First evidence of early neolithic archery from Cueva de los Murciélagos (Albuñol, Granada) revealed through combined chemical and morphological analysis.

The extraordinary preservation of Cueva de Los Murciélagos (Albuñol, Spain) provides a unique opportunity to identify the materials and the techniques involved in archery during the Early Neolithic period. Arrows with preserved feathers, tied fibres, adhesive substance, and two probable bowstrings have been studied trough an unprecedented multi-proxy investigation, including microscopy and biomolecular methods, to unravel archery techniques. The study has identified the oldest known sinew bowstrings, the first evidence for the use of olive tree (Olea europaea) and reed (Phragmites sp.

An experimental dataset on yields of pulses across Europe.

Future European agriculture should achieve high productivity while limiting its impact on the environment. Legume-supported crop rotations could contribute to these goals, as they request less nitrogen (N) fertilizer inputs, show high resource use efficiency and support biodiversity. However, legumes grown for their grain (pulses) are not widely cultivated in Europe.

The earliest basketry in southern Europe: Hunter-gatherer and farmer plant-based technology in Cueva de los Murciélagos (Albuñol).

Plant material culture can offer unique insights into the ways of life of prehistoric societies; however, its perishable nature has prevented a thorough understanding of its diverse and complex uses. Sites with exceptional preservation of organic materials provide a unique opportunity for further research. The burial site of Cueva de los Murciélagos in southern Iberia, uncovered during 19th-century mining activities, contained the best-preserved hunter-gatherer basketry in southern Europe, together with other unique organic artifacts associated with the first farming communities, such as sandals and a wooden hammer.

Aminoguanidine Hydrazone Derivatives as Nonpeptide NPFF1 Receptor Antagonists Reverse Opioid Induced Hyperalgesia.

Neuropeptide FF receptors (NPFF1R and NPFF2R) and their endogenous ligand neuropeptide FF have been shown previously to display antiopioid properties and to play a critical role in the adverse effects associated with chronic administrations of opiates including the development of opioid-induced hyperalgesia and analgesic tolerance. In this work, we sought to identify novel NPFF receptors ligands by focusing our interest in a series of heterocycles as rigidified nonpeptide NPFF receptor ligands, starting from already described aminoguanidine hydrazones (AGHs). Binding experiments and functional assays highlighted AGH 1n and its rigidified analogue 2-amino-dihydropyrimidine 22e for in vivo experiments.

Development of Dipeptidic hGPR54 Agonists.

A series of dipeptides were designed as potential agonists of the human KiSS1-derived peptide receptor (hGPR54). While the sequence Arg-Trp-NH was the most efficient in terms of affinity, we established a convergent synthetic strategy to optimize the N terminus. Using two successive Sonogashira cross-coupling reactions on a solid-supported peptide, we were able to introduce various alkynes at the N terminus to afford compounds with sub-micromolar affinities for hGPR54.

Effects of systematic N-terminus deletions and benzoylations of endogenous RF-amide peptides on NPFF1R, NPFF2R, GPR10, GPR54 and GPR103.

Mammalian RF-amide peptides including RF-amide-related peptides-1 and -3, neuropeptides AF and FF, Prolactin releasing peptides, Kisspeptins and RFa peptides are currently considered endogenous peptides for the GPCRs NPFF1R, NPFF2R, GPR10, GPR54 and GPR103, respectively. While NPFF1R and NPFF2R displayed high affinity for all the RF-amide peptides, GPR10, GPR54 and GPR103 only bind their cognate ligands. Through a systematic and sequential N-terminus deletion and benzoylation of either RF-amide neuropeptide (RFRP-3, NPFF, Kp-10, PrRP20, and 26RFa), we report the corresponding impact on affinity and activity towards all the RF-amide receptors (NPFF1R, NPFF2R, GPR10, GPR54 and GPR103).

Neuropeptide FF receptors as novel targets for limbic seizure attenuation.

Neuropeptide Y (NPY) is a well established anticonvulsant and first-in-class antiepileptic neuropeptide. In this study, the controversial role of NPY1 receptors in epilepsy was reassessed by testing two highly selective NPY1 receptor ligands and a mixed NPY1/NPFF receptor antagonist BIBP3226 in a rat model for limbic seizures. While BIBP3226 significantly attenuated the pilocarpine-induced seizures, neither of the highly selective NPY1 receptor ligands altered the seizure severity.

Development of a peptidomimetic antagonist of neuropeptide FF receptors for the prevention of opioid-induced hyperalgesia.

Through the development of a new class of unnatural ornithine derivatives as bioisosteres of arginine, we have designed an orally active peptidomimetic antagonist of neuropeptide FF receptors (NPFFR). Systemic low-dose administration of this compound to rats blocked opioid-induced hyperalgesia, without any apparent side-effects. Interestingly, we also observed that this compound potentiated opioid-induced analgesia.

A physical map of the short arm of wheat chromosome 1A.

Bread wheat (Triticum aestivum) has a large and highly repetitive genome which poses major technical challenges for its study. To aid map-based cloning and future genome sequencing projects, we constructed a BAC-based physical map of the short arm of wheat chromosome 1A (1AS). From the assembly of 25,918 high information content (HICF) fingerprints from a 1AS-specific BAC library, 715 physical contigs were produced that cover almost 99% of the estimated size of the chromosome arm.

Endogenous mammalian RF-amide peptides, including PrRP, kisspeptin and 26RFa, modulate nociception and morphine analgesia via NPFF receptors.

Mammalian RF-amide peptides are encoded by five different genes and act through five different G protein-coupled receptors. RF-amide-related peptides-1 and -3, neuropeptides AF and FF, Prolactin releasing peptides, Kisspeptins and RFa peptides are currently considered endogenous peptides for NPFF1, NPFF2, GPR10, GPR54 and GPR103 receptors, respectively. However, several studies suggest that the selectivity of these peptides for their receptors is low and indicate that expression patterns for receptors and their corresponding ligands only partially overlap.

A high density physical map of chromosome 1BL supports evolutionary studies, map-based cloning and sequencing in wheat.

Background: As for other major crops, achieving a complete wheat genome sequence is essential for the application of genomics to breeding new and improved varieties. To overcome the complexities of the large, highly repetitive and hexaploid wheat genome, the International Wheat Genome Sequencing Consortium established a chromosome-based strategy that was validated by the construction of the physical map of chromosome 3B. Here, we present improved strategies for the construction of highly integrated and ordered wheat physical maps, using chromosome 1BL as a template, and illustrate their potential for evolutionary studies and map-based cloning.

Development of sub-nanomolar dipeptidic ligands of neuropeptide FF receptors.

Based on our earlier reported neuropeptide FF receptors antagonist (RF9), we carried out an extensive structural exploration of the N-terminus part of the amidated dipeptide Arg-Phe-NH(2) in order to establish a structure-activity relationships (SAR) study towards both NPFF receptor subtypes. This SAR led to the discovery of dipeptides (12, 35) with subnanomolar affinities towards NPFF1 receptor subtype, similar to endogenous ligand NPVF. More particularly, compound 12 exhibited a potent in vivo preventive effect on opioid-induced hyperalgesia at low dose.

Cell-specific interaction of retinoic acid receptors with target genes in mouse embryonic fibroblasts and embryonic stem cells.

All-trans retinoic acid (RA) induces transforming growth factor beta (TGF-beta)-dependent autocrine growth of mouse embryonic fibroblasts (MEFs). We have used chromatin immunoprecipitation to map 354 RA receptor (RAR) binding loci in MEFs, most of which were similarly occupied by the RAR alpha and RAR gamma receptors. Only a subset of the genes associated with these loci are regulated by RA, among which are several critical components of the TGF-beta pathway.

Development of consistently crossable wheat genotypes for alien wheat gene transfer through fine-mapping of the Kr1 locus.

Breeders can force sexual hybridisation between wheat and related grass species to produce interspecific hybrids containing a dihaploid set of wheat and related chromosomes. This facilitates the introgression of desirable genes into wheat from the secondary gene pool. However, most elite European wheat varieties carry genes that suppress crossability, making the transfer of novel traits from exotic germplasm into elite wheat varieties difficult or impossible.

Detailed dissection of the chromosomal region containing the Ph1 locus in wheat Triticum aestivum: with deletion mutants and expression profiling.

Background And Aims: Understanding Ph1, a dominant homoeologous chromosome pairing suppressor locus on the long arm of chromosome 5B in wheat Triticum aestivum L., is the core of the investigation in this article. The Ph1 locus restricts chromosome pairing and recombination at meiosis to true homologues.

Genetic analysis of peroxisome proliferator-activated receptor gamma1 splice variants in human colorectal cell lines.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear hormone receptor family. In colon, this transcription factor is involved in differentiation of absorptive cells. PPARgamma participates also in colon carcinogenesis and cancer progression.

Molecular characterization of Ph1 as a major chromosome pairing locus in polyploid wheat.

The foundation of western civilization owes much to the high fertility of bread wheat, which results from the stability of its polyploid genome. Despite possessing multiple sets of related chromosomes, hexaploid (bread) and tetraploid (pasta) wheat both behave as diploids at meiosis. Correct pairing of homologous chromosomes is controlled by the Ph1 locus.

SSCP-SNP in pearl millet--a new marker system for comparative genetics.

A considerable array of genomic resources are in place in pearl millet, and marker-aided selection is already in use in the public breeding programme at ICRISAT. This paper describes experiments to extend these publicly available resources to a single nucleotide polymorphism (SNP)-based marker system. A new marker system, single-strand conformational polymorphism (SSCP)-SNP, was developed using annotated rice genomic sequences to initially predict the intron-exon borders in millet expressed sequence tags (ESTs) and then to design primers that would amplify across the introns.

Surveillance network for herpes simplex virus resistance to antiviral drugs: 3-year follow-up.

Herpes simplex virus (HSV) infections are very common in the general population and among immunocompromised patients. Acyclovir (ACV) is an effective treatment which is widely used. We deemed it essential to conduct a wide and coordinated survey of the emergence of ACV-resistant HSV strains.

Double-blind placebo cross-over study of long-acting (chlordesmethyldiazepam) versus short-acting (lorazepam) benzodiazepines in generalized anxiety disorders.

Chlordesmethyldiazepam a long-acting benzodiazepine was compared with lorazepam a short-acting one in a double-blind placebo cross-over study against generalized anxiety disorders. Chlordesmethyldiazepam therapy was more effective than lorazepam. Clinical efficacy, drowsiness and insomnia seem well correlated with pharmacokinetic properties of these two benzodiazepines.

[Affective disorders in general hospitals: the organic affective syndrome].

After a survey of the literature on secondary depression and mania caused by physical illness or drugs, a retrospective study on 77 inpatients (seen in the hospital psychiatric consultation service) is reported. Forty per cent of patients presented a diagnosis of depression; 58% of depressed patients had at least one of the "risk factors" for secondary depression (physical illness and drugs known to cause affective disturbances) compared to 24% and 16% of patients with other or no mental disorders (p less than 0.05).

[Clinical evaluation of clotiazepam in the ambulatory treatment of anxiety states].

To assess the therapeutic efficacy and tolerability of Clotiazepam in the treatment of anxiety, the drug was administered to 20 subjects suffering from anxiety (12 cases) or from nervous depression (8 cases), all of whom were without psychopharmacological drugs for at least one month prior to the trial. Treatment with Clotiazepam improved the anxiety and brought about a statistically significant reduction in both groups of patients regards the total score in the Hamilton Scale and in the two sub-scale scores (somatic and psychological symptoms). Tolerability to the drug was very satisfactory.

Orphenadrine serum levels in a poisoned patient.

A patient ingested about 5 g of orphenadrine hydrochloride. He had gastric lavage and oral administration of activated charcoal. The main symptoms were neuropsychiatric in nature.