On the organic carbon maximum on the continental slope of the eastern Arabian Sea

The sedimentary organic carbon maximum on the continental slope off western India is widely believed to be due to the preferential preservation of deposited organic matter at water depths where the intense oxygen minimum intersects the sea floor. This region is considered to constitute one of the modern analogues for the environment of formation of organic-rich sedimentary facies that are common in the geological record. We critically examine the hypothesis that the oxygen minimum in the eastern Arabian Sea is the site of enhanced organic matter accumulation and preservation using analyses of suites of samples with wide geographical coverage along this margin. Organic carbon and nitrogen reach maximum concentrations between 200 and 1600 m depth, whereas the lowest dissolved oxygen contents in the oxygen minimum lie between 200 and 800 m depth. The Corganic/N ratios and the δ13Corganic values show that the organic matter is overwhelmingly marine, and Rock-Eval pyrolysis data demonstrate that the hydrogen indices of the sediments are similar in the sediments accumulating within and outside the oxygen minimum. Thus, the organic carbon maximum extends over a larger depth range than the oxygen minimum (as is also evident on some other slopes), and there is no evidence for preferential preservation of the organic matter within the oxygen minimum. The distribution of organic matter on the western Indian continental margin is controlled by (1) variations in supply (decreasing westward away from the centers of coastal upwelling and also decreasing with increasing water depth), (2) dilution by other sedimentary components, and (3) the texture of the sediments (coarser-grained sediments having lower carbon contents), which is controlled in turn by sediment supply and reworking. The evidence available suggests that the organic carbon maximum on this slope is not related to the position of the oxygen minimum and, consequently, that oxygen minima cannot be used to explain the distribution of organic carbon at intermediate palaeodepths in the geological record

Ex vivo drug response profiling detects recurrent sensitivity patterns in drug-resistant acute lymphoblastic leukemia

Drug sensitivity and resistance testing on diagnostic leukemia samples should provide important functional information to guide actionable target and biomarker discovery. We provide proof of concept data by profiling 60 drugs on 68 acute lymphoblastic leukemia (ALL) samples mostly from resistant disease in cocultures of bone marrow stromal cells. Patient-derived xenografts retained the original pattern of mutations found in the matched patient material. Stromal coculture did not prevent leukemia cell cycle activity, but a specific sensitivity profile to cell cycle-related drugs identified samples with higher cell proliferation both in vitro and in vivo as leukemia xenografts. In patients with refractory relapses, individual patterns of marked drug resistance and exceptional responses to new agents of immediate clinical relevance were detected. The BCL2inhibitor venetoclax was highly active below 10 nM in B-cell precursor ALL (BCP-ALL) subsets, including MLL-AF4 and TCF3-HLF ALL, and in some T-cell ALLs (T-ALLs), predicting in vivo activity as a single agent and in combination with dexamethasone and vincristine. Unexpected sensitivity to dasatinib with half maximal inhibitory concentration values below 20 nM was detected in 2 independent T-ALL cohorts, which correlated with similar cytotoxic activity of the SRC inhibitor KX2-391 and inhibition of SRC phosphorylation. A patient with refractory T-ALL was treated with dasatinib on the basis of drug profiling information and achieved a 5-month remission. Thus, drug profiling captures disease-relevant features and unexpected sensitivity to relevant drugs, which warrants further exploration of this functional assay in the context of clinical trials to develop drug repurposing strategies for patients with urgent medical needs.Peer reviewe

Identifying the connection between Roman Conceptions of ‘Pure Air’ and Physical and Mental Health in Pompeian Gardens (c. 150 BC-AD 79): A Multi-Sensory Approach to Ancient Medicine

Different genres of Roman literature commented on the relationship between the condition of the environment and physical and mental health. They often refer to clear, pure, or good air as a beneficial aspect of the environment. Yet, unlike fetid air, they provide few descriptions of what constituted healthy air quality. Moreover, aside from pointing out the association between the environment and bodily condition, the writers also did not explain precisely how the link between the two was made. This paper utilizes a comparative study of ancient literature and the archaeological remains of Roman gardens in Pompeii: archaeobotanical samples, fresco paintings, location, and surviving features. Three questions are addressed in this study: First, how did the Romans identify and define pure? Second, how did air connect to the body? Third, what were the qualities of pure air and how did they benefit the body? Not only was inhalation a means of linking air to the body, but the two were also related through sensory perception. I argue that sight, sound, and olfaction were used to identify the qualities of pure air. Through the sensory process of identification, the beneficial properties of pure air were, in accordance with ancient perceptions of sensory function, taken into the body and affected health. Thus, sensory perception acted as the bridge between the environment and health

The Transcriptional Response to DNA-Double-Strand Breaks in Physcomitrella patens

The model bryophyte Physcomitrella patens is unique among plants in supporting the generation of mutant alleles by facile homologous recombination-mediated gene targeting (GT). Reasoning that targeted transgene integration occurs through the capture of transforming DNA by the homology-dependent pathway for DNA double-strand break (DNA-DSB) repair, we analysed the genome-wide transcriptomic response to bleomycin-induced DNA damage and generated mutants in candidate DNA repair genes. Massively parallel (Illumina) cDNA sequencing identified potential participants in gene targeting. Transcripts encoding DNA repair proteins active in multiple repair pathways were significantly up-regulated. These included Rad51, CtIP, DNA ligase 1, Replication protein A and ATR in homology-dependent repair, Xrcc4, DNA ligase 4, Ku70 and Ku80 in non-homologous end-joining and Rad1, Tebichi/polymerase theta, PARP in microhomology-mediated end-joining. Differentially regulated cell-cycle components included up-regulated Rad9 and Hus1 DNA-damage-related checkpoint proteins and down-regulated D-type cyclins and B-type CDKs, commensurate with the imposition of a checkpoint at G2 of the cell cycle characteristic of homology-dependent DNA-DSB repair. Candidate genes, including ATP-dependent chromatin remodelling helicases associated with repair and recombination, were knocked out and analysed for growth defects, hypersensitivity to DNA damage and reduced GT efficiency. Targeted knockout of PpCtIP, a cell-cycle activated mediator of homology-dependent DSB resection, resulted in bleomycin-hypersensitivity and greatly reduced GT efficiency

Fate and Uptake of Pharmaceuticals in Soil–Plant Systems

Pharmaceuticals have been detected in the soil environment where there is the potential for uptake into crops. This study explored the fate and uptake of pharmaceuticals (carbamazepine, diclofenac, fluoxetine, propranolol, sulfamethazine) and a personal care product (triclosan) in soil–plant systems using radish (Raphanus sativus) and ryegrass (Lolium perenne). Five of the six chemicals were detected in plant tissue. Carbamazepine was taken up to the greatest extent in both the radish (52 μg/g) and ryegrass (33 μg/g), whereas sulfamethazine uptake was below the limit of quantitation (LOQ) (<0.01 μg/g). In the soil, concentrations of diclofenac and sulfamethazine dropped below the LOQ after 7 days. However, all pharmaceuticals were still detectable in the pore water at the end of the experiment. The results demonstrate the ability of plant species to accumulate pharmaceuticals from soils with uptake apparently specific to both plant species and chemical. Results can be partly explained by the hydrophobicity and extent of ionization of each chemical in the soil

Genomics-assisted breeding in four major pulse crops of developing countries: present status and prospects

The global population is continuously increasing and is expected to reach nine billion by 2050. This huge population pressure will lead to severe shortage of food, natural resources and arable land. Such an alarming situation is most likely to arise in developing countries due to increase in the proportion of people suffering from protein and micronutrient malnutrition. Pulses being a primary and affordable source of proteins and minerals play a key role in alleviating the protein calorie malnutrition, micronutrient deficiencies and other undernourishment-related issues. Additionally, pulses are a vital source of livelihood generation for millions of resource-poor farmers practising agriculture in the semi-arid and sub-tropical regions. Limited success achieved through conventional breeding so far in most of the pulse crops will not be enough to feed the ever increasing population. In this context, genomics-assisted breeding (GAB) holds promise in enhancing the genetic gains. Though pulses have long been considered as orphan crops, recent advances in the area of pulse genomics are noteworthy, e.g. discovery of genome-wide genetic markers, high-throughput genotyping and sequencing platforms, high-density genetic linkage/QTL maps and, more importantly, the availability of whole-genome sequence. With genome sequence in hand, there is a great scope to apply genome-wide methods for trait mapping using association studies and to choose desirable genotypes via genomic selection. It is anticipated that GAB will speed up the progress of genetic improvement of pulses, leading to the rapid development of cultivars with higher yield, enhanced stress tolerance and wider adaptability