for Rb and Rc and corrected Zgamma interference. Identical to PRD submissio

Direct Measurements of A_b and A_c using Vertex/Kaon Charge Tags at SLD

Exploiting the manipulation of the SLC electron-beam polarization, we present precise direct measurements of the parity violation parameters A_c and A_b in the Z boson - c quark and Z boson - b quark coupling. Quark/antiquark discrimination is accomplished via a unique algorithm that takes advantage of the precise SLD CCD vertex detector, employing the net charge of displaced vertices as well as the charge of kaons that emanate from those vertices. From the 1996-98 sample of 400,000 Z decays, produced with an average beam polarization of 73.4%, we find A_c = 0.673 +/- 0.029 (stat.) +/- 0.023 (syst.) and A_b = 0.919 +/- 0.018 (stat.) +/- 0.017 (syst.).Comment: 11 pages, 2 figures, 2 tables, to be submitted to Physical Review Letters; version 2 reflects changes suggested by the refere

Use of local anaesthetics and adjuncts for spinal and epidural anaesthesia and analgesia at German and Austrian University Hospitals: an online survey to assess current standard practice

<p>Abstract</p> <p>Background</p> <p>The present anonymous multicenter online survey was conducted to evaluate the application of regional anaesthesia techniques as well as the used local anaesthetics and adjuncts at German and Austrian university hospitals.</p> <p>Methods</p> <p>39 university hospitals were requested to fill in an online questionnaire, to determine the kind of regional anaesthesia and preferred drugs in urology, obstetrics and gynaecology.</p> <p>Results</p> <p>33 hospitals responded. No regional anaesthesia is conducted in 47% of the minor gynaecological and 44% of the urological operations; plain bupivacaine 0.5% is used in 38% and 47% respectively. In transurethral resections of the prostate and bladder no regional anaesthesia is used in 3% of the responding hospitals, whereas plain bupivacaine 0.5% is used in more than 90%. Regional anaesthesia is only used in selected major gynaecological and urological operations. On the contrary to the smaller operations, the survey revealed a large variety of used drugs and mixtures. Almost 80% prefer plain bupivacaine or ropivacaine 0.5% in spinal anaesthesia in caesarean section. Similarly to the use of drugs in major urological and gynaecological operations a wide range of drugs and adjuncts is used in epidural anaesthesia in caesarean section and spontaneous delivery.</p> <p>Conclusions</p> <p>Our results indicate a certain agreement in short operations in spinal anaesthesia. By contrast, a large variety concerning the anaesthesiological approach in larger operations as well as in epidural analgesia in obstetrics could be revealed, the causes of which are assumed to be primarily rooted in particular departmental structures.</p

Measurement of the Charged Multiplicities in b, c and Light Quark Events from Z0 Decays

Average charged multiplicities have been measured separately in $b$, $c$ and light quark ($u,d,s$) events from $Z^0$ decays measured in the SLD experiment. Impact parameters of charged tracks were used to select enriched samples of $b$ and light quark events, and reconstructed charmed mesons were used to select $c$ quark events. We measured the charged multiplicities: $\bar{n}_{uds} = 20.21 \pm 0.10 (\rm{stat.})\pm 0.22(\rm{syst.})$, $\bar{n}_{c} = 21.28 \pm 0.46(\rm{stat.}) ^{+0.41}_{-0.36}(\rm{syst.})$ $\bar{n}_{b} = 23.14 \pm 0.10(\rm{stat.}) ^{+0.38}_{-0.37}(\rm{syst.})$, from which we derived the differences between the total average charged multiplicities of $c$ or $b$ quark events and light quark events: $\Delta \bar{n}_c = 1.07 \pm 0.47(\rm{stat.})^{+0.36}_{-0.30}(\rm{syst.})$ and $\Delta \bar{n}_b = 2.93 \pm 0.14(\rm{stat.})^{+0.30}_{-0.29}(\rm{syst.})$. We compared these measurements with those at lower center-of-mass energies and with perturbative QCD predictions. These combined results are in agreement with the QCD expectations and disfavor the hypothesis of flavor-independent fragmentation.Comment: 19 pages LaTex, 4 EPS figures, to appear in Physics Letters

Production of D∗+(2010)D^{*+}(2010) mesons by high energy neutrinos from the Tevatron

Charged vector $D^{*+}(2010)$ meson production is studied in a high energy neutrino bubble chamber experiment with mean neutrino energy of 141 GeV. The $D^{*+}$ are produced in $(5.6 \pm 1.8)\%$ of the neutrino charged current interactions, indicating a steep increase of cross section with energy. The mean fractional hadronic energy of the $D^{*+}$ meson is $0.55 \pm 0.06$