Eine Mutation der Augenfarbe und der Entwicklungsgeschwindigkeit bei der Mehlmotte Ephestia Kühniella Z.

Zusammenfassung Eine neu aufgetretene Mutation rotäugig bei der Mehlmotte wird rezessiv vererbt. Die AlleleA für Schwarzäugigkeit,a für Rotäugigkeit sind frei kombinierbar mit den AllelenB für Wildfarbig undb für Schwarzschuppig. Die GeneA bzw.a, B bzw.b und die genetische Konstitution des Geschlechts beeinflussen die Entwicklungsgeschwindigkeit. Hierbei wirkt die vom Wildtypus abweichende Mutationb beschleunigend, die vom Wildtypus abweichende Mutationa verlangsamend.     

Inheritance of some electrophoretic phenotypes of human hair

Summary Four isokeratin patterns were demonstrated by means of one-dimensional SDS electrophoresis of low sulfur proteins in human hair. The phenotypes had the following frequencies: K1 = 69.70%, K1m = 18.18%, K3 = 9.09%, K3m = 3.03%. Pedigree analysis and evaluation of observed and expected frequencies of the phenotypes gave rise to the conclusion that the phenotypes are controlled by genes of two independent autosomal loci K and m. We believe that ^*K3 and ^*m are dominant, whereas ^*K1 and ^*non-m are recessive.     

Relational Memory Is Evident in Eye Movement Behavior despite the Use of Subliminal Testing Methods

While it is generally agreed that perception can occur without awareness, there continues to be debate about the type of representational content that is accessible when awareness is minimized or eliminated. Most investigations that have addressed this issue evaluate access to well-learned representations. Far fewer studies have evaluated whether or not associations encountered just once prior to testing might also be accessed and influence behavior. Here, eye movements were used to examine whether or not memory for studied relationships is evident following the presentation of subliminal cues. Participants assigned to experimental or control groups studied scene-face pairs and test trials evaluated implicit and explicit memory for these pairs. Each test trial began with a subliminal scene cue, followed by three visible studied faces. For experimental group participants, one face was the studied associate of the scene (implicit test); for controls none were a match. Subsequently, the display containing a match was presented to both groups, but now it was preceded by a visible scene cue (explicit test). Eye movements were recorded and recognition memory responses were made. Participants in the experimental group looked disproportionately at matching faces on implicit test trials and participants from both groups looked disproportionately at matching faces on explicit test trials, even when that face had not been successfully identified as the associate. Critically, implicit memory-based viewing effects seemed not to depend on residual awareness of subliminal scene cues, as subjective and objective measures indicated that scenes were successfully masked from view. The reported outcomes indicate that memory for studied relationships can be expressed in eye movement behavior without awareness.     

Nucleotides. LXXIV Synthesis of a-D-Arabino-oligonucleotides

The 5 α-D-arabinofuranosylnucleosides α-araU (15), α-araT (18), α-araC (22), α-araA (25), and α-araG (28) have been synthesized by the modified silyl-method. The amino groups at the nucleobases and the 2′-hydroxy group at the sugar moiety were protected by the 2-(4-nitro-phenyl) ethoxycarbonyl (npeoc) group (37-40) and the amide function in α-araG was additionally blocked by the 2-(4-nitrophenyl)ethyl group (63) to improve solubility in organic solvents. Mono-and dimethoxytritylation of the 5′-OH group was performed in the usual manner to give 41-48, 64, and 65 in high yields and further substitution of the 3′-OH group led to the monomeric building blocks 66-75 as well as the 3′-O-succinoyl derivatives 76-85 functioning as starting units in solid-support oligonucleotide synthesis. A large number of oligo-α-arabinonucleotides have been prepared on modified CPG-material applying the npeoc/npe strategy as a very efficient synthetic tool for highly purified, homogenous oligomers. Hybridizations between α-arabinonucleotide strands revealed in analogy to earlier findings an antiparallel orientation whereas the combination of an oligo-α-D-arabinonucleotide with a complementary oligo-2′-deoxy-β-D-ribofuranosylnucleotide showed base-pairing only if a parallel polarity was present. The advantages in oligo-α-arabinonucleotide synthesis were furthermore demonstrated by the synthesis of the tα-ANA ^his a structural analog of the natural tRNA ^his of the phage T5.     

Induction of antagonistic soluble decoy receptor tyrosine kinases by intronic polyA activation

Alternative intronic polyadenylation (IPA) can generate truncated protein isoforms with significantly altered functions. Here, we describe 31 dominant-negative, secreted variant isoforms of receptor tyrosine kinases (RTKs) that are produced by activation of intronic poly(A) sites. We show that blocking U1-snRNP can activate IPA, indicating a larger role for U1-snRNP in RNA surveillance. Moreover, we report the development of an antisense-based method to effectively and specifically activate expression of individual soluble decoy RTKs (sdRTKs) to alter signaling, with potential therapeutic implications. In particular, a quantitative switch from signal transducing full-length vascular endothelial growth factor receptor-2 (VEGFR2/KDR) to a dominant-negative sKDR results in a strong antiangiogenic effect both on directly targeted cells and on naive cells exposed to conditioned media, suggesting a role for this approach in interfering with angiogenic paracrine and autocrine loops.     

Interaction of Bcl-2 with the Autophagy-related GABAA Receptor-associated Protein (GABARAP): BIOPHYSICAL CHARACTERIZATION AND FUNCTIONAL IMPLICATIONS*

Apoptosis and autophagy are fundamental homeostatic processes in eukaryotic organisms fulfilling essential roles in development and adaptation. Recently, the anti-apoptotic factor Bcl-2 has been reported to also inhibit autophagy, thus establishing a potential link between these pathways, but the mechanistic details are only beginning to emerge. Here we show that Bcl-2 directly binds to the phagophore-associated protein GABARAP. NMR experiments revealed that the interaction critically depends on a three-residue segment (EWD) of Bcl-2 adjacent to the BH4 region, which is anchored to one of the two hydrophobic pockets on the GABARAP molecule. This is at variance with the majority of GABARAP interaction partners identified previously, which occupy both hydrophobic pockets simultaneously. Bcl-2 affinity could also be detected for GEC1, but not for other mammalian Atg8 homologs. Finally, we provide evidence that overexpression of Bcl-2 inhibits lipidation of GABARAP, a key step in autophagosome formation, possibly via competition with the lipid conjugation machinery. These results support the regulatory role of Bcl-2 in autophagy and define GABARAP as a novel interaction partner involved in this intricate connection.     

Investigation on the precaecal and faecal digestibility of lactulose and inulin and their influence on nutrient digestibility and microbial characteristics

This study was conducted to determine the pre-caecal and faecal digestibility of lactulose and inulin and the influence of these substances on nutrient digestibility and microbial characteristics. In metabolic trials three of six male growing pigs (German Landrace?×?Pietrain) were fitted with an ileo-rectal anastomosis (IRA) in end-to-end technique with preserved ileo-caeco-colic valve. The metabolic trials were conducted from day 21?–?63 after surgery. The remaining pigs were used as intact partners (IN) for the IRA pigs. The experimental diets, based on corn, wheat, barley and soybean meal, were supplemented with either 1.5% lactulose or 2% inulin in replacement of diatomaceous earth (control). Pre-caecal digestibility of lactulose and inulin was assessed to be 79 and 98%, respectively, faecal digestibility was determined as 100%. The supplementation of lactulose and inulin had only minor effects on the pre-caecal and faecal digestibility of nutrients. Significant differences in nutrient digestibility were obvious between IRA and IN pigs, whereas the IRA pigs showed lower digestibility values with the exception of ether extracts (EE). Bacterial population in the digesta of IRA and IN pigs were not affected by the experimental diets except the concentration of gram-negative anaerobes, which inclined when the IRA pigs received the lactulose diet. The pH of chyme was significantly lower than the pH of faeces, however the pH was unaffected by the different supplemented diets. The concentration of volatile fatty acids (VFA) in pre-caecal chyme decreased significantly when IRA pigs received the lactulose supplemented diet whereas VFA in faeces were unaffected by the supplementation. IRA pigs administered with lactulose excreted more N via the urine, but the nitrogen balance remained unaffected. From the present investigation it can be concluded that lactulose and inulin did only partly or scarcely fulfill the expectation of acting as prebiotics in pigs.     

The plasma membrane channel ORAI1 mediates detrimental calcium influx caused by endogenous oxidative stress

The mouse hippocampal cell line HT22 is an excellent model for studying the consequences of endogenous oxidative stress. Addition of extracellular glutamate depletes the cells of glutathione (GSH) by blocking the glutamate−cystine antiporter system x_c⁻. GSH is the main antioxidant in neurons and its depletion induces a well-defined program of cell death called oxytosis, which is probably synonymous with the iron-dependent form of non-apoptotic cell death termed ferroptosis. Oxytosis is characterized by an increase of reactive oxygen species and a strong calcium influx preceding cell death. We found a significant reduction in store-operated calcium entry (SOCE) in glutamate-resistant HT22 cells caused by downregulation of the Ca²⁺ channel ORAI1, but not the Ca²⁺ sensors STIM1 or STIM2. Pharmacological inhibition of SOCE mimicked this protection similarly to knockdown of ORAI1 by small interfering RNAs. Long-term calcium live-cell imaging after induction of the cell death program showed a specific reduction in Ca²⁺-positive cells by ORAI1 knockdown. These results suggest that dysregulated Ca²⁺ entry through ORAI1 mediates the detrimental Ca²⁺ entry in programmed cell death induced by GSH depletion. As this detrimental Ca²⁺ influx occurs late in the course of the cell death program, it might be amenable to therapeutic intervention in diseases caused by oxidative stress.     

Post-transcriptional fine-tuning of COP9 signalosome subunit biosynthesis is regulated by the c-Myc/Lin28B/let-7 pathway

The COP9 signalosome (CSN) complex controls protein degradation via the ubiquitin (Ub) proteasome system (UPS) in eukaryotes. In mammalian cells, the multimeric CSN is composed of eight subunits (CSN1 - CSN8). It regulates cullin-RING Ub ligases (CRLs), which target essential regulatory proteins for ubiquitination and subsequent degradation. Thereby, the CSN cooperates with the UPS in a variety of essential cellular functions, including DNA repair, cell cycle and differentiation. Although functions of the CSN have been elucidated, mechanisms and regulatory principles of its de novo formation are completely unknown. Here, we show that there is a fundamental mechanism that allows a coordinated expression of all CSN subunits, a prerequisite for CSN assembly. CSN subunit mRNAs are targets of miRNAs of the let-7 family suppressing CSN subunit expression in human cells. Factors that reduce or block let-7 miRNAs induce the coordinated expression of CSN subunits. For instance, over-expression of CSN1 specifically traps let-7a-1 miRNA and elevates CSN subunit levels by two- to fourfold in a coordinated manner. CSN subunit expression is also increased by specific miRNA inhibitors or by interferon (IFN)-mediated induction of STAT1 and c-Myc reducing levels of let-7 miRNAs. Activation of STAT1 by IFNα or IFNγ induces c-Myc, which increases CSN subunit expression via the Lin28B/let-7 regulatory pathway. By contrast, a let-7a-1 mimic reduces CSN subunit expression. Our data show that let-7 miRNAs control the fine-tuning and coordinated expression of subunits for CSN de novo formation, presumably a general regulatory principle for other Zomes complexes as well.