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Background and Aims Throughout the Cenozoic, Africa underwent several climatic and geological changes impacting the evolution of tropical rain forests (TRFs). African TRFs are thought to have extended from east to west in a 'pan-African' TRF, followed by several events of fragmentation during drier climate periods. During the Miocene, climate cooling and mountain uplift led to the aridification of tropical Africa and open habitats expanded at the expense of TRFs, which probably experienced local extinctions. However, in plants, these drivers were previously inferred using limited taxonomic and molecular data. Here, we tested the impact of climate and geological changes on diversification within the diverse clade Monodoreae (Annonaceae) composed of 90 tree species restricted to African TRFs. Methods We reconstructed a near-complete phylogenetic tree, based on 32 nuclear genes, and dated using relaxed clocks and fossil calibrations in a Bayesian framework. We inferred the biogeographical history and the diversification dynamics of the clade using multiple birth–death models. Key Results Monodoreae originated in East African TRFs ~25 million years ago (Ma) and expanded toward Central Africa during the Miocene. We inferred range contractions during the middle Miocene and document important connections between East and West African TRFs after 15–13 Ma. Our results indicated a sudden extinction event during the late Miocene, followed by an increase in speciation rates. Birth–death models suggested that African elevation change (orogeny) is positively linked to speciation in this clade. Conclusion East Africa is inferred as an important source of Monodoreae species, and possibly for African plant diversity in general. Our results support a 'sequential scenario of diversification' in which increased aridification triggered extinction of TRF species in Monodoreae. This was quickly followed by fragmentation of rain forests, subsequently enhancing lagged speciation resulting from vicariance and improved climate conditions. In contrast to previous ideas, the uplift of East Africa is shown to have played a positive role in Monodoreae diversification. [ABSTRACT FROM AUTHOR]

Estimating time-dependent rates of speciation and extinction from dated phylogenetic trees of extant species (timetrees), and determining how and why they vary, is key to understanding how ecological and evolutionary processes shape biodiversity. Due to an increasing availability of phylogenetic trees, a growing number of process-based methods relying on the birth–death model have been developed in the last decade to address a variety of questions in macroevolution. However, this methodological progress has regularly been criticized such that one may wonder how reliable the estimations of speciation and extinction rates are. In particular, using lineages-through-time (LTT) plots, a recent study has shown that there are an infinite number of equally likely diversification scenarios that can generate any timetree. This has led to questioning whether or not diversification rates should be estimated at all. Here, we summarize, clarify, and highlight technical considerations on recent findings regarding the capacity of models to disentangle diversification histories. Using simulations, we illustrate the characteristics of newly proposed "pulled rates" and their utility. We recognize that the recent findings are a step forward in understanding the behavior of macroevolutionary modeling, but they in no way suggest we should abandon diversification modeling altogether. On the contrary, the study of macroevolution using phylogenetic trees has never been more exciting and promising than today. We still face important limitations in regard to data availability and methods, but by acknowledging them we can better target our joint efforts as a scientific community. [Birth–death models; extinction; phylogenetics; speciation.] [ABSTRACT FROM AUTHOR]

The article discusses a study which analyses that severity of diabetic foot ulceration is resulted from specific polymorphisms of the heat-shock protein 70 gene (HSPA1B). The study shows that amputation and hospital stay are needed for patients with HSPA1B genotype which is associated with the severity of diabetic foot ulceration. It mentions that DNA from venous blood of diabetic patients are extracted and is examined by polymerase chain reaction-restriction fragment length analysis.

Considerable effort has been expended on understanding the genetic networks that regulate leaf development and morphology, however, less attention has been given to the role of leaf carbon status in modulating the plant developmental programme. Unexpected changes in plant development have been observed in response to changes in leaf metabolism. The focus of this review will be to discuss how manipulation of leaf carbon metabolic pathways, such as the photosynthetic carbon reduction cycle and trehalose biosynthesis, has provided insights into links between metabolism and development. [ABSTRACT FROM AUTHOR]

Clinical trials of new cancer drugs should ideally include measurements of parameters such as molecular target expression, pharmacokinetic (PK) behavior, and pharmacodynamic (PD) endpoints that can be linked to measures of clinical effect. Appropriate PK/PD biomarkers facilitate proof-of-concept demonstrations for target modulation; enhance the rational selection of an optimal drug dose and schedule; aid decision-making, such as whether to continue or close a drug development project; and may explain or predict clinical outcomes. In addition, measurement of PK/PD biomarkers can minimize uncertainty associated with predicting drug safety and efficacy, reduce the high levels of drug attrition during development, accelerate drug approval, and decrease the overall costs of drug development. However, there are many challenges in the development and implementation of biomarkers that probably explain their disappointingly low implementation in phase I trials. The Pharmacodynamic/Pharmacokinetic Technologies Advisory committee of Cancer Research UK has found that submissions for phase I trials of new cancer drugs in the United Kingdom often lack detailed information about PK and/or PD endpoints, which leads to suboptimal information being obtained in those trials or to delays in starting the trials while PK/PD methods are developed and validated. Minimally invasive PK/PD technologies have logistic and ethical advantages over more invasive technologies. Here we review these technologies, emphasizing magnetic resonance spectroscopy and positron emission tomography, which provide detailed functional and metabolic information. Assays that measure effects of drugs on important biologic pathways and processes are likely to be more cost-effective than those that measure specific molecular targets. Development, validation, and implementation of minimally invasive PK/PD methods are encouraged. [ABSTRACT FROM AUTHOR]