Robust radiocarbon dating of wood samples by high-sensitivity liquid scintillation spectroscopy in the 50–70 kyr age range

Although high-sensitivity liquid scintillation (LS) spectroscopy is theoretically capable of producing finite radiocarbon ages in the 50,000- to 70,000-yr range, there is little evidence in the literature that meaningful dates in this time period have been obtained. The pressing need to undertake calibration beyond 26 kyr has resulted in the regular publication of ¹⁴C results in excess of 50 kyr, yet very little effort has been made to demonstrate their accuracy or precision. There is a paucity of systematic studies of the techniques required to produce reliable dates close to background and the methods needed to assess contamination from either in situ sources or laboratory handling and processing. We have studied the requirements for producing accurate and reliable dates beyond 50 kyr. Laboratory procedures include optimization of LS spectrometers to obtain low and stable non-¹⁴C background count rates, use of low-background counting vials, large benzene volumes, long counting times, and preconditioning of vacuum lines. We also discuss the need for multiple analyses of a suitable material containing no original ¹⁴C (background blank) and the application of an appropriate statistical model to compensate for variability in background contamination beyond counting statistics. Accurate and reproducible finite ages >60 kyr are indeed possible by high-sensitivity LS spectroscopy, but require corroborating background blank data to be defensible

Towards a radiocarbon calibration for oxygen isotope stage 3 using New Zealand kauri (Agathis australis)

It is well known that radiocarbon years do not directly equate to calendar time. As a result, considerable effort has been devoted to generating a decadally resolved calibration curve for the Holocene and latter part of the last termination. A calibration curve that can be unambiguously attributed to changes in atmospheric ¹⁴C content has not, however, been generated beyond 26 kyr cal BP, despite the urgent need to rigorously test climatic, environmental, and archaeological models. Here, we discuss the potential of New Zealand kauri (Agathis australis) to define the structure of the ¹⁴C calibration curve using annually resolved tree rings and thereby provide an absolute measure of atmospheric ¹⁴C. We report bidecadally sampled ¹⁴C measurements obtained from a floating 1050-yr chronology, demonstrating repeatable ¹⁴C measurements near the present limits of the dating method. The results indicate that considerable scope exists for a high-resolution ¹⁴C calibration curve back through OIS-3 using subfossil wood from this source

Specific refolding pathway of viscumin A chain in membrane-like medium reveals a possible mechanism of toxin entry into cell

How is a water-soluble globular protein able to spontaneously cross a cellular membrane? It is commonly accepted that it undergoes significant structural rearrangements on the lipid-water interface, thus acquiring membrane binding and penetration ability. In this study molecular dynamics (MD) simulations have been used to explore large-scale conformational changes of the globular viscumin A chain in a complex environment - comprising urea and chloroform/methanol (CHCl /MeOH) mixture. Being well-packed in aqueous solution, viscumin A undergoes global structural rearrangements in both organic media. In urea, the protein is "swelling" and gradually loses its long-distance contacts, thus resembling the "molten globule" state. In CHCl /MeOH, viscumin A is in effect turned "inside out". This is accompanied with strengthening of the secondary structure and surface exposure of hydrophobic epitopes originally buried inside the globule. Resulting solvent-adapted models were further subjected to Monte Carlo simulations with an implicit hydrophobic slab membrane. In contrast to only a few point surface contacts in water and two short regions with weak protein-lipid interactions in urea, MD-derived structures in CHCl /MeOH reveal multiple determinants of membrane interaction. Consequently it is now possible to propose a specific pathway for the structural adaptation of viscumin A with respect to the cell membrane - a probable first step of its translocation into cytoplasmic targets

Fluorescence lifetime spectroscopy of tissue autofluorescence in normal and diseased colon measured ex vivo using a fiber-optic probe

We present an ex vivo study of temporally and spectrally resolved autofluorescence in a total of 47 endoscopic excision biopsy/resection specimens from colon, using pulsed excitation laser sources operating at wavelengths of 375 nm and 435 nm. A paired analysis of normal and neoplastic (adenomatous polyp) tissue specimens obtained from the same patient yielded a significant difference in the mean spectrally averaged autofluorescence lifetime −570 ± 740 ps (p = 0.021, n = 12). We also investigated the fluorescence signature of non-neoplastic polyps (n = 6) and inflammatory bowel disease (n = 4) compared to normal tissue in a small number of specimens

Crystal and Molecular Structure and DFT Calculations of the Steroidal Oxime 6E-Hydroximino-androst-4-ene-3,17-dione (C₁₉H₂₅NO₃) a Molecule with Antiproliferative Activity

The single crystal X-ray structure of the novel steroid derivative, 6E-hydroximino-androst-4-ene-3,17-dione ( C19H25NO3) (code name RB-499), possessing antiproliferative activity against various cell lines is presented. The analysis produced the following results: chemical formula C19H25NO3; Mr = 315.40; crystals are orthorhombic space group P212121 with Z = 4 molecules per unit cell with a = 6.2609(2), b = 12.5711(4), c = 20.0517(4) Å,Vc = 1578.18(7) Å3, crystal density Dc = 1.327 g/cm³. Structure determination was performed by direct methods, Fourier and full-matrix least-squares refinement. Hydrogens were located in the electron density and refined in position with isotropic thermal parameters. The final R-index was 0.0324for 3140 reflections with I > 2σ and 308 parameters. The Absolute Structure Parameter − 0.07(5) confirms the correct allocation of the absolute configuration. The presence of the double bond C=O at position 3 in Ring A has caused a distortion from the usual chair conformation and created an unusual distorted sofa conformation folded across an approximate m-plane through C(1)–C(4). Ring B is a distorted chair, its conformation being influenced by the presence of the C(6)=N(6)–O(6)H group in position 6. Ring C is a symmetrical chair. Ring D exhibits both a distorted mirror symmetry conformation [influenced by the C(17)=O(17) group] and a distorted twofold conformation. DFT calculations indicated some degree of flexibility in rings A, C and D with ring A showing the greatest variation in torsion angles. The crystal packing is governed by H-bonds involving O(3), O(6) and O(17). DFT calculations of bond distances and angles, optimized at the B3LYP/6–31++G(d,p) level, were in good agreement with the X-ray structure

Weather and our food supply

The steep rate of increase in yield of grain crops in the United States since the mid-1950\u27s has resulted in the use of the term explosion in technology. Surplus grains piled up to such proportions after the 1960 · harvest that acreage control appeared. to be in order. But despite substantial reductions in acreages after 1960 the increased output per acre has just about compensated for acreage reductions. During this period of rapid increase in output per acre there has been a growing tendency to believe that technology has reduced the influence of weather on grain production so that we no longer need to fear shortages due to unfavorable weather. There is also a popular belief that acreage control$ fail to achieve the objective of production control, and that public funds are being wasted in storing surplus grains which we don\u27t need. There is increasing evidence, however, that a period of favorable weather interacted with technology to produce our recent high yields, and that perhaps half of the increase in yield per acre since 1950 has been due to a change to more favorable weather for grain crops. These findings have important implications in continued support for research in production technology and in the way in which we look at our surplus stocks of feed and food grains. If a period of favorable weather has been responsible for half of the increase in yields since 19501 then what can we expect if the weather trend reverses itself for a few years? Do we have periodicity in weather, and have we just passed through a run of favorable years that might be followed by a run of unfavorable years? Should we treat our surplus grains as reserves? How does our rate of growth in grain output compare with the needs of a growing world population? And of course I in the background of these questions is one big question -- how much of our recent high yields is really due to weather? To answer these important questions the Center for Agriculture and Economic Development invited outstanding authorities to present their ideas under three main headings: (1) Techniques for Evaluation of Weather Variables in Agricultural Production I (2) Periodicity in Weather Patterns: Implications in Agriculture I and (3) Weather Considerations in Agricultural Policy. The papers have been assembled in the order of their presentation under the general outline above.https://lib.dr.iastate.edu/card_reports/1021/thumbnail.jp

Macrofaunal ecology of sedimented hydrothermal vents in the Bransfield Strait, Antarctica

Sediment-hosted hydrothermal vents, where hot, mineral-rich water flows through sediment, are poorly understood globally, both in their distribution and the ecology of individual vent fields. We explored macrofaunal community ecology at a sediment-hosted hydrothermal vent in the Southern Ocean. This is the first such study of these ecosystems outside of the Pacific and the furthest south (62˚S) of any vent system studied. Sedimentary fauna were sampled at four sites in the Bransfield Strait (Southern Ocean), with the aim of contrasting community structure between vent and non-vent sites. Geochemical data were used to create and test a novel proxy index to quantify the degree of hydrothermal influence and its influence on deep-sea biota. Macrofaunal communities were clearly distinct between vent and non-vent sites, and diversity, richness and density declined towards maximum hydrothermal activity. This variation is in contrast to observations from similar systems in the Pacific and demonstrates the influence of factors other than chemosynthetic primary productivity in structuring infauna at deep-sea vent communities. Vent endemic fauna had limited abundance and were represented by a single siboglinid species at hydrothermally active areas, meaning that that the majority of local biota were those also found in other areas. Several taxa occupied all sampling stations but there were large differences in their relative abundances, suggesting communities were structured by niche variation rather than dispersal ability

Ultra-high resolution X-ray structures of two forms of human recombinant insulin at 100 K

The crystal structure of a commercially available form of human recombinant (HR) insulin, Insugen (I), used in the treatment of diabetes has been determined to 0.92 Å resolution using low temperature, 100 K, synchrotron X-ray data collected at 16,000 keV (λ = 0.77 Å). Refinement carried out with anisotropic displacement parameters, removal of main-chain stereochemical restraints, inclusion of H atoms in calculated positions, and 220 water molecules, converged to a final value of R = 0.1112 and Rfree = 0.1466. The structure includes what is thought to be an ordered propanol molecule (POL) only in chain D(4) and a solvated acetate molecule (ACT) coordinated to the Zn atom only in chain B(2). Possible origins and consequences of the propanol and acetate molecules are discussed. Three types of amino acid representation in the electron density are examined in detail: (i) sharp with very clearly resolved features; (ii) well resolved but clearly divided into two conformations which are well behaved in the refinement, both having high quality geometry; (iii) poor density and difficult or impossible to model. An example of type (ii) is observed for the intra-chain disulphide bridge in chain C(3) between Sγ6–Sγ11 which has two clear conformations with relative refined occupancies of 0.8 and 0.2, respectively. In contrast the corresponding S–S bridge in chain A(1) shows one clearly defined conformation. A molecular dynamics study has provided a rational explanation of this difference between chains A and C. More generally, differences in the electron density features between corresponding residues in chains A and C and chains B and D is a common observation in the Insugen (I) structure and these effects are discussed in detail. The crystal structure, also at 0.92 Å and 100 K, of a second commercially available form of human recombinant insulin, Intergen (II), deposited in the Protein Data Bank as 3W7Y which remains otherwise unpublished is compared here with the Insugen (I) structure. In the Intergen (II) structure there is no solvated propanol or acetate molecule. The electron density of Intergen (II), however, does also exhibit the three types of amino acid representations as in Insugen (I). These effects do not necessarily correspond between chains A and C or chains B and D in Intergen (II), or between corresponding residues in Insugen (I). The results of this comparison are reported

Semi-synthetic analogues of cryptolepine as a potential source of sustainable drugs for the treatment of malaria, human African trypanosomiasis, and cancer

The prospect of eradicating malaria continues to be challenging in the face of increasing parasite resistance to antimalarial drugs so that novel antimalarials active against asexual, sexual, and liver-stage malaria parasites are urgently needed. In addition, new antimalarials need to be affordable and available to those most in need and, bearing in mind climate change, should ideally be sustainable. The West African climbing shrub Cryptolepis sanguinolenta is used traditionally for the treatment of malaria; its principal alkaloid, cryptolepine (1), has been shown to have antimalarial properties, and the synthetic analogue 2,7-dibromocryptolepine (2) is of interest as a lead toward new antimalarial agents. Cryptolepine (1) was isolated using a two-step Soxhlet extraction of C. sanguinolenta roots, followed by crystallization (yield 0.8% calculated as a base with respect to the dried roots). Semi-synthetic 7-bromo- (3), 7, 9-dibromo- (4), 7-iodo- (5), and 7, 9-dibromocryptolepine (6) were obtained in excellent yields by reaction of 1 with N-bromo- or N-iodosuccinimide in trifluoroacetic acid as a solvent. All compounds were active against Plasmodia in vitro, but 6 showed the most selective profile with respect to Hep G2 cells: P. falciparum (chloroquine-resistant strain K1), IC50 = 0.25 µM, SI = 113; late stage, gametocytes, IC50 = 2.2 µM, SI = 13; liver stage, P. berghei sporozoites IC50 = 6.13 µM, SI = 4.6. Compounds 3–6 were also active against the emerging zoonotic species P. knowlesi with 5 being the most potent (IC50 = 0.11 µM). In addition, 3–6 potently inhibited T. brucei in vitro at nM concentrations and good selectivity with 6 again being the most selective (IC50 = 59 nM, SI = 478). These compounds were also cytotoxic to wild-type ovarian cancer cells as well as adriamycin-resistant and, except for 5, cisplatin-resistant ovarian cancer cells. In an acute oral toxicity test in mice, 3–6 did not exhibit toxic effects at doses of up to 100 mg/kg/dose × 3 consecutive days. This study demonstrates that C. sanguinolenta may be utilized as a sustainable source of novel compounds that may lead to the development of novel agents for the treatment of malaria, African trypanosomiasis, and cancer.UK Medical Research Council (MRC) and a Medicines for Malaria Venture Grant.http://www.frontiersin.org/Pharmacologyhj2022BiochemistryGeneticsMicrobiology and Plant PathologyUP Centre for Sustainable Malaria Control (UP CSMC