Targeted therapy of cognitive deficits in fragile X syndrome.

Breaking an impasse in finding mechanism-based therapies of neuropsychiatric disorders requires a strategic shift towards alleviating individual symptoms. Here we present a symptom and circuit-specific approach to rescue deficits of reward learning in Fmr1 knockout mice, a model of Fragile X syndrome (FXS), the most common monogenetic cause of inherited mental disability and autism. We use high-throughput, ecologically-relevant automated tests of cognition and social behavior to assess effectiveness of the circuit-targeted injections of designer nanoparticles, loaded with TIMP metalloproteinase inhibitor 1 protein (TIMP-1). Further, to investigate the impact of our therapeutic strategy on neuronal plasticity we perform long-term potentiation recordings and high-resolution electron microscopy. We show that central amygdala-targeted delivery of TIMP-1 designer nanoparticles reverses impaired cognition in Fmr1 knockouts, while having no impact on deficits of social behavior, hence corroborating symptom-specificity of the proposed approach. Moreover, we elucidate the neural correlates of the highly specific behavioral rescue by showing that the applied therapeutic intervention restores functional synaptic plasticity and ultrastructure of neurons in the central amygdala. Thus, we present a targeted, symptom-specific and mechanism-based strategy to remedy cognitive deficits in Fragile X syndrome.

Acceleration and transport of relativistic electrons in the jets of the microquasar SS 433.

SS 433 is a microquasar, a stellar binary system that launches collimated relativistic jets. We observed SS 433 in gamma rays using the High Energy Stereoscopic System (H.E.S.S.) and found an energy-dependent shift in the apparent position of the gamma-ray emission from the parsec-scale jets. These observations trace the energetic electron population and indicate that inverse Compton scattering is the emission mechanism of the gamma rays. Our modeling of the energy-dependent gamma-ray morphology constrains the location of particle acceleration and requires an abrupt deceleration of the jet flow. We infer the presence of shocks on either side of the binary system, at distances of 25 to 30 parsecs, and that self-collimation of the precessing jets forms the shocks, which then efficiently accelerate electrons.

V3 interneuron subpopulations in the mouse spinal cord undergo distinctive postnatal maturation processes.

Mice develop weight-bearing locomotion within the first 2-3 weeks of birth, a period during which motoneurons (MNs) and interneurons (INs) that control locomotor activities undergo rapid maturation. In this study, we investigate the maturation of two subpopulations of V3 INs in the mouse spinal cord during this period. To do this, we conducted whole-cell patch-clamp recordings of tdTomato fluorescent protein-expressing spinal V3 INs from Sim1(Cre/+);tdTom mice at post-natal day (P) 0, P4, P9 and P14 and compared their properties to those at P21. Combining electrophysiology with computational analyses, we show that dorsal and ventral V3 subpopulations are physiologically distinct at birth, but the electrophysiological properties of V3 INs change significantly during the first three post-natal weeks. We further reveal that there are multiple developmental phases of both V3 subpopulations during the maturation process. The different developmental trajectories of physiological properties also coincide with changes in an animal's locomotor behavior. These properties likely reflect the differential functions of V3 subpopulations in maturing spinal locomotor circuits.

Isolates from faba bean and soybean with lowered content of phytic acid and activity of the trypsin inhibitors.

For obtaining protein isolates, water, whey, and waste effluents from a potato processing plant were used as extraction solvents. Isolates obtained on laboratory conditions were subjected to chemical and organoleptic tests. It was shown that proper steering of the processing allowed for obtaining isolates with lower phytic acid content and decreased activity of the trypsin inhibitors, although the efficiency of the process decreased also. Modified processing was more efficient for elimination of the phytic acid from soybean isolates compared to faba bean. It was also shown that isolate neutralization considerably improved their solubility and decreased the activity of trypsin inhibitors.

[Improvement in the quality of rape seed by combining silage with fodder sugar beets. 2. Changes in glucosinolate derivatives and fat contents]. / Untersuchungen zur Verbesserung der Qualität von Rapssamen durch gemeinsame Silierung mit Futterzuckerrüben. 2. Mitt. Veränderungen des Gehaltes an Glucosinolatderivaten un Fett.

Industrial and laboratory-scale studies showed that the combined silage fermentation of rape-seed flakes with half sugar mangels leds to a very beneficial reduction in the content of glucosinolate derivatives, especially during the first week of fermentation and storage processes on the qualitative and quantitative fatty-acid parameters were but significant.

On rapeseed meals. Part XXVI. Some remarks on the biological value of rapeseed meal proteins after silage.

The influence of propionic bacteria on the biological value of potato-rapeseed meal protein ensilage was investigated. The inoculation of the ensilage with Propionibacterium Petersoni T 112 led to the reduction of the content of goitrogenous compounds (isothiocyanates and oxazolidinethiones) and to an increase of the nutritive value (NPU, PER) of the rapeseed protein. The increase of the protein value is greater by the application of propionic bacteria than by toasting of rapeseed meal.

[Improvement in the quality of rape seed by combining silage with fodder sugar beets. 1. Quality evaluation of the silages]. / Untersuchungen zur Verbesserung der Qualität von Rapssamen durch gemeinsame Silierung mit Futterzuckerrüben. 1. Mitt. Qualitätsbeurteilung der Silagen.

Industrial-scale studies showed that the addition of rape-seed flakes to half sugar mangels improves the feeding value and the quality of the silages. Furthermore, it was found that the development of yeasts was inhibited and that the propagation of acidifiers was retarded as the proportion of rape-seed increased. The microbiological analysis indicates that the amount of rape-seed added to the half sugar mangels should not exceed 10%.

Gastrointestinal changes in patients with hypogammaglobulinemia.

Three cases of hypogammaglobulinemia are described. In all cases the first symptoms of disease manifesting as pneumonia were preceded by diarrhea. In gastric biopsy there was atrophic gastritis with lack of plasmocytes. All patients demonstrated gastric achylia and symptoms of malabsorption syndrome. The causes of gastrointestinal changes, most probably infections, with simultaneous defective mucosal barrier are discussed.