An S-Locus Independent Pollen Factor Confers Self-Compatibility in ‘Katy’ Apricot

Loss of pollen-S function in Prunus self-compatible cultivars has been mostly associated with deletions or insertions in the S-haplotype-specific F-box (SFB) genes. However, self-compatible pollen-part mutants defective for non-S-locus factors have also been found, for instance, in the apricot (Prunus armeniaca) cv. ‘Canino’. In the present study, we report the genetic and molecular analysis of another self-compatible apricot cv. termed ‘Katy’. S-genotype of ‘Katy’ was determined as S ₁ S ₂ and S-RNase PCR-typing of selfing and outcrossing populations from ‘Katy’ showed that pollen gametes bearing either the S ₁- or the S ₂-haplotype were able to overcome self-incompatibility (SI) barriers. Sequence analyses showed no SNP or indel affecting the SFB ₁ and SFB ₂ alleles from ‘Katy’ and, moreover, no evidence of pollen-S duplication was found. As a whole, the obtained results are compatible with the hypothesis that the loss-of-function of a S-locus unlinked factor gametophytically expressed in pollen (M’-locus) leads to SI breakdown in ‘Katy’. A mapping strategy based on segregation distortion loci mapped the M’-locus within an interval of 9.4 cM at the distal end of chr.3 corresponding to ∼1.29 Mb in the peach (Prunus persica) genome. Interestingly, pollen-part mutations (PPMs) causing self-compatibility (SC) in the apricot cvs. ‘Canino’ and ‘Katy’ are located within an overlapping region of ∼273 Kb in chr.3. No evidence is yet available to discern if they affect the same gene or not, but molecular markers seem to indicate that both cultivars are genetically unrelated suggesting that every PPM may have arisen independently. Further research will be necessary to reveal the precise nature of ‘Katy’ PPM, but fine-mapping already enables SC marker-assisted selection and paves the way for future positional cloning of the underlying gene.     

The Geometry of Locomotive Behavioral States in C. elegans

We develop a new hidden Markov model-based method to analyze C elegans locomotive behavior and use this method to quantitatively characterize behavioral states. In agreement with previous work, we find states corresponding to roaming, dwelling, and quiescence. However, we also find evidence for a continuum of intermediate states. We suggest that roaming, dwelling, and quiescence may best be thought of as extremes which, mixed in any proportion, define the locomotive repertoire of C elegans foraging and feeding behavior.     

Citation Analysis May Severely Underestimate the Impact of Clinical Research as Compared to Basic Research

Background

Citation analysis has become an important tool for research performance assessment in the medical sciences. However, different areas of medical research may have considerably different citation practices, even within the same medical field. Because of this, it is unclear to what extent citation-based bibliometric indicators allow for valid comparisons between research units active in different areas of medical research.

Methodology

A visualization methodology is introduced that reveals differences in citation practices between medical research areas. The methodology extracts terms from the titles and abstracts of a large collection of publications and uses these terms to visualize the structure of a medical field and to indicate how research areas within this field differ from each other in their average citation impact.

Results

Visualizations are provided for 32 medical fields, defined based on journal subject categories in the Web of Science database. The analysis focuses on three fields: Cardiac & cardiovascular systems, Clinical neurology, and Surgery. In each of these fields, there turn out to be large differences in citation practices between research areas. Low-impact research areas tend to focus on clinical intervention research, while high-impact research areas are often more oriented on basic and diagnostic research.

Conclusions

Popular bibliometric indicators, such as the h-index and the impact factor, do not correct for differences in citation practices between medical fields. These indicators therefore cannot be used to make accurate between-field comparisons. More sophisticated bibliometric indicators do correct for field differences but still fail to take into account within-field heterogeneity in citation practices. As a consequence, the citation impact of clinical intervention research may be substantially underestimated in comparison with basic and diagnostic research.     

Saponins from the roots of Chiococca alba and their in vitro anti-inflammatory activity

Five triterpenoidal saponins were isolated from the roots of Chiococca alba (L.) Hitchc. (Rubiaceae). Two of the saponins, chiococcasaponin III (3-O-β-d-glucopyranurosyl-3β-hydroxyolean-12,15-dien-28-oic acid 28-O-β-d-xylopyranosyl (1 → 4)-α-l-rhamnopyranosyl (1 → 2)-α-l-arabinopyranosyl ester) and chiococcasaponin IV (3-O-β-d-glucopyranurosyl-3β-hydroxyolean-12,15-dien-28-oic acid 28-O-α-l-rhamnopyranosyl (1 → 2)-α-l-arabinopyranosyl ester) were new and their structures were elucidated on the basis of extensive application of NMR techniques and high resolution electrospray mass spectrometry together with acid hydrolysis product analysis. As part of our investigations on the chemical profile and pharmacological activity of the roots of C. alba, we report the results of the evaluation of the activity of the saponin fractions against in vitro lipopolysaccharide-induced inflammation. The results found, strongly support the fractions I, III and IV as having anti-inflammatory properties.     

Insulin-like growth factor binding protein-3 (IGFBP-3): Novel ligands mediate unexpected functions

In addition to its important role in the regulation of somatic growth by acting as the major circulating transport protein for the insulin-like growth factors (IGFs), IGF binding protein-3 (IGFBP-3) has a variety of intracellular ligands that point to its function within major signaling pathways. The discovery of its interaction with the retinoid X receptor has led to the elucidation of roles in regulating the function of several nuclear hormone receptors including retinoic acid receptor-α, Nur77 and vitamin D receptor. Its interaction with the nuclear hormone receptor peroxisome proliferator-activated receptor-γ is believed to be involved in regulating adipocyte differentiation, which is also modulated by IGFBP-3 through an interaction with TGFβ/Smad signaling. IGFBP-3 can induce apoptosis alone or in conjunction with other agents, and in different systems can activate caspases −8 and −9. At least two unrelated proteins (LRP1 and TMEM219) have been designated as receptors for IGFBP-3, the latter with a demonstrated role in inducing caspase-8-dependent apoptosis. In contrast, IGFBP-3 also has demonstrated roles in survival-related functions, including the repair of DNA double-strand breaks through interaction with the epidermal growth factor receptor and DNA-dependent protein kinase, and the induction of autophagy through interaction with GRP78. The ability of IGFBP-3 to modulate the balance between pro-apoptotic and pro-survival sphingolipids by regulating sphingosine kinase 1 and sphingomyelinases may be integral to its role at the crossroads between cell death and survival in response to a variety of stimuli. The pleiotropic nature of IGFBP-3 activity supports the idea that IGFBP-3 itself, or pathways with which it interacts, should be investigated as targets of therapy for a variety of diseases.     

Germline HOXB13 p.Gly84Glu mutation and risk of colorectal cancer

Introduction: The HOXB13 pGly84Glu mutation has recently been associated with an increased risk of prostate cancer but the association of other cancer sites with this allele has not been assessed. Data has suggested that HOXB13 expression levels are decreased in colorectal cancer (CRC) cell lines indicating this gene may be involved in colorectal tumourigenesis. Methods: To evaluate a potential association of this mutation with CRC, we genotyped the mutation in 2695 CRC cases and 4593 controls from population-based registries in Canada and Australia. Results: The HOXB13 pGly84Glu mutation was more common in CRC cases than controls (0.48% vs. 0.17%, P = 0.02) indicating a significant association between the HOXB13 variant and CRC risk (OR = 2.8; 95%CI: 1.2–6.8). This association was attenuated but remained significant with the inclusion of previously published and publicly available genotype data. Pedigree analysis of cases and controls revealed that 7/21 HOXB13 mutation carriers had a family history of prostate cancer. Discussion: This report is the first to suggest a risk of CRC associated with mutations in the HOXB13 gene. These findings require further validation but may be of importance in the screening and genetic counseling of families known to carry the HOXB13 pGly84Glu mutation.     

Are Treatments More Effective than Placebos? A Systematic Review and Meta-Analysis

BackgroundPlacebos are widely used in clinical practice in spite of ethical restrictions. Whether such use is justified depends in part on the relative benefit of placebos compared to ‘active’ treatments. A direct test for differences between placebo and ‘active’ treatment effects has not been conducted.ObjectivesWe aimed to test for differences between treatment and placebo effects within similar trial populations.ResultsIn trials with continuous outcomes (n = 115) we found no difference between treatment and placebo effects (MD = −0.29, 95% CI −0.62 to 0.05, P = 0.10). In trials with binary outcomes (n = 37) treatments were significantly more effective than placebos (RRR = 0.72, 95%CI = 0.61 to 0.86, P = 0.0003). Treatment and placebo effects were not different in 22 out of 28 predefined subgroup analyses. Of the six subgroups with differences treatments were more effective than placebos in five. However when all criteria for reducing bias were ruled out (continuous outcomes) placebos were more effective than treatments (MD = 1.59, 95% CI = 0.40 to 2.77, P = 0.009).

Conclusions and Implications

Placebos and treatments often have similar effect sizes. Placebos with comparatively powerful effects can benefit patients either alone or as part of a therapeutic regime, and trials involving such placebos must be adequately blinded.