The Conserved Dcw Gene Cluster of R. sphaeroides Is Preceded by an Uncommonly Extended 5’ Leader Featuring the sRNA UpsM

Cell division and cell wall synthesis mechanisms are similarly conserved among bacteria. Consequently some bacterial species have comparable sets of genes organized in the dcw (division and cell wall) gene cluster. Dcw genes, their regulation and their relative order within the cluster are outstandingly conserved among rod shaped and gram negative bacteria to ensure an efficient coordination of growth and division. A well studied representative is the dcw gene cluster of E. coli. The first promoter of the gene cluster (mraZ1p) gives rise to polycistronic transcripts containing a 38 nt long 5’ UTR followed by the first gene mraZ. Despite reported conservation we present evidence for a much longer 5’ UTR in the gram negative and rod shaped bacterium Rhodobacter sphaeroides and in the family of Rhodobacteraceae. This extended 268 nt long 5’ UTR comprises a Rho independent terminator, which in case of termination gives rise to a non-coding RNA (UpsM). This sRNA is conditionally cleaved by RNase E under stress conditions in an Hfq- and very likely target mRNA-dependent manner, implying its function in trans. These results raise the question for the regulatory function of this extended 5’ UTR. It might represent the rarely described case of a trans acting sRNA derived from a riboswitch with exclusive presence in the family of Rhodobacteraceae

Legal Implications of Digital Heritagization

Due to the development of information and communication technologies as well as the influence of the Internet, life and work of the contemporary society take increasingly place in virtual form and the approach towards knowledge and heritage fundamentally altered. The remarkable sign of this continuous process is the emergence of Digital Heritage, understood as the accumulation of computer-based, valuable materials, which constitutes a digital reflection of societal developments. Different “heritage institutions” from the public sector, such as archives, libraries, museums, but also private undertakings became involved in the related process of Digital Heritagization encompassing cultural, scientific and administrative resources. The objective aimed for is the preservation of the named resources in order to enable future generations to access the collective memory of our society by means of electronic records. Since the digitization of analogue resources and the utilization of born-digital content presupposes inter alia the reproduction and duplication of the content in question, the field of intellectual property law gains particular interest. Thereby, the discussion on the national and international level is characterized by the heterogeneous and partly restrictive legal framework. The contribution takes this new environment as opportunity to approach the legal framework of civil law as well as common law jurisdictions related to digital heritage from a copyright law perspective, with particular reference to the legal exemptions and fair dealings doctrine. In order to emphasize the high practical impact of the issue at stake, recent judgments of the ECJ, the Swiss Federal Tribunal and the S.D.N.Y. (Google Books Case) assessing the admissibility of the digitalization and related aspects are considered and critically evaluated. On that basis, the future need of legislative measures in order to balance personal proprietary rights and public interests is discussed.En raison du développement des technologies de l’information et de la communication et de l’influence d’Internet, la vie et le travail de notre société contemporaine s’inscrit de plus en plus dans des formes virtuelles et modifie fondamentalement le rapport au savoir et au patrimoine. Le signe le plus notable de ce processus continu est l’émergence du patrimoine numérique, entendu comme l’accumulation sur support informatique de matériel considéré comme signifiant, qui constitue le reflet numérique des développements sociétaux. Différentes institutions patrimoniales du secteur public, comme le monde des archives, bibliothèques, musées mais aussi des initiatives privées s’investissent dans le processus de patrimonialisation numérique qui y est associé et englobe des ressources culturelles, scientifiques et administratives. L’enjeu sous-jacent est la préservation de ces ressources afin de permettre aux générations futures d’accéder à la mémoire collective de nos sociétés par le biais d’enregistrements électroniques. Puisque la numérisation de ressources analogiques et l’utilisation de contenus nativement numériques présuppose, entre autres, leur reproduction et duplication, le droit de propriété intellectuelle est pertinent dans ce contexte. Par ailleurs, les discussions nationales et internationales sont caractérisées par un cadre juridique hétérogène et partiellement restrictif. Cet article considère la patrimonialisation numérique à l’aune du régime du droit d’auteur, en se référant tout particulièrement aux exceptions légales et la doctrine de l’ « usage raisonnable ». Des jugements récents émis par la Cour de justice européenne, le tribunal fédéral suisse et le tribunal du district Sud de New York (le célèbre « Google Books Case »), portant sur l’admissibilité de la numérisation et aspects corrélés, seront examinés. Sur cette base, l’article examine enfin les besoins futurs de mesures législatives visant à équilibrer les droits de propriété personnels et l’intérêt public

A versatile standard for bathochromic fluorescence based on intramolecular FRET.

A perylene and a terrylene tetracarboxylic bisimide dyad was prepared in which an efficient energy transfer from the former to the latter is observed. The absorption spectrum of this compound covers a broad range. Bathochromic fluorescence with a high quantum yield was obtained independent of excitation wavelengths (λ < 655 nm). The dyad can be recommended for the use of calibrating fluorescence spectrometers, as well as a fluorescence standard in the bathochromic region

A novel murine model to study the impact of maternal depression and antidepressant treatment on biobehavioral functions in the offspring

Antenatal psychopathology negatively affects obstetric outcomes and exerts long-term consequences on the offspring's wellbeing and mental health. However, the precise mechanisms underlying these associations remain largely unknown. Here, we present a novel model system in mice that allows for experimental investigations into the effects of antenatal depression-like psychopathology and for evaluating the influence of maternal pharmacological treatments on long-term outcomes in the offspring. This model system in based on rearing nulliparous female mice in social isolation prior to mating, leading to a depressive-like state that is initiated before and continued throughout pregnancy. Using this model, we show that the maternal depressive-like state induced by social isolation can be partially rescued by chronic treatment with the selective serotonin reuptake inhibitor, fluoxetine (FLX). Moreover, we identify numerous and partly sex-dependent behavioral and molecular abnormalities, including increased anxiety-like behavior, cognitive impairments and alterations of the amygdalar transcriptome, in offspring born to socially isolated mothers relative to offspring born to mothers that were maintained in social groups prior to conception. We also found that maternal FLX treatment was effective in preventing some of the behavioral and molecular abnormalities emerging in offspring born to socially isolated mothers. Taken together, our findings suggest that the presence of a depressive-like state during preconception and pregnancy has sex-dependent consequences on brain and behavioral functions in the offspring. At the same time, our study highlights that FLX treatment in dams with a depression-like state can prevent abnormal behavioral development in the offspring

Randomized clinical trial to evaluate the effects of a prepartum cholecalciferol injection on postpartum serum calcium dynamics and health and performance in early-lactation multiparous dairy cows

The objectives of the present study were (1) to evaluate the effect of prepartum cholecalciferol treatment on serum Ca concentration during the first 10 d after calving and (2) to evaluate the effect of treatment on subsequent health and performance. Multiparous Holstein cows (n = 377) from one dairy farm were fed a negative dietary cation-anion difference diet (−31 mEq/kg of DM) for the last 21 d of gestation. On d 275, the animals were randomly assigned to a control or a treatment group. Cows in the control group were left untreated, and cows in the treatment group received an injection of 12 × 106 IU of cholecalciferol intramuscularly on the day of enrollment. If treated cows did not deliver the calf within 6 d, they were reinjected with 10 × 106 IU of cholecalciferol. Blood samples were drawn on 1, 2, 3, 5, 7, and 10 days in milk (DIM) and analyzed for serum Ca, P, and Mg concentrations. In a subsample of cows (50 control cows, 35 cows treated once with cholecalciferol, and 15 cows treated twice) serum haptoglobin, nonesterified fatty acids, β-hydroxybutyrate, and 25-hydroxycholecalciferol concentrations were analyzed on 1, 5, and 10 DIM. Binary data [retained placenta (RP), metritis] were analyzed using logistic regression models. Repeated measures ANOVA with first-order autoregressive covariance was performed to evaluate the treatment effect on milk yield over the first 10 test days after parturition, 25-hydroxycholecalciferol, serum Ca, P, Mg, β-hydroxybutyrate, nonesterified fatty acids, and haptoglobin concentrations. Cox proportional hazards were used to model the time to event outcomes (time to pregnancy within 200 d, culling until 300 DIM). After enrollment of 31.4% of cows and a preliminary analysis, adverse reactions became apparent, and the study was stopped. Cows treated with cholecalciferol had a greater risk of incurring RP and metritis. The adjusted mean incidences were 2.0%, 7.7%, and 4.0% for RP, and 21.6%, 39.3%, and 33.3% for metritis for control cows, cows treated once, and cows treated twice with cholecalciferol, respectively. Compared with control cows, cows injected once with 12 × 106 IU of cholecalciferol produced less energy-corrected milk on the first (−3.76 kg) and second (−2.75 kg) test days, respectively. Cows injected twice with cholecalciferol (12 × 106 IU of cholecalciferol and 10 × 106 IU 1 wk later) had a reduced milk yield only at first test day (−3.80 kg). Treatment with cholecalciferol led to a significant increase in 25-hydroxycholecalciferol on d 1, 5, and 10 after calving. Serum Ca and P concentrations were significantly increased in cows treated with cholecalciferol, but serum Mg concentrations were significantly reduced. Haptoglobin concentrations were significantly increased on 5 DIM in cows injected once with 12 × 106 IU of cholecalciferol. Although we observed no effect of treatment on culling until 300 DIM, time to pregnancy was delayed by 34 d in cows injected once with 12 × 106 IU of cholecalciferol. In the present study, injection with 12 × 106 IU of cholecalciferol had detrimental effects on health and milk production despite the beneficial effects on Ca homeostasis

Photophysics, Molecular Reorientation in Solution and X-Ray Structure of a New Fluorescent Probe 1,7-Diazaperylene

A new fluorescent molecule 1,7-diazaperylene (DP) has been investigated by means of time-resolved and steady-state polarized fluorescence spectroscopy, as well as X-ray spectroscopy. Absorption and fluorescence spectra of DP in solution are similar to those of perylene. However, absorption and fluorescence spectra of 2,8-dimethoxy DP and 2,8-dipentyloxy DP in solution are red-shifted by ca. 55 nm relative to perylene. The fluorescence decay of DP is exponential with a lifetime of 5.1 ns in ethanol, 4.9 ns in glycerol and 4.3 ns in paraffin oil. The radiative lifetime in ethanol was calculated to be 6.3 ns for DP, 8.0 ns for 2,8-dimethoxy DP and 7.6 ns for 2,8-dipentyloxy DP. The calculated fluorescence quantum yields of 0.8 for DP and its alkoxy derivatives in ethanol, are in good agreement with those obtained from measurements. The calculated Förster radius is 37.2 ± 1 Å for DP and 41.9 ± 1 Å for its alkoxy derivatives in ethanol. Examining the S0 S1 transition, we obtain a limiting fluorescence anisotropy of r0 0.38 for DP and its alkoxy derivatives. The rotational rates of DP in paraffin oil and glycerol were compared to that of perylene. In paraffin oil both molecules show an almost identical biexponential decay of the fluorescence anisotropy, which is compatible with a rotational motion like an oblate ellipsoid. The fluorescence anisotropy is monoexponential for DP in glycerol, and DP appears to rotate like a spherical particle while perylene in glycerol appears to rotate like an oblate ellipsoid. Moreover, the rotational diffusion constant, corresponding to rotation about an axis in the aromatic plane (D), is the same for both DP and perylene in glycerol

VALUE trial: Long-term blood pressure trends in 13,449 patients with hypertension and high cardiovascular risk

Background: The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) study compares cardiovascular outcomes in 15,314 eligible patients from 31 countries randomized to valsartan or amlodipine-based treatment. Methods: The blood pressure (BP) trends are analyzed in 13,449 of VALUE study patients who had baseline BP and 24 months BP and treatment data. Results: In a cohort of 12,570 patients, baseline 24 and 30 months BP, but not 30 months treatment data, were available. Of 13,449 patients, 92% (N = 12,398) received antihypertensive therapy at baseline. The baseline BP was 153.5/86.9 mm Hg in treated compared to 168.1.8/95.3 mm Hg in 1051 untreated patients. After 6 months both groups had indistinguishable BP values. At 12 months the BP decreased to 141.2/82.9 mm Hg (P < .0001 for systolic BP and diastolic BP versus baseline), at 24 months to 139.1/80 mm Hg (P < .0001 v 12 months), and to 138/79 mm Hg at 30 months (P < .0001 v 24 months). The systolic BP control (<140 mm Hg) at 30 months increased from 21.9% at baseline to 62.2%, the diastolic BP (< 90 mm Hg) from 54.2% to 90.2% and the combined control (<140 and <90 mm Hg) from 18.9% to 60.5%. At 24 months 85.8% of patients were on protocol drugs: monotherapy = 39.7%, added hydrochlorothiazide = 26.6%, add-on drugs = 15.1%, and protocol drugs in nonstandard doses = 4.3%. Conclusions: The achieved BP control exceeds values reported in most published large-scale trials. The VALUE study is executed in regular clinical settings and 92% of the patients received antihypertensive drugs at baseline. When an explicit BP goal is set, and a treatment algorithm is provided, the physicians can achieve better control rates than in their regular practice. Am J Hypertens 2003;16: 544-548 @ 2003 American Journal of Hypertension, Lt

Investigating Slit-Collimator-Produced Carbon Ion Minibeams with High-Resolution CMOS Sensors

Particle minibeam therapy has demonstrated the potential for better healthy tissue sparing due to spatial fractionation of the delivered dose. Especially for heavy ions, the spatial fractionation could enhance the already favorable differential biological effectiveness at the target and the entrance region. Moreover, spatial fractionation could even be a viable option for bringing ions heavier than carbon back into patient application. To understand the effect of minibeam therapy, however, requires careful conduction of pre-clinical experiments, for which precise knowledge of the minibeam characteristics is crucial. This work introduces the use of high-spatial-resolution CMOS sensors to characterize collimator-produced carbon ion minibeams in terms of lateral fluence distribution, secondary fragments, track-averaged linear energy transfer distribution, and collimator alignment. Additional simulations were performed to further analyze the parameter space of the carbon ion minibeams in terms of beam characteristics, collimator positioning, and collimator manufacturing accuracy. Finally, a new concept for reducing the neutron dose to the patient by means of an additional neutron shield added to the collimator setup is proposed and validated in simulation. The carbon ion minibeam collimator characterized in this work is used in ongoing pre-clinical experiments on heavy ion minibeam therapy at the GSI

Taste-immune associative learning amplifies immunopharmacological effects and attenuates disease progression in a rat glioblastoma model

Mechanistic target of rapamycin (mTOR)-signaling is one key driver of glioblastoma (GBM), facilitating tumor growth by promoting the shift to an anti-inflammatory, pro-cancerogenic microenvironment. Even though mTOR inhibitors such as rapamycin (RAPA) have been shown to interfere with GBM disease progression, frequently chaperoned toxic drug side effects urge the need for developing alternative or supportive treatment strategies. Importantly, previous work document that taste-immune associative learning with RAPA may be utilized to induce learned pharmacological placebo responses in the immune system. Against this background, the current study aimed at investigating the potential efficacy of a taste-immune associative learning protocol with RAPA in a syngeneic GBM rat model. Following repeated pairings of a novel gustatory stimulus with injections of RAPA, learned immune-pharmacological effects could be retrieved in GBM-bearing animals when re-exposed to the gustatory stimulus together with administering 10 % amount of the initial drug dose (0.5 mg/kg). These inhibitory effects on tumor growth were accompanied by an up-regulation of central and peripheral pro-inflammatory markers, suggesting that taste-immune associative learning with RAPA promoted the development of a pro-inflammatory anti-tumor microenvironment that attenuated GBM tumor growth to an almost identical outcome as obtained after 100 % (5 mg/kg) RAPA treatment. Together, our results confirm the applicability of taste-immune associative learning with RAPA in animal disease models where mTOR overactivation is one key driver. This proof-of-concept study may also be taken as a role model for implementing learning protocols as alternative or supportive treatment strategy in clinical settings, allowing the reduction of required drug doses and side effects without losing treatment efficacy

Intraoperative fabrication of patient-specific moulded implants for skull reconstruction: single-centre experience of 28 cases

Background: Intraoperatively fabricated polymethylmethacrylate (PMMA) implants based on computer-designed moulds were used to improve cosmetic results after hard tissue replacement. To assess the implant's cosmetic and functional results we performed both subjective and objective assessments. Methods: This retrospective analysis was performed using a cohort of 28 patients who received PMMA implants between February 2009 and March 2012. The cosmetic and functional results were assessed using a patient questionnaire. Furthermore an objective volumetric subtraction score (0-100) was applied and implant thickness, as well as gaps and tiers, were measured. Results: Patients mainly judged their cosmetic result as "good”. Two of the 28 patients found their cosmetic result unfavourable. The functional result and stability was mainly judged to be good. Measurements of implant thickness showed a very high correlation with the thickness of the contralateral bone. Volumetric subtraction led to a median quality of 80 on a scale from 0 to 100. Median gaps around the margins of the implant were 1.5mm parietally, 1.7mm frontally and 3.5mm fronto-orbitally, and median tiers were 1.2mm, 0mm and 0mm respectively. The overall rate of surgical revisions was 10.7% (three patients). Two patients suffered from wound healing disturbances (7.1%). The overall complication rate was comparable to other reports in the literature. Conclusions: Implantation of intraoperatively fabricated patient-specific moulded implants is a cost-effective and safe technique leading to good clinical results with a low complication rate