Refine
Year of publication
- 2012 (1191) (remove)
Document Type
- Article (562)
- Part of Periodical (157)
- Conference Proceeding (137)
- Book (131)
- Doctoral Thesis (79)
- Working Paper (53)
- Report (32)
- Part of a Book (24)
- Review (8)
- Bachelor Thesis (2)
Language
- English (1191) (remove)
Is part of the Bibliography
- no (1191) (remove)
Keywords
- Pasolini, Pier Paolo (15)
- new species (13)
- taxonomy (11)
- Cape Verde Islands (8)
- Democracy (8)
- Law (6)
- apoptosis (6)
- human rights (6)
- law (6)
- radiation-induced nanostructures (6)
Institute
- Medizin (220)
- Rechtswissenschaft (103)
- Physik (86)
- Biowissenschaften (72)
- Biochemie und Chemie (70)
- Wirtschaftswissenschaften (45)
- Frankfurt Institute for Advanced Studies (FIAS) (41)
- Center for Financial Studies (CFS) (40)
- Geowissenschaften (30)
- Extern (29)
Manuele Gragnolati's paper 'Analogy and Difference: Multistable Figures in Pasolini's "Appunti per un'Orestiade africana"' discusses Pasolini's preference for the figure of contradiction and his opposition to Hegelian dialectics by exploring his attempt to look at Africa's process of modernization and democratization in the 1960s as analogous to the synthetic transformation of the Furies into Eumenides at the end of Aeschylus's trilogy. Gragnolati shows that Pasolini is aware of the dangers of analogy, which risks imposing the author's or filmmaker's symbolic order onto that of the 'other' represented in the text or film, and he argues that Pasolini seeks to deal with this danger by constantly shifting back and forth between differing positions. "Appunti per un'Orestiade africana" can thereby be thought as a multistable figure that is left suspended and not only resists synthesis, but also problematizes its own feasibility and challenges its own legitimacy.
BACKGROUND:
Horizontal gene transfer through natural transformation of members of the microbiota of the lower gastrointestinal tract (GIT) of mammals has not yet been described. Insufficient DNA sequence similarity for homologous recombination to occur has been identified as the major barrier to interspecies transfer of chromosomal DNA in bacteria. In this study we determined if regions of high DNA similarity between the genomes of the indigenous bacteria in the GIT of rats and feed introduced DNA could lead to homologous recombination and acquisition of antibiotic resistance genes.
RESULTS:
Plasmid DNA with two resistance genes (nptI and aadA) and regions of high DNA similarity to 16S rRNA and 23S rRNA genes present in a broad range of bacterial species present in the GIT, were constructed and added to standard rat feed. Six rats, with a normal microbiota, were fed DNA containing pellets daily over four days before sampling of the microbiota from the different GI compartments (stomach, small intestine, cecum and colon). In addition, two rats were included as negative controls. Antibiotic resistant colonies growing on selective media were screened for recombination with feed introduced DNA by PCR targeting unique sites in the putatively recombined regions. No transformants were identified among 441 tested isolates.
CONCLUSIONS:
The analyses showed that extensive ingestion of DNA (100 μg plasmid) per day did not lead to increased proportions of kanamycin resistant bacteria, nor did it produce detectable transformants among the aerobic microbiota examined for 6 rats (detection limit < 1 transformant per 1,1 × 108 cultured bacteria). The key methodological challenges to HGT detection in animal feedings trials are identified and discussed. This study is consistent with other studies suggesting natural transformation is not detectable in the GIT of mammals.
Invasive alien species (IAS) are a major global challenge requiring urgent action, and the Strategic Plan for Biodiversity (2011–2020) of the Convention on Biological Diversity (CBD) includes a target on the issue. Meeting the target requires an understanding of invasion patterns. However, national or regional analyses of invasions are limited to developed countries. We identified 488 IAS in China’s terrestrial habitats, inland waters and marine ecosystems based on available literature and field work, including 171 animals, 265 plants, 26 fungi, 3 protists, 11 procaryots, and 12 viruses. Terrestrial plants account for 51.6% of the total number of IAS, and terrestrial invertebrates (104 species) for 21.3%. Of the total numbers, 67.9% of plant IAS and 34.8% of animal IAS were introduced intentionally. All other taxa were introduced unintentionally despite very few animal and plant species that invaded naturally. In terms of habitats, 64.3% of IAS occur on farmlands, 13.9% in forests, 8.4% in marine ecosystems, 7.3% in inland waters, and 6.1% in residential areas. Half of all IAS (51.1%) originate from North and South America, 18.3% from Europe, 17.3% from Asia not including China, 7.2% from Africa, 1.8% from Oceania, and the origin of the remaining 4.3% IAS is unknown. The distribution of IAS can be divided into three zones. Most IAS are distributed in coastal provinces and the Yunnan province; provinces in Middle China have fewer IAS, and most provinces in West China have the least number of IAS. Sites where IAS were first detected are mainly distributed in the coastal region, the Yunnan Province and the Xinjiang Uyghur Autonomous Region. The number of newly emerged IAS has been increasing since 1850. The cumulative number of firstly detected IAS grew exponentially.
Legal practitioners and legal scientists need to have knowledge of the general rules that apply in the legal system. This involves both knowledge of the legislation and knowledge of the decisions by judges that function as general rules of law. Law students preparing themselves for the legal profession need to acquire these kinds of knowledge. A student has to have knowledge about where to look for decisions, understand the structure of decisions and learn to determine what makes a decision relevant to the body of applicable rules in the legal system. Legal education primarily aims at acquiring insight in the legal sources, their history and background. This basic knowledge is of great importance; legal problem solving is hardly possible without an understanding of the legal knowledge. To illustrate the use of this knowledge in practice, teachers work through decisions as examples. However, it is difficult, if not impossible, to learn by explanation or by imitation alone. A more effective way to obtain expertise is by actually performing the task, i.e. students should do the exercises, while the teacher provides feedback on their solutions. For effective learning, also the solution process should be monitored and provided with feedback. Furthermore it is desirable for students to be able to ask for help at any time during the process. They should also be able to practice over and over again. An ideal situation would have a teacher available for every student, monitoring the student while practicing and providing support where and whenever necessary. However, this being not practically feasible, the second best option is to offer the student electronic support.
CASE (Case Analysis and Structuring Environment) is an environment where a law student can practice with finding decisions, with structuring its text and with analysing the decision in order to be able to determine in what way it adds to the body of applicable rules in the legal system.
CASE is developed using a principled and structured design approach. A short description of this approach is followed by an analysis of the learning task, the difficulties law students experience and the remedies proposed on the basis of both the task analysis and the stated difficulties. This is followed by a description of architecture, functionality, platform and implementation of CASE and a description of a session with CASE and future work.
An exciting in vivo function of ATP-sensitive potassium channels in substantia nigra dopamine neurons Ð Implications for burst firing and novelty coding ÐPhasic burst activity is a key feature of dopamine (DA) midbrain neurons. This particular pattern of excitation of DA neurons occurs via a synaptically triggered transition from low-frequency background spiking to transient high-frequency discharges. Burst-firing mediated phasic DA release is critical for flexible switching of behavioural strategies in response to unexpected rewards, novelty and other salient stimuli. However, the cellular and molecular bases of burst signalling in distinct DA subpopulations of the substantia nigra (SN) or the ventral tegmental area (VTA) are unknown.
DA neuron excitability is controlled by synaptic network inputs, neurotransmitter receptors and ion channels, which generate action potentials and determine frequency and pattern of electrical activity in a complex interplay. ATP-sensitive potassium (K-ATP) channels are widely expressed throughout the brain, where in most cases they are believed to act as metabolically-controlled 'excitation brakes' by matching excitability to cellular energy states. However, their precise physiological in vivo function in DA neurons remains elusive.
To study burst firing and the underlying ionic mechanisms with single cell resolution, in vivo single-unit recordings were combined with juxtacellular neurobiotin labelling as well as immunohistochemical and anatomical identification of individual DA neurons. In vivo recordings were performed in adult isoflurane-anaesthetised wildtype (WT) and global K-ATP channel knockout mice, lacking the pore forming Kir6.2 subunit (Kir6.2-/-). In addition, DA cell-selective functional silencing of K-ATP channel activity in vivo was established using virus-mediated expression of dominant-negative Kir6.2 subunits. Careful control experiments ruled out any significant contributions from nonDA neurons as transduction was effectively limited to SN DA neurons rather than affecting those cells that innervate them. Virus-based K-ATP channel silencing in combination with juxtacellular recording and labelling was achieved to define the electrophysiological phenotype of individually identified, virally-transduced DA neurons in vivo.
Single-unit recordings revealed that K-ATP channels Ð in contrast to their conventional hyperpolarising role Ð in a subpopulation of DA neurons located in the medial SN (m-SN) act as cell-type selective gates for excitatory burst firing in vivo. The percentage of spikes in bursts was threefold reduced in Kir6.2-/- compared to WT mice. Classification of firing patterns based on visual inspection of autocorrelation histograms and on a newly developed spike-train-model confirmed the dramatic shift from phasic burst to tonic single-spike oscillatory firing in Kir6.2-/-. This significant decrease of burstiness was selective for m-SN DA neurons and was not exhibited by DA cells in the lateral SN or VTA. Virus-based K-ATP channel silencing in vivo unequivocally demonstrated that the activity of postsynaptic K-ATP channels was sufficient to disrupt bursting in m-SN DA neuron subtypes. Patch-clamp recordings in brain slices indicated an essential role of K-ATP channels for NMDA-mediated in vitro bursting. In accordance with previous studies in DA midbrain neurons, NMDA receptor stimulation triggered burst-like firing in m-SN DA cells in vitro, but only when K-ATP channels were co-activated in these neurons.
K-ATP channel-gated burst firing in m-SN DA neurons might be functionally relevant in awake, freely moving mice. To explore the behavioural consequences of SN DA neuron subtype-selective K-ATP channel suppression, spontaneous open field (OF) behaviour of mice with bilateral K-ATP silencing across the whole SN (medial + lateral) or in only the lateral SN was tested. Analysis of WT and global Kir6.2-/- mice showed reduced exploratory locomotor activity of Kir6.2-/- in a novel OF environment. Remarkably, K-ATP channel silencing in m-SN DA neurons phenocopied this novelty-exploration deficit, indicating that K-ATP channel-gated burst firing in medial but not lateral SN DA neurons is crucial for WT-like novelty-dependent exploratory behaviour.
In summary, a novel role of K-ATP channels in promoting the excitatory switch from tonic to phasic firing in vivo in a cell-type specific manner was discovered. The present PhD thesis provides several important insights into the pivotal function of K-ATP channels in medial SN DA cells, which project to the dorsomedial striatum, for burst firing and its important consequences for context-dependent exploratory behaviour.
In collaboration with two other research groups transcriptional up-regulation of K-ATP channel and NMDA receptor subunits and high levels of in vivo burst firing were detected in surviving SN DA neurons from Parkinson's disease (PD) patients Ð providing a potential link of K-ATP channel activity to neurodegenerative pathomechanisms of PD. Using high-resolution fMRI imaging another study in humans has recently identified distinct DA midbrain regions that are preferentially activated by either reward or novelty. Taken together, these human data and the results of the present PhD thesis suggest that burst-gating K-ATP channel function in SN DA neurons impacts on phenotypes in disease as well as in health.
The present contribution defends that remittances should be taken into account and integrated into an ethical framework on migration. This main thesis is two-fold. First, we argue that if a normative approach to migration is to claim practical relevance, it should integrate remittances as a relevant empirical parameter into an ethical framework. The empirical assessment of the scientific evidence available on remittances therefore proves to be extremely important. Secondly, assuming that remittances have to be taken seriously, we consider their positive and negative impacts against two backgrounds. First, we emphasize the increased autonomy of persons who pull themselves and their dependents out of economic hardship. Second, affluent states who enable this process through their labor legislation contribute to the fulfillment of their duty of assistance. In this respect, our thesis is to claim that remittances should be considered as an amplifying factor for normative arguments in favor of a liberalization of labor migration. Remittances stand for a liberal way of fulfilling a responsibility to help, namely through the elimination of obstacles which in turn allow people to support themselves and lead an autonomous life.
In succession of terrestrial ecosystem, bryophytes, algae and lichens constitute the primary components. Not only phylogenetically but also physically they are related to each other, as they are also found in close association and intermixed with each other on same substratum. A chlorophycean alga Ulothrix zonata (Weber & Mohr) Kützing has been found growing as an epiphyte on moss Macromitrium sulcatum (Hook.) Brid.. The association is peculiar as the algal filaments form a close net over the surface of moss leaves and axis.
A biodiversity inventory of the Lepidoptera of Pico Bonito National Park and vicinity, in the Department of Atlantida of northern Honduras, was initiated in 2009 to obtain baseline data. We present a revised checklist of Honduran butterfly species (updated from the initial 1967 lists), as well as the first comprehensive list of Honduran moths. Our updated list includes 550 species of Papilionoidea, 311 Hesperioidea, and 1,441 moth species.
Five new species of Hydroptila (Trichoptera: Hydroptilidae), H. murtlei sp. n., H. criokera sp. n, H. auriscuspa sp. n., H. santarosa sp. n., and H. ebroensis sp. n., from Florida are described and illustrated. We provide an annotated list of the 76 species known to occur in the state, including 10 species that represent new state records, one of which is also a new country record. New illustrations are presented for those species which were difficult to identify or exhibited new range extensions into Florida, namely: Hydroptila acadia Ross, H. ajax Ross, H. icona Mosely, H. latosa Ross, H. lloganae Blickle, H. maculata (Banks), H. novicola Blickle and Morse, H. wakulla Denning, Oxyethira arizona Ross, O. lumipollex Kelley and Harris, and O. simulatrix Flint.
We provide an illustrated list of species belonging to the genus Symmachia Hübner, [1819] (Lepidoptera: Riodinidae: Symmachiini) collected during an expedition conducted between September 10-21, 2011 in the northern part of the Parque Nacional da Serra do Divisor, Acre, Brazil, a remote region of Amazon rainforest. A total of 46 individuals were collected belonging to 15 species. For all recorded species, drawings of male genitalia and behavioral information are provided to support future studies on the taxonomy of the group. A new species, Symmachia divisora Dolibaina and Leite, sp. nov., is described, and a revised status for Symmachia hetaerina hesione Stichel, 1910, stat. rev., is proposed.
Synthesis of acetate from carbon dioxide and molecular hydrogen is considered to be the first carbon assimilation pathway on earth. It combines carbon dioxide fixation into acetyl-CoA with the production of ATP via an energized cell membrane. How the pathway is coupled with the net synthesis of ATP has been an enigma. The anaerobic, acetogenic bacterium Acetobacterium woodii uses an ancient version of this pathway without cytochromes and quinones. It generates a sodium ion potential across the cell membrane by the sodium-motive ferredoxin:NAD oxidoreductase (Rnf). The genome sequence of A. woodii solves the enigma: it uncovers Rnf as the only ion-motive enzyme coupled to the pathway and unravels a metabolism designed to produce reduced ferredoxin and overcome energetic barriers by virtue of electron-bifurcating, soluble enzymes.
The adaptive immune system protects against daily infections and malignant transformation. In this, the translocation of antigenic peptides by the transporter associated with antigen processing (TAP) into the ER lumen is an essential step in the antigen presentation by MHC I molecules. The heterodimeric ATP-binding cassette transporter (ABC) TAP consist of the two halftransporters TAP1 and TAP2. Each monomer contains an N-terminal transmembrane domain (TMD) and a conserved C-terminal nucleotide-binding domain (NBD). Together, the TMDs build the translocation core and the NBDs bind and hydrolyze ATP, energizing the peptide transport. TAP features an asymmetry in the two ATP-binding sites that are built of several conserved motifs. One motif is the D-loop with the consensus sequence SALD. The highly conserved aspartate of the D-loop of TAP1 reaches into the canonic ATP-binding site and contacts the Walker A motif and the H-loop of the opposite NBD, while the Asp of D-loop of TAP2 is part of the non-canonic ATP-binding site.
To examine this ABC transport complex in mechanistic detail, a purification and reconstitution procedure was established with the function of TAP being preserved. The heterodimeric TAP complex was purified via a His10-tag at TAP1 in a 1:1 ratio of the subunits. Nucleotide binding to the purified transporter was elucidated by tryptophan quenching assays and the affinity constants for MgADP and MgATP were determined to be 1.0 μM and 0.7 μM, respectevely. In addition, the TAP complex shows strict coupling between peptide binding and ATP hydrolysis, revealing no basal ATPase activity in the absence of peptides. Furthermore, TAP was reconstituted into proteoliposomes and the activity was tested by peptide transport and ATP hydrolysis. Interestingly, the kinetic parameters of the transporter in the reconstituted state are comparable to the data gained for TAP in microsomes.
To characterize the functional importance of the D-loop, D-loop mutants of either TAP1 or TAP2 were analyzed. Strikingly, TAP containing a mutated D-loop in TAP1 (D674A) shows an ATP-hydrolysis independent peptide translocation. Accordingly, the MHC I surface expression is similar to the wildtype situation. However, the same mutation in TAP2 (D638A) results in an ATPase dependent peptide transport similar to wildtype, whereas TAP containing mutations in both subunits leads to an inactive transporter. Although all D-loop mutants showed no altered peptide binding activity, the TAP1 mutant is inactive in peptide-stimulated ATPase activity. Strikingly, ATP or ADP binding is strictly required for the peptide translocation. Experiments carried out in proteoliposomes demonstrate that wildtype TAP can export peptides against their gradient when low peptide concentrations are offered. In contrast, the D674A mutant can facilitate peptide translocation along their concentration gradient in the two directions. At high peptide concentrations, TAP is trapped in a transport incompetent state induced by trans-inhibition. In conclusion, a TAP mutant that uncouples solute translocation from ATP hydrolysis was created. Since this passive substrate movement is strictly dependent on binding of ATP or ADP, an active transporter was turned into a “nucleotide-gated facilitator”.
In a cysteine cross-linking approach the conformational changes of TAP during peptide transport and the flexibility of the nucleotide binding domains were examined. Single cysteines were introduced in the D-loops of TAP1 and TAP2. Cross-linking by copper-phenantroline (CuPhe) was possible for all combinations. However, by adding ATP, ADP or peptide to the TAP complex no differences in the cross-linking efficiency were detected. By CuPhe cross-linking TAP was trapped in a conformation, in which the peptide binding site was not accessible. To complete a transport cycle, a flexibility of at least 17.8 Å of the NBDs is needed, since TAP cross-linked by CuPhe (2.0 Å) or bismaleimidoethane (BMOE, 8.0 Å) was transport inactive but when TAP was cross-linked by 1,11-bismaleimido-triethyleneglycol (BM[PEG]3, 17.8 Å) transport activity was preserved.
We show how Sestoft’s abstract machine for lazy evaluation of purely functional programs can be extended to evaluate expressions of the calculus CHF – a process calculus that models Concurrent Haskell extended by imperative and implicit futures. The abstract machine is modularly constructed by first adding monadic IO-actions to the machine and then in a second step we add concurrency. Our main result is that the abstract machine coincides with the original operational semantics of CHF, w.r.t. may- and should-convergence.
On 30 November 2012, we observed a white presumed Cape Verde buzzard Buteo bannermani Swann, 1919 in the northern mountains of Santo Antão, Cape Verde Islands. The bird was defending a territory on the west side of the road between Corda and Vila da Ribeira Grande. Judging from the amount of time it spent in aerial display, it probably concerned a male. RP managed to make a series of photos, including some of the bird perched at a distance of ca. 60 m (Fig. 1 & 2). In these it was possible to confirm that the eyes were dark and neither pale nor reddish, identifying the bird as an adult and excluding the possibility of an albino. Its apparent mate was a bird of normal appearance.
Amino acids can induce yeast cell adhesion but how amino acids are sensed and signal the modulation of the FLO adhesion genes is not clear. We discovered that the budding yeast Saccharomyces cerevisiae CEN.PK evolved invasive growth ability under prolonged nitrogen limitation. Such invasive mutants were used to identify amino acid transporters as regulators of FLO11 and invasive growth. One invasive mutant had elevated levels of FLO11 mRNA and a Q320STOP mutation in the SFL1 gene that encodes a protein kinase A pathway regulated repressor of FLO11. Glutamine-transporter genes DIP5 and GNP1 were essential for FLO11 expression, invasive growth and biofilm formation in this mutant. Invasive growth relied on known regulators of FLO11 and the Ssy1-Ptr3-Ssy5 complex that controls DIP5 and GNP1, suggesting that Dip5 and Gnp1 operates downstream of the Ssy1-Ptr3-Ssy5 complex for regulation of FLO11 expression in a protein kinase A dependent manner. The role of Dip5 and Gnp1 appears to be conserved in the S. cerevisiae strain ∑1278b since the dip5 gnp1 ∑1278b mutant showed no invasive phenotype.
Secondly, the amino acid transporter gene GAP1 was found to influence invasive growth through FLO11 as well as other FLO genes. Cells carrying a dominant loss-of-function PTR3647::CWNKNPLSSIN allele had increased transcription of the adhesion genes FLO1, 5, 9, 10, 11 and the amino acid transporter gene GAP1. Deletion of GAP1 caused loss of FLO11 expression and invasive growth. However, deletions of FLO11 and genes encoding components of the mitogen-activated protein kinase pathway or the protein kinase A pathway were not sufficient to abolish invasive growth, suggesting involvement of other FLO genes and alternative pathways. Increased intracellular amino acid pools in the PTR3647::CWNKNPLSSIN-containing strain opens the possibility that Gap1 regulates the FLO genes through alteration of the amino acid pool sizes.
The Alpine Region, constituting the Alps and the Dinaric Alps, has played a major role in the formation of current patterns of biodiversity either as a contact zone of postglacial expanding lineages or as the origin of genetic diversity. In our study, we tested these hypotheses for two widespread, sympatric microgastropod taxa - Carychium minimum O.F. Müller, 1774 and Carychium tridentatum (Risso, 1826) (Gastropoda, Eupulmonata, Carychiidae) - by using COI sequence data and species potential distribution models analyzed in a statistical phylogeographical framework. Additionally, we examined disjunct transatlantic populations of those taxa from the Azores and North America. In general, both Carychium taxa demonstrate a genetic structure composed of several differentiated haplotype lineages most likely resulting from allopatric diversification in isolated refugial areas during the Pleistocene glacial periods. However, the genetic structure of Carychium minimum is more pronounced, which can be attributed to ecological constraints relating to habitat proximity to permanent bodies of water. For most of the Carychium lineages, the broader Alpine Region was identified as the likely origin of genetic diversity. Several lineages are endemic to the broader Alpine Region whereas a single lineage per species underwent a postglacial expansion to (re)colonize previously unsuitable habitats, e.g. in Northern Europe. The source populations of those expanding lineages can be traced back to the Eastern and Western Alps. Consequently, we identify the Alpine Region as a significant 'hot-spot' for the formation of genetic diversity within European Carychium lineages. Passive dispersal via anthropogenic means best explains the presence of transatlantic European Carychium populations on the Azores and in North America. We conclude that passive (anthropogenic) transport could mislead the interpretation of observed phylogeographical patterns in general.
Background: Chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphatic leukemia (Ph + ALL) are caused by the t(9;22), which fuses BCR to ABL resulting in deregulated ABL-tyrosine kinase activity. The constitutively activated BCR/ABL-kinase "escapes" the auto-inhibition mechanisms of c-ABL, such as allosteric inhibition. The ABL-kinase inhibitors (AKIs) Imatinib, Nilotinib or Dasatinib, which target the ATP-binding site, are effective in Ph + leukemia. Another molecular therapy approach targeting BCR/ABL restores allosteric inhibition. Given the fact that all AKIs fail to inhibit BCR/ABL harboring the 'gatekeeper' mutation T315I, we investigated the effects of AKIs in combination with the allosteric inhibitor GNF2 in Ph + leukemia.
Methods: The efficacy of this approach on the leukemogenic potential of BCR/ABL was studied in Ba/F3 cells, primary murine bone marrow cells, and untransformed Rat-1 fibroblasts expressing BCR/ABL or BCR/ABL-T315I as well as in patient-derived long-term cultures (PDLTC) from Ph + ALL-patients.
Results: Here, we show that GNF-2 increased the effects of AKIs on unmutated BCR/ABL. Interestingly, the combination of Dasatinib and GNF-2 overcame resistance of BCR/ABL-T315I in all models used in a synergistic manner.
Conclusions: Our observations establish a new approach for the molecular targeting of BCR/ABL and its resistant mutants using a combination of AKIs and allosteric inhibitors.
Bruno Besana's article 'Badiou's Pasolini: The Problem of Subtractive Universalism' also deals with Pasolini's script about Saint Paul, but from the perspective of Alain Badiou's theoretical essay "Saint Paul and the Foundation of Universalism" and of Badiou's different thoughts on Pasolini, on the logic of emergence of novelty, and on its thwarted relation with universalism. Two main points appear in Besana's comparative reading. First, the idea that radical novelty or change can only be built in a 'subtractive manner', i.e. via the appearance of something that, by its sole presence, erodes the consistency upon which the present is structured. This is developed through Pasolini's ideas of 'inactuality' and 'forza del passato' and by Badiou's concept of 'event'. Second, a fundamental paradox inherent to the logic of change: change is only possible if it is organized in a set of coherent consequences, but the organized mode (for instance, the party) of such consequences inevitably reduces change to a constant compromise with the present.
Background: Otic neurons and sensory cells derive from common progenitors whose transition into mature cells requires the coordination of cell survival, proliferation and differentiation programmes. Neurotrophic support and survival of post-mitotic otic neurons have been intensively studied, but the bases underlying the regulation of programmed cell death in immature proliferative otic neuroblasts remains poorly understood. The protein kinase AKT acts as a node, playing a critical role in controlling cell survival and cell cycle progression. AKT is activated by trophic factors, including insulin-like growth factor I (IGF-I), through the generation of the lipidic second messenger phosphatidylinositol 3-phosphate by phosphatidylinositol 3-kinase (PI3K). Here we have investigated the role of IGF-dependent activation of the PI3K-AKT pathway in maintenance of otic neuroblasts.
Methodology/Principal Findings: By using a combination of organotypic cultures of chicken (Gallus gallus) otic vesicles and acoustic-vestibular ganglia, Western blotting, immunohistochemistry and in situ hybridization, we show that IGF-I-activation of AKT protects neural progenitors from programmed cell death. IGF-I maintains otic neuroblasts in an undifferentiated and proliferative state, which is characterised by the upregulation of the forkhead box M1 (FoxM1) transcription factor. By contrast, our results indicate that post-mitotic p27Kip-positive neurons become IGF-I independent as they extend their neuronal processes. Neurons gradually reduce their expression of the Igf1r, while they increase that of the neurotrophin receptor, TrkC.
Conclusions/Significance: Proliferative otic neuroblasts are dependent on the activation of the PI3K-AKT pathway by IGF-I for survival during the otic neuronal progenitor phase of early inner ear development.
Akrasia, or weak-will, is a term denoting a phenomenon when one acts freely and intentionally contrary to his or her better judgment. Discussion of akrasia originates in the Plato's Protagoras where he states that “No one who either knows or believes that there is another possible course of action, better than the one he is following, will ever continue on his present course”. However, in his influential article from 1970, Donald Davidson argued that akrasia is theoretically possible yet irrational. Some other critics of Plato's stance point out that phenomenon of akrasia is common in our everyday experience, therefore it must be possible.
These two arguments in favor of akrasia existence – theoretical and empirical – will be discussed from both – philosophical and psychological points of view. Especially, George Ainslie's argument that akrasia results from hyperbolic discounting will be taken into consideration to show how it affects traditional thinking about weak-willed actions.
Finally, the paper will discuss how the contemporary notion of akrasia may affect the idea of responsibility and free will. Implications for the philosophy of law will be shown, i.a. whether it is possible to claim that a given example of a weak-willed action was indeed free and intentional and one should be held responsible for its results.