A biomolecular archaeological approach to ‘Nordic grog’

The combined archaeological, biomolecular, and archaeobotanical evidence from four sites in Denmark (Nandrup, Kostræde, and Juellinge) and Sweden (Havor on the island of Gotland) provide key reference points for reconstructing ‘Nordic grog’ from ca. 1500 BC to the first century AD. In general, Nordic peoples preferred a hybrid beverage or ‘grog,’ in which many ingredients were fermented together, including locally available honey, local fruit (e.g., bog cranberry, and lingonberry) and cereals (wheat, rye, and/or barley), and sometimes grape wine imported from farther south in Europe. Local herbs/spices, such as bog myrtle, yarrow and juniper, and birch tree resin rounded out the concoction and provide the earliest chemical attestations for their use in Nordic fermented beverages. The aggregate ingredients probably served medicinal purposes, as well as contributing special flavors and aromas. They continued to be important ingredients for many kinds of beverages throughout medieval times and up to the present. The importation of grape wine from southern or central Europe as early as ca. 1100 BC, again chemically attested here for the first time, is of considerable cultural significance. It demonstrates the social and ceremonial prestige attached to wine, especially when it was served up as ‘Nordic grog’ in special wine-sets imported from the south. It also points to an active trading network across Europe as early as the Bronze Age in which amber might have been the principle good exchanged for wine. The presence of pine resin in the beverages likely derives from the imported wine, added as a preservative for its long journey northward

Does One Size Fit All? Drug Resistance and Standard Treatments: Results of Six Tuberculosis Programmes in Former Soviet Countries.

SETTING: After the collapse of the Soviet Union, countries in the region faced a dramatic increase in tuberculosis cases and the emergence of drug resistance. OBJECTIVE: To discuss the relevance of the DOTS strategy in settings with a high prevalence of drug resistance. DESIGN: Retrospective analysis of one-year treatment outcomes of short-course chemotherapy (SCC) and results of drug susceptibility testing (DST) surveys of six programmes located in the former Soviet Union: Kemerovo prison, Russia; Abkhasia, Georgia; Nagorno-Karabagh, Azerbaijan; Karakalpakstan, Uzbekistan; Dashoguz Velayat, Turkmenistan; and South Kazakhstan Oblast, Kazakhstan. Results are reported for new and previously treated smear-positive patients. RESULTS: Treatment outcomes of 3090 patients and DST results of 1383 patients were collected. Treatment success rates ranged between 87% and 61%, in Nagorno-Karabagh and Kemerovo, respectively, and failure rates between 7% and 23%. Any drug resistance ranged between 66% and 31% in the same programmes. MDR rates ranged between 28% in Karakalpakstan and Kemerovo prison and 4% in Nagorno-Karabagh. CONCLUSION: These results show the limits of SCC in settings with a high prevalence of drug resistance. They demonstrate that adapting treatment according to resistance patterns, access to reliable culture, DST and good quality second-line drugs are necessary

Beginning of Viniculture in France

Chemical analyses of ancient organic compounds absorbed into the pottery fabrics of imported Etruscan amphoras (ca. 500-475 B.C.) and into a limestone pressing platform (ca. 425-400 B.C.) at the ancient coastal port site of Lattara in southern France provide the earliest biomolecular archaeological evidence for grape wine and viniculture from this country, which is crucial to the later history of wine in Europe and the rest of the world. The data support the hypothesis that export of wine by ship from Etruria in central Italy to southern Mediterranean France fueled an ever-growing market and interest in wine there, which, in turn, as evidenced by the winepress, led to transplantation of the Eurasian grapevine and the beginning of a Celtic industry in France. Herbal and pine resin additives to the Etruscan wine point to the medicinal role of wine in antiquity, as well as a means of preserving it during marine transport

HST/NICMOS detection of a partially embedded, intermediate-mass pre-main-sequence population in the 30 Doradus Nebula

We present the detection of an intermediate-mass pre-main-sequence population embedded in the nebular filaments surrounding the 30 Doradus region in the Large Magellanic Cloud (LMC) using HST/NICMOS. In addition to four previously known luminous Class I infrared ``protostars,'' the NICMOS data reveal 20 new sources with intrinsic infrared excess similar to Galactic pre-main sequence stars. Based on their infrared brightness, these objects can be identified as the LMC equivalent of Galactic pre-main sequence stars. The faintest LMC Young Stellar Objects in the sample have colors similar to T Tauri and have about the same brightness as T Tauri if placed at the distance of the LMC. We find no evidence for a lower-mass cut-off in the initial mass function. Instead, the whole spectrum of stellar masses from pre-main sequence stars with ~1.5Mo to massive O stars still embedded in dense knots appears to be present in the nebular filaments. The majority of the young stellar objects can be found to the north of the central starburst cluster R136. This region is very likely evolving into an OB association.Comment: 9 pages, 4 figures, uses emulateapj.sty and psfig.sty. accepted for publication in the Astronomical Journal (August 2001 issue

Voltammetric Characterization of Redox-Inactive Guest Binding to Ln III [15-Metallacrown-5] Hosts Based on Competition with a Redox Probe

A novel competitive binding assay was implemented to monitor the binding of a redox inactive substrate to a redox inactive metallacrown host based on its competition with ferrocene carboxylate (FcC − ) using cyclic voltammetry (CV). First, the binding of FcC − to Ln III [15-MC Cu II ,N,L-pheHA -5] (LnMC) hosts was characterized by cyclic voltammetry. It was shown that the voltammetric half wave potentials, E 1/2 , shifted to more positive potentials upon the addition of LnMC. The explicit dependence of E 1/2 with the concentration of LnMC was used to determine the association constants for the complex. The FcC − binding strength decreased with larger central lanthanide metals in the LnMC hosts, and substantially weaker binding was observed with La III . X-ray crystallography revealed that the hydrophobic host cavity incompletely encapsulated FcC − when the guest was bound to the nine-coordinate La III , suggesting the LnMC’s ligand side chains play a substantial role in guest recognition. With knowledge of the MC-FcC − solution thermodynamics, the binding affinity of a redox inactive guest was then assessed. Addition of sodium benzoate to a LnMC and FcC − mixture resulted in E 1/2 shifting back to the value observed for FcC − in the absence of LnMC. The association constants between benzoate and LnMC’s were calculated via the competitive binding approach. Comparison with literature values suggests this novel assay is a viable method for determining association constants for host–guest systems that exhibit the proper electrochemical behavior. Notably, this CV competitive binding approach does not require the preparation of a modified electrode or a tethered guest, and thus can be generalized to a number of host–guest systems.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77442/1/chem_200903015_sm_miscellaneous_information.pd

Solvent effects and redox control on host-guest binding phenomena

In the first chapter the binding constant between the cyclophane host cyclobis(paraquat-p-phenylene) and the guests indole and catechol was found to exhibit strong solvent dependence. With both guests, the measured free energy of complexation correlated linearly with the solvent Z- and E\sb{\rm T}(30) values, which were proven to be more suitable measurements of solvent polarity. The results obtained were consistent with the concept of enthalpically-driven hydrophobic effect for inclusion type complexation by cyclophane receptors, which is a result of (i) strong cohesive interactions between polar solvent molecules, and (ii) less favorable solvent-solute interactions between highly polarizable apolar hydrocarbon surfaces and the less polarizable molecules of the polar solvent. Charge-transfer interactions between the $\pi$-electron rich guest and the $\pi$-electron deficient cavity of the cyclophane were found to play a minor role in the stabilization of the complex, while solvophobic interactions were shown to act as the governing binding force.The complexation properties of the hydrophilic viologens 4,4\sp\prime-bipyridinium-N,N\sp\prime- di-(2-(2-(2-ethoxy)ethoxy)ethanol), 4,4\sp\prime-bipyridinium-N,N\sp\prime-di-(carboxyhexane), 4,4\sp\prime-bipyridinium-N,N\sp\prime-di-(propylsulfonate) with the hosts $\beta$-cyclodextrin ($\beta$-CD) and heptakis-(2,6-O-dimethyl)-$\beta$-cyclodextrin (DM-$\beta$-CD) were investigated in the chapter II using electrochemical and digital simulation techniques. The hydrophilic substituents of these viologens allowed their full electrochemical characterization without problems associated with the precipitation of reduced viologen species. Detailed analysis of the voltammetric results using digital simulation techniques revealed that the oxidized forms of the guests did not interact appreciably with either CD host, the 2-electron reduced guests formed extremely stable inclusion complexes, with association constants in the range \rm10\sp3{-}10\sp4\ M\sp{-1}, while the cation radical forms exhibited intermediate binding affinities \rm({\sim}10\sp2\ M\sp{-1}). In all cases, DM-$\beta$-CD was found to form more stable complexes than unmodified $\beta$-CD.The synthesis and characterization of water soluble electroactive 4,4\sp\prime-bipyridinium derivatives was described in chapter III. The complexation properties of these compounds in aqueous solution were studied electrochemically. All four $\beta$-CD derivatives were found to exhibit a novel phenomenon of concentration dependent and electrochemically driven intermolecular self-complexation, where their reduced species of form head-to-head type intermolecular dimer complexes in aqueous solution. These complexes are destabilized in the presence of a competing water soluble guest (1-adamantane carboxylic acid or 1-adamantane tetramethylammonium chloride) or a host (DM-$\beta$-CD)

Modulation of neuronal nicotinic acetylcholine receptors by mercury

Mercuric chloride exerted a biphasic modulatory effect on rat neuronal nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus laevis oocytes as heteromers of the alpha3 or alpha4 and beta2 or beta4 subunits. The degree of modulation was subunit-dependent, with beta4-containing receptors displaying greater potentiation and alpha4-containing receptors displaying greater inhibition. Thus, alpha4beta4 receptors displayed both robust potentiation and robust inhibition. During prolonged coapplication of HgCl(2), first potentiation then inhibition of the acetylcholine (ACh) response was observed. Upon coapplication of 1 microM HgCl(2), a 2-fold increase in ACh-induced current was achieved in 55 +/- 1 s. With continued HgCl(2) application, the ACh response was slowly inhibited until, after 5 min, less than 10% of the initial response remained. By measuring potentiation at its peak and inhibition 5 min after the start of HgCl(2) coapplication, we obtained EC(50) and IC(50) values of 262 +/- 75 and 430 +/- 72 nM, respectively. HgCl(2) potentiation was voltage-dependent, increasing at more positive holding potentials. Upon washout of mercury chloride, potentiation reversed with a t(1/2) of 4.6 min. Inhibition reversed more slowly, with less than half the initial response recovered after 15 min of wash. Although free cysteine residues are common targets for mercury, elimination of all free cysteines located in the extracellular domains of the alpha4 and beta4 subunits did not alter the effects of mercuric chloride. Potentiation and inhibition of neuronal nAChRs may occur through action at a transmembrane or cytoplasmic location after passive diffusion of mercuric chloride across the plasma membrane

Reactive Pseudorotaxanes: Inclusion Complexation of Reduced Viologens by the Hosts β‐Cyclodextrin and Heptakis(2,6‐di‐o‐Methyl)‐β‐Cyclodextrin

The complexation of three guests containing 4,4′‐bipyridinium redoxactive residues by β‐cyclodextrin (β‐CD) and its heptakis‐(2,6‐O‐dimethyl) analogue (DM‐β‐CD) was investigated by means of voltammetric techniques. The three 4,4′‐bipyridinium (viologen) derivatives used as guests were designed to be water‐soluble in all three accessible oxidation states. The N‐substituents chosen to enhance aqueous solubility were: 2‐(2‐(2‐ethoxy)ethoxy)ethanol (guest 12+), 6‐hexanoate (guest 2), and 3‐propanesulfonate (guest 3). Detailed analysis of the voltammetric results by digital simulation techniques revealed that the oxidized forms of the guests did not interact appreciably with either CD host; the two‐electron reduced guests formed extremely stable inclusion complexes, with association constants in the range 103–104M−1, while the cation radical forms exhibited intermediate binding affinities (≈︁102M−1). In all cases, DM‐β‐CD was found to form more stable complexes than unmodified β‐CD. Redox switchable and highly stable inclusion complexes are formed between β‐cyclodextrin or its heptakis(2,6‐di‐O‐methyl) analogue and the two‐electron reduced forms of a series of viologen guests functionalized to increase their aqueous solubility in all three oxidation states (see Scheme). These complexes exhibit a pseudorotaxane structure and the unusual feature that the cyclodextrin includes an electrochemically generated subunit, which, therefore, is highly reactive