Filices, lichenastra, muscos et lichenes

Teil von: Flora cryptogamica Germaniae / Wallroth, Karl Friedrich Wilhelm ; 1 Compendium florae Germanicae / Bluff, Matthias Joseph ; 3 : Sectio II, Plantae cryptogamicae s. cellulosa

Phosphoinositide regulation of endolysosomal membrane dynamics and nutrient signaling

The mammalian target of rapamycin complex 1 (mTORC1) on lysosomes and late endosomes (Ly/LEs) integrates intra- and extracellular nutrient signals and regulates metabolic pathways such as protein synthesis, lysosome biogenesis and autophagy. Many factors stimulate mTORC1 activity, including the production of phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] by class I phosphatidylinositol 3-kinases (PI3Ks) at the plasma membrane and phosphatidylinositol 3-phosphate [PI(3)P] by class III phosphatidylinositol 3-kinase at endosomes. In contrast, within the course of this thesis phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2], synthesized by class II PI3K b was identified as a negative regulator of mTORC1. PI3KC2b is shown to repress mTORC1 activity locally on Ly/LEs, whereas loss of PI3KC2b hyperactivates mTORC1. Growth factor deprivation induces the association of PI3KC2b with the Raptor subunit of mTORC1 and local PI(3,4)P2 synthesis triggers repression of mTORC1 activity through association of Raptor with inhibitory 14-3-3 proteins. We used SILAC (stable isotope labeling with amino acids in cell culture) based quantitative mass spectrometry to identify growth factor dependent interaction partners and post- translational modifications of PI3KC2b. We could show that 14-3-3 protein binding to phosphorylated threonine 279 in the presence of growth factors competes with the recruitment of PI3KC2b to mTORC1 and to Ly/LEs. Furthermore, protein kinase N 2 (PKN2) was found to be the major kinase that phosphorylates PI3KC2b at T279, thereby triggering its complex formation and cytosolic sequestration with inhibitory 14-3-3 proteins to activate mTORC1. Conversely, loss of PKN2 or mutational inactivation of its target phosphorylation site in PI3KC2b repress nutrient signaling via mTORC1. Furthermore, mammalian target of Rapamycin Complex 2 (mTORC2) was shown to activate PKN2, while mTORC2 inhibition mimicked the effects of PKN2-loss upon PI3KC2b. Together, these results uncover a novel mechanism that couples mTORC2-dependent activation of PKN2 to the regulation of mTORC1-mediated nutrient signaling via PI3KC2b- mediated PI(3,4)P2 synthesis

WyWallet - Variabler som påverkar användarnas acceptans mot WyWallet

SMS-betalningar var fram till den första februari 2013 en mobil betalmetod på frammarsch i Sverige då det var den mest använda mobila betalningsmetoden. I augusti 2010 infördes krav på att företag som erbjuder betaltjänster måste ha tillstånd från Finansinspektionen. Mobiloperatörer som förmedlar SMS-betalningar omfattas av detta krav och som svar till detta introducerade man tjänsten WyWallet. För att utföra en SMS -betalning numera krävs det att användaren först registrerar sig hos WyWallet. Innan införandet av WyWallet sålde kollektivtrafikföretaget Skånetrafiken ungefär 8000 SMS-biljetter per dag. Första månaden med den nya betalningstjänsten halverades denna försäljning och hjälporganisationen SOS Barnbyar meddelar att man haft en ungefärlig minskning på 88 procent i SMS-donationer. Vi ställer oss därför frågande till vad användarnas låga acceptans mot WyWallet beror på? I studien presenteras TAM2 vilket är en väletablerad modell för att förutsäga och mäta användarens acceptans jämtemot nya system. Empirisk data samlades in genom en kvantitativ undersökning i form av webbaserade enkäter. Undersökning och dess påståenden utformades med hjälp av en modifierad version av TAM2 som teoretiskt ramverk. Enkäten publicerades på sociala medier samt flera nätforum för att komma i kontakt med så många potentiella respondenter som möjligt. Genom analys av den insamlade empirin kunde vi sedan tolka och diskutera datan för att nå vårt slutresultat. Vi kom fram till att negativa subjektiva normer från omgivningen har avskräckt potentiella användare från att testa WyWallet och istället antar att tjänsten är krånglig och dålig. Användare som testat WyWallet anser inte att tjänsten är användarvänlig vilket spär på den negativa ryktesbildningen kring WyWallet ytterligare. Detta påverkar i sin tur tjänstens uppfattade nytta negativt. Den uppfattade nyttan i sig är redan låg då användarna inte förstår poängen med WyWallet och varför operatörerna ändrat på SMS-betalningar från sin föregående form då dessa fungerade bra

Cavovarus deformity in Charcot-Marie-Tooth disease: is there a hindfoot equinus deformity that needs treatment?

Background: Charcot-Marie-Tooth disease (CMT), one of the most common hereditary neurologic disorders, often results in debilitating cavovarus foot deformities. The deformities are still not fully understood, and the treatment recommendations are consequently heterogeneous, often including calf muscle or Achilles tendon lengthening. Methods: We examined 40 patients (80 feet) with CMT and bilateral cavovarus deformities (19 men and 21 women, mean age 33.6 ± 14.6 years) and the feet of a healthy control population of 13 individuals (7 men and 6 women, mean age 43.9 ± 10.8 years). In all cases 3D instrumented gait analysis results with both conventional Plug-in-Gait analysis and the Heidelberg Foot Measurement Method (HFMM) were used to determine the sagittal plane kinematics, dorsi-plantar flexion (DPF), tibio-talar dorsiflexion (TTDF), and medial arch angle (MAA), and the results of patients and the control group were compared using the 2 methods. Decreased and increased dorsiflexion using TTDF was defined as 1 standard deviation below or above the mean of the control. Comparisons were done using descriptive statistics, the Pearson correlation coefficient and ANOVA. Results: The TTDF was found to be decreased in 18 of the 80 feet examined (22.5 %), normal in 31 feet (38.75 %), and increased in 31 feet (38.75 %). The Pearson coefficient showed a positive correlation with R = 0.765, p < 0.001 between decreased TTDF values found by HFMM and decreased DPF values found with conventional Plug-in-Gait analysis, but a very weak correlation in patients with normal TTDF (R = -0.118) and increased TTDF (R = 0.078). Also, in patients with decreased TTDF values, there was a weak to moderate correlation with the MAA (R = 0.335), but no correlation between the MAA and DPF (R = 0.023). Conclusions: The HFMM, unlike the conventional Plug-in-Gait analysis, distinguishes between the segments of the foot in foot deformities and facilitates evaluation of the hindfoot equinus component in patients with CMT and cavovarus deformity. Although there is a significant correlation between decreased TTDF with HFMM and decreased DPF with conventional Plug-in-Gait analysis, this correlation was not seen in patients with normal or increased TTDF values. Conventional Plug-in-Gait analysis alone does not indicate if an increased plantar flexion deformity is the result of either a cavus deformity or hindfoot equinus deformity, which limits its usefulness in assisting in treatment decision making

Comparison of normalization methods for the analysis of metagenomic gene abundance data

Background: In shotgun metagenomics, microbial communities are studied through direct sequencing of DNA without any prior cultivation. By comparing gene abundances estimated from the generated sequencing reads, functional differences between the communities can be identified. However, gene abundance data is affected by high levels of systematic variability, which can greatly reduce the statistical power and introduce false positives. Normalization, which is the process where systematic variability is identified and removed, is therefore a vital part of the data analysis. A wide range of normalization methods for high-dimensional count data has been proposed but their performance on the analysis of shotgun metagenomic data has not been evaluated. Results: Here, we present a systematic evaluation of nine normalization methods for gene abundance data. The methods were evaluated through resampling of three comprehensive datasets, creating a realistic setting that preserved the unique characteristics of metagenomic data. Performance was measured in terms of the methods ability to identify differentially abundant genes (DAGs), correctly calculate unbiased p-values and control the false discovery rate (FDR). Our results showed that the choice of normalization method has a large impact on the end results. When the DAGs were asymmetrically present between the experimental conditions, many normalization methods had a reduced true positive rate (TPR) and a high false positive rate (FPR). The methods trimmed mean of M-values (TMM) and relative log expression (RLE) had the overall highest performance and are therefore recommended for the analysis of gene abundance data. For larger sample sizes, CSS also showed satisfactory performance. Conclusions: This study emphasizes the importance of selecting a suitable normalization methods in the analysis of data from shotgun metagenomics. Our results also demonstrate that improper methods may result in unacceptably high levels of false positives, which in turn may lead to incorrect or obfuscated biological interpretation

Local synthesis of the phosphatidylinositol-3,4-bisphosphate lipid drives focal adhesion turnover

Focal adhesions are multifunctional organelles that couple cell-matrix adhesion to cytoskeletal force transmission and signaling and to steer cell migration and collective cell behavior. Whereas proteomic changes at focal adhesions are well understood, little is known about signaling lipids in focal adhesion dynamics. Through the characterization of cells from mice with a kinase-inactivating point mutation in the class II PI3K-C2β, we find that generation of the phosphatidylinositol-3,4-bisphosphate (PtdIns(3,4)P2) membrane lipid promotes focal adhesion disassembly in response to changing environmental conditions. We show that reduced growth factor signaling sensed by protein kinase N, an mTORC2 target and effector of RhoA, synergizes with the adhesion disassembly factor DEPDC1B to induce local synthesis of PtdIns(3,4)P2 by PI3K-C2β. PtdIns(3,4)P2 then promotes turnover of RhoA-dependent stress fibers by recruiting the PtdIns(3,4)P2-dependent RhoA-GTPase-activating protein ARAP3. Our findings uncover a pathway by which cessation of growth factor signaling facilitates cell-matrix adhesion disassembly via a phosphoinositide lipid switch

Tomato: a crop species amenable to improvement by cellular and molecular methods

Tomato is a crop plant with a relatively small DNA content per haploid genome and a well developed genetics. Plant regeneration from explants and protoplasts is feasable which led to the development of efficient transformation procedures. In view of the current data, the isolation of useful mutants at the cellular level probably will be of limited value in the genetic improvement of tomato. Protoplast fusion may lead to novel combinations of organelle and nuclear DNA (cybrids), whereas this technique also provides a means of introducing genetic information from alien species into tomato. Important developments have come from molecular approaches. Following the construction of an RFLP map, these RFLP markers can be used in tomato to tag quantitative traits bred in from related species. Both RFLP's and transposons are in the process of being used to clone desired genes for which no gene products are known. Cloned genes can be introduced and potentially improve specific properties of tomato especially those controlled by single genes. Recent results suggest that, in principle, phenotypic mutants can be created for cloned and characterized genes and will prove their value in further improving the cultivated tomato.

CAnceR IN PreGnancy (CARING) - a retrospective study of cancer diagnosed during pregnancy in the United Kingdom

BACKGROUND: The incidence of cancer diagnosed during pregnancy is increasing. Data relating to investigation and management, as well as maternal and foetal outcomes is lacking in a United Kingdom (UK) population.METHODS: In this retrospective study we report data from 119 patients diagnosed with cancer during pregnancy from 14 cancer centres in the UK across a five-year period (2016-2020).RESULTS: Median age at diagnosis was 33 years, with breast, skin and haematological the most common primary sites. The majority of cases were new diagnoses (109 patients, 91.6%). Most patients were treated with radical intent (96 patients, 80.7%), however, gastrointestinal cancers were associated with a high rate of palliative intent treatment (63.6%). Intervention was commenced during pregnancy in 68 (57.1%) patients; 44 (37%) had surgery and 31 (26.1%) received chemotherapy. Live births occurred in 98 (81.7%) of the cases, with 54 (55.1%) of these delivered by caesarean section. Maternal mortality during the study period was 20.2%.CONCLUSIONS: This is the first pan-tumour report of diagnosis, management and outcomes of cancer diagnosed during pregnancy in the UK. Our findings demonstrate proof of concept that data collection is feasible and highlight the need for further research in this cohort of patients.</p

A conserved myotubularin-related phosphatase regulates autophagy by maintaining autophagic flux

Macroautophagy (autophagy) targets cytoplasmic cargoes to the lysosome for degradation. Like all vesicle trafficking, autophagy relies on phosphoinositide identity, concentration, and localization to execute multiple steps in this catabolic process. Here, we screen for phosphoinositide phosphatases that influence autophagy in Drosophila and identify CG3530. CG3530 is homologous to the human MTMR6 subfamily of myotubularin-related 3-phosphatases, and therefore, we named it dMtmr6. dMtmr6, which is required for development and viability in Drosophila, functions as a regulator of autophagic flux in multiple Drosophila cell types. The MTMR6 family member MTMR8 has a similar function in autophagy of higher animal cells. Decreased dMtmr6 and MTMR8 function results in autophagic vesicle accumulation and influences endolysosomal homeostasis