Susceptibility to klebsiella pneumonaie infection in collaborative cross mice is a complex trait controlled by at least three loci acting at different time points

Background

Klebsiella pneumoniae (Kp) is a bacterium causing severe pneumonia in immunocompromised hosts and is often associated with sepsis. With the rise of antibiotic resistant bacteria, there is a need for new effective and affordable control methods; understanding the genetic architecture of susceptibility to Kp will help in their development. We performed the first quantitative trait locus (QTL) mapping study of host susceptibility to Kp infection in immunocompetent Collaborative Cross mice (CC). We challenged 328 mice from 73 CC lines intraperitoneally with 10⁴ colony forming units of Kp strain K2. Survival and body weight were monitored for 15 days post challenge. 48 of the CC lines were genotyped with 170,000 SNPs, with which we mapped QTLs.

Results

CC lines differed significantly (P < 0.05) in mean survival time, between 1 to 15 days post infection, and broad sense heritability was 0.45. Distinct QTL were mapped at specific time points during the challenge. A QTL on chromosome 4 was found only on day 2 post infection, and QTL on chromosomes 8 and 18, only on day 8. By using the sequence variations of the eight inbred strain founders of the CC to refine QTL localization we identify several candidate genes.

Conclusion

Host susceptibility to Kp is a complex trait, controlled by multiple genetic factors that act sequentially during the course of infection.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-865) contains supplementary material, which is available to authorized users.     

Synthesis and active oxygen generation by new emodin derivatives and their gonadotropin-releasing hormone conjugates

In an attempt to develop efficient chemotherapeutic agents targeted at malignant cells that express receptors, we synthesized five new emodin derivatives and their gonadotropin-releasing hormone (GnRH) conjugates to be used as potential photoactive conjugates. Emodin was modified at its hydroxy groups and included different spacers for conjugation of the peptide. We used electron spin resonance (ESR) and spin trapping techniques to study the light-stimulated redox properties of the emodin derivatives and their GnRH conjugates. Upon irradiation, all new emodin derivatives and their conjugates stimulated the formation of singlet oxygen, that is, (1)O(2), and oxygen radicals, that is, O(2)(-)(*) and OH(*). However, substantial differences were found between the tested derivatives as to the efficacy of reactive oxygen species (ROS) production. Because of its superior ROS production properties, [d-Lys(6)(MeoEmo)]GnRH was selected as a leading conjugate. En-route to evaluate its targeting capacity, this potentially cytotoxic conjugate was tested in vitro to determine its hormonal activity and binding affinity to GnRH receptors.     

Sharing economy rebound: The case of peer-to-peer sharing of food waste

The digital sharing economy is commonly thought to promote sustainable consumption and improve material efficiency through better utilization of existing product stocks. However, the cost savings and convenience of using digital sharing platforms can ultimately stimulate additional demand for products and services. As a result, some or even all of the expected environmental benefits attributed to sharing could be offset, a phenomenon known as the rebound effect. Relying on a unique dataset covering over 750,000 food items shared in the United Kingdom through a free peer-to-peer food-sharing platform, we use econometric modeling, geo-spatial network analysis, and environmentally extended input–output analysis to quantify how much of the expected environmental benefits attributed to sharing are offset via rebound effects under seven re-spending scenarios. We find that rebound effects can offset 59–94% of expected greenhouse gas (GHG) emission reduction, 20–81% of expected water depletion benefits, and 23–90% of land use benefit as platform users re-spent the money saved from food sharing on other goods and services. Our results demonstrate that rebound effects could limit the potential to achieve meaningful reductions in environmental burdens through sharing, and highlight the importance of incorporating rebound effects in environmental assessments of the digital sharing economy.     

Prediction of response to robot-aided motor neuro-rehabilitation of children with cerebral palsy

Robot-aided neuro-rehabilitation is increasingly being incorporated into rehabilitation practices. The aim of this study was to search for patterns in the data acquired by a robot in the baseline evaluation session which could predict progress over the next therapy sessions. Kinematic and kinetic data were acquired during robot-mediated evaluation sessions of 12 children with motor impairments due to hemiplegic cerebral palsy (CP). Time and wavelets features were extracted from the data and used for K-means clustering. The data were labeled by the Quality of Upper Extremity Skills Test (QUEST) and the gradient of improvement change in the QUEST between the baseline assessment and therapy follow-up one month after completion of 16 robot-mediated therapy sessions. Two distinct clusters segregated these 12 children into performers and non-performers in terms of the QUEST.     

Paleopathology and the origin of agriculture in the Levant

This study addresses changes in health which were consequential to the Neolithic transition in the southern Levant, judged on the basis of the study of specific and nonspecific stress indicators, trauma, and degenerative joint disease in 200 Natufian (hunter‐gatherer) skeletons (10,500–8300 BC) and 205 Neolithic (agricultural) skeletons (8300–5500 BC) from the southern Levant. The comparison of the health profiles of pre‐Neolithic (Natufian) and Neolithic populations reveals a higher prevalence of lesions indicative of infectious diseases among the Neolithic population, and an overall reduction in the prevalence of skull trauma among males. No change over time was observed in the prevalence of degenerative joint disease. These results indicate that in the southern Levant the Neolithic transition did not simply lead to an overall deterioration in health but rather resulted in a complex health profile which was shaped by 1) an increase exposure to disease agents, 2) changes in diet, 3) population aggregation in larger and denser settlements, 4) changes in activity patterns and the division of labor, and possibly 5) a higher resistant immunological system and response capacity to environmental aggressions (mainly infections). Am J Phys Anthropol 143:121–133, 2010. © 2010 Wiley‐Liss, Inc.     

Variation in Endogenous Gibberellins,Abscisic Acid,and Carbohydrate Content During the Growth Cycle of Colored <Emphasis Type="Italic">Zantedeschia</Emphasis> spp., a Tuberous Geophyte

Phenologic changes and variation in the level of endogenous gibberellins (GAs), abscisic acid (ABA), carbohydrate content, and α-amylase activity were examined in colored Zantedeschia spp. cv. Cala Gold. These changes were examined in the primary bud tissues and in the attached tuber tissue during the growth cycle. Dormant tubers were dry-stored at 20°C for 3 months, planted in a phytotron, and grown under 22/16 ± 1°C. Plant development was monitored under continued irrigation until leaf senescence and tuber dormancy. GAs and ABA were extracted from the primary bud tissues, fractionated by HPLC, and analyzed using GC-SIM. Starch, glucose, soluble protein, and α-amylase activity were monitored in the tuber tissue attached to the primary bud. Endogenous changes in GAs and ABA in the primary bud were correlated with endogenous changes in carbohydrate content and α-amylase activity in the attached tuber tissue. These correlations were observed during the rest and the growth periods and were associated with developmental changes in the plant, that is, bud dormancy relaxation, bud growth, and inflorescence differentiation. ABA content decreased and a transient pulse of GA was measured in the primary bud concomitantly with the onset of shoot elongation in dry tubers during storage, before planting. The sharp increase of GAs in the bud preceded inflorescence differentiation as observed in dissected apices by about 15 days, as well as the increase in α-amylase activity in the attached tuber tissue. A steep decrease in starch level was measured in the tuber after planting, concomitantly with massive plant growth. These findings suggest a possible involvement of gibberellin in the initiation of α-amylase activity during dormancy relaxation in colored Zantedeschia and in the autonomous induction of flowering.     

Direction finding by hornets in a vertically rotating centrifuge

In a vertically rotating centrifuge, the direction of the resultant gravitational and centrifugal forces is constantly changing. Hornets placed in such a centrifuge will build their combs in the direction of the resultant only if the centrifuge is stopped every day and left in the same position for at least half an hour, because during the cessation of motion, they presumably “learn” some geometrical cues which enable them to determine the preferred angle of building. Hornets can detect and respond to a centrifugal force as small as 0·18% of the earth's gravitational force. At a rotational rate of 1/8 of a revolution per minute there was no comb construction whatsoever and hornet mortality rate was 100% within three days.     

Cell wall structure and composition in the comb built by hornets and wasps (Vespinae,hymenoptera)

Morphological, mineralogical, and chemical investigations were undertaken to determine the structure and composition of the cell walls of the comb in the nest of Vespa orientalis, Paravespula germanica, and Vespacrabro. Nests of V. orientalis were from three sites having different soil types, namely, Khamra soil, Gramosol soil, and organically rich soil from the city dump in Tel Aviv. Nests of P. germanica were from areas rich in organic matter, and those of V. crabro, shipped from Austria, were similarly comprised of organic matter. Structure and composition of cell walls in the three species differed; furthermore, grain size in the combs differed from that of particles in the surrounding soil.