Optimising human community sizes

We examine community longevity as a function of group size in three historical, small scale agricultural samples. Community sizes of 50, 150 and 500 are disproportionately more common than other sizes; they also have greater longevity. These values mirror the natural layerings in hunter-gatherer societies and contemporary personal networks. In addition, a religious ideology seems to play an important role in allowing larger communities to maintain greater cohesion for longer than a strictly secular ideology does. The differences in optimal community size may reflect the demands of different ecologies, economies and social contexts, but, as yet, we have no explanation as to why these numbers seem to function socially so much more effectively than other values.     

Structurally diverse low molecular weight activators of the mammalian pre-mRNA 3′ cleavage reaction

The 3′ end formation of mammalian pre-mRNA contributes to gene expression regulation by setting the downstream boundary of the 3′ untranslated region, which in many genes carries regulatory sequences. A large number of protein cleavage factors participate in this pre-mRNA processing step, but chemical tools to manipulate this process are lacking. Guided by a hypothesis that a PPM1 family phosphatase negatively regulates the 3′ cleavage reaction, we have found a variety of new small molecule activators of the in vitro reconstituted pre-mRNA 3′ cleavage reaction. New activators include a cyclic peptide PPM1D inhibitor, a dipeptide with modifications common to histone tails, abscisic acid and an improved l-arginine β-naphthylamide analog. The minimal concentration required for in vitro cleavage has been improved from 200 μM to the 200 nM–100 μM range. These compounds provide unexpected leads in the search for small molecule tools able to affect pre-mRNA 3′ end formation.     

First Evidence for Homologous Recombination-mediated Large DNA Inversion on the Bacillus subtilis 168 Chromosome

A Bacillus subtilis 168 strain carrying an inversion of about 1600kb-long chromosomal DNA was isolated. Physical and genetic analyses demonstrated that the inversion was generated as a result of homologous recombination between two homologous sequences integrated at the met and leuB loci. This is the first clear evidence of a large stable chromosomal inversion induced by homologous recombination in B. subtilis.     

Simultaneous production of mixed electron–photon beam in a medical LINAC: A feasibility study

PurposeThe electron or photon beams might be used for treatment of tumors. Each beam has its own advantage and disadvantages. Combo beam can increase the advantages. No investigation has been performed for producing simultaneous mixed electron and photon beam. In current study a device has been added to the Medical Linac to produce a mixed photon–electron beam.MethodsFirstly a Varian 2300CD head was simulated by MCNP Monte Carlo Code. Two sets of perforated lead sheets with 1 and 2 mm thickness and 0.2, 0.3, and 0.5 cm punches then placed at the top of the applicator holder tray. This layer produces bremsstrahlung x-ray upon impinging fraction electrons on it. The remaining fraction of electrons passes through the holes. The simulation was performed for 10 × 10, 6 × 6, and 4 × 4 cm² field size.ResultsFor 10 × 10 cm² field size, among the punched targets, the largest penumbra difference between the depth of 1 and 7 cm was 72%. This difference for photon and electron beams were 31% and 325% respectively. A maximum of 39% photon percentage was produced by 2 mm target with 0.2 cm holes diameter layer. The minimum surface dose value was 4% lesser than pure electron beam. For small fields, unlike the pure electron beam, the PDD, penumbra, and flatness variations were negligible.ConclusionsThe advantages of mixing the electron and photon beam is reduction of pure electron's penumbra dependency with the depth, especially for small fields, also decreasing of dramatic changes of PDD curve with irradiation field size.     

Nippostrongylus brasiliensis: Mast cell kinetics at small intestinal sites in infected rats

Mast cell kinetics during infection with the nematode Nippostrongylus brasiliensis were studied at various sites in the small bowel of rats and in heterotopically transplanted isografts of foetal small intestine placed under the kidney capsule. Infection produced an increase in the number of mast cells not only in the proximal jejunum, where most of the worms are located, but also in the distal ileum and in isografts of small intestine. However, globule leucocyte infiltration of the gut epithelium was confined to the proximal small intestine and did not occur in the distal ileum or isografts. These results show that the mast cell increase in the small bowel of N. brasiliensis-infected rats is a property of the whole organ, and is not restricted to sites of worm infection; but that in contrast, globule leucocyte infiltration of the epithelium is dependent upon the presence of worms within the bowel lumen.     

Is vegetation inside Carex sempervirens tussocks highly specific or an image of the surrounding vegetation?

Questions : How do species diversity, frequency and composition in tussocks differ from those in similar sized plots outside tussocks? Does the extent of the differences depend on community types or environmental conditions? Location : A sub‐alpine grassland in the Swiss National Park. Methods : In each of the two communities (short grass and tall graminoid) differing in species composition, grazing intensity and soil nutrient availability, relevés were made in 40 pairs of small circular plots, with one plot located inside a randomly selected Carex sempervirens tussock and the other outside. Results : We found 92 vascular species, of which 46 had a frequency higher than 5%. Species richness (S), pooled cover, Shannon's diversity (H) and cumulative species number (CS) were higher outside than inside the C. sempervirens tussocks, but evenness (J) was lower. S, H and CS differed more in the tall graminoid community than in the short grass community. However, dissimilarity between the paired relevés inside and outside tussocks did not differ between the two communities. Of the 46 most frequent species, 12 were statistically more and only one less frequent outside than inside the tussocks. Vegetation inside and outside tussocks could be clearly distinguished in the ordination space. Conclusion : Vegetation inside C. sempervirens tussocks is different from that in the surrounding area and represents an impoverished but homogenized version of the surrounding vegetation. Although tussocks of C. sempervirens were systematically avoided by grazers, there is little evidence that tussocks facilitate the species growing inside them.     

A glance at the emerging diagnostic biomarkers in the most prevalent genitourinary cancers

Genitourinary cancers comprise of a heterogenous group of cancers of which renal cell carcinoma, urothelial bladder carcinoma, and prostate adenocarcinoma are the most commonly encountered subtypes. A lot of research is ongoing using various strategies for exploration of novel biomarkers for genitourinary cancers. These biomarkers would not reduce the need for invasive diagnostic techniques but also could be used for early and accurate diagnosis to improve the clinical management required for the disease. Moreover, selecting the appropriate treatment regimen for the responsive patients based on these biomarkers would reduce the treatment toxicity as well as cost. Biomarkers identified using various advanced techniques like next generation sequencing and proteomics, which have been classified as immunological biomarkers, tissue-specific biomarkers and liquid biomarkers. Immunological biomarkers include markers of immunological pathways such as CTLA4, PD-1/PDl-1, tissue biomarkers include tissue specific molecules such as PSA antigen and liquid biomarkers include biomarkers detectable in urine, circulating cells etc.The purpose of this review is to provide a brief introduction to the most prevalent genitourinary malignancies, including bladder, kidney, and prostate cancers along with a major focus on the novel diagnostic biomarkers and the importance of targeting them prior to genitourinary cancers treatment. Understanding these biomarkers and their potential in diagnosis of genitourinary cancer would not help in early and accurate diagnosis as mentioned above but may also lead towards a personalized approach for better diagnosis, prognosis and specified treatment approach for an individual.     

Actin assembly controlled by GDP-Rab27a is essential for endocytosis of the insulin secretory membrane

We have recently reported that GDP-bound Rab27a regulates endocytosis of the insulin secretory membrane via its binding to coronin 3, an actin-binding protein. The aim of this study was to examine the participation of actin assembly in the Rab27a-dependent regulation of endocytosis using a pancreatic beta cell line, MIN6. Coronin 3 promoted F-actin bundling only in the presence of GDP-Rab27a. This effect was independent of coronin-3-binding to the actin-related proteins 2 and 3 (Arp2/3). Uptake of anti-phogrin-lumen antibody into MIN6 was inhibited by anti-coronin-3-C antibody which recognizes the actin-binding site. This inhibition was also observed with coronin-3-R28D, which lacks in actin binding. These results suggest that coronin 3 is a genuine GDP-Rab27a effector, and that controls endocytosis of the secretory membrane via modulating actin assembly in pancreatic β-cells.     

Computational-aided design of a library of lactams through a diversity-oriented synthesis strategy

Small molecule libraries for virtual screening are becoming a well-established tool for the identification of new hit compounds. As for experimental assays, the library quality, defined in terms of structural complexity and diversity, is crucial to increase the chance of a successful outcome in the screening campaign. In this context, Diversity-Oriented Synthesis has proven to be very effective, as the compounds generated are structurally complex and differ not only for the appendages, but also for the molecular scaffold. In this work, we automated the design of a library of lactams by applying a Diversity-Oriented Synthesis strategy called Build/Couple/Pair. We evaluated the novelty and diversity of these compounds by comparing them with lactam moieties contained in approved drugs, natural products, and bioactive compounds from ChEMBL. Finally, depending on their scaffold we classified them into β-, γ-, δ-, ε-, and isolated, fused, bridged and spirolactam groups and we assessed their drug-like and lead-like properties, thus providing the value of this novel in silico designed library for medicinal chemistry applications.