Communication

The geometry of reaction compartments can affect the local outcome of interface-restricted reactions. Giant unilamellar vesicles (GUVs) are commonly used to generate cell-sized, membrane-bound reaction compartments, which are, however, always spherical. Herein, we report the development of a microfluidic chip to trap and reversibly deform GUVs into cigar-like shapes. When trapping and elongating GUVs that contain the primary protein of the bacterial Z ring, FtsZ, we find that membrane-bound FtsZ filaments align preferentially with the short GUV axis. When GUVs are released from this confinement and membrane tension is relaxed, FtsZ reorganizes reversibly from filaments into dynamic rings that stabilize membrane protrusions; a process that allows reversible GUV deformation. We conclude that microfluidic traps are useful for manipulating both geometry and tension of GUVs, and for investigating how both affect the outcome of spatially-sensitive reactions inside them, such as that of protein self-organization.We acknowledge the MPIB Biochemistry Core Facility for assistance in protein purification

a pilot study

Muscular weakness in myasthenia gravis (MG) is commonly assessed using Quantitative Myasthenia Gravis Score (QMG). More objective and quantitative measures may complement the use of clinical scales and might detect subclinical affection of muscles. We hypothesized that muscular weakness in patients with MG can be quantified with the non-invasive Quantitative Motor (Q-Motor) test for Grip Force Assessment (QGFA) and Involuntary Movement Assessment (QIMA) and that pathological findings correlate with disease severity as measured by QMG. Methods This was a cross-sectional pilot study investigating patients with confirmed diagnosis of MG. Data was compared to healthy controls (HC). Subjects were asked to lift a device (250 and 500 g) equipped with electromagnetic sensors that measured grip force (GF) and three- dimensional changes in position and orientation. These were used to calculate the position index (PI) and orientation index (OI) as measures for involuntary movements due to muscular weakness. Results Overall, 40 MG patients and 23 HC were included. PI and OI were significantly higher in MG patients for both weights in the dominant and non-dominant hand. Subgroup analysis revealed that patients with clinically ocular myasthenia gravis (OMG) also showed significantly higher values for PI and OI in both hands and for both weights. Disease severity correlates with QIMA performance in the non-dominant hand. Conclusion Q-Motor tests and particularly QIMA may be useful objective tools for measuring motor impairment in MG and seem to detect subclinical generalized motor signs in patients with OMG. Q-Motor parameters might serve as sensitive endpoints for clinical trials in MG

Developing SOEPsurvey and SOEPservice: The (Near) Future of the German Socio-Economic Panel Study (SOEP)

Das Sozio-oekonomische Panel (SOEP) ist als multidisziplinäres Haushaltspanel, das Informationen zu allen Personen, die in einem Panel-Haushalt leben, erhebt und damit alle Altersjahrgänge abdeckt, nach 25 Jahren Laufzeit auch zu einer Kohorten- Studie geworden. Der zunehmende Erfolg der Forschungsinfrastruktur-Einrichtung SOEP speist sich in erster Linie daraus, dass die Analysekraft von Längsschnittstudien mit jedem weiteren Erhebungsjahr zunimmt. Hinzu kommen im Falle des SOEP seit Beginn an eine lange Reihe von Innovationen bei der Erhebung, Datenaufbereitung und Nutzer-Service. Deswegen gilt es zu überlegen, wie die wissenschaftliche Power des SOEP weiter gestärkt werden kann. Nicht zuletzt auch, da es für neue, spezialisierte Panel-Studien (wie das Nationale Bildungspanel oder das DFG-geförderte Familienpanel PAIRFAM) eine Referenz und ggf. Verankerung der Hochrechnung darstellt. Zudem kann das SOEP künftig eine größere Rolle als ,,Kontroll-Stichprobe" für Interventions-Studien spielen; etwa im Bereich der Kindheitsentwicklung. Auf diese neuen Rollen muss es vorbereitet sein. Die im SOEP in den letzten Jahren realisierten Erhebungsinnovationen wie z. B. die Inkorporation psychologischer Konzepte, physische Gesundheitsmessungen (Greifkraft), die Messung kognitiver Fähigkeiten und die Erprobung von Verhaltens- Experimenten werden in anderen Panel-Studien aufgegriffen und auf eine größere Stichprobenbasis gestellt. Im UK wird mit ,,Understanding Society" ein Haushaltspanel mit 40.000 Haushalten begonnen; in den Niederlanden wird mit MESS ein Haushaltspanel von über 5.000 Haushalten für innovative Messmethoden zur Verfügung gestellt. Die Erhebungsinhalte des SOEP werden von den Forschungs- und Politikberatungs-Communities unverändert stark nachgefragt. In UK hat ein für ,,Understanding Society" breit angelegter Konsultationsprozess keine grundsätzlich neuen Befragungsinhalte zu Tage gefördert, die das SOEP nicht bereits enthält oder die für das SOEP ohnehin im Gespräch sind. Wichtiger als die ,,Entdeckung" völlig neuer Erhebungsinhalte ist das thematische wie zeitliche ,,Zuschneiden" der Details von Befragungsinhalten auf (zugespitzte) neue (theoretische) Fragestellungen und dabei gleichzeitig bewährte sowie viel genutzte zentrale Befragungsinhalte und deren Befragungsrhythmen beizubehalten. Das ,,Maßschneidern" von Erhebungsinhalten wird in den nächsten Jahren die eigentliche Herausforderung für Infrastruktur- Erhebungen wie die PSID, ,,Understanding Society" und das SOEP sein. Bei den Erhebungsinhalten sollten die ,,Ränder" des Lebenslaufs eine größere Rolle spielen, da diese von Haushalts-Panels besonders gut erfasst werden können. Diese Verbesserungen der Erhebungen beziehen sich einerseits auf die fötale Phase von in das SOEP hineingeborenen Kindern und die (frühe) Kindheit, andererseits auf die letzte Lebensphase und das Sterben. In der Mitte des Lebenslaufs werden verbesserte Fragen zum Einkommen, Sparen und Vermögen sowie auch psychologische Konstrukte eine zentrale Rolle spielen, außerdem gezielte Fragen (event triggered questionnaires) in Verbindung mit zentralen Lebensereignissen wie z. B. Eheschließung, Scheidung, Eintritt in und Austritt aus Arbeitslosigkeit. Es wird die Etablierung einer SOEP-"Innovations-Stichprobe" vorbereitet, um theoriegeleitete Forschungsfragen gezielter unterstützen zu können. Dazu wird es auch notwendig sein, neue Messkonzepte zu erproben (z. B. die Erhebung von Biomarkern, qualitative Erhebungen, aber auch Experimente und gezielte Interventionsstudien). Um die Power von Längsschnittdaten von Anfang an für die Innovations-Stichprobe ausnutzen zu können, ist geplant, zwei kleinere Teilstichproben des SOEP, die seit 1998 bzw. 2006 laufen (Subsamples E und H), in die Innovationsstichprobe zu überführen. Um die statistische Power langlaufender Längsschnittdaten entscheidend zu verbessern, schätzen wir eine Mindestfallzahl von etwa 500 Personen pro Geburtsund Alterskohorte für ausreichend ein. Um dieses Ziel zu erreichen, muss die Fallzahl des SOEP-Standard-Samples erhöht werden. Als ,,Nebeneffekt" werden dadurch wesentlich bessere Analysen für relativ kleine Gruppen in der Bevölkerung möglich; etwa für allein Erziehende oder bestimme Immigrantengruppen. Außerdem verbessern sich als weiterer ,,Nebeneffekt" auch regionale Analysemöglichkeiten, z. B. für die meisten Bundesländer und in großen Bundesländern bis hin zu Regierungsbezirken (oder ähnlich abgegrenzten regionalen Einheiten). In letzter Zeit wird immer deutlicher, welche große Bedeutung das SOEP als ,,Referenz-Datensatz" für spezialisierte und vom SOEP völlig unabhängige Erhebungen hat (neben Beobachtungsstudien, wie etwa Zwillings-Studien, auch Labor- und Interventions-Studien). Zur Unterstützung dieser Funktion ist eine neue Art von Service, der in Deutschland bislang nicht vorgehalten wird, notwendig (Beratung von Spezial-Erhebungen; ggf. Datenaufbereitung von längsschnittlichen Spezial-Erhebungen), der auch in ein Datenservicezentrum eingebracht werden könnte. After 25 years as a multidisciplinary household panel containing information on all individuals residing in panel households and thus covering all age cohorts, the German Socio-Economic Panel (SOEP) has become a true cohort study as well. The increasing success of the SOEP research infrastructure comes above all from the increasing analytical power that longitudinal studies attain with each successive survey year. In the case of SOEP, a long series of innovations in surveying, data preparation, and user service have also played a major role. For this reason, it is important to consider how the scientific capacity of SOEP can be further enhanced-- not least of all since the SOEP can form a key point of reference (or "anchor") for new, specialized panel studies (such as the National Educational Panel and the family panel PAIRFAM, funded by the German Research Foundation). Furthermore SOEP can become a kind of "control sample" for intervention studies, for example, in the field of child development. The SOEP survey and its governance structures must be prepared for these new tasks. The numerous innovations introduced into SOEP in recent years--questions dealing with psychological concepts, physical health measures (grip strength), measures of cognitive capabilities, and behavioral experiments--have been incorporated into other panel studies as well, and thus provided with a larger sample base. In the UK, the "Understanding Society" household panel study was launched with 40,000 households; in the Netherlands, the MESS household panel study of over 5,000 households offered a new basis for testing innovative measurement methods. The results of the SOEP survey are in continuing high demand in the research and policy advisory community. From our point of view, the large-scale consultation process conducted to define the content of the UK survey "Understanding Society" failed to identify any fundamentally new survey content that the SOEP either did not already contain or that was not already being discussed for the SOEP. More important than "discovering" entirely new survey areas is "tailoring" the details of existing survey content to address new, more specific (theoretical) questions, and thus maintaining proven and widely used elements of survey content. The "tailoring" of survey content will be the real challenge facing infrastructure surveys like PSID, "Understanding Society," and the SOEP in the coming years. In the future, the "margins" of the life course should play a stronger role in survey content, since household panels are able to provide outstanding data of these life phases. The SOEP, and other household panel surveys, can be improved, on the one hand, by including the fetal phase of life and early childhood for children born into the panel, and on the other, by including late life and death. In the middle of the life course, improved questions on income, savings, and wealth as well as psychological constructs will play a central role, as will specific questions (in "eventtriggered" questionnaires) on central life occurrences such as marriage, divorce, and entry into and exit from unemployment. Current plans for SOEP foresee the addition of an "Innovation Sample" that will make it possible to better address theory-based research questions required for testing new measurement concepts (e.g., the surveying of biomarkers, qualitative surveys, but also experiments and targeted intervention studies). In order to exploit the power of longitudinal data from the outset, we plan to incorporate two smaller SOEP subsamples that have been running since 1998 and 2006 (Subsamples E and H, respectively) into the Innovation Sample. In order to decisively improve the statistical power of long-term longitudinal data, we believe that a minimum case number of about 500 persons per birth and age cohort is required. In order to reach this goal, the case number in the SOEP standard samples needs to be increased. A positive side-effect of this enlargement would be a significantly improved potential for analyses of relatively small groups within the population: for example, lone parents or specific immigrant groups. Another positive side-effect would be an improved potential for regional analyses: for example, for the majority of federal states. In recent times, the importance of SOEP as a "reference dataset" for specialized surveys which are independent from SOEP (observational studies such as twin studies, and laboratory and intervention studies) has become strikingly evident. To enhance this important function, new types of service are needed (advice on special surveys, possibly also data preparation for special surveys), which could become part of a Data Service Center.Household Panels, German Socio-Economic Panel Study, SOEP

Meridional transport of dissolved inorganic carbon in the South Atlantic Ocean

The meridional oceanic transports of dissolved inorganic carbon and oxygen were calculated using six transoceanic sections occupied in the South Atlantic between 11 degrees S and 30 degrees S. The total dissolved inorganic carbon (TCO2) data were interpolated onto conductivity-temperature-depth data to obtain a high-resolution data set, and Ekman, depth-dependent and depth-independent components of the transport were estimated. Uncertainties in the depth-independent velocity distribution were reduced using an inverse model. The inorganic carbon transport between 11 degrees S and 30 degrees S was southward, decreased slightly toward the south, and was -2150 +/- 200 kmol s(-1) (-0.81 +/- 0.08 Gt C yr(-1)) at 20 degrees S. This estimate includes the contribution of net mass transport required to balance the salt transport through Bering Strait. Anthropogenic CO2 concentrations were estimated for the sections. The meridional transport of anthropogenic CO2 was northward, increased toward the north, and was 430 kmol s(-1) (0.16 Gt C yr(-1)) at 20 degrees S. The calculations imply net southward inorganic carbon transport of 2580 kmol s(-1) (1 Gt C yr(-1)) during preindustrial times. The slight contemporary convergence of inorganic carbon between 10 degrees S and 30 degrees S is balanced by storage of anthropogenic CO2 and a sea-to-air flux implying little local divergence of the organic carbon transport. During the preindustrial era, there was significant regional convergence of both inorganic carbon and oxygen, consistent with a sea-to-air gas flux driven by warming. The northward transport of anthropogenic CO2 carried by the meridional overturning circulation represents an important source for anthropogenic CO2 currently being stored within the North Atlantic Ocean

Toward Regional Characterizations of the Oceanic Internal Wavefield

Many major oceanographic internal wave observational programs of the last 4 decades are reanalyzed in order to characterize variability of the deep ocean internal wavefield. The observations are discussed in the context of the universal spectral model proposed by Garrett and Munk. The Garrett and Munk model is a good description of wintertime conditions at Site-D on the continental rise north of the Gulf Stream. Elsewhere and at other times, significant deviations in terms of amplitude, separability of the 2-D vertical wavenumber - frequency spectrum, and departure from the model's functional form are noted. Subtle geographic patterns are apparent in deviations from the high frequency and high vertical wavenumber power laws of the Garrett and Munk spectrum. Moreover, such deviations tend to co-vary: whiter frequency spectra are partnered with redder vertical wavenumber spectra. Attempts are made to interpret the variability in terms of the interplay between generation, propagation and nonlinearity using a statistical radiative balance equation. This process frames major questions for future research with the insight that such integrative studies could constrain both observationally and theoretically based interpretations

The future for beef

Beef is a fast-growing, multi -billion dollar industry today in the United States. And the outlook for tomorrow is most favorable. Beef consumption has increased by 26 pounds per capita during the past 15 years, hitting an all-time high of 90 pounds per capita in 1962. During the same period quality has improved, and now. beef commands even wider consumer acceptance than in the mid-1940\u27s. New technology has lowered production and marketing costs. But even a strong, healthy industry must be sensitive to change--and take advantage of new opportunities for growth and improvement. The beef industry is no exception.https://lib.dr.iastate.edu/card_reports/1016/thumbnail.jp

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Engineering yield and rate of reductive biotransformation in Escherichia coli by partial cyclization of the pentose phosphate pathway and PTS-independent glucose transport

Optimization of yields and productivities in reductive whole-cell biotransformations is an important issue for the industrial application of such processes. In a recent study with Escherichia coli, we analyzed the reduction of the prochiral β-ketoester methyl acetoacetate by an R-specific alcohol dehydrogenase (ADH) to the chiral hydroxy ester (R)-methyl 3-hydroxybutyrate (MHB) using glucose as substrate for the generation of NADPH. Deletion of the phosphofructokinase gene pfkA almost doubled the yield to 4.8 mol MHB per mole of glucose, and it was assumed that this effect was due to a partial cyclization of the pentose phosphate pathway (PPP). Here, this partial cyclization was confirmed by 13C metabolic flux analysis, which revealed a negative net flux from glucose 6-phosphate to fructose 6-phosphate catalyzed by phosphoglucose isomerase. For further process optimization, the genes encoding the glucose facilitator (glf) and glucokinase (glk) of Zymomonas mobilis were overexpressed in recombinant E. coli strains carrying ADH and deletions of either pgi (phosphoglucose isomerase), or pfkA, or pfkA plus pfkB. In all cases, the glucose uptake rate was increased (30–47%), and for strains Δpgi and ΔpfkA also, the specific MHB production rate was increased by 15% and 20%, respectively. The yield of the latter two strains slightly dropped by 11% and 6%, but was still 73% and 132% higher compared to the reference strain with intact pgi and pfkA genes and expressing glf and glk. Thus, metabolic engineering strategies are presented for improving yield and rate of reductive redox biocatalysis by partial cyclization of the PPP and by increasing glucose uptake, respectively