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Understanding how to achieve efficient transduction of hematopoietic stem and progenitor cells (HSPCs), while preserving their long-term ability to self-reproduce, is key for applying lentiviral-based gene engineering methods. SAMHD1 is an HIV-1 restriction factor in myeloid and resting CD4+ T cells that interferes with reverse transcription by decreasing the nucleotide pools or by its RNase activity. Here we show that SAMHD1 is expressed at high levels in HSPCs cultured in a medium enriched with cytokines. Thus, we hypothesized that degrading SAMHD1 in HSPCs would result in more efficient lentiviral transduction rates. We used viral like particles (VLPs) containing Vpx, shRNA against SAMHD1, or provided an excess of dNTPs or dNs to study this question. Regardless of the method applied, we saw no increase in the lentiviral transduction rate. The result was different when we used viruses (HR-GFP-Vpx+) which carry Vpx and encode GFP. These viruses allow assessment of the effects of Vpx specifically in the transduced cells. Using HR-GFP-Vpx+ viruses, we observed a modest but significant increase in the transduction efficiency. These data suggest that SAMHD1 has some limited efficacy in blocking reverse transcription but the major barrier for efficient lentiviral transduction occurs before reverse transcription.
Der vorliegende Artikel beschäftigt sich mit dem im Westen noch weitgehend unbekannten Genre des chinesischen Kriminalromans "gongàn xiaoshuo", sowie dessen produktiver Rezeption durch den niederländischen Diplomaten und Schriftsteller Robert H. van Gulik (*09.08.1910, †24.09.1967). Als Verständnisgrundlage sollen dabei zunächst einige grundsätzliche Ausführungen und Erläuterungen zu besagtem Genre getätigt werden. Danach wird sich der Text van Guliks "Richter Di" zuwenden, jener Romanreihe, der der Sinologe seine bis heute anhaltende Bekanntheit, auch über wissenschaftliche Kreise hinaus, verdankt. Um den Rahmen dieser Aufsatzes nicht zu sprengen, soll sich jedoch vorwiegend auf die durch van Gulik angefertigte und veröffentlichte Übersetzung des ursprünglichen chinesischen Originals, 'Wǔ Zétian sì dà qí àn' ( 武則天四大奇案 , "Vier außerordentlich seltsame Fälle in der Regierungszeit der Kaiserin Wu") (auch: 'Dee Goong An' ( 狄公案, "Richter Dis Fälle")), sowie den dritten Roman der Reihe, 'Geisterspuk in Peng-lai', konzentriert werden, da in diesem der Beginn der Karriere Richter Dis beschrieben wird. Auf diese Weise kann sowohl die besondere Form des chinesischen Kriminalromans - die van Gulik in seinen übrigen "Richter Di"- Romanen übernimmt -, wie auch das tradierte China-Bild und die Anklänge konfuzianischer Philosophie in angemessenem Umfang bearbeitet werden. Die in den Romanen dargestellten Formen des Alltagslebens, die Regierungsstrukturen, die politischen Verschwörungen und die Angriffe von außen, sind historisch korrekt beschrieben und gewähren somit einen faszinierenden Einblick in die Welt des historischen Chinas.
Sobre la base de estudios fisonómicos y cartográficos recientes de la vegetación de las provincias de San Luis y de La Pampa, se propone un nuevo trazado del limite occidental del pastizal pampeano. Un análisis preliminar del material fitosociológico existente y de los conocimientos sobre la dinámica de las comunidades de la región, en relación con el uso pas-turil y agrícola, permite postular al pastizal considerado como integrante del Distrito Psamofitico de la Provincia Pampeana.
Se considera la temprana colonización arbórea del pastizal y se la relaciona con los disturbios provocados por los rodeos vacunos movilizados por los indígenas durante el siglo pasado Se señala la relación que tienen los fundamentos que se esgrimieron para el cambio del limite fitogeográfico con la forma de encarar los problemas que derivan de la invasión de Geoffroea decorticans y de Prosopis caldenia sobre parte del área de pastizales, por influencia antrópica.
Wild plant species are important nutritious supplements to otherwise nutrient poor diets of rural populations in West Africa. Consequently, a decline of wild food species has a direct negative impact on the nutritional status of local households. In this study, we firstly investigated the preferred wild food species in south-east Burkina Faso, their perceived change in abundance as well as their contribution to wild food income. Secondly, we studied how these species might be substituted in times of species shortfall. Thirdly, we investigated the impact of socio-economic variables on the substitution choice. We conducted 155 household interviews in two villages and found 21 wild food species. With a contribution of almost 70% to wild food income, Vitellaria paradoxa and Parkia biglobosa were economically most important. All species were considered declining to some degree. The wide range of cited substitutes for the ten most important wild food species indicates a great knowledge on alternative plant species in the area. For the majority, the substitution choice did not depend on socio-economic characteristics. Cited as surrogate for several important wild food species, the native tree Balanites aegyptiaca was the most important substitute species. Many valued wild food species were substituted with other highly valued wild food species and therefore the decline of one species can lead to a shortfall of another substitute. Thus, even though our results suggest that people are able to counteract the decrease or absence of wild food species, growing decline of one species would concurrently increase the pressure on other native food species.
Rpn13 is an intrinsic ubiquitin receptor of the 26S proteasome regulatory subunit that facilitates substrate capture prior to degradation. Here we show that the C-terminal region of Rpn13 binds to the tetratricopeptide repeat (TPR) domain of SGTA, a cytosolic factor implicated in the quality control of mislocalised membrane proteins (MLPs). The overexpression of SGTA results in a substantial increase in steady-state MLP levels, consistent with an effect on proteasomal degradation. However, this effect is strongly dependent upon the interaction of SGTA with the proteasomal component Rpn13. Hence, overexpression of the SGTA-binding region of Rpn13 or point mutations within the SGTA TPR domain both inhibit SGTA binding to the proteasome and substantially reduce MLP levels. These findings suggest that SGTA can regulate the access of MLPs to the proteolytic core of the proteasome, implying that a protein quality control cycle that involves SGTA and the BAG6 complex can operate at the 19S regulatory particle. We speculate that the binding of SGTA to Rpn13 enables specific polypeptides to escape proteasomal degradation and/or selectively modulates substrate degradation.
Highlights
• High resolution profile of C. pipiens' sugar diet has been obtained using UHPLC-MS.
• Artificial feeding using ornamental plants provides similar sugar profiles as observed in field collected mosquitoes.
• Metabolomic profiling found secondary metabolites and pollutants of anthropogenic use.
Abstract: Culex pipiens (Linnaeus, 1758) mosquitoes search plant sources of sugars to cope with the energetic demand of various physiological processes. The crop as part of the digestive system is devoted to the storage of sugar-based meal obtained from various nectars sources. The profiling of sugars and metabolites in the Culex pipiens’ crop is scarce, and only few studies used Liquid Chromatography – Mass Spectrometry (LC-MS), which provides broad detection for biomonitoring environmental substances and even contaminants in the sugar diet of mosquitoes populations.
Therefore, sugar and metabolite profiling were performed on crops obtained from mosquitoes exposed to plant nectar under laboratory or natural conditions by Ultra High-Performance LC-MS (UHPLC-MS). This method allowed us a precise quantitative and qualitative identification of sugar diet and associated environmental compounds in the crop of the mosquito C. pipiens. Under laboratory condition, mosquitoes were allowed to feed on either glucose solution, commercially-available flowers or field collected flowers. In addition, we collected mosquitoes from the field to compare those crop metabolomes with metabolome patterns occurring after nectar feeding in the lab.
The sugar quantities and quality obtained from the crops of mosquitoes collected in the field were similar to those crops obtained from mosquitoes that fed on commercially-available flowers and from field collected flowers with a limit of detection of 10 μg/L for sucrose, glucose and sucrose. Next to sugar compounds, we identified 2 types of amino acids, 12 natural products, and 9 pesticides.
Next to the diversity of sugar compounds, we could confirm that secondary metabolites and environmental pollutants are typically up taken from floral nectar sources by C. pipiens. The in-depth knowledge on mosquito–plant interactions may inspire the development and further optimization of mosquito trap systems and arboviral surveillance systems.
The influence of biological maturity status (BMS) on talent identification and development within elite youth soccer is critically debated. During adolescence, maturity-related performance differences within the same age group may cause greater chances of being selected for early maturing players. Therefore, coaches need to consider players' BMS. While standard methods for assessing BMS in adolescents are expensive and time-consuming imaging techniques (i.e., X-ray and MRI), there also exist more pragmatic procedures. This study aimed to evaluate commonly used methods to assess BMS within a highly selected sample of youth soccer players. A total of N = 63 elite male soccer players (U12 and U14) within the German Soccer Association's talent promotion program completed a test battery assessing BMS outcomes. Utilizing MRI diagnostics, players' skeletal age (SAMRI) was determined by radiologists and served as the reference method. Further commonly used methods included skeletal age measured by an ultrasound device (SAUS), the maturity offset (MOMIR), and the percentage of adult height (PAHKR). The relation of these alternative BMS outcomes to SAMRI was examined using different perspectives: performing bivariate correlation analyses (1), modeling BMS as a latent variable (BMSlat) based on the multiple alternative diagnostics (2), and investigating individual differences in agreement (3). (1) Correlations of SAMRI and the further BMS variables ranked from r = 0.80 to r = 0.84 for the total sample and were lower for U12 (0.56 ≤ r ≤ 0.66), and U14 (0.61 ≤ r ≤ 0.74) (2). The latent structural equation modeling (SEM) (R2 = 51%) revealed a significant influence on BMSlat for MOMIR (β = 0.51, p <0.05). The additional contribution of PAHKR (β = 0.27, p = 0.06) and SAUS (β = −0.03, p = 0.90) was rather small (3). The investigation of individual differences between the reference method and alternative diagnostics indicated a significant bias for MOMIR (p <0.01). The results support the use of economical and time-efficient methods for assessing BMS within elite youth soccer. Bivariate correlation analyses as well as the multivariate latent variable approach highlight the measures' usefulness. However, the observed individual level differences for some of the utilized procedures led to the recommendation for practitioners to use at least two alternative assessment methods in order to receive more reliable information about players' BMS within the talent promotion process.
Es ist mir eine große Freude, heute abend hier - sozusagen als Schlußlicht Ihrer Vortragsreihe - ein wenig über die Möglichkeiten der Verhaltensforschung am Menschen zu plaudern. Ich weiß, daß in den letzten Jahren infolge einer Reihe von mehr oder weniger populären, zum Teil weit bekannt gewordenen Büchern in der Offentlichkeit ein etwas schiefes Bild entstanden ist vom Ehrgeiz der Verhaltensforscher, derart, daß die jetzt eigentlich alles alleine machen möchten nach dem Schema: "Hoppla, jetzt komm ich, und alles das, was vorher war, werfen wir jetzt auf den Müllhaufen." Was wir jedoch wirklich behaupten und auch - glaube ich - recht gut nachweisen können, ist folgendes: Neue Methoden, neue Möglichkeiten der Forschung bringen Dinge ans Tageslicht, die bisher und mit den Methoden der anderen Disziplinen, die sich mit der Forschung am Menschen und am menschlichen Verhalten befassen, nicht oder nicht so gut faßbar waren und sind. Wir erweitern so ein wenig den Horizont dessen, was faßbar wird.