Adjunctive strategies to enhance peripheral warming: clinical techniques

This study investigates common successful strategies to increase peripheral temperature with biofeedback. Eighteen BCIA-certified therapists (average years of practice, 7.5) were interviewed by telephone for 30 to 45 minutes regarding successful peripheral warming strategies. The practitioners reported using multiple teaching strategies, either concurrently or sequentially. These responses were organized into an interrelated four-category model that consists of the following: (1) Attentional Category--shifting from active to passive attention; (2) General Arousal Category--shifting from hyper- to hypoarousal; (3) Proprioceptive/Kinesthetic Awareness Category--shifting from decreased to increased body awareness; (4) Self-Image/Self-Esteem Category--shifting from negative to positive self-image/self-esteem. These four categories and their corresponding techniques can be used to facilitate peripheral warming.     

Comparative proteomics of stenotopic caddisfly Crunoecia irrorata identifies acclimation strategies to warming

Species' ecological preferences are often deduced from habitat characteristics thought to represent more or less optimal conditions for physiological functioning. Evolution has led to stenotopic and eurytopic species, the former having decreased niche breadths and lower tolerances to environmental variability. Species inhabiting freshwater springs are often described as being stenotopic specialists, adapted to the stable thermal conditions found in these habitats. Whether due to past local adaptation these species have evolved or have lost intra‐generational adaptive mechanisms to cope with increasing thermal variability has, to our knowledge, never been investigated. By studying how the proteome of a stenotopic species changes as a result of increasing temperatures, we investigate if the absence or attenuation of molecular mechanisms is indicative of local adaptation to freshwater springs. An understanding of compensatory mechanisms is especially relevant as spring specialists will experience thermal conditions beyond their physiological limits due to climate change. In this study, the stenotopic species Crunoecia irrorata (Trichoptera: Lepidostomatidae, Curtis 1834) was acclimated to 10, 15 and 20°C for 168 hr. We constructed a homology‐based database and via liquid chromatography‐tandem mass spectrometry (LC‐MS/MS)‐based shotgun proteomics identified 1,358 proteins. Differentially abundant proteins and protein norms of reaction revealed candidate proteins and molecular mechanisms facilitating compensatory responses such as trehalose metabolism, tracheal system alteration and heat‐shock protein regulation. A species‐specific understanding of compensatory physiologies challenges the characterization of species as having narrow tolerances to environmental variability if that characterization is based on occurrences and habitat characteristics alone.     

Feeding the extra billions: strategies to improve crops and enhance future food security

The ability to feed an expanding world population poses one of the greatest challenges to mankind in the future. Accompanying the increased demand for food by the expected nine billion inhabitants of Earth in 2050 will be a continual decrease in arable land area, together with a decline in crop yield due to a variety of stresses. For these formidable challenges to be met, future crops should not only by high-yielding, but also stress-tolerant and disease-resistant. In this review, we highlight the importance of genetic engineering as an indispensable tool to generate just such future crops. We briefly discuss strategies and available tools for biotechnological crop improvement and identify selected examples of candidate genes that may be manipulated so that current biological maxima in yield may be surpassed by comfortable margins. Future prospects and the necessity for basic research aimed at identifying novel target genes are also discussed.     

Specialization versus adaptation: two strategies employed by cyanophages to enhance their translation efficiencies

Effective translation of the viral genome during the infection cycle most likely enhances its fitness. In this study, we reveal two different strategies employed by cyanophages, viruses infecting cyanobacteria, to enhance their translation efficiency. Cyanophages of the T7-like Podoviridae family adjust their GC content and codon usage to those of their hosts. In contrast, cyanophages of the T4-like Myoviridae family maintain genomes with low GC content, thus sometimes differing from that of their hosts. By introducing their own specific set of tRNAs, they appear to modulate the tRNA pools of hosts with tRNAs that fit the viral low GC preferred codons. We assessed the possible effects of those viral tRNAs on cyanophages and cyanobacterial genomes using the tRNA adaptation index, which measures the extent to which a given pool of tRNAs translates efficiently particular genes. We found a strong selective pressure to gain and maintain tRNAs that will boost translation of myoviral genes when infecting a high GC host, contrasted by a negligible effect on the host genes. Thus, myoviral tRNAs may represent an adaptive strategy to enhance fitness when infecting high GC hosts, thereby potentially broadening the spectrum of hosts while alleviating the need to adjust global parameters such as GC content for each specific host.     

Predictive model identifies strategies to enhance TSP1-mediated apoptosis signaling

Background

Thrombospondin-1 (TSP1) is a matricellular protein that functions to inhibit angiogenesis. An important pathway that contributes to this inhibitory effect is triggered by TSP1 binding to the CD36 receptor, inducing endothelial cell apoptosis. However, therapies that mimic this function have not demonstrated clear clinical efficacy. This study explores strategies to enhance TSP1-induced apoptosis in endothelial cells. In particular, we focus on establishing a computational model to describe the signaling pathway, and using this model to investigate the effects of several approaches to perturb the TSP1-CD36 signaling network.

Methods

We constructed a molecularly-detailed mathematical model of TSP1-mediated intracellular signaling via the CD36 receptor based on literature evidence. We employed systems biology tools to train and validate the model and further expanded the model by accounting for the heterogeneity within the cell population. The initial concentrations of signaling species or kinetic rates were altered to simulate the effects of perturbations to the signaling network.

Results

Model simulations predict the population-based response to strategies to enhance TSP1-mediated apoptosis, such as downregulating the apoptosis inhibitor XIAP and inhibiting phosphatase activity. The model also postulates a new mechanism of low dosage doxorubicin treatment in combination with TSP1 stimulation. Using computational analysis, we predict which cells will undergo apoptosis, based on the initial intracellular concentrations of particular signaling species.

Conclusions

This new mathematical model recapitulates the intracellular dynamics of the TSP1-induced apoptosis signaling pathway. Overall, the modeling framework predicts molecular strategies that increase TSP1-mediated apoptosis, which is useful in many disease settings.

     

Conventional and transgenic strategies to enhance the acid soil tolerance of barley

The aluminum (Al³⁺) tolerance of barley cultivars predominately from Brazil was compared to that of cultivars from other countries, wild barley accessions, and a transgenic line (L5) over-expressing TaALMT1, the major Al³⁺ tolerance gene from wheat. After screening conventional germplasm for Al³⁺ tolerance in hydroponics, 18 genotypes were further characterized in a short-term soil experiment. Among the Brazilian cultivars, Antarctica 01 and BRS Mariana showed the greatest relative root length (RRL) in acid soil. However, these cultivars were significantly less tolerant than the foreign cultivars Dayton (USA) and Murasakimochi (Japan) and the transgenic line L5 which out-performed all conventional genotypes. In long-term growth trials, the transgenic line produced the greatest relative root and relative shoot dry weight. Relative grain yield was greatest in the transgenic line and Dayton. All genotypes were also scored for two genetic markers linked to HvAACT1, the major Al³⁺ tolerance gene in barley. One marker detects a 1-kb insertion in the promoter that increases gene expression and leads to increased Al³⁺-activated citrate efflux from root apices. The other marker detects a 21-bp indel downstream of the coding region. The 1-kb insertion was only detected in Dayton and Murasakimochi that were the best performing cultivars among the non-transgenic germplasm. Interestingly, the Brazilian cultivars with an intermediate level of tolerance, Antarctica 01 and BRS Mariana, lacked the 1-kb insertion but had enhanced HvAACT1 expression compared to an Al³⁺-sensitive cultivar. No clear correlation was observed between Al³⁺ tolerance and the 21-bp indel marker in the short-term soil trials. We conclude that improved Al³⁺ tolerance in barley could be achieved by combining the best allele of HvAACT1 along with TaALMT1 as a transgene.     

Microbial responses to warming enhance soil carbon loss following translocation across a tropical forest elevation gradient

Tropical soils contain huge carbon stocks, which climate warming is projected to reduce by stimulating organic matter decomposition, creating a positive feedback that will promote further warming. Models predict that the loss of carbon from warming soils will be mediated by microbial physiology, but no empirical data are available on the response of soil carbon and microbial physiology to warming in tropical forests, which dominate the terrestrial carbon cycle. Here we show that warming caused a considerable loss of soil carbon that was enhanced by associated changes in microbial physiology. By translocating soils across a 3000 m elevation gradient in tropical forest, equivalent to a temperature change of ± 15 °C, we found that soil carbon declined over 5 years by 4% in response to each 1 °C increase in temperature. The total loss of carbon was related to its original quantity and lability, and was enhanced by changes in microbial physiology including increased microbial carbon‐use‐efficiency, shifts in community composition towards microbial taxa associated with warmer temperatures, and increased activity of hydrolytic enzymes. These findings suggest that microbial feedbacks will cause considerable loss of carbon from tropical forest soils in response to predicted climatic warming this century.     

Cryopreservation of human peripheral blood stem cells: optimal cooling and warming conditions

Peripheral blood stem cells are being used to reconstitute human bone marrow function after ablative therapy of blast transformation of chronic myelogenous leukemia. Studies were undertaken to establish the optimum cooling and warming conditions of the preservation of colonyforming activity in the peripheral blood of patients with CML.The results show that maximum recovery of CFU-c activity occurs after cooling at 3 °C/min, an average of 50% better than the recovery following cooling at 1 °C/min. CFU-c recovery decreased with decreasing warming rate, but high recovery was obtained with warming rates as low as 10 °C/ min. Viable cell count did not correlate with CFU-c recovery, therefore it represents a poor index for quality control.These results suggest that for clinical purposes bulk samples in flat bags with high surface area to volume ratios, frozen at a rate of 3 °C/min and thawed as rapidly as possible, should give maximum recovery of stem cell activity.     

Bioremediation technologies for treatment of PAH-contaminated soil and strategies to enhance process efficiency

The complex and diverse structural configurations of polycyclic aromatic hydrocarbons (PAHs), combined with their low bioavailability, hydrophobic nature, strong sorption phenomena, and high persistence in soil makes the design of effective bioremediation methodologies a challenge. The multi-phasic nature of the bioremediation process, restricted mass transfer and non-availability of degrading soil microflora further compound the problem. In this direction, this communication presents a focused review of bioremediation technologies used recently for the treatment of PAH-contaminated soils. The specific roles of important factors affecting bioremediation process efficiency are discussed. Finally some of the recently used strategies to enhance bioremediation process efficiency, including bioaugmentation, biostimulation, rhizoremediation, the use of chemotaxins, the biomimetic catalytic system approach, and integrated techniques, are reviewed.     

Adjunctive therapy to promote stone passage

The majority of individuals with nephrolithiasis have small ureteral stones that pass spontaneously. However, patients may experience severe pain during this process, which significantly alters their quality of life and may limit their vocational responsibilities. Therefore, measures to facilitate stone passage are uniformly embraced. We discuss methods to enhance spontaneous stone passage as well as the elimination of fragments generated with extracorporeal shock-wave lithotripsy.     

Simple strategies to enhance discovery of acetylation post-translational modifications by quadrupole-orbitrap LC-MS/MS

Enzyme-dependent post-translational modifications (PTMs) mediate the cellular regulation of proteins and can be discovered using proteomics. However, even where the peptides of interest can be enriched for analysis with state-of-the-art LC-MS/MS tools and informatics, only a fraction of peptide ions can be identified confidently. Thus, many PTM sites remain undiscovered and unconfirmed. In this minireview, we use a case study to discuss how the use of inclusion lists, turning off isotopic exclusion, and manual validation significantly increased depth of coverage, facilitating discovery of acetylation sites in targets of an acetyltransferase virulence factor. These underutilized strategies have the potential to help answer many mechanistic biological questions that large-scale proteomic studies cannot.