The perforated stones of the Doi Pha Kan burials (Northern Thailand): A Mesolithic singularity?

Throughout continental Southeast Asia, the Hoabinhian techno-complex stands out in clear contrast with the universal chrono-cultural model essentially established on the basis of western prehistory. Following this model, early authors considered perforated stones and associated lithic artefacts as markers of what was then believed to pertain to a Southeast Asian Mesolithic. However, Southeast Asian Mesolitithic has progressively been abandoned in favour of a ubiquitous Hoabinhian spanning from 30,000 to 3000 BP. Here, we present and discuss the discovery of perforated stones at the Doi Pha Kan site in northern Thailand. Perforated stones have almost never been found in undisturbed stratigraphic conditions nor dated with any sufficient degree of certainty. At Doi Pha Kan site, such a kind of artefacts was found in burials intersecting sedimentary layers that could be ascertained as Hoabinhian. In contrast with similar perforated stones described in the literature, that found at Doi Pha Kan are well-dated (13,000 BP), thus providing a time-reference for a putative Southeast Asian Mesolithic. We therefore advocate that such non-Hoabinhian artefacts support the early authors’ hypothesis of the existence of a Southeast Asian Mesolithic. Finally, the funerary practices, the unusually high stature of individuals found at Doi Pha Kan in conjunction with the particular lithic assemblages further contributes to raise the question of the co-occurrence of several cultures or populations at the Pleistocene–Holocene interface in continental Southeast Asia.     

Water soluble prodrug of a COX-2 selective inhibitor suitable for intravenous administration in models of cerebral ischemia

A water soluble choline prodrug (17) of a COX-2 selective inhibitor (16) suitable for intravenous dosing in models of cerebral ischemia has been developed. Constant infusion studies using 17 demonstrate that extrapolated brain levels of 16 may be maintained for over 24h in rats.     

Notch signalling inhibits the adipogenic differentiation of single‐cell‐derived mesenchymal stem cell clones isolated from human adipose tissue

ADSCs (adipose‐derived mesenchymal stem cells) are candidate adult stem cells for regenerative medicine. Notch signalling participates in the differentiation of a heterogeneous ADSC population. We have isolated, human adipose tissue‐derived single‐cell clones using a cloning ring technique and characterized for their stem cell characteristics. The role of Notch signalling in the differentiation capacity of these adipose‐derived single‐cell‐clones has also been investigated. All 14 clones expressed embryonic and mesenchymal stem cell marker genes. These clones could differentiate into both osteogenic and adipogenic lineages. However, the differentiation potential of each clone was different. Low adipogenic clones had significantly higher mRNA expression levels of Notch 2, 3 and 4, Jagged1, as well as Delta1, compared with those of high adipogenic clones. In contrast, no changes in expression of Notch signalling component mRNA between low and high osteogenic clones was found. Notch receptor mRNA expression decreased with the adipogenic differentiation of both low and high adipogenic clones. The γ‐secretase inhibitor, DAPT (N‐[N‐(3,5‐difluorophenacetyl)‐l ‐alanyl]‐(S)‐phenylglycine t‐butyl ester), enhanced adipogenic differentiation. Correspondingly, cells seeded on a Notch ligand (Jagged1) bound surface showed lower intracellular lipid accumulation. These results were noted in both low and high adipogenic clones, indicating that Notch signalling inhibited the adipogenic differentiation of adipose ADSC clones, and could be used to identify an adipogenic susceptible subpopulation for soft‐tissue augmentation application.     

Growth of human keratinocytes and fibroblasts on bacterial cellulose film

Thin films of bacterial cellulose (BC) from a nata de coco culture system were developed, characterized, and investigated for the growth of human keratinocytes and fibroblasts. The average pore diameter and total surface area of the dried BC films estimated by BET were 224 A and 12.62 m(2)/g, respectively. With an film thickness of 0.12 mm, the average tensile strength and break strain of the dried films were 5.21 MPa and 3.75%, whereas those of the wet films were 1.56 MPa and 8.00%, respectively. The water absorption capacity of air-dried film was 5.09 g water/g dried films. For uses in the therapy of skin wounds, the potential biological mechanism of action of BC film was evaluated by using human keratinocytes and fibroblasts. Our results were the first direct demonstration that BC film supported the growth, spreading, and migration of human keratinocytes but not those of human fibroblasts. Expressions of E-cadherin and the alpha-3 chain of laminin confirmed the phenotype of human keratinocytes on BC film.     

Novel tricyclic antagonists of the prostaglandin D2 receptor DP2 with efficacy in a murine model of allergic rhinitis

The synthesis of a series of tricyclic antagonists for the prostaglandin D₂ receptor DP2 (CRTH2) is disclosed. The activities of the compounds were evaluated in a human DP2 binding assay and a human whole blood eosinophil shape change assay. Potential metabolic liabilities of the compounds were addressed through in vitro CYP studies. The lead compound was demonstrated to have efficacy in a mouse model of allergic rhinitis following oral dosing.     

Drug resistance and IS6110‐RFLP patterns of Mycobacterium tuberculosis in patients with recurrent tuberculosis in northern Thailand

The emergence of drug resistant Mycobacterium tuberculosis has become a global threat to tuberculosis (TB) prevention and control efforts. This study aimed to determine the drug resistance profiles and DNA fingerprints of M. tuberculosis strains isolated from patients with relapsed or retreatment pulmonary TB in Chiang Rai province in northern Thailand. Significant differences in multidrug resistance (MDR) (P = 0.025) and resistance to isoniazid (P = 0.025) and rifampin (P = 0.046) between first and second registrations of patients with retreatment TB were found. However, there were no significant differences in resistance to any drugs in patients with relapsed TB. The rate of MDR‐TB strains was 12.2% among new patients at first registration, 22.5% among patients with recurrence who had previously undergone treatment at second registration and 12.5% at third registration. Two retreatment patients whose initial treatment had failed had developed MDR‐TB with resistance to all TB drugs tested, including rifampin, isoniazid, streptomycin and ethambutol. IS6110‐RFLP analysis revealed that 66.7% (10/15 isolates) of MDR‐TB belonged to the Beijing family. In most cases, IS6110‐RFLP patterns of isolates from the same patients were identical in relapse and retreatment groups. However, some pairs of isolates from retreatment patients after treatment failure had non‐identical IS6110‐RFLP patterns. These results suggest that, after failure and default treatment, patients with retreatment tuberculosis have a significantly greater risk of MDR‐TB, isoniazid and rifampin resistance than do other patients.     

Development of L-689,065 - the prototype of a new class of potent 5-lipoxygenase inhibitors

The combination of a 5-phenylpyridine substituent and a novel, substituted thiopyrano[2,3,4-c,d]indole ring system yields a potent and selective 5-lipoxygenase inhibitor, L-689,065.     

Reforestations of Tropical Forests Alter Interactions Between Web-Building Spiders and Their Prey

Ecosystems - Immense effort has been devoted to mitigating the negative effect of deforestation, one of the main factors causing global change. However, the effect of reforestation management on...