The Role of Sleep in Memory Consolidation with an Induced Sleep-Like State in Drosophila AND The Role of Alpha-synuclein in Fatty Acid Metabolism

The Role of Sleep in Memory Consolidation with an Induced Sleep-like State in Drosophila Introduction: Sleep plays an important role in memory consolidation. However, the underlying mechanism remains elusive. The importance of sleep in the memory consolidation process has been demonstrated by sleep deprivation studies in which sleep loss corresponded to poor performance on memory tasks. A sleep induction approach, that allows us to study sleep-mediated changes in the presence of sleep, provides further understanding of sleep\u27s role in the memory consolidation process. Method: We first developed a pharmacological method to induce a sleep-like state and examined if the induced sleep-like state modulates memory consolidation in flies. Using sleep induction, we then evaluated if changes in duration and timing of the induced sleep cause the changes in memory outcomes to further understand the role of sleep in the memory consolidation process. Results: Gaboxadol, an extra-synaptic GABAA receptor agonist, induced a sleep-like state that meets all the behavioral criteria of a spontaneous sleep-like state in flies. The induced sleep-like state following Gaboxadol treatment facilitated the formation of long-term memory in Wild-type flies. Inducing a sleep-like state in different strains of flies (ex. a series of memory mutants) and under various experimental conditions (ex. following sleep deprivation) revealed the beneficial role of induced sleep in memory processes, as supported by the observations that an increased sleep-like state rescued memory deficits in memory mutants and may compensate memory impairment caused by sleep-deprivation. By altering the duration and timing of sleep induction following the training protocol that is only able to induce a short-term memory by itself, we observed that a short-term memory was consolidated into a long-term memory even at when a sleep-like state was induced for a short period of time (\u3c4hrs) or induced at later time (\u3e24hrs) following the training. Discussion: Incorporating Gaboxadol into food is a novel method to increase a sleep-like state that was behaviorally and functionally equivalent to a spontaneous sleep-like state in flies. The ability of an induced sleep to sustain the formation of long-term memory following interference periods supports the active role of sleep in the memory consolidation process. Future studies using sleep induction could complement studies from sleep deprivation and contribute to identifying genes and neuronal circuits that link sleep with memory. The Role of Alpha-synuclein in Fatty Acid Metabolism Introduction: Accumulation of aggregated alpha-synuclein protein is the defining pathologic feature of Parkinson\u27s disease (PD). However, the molecular mechanisms underlying protein aggregation remain to be defined. Because the physiological function of alpha-synuclein remains unclear and previous studies have indicated a role in fatty acid metabolism and specifically acyl CoA synthesis, further studies that examine the interaction of alpha-synuclein with free fatty acids could provide a better understanding of the protein\u27s normal function. Method: We examined the interaction of alpha-synuclein with oleic acid, a monounsaturated free fatty acid, using a scintillation proximity assay (SPA). We characterized the regions of alpha-synuclein protein that are required for oleic acid binding using mutagenesis studies. We over-expressed alpha-synuclein in HEK293FT cells and measured its effect on the rate at which oleic acid is incorporated into phospholipids, which is determined by the rate at which oleic acid is converted to oleyl CoA by acyl CoA synthetase enzymes. Results: We found that alpha-synuclein cooperatively binds to monomeric oleic acid. Mutations that change either amino acids 30 or 46 in the alpha-synuclein protein disrupt the alpha-synuclein-oleic acid interaction. Over-expression of WT alpha-synuclein, but not A30P alpha-synuclein, in HEK293FT cells increased the rate of oleic acid incorporation into phosphatidylcholine (PC). Discussion: SPA is a novel approach to characterize the binding of alpha-synuclein to oleic acids. Alpha-synuclein promotes an increase in the oleic acid incorporation rate in HEK293FT cells. The absence of oleic acid binding by A30P alpha-synuclein and the corresponding absence of an effect of A30P alpha-synuclein on the incorporation rate in cells further supports the hypothesis that alpha-synuclein promotes acyl CoA synthesis by binding to free fatty acids

The Development of Labial Clusters in the Aśokan Rock Edicts

The original range of consonant clusters in Indo-Aryan reduced significantly over time, developing into geminates, homorganic nasal-stop clusters, and sonorant-h clusters in Middle Indo-Aryan. Early Middle Indo-Aryan, as represented in the Aśokan inscriptions, however, still maintained the original clusters, or what appear to be transitional stages of the extensive changes. Salient among those cluster changes that are observed in the Aśokan inscriptions are the changes tm, tv> tp and dv > db in Girnār in the west; sm, sv > sp in Shāhbāzgaṛhī and Mānsehrā in the north-west; and mh > mbh in Kālsī in the north and in Dhaulī and Jaugaḍa in the east. The idiosyncratic nature of these changes lies in the development of a stop from m or v, where the more usual changes would be loss or assimilation of m after a stop and of v after a stop or a sibilant, while sm and hm would normally change to mh. This paper examines the manner assimilation of the “labial” clusters (that is, the clusters with m or v that normally do not incur assimilation of the adjacent consonant) in the Aśokan Rock Edicts. It discusses the conditions, the motivation, the course of the change of m/v to a labial stop, and the dialectal differences associated with this change

Contraction in Old English Beowulf

This paper discusses contracted forms or what Zwicky (1977) terms `simple clitics\u27 that are found in the Old English alliterative verse Beowulf. The most frequent is cliticization of the negative particle to the following verb, e.g. naes `not-was\u27 (< ne naes), nis `not-is\u27 (< ne is), nolde `not-would\u27 (< ne wolde). Other examples include the verb-pronoun sequence wen\u27ic `think-I\u27(< wene ic), and the conjunction-particle sequence patte `that-which\u27(<paet pe) (cf. Klaeber 1950, Campbell 1959, Brunner 1965). The elements that may become simple clitics, i.e. the negative particle ne, the subject pronoun ic, and the relative particle pe, consistently occur in a metrically unstressed position. This fact indicates that lack of stress is a necessary condition for cliticization. In parallel with clitic phenomena in Present-day English, contraction in Beowulf tends to be observed with high frequency collocations and is subject to phonotactic factors (cf. Zwicky 1970, 1977, Selkirk 1984, Kaisse 1985, Bybee 2001). For example, the negative particle ne is cliticized to auxiliaries and auxiliary-like verbs that begin with a vowel, h, or w. Although there is some indication that full forms are more often stressed than the corresponding contracted forms (cf. Jack 1999), the factors which distinguish between the two are not entirely clear

Towards a linguistic interpretation of Kuhn\u27s Laws:With special reference to Old English Beowulf (Part 2)

Kuhn\u27s (1933) two Laws concern clause-initial clustering of what he calls \u27satzpartikel\u27 such as pronouns, short adverbs, and light finite verbs in Germanic alliterative verse. The Laws are formulated in metrical terms and are claimed by the proponent to reflect archaic linguistic features preserved in poetry. This paper critically evaluates Kuhn\u27s Laws from a linguistic perspective based on examination of Old English Beowulf. Part I (Volume 95) first discussed cliticization phenomenon of pronouns, adverbs, and light finite verbs in early Germanic, especially Beowulf (section 2). With this as background, it then examined Kuhn\u27s definition of clause particles (section 3) and the first type of violations of the First Law (section 4), showing, contrary to what Kuhn intends, that only part of Kuhn\u27s clause particles are clitics and that only part of the First Law violations reflects the innovative word order. Part II (this volume) begins with the second type of violations of the First Law and discusses the issue of Kuhn\u27s Laws as metrical conventions in Section 4. Section 5 examines the Second Law and shows that it reflects linguistic archaism only in an indirect way. The paper then takes up the issue that affects application of the Laws: the distinction between clause and phrase particles in section 6. This section continues through Part III (Volume 97), which also discusses metrical analyses in relation to the Laws

On Characterizing Sanskrit Gemination

In Sanskrit, various intervocalic biconsonantal clusters are affected by gemination, which istypically summarized by phonetic treatises as follows. First, postvocalic consonants followedby another consonant is geminated as in sapta- `seven\u27 > sappta- and cakra- `wheel\u27 > cakkra- .Second, consonants that follow r or h is geminated, as in artha- `purpose\u27 > arttha- and jihma-`oblique\u27 > jihmma- . In addition to these two major rules, there are subsidiary processes anddifferent dialects show different variations. Given that Sanskrit gemination affects consonantclusters, earlier studies have analyzed the process in terms of syllable structure, but there arecounterexamples that indicate that the syllable-only approaches are inadequate. This paper reexamines the conditioning factors and restrictions of Sanskrit geminationand concludes that the following three tendencies, which are independent and partly overlapor contradict, interact to produce the observed extensiveness and variations. First, as some ofthe earlier syllable-based approaches claim, syllable-initial and especially word-initial consonantis geminated. Second, consonants with an oral gesture, especially an oral closure, are preferredtargets over those without one, which is in accordance with the cross-linguistic tendency ofgemination. Third, the first consonant of the cluster tends to be geminated, which is attributedto the articulatory and perceptual problems associated with preconsonantal consonants

The alliterating verb in Beowulf 2717b seah on enta geweorc (Part 1)

In Old English Beowulf, the finite verb in verse 2717b seah on enta geweorc takes precedence over two nouns in alliteration. This verse has been considered a serious violation of the so-called Sieverss Rule of Precedence, according to which finite verbs do not take precedence over nominals in alliteration (e.g. Bliss 1967; Stanley 1975; Donoghue 1987). However, the effect of Sieverss Rule of Precedence, namely, the tendency for verbs to receive weaker stress than nominals, is not something peculiar to Germanic alliterative verse but is also observed in Present-day English (Cruttenden 1997; Ladd 2008; Calhoun 2010). The rule, therefore, reflects natural prosody and there is no evidence that it is obeyed without exception in verse composition. Further, although the verb to see generally does not bear a high semantic load (Bolinger 1986, 1989), finite lexical verbs in contrast to auxiliaries show a certain amount of stress in their metrical behavior. Moreover, the alliterating verb in 2717b occurs in clause-initial position where finite verbs show a higher ratio of alliteration than in other positions in the clause (Orton 1985; Y. Suzuki 2008). Lastly, enta geweorc, which cooccurs with the alliterating verb in 2717b, as a formulaic expression rephrased elsewhere may not be strongly stressed. The unusual alliterative pattern in Beowulf 2717b, therefore, can be attributed to natural prosody and does not provide motivation for emendation as Donoghue (1987) proposes

Sanskrit RUKI Revisited

In Sanskrit the dental sibilant s became retroflex s after the two consonants r and k and vowels other than a/ā when, as a rule, it is not word-final and not followed by r. From this uniqueenvironment arises the name ‘RUKI’ and a number of studies have been dedicated to the interpretation of the environment, which apparently does not form a natural class, a number of exceptions, and variability. This paper tackles the problem of the interpretation and implications of the unique conditioning factors of the Sanskrit RUKI rule and claims that RUKI is partial place assimilationwith multiple origins. While all the four triggers are behind dental in place, they are phoneticallyheterogeneous, i.e. vowels and consonants that in turn consists of an obstruent and a sonorantwith varying distances from the dental. They also show distinct phonological behaviors: while rand u are common retroflexion triggers, i often triggers palatalization and deretroflexion, and kis not known as a retroflexion trigger. A careful examination of Ṙ gveda shows further thatirregularities and phrase-level application depend on whether the triggers are vowels orconsonants. These phonetic and phonological differences, together with comparative evidence, suggest that RUKI originally consisted of a series of retraction processes, whose outcomeseventually merged as a retroflex sibilant in Sanskrit. The nature of the triggers has implicationson how the process as a whole arose and developed

The class of semivowels in Sanskrit

In Sanskrit, both liquids /l r/ and glides /j w/ alternate with their syllabic counterparts and form a single class of semivowels in the traditional grammar. The four semivowels, however, show distinct behaviors in various phonological processes. That is, in consonantclusters, /w/ but not the others may occur before another semivowel in the onset. As a target of sandhis, final /r/ merges with the dental sibilant /s/ in most contexts. As a trigger of sandhis, /l/ showscomparable behaviors to oral stops in causing oral gesture assimilation while /r/ tends to cause debuccalization of the preceding consonant. In gemination, /w/ and /l/ may become the target instead of the adjacent non-continuant while /r/ is excluded from the target. In Middle Indo-Aryan assimilation and initial cluster simplification, the four semivowels show different degrees of resistance to loss.Asymmetrical behaviors of semivowels are attributed to the phonetic differences of these four sounds instead of the universal feature system, sonority, or the prosodic structure. The phonetic properties that lead to idiosyncratic behaviors are: /l/ with a lingual contact in parallelwith stops, /w/ realized as a voiced fricative instead of an approximant, and /r/ with a wider aperture than the other three semivowels. These articulatory properties lead to the hierarchy /l/ < /w/ < /j/ < /r/ with an ascending order of vocalicity, which in turn dominates theirphonological behaviors

The sixth type of Germanic alliterative verse : the case of Old English Beowulf (Part 2)

According to Sievers (1885, 1893), there are five metrical types of Germanic alliterative poetry based on two stressed positions and two unstressed positions. With S and W representing a strong position and a weak position, respectively, these five are SWSW (Type A), WSWS (Type B), WSSW (Type C), SSWW (Type D), and SWWS (Type E), with the sixth possible combination WWSS lacking from the inventory. However, critical evaluation of earlier metrical analyses reveals that this sixth type is in fact present in Old English Beowulf. The two patterns of this type WWSS are verses with a disyllabic compound, as Me pone waelraes \u27... me for the murderous onslaught\u27, and verses with a \u27contracted\u27 vowel (i.e. a vowel that has arisen from hiatus) as the second lift, as Swa sceal man don \u27as a man should do\u27. Previous analyses subsumed the above verses under the basic five by stipulation of metrical stress and by an interpretive device that \u27decontracts\u27 a monosyllabic word form into the stem syllable and the ending syllable (cf. Sievers 1885, 1893, Bliss 1967, Fulk 1992, Hutcheson 1995, Suzuki 1996 among others). However, not only is metrical stress relative by nature, but also \u27decontraction\u27 as a metrical device presupposes Sievers\u27s scansion and lacks independent motivation. Arranging strong and week positions in alliterative verse is not restricted in the way in which WWSS pattern is prohibited