G2 restriction point within populations of hepatocytes and tongue keratinocytes in young, growing mice

The authors studied the effect of either extracts from liver (LE) or the malignant tumour ES2 (TE) or plasma from intact mice (PI) or tumour-bearing animals (PT) on the mitotic activity of the hepatocytes and tongue keratinocytes in young, growing C3H/s male mice (28+/-1 days old). Animals standardized for periodicity analysis were injected intraperitoneally with either TE, LE, PI, PT, or saline (S) at 16:00 h with 0.01 ml of sample/g of body weight and were then killed at (time of day/h post-injection) 20:00/04, 00:00/08, and 04:00/12. Colchicine (2 microg/g) was injected 4 h before death. Samples of the liver and tongue from each animal were processed for histology and assessment of mitotic index. The results were expressed as colchicine-arrested metaphases/1000 nuclei. The TE and LE stimulated the mitotic activity of hepatocytes and tongue keratinocytes. Taking into account the time elapsed between the injections and the measurements made in these light-dark synchronized animals, we conclude that the increase in mitotic index observed in those tissues stemmed from a reinitiation of cell-cycle traverse in a subpopulation of G2-arrested, noncycling cells.     

Spontaneous activity of the mitochondrial apoptosis pathway drives chromosomal defects,the appearance of micronuclei and cancer metastasis through the Caspase-Activated DNAse

Micronuclei are DNA-containing structures separate from the nucleus found in cancer cells. Micronuclei are recognized by the immune sensor axis cGAS/STING, driving cancer metastasis. The mitochondrial apoptosis apparatus can be experimentally triggered to a non-apoptotic level, and this can drive the appearance of micronuclei through the Caspase-activated DNAse (CAD). We tested whether spontaneously appearing micronuclei in cancer cells are linked to sub-lethal apoptotic signals. Inhibition of mitochondrial apoptosis or of CAD reduced the number of micronuclei in tumor cell lines as well as the number of chromosomal misalignments in tumor cells and intestinal organoids. Blockade of mitochondrial apoptosis or deletion of CAD reduced, while experimental activation CAD, STING-dependently, enhanced aggressive growth of tumor cells in vitro. Deletion of CAD from human cancer cells reduced metastasis in xenograft models. CAD-deficient cells displayed a substantially altered gene-expression profile, and a CAD-associated gene expression ‘signature’ strongly predicted survival in cancer patients. Thus, low-level activity in the mitochondrial apoptosis apparatus operates through CAD-dependent gene-induction and STING-activation and has substantial impact on metastasis in cancer.Subject terms: Metastasis, Apoptosis     

New 1,2,3-triazole linked ciprofloxacin-chalcones induce DNA damage by inhibiting human topoisomerase I& II and tubulin polymerization

A series of novel 1,2,3-triazole-linked ciprofloxacin-chalcones 4a-j were synthesised as potential anticancer agents. Hybrids 4a-j exhibited remarkable anti-proliferative activity against colon cancer cells. Compounds 4a-j displayed IC₅₀s ranged from 2.53-8.67 µM, 8.67–62.47 µM, and 4.19–24.37 µM for HCT116, HT29, and Caco-2 cells; respectively, whereas the doxorubicin, showed IC₅₀ values of 1.22, 0.88, and 4.15 µM. Compounds 4a, 4b, 4e, 4i, and 4j were the most potent against HCT116 with IC₅₀ values of 3.57, 4.81, 4.32, 4.87, and 2.53 µM, respectively, compared to doxorubicin (IC₅₀ = 1.22 µM). Also, hybrids 4a, 4b, 4e, 4i, and 4j exhibited remarkable inhibitory activities against topoisomerase I, II, and tubulin polymerisation. They increased the protein expression level of γH2AX, indicating DNA damage, and arrested HCT116 in G2/M phase, possibly through the ATR/CHK1/Cdc25C pathway. Thus, the novel ciprofloxacin hybrids could be exploited as potential leads for further investigation as novel anticancer medicines to fight colorectal carcinoma.     

Altered renal immune complexes deposition in female BWF1 lupus mice following Plasmodium chabaudi infection

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that has a mysterious relationship with malaria infection. The current study was designated to compare between the effect of the live and the gamma irradiated Plasmodium chabaudi infection on BWF1 lupus murine model. A total of 30 female BWF1 mice were randomly divided into three groups (10 mice/group) as follows: group (I) lupus group (lupus non infected); group (II) live malaria infected group (lupus + live malaria infection); and group (III) irradiated malaria-infected group (lupus + gamma irradiated malaria infection). Live P. chabaudi infection was accompanied with a decrease in survival rate and food consumption in comparison to the control group of mice while gamma irradiated P. chabaudi -infection was unable to do this effect. Additionally, live P. chabaudi infection was accompanied with an increased level of proteinuria and increased rate of immune complexes deposition in kidney. Moreover, infection with live, but not gamma-irradiated P. chabaudi was accompanied with an increase in nitric oxide (NO), hydrogen peroxide (H₂O₂), and malondialdehyde (MDA) levels in plasma of lupus mice. The levels of both total cholesterol and triglycerides in plasma of lupus mice after live P. chabaudi infection were obviously decreased in comparison to the control group. On the other hand, gamma-irradiated P. chabaudi infection resembled the control group. Our data revealed that infection of lupus mice with live but not gamma-irradiated P. chabaudi has several histological and biochemical effects.     

Speciation and Species Separation in Hordeum L. (Poaceae) Resolved by Discontinuous Molecular Markers1

Abstract: Amplified fragment length polymorphisms (AFLPs) were used to evaluate the capacity of discontinuous markers to reveal genetic structure within Hordeum , a challenging higher plant genus from the standpoint of natural systematics. Phylogenies of 63 accessions encompassing nine species from four Hordeum sections were inferred from polymorphisms scored at 600 loci. Phylogenies based on sequences from the nuclear internal transcribed spacer (ITS) region were constructed for comparison, but revealed severe sampling errors inherent to single genes. Although superior by virtue of providing genome-wide estimates of genetic similarity, the adoption of AFLPs in infrageneric studies requires caution. Comigrating AFLP bands studied here could be divided on the basis of band intensity variation into two types that are □ 100 % identical and < 40 % identical in DNA sequence, respectively, in infrageneric comparisons. Thus, the careful selection of AFLP bands to be analyzed bears heavily upon their phylogenetic utility. Within the H. murinum complex, which encompasses three morphologically distinct subspecies, AFLP data from 37 accessions reveal unexpected genetic differentiation between H. murinum, glaucum populations to the east and west of Alexandria (Egypt), suggesting the presence of allopatric speciation in the wake of human settlement.     

Bacteriophage therapy as an alternative technique for treatment of multidrug-resistant bacteria causing diabetic foot infection

International Microbiology - Diabetic foot ulcer (DFU) represented the most feared diabetic complication that caused the hospitalization of the diabetic patient. DFU was usually characterized with...     

Effects of NREM sleep on dynamic within-breath changes in upper airway patency in humans

Morrell, M. J., and M. S. Badr. Effects of NREM sleepon dynamic within-breath changes in upper airway patency in humans. J. Appl. Physiol. 84(1): 190-199, 1998.The purpose of our study was to compare inspiratory- andexpiratory-related changes in retropalatal cross-sectional area (CSA)during wakefulness to those during non-rapid-eye-movement (NREM) sleep.We studied 18 subjects in whom the severity of sleep-disorderedbreathing varied. Relative changes in CSA were visualized by usingfiber-optic endoscopy. For each breath analyzed (wakefulnessn = 4-13; sleepn = 7-16), the CSA was measuredat fixed points within inspiration and expiration (0, 25, 50, and 100%of the inspiratory and expiratory duration); these measurements wereexpressed as a percentage of the CSA that occurred at the start ofinspiration. During wakefulness, there was a statistically significantincrease in the retropalatal CSA (compared with the start ofinspiration) only during early expiration (group mean: expiration, 0% = 112.6 ± 3.2 (SE) %; 25% = 122.8 ± 6.2%; 50% = 110.6 ± 3.8%). In contrast, during sleep, significant changes in CSA occurredduring both inspiration and expiration (group mean: inspiration, 25% = 75.3 ± 6.0%; 50% = 66.7 ± 7.7%; 75% = 64.6 ± 8.1%;expiration, 0% = 126.8 ± 11.8%; 25% = 125.3 ± 6.9%). Theexpiratory-related increase in CSA was followed by narrowing such thatat end expiration the caliber of the airway was returned to thatoccurring at the beginning of inspiration (group mean at end expiration = 98.6 ± 3.1%). The largest changes in CSA occurred in thesubjects with an increased body mass index (BMI). We conclude that,during NREM sleep, significant changes in CSA occur during bothinspiration and expiration and that the magnitude of these changes issignificantly influenced by BMI.

     

Orbicules in angiosperms: Morphology, function, distribution, and relation with tapetum types

Orbicules, or Ubisch bodies, are sporopollenin particles lining the inner tangential and sometimes also the radial tapetal cell walls. They occur only in species with a secretory tapetum. The surface ornamentation of orbicules and pollen of the same species is often strikingly similar. Although orbicules were discovered more than a century ago, these structures remain enigmatic since their function is still obscure. Proposed hypotheses about their possible function are discussed. We also deal here with topics such as the possible allergenicity of orbicules and their representation in the fossil record. The use of orbicule characters for systematics is reviewed. The distribution of orbicules throughout the angiosperms, based on a literature review from the first report until today, is shown in a list with 314 species from 72 families. Those species found in the literature without orbicules are presented together with their tapetum type. We plotted this information on a dahlgrenogram to visualize the distribution of orbicules. Orbicules occur in all subclasses of the angiosperms. Their occurrence is not correlated with certain modes of pollination or habitats.

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Résumé  Les orbicules, ou corps d’Ubisch, sont des particules de sporopollénine couvrant la surface intérieure tangentiale et parfois la surface radiale des cellules du tapétum. On ne les retrouve que dans les espèces possédant un tapétum sécréteur. L’ornementation superficielle des orbicules et celle du pollen d’une même espèce est souvent remarquablement similaire. Malgré le fait que les orbicules ont été découvert il y a plus d’un siècle, ces structures restent énigmatiques et leur fonction est toujours méconnue. Les hypothèses proposées concernant la fonction éventuelle des orbicules sont commentées dans cet article. Nous avons également traité des sujets tels que les éventuels effets allergènes des orbicules ainsi que leur présence dans les strates fossiles. L’utilisation de caractères orbiculaires dans la systématique est analysée. Nous présentons une liste de 314 espèces appartenant à 72 familles possédant des orbicules, sur base d’une analyse de la litérature à partir de la première observation jusqu’au présent. Pour les espèces rapportées dans la litérature qui ne possèdent pas d’orbicules, nous présentons aussi leur type de tapétum. Nous avons projeté cette information sur un Dahlgrenogramme afin de visualiser la distribution des orbicules. Nous les retrouvons dans toutes les sous-classes des angiospermes. Leur présence n’est pas correlée avec certains modes de pollinisation ou avec divers types d’habitat.

     

Selective inhibition of hepatic peroxisomal fatty acid beta-oxidation by enoximone.

Although beta-oxidation of fatty acids occurs in both peroxisomes and mitochondria, beta-oxidizing enzymes in these organelles have distinct differences in their specifity and sensitivity to inhibitors. In this study, the effects of the phosphodiesterase inhibitor enoximone on hepatic peroxisomal and mitochondrial beta-oxidation were investigated. In liver homogenates from control rats, cyanide-insensitive peroxisomal beta-oxidation of palmitoyl-CoA was inhibited progressively by increasing concentrations of enoximone. Similar results were obtained in liver homogenates from rats pretreated with the known peroxisomal proliferator diethylhexylphthalate. In contrast, mitochondrial beta-oxidation of palmitoyl-CoA was not inhibited by enoximone. These data show that enoximone selectively inhibits basal as well as induced peroxisomal, but not mitochondrial, beta-oxidation of the CoA thioester of long-chain fatty acids. The availability of specific inhibitors of peroxisomal beta-oxidation should prove useful in elucidating regulatory mechanisms operative in this pathway in normal as well as in proliferated peroxisomes.