Analysis of the E1-ubiquitin activating enzyme, Uba1, in cell death and tissue growth in Drosophila

Ubiquitination is an essential process involved in basic biological processes such as the cell cycle and cell death. Ubiquitination is initiated by ubiquitin-activating enzymes (E1), which activate and transfer ubiquitin to ubiquitin-conjugating enzymes (E2). Subsequently, ubiquitin is transferred to target proteins via ubiquitin ligases (E3). Defects in ubiquitin conjugation have been implicated in several forms of malignancy, the pathogenesis of several genetic diseases, immune surveillance/viral pathogenesis, and the pathology of muscle wasting. However, the consequences of partial or complete loss of ubiquitin conjugation in multi-cellular organisms are not well understood. Here, we report the characterization of nba1, the sole E1 in Drosophila. We have determined that weak and strong nba1 alleluias behave genetically different and sometimes in opposing phenotypes. For example, weak uba1 alleluias protect cells from cell death whereas cells containing strong loss-of-function alleluias are highly apoptotic. These opposing phenotypes are due to differing sensitivities of cell death pathway components to ubiquitination level alterations. In addition, strong uba1 alleluias induce cell cycle arrest due to defects in the protein degradation of Cyclins. Surprisingly, clones of strong uba1 mutant alleluias stimulate neighboring wild-type tissue to undergo cell division in a non-autonomous manner resulting in severe overgrowth phenotypes in the mosaic fly. I have determined that the observed overgrowth phenotypes were due to a failure to downregulate the Notch signaling pathway in nba1 mutant cells. Aberrant Notch signaling results in the secretion of a local cytokine and activation of JAK/STAT pathway in neighboring cells. In addition, we elucidated a model describing the regulation of the caspase Dronc in surviving cells. Binding of Dronc by its inhibitor Diap1 is necessary but not sufficient to inhibit Dronc function. Ubiquitin conjugation and Uba1 function is necessary for the negative regulation of Dronc. ^

Radiocarbon ages and diatom abundance in samples obtained from Qarlikturvik Valley, Bylot Island

The formation of many arctic wetlands is associated with the occurrence of polygon-patterned permafrost. Existing scenarios to describe and explain surface landforms in arctic wetlands (low-center and high-center polygons and polygon ponds) invoke competing hypotheses: a cyclic succession (the thaw-lake hypothesis) or a linear succession (terrestrialization). Both hypotheses infer the predictable development of polygon-patterned wetlands over millennia. However, very few studies have applied paleoecological techniques to reconstruct long-term succession in tundra wetlands and thereby test the validity of existing hypotheses. This paper uses the paleoecological record of diatoms to investigate long-term development of individual polygons in a High Arctic wetland. Two landform processes were examined: (1) the millennial-scale development of a polygon-pond, and (2) the transition from low-center to erosive high-center polygons. Diatom assemblages were quantified from habitats associated with contrasting landforms in the present-day landscape, and used as an analog to reconstruct past transitions between polygon types. On the basis of this evidence, the paleoecological record does not support either of the existing models describing the predictable succession of polygon landforms in an arctic wetland. Our results indicate a need for greater paleoecological understanding, in combination with in situ observations in present-day geomorphology, in order to identify patterns of polygon wetland development and elucidate the long-term drivers of these landform transitions.

Rates of ubiquitin conjugation increase when muscles atrophy, largely through activation of the N-end rule pathway

The rapid loss of muscle mass that accompanies many disease states, such as cancer or sepsis, is primarily a result of increased protein breakdown in muscle, and several observations have suggested an activation of the ubiquitin–proteasome system. Accordingly, in extracts of atrophying muscles from tumor-bearing or septic rats, rates of 125I-ubiquitin conjugation to endogenous proteins were found to be higher than in control extracts. On the other hand, in extracts of muscles from hypothyroid rats, where overall proteolysis is reduced below normal, the conjugation of 125I-ubiquitin to soluble proteins decreased by 50%, and treatment with triiodothyronine (T3) restored ubiquitination to control levels. Surprisingly, the N-end rule pathway, which selectively degrades proteins with basic or large hydrophobic N-terminal residues, was found to be responsible for most of these changes in ubiquitin conjugation. Competitive inhibitors of this pathway that specifically block the ubiquitin ligase, E3α, suppressed most of the increased ubiquitin conjugation in the muscle extracts from tumor-bearing and septic rats. These inhibitors also suppressed ubiquitination in normal extracts toward levels in hypothyroid extracts, which showed little E3α-dependent ubiquitination. Thus, the inhibitors eliminated most of the differences in ubiquitination under these different pathological conditions. Moreover, 125I-lysozyme, a model N-end rule substrate, was ubiquitinated more rapidly in extracts from tumor-bearing and septic rats, and more slowly in those from hypothyroid rats, than in controls. Thus, the rate of ubiquitin conjugation increases in atrophying muscles, and these hormone- and cytokine-dependent responses are in large part due to activation of the N-end rule pathway.

Relating two simultaneous events in discourse: the role of on-goingness devices in L1 Tunisian Arabic, L1 French and L2 French by Tunisian learners

Our PhD study focuses on the role of aspectual marking in expressing simultaneity of events in Tunisian Arabic as a first language, French as a first language, as well as in French as a second language by Tunisian learners at different acquisitional stages. We examine how the explicit markers of on-goingness qa:’id and «en train de» in Tunisian Arabic and in French respectively are used to express this temporal relation, in competition with the simple forms, the prefixed verb form in Tunisian Arabic and the présent de l’indicatif in French. We use a complex verbal task of retelling simultaneous events sharing an interval on the time axis based on eight videos presenting two situations happening in parallel. Two types of simultaneity are exploited: perfect simultaneity (when the two situations are parallel to each other) and inclusion (one situation is framed by the second one). Our informants in French and in Tunisian Arabic have two profiles, highly educated and low educated speakers. We show that the participants’ response to the retelling task varies according to their profiles, and so does their use of the on-goingness devices in the expression of simultaneity. The differences observed between the two profile groups are explained by the degree to which the speakers have developed a habit of responding to tasks. This is a skill typically acquired during schooling. We notice overall that the use of qa:’id as well as of «en train de» is less frequent in the data than the use of the simple forms. However, qa:’id as well as «en train de» are employed to play discursive roles that go beyond the proposition level. We postulate that despite the shared features between Tunisian Arabic and French regarding marking the concept of on-goingness, namely the presence of explicit lexical, not fully grammaticalised markers competing with other non-marked forms, the way they are used in the discourse of simultaneous events shows clear differences. We explain that «en train de» plays a more contrastive role than qa:’id and its use in discourse obeys a stricter rule. In cases of the inclusion type of simultaneity, it is used to construe the ‘framing’ event that encloses the second event. In construing perfectly simultaneneous events, and when both «en train de» and présent de l’indicatif are used, the proposition with «en train de» generally precedes the proposition with présent de l’indicatif, and not the other way around. qa:id obeys, but to a less strict rule as it can be used interchangeably with the simple form regardless of the order of propositions. The contrastive analysis of French L1 and L2 reveals learners’ deviations from natives’ use of on-goingness devices. They generalise the use of «en train de» and apply different rules to the interaction of the different marked and unmarked forms in discourse. Learners do not master its role in discourse even at advanced stages of acquisition despite its possible emergence around the basic and intermediate varieties. We conclude that the native speakers’ use of «en train de» involves mastering its role at the macro-structure level. This feature, not explicitly available to learners in the input, might persistently present a challenge to L2 acquisition of the periphrasis.

Exceeding the nonlinear-shannon limit using Raman laser based amplification and optical phase conjugation

We demonstrate that a combination of Raman laser based amplification and optical phase conjugation enables transmission beyond the nonlinear-Shannon limit. We show nonlinear compensation of 7x114Gbit/s DP-QPSK channels, increasing system reach by 30%. © 2013 Optical Society of America.

Politeness in computer-mediated discourse of a virtual team

Drawing on the newest findings of politeness research, this paper proposes an interactionally grounded approach to computer-mediated discourse (CMD). Through the analysis of naturally occurring text-based synchronous interactions of a virtual team the paper illustrates that the interactional politeness approach can account for linguistic phenomena not yet fully explored in computer-mediated discourse analysis. Strategies used for compensating for the lack of audio-visual information in computer-mediated communication, strategies to compensate for the technological constraints of the medium, and strategies to aid interaction management are examined from an interactional politeness viewpoint and compared to the previous findings of CMD analysis. The conclusion of this preliminary research suggests that the endeavour to communicate along the lines of politeness norms in a work-based virtual environment contradicts some of the previous findings of CMD research (unconventional orthography, capitalization, economizing), and that other areas (such as emoticons, backchannel signals and turn-taking strategies) need to be revisited and re-examined from an interactional perspective to fully understand how language functions in this merely text-based environment.

Enhanced superchannel transmission using phase conjugation

We demonstrate polarisation insensitive dual-band optical phase conjugation for multiple 400Gbit/s optical superchannels using a Raman amplified transmission link with a realistic span length of 75km. The resultant increase in transmission distance is confirmed analytically.

The impact of phase conjugation on the nonlinear-Shannon limit:the difference between optical and electrical phase conjugation

We show that optical and electrical phase conjugation enable effective nonlinear compensation, The impact of polarization mode dispersion and finite processing bandwidth on the ultimate limits are also considered.

Characteristics of samples obtained during Pokhodsk 2012-2013 campaigns in the joint Russian-German POLYGON Project

Polygonal tundra, thermokarst basins and pingos are common and characteristic periglacial features of arctic lowlands underlain by permafrost in Northeast Siberia. Modern polygonal mires are in the focus of biogeochemical, biological, pedological, and cryolithological research with special attention to their carbon stocks and greenhouse-gas fluxes, their biodiversity and their dynamics and functioning under past, present and future climate scenarios. Within the frame of the joint German-Russian DFG-RFBR project Polygons in tundra wetlands: state and dynamics under climate variability in Polar Regions (POLYGON) field studies of recent and of late Quaternary environmental dynamics were carried out in the Indigirka lowland and in the Kolyma River Delta in summer 2012 and summer 2013. Using a multidisciplinary approach, several types of polygons and thermokarst lakes were studied in different landscapes units in the Kolyma Delta in 2012 around the small fishing settlement Pokhodsk. The floral and faunal associations of polygonal tundra were described during the fieldwork. Ecological, hydrological, meteorological, limnological, pedological and cryological features were studied in order to evaluate modern and past environmental conditions and their essential controlling parameters. The ecological monitoring and collection program of polygonal ponds were undertaken as in 2011 in the Indigirka lowland by a former POLYGON expedition (Schirrmeister et al. [eds.] 2012). Exposures, pits and drill cores in the Kolyma Delta were studied to understand the cryolithological structures of frozen ground and to collect samples for detailed paleoenvironmental research of the late Quaternary past. Dendrochronological and ecological studies were carried out in the tree line zone south of the Kolyma Delta. Based on previous work in the Indigirka lowland in 2011 (Schirrmeister et al. [eds.] 2012), the environmental monitoring around the Kytalyk research station was continued until the end of August 2012. In addition, a classical exposure of the late Pleistocene permafrost at the Achchaygy Allaikha River near Chokurdakh was studied. The ecological studies near Pokhodsk were continued in 2013 (chapter 13). Other fieldwork took place at the Pokhodsk-Yedoma-Island in the northwestern part of the Kolyma Delta.

Grammar in dictionaries revisited: the case of verbs with se

This paper is a study about the way in which se structures are represented in 20 verb entries of nine dictionaries of Spanish language. There is a large number of these structures and they are problematic for native and non native speakers. Verbs of the analysis are middle-high frequency and, in the most part of the cases, very polysemous, and this allows to observe interconnections between the different se structures and the different meanings of each verb. Data of the lexicographic analysis are cross-checked with corpus analysis of the same units. As a result, it is observed that there is a large variety in the data which are offered in each dictionary and in the way they are offered, inter and intradictionary. The reasons range from the theoretical overall of each Project to practical performance. This leads to the conclusion that it is necessary to further progress in the dictionary model it is being handled, in order to offer lexico-grammatical phenomenon such as se verbs in an accurate, clear and exhaustive way.

[n]cycloparaphenylenes with charges: cyclic conjugation at last

Oligophenylenes (polyphenylenes) are constituted by an array of conjugated benzenes where inter-ring electron delocalization tends to extend over the whole chain (linear conjugation) being intrinsically limited, among other factors, by terminal effects. Alternatively, cyclic conjugation is envisaged as the unlimited free-boundary versionofconjugation which will impact the structure of molecules in rather unknown ways. The cyclic version of oligophenylenes, cycloparaphenylenes ([n]CPPs with n the number of phenyl rings) were first synthesized in 2008 by Beztozzi and Jasti.1 Today the whole [n]CPP series from [5]CPP to [18]CPP has been prepared. [n]CPPs represent ideal models to investigate new insights of the electronic structure of molecules and cyclic conjugation when electrons or charges circulate in a closed circuit without boundaries. Radical cations and dications of [n]CPP from n=5 to n=12 have been prepared and studied by Raman spectroscopy.2 Small [n]CPP dications own their stability to the closed-shell electronic configuration imposed by cyclic conjugation. However, in large [n]CPP dications cyclic conjugation is minimal and these divalent species form open-shell biradicals. The Raman spectra reflect the effect of cyclic conjugation in competition with cyclic strain and biradicaloid aromatic stabilization. Cyclic conjugation provokes the existence of a turning point or V-shape behavior of the frequencies of the G bands as a function of n. In this communication we will show the vibrational spectroscopic fingerprint of this rare form of conjugation. [1] R. Jasti, J. Bhattacharjee, J. B. Neaton, C. R. Bertozzi, “Synthesis, Characterization, and Theory of [9]-, [12]-, and [18]Cycloparaphenylene: Carbon Nanohoop Structures”, J. Am. Chem. Soc. 130 (2008), 17646–17647. [2] M. P. Alvarez, P. M. Burrezo, M. Kertesz, T. Iwamoto, S. Yamago, J. Xia, R. Jasti, J. T. L. Navarrete, M. Taravillo, V. G. Baonza, J. Casado, “Properties of Sizeable [n]CycloParaPhenylenes As Molecular Models of Single-Wall Carbon Nanotubes By Raman Spectroscopy: Structural and Electron-Transfer Responses Under Mechanical Stress”, Angew. Chem. Int. Ed. 53, (2014), 7033−7037.