Mitotic catastrophe triggered in human cancer cells by the viral protein apoptin

Mitotic catastrophe is an oncosuppressive mechanism that senses mitotic failure leading to cell death or senescence. As such, it protects against aneuploidy and genetic instability, and its induction in cancer cells by exogenous agents is currently seen as a promising therapeutic end point. Apoptin, a small protein from Chicken Anemia Virus (CAV), is known for its ability to selectively induce cell death in human tumor cells. Here, we show that apoptin triggers p53-independent abnormal spindle formation in osteosarcoma cells. Approximately 50% of apoptin-positive cells displayed non-bipolar spindles, a 10-fold increase as compared to control cells. Besides, tumor cells expressing apoptin are greatly limited in their progress through anaphase and telophase, and a significant drop in mitotic cells past the meta-to-anaphase transition is observed. Time-lapse microscopy showed that mitotic osteosarcoma cells expressing apoptin displayed aberrant mitotic figures and/or had a prolonged cycling time during mitosis. Importantly, all dividing cells expressing apoptin eventually underwent cell death either during mitosis or during the following interphase. We infer that apoptin can efficiently trigger cell death in dividing human tumor cells through induction of mitotic catastrophe. However, the killing activity of apoptin is not only confined to dividing cells, as the CAV-derived protein is also able to trigger caspase-3 activation and apoptosis in non-mitotic cancer cells.     

ZNF674: a new kruppel-associated box-containing zinc-finger gene involved in nonsyndromic X-linked mental retardation

Array-based comparative genomic hybridization has proven to be successful in the identification of genetic defects in disorders involving mental retardation. Here, we studied a patient with learning disabilities, retinal dystrophy, and short stature. The family history was suggestive of an X-linked contiguous gene syndrome. Hybridization of full-coverage X-chromosomal bacterial artificial chromosome arrays revealed a deletion of ~1 Mb in Xp11.3, which harbors RP2, SLC9A7, CHST7, and two hypothetical zinc-finger genes, ZNF673 and ZNF674. These genes were analyzed in 28 families with nonsyndromic X-linked mental retardation (XLMR) that show linkage to Xp11.3; the analysis revealed a nonsense mutation, p.E118X, in the coding sequence of ZNF674 in one family. This mutation is predicted to result in a truncated protein containing the Kruppel-associated box domains but lacking the zinc-finger domains, which are crucial for DNA binding. We characterized the complete ZNF674 gene structure and subsequently tested an additional 306 patients with XLMR for mutations by direct sequencing. Two amino acid substitutions, p.T343M and p.P412L, were identified that were not found in unaffected individuals. The proline at position 412 is conserved between species and is predicted by molecular modeling to reduce the DNA-binding properties of ZNF674. The p.T343M transition is probably a polymorphism, because the homologous ZNF674 gene in chimpanzee has a methionine at that position. ZNF674 belongs to a cluster of seven highly related zinc-finger genes in Xp11, two of which (ZNF41 and ZNF81) were implicated previously in XLMR. Identification of ZNF674 as the third XLMR gene in this cluster may indicate a common role for these zinc-finger genes that is crucial to human cognitive functioning.     

Immunohistochemical localization of irisin in skin,eye, and thyroid and pineal glands of the crested porcupine (Hystrix cristata)

Irisin was first identified in muscle cells. We detected irisin immunoreactivity in various organs of the crested porcupine (Hystrix cristata). In the epidermis, irisin immunoreactivity was localized mainly in stratum basale, stratum spinosum and stratum granulosum layers; immunoreactivity was not observed in the stratum corneum. In the dermis, irisin was found in the external and internal root sheath, cortex and medulla of hair follicles, and in sebaceous glands. Irisin immunoreactivity was found in the neural retina and skeletal muscle fibers associated with the eye. The pineal and thyroid glands also exhibited irisin immunoreactivity.     

Streptococcus suis Meningitis: A Systematic Review and Meta-analysis

Background

Streptococcus suis is the most common cause of meningitis in pork consuming and pig rearing countries in South-East Asia. We performed a systematic review of studies on S. suis meningitis to define the clinical characteristics, predisposing factors and outcome.

Methodology

Studies published between January 1, 1980 and August 1, 2015 were identified from main literature databases and reference lists. Studies were included if they were written in West-European languages and described at least 5 adult patients with S. suis meningitis in whom at least one clinical characteristic was described.

Findings

We identified 913 patients with S. suis meningitis included in 24 studies between 1980 and 2015. The mean age was 49 years and 581 of 711 patients were male (82%). Exposure to pigs or pork was present in 395 of 648 patients (61%) while other predisposing factors were less common. 514 of 528 patients presented with fever (97%), 429 of 451 with headache (95%), 462 of 496 with neck stiffness (93%) and 78 of 384 patients (20%) had a skin injury in the presence of pig/pork contact. The case fatality rate was 2.9% and hearing loss was a common sequel occurring in 259 of 489 patients (53%). Treatment included dexamethasone in 157 of 300 (52%) of patients and was associated with reduced hearing loss in S. suis meningitis patients included in a randomized controlled trial.

Conclusion

S. suis meningitis has a clear association with pig and pork contact. Mortality is low, but hearing loss occurs frequently. Dexamethasone was shown to reduce hearing loss.     

Plant metabolomics and its potential application for human nutrition

With the growing interest in the use of metabolomic technologies for a wide range of biological targets, food applications related to nutrition and quality are rapidly emerging. Metabolomics offers us the opportunity to gain deeper insights into, and have better control of, the fundamental biochemical basis of the things we eat. So doing will help us to design modified breeding programmes aimed at better quality produce; optimised food processing strategies and ultimately, improved (micro)nutrient bioavailability and bioefficacy. A better understanding of the pathways responsible for the biosynthesis of nutritionally relevant metabolites is key to gaining more effective control of the absence/level of presence of such components in our food. Applications of metabolomic technologies in both applied and fundamental science strategies are therefore growing rapidly in popularity. Currently, the world has two highly contrasting nutrition-related problems--over-consumption and under-nourishment. Dramatic increases in the occurrence of overweight individuals and obesity in developed countries are in staggering contrast to the still-familiar images of extreme malnutrition in many parts of the developing world. Both problems require a modified food supply, achieved through highly contrasting routes. For each, metabolomics has a future role to play and this review shall deal with this key dichotomy and illustrate where metabolomics may have a future part to play. In this short overview, attention is given to how the various technologies have already been exploited in a plant-based food context related to key issues such as biofortification, bioprotectants and the general link between food composition and human health. Research on key crops such as rice and tomato are used as illustration of potentially broader application across crop species. Although the focus is clearly on food supply, some attention is given to the complementary field of research, nutrigenomics, where similar technologies are being applied to understand nutrition better from the human side.     

Experimental evaluation of sex differences in territory acquisition in a cooperatively breeding bird

In many species, territory ownership is a prerequisite for reproduction;consequently, factors that affect success in territory acquisitioncan have a large impact on fitness. When competing for territories,some individuals may have an advantage if, for example, theyare phenotypically superior or more familiar with the site thanothers. The relative importance of the many factors involvedin territory acquisition is, at present, unclear. We studiedpatterns of natural territory acquisition in a closed and saturatedpopulation of Seychelles warblers. Furthermore, by removingbreeders, we experimentally investigated the relative importance,to territory acquisition, of a range of factors and assessedwhether this differed between the sexes. In both sexes, themain route to natural territory acquisition was to dispersefrom the natal territory to immediately claim a vacant dominantposition. Males were older than females when acquiring a territoryfor the first time. In the removal experiment, for both sexes,the proximity of an individual's natal territory to a vacantdominant position was positively related to the individual'schance of claiming the vacancy. Older males were more likelyto gain an experimental vacant dominant position than were youngmales, whereas age did not affect territory acquisition in females.In the Seychelles warbler, the degree of intrasexual competitionfor territory ownership may be stronger for males than for femalesbecause territory ownership is a prerequisite for male reproduction,whereas females can reproduce on their natal territory. In suchcompetition, young males subsequently lose out to older ones.     

Dephytinisation with Intrinsic Wheat Phytase and Iron Fortification Significantly Increase Iron Absorption from Fonio (Digitaria exilis) Meals in West African Women

Low iron and high phytic acid content make fonio based meals a poor source of bioavailable iron. Phytic acid degradation in fonio porridge using whole grain cereals as phytase source and effect on iron bioavailability when added to iron fortified fonio meals were investigated. Grains, nuts and seeds collected in Mali markets were screened for phytic acid and phytase activity. We performed an iron absorption study in Beninese women (n = 16), using non-dephytinised fonio porridge (FFP) and dephytinised fonio porridge (FWFP; 75% fonio-25% wheat), each fortified with ⁵⁷Fe or ⁵⁸Fe labeled FeSO₄. Iron absorption was quantified by measuring the erythrocyte incorporation of stable iron isotopes. Phytic acid varied from 0.39 (bambara nut) to 4.26 g/100 g DM (pumpkin seed), with oilseeds values higher than grains and nuts. Phytase activity ranged from 0.17±1.61 (fonio) to 2.9±1.3 phytase unit (PU) per g (whole wheat). Phytic acid was almost completely degraded in FWFP after 60 min of incubation (pH≈5.0, 50°C). Phytate∶iron molar ratios decreased from 23.7∶1 in FFP to 2.7∶1 in FWFP. Iron fortification further reduced phytate∶iron molar ratio to 1.9∶1 in FFP and 0.3∶1 in FWFP, respectively. Geometric mean (95% CI) iron absorption significantly increased from 2.6% (0.8–7.8) in FFP to 8.3% (3.8–17.9) in FWFP (P<0.0001). Dephytinisation of fonio porridge with intrinsic wheat phytase increased fractional iron absorption 3.2 times, suggesting it could be a possible strategy to decrease PA in cereal-based porridges.     

Vertebrate aristaless-related genes

Aristaless-related genes, a subset of the Paired-related homeobox genes, have in the past few years emerged as a group of regulators of essential events during vertebrate embryogenesis. One group of aristaless-related genes has been linked to the morphogenesis of the craniofacial and appendicular skeleton by their expression patterns and by the phenotypes of natural and artificial mouse mutants. Expression and function in the nervous system characterise a second group, and a third group, the Pitx genes, have been shown to have many different roles, including functions in the pituitary, left-right determination and limb development.     

Folate fortification of rice by metabolic engineering

Rice, the world's major staple crop, is a poor source of essential micronutrients, including folates (vitamin B9). We report folate biofortification of rice seeds achieved by overexpressing two Arabidopsis thaliana genes of the pterin and para-aminobenzoate branches of the folate biosynthetic pathway from a single locus. We obtained a maximal enhancement as high as 100 times above wild type, with 100 g of polished raw grains containing up to four times the adult daily folate requirement.     

Binpairs: Utilization of Illumina Paired-End Information for Improving Efficiency of Taxonomic Binning of Metagenomic Sequences

Motivation

Paired-end sequencing protocols, offered by next generation sequencing (NGS) platforms like Illumia, generate a pair of reads for every DNA fragment in a sample. Although this protocol has been utilized for several metagenomics studies, most taxonomic binning approaches classify each of the reads (forming a pair), independently. The present work explores some simple but effective strategies of utilizing pairing-information of Illumina short reads for improving the accuracy of taxonomic binning of metagenomic datasets. The strategies proposed can be used in conjunction with all genres of existing binning methods.

Results

Validation results suggest that employment of these “Binpairs” strategies can provide significant improvements in the binning outcome. The quality of the taxonomic assignments thus obtained are often comparable to those that can only be achieved with relatively longer reads obtained using other NGS platforms (such as Roche).

Availability

An implementation of the proposed strategies of utilizing pairing information is freely available for academic users at https://metagenomics.atc.tcs.com/binning/binpairs.