Casares’ map function: no need for a ‘corrected’ Haldane’s map function

A genetic map function M(d) = RF provides a mapping from the additive genetic distance d to the non-additive recombination fraction RF between a given pair of loci, where the recombination fraction is the proportion of gametes that are recombinant between the two loci. Genetic map functions are needed because in most experiments all we can directly observe are the recombination events. However, since a recombination event is only observed if there are an odd number of crossovers between the two loci, recombination fractions are not additive. One of the most widely used map functions is Haldane’s map function, which is derived under the assumptions of no chiasma and no chromatid interference, and has been in widespread use since 1919. However, Casares recently proposed a ‘corrected’ Haldane’s map function – we show here that this ‘corrected’ map function is not correct due to faulty assumptions and mistakes in its derivation.     

Upset in response to a Sibling’s partner’s infidelities

Using data collected from people with at least one brother and one sister, and consistent with an evolutionary perspective, we find that older men and women (a) are more upset by a brother’s partner’s sexual infidelity than by her emotional infidelity and (b) are more upset by a sister’s partner’s emotional infidelity than by his sexual infidelity. There were no effects of participant sex or sex of in-law on upset over a sibling’s partner’s infidelities, but there was an effect of participant sex on reports of upset over one’s own partner’s infidelities. The results suggest that the key variable among older participants is the sex of the sibling or, correspondingly, the sex of the sibling’s partner, as predicted from an evolutionary analysis of reproductive costs, and not the sex of the participant, as predicted from a socialization perspective. Discussion offers directions for future work on jealousy.     

Differential expression, function and response to inflammatory stimuli of 11β-hydroxysteroid dehydrogenase type 1 in human fibroblasts: a mechanism for tissue-specific regulation of inflammation

Stromal cells such as fibroblasts play an important role in defining tissue-specific responses during the resolution of inflammation. We hypothesized that this involves tissue-specific regulation of glucocorticoids, mediated via differential regulation of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Expression, activity and function of 11β-HSD1 was assessed in matched fibroblasts derived from various tissues (synovium, bone marrow and skin) obtained from patients with rheumatoid arthritis or osteoarthritis. 11β-HSD1 was expressed in fibroblasts from all tissues but mRNA levels and enzyme activity were higher in synovial fibroblasts (2-fold and 13-fold higher mRNA levels in dermal and synovial fibroblasts, respectively, relative to bone marrow). Expression and activity of the enzyme increased in all fibroblasts following treatment with tumour necrosis factor-α or IL-1β (bone marrow: 8-fold and 37-fold, respectively, compared to vehicle; dermal fibroblasts: 4-fold and 14-fold; synovial fibroblasts: 7-fold and 31-fold; all P < 0.01 compared with vehicle). Treatment with IL-4 or interferon-γ was without effect, and there was no difference in 11β-HSD1 expression between fibroblasts (from any site) obtained from patients with rheumatoid arthritis or osteoarthritis. In the presence of 100 nmol/l cortisone, IL-6 production – a characteristic feature of synovial derived fibroblasts – was significantly reduced in synovial but not dermal or bone marrow fibroblasts. This was prevented by co-treatment with an 11β-HSD inhibitor, emphasizing the potential for autocrine activation of glucocorticoids in synovial fibroblasts. These data indicate that differences in fibroblast-derived glucocorticoid production (via the enzyme 11β-HSD1) between cells from distinct anatomical locations may play a key role in the predeliction of certain tissues to develop persistent inflammation.     

Metaheuristics and Pontryagin’s minimum principle for optimal therapeutic protocols in cancer immunotherapy: a case study and methods comparison

Journal of Mathematical Biology - In this paper, the performance appropriateness of population-based metaheuristics for immunotherapy protocols is investigated on a comparative basis while the goal...     

It’s a wrap: encapsulation as a management tool for marine biofouling

Encapsulation of fouled structures is an effective tool for countering incursions by non-indigenous biofoulers. However, guidelines for the implementation of encapsulation treatments are yet to be established. This study evaluated the effects of temperature, biomass, community composition, treatment duration and the biocide acetic acid on biofoulers. In laboratory trials using the model organisms Ciona spp. and Mytilus galloprovincialis, increasing the temperature or biomass speeded up the development of a toxic environment. Total mortality for Ciona spp. occurred within 72 and 24 h at 10 and 19°C, respectively. M. galloprovincialis survived up to 18 days, with high biomass increasing mortality at 10°C only. In a field study, three-month-old and four-year-old communities were encapsulated with and without acetic acid. Mortality took up to 10 days for communities encapsulated without acetic acid, compared to 48 h with acetic acid. The insights gained from this study will be useful in developing standardised encapsulation protocols.     

PSI:Biology-materials repository: a biologist’s resource for protein expression plasmids

The Protein Structure Initiative:Biology-Materials Repository (PSI:Biology-MR; MR; ) sequence-verifies, annotates, stores, and distributes the protein expression plasmids and vectors created by the Protein Structure Initiative (PSI). The MR has developed an informatics and sample processing pipeline that manages this process for thousands of samples per month from nearly a dozen PSI centers. DNASU (), a freely searchable database, stores the plasmid annotations, which include the full-length sequence, vector information, and associated publications for over 130,000 plasmids created by our laboratory, by the PSI and other consortia, and by individual laboratories for distribution to researchers worldwide. Each plasmid links to external resources, including the PSI Structural Biology Knowledgebase (), which facilitates cross-referencing of a particular plasmid to additional protein annotations and experimental data. To expedite and simplify plasmid requests, the MR uses an expedited material transfer agreement (EP-MTA) network, where researchers from network institutions can order and receive PSI plasmids without institutional delays. As of March 2011, over 39,000 protein expression plasmids and 78 empty vectors from the PSI are available upon request from DNASU. Overall, the MR’s repository of expression-ready plasmids, its automated pipeline, and the rapid process for receiving and distributing these plasmids more effectively allows the research community to dissect the biological function of proteins whose structures have been studied by the PSI.     

Machine learning methods for optimal prediction of motor outcome in Parkinson’s disease

PurposeIt is vital to appropriately power clinical trials towards discovery of novel disease-modifying therapies for Parkinson’s disease (PD). Thus, it is critical to improve prediction of outcome in PD patients.MethodsWe systematically probed a range of robust predictor algorithms, aiming to find best combinations of features for significantly improved prediction of motor outcome (MDS-UPDRS-III) in PD. We analyzed 204 PD patients with 18 features (clinical measures; dopamine-transporter (DAT) SPECT imaging measures), performing different randomized arrangements and utilizing data from 64%/6%/30% of patients in each arrangement for training/training validation/final testing. We pursued 3 approaches: i) 10 predictor algorithms (accompanied with automated machine learning hyperparameter tuning) were first applied on 32 experimentally created combinations of 18 features, ii) we utilized Feature Subset Selector Algorithms (FSSAs) for more systematic initial feature selection, and iii) considered all possible combinations between 18 features (262,143 states) to assess contributions of individual features.ResultsA specific set (set 18) applied to the LOLIMOT (Local Linear Model Trees) predictor machine resulted in the lowest absolute error 4.32 ± 0.19, when we firstly experimentally created 32 combinations of 18 features. Subsequently, 2 FSSAs (Genetic Algorithm (GA) and Ant Colony Optimization (ACO)) selecting 5 features, combined with LOLIMOT, reached an error of 4.15 ± 0.46. Our final analysis indicated that longitudinal motor measures (MDS-UPDRS-III years 0 and 1) were highly significant predictors of motor outcome.ConclusionsWe demonstrate excellent prediction of motor outcome in PD patients by employing automated hyperparameter tuning and optimal utilization of FSSAs and predictor algorithms.     

Wolff’s law in action: a mechanism for early knee osteoarthritis

There is growing interest in the role of bone in knee osteoarthritis. Bone is a dynamic organ, tightly regulated by a multitude of homeostatic controls, including genetic and environmental factors. One such key environmental regulator of periarticular bone is mechanical stimulation, which, according to Wolff’s law, is a key determinant of bone properties. Wolff’s law theorizes that repetitive loading of bone will cause adaptive responses enabling the bone to better cope with these loads. Despite being an adaptive response of bone, the remodeling process may inadvertently trigger maladaptive responses in other articular structures. Accumulating evidence at the knee suggests that expanding articular bone surface area is driven by mechanical stimulation and is a strong predictor of articular cartilage loss. Similarly, fractal analysis of bone architecture provides further clues that bone adaptation may have untoward consequences for joint health. This review hypothesizes that adaptations of periarticular bone in response to mechanical stimulation cause maladaptive responses in other articular structures that mediate the development of knee osteoarthritis. A potential disease paradigm to account for such a hypothesis is also proposed, and novel therapeutic targets that may have a bone-modifying effect, and therefore potentially a disease-modifying effect, are also explored.