Verbal compounding in Latin: the case of -MAKE verbs

This paper aims at describing Latin compound verbs (CVs) whose second member is a verbal constituent connected with facio ‘to make’. Though there is a large literature on CVs in other languages, little has been said on Latin (Flobert 1978; Fruyt 2001 inter al.). CVs are extremely interesting in several respects. First, compared to Latin nominal compounds, whose core consists of exocentric formations, -MAKE CVs are endocentric constructions (Brucale 2012). Second, they represent an island of productivity in the generally unproductive area of verbal compounding in Latin. Third, they can be compared to analogous constructions in other Indo-European languages, viz. Persian and Hindi, which exhibit the same pattern. Two subclasses of -MAKE CVs can be found: 1) -fico verbs, whose first constituent can be either a noun, e.g. aedifico ‘to erect a building’, or an adjective, e.g. beatifico ‘to make happy’. In the former case, the noun is syntactically the direct internal argument of the verb. In the latter, the adjective has a predicative function and the compound conveys the causative meaning ‘make Q’ (or ‘factitive’, Lehmann fc.), where Q is a quality/state/condition (Kulikov 2001). 2) -facio verbs, which includes many types of compounds, the most productive of which is the so-called Causative subtype (Hahn 1947). This subtype is further divisible into three classes: a) CVs quite regularly connected to intransitive verbs in -eo (e.g. caleo ‘to be hot’) denoting states/conditions. This type is particularly productive and is used in causative CVs (e.g. calefacio ‘to make hot’), sharing with the -fico compounds above the meaning ‘make Q’. b) CVs in which the presence of facio does not yield any causative meaning nor introduces any semantic change in the first member, which already possesses a causative meaning, e.g. perterrefacio ‘to terrify’. c) compounds not related to any existent verb in -eo: - CVs connected with inchoative -sco verbs (e.g. assuesco ‘to become accustomed’/assuefacio ‘to accustom’). These are often ‘labile verbs’ which can be employed both as causatives and corresponding non-causatives with no overt formal change in the verb. The meaning of the corresponding -facio CV, therefore, will equal the meaning at work in the causative use of the verb in the first member. - CVs involving verbs of 1st (e.g. maturo ‘to ripen’/maturefacio ‘to ripen’) and 3rd conjugation (e.g. expergo ‘to arouse’/expergefacio ‘to arouse’). In this group are listed many causative verbs whose meaning is not altered by the compounding operation with –facio. In this work, we intend to provide an accurate description of the range of Latin -MAKE CVs, in order to find a rationale allowing for a perspicuous classification of these data. In particular, we attempt to clarify the morpho-syntactic status of causative CVs, and to further investigate which kind of causativization strategies they instantiate (Lehmann fc). References Brucale, Luisa 2012. Latin Compounds. Probus 24/1 : 93-117. Flobert, Pierre 1978. La composition verbale en latin. In: Etrennes de septantaine: travaux de linguistique et de grammaire comparee offerts a Michel Lejeune par un groupe de ses eleves, 85–94. Paris. Fruyt, Michèle 2001, Réflexions sur la notion de mot en latin: les verbes du type calefacio. In: Claude Moussy (ed.), De lingua Latina novae quaestiones. Actes du Xe Colloque International de Linguistique Latine, 81-94. Louvain. Hahn, Adelaide 1947. The Type calefacio. Transactions and Proceedings of the American Philological Association 78: 301–335. Kulikov, Leonid 2001. Causatives. In: Martin Haspelmath, Ekkehard Konig, Wulf Oesterreicher, Wolfgang Raible (eds), Language Typology and Language Universals. Vol. 2, 886–898. Berlin-New York. Lehmann, Christian (fc). Latin causativization in typological perspective. In: Muriel Lenoble & Dominique Longrée (eds.), Actes du 13ème Colloque International de Linguistique Latine. Louvain

The semantic network of the Latin preposition per: a diachronic investigation.

This paper explores the semantic network of the Latin preposition per (“through”) in a diachronic perspective derived from the analysis of two electronic corpora of 3rd century BCE – 4th century CE (PHI5; Intratext Digital Library). Drawing upon the insights of Cognitive Grammar (e.g. Langacker 1991), we analyze the role of the schematic import of per in the spread from basic to abstract meanings, thus accounting for the interconnections among the various senses of the polysemous entity. This theoretical position is integrated with Croft’s (1991) model of causal structure of events, as well as the results of an extensive analysis of Early Latin (Brucale & Mocciaro fc.), in order to address the following issues: 1. the diachronic shifts in the ratio of spatial to abstract meanings: spatial meanings are predominant in Early Latin (e.g. per urbem ire, Pl., Poen 522; per cribrum transire, Cat., De Agr. 76.3.4), while the only abstract values which are fully grammaticalized at this stage are MEANS (a less prototypical and abstract instrument: per vim retinere, Pl., Bacch. 843; see Croft 1991: 178) and REASON (the motivation for an agent to act: per metum mussari, Pl., Aul. 131; see Pinkster 1990). We aim at tracing back the path(s) through which new abstract meanings arise. 2. the role of Animacy: MEANS and REASON involve non-animate (abstract) participants, whereas the spread to Animacy represents a secondary development within the area of Causation, documented in Early Latin in a few instances of CAUSE (the motivation of a non- agentive event: per aliquem vivere, Pl., Poen. 1187) and INTERMEDIARY (per me interpretem, Pl., Mil. 910). Out of the causal domain, however,, Animacy is a rather ancient feature, represented in the expressions of Appeal (with performative verbs such as iuro, e.g. per Iovem iurare, Pl. Amph. 435) and Judgment of licitness (per me licet, Pl., Merc., 989). On the other hand, the expression of (concrete) INSTRUMENT represents a later development (cf. Luraghi 2010: per nauiculam uenire, Itala, cod. d., Ioh. 21, 8). In other words, the spread from concrete to abstract meanings appears to be non-unidirectional, rather drawing the following trajectory: SPATIAL (CONCRETE) > ABSTRACT > ANIMATE > INANIMATE (CONCRETE). 3. the grammaticalization of the expression of PURPOSE: another later development, which is based on an extension of Reason: “The objects we aspire for are usually also the cause for our aspiration” (Radden 1989: 562; see also Croft 1991: 293). Finally we propose a semantic map of the range of values conveyed by per, showing that they do not arrange on a linear continuum, but rather represent a multi-directional configuration originating from the progressive (metonymical) extension of a prototypical nucleus over time. Brucale, L. & Mocciaro, E. (fc.), Continuity and discontinuity in the semantics of the Latin preposition per: a cognitive hypothesis, in STUF 63/1. Croft, W. (1991), Syntactic Categories and Grammatical Relations. Chicago: Chicago University Press. Hewson, J. & Bubenik, V. (2006), From Case to Adposition: The development of configurational syntax in Indo-European Languages. Amsterdam/Philadelphia: John Benjamins. Langacker, R. (1991), Foundations of Cognitive Grammar. Stanford: Stanford University Press. Luraghi, S. 2010, Adverbial Phrases, in P. Baldi & P. Cuzzolin (eds), New Perspectives on Historical Latin Syntax, 2. Amsterdam/Philadelphia: John Benjamins. Pinkster, H. (1990), Latin Syntax and Semantics. London: Routledge. Radden, G. (1989), Semantic roles, in R. Dirven, & R. Geiger (eds), A User’s Grammar of English. Frankfurt am Main: Peter Lang, 421–471

Curcumin affects HSP60 folding activity and levels in neuroblastoma cells

The fundamental challenge in fighting cancer is the development of protective agents able to interfere with the classical pathways of malignant transformation, such as extracellular matrix remodeling, epithelial\u2013mesenchymal transition and, alteration of protein homeostasis. In the tumors of the brain, proteotoxic stress represents one of the main triggering agents for cell transformation. Curcumin is a natural compound with anti-inflammatory and anti-cancer properties with promising potential for the development of therapeutic drugs for the treatment of cancer as well as neurodegenerative diseases. Among the mediators of cancer development, HSP60 is a key factor for the maintenance of protein homeostasis and cell survival. High HSP60 levels were correlated, in particular, with cancer development and progression, and for this reason, we investigated the ability of curcumin to affect HSP60 expression, localization, and post-translational modifications using a neuroblastoma cell line. We have also looked at the ability of curcumin to interfere with the HSP60/HSP10 folding machinery. The cells were treated with 6, 12.5, and 25 \ub5M of curcumin for 24 h, and the flow cytometry analysis showed that the compound induced apoptosis in a dose-dependent manner with a higher percentage of apoptotic cells at 25 \ub5M. This dose of curcumin-induced a decrease in HSP60 protein levels and an upregulation of HSP60 mRNA expression. Moreover, 25 \ub5M of curcumin reduced HSP60 ubiquitination and nitration, and the chaperonin levels were higher in the culture media compared with the untreated cells. Furthermore, curcumin at the same dose was able to favor HSP60 folding activity. The reduction of HSP60 levels, together with the increase in its folding activity and the secretion in the media led to the supposition that curcumin might interfere with cancer progression with a protective mechanism involving the chaperonin

Prophylactic salpingectomy in premenopausal low-risk women for ovarian cancer: Primum non nocere

Abstract Objective The objective of this study is to compare ovarian function and surgical outcomes between patients affected by benign uterine pathologies submitted to total laparoscopic hysterectomy (TLH) plus salpingectomy and women in which standard TLH with adnexal preservation was performed. Methods We retrospectively compared data of 79 patients who underwent TLH plus bilateral salpingectomy (group A), with those of 79 women treated by standard TLH without adnexectomy (sTLH) (group B). Ovarian reserve modification, expressed as the difference between 3months post-operative and pre-operative values of Anti-Mullerian Hormone (AMH), Follicle Stimulating Hormone (FSH), Antral Follicle Count (AFC), mean ovarian diameters and Peak Systolic Velocity (PSV), was recorded for each patient. For each surgical procedure, operative time, variation of hemoglobin level (ΔHb), postoperative hospital stay, postoperative return to normal activity, and complication rate were recorded as secondary outcomes. Results According to our post-hoc analysis , this equivalence study resulted to have a statistical power of 96.8%. Significant difference was not observed between groups with respect to ΔAMH ( p = 0.35 ), ΔFSH ( p = 0.15 ), ΔAFC ( p = 0.09 ), Δ mean ovarian diameters ( p = 0.57 ) and ΔPSV ( p = 0.61 ). In addition, secondary outcomes such as operative time ( p = 0.79 ), ΔHb ( p = 0.41 ), postoperative hospital stay ( p = 0.16 ), postoperative return to normal activity ( p = 0.11 ) and complication rate also did not show any significant difference. Conclusions The addition of bilateral salpingectomy to TLH for prevention of ovarian cancer in women who do not carry a BRCA1/2 mutations do not show negative effects on the ovarian function. In addition, no perioperative complications are related to the salpingectomy step in TLH

Quantitative patterns of Hsps in tubular adenoma compared with normal and tumor tissues reveal the value of Hsp10 and Hsp60 in early diagnosis of large bowel cancer

Large bowel carcinogenesis involves accumulation of genetic alterations leading to transformation of normal mucosa into dysplasia and, lastly, adenocarcinoma. It is pertinent to elucidate the molecular changes occurring in the pre-neoplastic lesions to facilitate early diagnosis and treatment. Heat shock proteins (Hsps), many of which are molecular chaperones, are implicated in carcinogenesis, and their variations with tumor progression encourage their study as biomarkers. There are many reports on Hsps and cancer but none to our knowledge on their systematic quantification in pre-neoplastic lesions of the large bowel. We performed immunohistochemical determinations of Hsp10, Hsp60, Hsp70, and Hsp90 in biopsies of large bowel tubular adenomas with moderate grade of dysplasia and compared to normal mucosa and adenocarcinoma with a moderate grade of differentiation (G2). A significant elevation of Hsp10 and Hsp60 only, i.e., in the absence of elevation of Hsp70 or Hsp90, in both epithelium and lamina propria was found in tubular adenoma by comparison with normal mucosa. In contrast, adenocarcinoma was characterized by the highest levels of Hsp10 and Hsp60 in epithelium and lamina propria, accompanied by the highest levels of Hsp70 only in epithelium and of Hsp90 only in lamina propria, by comparison with normal and tubular adenoma counterparts. Hsp10 and Hsp60 are promising biomarkers for early diagnosis of tubular adenoma and for its differentiation from more advanced malignant lesions. Hsp10 and Hsp60 may be implicated in carcinogenesis from its very early steps and, thus, are potentially convenient targets for therapy

COLORECTAL CANCER IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: PRELIMINARY RESULTS FROM AN ONGOING CASE-CONTROL STUDY

Background and Aim:Understanding the risk factors for colorectal cancer (CRC) is crucial to the development of effective strategies for its prevention. meta-analysis and epidemiological studies have already shown that type 2 diabetes mellitus (DM) is associated with an increased risk of CRC and have provided data to support a positive relationship between these diseases. Material and Methods: We retrospectively evaluated 741 consecutive caucasian patients with type 2 DM who underewnt colonoscopic screening cof CRC and followed in our tertiary referrral center in 200-208 for incidence of CRC. Patients were stratified based on gender, age, body mass index (MBI), alchool and NSAIDS assumption, family history for cancer blood glycated hemoglobin levels, hypertension, hypertrigliceridemia, age at diabetes onset and duration, treatment with insulin or other hypoglicemic drugs. A total of 257 consecutive control patients were selected from a cohort of patients followed as outpatients for thyroid diseases. Results: At a median follow-up of 132,5 months (range 33,3-175,7) 56 cases of cancer (prevalence 7,56%) occurred; among these, 14 cases of CRC were reported (prevalence 18,8%) among the diabetic patients, while only one case (prevalence 0,004%) occurred in the control group, although this difference is not statistically significant (chi-square 2,9, P=0,08). Median duration of DM to CRC diagnosis was 156 months (range 1-768). At the univariate analysis older age (p=0,001), and diabetes duration (p=0,001) were related to higher risk of cancer, while metformin seems to be protective towards cancer (p=0,058). in the subset of patients with CRC, older age (p=0,001) and diabetes duration (p=0,001) were related to higher risk of CRC, such as treatment with sulphonylureas (p=0,01). Conclusions: Our preliminbar data show that the prevalence of CRC in the cohort of patients with type 2 DM was higher compared to that from our control group, and to that from the National Tumor Register up 2010 (0,5%). Furthermore we could interestingly hypotize that sulphonylureas may play a role in CRC carcinogenesis altering the physiological insulin secretion

Lipid Remodeling in Hepatocyte Proliferation and Hepatocellular Carcinoma

Background and Aims: Hepatocytes undergo profound metabolic rewiring when primed to proliferate during compensatory regeneration and in hepatocellular carcinoma (HCC). However, the metabolic control of these processes is not fully understood. In order to capture the metabolic signature of proliferating hepatocytes, we applied state-of-the-art systems biology approaches to models of liver regeneration, pharmacologically and genetically activated cell proliferation, and HCC. Approach and Results: Integrating metabolomics, lipidomics, and transcriptomics, we link changes in the lipidome of proliferating hepatocytes to altered metabolic pathways including lipogenesis, fatty acid desaturation, and generation of phosphatidylcholine (PC). We confirm this altered lipid signature in human HCC and show a positive correlation of monounsaturated PC with hallmarks of cell proliferation and hepatic carcinogenesis. Conclusions: Overall, we demonstrate that specific lipid metabolic pathways are coherently altered when hepatocytes switch to proliferation. These represent a source of targets for the development of therapeutic strategies and prognostic biomarkers of HCC

The dissociation of the Hsp60/pro-Caspase-3 complex by bis(pyridyl)oxadiazole copper complex (CubipyOXA) leads to cell death in NCI-H292 cancer cells

Cell survival and proliferation are central to carcinogenesis, involving various mechanisms among which those that impede apoptosis are important. In this, the role of the molecular chaperone Hsp60 is unclear since it has been reported that it can be both, pro- or anti-apoptotic. A solution to this riddle is crucial to the development of anti-cancer therapies targeting Hsp60. We addressed this question using a tumor cell line, NCI-H292, and [Cu(3,5-bis(2′-pyridyl)-1,2,4-oxadiazole)2(H2O)2](ClO4)2, CubipyOXA, a copper-containing compound with cytotoxic properties. We treated cells with various doses of the compound and measured cell viability; apoptosis indicators; and levels of Hsp60, pro-Caspase-3 (pC3), Caspase-3 (C3), and complex Hsp60/pC3, with complementary methods. The quantitative dose-response curves of the levels of Hsp60, activated C3, inactivated pC3, Hsp60/pC3 complex and indicators of cell apoptosis, and cell death, all coincided to show that CubipyOXA has pro-apoptotic activity and promotes cell death. The curves also indicate that the pro-apoptotic effects of CubipyOXA could likely be due to a lowering of Hsp60 levels and to its blocking the formation of the Hsp60/pC3 complex and/or its dissociating the complex when already formed, thus, interfering with the anti-apoptotic action of Hsp60. These findings shed some light on how a tumor cell may avert apoptosis using Hsp60 and point to the anti-cancer potential of drugs, such as CubipyOXA, which interfere with Hsp60/pC3 complex formation, and thus allow the apoptotic cascade to proceed. In view of these findings it becomes clear that the novel compound CubipyOXA should be considered a potential, high-efficiency antitumor agent deserving further testing