The anthropometric history of Argentina, Brazil and Peru during the 19th and early 20th century

This anthropometric study focuses on the histories of three important Latin American countries - Brazil, Peru, and Argentina - during the 19th century, and tests hypotheses concerning their welfare trends. While non-farm Brazil and Lima, Peru, started at relatively low height levels, Brazil made substantial progress in nutritional levels from the 1860s to the 1880s. In contrast, Lima remained at low levels. Argentinean men were tall to begin with, but heights stagnated until 1910. The only exception were farmers and landowners, who benefited from the export boom.     

Infections after bone allograft surgery: a prospective study by a hospital bone bank using frozen femoral heads from living donors

In the advent of the EU guidelines 2004/23/EG and 2006/17/EG requiring extensive safety and quality steps in bone banking, the prevalence and risk of infection disease transmission from bone allograft needs to be reconsidered. Therefore, we prospectively reviewed the screening process of bone donations and the outcome of surgeries utilizing bone allografts from our internal hospital bone bank with regard to infections according to CDC criteria. One-hundred and eighty-eight allogenic bone transplantation procedures in 160 patients were followed-up for 12–64 months (mean 32 months). Bacterial infection occurred in 11 patients, the overall infection rate therefore was 6.9%. After review of the clinical and intraoperative findings, none of the infections were likely to have been caused by the bone graft. Although no follow-up serologic testing was performed, no HIV of hepatitis infections were observed. Frozen bone allografts derived from live donors and provided by hospitals can generally be considered safe. However, without new and relevant clinical expertise, continuing this technique will be impeded by the new EU guidelines and their national implementations.     

A transglucosidase necessary for starch degradation and maltose metabolism in leaves at night acts on cytosolic heteroglycans (SHG)

The recently characterized cytosolic transglucosidase DPE2 (EC 2.4.1.25) is essential for the cytosolic metabolism of maltose, an intermediate on the pathway by which starch is converted to sucrose at night. In in vitro assays, the enzyme utilizes glycogen as a glucosyl acceptor but the in vivo acceptor molecules remained unknown. In this communication we present evidence that DPE2 acts on the recently identified cytosolic water-soluble heteroglycans (SHG) as does the cytosolic phosphorylase (EC 2.4.1.1) isoform. By using in vitro two-step ¹⁴C labeling assays we demonstrate that the two transferases can utilize the same acceptor sites of the SHG. Cytosolic heteroglycans from a DPE2-deficient Arabidopsis mutant were characterized. Compared with the wild type the glucose content of the heteroglycans was increased. Most of the additional glucosyl residues were found in the outer chains of SHG that are released by an endo- α -arabinanase (EC 3.2.1.99). Additional starch-related mutants were characterized for further analysis of the increased glucosyl content. Based on these data, the cytosolic metabolism of starch-derived carbohydrates is discussed.     

Therapeutic implications of the enhanced short and long-term cytotoxicity of radiation treatment followed by oncolytic parvovirus H-1 infection in high-grade glioma cells

The prognosis of malignant brain tumors remains extremely bad in spite of moderate improvements of conventional treatments. A promising alternative approach is the use of oncolytic viruses. Strategies to improve viral toxicity include the combination of oncolytic viruses with standard therapies. Parvovirus H-1 (H-1PV) is an oncolytic virus with proven toxicity in glioma cells. Recently it has been demonstrated that the combination of ionizing radiation (IR) with H-1PV showed promising results. Previously irradiated glioma cells remained fully permissive for H-1PV induced cytotoxicity supporting the use of H-1PV for recurrent gliomas, which typically arise from irradiated cell clones. When glioma cells were infected with H-1PV shortly (24 h) after IR, cell killing improved and only the combination of both treatments lead to complete long-term tumor cell killing. The latter finding raises the question whether IR in combination with H-1PV exerts an additional therapeutic effect on highly resistant glioma stem cells. A likely translation into current clinical treatment protocols is to use stereotactic radiation of non-resectable recurrent gliomas followed by intratumoral injection of H-1PV to harvest the synergistic effects of combination treatment.     

Food Form and Portion Size Affect Postprandial Appetite Sensations and Hormonal Responses in Healthy,Nonobese, Older Adults

Data are limited concerning the dietary factors that influence appetite control in older adults. This study examined the effects of food form and portion size on appetite in 43 older adults (age: 72 ± 1 years; BMI: 25.6 ± 0.3 kg/m²). Subjects were assigned to groups based on portion size of the test meal (12.5% (n = 18) vs. 25% (n = 25) of estimated energy need). Subjects randomly consumed, on two separate days, the respective solid or beverage test meal. Appetite sensations and hormonal responses were measured over 4 h. Main effects of food form (P < 0.05) and/or portion size (P < 0.05) were observed for each appetite sensation. Postprandial hunger and desire to eat were greater following beverage vs. solid meal (between 12.5% vs. 25%), whereas fullness was lower after beverage vs. solid meal (P < 0.05). Main effects of food form and/or portion size were observed for glucose, insulin, and ghrelin. Postprandial glucose and insulin concentrations were lower after beverage vs. solid meal (between 12.5% vs. 25%; all comparisons, P < 0.05) whereas beverage meal led to greater 4‐h ghrelin vs. solid meal (P = 0.09). No main effects were observed for glucagon‐like peptide‐1 (GLP‐1) or cholecystokinin (CCK). When adjusting for age, food form remained significant for postprandial hunger and fullness; portion size remained significant for postprandial glucose. Greater hunger and reduced satiety with accompanying glucose, insulin, and ghrelin following the beverage vs. solid meals, and to some extent, in smaller vs. larger portions suggest that appetite control is influenced by food form and portion size in older adults. These findings may enhance the development of appropriate dietary strategies that help to regulate energy balance.     

Shigella Mediated Depletion of Macrophages in a Murine Breast Cancer Model Is Associated with Tumor Regression

A tumor promoting role of macrophages has been described for a transgenic murine breast cancer model. In this model tumor-associated macrophages (TAMs) represent a major component of the leukocytic infiltrate and are associated with tumor progression. Shigella flexneri is a bacterial pathogen known to specificly induce apotosis in macrophages. To evaluate whether Shigella-induced removal of macrophages may be sufficient for achieving tumor regression we have developed an attenuated strain of S. flexneri (M90TΔaroA) and infected tumor bearing mice. Two mouse models were employed, xenotransplantation of a murine breast cancer cell line and spontanous breast cancer development in MMTV-HER2 transgenic mice. Quantitative analysis of bacterial tumor targeting demonstrated that attenuated, invasive Shigella flexneri primarily infected TAMs after systemic administration. A single i.v. injection of invasive M90TΔaroA resulted in caspase-1 dependent apoptosis of TAMs followed by a 74% reduction in tumors of transgenic MMTV-HER-2 mice 7 days post infection. TAM depletion was sustained and associated with complete tumor regression.These data support TAMs as useful targets for antitumor therapy and highlight attenuated bacterial pathogens as potential tools.     

Double Knockout Mutants of Arabidopsis Grown under Normal Conditions Reveal that the Plastidial Phosphorylase Isozyme Participates in Transitory Starch Metabolism

In leaves of two starch-related single-knockout lines lacking either the cytosolic transglucosidase (also designated as disproportionating enzyme 2, DPE2) or the maltose transporter (MEX1), the activity of the plastidial phosphorylase isozyme (PHS1) is increased. In both mutants, metabolism of starch-derived maltose is impaired but inhibition is effective at different subcellular sites. Two constitutive double knockout mutants were generated (designated as dpe2-1 × phs1a and mex1 × phs1b) both lacking functional PHS1. They reveal that in normally grown plants, the plastidial phosphorylase isozyme participates in transitory starch degradation and that the central carbon metabolism is closely integrated into the entire cell biology. All plants were grown either under continuous illumination or in a light-dark regime. Both double mutants were compromised in growth and, compared with the single knockout plants, possess less average leaf starch when grown in a light-dark regime. Starch and chlorophyll contents decline with leaf age. As revealed by transmission electron microscopy, mesophyll cells degrade chloroplasts, but degradation is not observed in plants grown under continuous illumination. The two double mutants possess similar but not identical phenotypes. When grown in a light-dark regime, mesophyll chloroplasts of dpe2-1 × phs1a contain a single starch granule but under continuous illumination more granules per chloroplast are formed. The other double mutant synthesizes more granules under either growth condition. In continuous light, growth of both double mutants is similar to that of the parental single knockout lines. Metabolite profiles and oligoglucan patterns differ largely in the two double mutants.During the last two decades, biochemical analyses of starch metabolism in higher plants have been favored by the availability of large sets of insertion mutants deficient in a single starch-related gene product. Based on phenotypical characterization of these mutants followed by the identification of the respective locus in the genome, novel starch-related proteins were discovered that reside inside the plastid, in the cytosol, in the nucleus, and in the plastidial envelope membranes. Taken together, these results have largely altered the current view on starch metabolism (Zeeman et al., 2010; Fettke et al., 2012a; Smith, 2012).Despite this progress, phenotypical analyses of starch-related mutants are complex and, under certain circumstances, yield misleading conclusions. Loss of function of metabolic steps may cause the entire starch synthesizing or degrading process to become nonfunctional. In this case, mutants are expected to have starch levels that are significantly altered. If, however, single knockout mutants are capable of partially or fully compensating the loss of function by other routes, the resulting phenotypes are less obvious and more difficult to predict. Carbon fluxes through existing paths may be enhanced, or novel metabolic routes may be established that compensate the lost function. As an example, leaves of Arabidopsis (Arabidopsis thaliana) mutants constitutively lacking the plastidial hexose-phosphate isomerase strongly express a distinct plastidial Glc-6-P/orthophosphate antiporter isoform that in wild-type plants is found only in heterotrophic tissues (Kunz et al., 2010). In mesophyll cells of the mutant, the reductive pentose phosphate cycle cannot drive assimilatory starch biosynthesis, as chloroplasts are unable to convert Fru-6-P to Glc-6-P. However, their capacity of transporting Glc-6-P between the cytosolic and the chloroplastic compartment is strongly increased. Furthermore, nonfunctionality of some starch-related proteins can lead to enlarged or diminished metabolite pools that via sensing processes, lead to cellular alterations distant from central carbon metabolism. This complexity is evidenced by several starch-related Arabidopsis mutants that possess a largely altered plastidial ultrastructure and exhibit premature degradation of the entire chloroplast (Stettler et al., 2009; Cho et al., 2011).Furthermore, several starch-related enzymes are capable of forming homomeric or heteromeric complexes that are functionally relevant but, to some extent, variable (Delatte et al., 2005; Utsumi and Nakamura, 2006; Kubo et al., 2010; Emes and Tetlow, 2012; Nakamura et al., 2012; Streb et al., 2012).In starch or glycogen storing prokaryotic and eukaryotic cells, α-glucan phosphorylase (EC 2.4.1.1) is common. Initially, this enzyme was considered to be the main starch synthesizing activity (Hanes, 1940). Later, both starch and glycogen synthases have been discovered that utilize either ADPglucose or UDPglucose (or both; Deschamps et al., 2006) as hexosyl donor. Ample evidence has been presented that these enzymes are essential biosynthetic enzymes (Ballicora et al., 2003; Zeeman et al., 2010; Roach et al., 2012; Palm et al., 2013). Furthermore, it is widely accepted that in glycogen-storing cells, phosphorylase is indispensible for the degradation of the storage polysaccharide (Hwang et al., 1989; Alonso-Casajús et al., 2006; Wilson et al., 2010; Roach et al., 2012; Gazzerro et al., 2013).In plant cells, the metabolic function of phosphorylase is more complex and far from being clear. In lower and higher plants, two distinct phosphorylase types exist as plastid- and cytosol-specific isozymes and are designated as Pho1 (or, in Arabidopsis, PHS1) and Pho2 (PHS2), respectively. Based on the large differences in the affinities for glycogen, the plastidial and the cytosolic phosphorylases are also named as low-affinity (L-type) and high-affinity (H-type) isozymes, respectively. As starch is restricted to the plastids, only the Pho1 (PHS1) type appears to possess direct access to native starch and/or plastidial starch-derived α-glucans.Conflicting phenotypical features have been reported for several mutants possessing altered levels of the plastidial phosphorylase isozyme(s). In the starch-related mutant4 of the unicellular green alga Chlamydomonas reinhardtii, the lack of one plastidial Pho1 isozyme (designated as PhoB) was associated with a lower cellular starch content, abnormally shaped granules, a modified amylopectin structure, and an elevated amylose-to-amylopectin ratio when the cells were kept under nitrogen limitation (Dauvillée et al., 2006). These phenotypical features suggest an involvement of the plastidial phosphorylase PhoB in the biosynthesis of a storage polysaccharide resembling the reserve starch of higher plants. Similarly, a rapid incorporation of ¹⁴C into starch was observed when tuber discs from various transgenic potato lines were incubated with [U-¹⁴C]Glc-1-P. The rate of starch labeling was found to reflect the activity of the plastidial phosphorylase isozyme Pho1 (Fettke et al., 2010, 2012b). By contrast, transgenic potato (Solanum tuberosum) lines have been generated that due to expression of an antisense construct, possess a largely diminished total Pho1 activity in leaves. Leaf starch content is essentially unchanged compared with that of the wild-type plants, suggesting that under normal growth conditions, the plastidial phosphorylase is not necessarily involved in starch metabolism or, alternatively, can easily be replaced by other enzymes (Sonnewald et al., 1995). Likewise, the phenotype (including leaf starch content) of an Arabidopsis mutant lacking functional PHS1 has been reported not to differ from the wild type when the plants were grown under normal conditions. However, under water stress conditions, significantly more local leaf lesions have been reported to occur (Zeeman et al., 2004).When leaf discs from bean (Phaseolus vulgaris) or Arabidopsis plants were exposed to conditions favoring photorespiration (i.e. an atmosphere consisting of 30% [v/v] O₂ and 70% [v/v] N₂ but lacking CO₂), transitory starch was degraded in the light at a high rate and the plastidial Glc-6-P pool increased. In Arabidopsis mutants deficient in PHS1, the Glc monophosphate pool did not respond to photorespiratory conditions (Weise et al., 2006). These data lead to the conclusion that in illuminated leaves with very high rates of photorespiration, PHS1 is involved in the conversion of starch to Glc monophosphates but does not to participate in the nocturnal starch degradation.When studying several starch-related Arabidopsis mutants, we noticed that two single knockout mutations that both affect the maltose metabolism but differ in the subcellular location of the target protein possess a significantly increased PHS1 activity (Malinova et al., 2011a, 2011b). One mutant constitutively lacks the functional cytosolic transglucosidase (also designated as disproportionating enzyme2; DPE2) and, therefore, the cytosolic route of starch-derived maltose metabolism is impaired (Chia et al., 2004; Lu and Sharkey, 2004). The other mutant does not express the plastidial maltose transporter MEX1, resulting in a massively enlarged maltose pool (Niittylä et al., 2004). Thus, in the two mutants, the metabolism of starch-derived maltose is blocked at different subcellular sites, i.e. the cytosol and the chloroplast. The enhanced PHS1 activity as observed for the two mutants is difficult to explain unless a more general function of the phosphorylase isozyme in starch metabolism is assumed.For a detailed functional analysis of PHS1-related processes, we generated two types of constitutive PHS1-deficient double knockout mutants (DPE2 plus PHS1 or MEX1 plus PHS1) and studied their phenotypes in more detail under various experimental conditions. Shoot growth and leaf chlorophyll content are reduced when the plants are grown under a light-dark regime, but under continuous illumination, both effects are far less pronounced. Based on these data, we propose that the plastidial phosphorylase participates in both the turnover of transitory starch and in the maintenance of intact chloroplasts.