Change in kyphosis does not affect the risk of falling in postmenopausal osteopenic and osteoporotic women

Objectives:To examine the influence of the annual change in kyphosis on the risk of falling in postmenopausal osteopenic and osteoporotic women.Methods:This prospective observational study included 498 postmenopausal Greek women over the age of 50, suffering from either osteoporosis or osteopenia. Data on age, height, weight, and self-reported falls were collected. Additionally, we evaluated the degree of the kyphosis angle, the balance, the mobility, the functionality and the handgrip strength on both hands of each subject using the Debrunner kyphometer, the Berg Balance Scale, the Timed-Up-and-Go test, the 30 Seconds Sit-to-Stand test and the Jamar Hydraulic Hand Dynamometer, respectively. All the above data were recorded at the baseline visit and the 12-month follow-up visit for each participant.Results:All examined variables presented a statistically significant change at the 12-month follow-up visit. Nevertheless, the annual change in kyphosis did not show any association with the risk of falling.Conclusion:No association was shown between the annual change in kyphosis and the risk of falling in postmenopausal osteopenic and osteoporotic women, nor bears any substantial prognostic value for future falls.     

Investigating the reference domain influence in personalised models of cardiac mechanics

Biomechanics and Modeling in Mechanobiology - A major concern in personalised models of heart mechanics is the unknown zero-pressure domain, a prerequisite for accurately predicting cardiac...     

Probabilistic inference of molecular networks from noisy data sources

Information on molecular networks, such as networks of interacting proteins, comes from diverse sources that contain remarkable differences in distribution and quantity of errors. Here, we introduce a probabilistic model useful for predicting protein interactions from heterogeneous data sources. The model describes stochastic generation of protein-protein interaction networks with real-world properties, as well as generation of two heterogeneous sources of protein-interaction information: research results automatically extracted from the literature and yeast two-hybrid experiments. Based on the domain composition of proteins, we use the model to predict protein interactions for pairs of proteins for which no experimental data are available. We further explore the prediction limits, given experimental data that cover only part of the underlying protein networks. This approach can be extended naturally to include other types of biological data sources.     

The BH3 Mimetic Obatoclax Accumulates in Lysosomes and Causes Their Alkalinization

Obatoclax belongs to a class of compounds known as BH3 mimetics which function as antagonists of Bcl-2 family apoptosis regulators. It has undergone extensive preclinical and clinical evaluation as a cancer therapeutic. Despite this, it is clear that obatoclax has additional pharmacological effects that contribute to its cytotoxic activity. It has been claimed that obatoclax, either alone or in combination with other molecularly targeted therapeutics, induces an autophagic form of cell death. In addition, obatoclax has been shown to inhibit lysosomal function, but the mechanism of this has not been elucidated. We have evaluated the mechanism of action of obatoclax in eight ovarian cancer cell lines. Consistent with its function as a BH3 mimetic, obatoclax induced apoptosis in three cell lines. However, in the remaining cell lines another form of cell death was evident because caspase activation and PARP cleavage were not observed. Obatoclax also failed to show synergy with carboplatin and paclitaxel, chemotherapeutic agents which we have previously shown to be synergistic with authentic Bcl-2 family antagonists. Obatoclax induced a profound accumulation of LC-3 but knockdown of Atg-5 or beclin had only minor effects on the activity of obatoclax in cell growth assays suggesting that the inhibition of lysosomal function rather than stimulation of autophagy may play a more prominent role in these cells. To evaluate how obatoclax inhibits lysosomal function, confocal microscopy studies were conducted which demonstrated that obatoclax, which contains two basic pyrrole groups, accumulates in lysosomes. Studies using pH sensitive dyes demonstrated that obatoclax induced lysosomal alkalinization. Furthermore, obatoclax was synergistic in cell growth/survival assays with bafilomycin and chloroquine, two other drugs which cause lysosomal alkalinization. These studies explain, for the first time, how obatoclax inhibits lysosomal function and suggest that lysosomal alkalinization contributes to the cytotoxic activity of obatoclax.     

Walking kinematics and kinetics following eccentric exercise-induced muscle damage

The goal of this investigation was to investigate how walking patterns are affected following muscle-damaging exercise by quantifying both lower limb kinematics and kinetics. Fifteen young women conducted a maximal isokinetic eccentric exercise (EE) muscle damage protocol (5 × 15) of the knee extensors and flexors of both legs at 60°/s. Three-dimensional motion data and ground reaction forces (GRFs) were collected 24 h pre-EE while the participants walked at their preferred self-selected walking speed (SWS). Participants were asked to perform two gait conditions 48 h post-EE. The first condition (COND1) was to walk at their own speed and the second condition (COND2) to maintain the SWS (±5%) they had 24 h pre-EE. Walking speed during COND1 was significantly lower compared to pre-exercise values. When walking speed was controlled during COND2, significant effects of muscle damage were noticed, among other variables, for stride frequency, loading rate, lateral and vertical GRFs, as well as for specific knee kinematics and kinetics. These findings provide new insights into how walking patterns are adapted to compensate for the impaired function of the knee musculature following muscle damage. The importance to distinguish the findings caused by muscle damage from those exhibited in response to changes in stride frequency is highlighted.     

Side‐chain interactions in the regulatory domain of human glutamate dehydrogenase determine basal activity and regulation

Glutamate Dehydrogenase (GDH) is central to the metabolism of glutamate, a major excitatory transmitter in mammalian central nervous system (CNS). hGDH1 is activated by ADP and L‐leucine and powerfully inhibited by GTP. Besides this housekeeping hGDH1, duplication led to an hGDH2 isoform that is expressed in the human brain dissociating its function from GTP control. The novel enzyme has reduced basal activity (4–6% of capacity) while remaining remarkably responsive to ADP/L‐leucine activation. While the molecular basis of this evolutionary adaptation remains unclear, substitution of Ser for Arg443 in hGDH1 is shown to diminish basal activity (< 2% of capacity) and abrogate L‐leucine activation. To explore whether the Arg443Ser mutation disrupts hydrogen bonding between Arg443 and Ser409 of adjacent monomers in the regulatory domain (‘antenna’), we replaced Ser409 by Arg or Asp in hGDH1. The Ser409Arg‐1 change essentially replicated the Arg443Ser‐1 mutation effects. Molecular dynamics simulation predicted that Ser409 and Arg443 of neighboring monomers come in close proximity in the open conformation and that introduction of Ser443‐1 or Arg409‐1 causes them to separate with the swap mutation (Arg409/Ser443) reinstating their proximity. A swapped Ser409Arg/Arg443Ser‐1 mutant protein, obtained in recombinant form, regained most of the wild‐type hGDH1 properties. Also, when Ser443 was replaced by Arg443 in hGDH2 (as occurs in hGDH1), the Ser443Arg‐2 mutant acquired most of the hGDH1 properties. Hence, side‐chain interactions between 409 and 443 positions in the ‘antenna’ region of hGDHs are crucial for basal catalytic activity, allosteric regulation, and relative resistance to thermal inactivation.

     

UASB/Flash aeration enable complete treatment of municipal wastewater for reuse

A simple, efficient and cost-effective method for municipal wastewater treatment is examined in this paper. The municipal wastewater is treated using an upflow anaerobic sludge bed (UASB) reactor followed by flash aeration (FA) as the post-treatment, without implementing aerobic biological processes. The UASB reactor was operated without recycle, at hydraulic retention time (HRT) of 8 h and achieved consistent removal of BOD, COD and TSS of 60-70% for more than 12 months. The effect of FA on UASB effluent post-treatment was studied at different HRT (15, 30 and 60 min) and dissolved oxygen (DO) concentrations (low DO = 1-2 mg/L and high DO = 5-6 mg/L). The optimum conditions for BOD, COD and sulfide removal were 30-60 min HRT and high DO concentration inside the FA tank. The final effluent after clarification was characterized by BOD and COD values of 28-35 and 50-58 mg/L, respectively. Sulfides were removed by more than 80%, but the fecal coliform only by ~2 log. The UASB followed by FA is a simple and efficient process for municipal wastewater treatment, except for fecal coliform, enabling water and nutrients recycling to agriculture.     

Effect of ascorbate oxidase over-expression on ascorbate recycling gene expression in response to agents imposing oxidative stress

Ascorbate oxidase (AO) is a cell wall-localized enzyme that uses oxygen to catalyse the oxidation of ascorbate (AA) to the unstable radical monodehydroascorbate (MDHA) which rapidly disproportionates to yield dehydroascorbate (DHA) and AA, and thus contributes to the regulation of the AA redox state. Here, it is reported that in vivo lowering of the apoplast AA redox state, through increased AO expression in transgenic tobacco (Nicotiana tabacum L. cv. Xanthi), exerts no effects on the expression levels of genes involved in AA recycling under normal growth conditions, but plants display enhanced sensitivity to various oxidative stress-promoting agents. RNA blot analyses suggest that this response correlates with a general suppression of the plant's antioxidative metabolism as demonstrated by lower expression levels of AA recycling genes. Furthermore, studies using Botrytis cinerea reveal that transgenic plants exhibit increased sensitivity to fungal infection, although the response is not accompanied by a similar suppression of AA recycling gene expression. Our current findings, combined with previous studies which showed the contribution of AO in the regulation of AA redox state, suggest that the reduction in the AA redox state in the leaf apoplast of these transgenic plants results in shifts in their capacity to withstand oxidative stress imposed by agents imposing oxidative stress.