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In optogenetics, rhodopsins were established as light-driven tools to manipulate neuronal activity. However, during long-term photostimulation using channelrhodopsin (ChR), desensitization can reduce effects. Furthermore, requirement for continuous presence of the chromophore all-trans retinal (ATR) in model systems lacking sufficient endogenous concentrations limits its applicability. We tested known, and engineered and characterized new variants of de- and hyperpolarizing rhodopsins in Caenorhabditis elegans. ChR2 variants combined previously described point mutations that may synergize to enable prolonged stimulation. Following brief light pulses ChR2(C128S;H134R) induced muscle activation for minutes or even for hours (‘Quint’: ChR2(C128S;L132C;H134R;D156A;T159C)), thus featuring longer open state lifetime than previously described variants. Furthermore, stability after ATR removal was increased compared to the step-function opsin ChR2(C128S). The double mutants C128S;H134R and H134R;D156C enabled increased effects during repetitive stimulation. We also tested new hyperpolarizers (ACR1, ACR2, ACR1(C102A), ZipACR). Particularly ACR1 and ACR2 showed strong effects in behavioral assays and very large currents with fast kinetics. In sum, we introduce highly light-sensitive optogenetic tools, bypassing previous shortcomings, and thus constituting new tools that feature high effectiveness and fast kinetics, allowing better repetitive stimulation or investigating prolonged neuronal activity states in C. elegans and, possibly, other systems.
The increased susceptibility to infections of neonates is caused by an immaturity of the immune system as a result of both qualitative and quantitative differences between neonatal and adult immune cells. With respect to B cells, neonatal antibody responses are known to be decreased. Accountable for this is an altered composition of the neonatal B cell compartment towards more immature B cells. However, it remains unclear whether the functionality of individual neonatal B cell subsets is altered as well. In the current study we therefore compared phenotypical and functional characteristics of corresponding neonatal and adult B cell subpopulations. No phenotypic differences could be identified with the exception of higher IgM expression in neonatal B cells. Functional analysis revealed differences in proliferation, survival, and B cell receptor signaling. Most importantly, neonatal B cells showed severely impaired class-switch recombination (CSR) to IgG and IgA. This was associated with increased expression of miR-181b in neonatal B cells. Deficiency of miR-181b resulted in increased CSR. With this, our results highlight intrinsic differences that contribute to weaker B cell antibody responses in newborns.
Deutschland und Europa
(2018)
Otmar Issing erörtert die Reaktionen in Deutschland auf die Pläne des französischen Präsidenten Macron aus dessen viel beachteter Rede zur Zukunft Europas an der Pariser Sorbonne. Issing wertet das Ergebnis der Sondierungsgespräche zwischen CDU/CSU und SPD als Abschied von der Vorstellung einer auf Stabilität gerichteten europäischen Gemeinschaft und mahnt an, den einheitlichen Markt und die damit verbundenen Freiheiten nicht durch überzogene Ambitionen zu gefährden und damit zunehmendes Misstrauen gegenüber Europa zu fördern.
Insbesondere in der geplanten Weiterentwicklung des ESM zu einem im Unionsrecht verankerten Europäischen Währungsfonds sieht Issing die Auslieferung der durch den Fonds zur Verfügung gestellten Mittel an eine politische Mehrheit. Zudem führe die Bestellung eines europäischen Finanzministers zur Schaffung einer die Währungsunion ergänzenden Fiskalunion und damit zur Verlagerung finanzpolitischer Kompetenz von der nationalen auf die europäische Ebene. In letzter Konsequenz bedeute dies eine Aufgabe des grundlegenden Prinzips der demokratischen Legitimierung und Kontrolle finanzpolitischer Entscheidungen.
Das Ergebnis der Sondierungsgespräche muss man als Abschied von der Vorstellung einer auf Stabilität gerichteten europäischen Gemeinschaft verstehen. Damit werden die Versprechen gebrochen, die man den Bürgern in Deutschland vor der Einführung des Euros gegeben hat.
Background: Leaf venation traits are important for many research fields such as systematics and evolutionary biology, plant physiology, climate change, and paleoecology. In spite of an increasing demand for vein trait data, studies are often still data-limited because the development of methods that allow rapid generation of large sets of vein data has lagged behind. Recently, non-destructive X-ray technology has proven useful as an alternative to traditional slow and destructive chemical-based methods. Non-destructive techniques more readily allow the use of herbarium specimens, which provide an invaluable but underexploited resource of vein data and related environmental information. The utility of 2D X-ray technology and microfocus X-ray computed tomography, however, has been compromised by insufficient image resolution. Here, we advanced X-ray technology by increasing image resolution and throughput without the application of contrast agents.
Results: For 2D contact microradiography, we developed a method which allowed us to achieve image resolutions of up to 7 µm, i.e. a 3.6-fold increase compared to the industrial standard (25 µm resolution). Vein tracing was further optimized with our image processing standards that were specifically adjusted for different types of leaf structure and the needs of higher imaging throughput. Based on a test dataset, in 91% of the samples the 7 µm approach led to a significant improvement in estimations of minor vein density compared to the industrial standard. Using microfocus X-ray computed tomography, very high-resolution images were obtained from a virtual 3D–2D transformation process, which was superior to that of 3D images.
Conclusions: Our 2D X-ray method with a significantly improved resolution advances rapid non-destructive bulk scanning at a quality that in many cases is sufficient to determine key venation traits. Together with our high-resolution microfocus X-ray computed tomography method, both non-destructive approaches will help in vein trait data mining from museum collections, which provide an underexploited resource of historical and recent data on environmental and evolutionary change. In spite of the significant increase in effective image resolution, a combination of high-throughput and full visibility of the vein network (including the smallest veins and their connectivity) remains challenging, however.
Die Wahrscheinlichkeit einer pathologischen Komplettremission (pCR) bei Brustkrebs nach neoadjuvanter Chemotherapie (NACT) nimmt zu; vor allem in den Subgruppen der tripel-negativen und HER-2-positiven Tumoren. Daher stellt sich die Frage, ob bei einer Komplettremission nach NACT eine operative Therapie der Brust notwendig ist, und ob es einen Vorteil für das onkologische Behandlungsergebnis hat, wenn kein Tumor mehr nachgewiesen werden kann. Ein Verzicht auf die Operation und gegebenenfalls auch auf die Radiotherapie ist jedoch nur auf der Basis einer verlässlichen pCR-Diagnose ohne Operation denkbar. Bildgebende Verfahren erreichen derzeit nicht die nötige Sensitivität und Spezifität, um die Diagnose einer pathologischen Komplettremission sicher zu stellen. Daher sind weitere Studien nötig, um herauszufinden, welche Methode die bestmögliche Evaluation des Tumoransprechens auf NACT erlaubt. Erste vielversprechende Ergebnisse zeigen sich in Studien zu bildgebungsgesteuerten, minimalinvasiven Biopsien nach NACT. Diese evaluieren die Möglichkeit einer pCR-Diagnose vor der Operation und könnten die Grundlage für weitere Studien zu einem möglichen Verzicht auf eine Operation in diesem ausgewählten Kollektiv sein.
The likelihood of pathological complete remission (pCR) of breast cancer following neoadjuvant chemotherapy (NACT) is increasing; most of all in the triple negative and HER2 positive tumour subgroups. The question thus arises whether or not breast surgery is necessary when there is complete remission after NACT, and whether it provides any improvement of the oncological treatment result when tumour is no longer detectable. Avoiding surgery and possibly even radiotherapy would only be conceivable on the basis of a reliable diagnosis of pCR without operating. Current imaging does not achieve the necessary sensitivity and specificity to assure the diagnosis of pathological complete remission. Further studies are therefore required to determine which methods are best able to evaluate tumour response to NACT. Studies on image-guided, minimally invasive biopsies after NACT have delivered first promising results towards diagnosing pCR before surgery and could provide the basis for further studies on the possibility of avoiding surgery in this specific patient collective.
I present a new business cycle model in which decision making follows a simple mental process motivated by neuroeconomics. Decision makers first compute the value of two different options and then choose the option that offers the highest value, but with errors. The resulting model is highly tractable and intuitive. A demand function in level replaces the traditional Euler equation. As a result, even liquid consumers can have a large marginal propensity to consume. The interest rate affects consumption through the cost of borrowing and not through intertemporal substitution. I discuss the implications for stimulus policies.
This paper analyses whether the post-crisis regulatory reforms developed by global-standard-setting bodies have created appropriate incentives for different types of market participants to centrally clear Over-The-Counter (OTC) derivative contracts. Beyond documenting the observed facts, we analyze four main drivers for the decision to clear: 1) the liquidity and riskiness of the reference entity; 2) the credit risk of the counterparty; 3) the clearing member’s portfolio net exposure with the Central Counterparty Clearing House (CCP) and 4) post trade transparency. We use confidential European trade repository data on single-name Sovereign Credit Derivative Swap (CDS) transactions, and show that for all the transactions reported in 2016 on Italian, German and French Sovereign CDS 48% were centrally cleared, 42% were not cleared despite being eligible for central clearing, while 9% of the contracts were not clearable because they did not satisfy certain CCP clearing criteria. However, there is a large difference between CCP clearing members that clear about 53% of their transactions and non-clearing members, even those that are subject to counterparty risk capital requirements, that almost never clear their trades. Moreover, we find that diverse factors explain clearing members’ decision to clear different CDS contracts: for Italian CDS, counterparty credit risk exposures matter most for the decision to clear, while for French and German CDS, margin costs are the most important factor for the decision. Clearing members use clearing to reduce their exposures to the CCP and largely clear contracts when at least one of the traders has a high counterparty credit risk.
The longevity of the population in the Okinawa Islands of Japan has been ascribed to genetic factors and the traditional Okinawa cuisine, which is low in calories and high in plant content. This diet includes shell ginger (Alpinia zerumbet (Pers.) B.L. Burtt & R.M. Sm) of the ginger family (Zingiberaceae). Due to its local popularity, Alpinia zerumbet has become the subject of a good deal of study at the University of the Ryukyus in Okinawa. Personal local experience and review of the literature now suggest that culinary shell ginger may contribute to longevity among the population in Okinawa. This is supported by its abundant phytochemical content, with antioxidant and anti-obesity properties. The major bioactive phytochemicals are dihydro-5,6-dehydrokawain (DDK; 80–410 mg g−1 fresh weight), 5,6-dehydrokawain (DK; ≤100 mg g−1), and essential oils, phenols, phenolic acids, and fatty acids (≤150 mg g−1 each). Further, Alpinia zerumbet extends the lifespan in animals by 22.6%. In conclusion, culinary shell ginger may significantly contribute to human longevity in Okinawa.
The blue light-dependent interaction between the proteins iLID and Nano allows recruiting and patterning proteins on GUV membranes, which thereby capture key features of patterns observed in nature. This photoswitchable protein interaction provides non-invasive, reversible and dynamic control over protein patterns of different sizes with high specificity and spatiotemporal resolution.
Compared to their protein-coding counterparts, almost nothing is known about the role of long noncoding RNAs (lncRNAs) in cardiac fibrosis. In the current report, Liang and Pan et al. characterized the pro-fibrotic lncRNA PFL in respect to cardiac fibrosis in mice. PFL was upregulated in the hearts of mice after myocardial infarction and in fibrotic cardiac fibroblasts. Moreover, PFL competitively sponged the cardio-protective miRNA let-7d in cardiac fibroblasts. Knockdown of platelet activating factor receptor (PTAFR) was shown to affect the pro-fibrotic collagen production mediated by PFL. PTAFR overexpression also led to collagen production and RNA abundance of PTAFR was also regulated by miRNA let-7d. Therefore, the PFL/PTAFR/let-7d-dependent gene regulatory mechanism proposed by the authors manifests the hypothesis of competing endogenous RNAs to cardiac fibrosis.
Digitalization expands the possibility for corporations to reduce taxes, mainly, but not exclusively, by allowing improved planning where profits can be shifted. Against this background, the European Commission and several countries emphatically demand and design new tax instruments. However, a selective turning away from internationally accepted principles of international taxation will bring up more questions than solutions. While there are good reasons to think about a fundamental regime switch in international corporate taxation, there are also good arguments for not turning to ad hoc measures that selectively target the relatively small market of Google and Facebook and raise only negligible tax revenues.
Monetary policy and prudential supervision – from functional separation to a holistic approach?
(2018)
When prudential supervision was put in the hands of the European Central Bank (ECB), it was the political understanding that the ECB should follow a policy of meticulous separation between monetary policy and financial supervision. However, the financial crisis showed that monetary policy and prudential supervision deeply affect each other and that an overly strict separation might generate systemic risk. As a consequence, the prevalent model of “functional separation” – central banking and financial supervision in separate entities – has been questioned and calls for a more holistic approach increased.
This policy letter states that from a legal perspective, such a holistic approach would be in conformity with the current legal framework of the Economic and Monetary Union. Although the realization of a holistic approach might intensify the doubts of democratic legitimation under the framework of the ESCB, the independence of the ECB should not be given up. As viable alternatives to protect monetary policy against the time inconsistency problem that would render central bank independence moot do not seem to be available and given the great importance of the independence of the European institutions for the European integration, the democratic control over the ECB should be strengthened instead of stripping the ECB of its independence.
Se registra por primera vez el ácaro rojo de las palmas, Raoiella indica Hirst (Acari: Tenuipalpidae), en Guatemala. Este ácaro invasivo se encontró en los departamentos de Petén e Izabal infestando palma de coco (Cocos nucifera), palma de Navidad (Adonidia merrillii) y palmera robeleni (Phoenix roebelenii).
En este estudio se describen dos nuevas especies de hemípteros del género Aleuropleurocelus (Hemiptera: Aleyrodidae): Aleuropleurocelus mexicanus Carapia y Sánchez sp. nov., encontrada en los estados de Coahuila, México, Puebla, Sonora, y Tlaxcala en hojas de Quercus agrifolia Née y Quercus sp., y Aleuropleurocelus anahuac Carapia y Sánchez sp. nov. encontrada en los estados de México, Morelos y Puebla en el envés de hojas de Quercus. Se proporcionan microfotografías de estructuras morfológicas de puparios y se discute la separación con otras especies ovales de Aleuropleurocelus.
An early, overlooked description of the genus Atelodesmis (Coleoptera, Cerambycidae, Lamiinae) is attributed to Chevrolat (in Duponchel and Chevrolat 1841), with A. mannerheimii Duponchel and Chevrolat, 1841 as its type species, and the genus redescribed. Atelodesmis Buquet, 1857, is a junior synonym and primary homonym of Atelodesmis Chevrolat. Atelodesmis hirticornis Buquet, 1857 and A. vestita Buquet, 1857 are synonymized with A. mannerheimii. Fallaxdesmis is described as a new genus with Atelodesmis unicolor Buquet, 1857 as type species. Atelodesmis piperita Bates, 1855 is transferred to Eupogonius and newly recorded for the state of Oaxaca, Mexico. A new species for Mexico and Guatemala, Eupogonius giesberti, is described. The following new combinations are established: Fallaxdesmis unicolor (Buquet, 1857) and Eupogonius piperita (Bates, 1855). Illustrations of A. mannerheimii, Fallaxdesmis unicolor, and the holotypes of A. hirticornis, A. vestita, A. unicolor, A. piperita and Eupogonius giesberti are included.
The Trichoptera of Panama V. Descriptions of new species, new country records, and a synonymy
(2018)
The Río Chiriqui basin is one of 52 major watershed areas, or cuencas, in the Republic of Panama. It occurs in western Panama, discharges into the Pacific Ocean, and includes portions of Volcán Barú on its northern extent. The Río Caldera occupies the northernmost subbasin of this basin. Two of its tributaries, Quebrada Grande and Quebrada Jaramillo, occur in close proximity and on opposite sides, and have different recent geologic histories and current land use patterns. During the course of investigating the caddisfly fauna of these two drainages, three new species of the microcaddisfly genus Neotrichia Morton (Trichoptera: Hydroptilidae) were identified: N. collierorum and N. anzuelo from Quebrada Jaramillo and N. tatianae from Quebrada Grande. These are described and figured herein. We also add one new genus (Rhyacopsyche Mueller) and five new country records (Hydroptila paschia Mosely, Metrichia ancora Bueno-Soria and Holzenthal, Ochrotrichia jolandae BuenoSoria and Holzenthal, Rhyacopsyche obliqua Flint, and Chimarra (Curgia) maritza Flint) for Panama. Finally, we designate Ochrotrichia abrelata Harris and Armitage, 2015 as a junior synonym of Ochrotrichia jolandae Bueno-Soria and Holzenthal, 2008. This synonymy and the newly recorded species and country records increase Panama’s known trichopteran fauna to 350 species, distributed among 15 families and 52 genera.
After publication of Blahnik and Holzenthal (2017), it was noticed that a large portion of the text had been accidentally removed from the "Phylogenetic and evolutionary comments" section during the proofing stage. The beginning of the deleted section completes the sentence on line 6 of page 129, which begins "The species included in the subgenus...". The Insecta Mundi editorial staff apologizes for this oversight. In order to provide context for the deleted excerpt, the entire "Phylogenetic and evolutionary comments" section is reproduced here, with the deleted text reincorporated. Insecta Mundi has also released a revised version of the Blahnik and Holzenthal (2017) manuscript, with this error corrected. However, the revised version is merely for convenience, and not an official peerreviewed article. Anyone wishing to reference the findings of Blahnik and Holzenthal (2017) should cite the original 2017 manuscript or this erratum. The references and figure plates cited in this section have also been reproduced here. ...
Automated deduction in higher-order program calculi, where properties of transformation rules are demanded, or confluence or other equational properties are requested, can often be done by syntactically computing overlaps (critical pairs) of reduction rules and transformation rules. Since higher-order calculi have alpha-equivalence as fundamental equivalence, the reasoning procedure must deal with it. We define ASD1-unification problems, which are higher-order equational unification problems employing variables for atoms, expressions and contexts, with additional distinct-variable constraints, and which have to be solved w.r.t. alpha-equivalence. Our proposal is to extend nominal unification to solve these unification problems. We succeeded in constructing the nominal unification algorithm NomUnifyASC. We show that NomUnifyASC is sound and complete for these problem class, and outputs a set of unifiers with constraints in nondeterministic polynomial time if the final constraints are satisfiable. We also show that solvability of the output constraints can be decided in NEXPTIME, and for a fixed number of context-variables in NP time. For terms without context-variables and atom-variables, NomUnifyASC runs in polynomial time, is unitary, and extends the classical problem by permitting distinct-variable constraints.
1998 ACM Subject Classification F.4.1 Mathematical Logic