Multifraction radiation response of mouse lung

The response of mouse lung to repeated doses of 60Co gamma-rays of as low as 115 cGy per fraction was measured using death from pneumonitis between 80 and 120 days after irradiation as the endpoint. A fractionation interval of 3 h was maintained for most regimens but in the longer experiments some 12 h intervals were introduced for logistic reasons. The longest overall duration (for a 43 fraction regimen) was 8 days. The total doses required to produce 50 per cent mortality increased continuously as dose/fraction was decreased, even from 160 to 115 cGy per fraction. Of clinical relevance, the steepness of the isoeffect curve over the dose range 115-500 cGy indicates that the lung shows greater sparing from dose fractionation than is characteristic of more rapidly-responding normal tissues, resembling, in this respect, other more slowly-responding tissues such as spinal cord. The plot of the reciprocal of the LD50 values as a function of dose per fraction was non-linear, suggesting that a linear quadratic dose response model may not be appropriate or that repair of cellular injury in lung is not complete in 3 h, or both.     

Fitting the linear-quadratic model using time of occurrence as the end-point for quantal response multifraction experiments

A statistical technique is given for fitting the linear-quadratic model to experimental quantal response multifraction data using the time of the response as the end-point. The analysis used is based on the Cox Proportional Hazards model. The technique is useful for late effects where the time of occurrence of the response is dose dependent. The technique is compared to logistic regression analysis and the advantages and disadvantages are discussed. Both methods are applied to a lung pneumonitis experiment and a kidney experiment.     

Nicotine is neuroprotective when administered before but not after nigrostriatal damage in rats and monkeys

Nicotine reduces dopaminergic deficits in parkinsonian animals when administered before nigrostriatal damage. Here we tested whether nicotine is also beneficial when given to rats and monkeys with pre-existing nigrostriatal damage. Rats were administered nicotine before and after a unilateral 6-hydroxydopamine lesion of the medial forebrain bundle, and the results compared with those in which rats received nicotine only after lesioning. Nicotine pre-treatment attenuated behavioral deficits and lessened lesion-induced losses of the striatal dopamine transporter, and α6β2* and α4β2* nicotinic receptors (nAChRs). By contrast, nicotine administered 2 weeks after lesioning, when 6-hydroxydopamine-induced neurodegenerative effects are essentially complete, did not improve these same measures. Similar results were observed in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned monkeys. Nicotine did not enhance striatal markers when administered to monkeys with pre-existing nigrostriatal damage, in contrast to previous data that showed improvements when nicotine was given to monkeys before lesioning. These combined findings in two animal models suggest that nicotine is neuroprotective rather than neurorestorative against nigrostriatal damage. Receptor studies with ¹²⁵I-α-conotoxinMII and the α-conotoxinMII analog E11A were next performed to determine whether nicotine treatment pre- or post-lesioning differentially affected expression of α6α4β2* and α6(nonα4)β2* nAChR subtypes in striatum. The observations suggest that protection against nigrostriatal damage may be linked to striatal α6α4β2* nAChRs.     

Ligand-based virtual screening,molecular docking,QSAR and pharmacophore analysis of quercetin-associated potential novel analogs against epidermal growth factor receptor

The present study was to explore expectation and examination of therapeutic potential quercetin analogs as efficient anticancer agents against human epidermal growth factor receptor (EGFR), which is a consistent hallmark for moderating the non-small-cell lung carcinoma (NSCLC). Here, ligand-based virtual screening, pharmacophore approach and molecular docking were established as rational strategies for recognition of small analogs against the ligand binding domain of EGFR (PDB code: 1XKK). Adverse effects, toxicogenomics and pharmacokinetics reported that 10 candidates showed reliable consequences with less side effects and more efficient for target receptor. Protein–ligand interaction profiles revealed that the probable H-bonds, atomic-π contacts, salt bridges and van der Waals interactions sustain the complexity and stability of receptor structure; thus, they could complicate to generate single alteration acquired for drug resistance. In silico anticancer properties explain the lead scaffolds which are assumed to be flexible and experimentally proved chemicals. The overall consequences indicated that recognized leads could be utilized as reference skeletons for new inhibitors envisaging toward EGFR to ameliorate NSCLC and other malignant disorders.     

How the discovery of ribozymes cast RNA in the roles of both chicken and egg in origin-of-life theories

Scientific theories about the origin-of-life theories have historically been characterized by the chicken-and-egg problem of which essential aspect of life was the first to appear, replication or self-sustenance. By the 1950s the question was cast in molecular terms and DNA and proteins had come to represent the carriers of the two functions. Meanwhile, RNA, the other nucleic acid, had played a capricious role in origin theories. Because it contained building blocks very similar to DNA, biologists recognized early that RNA could store information in its linear sequences. With the discovery in the 1980s that RNA molecules were capable of biological catalysis, a function hitherto ascribed to proteins alone, RNA took on the role of the single entity that could act as both chicken and egg. Within a few years of the discovery of these catalytic RNAs (ribozymes) scientists had formulated an RNA World hypothesis that posited an early phase in the evolution of life where all key functions were performed by RNA molecules. This paper traces the history the role of RNA in origin-of-life theories with a focus on how the discovery of ribozymes influenced the discourse.     

Effect of different cooking methods on loss of iron and zinc micronutrients in fortified and non-fortified rice

Malnutrition is considered as major public health concern and is emerging challenge to food and nutrition security particularly in developing countries. Rice is the staple food and consumed by the half of the world's population which is the source of daily requirement of the nutrients. Attempts are being made to fortify rice with micronutrients, but the loss or retention of these micronutrients in different cooking methods is not well studied and documented especially in fortified rice. In the present study, paddy seeds of six Indian varieties were fortified with iron and zinc by parboiling process. Consequently, fortified polished rice had higher micronutrient contents (Fe, 106.31 ± 12.56; Zn, 97.72 ± 9.75) than non-fortified polished rice (Fe, 7.44 ± 1.05; Zn, 14.74 ± 2.94) expressed in ppm. Polished rice of both fortified and non-fortified were cooked under five different cooking conditions and analyzed for remaining iron and zinc content. Cooking rice in rice cooker without prior washing (NRC) retained highest concentration of Fe and Zinc in both fortified and non-fortified rice varieties. It also showed that fortified rice suffered higher percentage loss of micronutrient, than the non-fortified rice. But the average retained micronutrient amount measured in ppm, was higher in fortified rice (Fe, 43.54 ± 6.88; Zn, 36.7 ± 3.12) than in non-fortified rice (Fe, 4.24 ± 0.87; Zn, 9.3 ± 2.11). Hence, adopting appropriate cooking method, higher amount of micronutrients will be retained in the cooked food which will in turn help in combating the malnutrition and improve health.     

Fire alters diversity,composition, and structure of dry tropical forests in the Eastern Ghats

Fire is known to have dramatic consequences on forest ecosystems around the world and on the livelihoods of forest‐dependent people. While the Eastern Ghats of India have high abundances of fire‐prone dry tropical forests, little is known about how fire influences the diversity, composition, and structure of these communities. Our study aimed to fill this knowledge gap by examining the effects of the presence and the absence of recent fire on tropical dry forest communities within the Kadiri watershed, Eastern Ghats. We sampled plots with and without evidence of recent fire in the Eswaramala Reserve Forest in 2008 and 2018. Our results indicate that even though stem density increases in the recently burned areas, species richness is lower because communities become dominated by a few species with fire resistance and tolerance traits, such as thick bark and clonal sprouting. Further, in the presence of fire, the size structure of these fire‐tolerant species shifts toward smaller‐sized, resprouting individuals. Our results demonstrate that conservation actions are needed to prevent further degradation of forests in this region and the ecosystem services they provide.