Funktionelle Analyse des Rab3/Rabphilin-Zyklus in Maus-Nullmutanten

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Alternative N-Terminal Domains of PSD-95 and SAP97 Govern Activity-Dependent Regulation of Synaptic AMPA Receptor Function

SummaryPSD-95 and SAP97 are scaffolding proteins that have been implicated in regulating AMPA receptor incorporation and function at synapses. Gain- and loss-of-function approaches, however, have generated conflicting results. To minimize adaptations during development and potential dominant-negative effects of overexpression, we have combined silencing of endogenous PSD-95 in mature neurons with heterologous expression of specific SAP97 or PSD-95 isoforms. We find that both PSD-95 and SAP97 contain alternative N termini expressing either double cysteines that normally are palmitoylated (α-isoforms) or an L27 domain (β-isoforms). Whereas α-isoforms of PSD-95 and SAP97 influence AMPA receptor-mediated synaptic strength independent of activity, the effects of β-isoforms are regulated by activity in a CaMKII-dependent manner. Importantly, the synaptic effects of the β-isoforms are masked by the endogenous α-isoform of PSD-95. These results demonstrate that the different N termini of the predominant endogenous forms of PSD-95 (α-isoform) and SAP97 (β-isoform) govern their role in regulating synaptic function

An Unusual Suspect in Cocaine Addiction

Development of drug addiction is extremely complex, but its initiation can be as simple as the flip-flop of glutamatergic receptor subtypes triggered by an “unusual” type of NMDA receptors, as suggested by Yuan et al. (2013) in this issue of Neuron

Effect of Cereal α-Amylase/Trypsin Inhibitors on Developmental Characteristics and Abundance of Digestive Enzymes of Mealworm Larvae (Tenebrio molitor L.)

The objective of this work was to investigate the potential effect of cereal α-amylase/trypsin inhibitors (ATIs) on growth parameters and selective digestive enzymes of Tenebrio molitor L. larvae. The approach consisted of feeding the larvae with wheat, sorghum and rice meals containing different levels and composition of α-amylase/trypsin inhibitors. The developmental and biochemical characteristics of the larvae were assessed over feeding periods of 5 h, 5 days and 10 days, and the relative abundance of α-amylase and selected proteases in larvae were determined using liquid chromatography tandem mass spectrometry. Overall, weight gains ranged from 21% to 42% after five days of feeding. The larval death rate significantly increased in all groups after 10 days of feeding (p < 0.05), whereas the pupation rate was about 25% among larvae fed with rice (Oryza sativa L.) and Siyazan/Esperya wheat meals, and only 8% and 14% among those fed with Damougari and S35 sorghum meals. As determined using the Lowry method, the protein contents of the sodium phosphate extracts ranged from 7.80 ± 0.09 to 9.42 ± 0.19 mg/mL and those of the ammonium bicarbonate/urea reached 19.78 ± 0.16 to 37.47 ± 1.38 mg/mL. The total protein contents of the larvae according to the Kjeldahl method ranged from 44.0 and 49.9 g/100 g. The relative abundance of α-amylase, CLIP domain-containing serine protease, modular serine protease zymogen and C1 family cathepsin significantly decreased in the larvae, whereas dipeptidylpeptidase I and chymotrypsin increased within the first hours after feeding (p < 0.05). Trypsin content was found to be constant independently of time or feed material. Finally, based on the results we obtained, it was difficult to substantively draw conclusions on the likely effects of meal ATI composition on larval developmental characteristics, but their effects on the digestive enzyme expression remain relevant

Composite materials for innovative urban farming of alternative food sources (macroalgae and crickets)

Facing an inexorable growth of the human population along with substantial environmental changes, the assurance of food security is a major challenge of the present century. To ensure responsible food consumption and production (SDG 12), new approaches in the food system are required. Thus, environmentally controlled, sustainable production of alternative food sources are of key interest for both urban agriculture and food research. To face the current challenge of integrating food production systems within existing structures, multidisciplinary discourses are required. Here, we bring together novel technologies and indoor farming techniques with the aim of supporting the development of sustainable food production systems. For this purpose, we investigated the feasibility of 10 composite materials for their innovative use as structural support in macroalgal cultivation (settlement substrates) and cricket rearing (housing). Considering material resistance, rigidity, and direct material-organism interactions, the bio-based composite polylactic acid (PLA) was identified as a suitable material for joint farming. For macroalgae cultivation, PLA sustained the corrosive cultivation conditions and provided a suitable substrate without affecting the macroalgal physiology or nutritional composition (carotenoids and chlorophylls). For cricket rearing, PLA provided a suitable and recyclable shelter, which was quickly accepted by the animals without any observed harm. In contrast, other common composite components like phenolic resin or aramid were found to be unsuitable due to being harmful for the cultivated organisms or instable toward the applied sterilization procedure. This multidisciplinary study not only provides profound insights in the developing field of urban indoor food production from a new perspective, but also bridges material science and farming approaches to develop new sustainable and resilient food production systems

Circuit-wide Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulating Depression Susceptibility

Depression is a complex, heterogeneous disorder and a leading contributor to the global burden of disease. Most previous research has focused on individual brain regions and genes contributing to depression. However, emerging evidence in humans and animal models suggests that dysregulated circuit function and gene expression across multiple brain regions drive depressive phenotypes. Here we performed RNA-sequencing on 4 brain regions from control animals and those susceptible or resilient to chronic social defeat stress at multiple time points. We employed an integrative network biology approach to identify transcriptional networks and key driver genes that regulate susceptibility to depressive-like symptoms. Further, we validated in vivo several key drivers and their associated transcriptional networks that regulate depression susceptibility and confirmed their functional significance at the levels of gene transcription, synaptic regulation and behavior. Our study reveals novel transcriptional networks that control stress susceptibility and offers fundamentally new leads for antidepressant drug discovery

Laser-induced acceleration of Helium ions from unpolarized gas jets

In order to develop a laser-driven spin-polarized ³He-ion beam source available for nuclear-physics experiments as well as for the investigation of polarized nuclear fusion, several challenges have to be overcome. Apart from the provision of a properly polarized ³He gas-jet target, one of the biggest milestones is the demonstration of the general feasibility of laser-induced ion acceleration out of gas-jet targets. Of particular importance is the knowledge about the main ion-emission angles as well as the achievable ion-energy spectra (dependent on the optimal set of laser and target parameters). We report on the results of such a feasibility study performed at PHELIX, GSI Darmstadt. Both ³He- and ⁴He-gas jets (ngas ∼ 10¹⁹ cm⁻³) were illuminated with high-intensity laser pulses, IL ∼ O (10¹⁹ W cm⁻²). The main ion-emission angles could be identified (±90° with respect to the laser-propagation direction) and the ion-energy spectra for all ion species could be extracted: for the optimal laser and target parameters, the high-energy cut-offs for He ²⁺,¹⁺ ions were 4.65 MeV (with a normalized energy uncertainty of Δ ɛ​ ɛ​⁻¹ = 0.033) and 3.27 MeV (Δ ɛ​ ɛ​⁻¹= 0.055), respectively

Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil

Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness