Individualized Exercise Training at Maximal Fat Oxidation Combined with Fruit and Vegetable-Rich Diet in Overweight or Obese Women: The LIPOXmax-Réunion Randomized Controlled Trial

Objectives

Lifestyle combined interventions are a key strategy for preventing type-2 diabetes (T2DM) in overweight or obese subjects. In this framework, LIPOXmax individualized training, based on maximal fat oxidation [MFO], may be a promising intervention to promote fat mass (FM) reduction and prevent T2DM. Our primary objective was to compare three training programs of physical activity combined with a fruit- and vegetable-rich diet in reducing FM in overweight or obese women.

Design and setting

A five months non-blinded randomized controlled trial (RCT) with three parallel groups in La Réunion Island, a region where metabolic diseases are highly prevalent.

Subjects

One hundred and thirty-six non-diabetic obese (body mass index [BMI]: 27–40 kg/m²) young women (aged 20–40) were randomized (G1: MFO intensity; G2: 60% of VO₂-peak intensity; G3: free moderate-intensity at-home exercise following good physical practices).

Outcomes

Anthropometry (BMI, bodyweight, FM, fat-free mass), glucose (fasting plasma glucose, insulin, HOMA-IR) and lipid (cholesterol and triglycerides) profiles, and MFO values were measured at month-0, month-3 and month-5.

Results

At month-5, among 109 women assessed on body composition, the three groups exhibited a significant FM reduction over time (G1: -4.1±0.54 kg; G2: -4.7±0.53 kg; G3: -3.5±0.78 kg, p<0.001, respectively) without inter-group differences (p = 0.135). All groups exhibited significant reductions in insulin levels or HOMA-IR index, and higher MFO values over time (p<0.001, respectively) but glucose control improvement was higher in G1 than in G3 while MFO values were higher in G1 than in G2 and G3. Changes in other outcome measures and inter-group differences were not significant.

Conclusion

In our RCT the LIPOXmax intervention did not show a superiority in reducing FM in overweight or obese women but is associated with higher MFO and better glucose control improvements. Other studies are required before proposing LIPOXmax training for the prevention of T2DM in overweight or obese women.

Trial Registration

ClincialTrials.gov NCT01464073     

Mycoheterotrophy evolved from mixotrophic ancestors: evidence in Cymbidium (Orchidaceae)

Background and Aims

Nutritional changes associated with the evolution of achlorophyllous, mycoheterotrophic plants have not previously been inferred with robust phylogenetic hypotheses. Variations in heterotrophy in accordance with the evolution of leaflessness were examined using a chlorophyllous–achlorophyllous species pair in Cymbidium (Orchidaceae), within a well studied phylogenetic background.

Methods

To estimate the level of mycoheterotrophy in chlorophyllous and achlorophyllous Cymbidium, natural ¹³C and ¹⁵N contents (a proxy for the level of heterotrophy) were measured in four Cymbidium species and co-existing autotrophic and mycoheterotrophic plants and ectomycorrhizal fungi from two Japanese sites.

Key Results

δ¹³C and δ¹⁵N values of the achlorophyllous C. macrorhizon and C. aberrans indicated that they are full mycoheterotrophs. δ¹³C and δ¹⁵N values of the chlorophyllous C. lancifolium and C. goeringii were intermediate between those of reference autotrophic and mycoheterotrophic plants; thus, they probably gain 30–50 % of their carbon resources from fungi. These data suggest that some chlorophyllous Cymbidium exhibit partial mycoheterotrophy (= mixotrophy).

Conclusions

It is demonstrated for the first time that mycoheterotrophy evolved after the establishment of mixotrophy rather than through direct shifts from autotrophy to mycoheterotrophy. This may be one of the principal patterns in the evolution of mycoheterotrophy. The results also suggest that the establishment of symbiosis with ectomycorrhizal fungi in the lineage leading to mixotrophic Cymbidium served as pre-adaptation to the evolution of the mycoheterotrophic species. Similar processes of nutritional innovations probably occurred in several independent orchid groups, allowing niche expansion and radiation in Orchidaceae, probably the largest plant family.     

The head-fixed behaving rat--procedures and pitfalls

This paper describes experimental techniques with head-fixed, operantly conditioned rodents that allow the control of stimulus presentation and tracking of motor output at hitherto unprecedented levels of spatio-temporal precision. Experimental procedures for the surgery and behavioral training are presented. We place particular emphasis on potential pitfalls using these procedures in order to assist investigators who intend to engage in this type of experiment. We argue that head-fixed rodent models, by allowing the combination of methodologies from molecular manipulations, intracellular electrophysiology, and imaging to behavioral measurements, will be instrumental in combining insights into the functional neuronal organization at different levels of observation. Provided viable behavioral methods are implemented, model systems based on rodents will be complementary to current primate models--the latter providing highest comparability with the human brain, while the former offer hugely advanced methodologies on the lower levels of organization, for example, genetic alterations, intracellular electrophysiology, and imaging.     

Synthesis of fluorinated C-mannopeptides as sialyl Lewisx mimics for E- and P-selectin inhibition

The synthesis of fluorinated C-mannopeptides and their evaluation as E- and P-selectin inhibitors is described. These molecules are difluorinated analogues of CH₂-glycopeptides already reported to act as sLe^x mimics. The α and β anomers of these CF₂-glycopeptides have been prepared, as well as their 1-hydroxy analogues which were present in solution as an equilibrium mixture of α- and β-pyranose and α- and β-furanose forms. These molecules showed inhibitory activities comparable to their CH₂ counterparts with a moderate influence of the pseudo-anomeric center configuration.     

New evidence for a 67,000-year-old human presence at Callao Cave, Luzon, Philippines

Documentation of early human migrations through Island Southeast Asia and Wallacea en route to Australia has always been problematic due to a lack of well-dated human skeletal remains. The best known modern humans are from Niah Cave in Borneo (40-42 ka), and from Tabon Cave on the island of Palawan, southwest Philippines (47 ± 11 ka). The discovery of Homo floresiensis on the island of Flores in eastern Indonesia has also highlighted the possibilities of identifying new hominin species on islands in the region. Here, we report the discovery of a human third metatarsal from Callao Cave in northern Luzon. Direct dating of the specimen using U-series ablation has provided a minimum age estimate of 66.7 ± 1 ka, making it the oldest known human fossil in the Philippines. Its morphological features, as well as size and shape characteristics, indicate that the Callao metatarsal definitely belongs to the genus Homo. Morphometric analysis of the Callao metatarsal indicates that it has a gracile structure, close to that observed in other small-bodied Homo sapiens. Interestingly, the Callao metatarsal also falls within the morphological and size ranges of Homo habilis and H. floresiensis. Identifying whether the metatarsal represents the earliest record of H. sapiens so far recorded anywhere east of Wallace’s Line requires further archaeological research, but its presence on the isolated island of Luzon over 65,000 years ago further demonstrates the abilities of humans to make open ocean crossings in the Late Pleistocene.     

Evolutionary dynamics of two related malignant plasma cell lines

Cancer is the consequence of sequential acquisition of mutations within somatic cells. Mutations alter the relative reproductive fitness of cells, enabling the population to evolve in time as a consequence of selection. Cancer therapy itself can select for or against specific subclones. Given the large population of tumor cells, subclones inevitably emerge and their fate will depend on the evolutionary dynamics that define the interactions between such clones. Using a combination of in vitro studies and mathematical modeling, we describe the dynamic behavior of two cell lines isolated from the same patient at different time points of disease progression and show how the two clones relate to one another. We provide evidence that the two clones coexisted at the time of initial presentation. The dominant clone presented with biopsy-proven cardiac AL amyloidosis. Initial therapy selected for the second clone that expanded leading to a change in the diagnosis to multiple myeloma. The evolutionary dynamics relating the two cell lines are discussed and a hypothesis is generated in regard to the mechanism of one of the phenotypic characteristics that is shared by these two cell lines.Key words: multiple myeloma, amyloidosis, chemotherapy, clonal evolution, selection     

Genotypic characterization and clinical evaluation of an influenza A/Texas/1/77 (H3N2)-like recombinant: RIT 4199.

The RIT 4199 (H3N2) strain was obtained by recombination of PR/8/34 (H0N1) and A/Alaska/5/77 (H3N2) isolates. Its genetic composition was determined by RNA-RNA hybridization and by identification by gel electrophoresis of the double-standard RNA formed. The RIT 4199 was inoculated intranasally to 27 seronegative volunteers at a dose of 10(7.3)EID50. The results show that it is suitable for live vaccine strain.     

2-Nitro and 4-nitro-quinone-methides are not irreversible inhibitors of bovine beta-glucuronidase.

4-Benzylamino-(and 4-chloromethyl)-2-nitro-beta-D-glucuronides (4, 10) and their 2-substituted-4-nitro regioisomers (7, 13) were prepared by glycosidation of the 3-nitro-4-hydroxy- and the 2-hydroxy-5-nitro-benzylic alcohol, respectively, with a glucuronyl donor. Carbonate activation followed by reaction with benzylamine or methanesulfonyl chloride afforded, after complete deprotection, the target molecules 4, 7, 10 and 13. These compounds have been synthesized to determine whether these molecules are (or not) glucuronidase inhibitors. After incubation with bovine liver beta-glucuronidase, none of the cleavage products (the titled quinone-methides) showed to be irreversible inhibitors of this enzyme.     

Fire history and the global carbon budget: a 1°× 1° fire history reconstruction for the 20th century

A yearly global fire history is a prerequisite for quantifying the contribution of previous fires to the past and present global carbon budget. Vegetation fires can have both direct (combustion) and long‐term indirect effects on the carbon cycle. Every fire influences the ecosystem carbon budget for many years, as a consequence of internal reorganization, decomposition of dead biomass, and regrowth. We used a two‐step process to estimate these effects. First we synthesized the available data available for the 1980s or 1990s to produce a global fire map. For regions with no data, we developed estimates based on vegetation type and history. Second, we then worked backwards to reconstruct the fire history. This reconstruction was based on published data when available. Where it was not, we extrapolated from land use practices, qualitative reports and local studies, such as tree ring analysis. The resulting product is intended as a first approximation for questions about consequences of historical changes in fire for the global carbon budget. We estimate that an average of 608 Mha yr^?1 burned (not including agricultural fires) at the end of the 20th century. 86% of this occurred in tropical savannas. Fires in forests with higher carbon stocks consumed 70.7 Mha yr^?1 at the beginning of the century, mostly in the boreal and temperate forests of the Northern Hemisphere. This decreased to 15.2 Mha yr^?1 in the 1960s as a consequence of fire suppression policies and the development of efficient fire fighting equipment. Since then, fires in temperate and boreal forests have decreased to 11.2 Mha yr^?1. At the same time, burned areas increased exponentially in tropical forests, reaching 54 Mha yr^?1 in the 1990s, reflecting the use of fire in deforestation for expansion of agriculture. There is some evidence for an increase in area burned in temperate and boreal forests in the closing years of the 20th century.     

A Microenvironment Based Model of Antimitotic Therapy of Gompertzian Tumor Growth

A model of tumor growth, based on two-compartment cell population dynamics, and an overall Gompertzian growth has been previously developed. The main feature of the model is an inter-compartmental transfer function that describes the net exchange between proliferating (P) and quiescent (Q) cells and yields Gompertzian growth for tumor cell population N = P + Q. Model parameters provide for cell reproduction and cell death. This model is further developed here and modified to simulate antimitotic therapy. Therapy decreases the reproduction-rate constant and increases the death-rate constant of proliferating cells with no direct effect on quiescent cells. The model results in a system of two ODE equations (in N and P/N) that has an analytical solution. Net tumor growth depends on support from the microenvironment. Indirectly, this is manifested in the transfer function, which depends on the proliferation ratio, P/N. Antimitotic therapy will change P/N, and the tumor responds by slowing the transfer rate from P to Q. While the cellular effects of therapy are modeled as dependent only on antimitotic activity of the drug, the tumor response also depends on the tumor age and any previous therapies—after therapy, it is not the same tumor. The strength of therapy is simulated by the parameter λ, which is the ratio of therapy induced net proliferation rate constant versus the original. A pharmacodynamic factor inversely proportional to tumor size is implemented. Various chemotherapy regimens are simulated and the outcomes of therapy administered at different time points in the life history of the tumor are explored. Our analysis shows: (1) for a constant total dose administered, a decreasing dose schedule is marginally superior to an increasing or constant scheme, with more pronounced benefit for faster growing tumors, (2) the minimum dose to stop tumor growth is age dependent, and (3) a dose-dense schedule is favored. Faster growing tumors respond better to dose density.