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Magnetic microcalorimeters (MMCs) are cryogenic, energy-dispersive single-particle detectors providing excellent energy resolution, intrinsically fast signal rise time, quantum efficiency close to 100\%, large dynamic range as well as almost ideal linear response. One of the remaining challenges to be overcome to ultimately allow for the utilization of large-scale MMC based detector arrays with thousands to millions of individual pixels is the realization of a SQUID based multiplexing technique particularly tailored for MMC readout. Within this context, we report on the first truly multiplexed readout of an MMC based detector array using a frequency-division multiplexing approach realized by a custom microwave SQUID multiplexer based readout system., Comment: Conference: ASC2022 (accepted for publication in IEEE Transactions on Applied Superconductivity)

Background: Nutritional beliefs play an important role when it comes to food choice. However, little attention has been paid to which foods individuals believe to be comforting when experiencing stress. With increasing health awareness in the general public, this study aims to examine whether the nutritional belief exists that only healthy foods relieve stress. If so, we are interested in its relationship to Orthorexia Nervosa (ON) tendencies. Methods: 175 participants (mean age 28.5 ± 7.8 years, 124 females) completed questionnaires to assess beliefs about stress-relieving foods and ON tendencies. Principal component analysis was used to reduce foods to food groups. Subsequently, a latent profile analysis was performed to identify groups with distinct nutritional beliefs. Results: Among eight distinct groups, one group (8% of the sample) reported the belief that exclusively healthy foods relieve stress. Multinominal logistic regressions showed that higher ON tendencies were associated with that group. Conclusions: Our findings suggest that individuals with stronger ON tendencies believe that, in particular, healthy foods relieve stress. This indicates that nutritional beliefs in ON concern not only the somatic consequences of certain foods, but also psychological consequences, which might also drive orthorexic behaviour. This offers a new target for the diagnosis and treatment of ON.

Nutritional beliefs play an important role when it comes to food choice. However, little attention has been paid to which foods individuals believe to be comforting when experiencing stress. With increasing health awareness in the general public, this study aims to examine whether the nutritional belief exists that only healthy foods relieve stress. If so, we are interested in its relationship to Orthorexia Nervosa (ON) tendencies.175 participants (mean age 28.5 ± 7.8 years, 124 females) completed questionnaires to assess beliefs about stress-relieving foods and ON tendencies. Principal component analysis was used to reduce foods to food groups. Subsequently, a latent profile analysis was performed to identify groups with distinct nutritional beliefs.Among eight distinct groups, one group (8% of the sample) reported the belief that exclusively healthy foods relieve stress. Multinominal logistic regressions showed that higher ON tendencies were associated with that group.Our findings suggest that individuals with stronger ON tendencies believe that, in particular, healthy foods relieve stress. This indicates that nutritional beliefs in ON concern not only the somatic consequences of certain foods, but also psychological consequences, which might also drive orthorexic behaviour. This offers a new target for the diagnosis and treatment of ON.

The COVID-19 pandemic is a global stressor with inter-individually differing influences on mental health trajectories. Polygenic Risk Scores (PRSs) for psychiatric phenotypes are associated with individual mental health predispositions. Elevated hair cortisol concentrations (HCC) and high PRSs are related to negative mental health outcomes. We analyzed whether PRSs and HCC are related to different mental health trajectories during the first COVID lockdown in Germany. Among 523 participants selected from the longitudinal resilience assessment study (LORA), we previously reported three subgroups (acute dysfunction, delayed dysfunction, resilient) based on weekly mental health (GHQ-28) assessment during COVID lockdown. DNA from blood was collected at the baseline of the original LORA study (n = 364) and used to calculate the PRSs of 12 different psychopathological phenotypes. An explorative bifactor model with Schmid-Leiman transformation was calculated to extract a general genetic factor for psychiatric disorders. Hair samples were collected quarterly prior to the pandemic for determining HCC (n = 192). Bivariate logistic regressions were performed to test the associations of HCC and the PRS factors with the reported trajectories. The bifactor model revealed 1 general factor and 4 sub-factors. Results indicate a significant association between increased values on the general risk factor and the allocation to the acute dysfunction class. The same was found for elevated HCC and the exploratorily tested sub-factor "childhood-onset neurodevelopmental disorders". Genetic risk and long-term cortisol secretion as a potential indicator of stress, indicated by PRSs and HCC, respectively, predicted different mental health trajectories. Results indicate a potential for future studies on risk prediction.

Due to their excellent energy resolution, the intrinsically fast signal rise time, the huge energy dynamic range, and the almost ideally linear detector response, metallic magnetic calorimeters (MMC)s are very well suited for a variety of applications in physics. In particular, the ECHo experiment aims to utilize large-scale MMC-based detector arrays to investigate the mass of the electron neutrino. Reading out such arrays is a challenging task which can be tackled using microwave SQUID multiplexing. Here, the detector signals are transduced into frequency shifts of superconducting microwave resonators, which can be deduced using a high-end software-defined radio (SDR) system. The ECHo SDR system is a custom-made modular electronics, which provides 400 channels equally distributed in a 4 to 8 GHz frequency band. The system consists of a superheterodyne RF frequency converter with two successive mixers, a modular conversion, and an FPGA board. For channelization, a novel heterogeneous approach, utilizing the integrated digital down conversion (DDC) of the ADC, a polyphase channelizer, and another DDC for demodulation, is proposed. This approach has excellent channelization properties while being resource-efficient at the same time. After signal demodulation, on-FPGA flux-ramp demodulation processes the signals before streaming it to the data processing and storage backend.

Inhibition of PIKfyve phosphoinositide kinase selectively kills autophagy-dependent cancer cells by disrupting lysosome homeostasis. Here, we show that PIKfyve inhibitors can also selectively eliminate pluripotent embryonal carcinoma cells (ECCs), embryonic stem cells, and induced pluripotent stem cells under conditions where differentiated cells remain viable. PIKfyve inhibitors prevented lysosome fission, induced autophagosome accumulation, and reduced cell proliferation in both pluripotent and differentiated cells, but they induced death only in pluripotent cells. The ability of PIKfyve inhibitors to distinguish between pluripotent and differentiated cells was confirmed with xenografts derived from ECCs. Pretreatment of ECCs with the PIKfyve specific inhibitor WX8 suppressed their ability to form teratocarcinomas in mice, and intraperitoneal injections of WX8 into mice harboring teratocarcinoma xenografts selectively eliminated pluripotent cells. Differentiated cells continued to proliferate, but at a reduced rate. These results provide a proof of principle that PIKfyve specific inhibitors can selectively eliminate pluripotent stem cells in vivo as well as in vitro.

Resilience has been defined as the maintenance or quick recovery of mental health during and after times of adversity. How to operationalize resilience and to determine the factors and processes that lead to good long-term mental health outcomes in stressor-exposed individuals is a matter of ongoing debate and of critical importance for the advancement of the field. One of the biggest challenges for implementing an outcome-based definition of resilience in longitudinal observational study designs lies in the fact that real-life adversity is usually unpredictable and that its substantial qualitative as well as temporal variability between subjects often precludes defining circumscribed time windows of inter-individually comparable stressor exposure relative to which the maintenance or recovery of mental health can be determined. To address this pertinent issue, we propose to frequently and regularly monitor stressor exposure (E) and mental health problems (P) throughout a study's observation period [Frequent Stressor and Mental Health Monitoring (FRESHMO)-paradigm]. On this basis, a subject's deviation at any single monitoring time point from the study sample's normative E–P relationship (the regression residual) can be used to calculate that subject's current mental health reactivity to stressor exposure (“stressor reactivity,” SR). The SR score takes into account the individual extent of experienced adversity and is comparable between and within subjects. Individual SR time courses across monitoring time points reflect intra-individual temporal variability in SR, where periods of under-reactivity (negative SR score) are associated with accumulation of fewer mental health problems than is normal for the sample. If FRESHMO is accompanied by regular measurement of potential resilience factors, temporal changes in resilience factors can be used to predict SR time courses. An increase in a resilience factor measurement explaining a lagged decrease in SR can then be considered to index a process of adaptation to stressor exposure that promotes a resilient outcome (an allostatic resilience process). This design principle allows resilience research to move beyond merely determining baseline predictors of resilience outcomes, which cannot inform about how individuals successfully adjust and adapt when confronted with adversity. Hence, FRESHMO plus regular resilience factor monitoring incorporates a dynamic-systems perspective into resilience research.

Substantial evidence shows that physical activity and fitness play a protective role in the development of stress related disorders. However, the beneficial effects of fitness for resilience to modern life stress are not fully understood. Potentially protective effects may be attributed to enhanced resilience via underlying psychosocial mechanisms such as self-efficacy expectations. This study investigated whether physical activity and fitness contribute to prospectively measured resilience and examined the mediating effect of general self-efficacy. 431 initially healthy adults participated in fitness assessments as part of a longitudinal-prospective study, designed to identify mechanisms of resilience. Self-efficacy and habitual activity were assessed in parallel to cardiorespiratory and muscular fitness, which were determined by a submaximal step-test, hand strength and standing long jump test. Resilience was indexed by stressor reactivity: mental health problems in relation to reported life events and daily hassles, monitored quarterly for nine months. Hierarchical linear regression models and bootstrapped mediation analyses were applied. We could show that muscular and self-perceived fitness were positively associated with stress resilience. Extending this finding, the muscular fitness–resilience relationship was partly mediated by self-efficacy expectations. In this context, self-efficacy expectations may act as one underlying psychological mechanism, with complementary benefits for the promotion of mental health. While physical activity and cardiorespiratory fitness did not predict resilience prospectively, we found muscular and self-perceived fitness to be significant prognostic parameters for stress resilience. Although there is still more need to identify specific fitness parameters in light of stress resilience, our study underscores the general relevance of fitness for stress-related disorders prevention.

The COVID-19 pandemic and resulting measures can be regarded as a global stressor. Cross-sectional studies showed rather negative impacts on people’s mental health, while longitudinal studies considering pre-lockdown data are still scarce. The present study investigated the impact of COVID-19 related lockdown measures in a longitudinal German sample, assessed since 2017. During lockdown, 523 participants completed additional weekly online questionnaires on e.g., mental health, COVID-19-related and general stressor exposure. Predictors for and distinct trajectories of mental health outcomes were determined, using multilevel models and latent growth mixture models, respectively. Positive pandemic appraisal, social support, and adaptive cognitive emotion regulation were positively, whereas perceived stress, daily hassles, and feeling lonely negatively related to mental health outcomes in the entire sample. Three subgroups (“recovered,” 9.0%; “resilient,” 82.6%; “delayed dysfunction,” 8.4%) with different mental health responses to initial lockdown measures were identified. Subgroups differed in perceived stress and COVID-19-specific positive appraisal. Although most participants remained mentally healthy, as observed in the resilient group, we also observed inter-individual differences. Participants’ psychological state deteriorated over time in the delayed dysfunction group, putting them at risk for mental disorder development. Consequently, health services should especially identify and allocate resources to vulnerable individuals.

The COVID-19 pandemic and resulting measures can be regarded as a global stressor. Cross-sectional studies showed rather negative impacts on people’s mental health, while longitudinal studies considering pre-lockdown data are still scarce. The present study investigated the impact of COVID-19 related lockdown measures in a longitudinal German sample, assessed since 2017. During lockdown, 523 participants completed additional weekly online questionnaires on e.g., mental health, COVID-19-related and general stressor exposure. Predictors for and distinct trajectories of mental health outcomes were determined, using multilevel models and latent growth mixture models, respectively. Positive pandemic appraisal, social support, and adaptive cognitive emotion regulation were positively, whereas perceived stress, daily hassles, and feeling lonely negatively related to mental health outcomes in the entire sample. Three subgroups (“recovered,” 9.0%; “resilient,” 82.6%; “delayed dysfunction,” 8.4%) with different mental health responses to initial lockdown measures were identified. Subgroups differed in perceived stress and COVID-19-specific positive appraisal. Although most participants remained mentally healthy, as observed in the resilient group, we also observed inter-individual differences. Participants’ psychological state deteriorated over time in the delayed dysfunction group, putting them at risk for mental disorder development. Consequently, health services should especially identify and allocate resources to vulnerable individuals.

Versatile high-throughput method can isolate single cells based on spatiotemporal phenotypes., Unraveling the genetic and epigenetic determinants of phenotypes is critical for understanding and re-engineering biology and would benefit from improved methods to separate cells based on phenotypes. Here, we report SPOTlight, a versatile high-throughput technique to isolate individual yeast or human cells with unique spatiotemporal profiles from heterogeneous populations. SPOTlight relies on imaging visual phenotypes by microscopy, precise optical tagging of single target cells, and retrieval of tagged cells by fluorescence-activated cell sorting. To illustrate SPOTlight’s ability to screen cells based on temporal properties, we chose to develop a photostable yellow fluorescent protein for extended imaging experiments. We screened 3 million cells expressing mutagenesis libraries and identified a bright new variant, mGold, that is the most photostable yellow fluorescent protein reported to date. We anticipate that the versatility of SPOTlight will facilitate its deployment to decipher the rules of life, understand diseases, and engineer new molecules and cells.

Resilience has been defined as the maintenance or quick recovery of mental health during and after times of adversity. Such good longer-term mental health outcomes despite adversity presumably result from complex and dynamic processes of adaptation to stressor exposure (‘resilience processes’), which in many cases include changes in individual properties. Measuring resilience and identifying resilience processes in observational studies requires longitudinal designs involving repeated and frequent monitoring of mental health, stressor exposure, and potential adaptations. We here present a generic design solution that is currently employed in two cohort studies, the Mainz Resilience Project (MARP) and the Longitudinal Resilience Assessment (LORA). Both projects focus on resilience to everyday life stressors (i.e., microstressors), but we argue that the design scheme is also suitable for studying resilience to macrostressors, or trauma, and can solve some of the pertinent problems of trauma resilience research. We quantify resilience by indexing the reactivity of individuals’ mental health to stressors during a time interval of several months in a ‘stressor reactivity’ (SR) score, derived using a previously introduced residualization approach. SR scores are regularly re-calculated in sliding time windows, to thus build SR time courses that reflect intra-individual temporal variability in resilience. By linking these time courses to repeated measures of (temporally varying) individual properties, resilience processes can be identified. We finish by a discussion of limitations of our approach and potential future developments.

Resilience is the maintenance and/or quick recovery of mental health during and after periods of adversity. It is conceptualized to result from a dynamic process of successful adaptation to stressors. Up to now, a large number of resilience factors have been proposed, but the mechanisms underlying resilience are not yet understood. To shed light on the complex and time-varying processes of resilience that lead to a positive long-term outcome in the face of adversity, the Longitudinal Resilience Assessment (LORA) study has been established. In this study, 1191 healthy participants are followed up at 3- and 18-month intervals over a course of 4.5 years at two study centers in Germany. Baseline and 18-month visits entail multimodal phenotyping, including the assessment of mental health status, sociodemographic and lifestyle variables, resilience factors, life history, neuropsychological assessments (of proposed resilience mechanisms), and biomaterials (blood for genetic and epigenetic, stool for microbiome, and hair for cortisol analysis). At 3-monthly online assessments, subjects are monitored for subsequent exposure to stressors as well as mental health measures, which allows for a quantitative assessment of stressor-dependent changes in mental health as the main outcome. Descriptive analyses of mental health, number of stressors including major life events, daily hassles, perceived stress, and the ability to recover from stress are here presented for the baseline sample. The LORA study is unique in its design and will pave the way for a better understanding of resilience mechanisms in humans and for further development of interventions to successfully prevent stress-related disorder. Electronic supplementary material The online version of this article (10.1007/s00406-020-01159-2) contains supplementary material, which is available to authorized users.

The European physical journal / C Particles and fields C 79(12), 1026 (2019). doi:10.1140/epjc/s10052-019-7513-x, Published by Springer, Heidelberg

To our present best knowledge, microwave SQUID multiplexing ( $$\mu $$ MUXing) is the most suitable technique for reading out large-scale low-temperature microcalorimeter arrays that consist of hundreds or thousands of individual pixels which require a large readout bandwidth per pixel. For this reason, the present readout strategy for metallic magnetic calorimeter (MMC) arrays combining an intrinsic fast signal rise time, an excellent energy resolution, a large energy dynamic range, a quantum efficiency close to $$100\%$$ as well as a highly linear detector response is based on $$\mu $$ MUXing. Within this paper, we summarize the state of the art in MMC $$\mu $$ MUXing and discuss the most recent results. This particularly includes the discussion of the performance of a 64-pixel detector array with integrated, on-chip microwave SQUID multiplexer, the progress in flux ramp modulation of MMCs as well as the status of the development of a software-defined radio-based room-temperature electronics which is specifically optimized for MMC readout.

ZusammenfassungAktuelle epidemiologische Daten zeigen in den letzten Jahren einen Anstieg der Tuberkulose im Kindes- und Jugendalter. Es findet sich zudem auch in Deutschland ein Anstieg von Infektionen mit gegenüber Tuberkulosemedikamenten resistenten Erregern. In diesem Zusammenhang stellt die Diagnose, Prävention und Therapie der Tuberkulose vor allem im Kindesalter eine Herausforderung dar.Leitlinien für die Diagnostik und Therapie der Tuberkulose im Erwachsenenalter können nicht generell auf das Kindesalter übertragen werden, da hier relevante altersabhängige Unterschiede bzgl. der Krankheitsprogression, Krankheitsmanifestation, Unterschiede in der Anwendung von diagnostischen Maßnahmen und der Therapie bestehen.Unter Federführung der Deutschen Gesellschaft für Pädiatrische Infektiologie (DGPI) e. V. wurde die S2k-Leitlinie für die Diagnostik, Prävention und Therapie der Tuberkulose im Kindes- und Jugendalter verfasst, um die adäquate Versorgung von Kindern und Jugendlichen mit Tuberkulose-Exposition, Infektion oder Erkrankung nach neuesten wissenschaftlichen Erkenntnissen zu sichern.Aktualisierte Dosierungsempfehlungen berücksichtigen die altersabhängige Pharmakokinetik in der Therapie der medikamentensensiblen, aber auch resistenten Tuberkulose. Darüber hinaus werden die Themen perinatale Exposition und Erkrankung sowie die im Kindesalter häufigeren extrapulmonalen Manifestationsformen gesondert behandelt.

Recently, epidemiological data shows an increase of childhood tuberculosis in Germany. In addition to this, drug resistant tuberculosis becomes more frequent. Therefore, diagnosis, prevention and therapy in childhood and adolescence remain a challenge. Adult guidelines do not work for children, as there are age specific differences in manifestation, risk of progression and diagnostic as well as therapeutic pathways.The German Society for Pediatric Infectious Diseases (DGPI) has initiated a consensus-based (S2k) process and completed a paediatric guideline in order to improve and standardize care for children and adolescents with tuberculosis exposure, infection or disease.Updated dosage recommendations take age dependant pharmacokinetics in the treatment of drug sensitive but also drug resistant tuberculosis in account. In addition to this, there is a detailed chapter on perinatal exposure and disease as well as extrapulmonary manifestations.Aktuelle epidemiologische Daten zeigen in den letzten Jahren einen Anstieg der Tuberkulose im Kindes- und Jugendalter. Es findet sich zudem auch in Deutschland ein Anstieg von Infektionen mit gegenüber Tuberkulosemedikamenten resistenten Erregern. In diesem Zusammenhang stellt die Diagnose, Prävention und Therapie der Tuberkulose vor allem im Kindesalter eine Herausforderung dar.Leitlinien für die Diagnostik und Therapie der Tuberkulose im Erwachsenenalter können nicht generell auf das Kindesalter übertragen werden, da hier relevante altersabhängige Unterschiede bzgl. der Krankheitsprogression, Krankheitsmanifestation, Unterschiede in der Anwendung von diagnostischen Maßnahmen und der Therapie bestehen.Unter Federführung der Deutschen Gesellschaft für Pädiatrische Infektiologie (DGPI) e. V. wurde die S2k-Leitlinie für die Diagnostik, Prävention und Therapie der Tuberkulose im Kindes- und Jugendalter verfasst, um die adäquate Versorgung von Kindern und Jugendlichen mit Tuberkulose-Exposition, Infektion oder Erkrankung nach neuesten wissenschaftlichen Erkenntnissen zu sichern.Aktualisierte Dosierungsempfehlungen berücksichtigen die altersabhängige Pharmakokinetik in der Therapie der medikamentensensiblen, aber auch resistenten Tuberkulose. Darüber hinaus werden die Themen perinatale Exposition und Erkrankung sowie die im Kindesalter häufigeren extrapulmonalen Manifestationsformen gesondert behandelt.

Reactions of the hydroxide ion OH–(H2O)0,1,2,3, solvated with 0–3 water molecules, have been studied in the gas phase using flow-tube and ion-beam techniques. The reactions studied included proton transfer, nucleophilic displacement and isotope exchange. The experiments measure, as a function of the reactant solvation number, the dependence of rate constant on temperature or of cross-section on energy, for each of the possible solvation numbers of the products. The experiments reveal the pathway of the solvent molecules in the reaction and their kinetic role in facilitating or quenching reaction. Proton transfer is usually facile, unaffected by solvent molecules, giving solvated products: solvent molecules quench nucleophilic displacement, giving unsolvated products. For solvent molecules to transfer from reactants to product, they must track the charge as it moves in the reaction intermediate. This is governed by the structure of the transition state, possible for proton transfer but not for nucleophilic displacement. A complete description of the isotope exchange reaction OH–+ D2⇌ OD–+ HD is given throughout the full range of solvation. The gas-phase studies identify the intermediate in solution and predict correctly the activation energy in solution. Throughout we consider if solvated-ion reactions ‘bridge the gap’ between studies without solvation in the gas phase and studies with complete solvation in solution.

Three digestibility experiments were conducted to evaluate the potential of determination of apparent ileal digestibilities (AID) of crude protein (CP) and amino acids (AA) by the mobile nylon bag technique (MNBT) using 21 feedstuffs and three mixed diets. In two conventional digestibility experiments (Exp. 1 and 2), AID were determined using in total 10 barrows (BW 35 kg) fitted with simple T-cannulas at the terminal ileum. For the MNBT studies, four pigs were fitted with a simple T-cannula at the proximal duodenum and a Post-Valve T-Caecum (PVTC) cannula at the terminal ileum. The MNBT studies included the feedstuffs (n = 10) from Exp. 1 and 2 as well as 14 further feedstuffs and mixed diets in which AID coefficients had been determined in previous trials. For each feedstuff 60 nylon bags were used. In vitro digestion of the bags was carried out in pepsin-HCl solution with 450 IU pepsin/l at pH 2.0 and 37°C for 4 h. In the 28-day in vivo experiment, 15 nylon bags per pig and day were inserted through the duodenal cannula and collected through the PVTC cannula after passage through the small intestine. Coefficients of AID were calculated based on the disappearance of CP and AA from the nylon bags during the in vitro and in vivo phase. In comparison with AID determined by the conventional method, AID of CP was on average 2.4% lower, whereas AID of lysine was on average 8.5% higher when determined by the MNBT. There was no significant (P > 0.05) correlation between AID coefficients of CP and AA determined by the conventional method and the MNBT, when all feedstuffs were taken into account. However, in cereals (n = 11), the correlation between AID coefficients determined by both methods was significant (P < 0.05) for CP (r = 0.61) and some AA (r ranging between 0.62 and 0.72). In conclusion, the potential of the MNBT to determine AID of CP and AA is rather limited. Differences in coefficients of AID of CP and AA were attributed to several factors such as diffusion of sample particles or endogenous protein through the nylon bags as well as to the presence of anti-nutritional factors (e.g. in legume seeds and oilseed meals). Three digestibility experiments were conducted to evaluate the potential of determination of apparent ileal digestibilities (AID) of crude protein (CP) and amino acids (AA) by the mobile nylon bag technique (MNBT) using 21 feedstuffs and three mixed diets. In two conventional digestibility experiments (Exp. 1 and 2), AID were determined using in total 10 barrows (BW 35 kg) fitted with simple T-cannulas at the terminal ileum. For the MNBT studies, four pigs were fitted with a simple T-cannula at the proximal duodenum and a Post-Valve T-Caecum (PVTC) cannula at the terminal ileum. The MNBT studies included the feedstuffs (n = 10) from Exp. 1 and 2 as well as 14 further feedstuffs and mixed diets in which AID coefficients had been determined in previous trials. For each feedstuff 60 nylon bags were used. In vitro digestion of the bags was carried out in pepsin-HCl solution with 450 IU pepsin/l at pH 2.0 and 37°C for 4 h. In the 28-day in vivo experiment, 15 nylon bags per pig and day were inserted through the duodenal cannula and collected through the PVTC cannula after passage through the small intestine. Coefficients of AID were calculated based on the disappearance of CP and AA from the nylon bags during the in vitro and in vivo phase. In comparison with AID determined by the conventional method, AID of CP was on average 2.4% lower, whereas AID of lysine was on average 8.5% higher when determined by the MNBT. There was no significant (P > 0.05) correlation between AID coefficients of CP and AA determined by the conventional method and the MNBT, when all feedstuffs were taken into account. However, in cereals (n = 11), the correlation between AID coefficients determined by both methods was significant (P < 0.05) for CP (r = 0.61) and some AA (r ranging between 0.62 and 0.72). In conclusion, the potential of the MNBT to determine AID of CP and AA is rather limited. Differences in coefficients of AID of CP and AA were attributed to several factors such as diffusion of sample particles or endogenous protein through the nylon bags as well as to the presence of anti-nutritional factors (e.g. in legume seeds and oilseed meals).

Zusammenfassung Es wurden an Minischweinen mit Blinddarmfistel die Dickdarmfermentation (pH, FFS, NH3) und die N-Verhaltnisse (Anteil BN) im Kot bei caecaler Infusion von 45, 60 g oder 75 g/Tag Laktose, Glukose, Maisstarke, Zellulose und Pektin untersucht. In weiteren Versuchen wurde der Einflus verschiedener Eiweise (Kasein, Sojaproteinisolat, Sojaextraktionsschrot, Gerste, Weizen und einer gemischten Ration) sowie einer fettarmen und N-freien Ration auf die Ausscheidungen an Gesamtstickstoff im Kot (KN) und Bakterienstickstoff (BN) im Kot untersucht. Mit Hilfe von Diaminopimelinsaure (DAP) als Marker erfolgte die Bestimmung von BN. Mit Ausnahme der Zellulose (57,3%) wurden die einzelnen Kohlenhydrate vollstandig fermentiert. Der Anstieg der Konzentration an fluchtigen Fettsauren (FFS) im Blinddarminhalt bzw. der sehr geringe Verlust an FFS im Kot ergab, das aus der Fermentation von Kohlenhydraten prinzipiell Energie fur den Ansatz verfugbar ist. Auserdem waren entsprechend der Fermentation der pH-Wert im Dickdarm, sowie die NH3-Konzentration gesenkt. Diese Befunde werden als wichtige Regulationen angesehen. Der aus den isolierten Kotbakterien ermittelte Umrechnungsfaktor von DAP in BN betrug im Mittel 19,5 und erwies sich bei verschiedenen Infusionen und Rationen als sehr konstant. Unterstutzend zu diesem Befund ergab der Limulus-Test, das die Keimzahlen relativ konstant und die gram-negativen Keime die vorherrschende Flora waren. Die Infusion der Kohlenhydrate ergab im Mittel eine BN-Syntheserate von 0,9 g BN/100 g fermentiertes Kohlenhydrat, mit Ausnahme wieder der Zellulose (2,3 g BN). Die Unterschiede zu den Verhaltnissen im Pansen werden diskutiert. Hinsichtlich der N-Verhaltnisse im Kot zeigte sich, das die Erhohung der Menge an KN ausschlieslich durch BN hervorgerufen wurde, wobei das Ausmas der BN-Synthese von der Menge an verfugbarer Energie im Dickdarm abhangig war. Zur Ausschaltung dieses Dickdarm-einflusses auf die N-Verdaulichkeit wurde eine „BN-korrigierte” Verdaulichkeit berechnet: Entsprechend dieser Formel errechnen sich fur die verwendeten Eiweise hohe „BN-korr.”-Verdaulichkeiten zwischen 93% und 98%. In wieweit diese „BN-korr.”-Verdaulichkeit der echten Verdaulichkeit entspricht, wird diskutiert.

Minipigs were fed a “Western-style”, high-cholesterol diet for a baseline period, followed by the diet containing a mixture of three Lactobacillus strains with potential probiotic features, after which a normal pig diet was followed. The faecal enzyme activity for β-glucuronidase and azoreductase, which are commonly considered as markers for procarcinogenic activity, was significantly reduced during the 5 weeks of “probiotic” supplementation. During the period of Lactobacillus administration, the cell counts for total anaerobes increased, whereas the total number of aerobes showed no change.

The effect of nitric oxide (NO) on ion transport in the porcine proximal colon was investigated in slide-stripped epithelia mounted in Ussing chambers. The serosal addition of the NO-donors sodium nitroprusside (SNP, 0.5 mM) or S-nitroso-N-acetylpenicillamine (SNAP, 0.5 mM) induced a steep increase of short-circuit current ( I sc). The stimulatory effect of SNP on I sc could not be blocked by piroxicam or tetrodotoxin. Potassium channel inhibitors (quinidine, tetraethylammonium or barium) added serosally reduced the SNP- or SNAP-induced increases of I sc. In chloride-free solutions, the SNP-induced increase of I sc was smaller than in chloride-containing solutions. Cl− and Na+ flux measurements demonstrated that SNP diminished Cl− and Na+ net absorption. Pre-treatment with barium was able to block the inhibitory effect of SNP on NaCl net absorption totally. NO effects on paracellular pathways were assessed by measuring flux rates of [14C]-D-mannitol. SNP did not change unidirectional D-mannitol flux rates. In conclusion, NO inhibits NaCl net absorption in the proximal colon of pigs by acting directly on the enterocyte. The antiabsorptive (and/or prosecretory) effect of NO depends on a functional basolateral potassium conductance.

The ability to compute the difference between two frequencies depends on a nonlinear operation that mixes two periodic signals. Behavioral and psychophysical evidence suggest that such mixing is likely to occur in the mammalian nervous system as a means to compare two rhythmic sensory signals, such as occurs in human audition, and as a means to lock an intrinsic rhythm to a sensory input. However, a neurological substrate for mixing has not been identified. Here we address the issue of nonlinear mixing of neuronal activity in the vibrissa primary sensory cortex of rat, a region that receives intrinsic as well as sensory-driven rhythmic input during natural whisking. In our preparation, the intrinsic signal originates from cortical oscillations that were induced by anesthetics, and the extrinsic input is introduced by periodic stimulation of vibrissae. We observed that the local extracellular current in vibrissa primary sensory cortex contained oscillatory components at the sum and difference of the intrinsic and extrinsic frequencies. In complementary experiments, we observed that the simultaneous stimulation of contralateral and ipsilateral vibrissae at different frequencies also led to current flow at the sum and difference frequencies. We show theoretically that the relative amplitudes of the observed mixture terms can be accounted for by a threshold nonlinearity in the input–output relation of the underlying neurons. In general, our results provide a neurological substrate for the modulation and demodulation of rhythmic neuronal signals for sensory coding and feedback stabilization of motor output.

Zusammenfassung In zwei getrennt voneinander durchgefuhrten Versuchen erhielten Gruppen von sechs und vier pansenfistulierten Angler Ochsen zweimal taglich Rationen aus Silagen von Winterweizen-Ganzpflanzen (WWGPS) und Deutschem Weidelgras (DWS), die zu verschiedenen Reifestadien einsiliert worden waren. Die Versuchsanordnung folgte in Versuch 1 einem doppelt besetzten 3 times 3 Lateinischen Quadrat und in Versuch 2 einem 4 times 4 Lateinischen Quadrat. Bei Rohproteingehalten

An experiment was carried out to examine the effects of supplementation of formic acid to semipurified diets containing fish meal for weanling pigs with low and high buffering capacity on nutrient digestion and bacterial populations and metabolites in the small intestine. Twelve barrows, weaned at 21 d, were fitted with a simple T-cannula at the distal ileum. The BW of the pigs at weaning and at the conclusion of the experiment were 7.8 and 13.8 kg, respectively. The pigs were fed four corn starch-based fish meal diets according to a two-period change-over design. The diets were formulated to contain 18% CP. For two of the diets, referred to as NCaP, fish meal was the calcium and phosphorus source. For the remaining two diets, referred to as HCaP, the levels of calcium and phosphorus were doubled (compared with the NCaP diets) by the addition of calcium carbonate and dicalcium phosphate. The diets were supplemented with (+NCaP and +HCaP) or without (−NCaP and −HCaP) 1% (wt/wt) formic acid. The buffering capacity of the HCaP diets increased (P 0.05) the apparent ileal digestibilities of AA. The pH, ammonia and VFA concentrations, bacterial populations in ileal digesta and the incidence of diarrhea were also not affected (P > 0.05). Therefore, the supplementation of 1% (wt/wt) formic acid to corn starch-based fish meal diets with low and high buffering capacity for weanling pigs (7.8–13.8 kg) does not affect nutrient digestibilities and bacterial populations in the small intestine. Key words: Pigs, formic acid, buffering capacity, digestibility, bacteria

An experiment was carried out to examine the effects of supplementing diets for weanling pigs with oligosaccharides and LAC on nutrient digestion and bacterial populations and metabolites in the small intestine. Twelve barrows, weaned at 28 d, were fitted with a simple T-cannula at the distal ileum. The BW of the pigs at weaning and at the conclusion of the experiment were 9.1 and 13.8 kg, respectively. The pigs were fed four diets based on barley, wheat and soybean meal according to a two-period change-over design. The diets were formulated to contain 18% CP. Transgalactosylated oligosaccharides (0.2%), GUO (0.2%) and LAC (1%, 4-O-β-D-galactopyranosyl-D-sorbitol) were included at the expense of corn starch. Supplementation with oligosaccharides or LAC had little effect on the apparent ileal digestibilities of AA and monosaccharides. Supplementation of diets with oligosaccharides or LAC did not affect (P > 0.05) the monosaccharide concentrations in ileal digesta except for galactose which was higher (P 0.05). Therefore, the supplementation of diets for weanling pigs (9.1–13.8 kg) with oligosaccharides or LAC at these levels does not affect nutrient digestibilities and bacterial populations in the small intestine. Key words: Pigs, oligosaccharides, lactitol, digestibility, bacteria

A fluorescent voltage sensor protein “Flare” was created from a Kv1.4 potassium channel with YFP situated to report voltage-induced conformational changes in vivo. The RNA virus Sindbis introduced Flare into neurons in the binocular region of visual cortex in rat. Injection sites were selected based on intrinsic optical imaging. Expression of Flare occurred in the cell bodies and dendritic processes. Neurons imaged in vivo using two-photon scanning microscopy typically revealed the soma best, discernable against the background labeling of the neuropil. Somatic fluorescence changes were correlated with flashed visual stimuli; however, averaging was essential to observe these changes. This study demonstrates that the genetic modification of single neurons to express a fluorescent voltage sensor can be used to assess neuronal activity in vivo.

This investigation was conducted to quantify the purine excretion of cows and to evaluate milk allantoin as an estimator of synthesis of microbial protein in the rumen. Concentrations in plasma of allantoin and uric acid and their excretion in urine and milk were determined using 16 Holstein cows at 21 to 315 d of lactation and yielding 8 to 36 kg/d of milk. The mean daily intake of a 55:45 roughage and concentrate diet was 16.3 kg of DM with 106 MJ of NEL and 13.8 to 16.0% CP. Total urine was collected over 24 h, plasma samples collected four times, and milk samples collected twice on the same day. Analyses of purine metabolites were performed with HPLC. On average, excretion of allantoin in urine and milk was about 294 and 4.1 mmol/d for allantoin and 35 and 1.1 mmol/d for uric acid. Excretion of allantoin in milk was correlated to concentration in plasma (r = .84). As milk yield increased, percentage of milk allantoin increased from .6 to 2.4% of total allantoin excretion (r = .85). The correlations of NEL intake with allantoin excretion in milk (r = .80) and in urine (r = .84) were similar. Daily milk yield was correlated with plasma allantoin (r = .78) and milk allantoin excretion (r = .95). We concluded that determination of milk allantoin is a useful, noninvasive method to monitor rumen microbial protein synthesis.

The putative excitatory and inhibitory cell classes within the mouse primary visual cortex V1 have different functional properties as studied using recording microelectrode. Excitatory neurons show high selectivity for the orientation angle of moving gratings while the putative inhibitory neurons show poor selectivity. However, the study of selectivity of the genetically identified interneurons and their subtypes remain controversial. Here we use novel Cre-driver and reporter mice to identify genetic subpopulations in vivo for two photon calcium dye imaging: Wfs1(+) / Gad1(-) mice that labels layer 2/3 excitatory cell population and Pvalb(+) / Gad1(+) mice that labels a genetic subpopulation of inhibitory neurons. The cells in both mice were identically labeled with a tdTomato protein, visible in vivo, using a Cre-reporter line. We found that the Wfs1(+) cells exhibited visual tuning properties comparable to the excitatory population, i.e. high selectivity and tuning to the angle, direction and spatial frequency of oriented moving gratings. The functional tuning of Pvalb(+) neurons was consistent with previously reported narrow spiking interneurons in microelectrode studies, exhibiting poorer selectivity than the excitatory neurons. This study demonstrates the utility of Cre-transgenic mouse technology in selective targeting of subpopulations of neurons and makes them amenable to structural, functional and connectivity studies.

Six gilts, with an average BW of 70 kg, were fitted with a simple T-cannula at the distal ileum to study the effect of continuous starch infusion on urea kinetics by means of a radioisotope dilution technique. The pigs were fed twice daily 600 g of a cornstarch-based diet formulated to contain 16% CP by supplementation with isolated soy protein. Infusion of starch, compared with water, decreased (P .05). Expressed as a percentage of total entry rate, approximately 40% of urea was recycled into the digestive tract in both infusion treatments. The stimulation of microbial fermentation in the large intestine resulted in an increase (P < .05) in fecal N excretion, which was mainly due to an increased excretion of bacterial N. This increase could not be attributed to a greater secretion of urea into the large intestine and its subsequent utilization by the intestinal microflora. The increased bacterial N assimilation after starch infusion led to a reduction in ammonia absorption from the large intestine, which in turn was reflected by a reduced urinary N excretion. As a result, the overall N balance was not affected. In a second experiment, two barrows, with an average BW of 80 kg, were fed twice daily 1.4 kg of a cereal-based diet. The body urea pool of both pigs was labeled with a single injection of 1 g and 2 g of [15N]urea, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

A total of six barrows (Yorkshire X Lacombe), with an average body weight of 50 kg, were surgically fitted with two simple T-cannulas, one at the distal ileum and one in the cecum. Following recovery, four of the pigs were fed one of four diets according to a 4 × 4 Latin square design. The basal diet (Treatment 1) contained 15% soya-bean meal, 61.9% barley, 10% wheat bran, 10% beet pulp, 2.6% of a vitamin-mineral mixture and 0.5% chromic oxide as a digestibility marker. Treatments 2, 3 and 4 were the basal diet supplemented with 2% propionic acid (PA), 2.5% siliceous earth (SE), and a combination of 2% PA and 2.5% SE, respectively. The pigs were fed twice daily: the daily dietary allowances were 1.8 kg, 1.84 kg, 1.85 kg and 1.88 kg for Treatments 1, 2, 3 and 4, respectively. Each experimental period lasted 12 days. Following an 8 day adaptation period, feces were collected for 2 days followed by a 12 h collection of cecal digesta on Day 11 and a 12 h collection of ileal digesta on Day 12. Apparent ileal digestibilities of dry matter, organic matter, crude protein, ash or energy were not affected (P > 0.05) when PA or a combination of PA and SE, were supplemented. However, the supplementation of PA improved (P 0.05) the ileal amino acid digestibilities. The supplementation of PA or SE, or a combination of these, had little effect on the apparent amino acid digestibilities when these were measured with the fecal analysis method. There was no effect (P > 0.05) on the concentration of putrescine, cadaverine and ammonia in ileal digesta when PA, SE or a combination of these were supplemented. However, the supplementation of PA decreased (P