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During this study, one new coumarin; 7-O-β-D-glucopyranoside-2H-1-benzopyran-2-one (1) and three quinoline alkaloids; 3-hydroxy, 2, 2, 6-trimethyl–3, 4, 5, 6-tetrahydro-2H-pyrano[3,2-c] quinoline 5-one (2), ribalinine (3) and methyl isoplatydesmine (4) were isolated from the aerial parts of Skimmia laureola and their structures established by spectroscopic studies. Compounds 2-4 were found to be linear mixed type inhibitors of acetylcholinesterase (Ki = 110.0, 30.0 and 30.0 μM, respectively). Compounds 2 and 3 were also found to be linear mixed type inhibitors of butyrylcholinesterase, while compound 4 was a noncompetitive inhibitor of the enzyme (Ki = 90.0, 70.0 and 19.0 μM, respectively). The inhibition of acetyl- and butyryl-cholinesterase enzymes persists as the most promising therapeutic strategy for activating the impaired cholinergic functions in Alzheimer's disease and related dementias.Compound 4 also showed dose-dependent spasmolytic activity in the isolated rabbit jejunum intestinal preparation by relaxing the spontaneous (EC50 = 0.1 mg/mL) and K+-induced contractions (EC50 = 0.4 mg/mL), suggesting that the spasmolytic effect of compound 4 is mediated through the blockade of voltage-dependent Ca2 + channels. [ABSTRACT FROM AUTHOR]

One of the major problems faced by the reconstructive surgeon is how to cover soft tissue defects having exposed bones and tendons in the lower third of the leg, ankle, heel, and foot. The distally based superficial sural artery flap is an effective alternative for such reconstructions. The distally based superficial sural artery adipofasciocutaneous flap is supplied by the perforators of peroneal artery as a reverse flow flap. From 1999 to 2004, we used a distally based superficial sural artery flap for the reconstruction of the ankle heel and foot in 11 patients. The largest flap used was 15 cm in width and 18 cm in length. Nine flaps survived completely and two necrosed partially. Mild edema and congestion were observed in most of the flaps, but these observed conditions improved with time. The main advantages included reliable blood supply without sacrificing any major artery of the limb and easy, simple, and quick elevation. [ABSTRACT FROM AUTHOR]

To achieve replicative immortality, cancer cells must activate telomere maintenance mechanisms. In 10 to 15% of cancers, this is enabled by recombination-based alternative lengthening of telomeres pathways (ALT). ALT cells display several hallmarks including heterogeneous telomere length, extrachromosomal telomeric repeats, and ALT-associated PML bodies. ALT cells also have high telomeric replication stress (RS) enhanced by fork-stalling structures (R-loops and G4s) and altered chromatin states. In ALT cells, telomeric RS promotes telomere elongation but above a certain threshold becomes detrimental to cell survival. Manipulating RS at telomeres has thus been proposed as a therapeutic strategy against ALT cancers. Through analysis of genome-wide CRISPR fitness screens, we identified ALT-specific vulnerabilities and describe here our characterization of the roles of SUB1, a ssDNA-binding protein, in telomere stability. SUB1 depletion increases RS at ALT telomeres, profoundly impairing ALT cell growth without impacting telomerase-positive cells. During RS, SUB1 is recruited to stalled forks and ALT telomeres via its ssDNA-binding domain. This recruitment is potentiated by RPA depletion, suggesting that these factors may compete for ssDNA. The viability of ALT cells and their resilience toward RS also requires ssDNA binding by SUB1. SUB1 depletion accelerates cell death induced by FANCM depletion, triggering unsustainable levels of telomeric damage in ALT cells. Finally, combining SUB1 depletion with RS-inducing drugs rapidly induces replication catastrophe in ALT cells. Altogether, our work identifies SUB1 as an ALT susceptibility with roles in the mitigation of RS at ALT telomeres and suggests advanced therapeutic strategies for a host of still poorly managed cancers., Competing Interests: Competing interests statement:The authors declare no competing interest.

Cotton is one of the most important natural fiber crops in the world. Its growth and yield is greatly limited by drought. A quantitative trait locus (QTL) analysis was therefore conducted to investigate the genetic basis of drought tolerance in cotton (Gossypium spp) using 188 F2:3 lines developed from an inter-specific cross between a wild cotton species, G. tomentosum, and an upland cotton, G. hirsutum (CRI-12). A genetic map was constructed using 1295 simple sequence repeat markers, which amplified 1342 loci, distributed on 26 chromosomes, covering 3328.24 cM. A field experiment was conducted in two consecutive years (2014 and 2015) and 11 morphological and physiological traits were recorded under water-limited (W1)/well-watered (W2) regimes at three growth stages (bud, flowering, and full boll). The traits measured included chlorophyll content, plant height, leaf area, leaf number, leaf fresh weight, leaf dry weight, boll weight, number of bolls per plant, and the number of fruiting branches. Sixty-seven and 35 QTLs were found under the W1 and W2 conditions, respectively. Of these, the majority exhibited partial dominance or over-dominance genetic effects for increasing the trait values. Four consistent QTLs were found under the W1 treatment on chromosomes 5, 8, 9, and 16, whereas no consistent QTL was found in W2. Thirteen QTL clusters were also identified on nine chromosomes (2, 3, 5, 6, 9, 14, 15, 16, and 21). These results will help to elucidate the genetic basis of drought tolerance in cotton.

Background: Chromosomal abnormalities are the most common cause of recurrent abortions and miscarriages (RAM), but micro-variations on chromosomes causing RAM have never been previously studied. Single nucleotide polymorphisms (SNPs) are the single nucleotide variations frequently present at genome with the density of at least one common (>20% allele frequency) SNP per kilobase pair. It has already been reported that SNP array examination for chromosomal abnormalities has better performance than the conventional cytogenetic karyotyping., Methods: We applied SNP array to detect the chromosomal defects in 80 placental villi and foetal tissues of abnormal foetus and spontaneous abortions., Results: The analyses of data revealed that total 52.5% (42/80) cases were found to have chromosomal abnormalities. The trisomies were most commonly found 26/42 (61.9%) in current samples. Total 8/42 (19.1%) cases were found to have other structural aberrations including translocations in 2/8 (25%), duplications and deletions in 3/8 (37.5%) cases, respectively. SNP analysis also successfully detected triploidy 69,XXX and tetraploidy 92,XXXY. Total 12/80 cases were performed by cytogenetic karyotyping and results were compared with SNP data. Total 5/12 (41.7%) cases were found to have same findings with SNP data while results of 2/12 (16.7%) cases had partial similarity between both techniques. Four cases were declared as karyotypically normal (46,XY or 46,XX) by cytogenetic examination, but later on these four cases were found to have small chromosomal variation which could be the cause of RAM in women., Conclusion: Therefore, we conclude that use of a high-density SNP platform in diagnosis can give better understanding of molecular causes of pregnancy loss and foetal abnormalities.