Targeting the Glutamine-Arginine-Proline Metabolism Axis in Cancer

Metabolic abnormalities are an important feature of tumours. The glutamine-arginine-proline axis is an important node of cancer metabolism and plays a major role in amino acid metabolism. This axis also acts as a scaffold for the synthesis of other nonessential amino acids and essential metabolites. In this paper, we briefly review (1) the glutamine addiction exhibited by tumour cells with accelerated glutamine transport and metabolism; (2) the methods regulating extracellular glutamine entry, intracellular glutamine synthesis and the fate of intracellular glutamine; (3) the glutamine, proline and arginine metabolic pathways and their interaction; and (4) the research progress in tumour therapy targeting the glutamine-arginine-proline metabolic system, with a focus on summarising the therapeutic research progress of strategies targeting of one of the key enzymes of this metabolic system, P5CS (ALDH18A1). This review provides a new basis for treatments targeting the metabolic characteristics of tumours

Scaling relationships between leaf shape and area of 12 rosaceae species

CITATION: Yu, X., et al. 2019. Scaling relationships between leaf shape and area of 12 rosaceae species. Symmetry, 11(10):1255, doi:10.3390/sym11101255.The original publication is available at https://www.mdpi.comPublisher's versionLeaf surface area (A) and leaf shape have been demonstrated to be closely correlated with photosynthetic rates. The scaling relationship between leaf biomass (both dry weight and fresh weight) and A has been widely studied. However, few studies have focused on the scaling relationship between leaf shape and A. Here, using more than 3600 leaves from 12 Rosaceae species, we examined the relationships of the leaf-shape indices including the left to right side leaf surface area ratio (AR), the ratio of leaf perimeter to leaf surface area (RPA), and the ratio of leaf width to length (RWL) versus A. We also tested whether there is a scaling relationship between leaf dry weight and A, and between PRA and A. There was no significant correlation between AR and A for each of the 12 species. Leaf area was also found to be independent of RWL because leaf width remained proportional to leaf length across the 12 species. However, there was a negative correlation between RPA and A. The scaling relationship between RPA and A held for each species, and the estimated scaling exponent of RPA versus A approached −1/2; the scaling relationship between leaf dry weight and A also held for each species, and 11 out of the 12 estimated scaling exponents of leaf dry weight versus A were greater than unity. Our results indicated that leaf surface area has a strong scaling relationship with leaf perimeter and also with leaf dry weight but has no relationship with leaf symmetry or RWL. Additionally, our results showed that leaf dry weight per unit area, which is usually associated with the photosynthetic capacity of plants, increases with an increasing A because the scaling exponent of leaf dry weight versus A is greater than unity. This suggests that a large leaf surface area requires more dry mass input to support the physical structure of the leaf.https://www.mdpi.com/2073-8994/11/10/125

BAC library resources for map-based cloning and physical map construction in barley (Hordeum vulgare L.)

Background: Although second generation sequencing (2GS) technologies allow re-sequencing of previously gold-standard-sequenced genomes, whole genome shotgun sequencing and de novo assembly of large and complex eukaryotic genomes is still difficult. Availability of a genome-wide physical map is therefore still a prerequisite for whole genome sequencing for genomes like barley. To start such an endeavor, large insert genomic libraries, i.e. Bacterial Artificial Chromosome (BAC) libraries, which are unbiased and representing deep haploid genome coverage, need to be ready in place. Result: Five new BAC libraries were constructed for barley (Hordeum vulgare L.) cultivar Morex. These libraries were constructed in different cloning sites (HindIII, EcoRI, MboI and BstXI) of the respective vectors. In order to enhance unbiased genome representation and to minimize the number of gaps between BAC contigs, which are often due to uneven distribution of restriction sites, a mechanically sheared library was also generated. The new BAC libraries were fully characterized in depth by scrutinizing the major quality parameters such as average insert size, degree of contamination (plate wide, neighboring, and chloroplast), empty wells and off-scale clones (clones with 250 fragments). Additionally a set of gene-based probes were hybridized to high density BAC filters and showed that genome coverage of each library is between 2.4 and 6.6 X. Conclusion: BAC libraries representing >20 haploid genomes are available as a new resource to the barley research community. Systematic utilization of these libraries in high-throughput BAC fingerprinting should allow developing a genome-wide physical map for the barley genome, which will be instrumental for map-based gene isolation and genome sequencing.Daniela Schulte, Ruvini Ariyadasa, Bujun Shi, Delphine Fleury, Chris Saski, Michael Atkins, Pieter deJong, Cheng-Cang Wu, Andreas Graner, Peter Langridge and Nils Stei

Post-translational modifications of voltage-gated sodium channels in chronic pain syndromes.

In the peripheral sensory nervous system the neuronal expression of voltage-gated sodium channels (Navs) is very important for the transmission of nociceptive information since they give rise to the upstroke of the action potential (AP). Navs are composed of nine different isoforms with distinct biophysical properties. Studying the mutations associated with the increase or absence of pain sensitivity in humans, as well as other expression studies, have highlighted Nav1.7, Nav1.8, and Nav1.9 as being the most important contributors to the control of nociceptive neuronal electrogenesis. Modulating their expression and/or function can impact the shape of the AP and consequently modify nociceptive transmission, a process that is observed in persistent pain conditions. Post-translational modification (PTM) of Navs is a well-known process that modifies their expression and function. In chronic pain syndromes, the release of inflammatory molecules into the direct environment of dorsal root ganglia (DRG) sensory neurons leads to an abnormal activation of enzymes that induce Navs PTM. The addition of small molecules, i.e., peptides, phosphoryl groups, ubiquitin moieties and/or carbohydrates, can modify the function of Navs in two different ways: via direct physical interference with Nav gating, or via the control of Nav trafficking. Both mechanisms have a profound impact on neuronal excitability. In this review we will discuss the role of Protein Kinase A, B, and C, Mitogen Activated Protein Kinases and Ca++/Calmodulin-dependent Kinase II in peripheral chronic pain syndromes. We will also discuss more recent findings that the ubiquitination of Nav1.7 by Nedd4-2 and the effect of methylglyoxal on Nav1.8 are also implicated in the development of experimental neuropathic pain. We will address the potential roles of other PTMs in chronic pain and highlight the need for further investigation of PTMs of Navs in order to develop new pharmacological tools to alleviate pain

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

ALDEFLUOR activity, ALDH isoforms, and their clinical significance in cancers

AbstractHigh aldehyde dehydrogenase (ALDH) activity is a metabolic feature of adult stem cells and various cancer stem cells (CSCs). The ALDEFLUOR system is currently the most commonly used method for evaluating ALDH enzyme activity in viable cells. This system is applied extensively in the isolation of normal stem cells and CSCs from heterogeneous cell populations. For many years, ALDH1A1 has been considered the most important subtype among the 19 ALDH family members in determining ALDEFLUOR activity. However, in recent years, studies of many types of normal and tumour tissues have demonstrated that other ALDH subtypes can also significantly influence ALDEFLUOR activity. In this article, we briefly review the relationships between various members of the ALDH family and ALDEFLUOR activity. The clinical significance of these ALDH isoforms in different cancers and possible directions for future studies are also summarised

Internode morphometrics and allometry of Tonkin Cane Pseudosasa amabilis

CITATION: Cheng, L. et al. 2017. Internode morphometrics and allometry of Tonkin Cane Pseudosasa amabilis. Ecology & Evolution, 7(222):9651-9660. doi:10.1002/ece3.3483.The original publication is available at https://onlinelibrary.wiley.comPseudosasa amabilis (McClure) (Poales: Gramineae) is a typical bamboo species naturally distributed in large area of south China and famous for its culm strength. Although bamboos were found to share the same development rule, the detailed internode morphology of bamboo culm was actually not fully expressed. We explored internode morphology of P. amabilis using 11 different physical parameters in different dimensions (1–4). As Taylor’s power law (TPL) is generally applicable to describe relationship between mean and variance of population density, here we used TPL to evaluate the differences between internodes, and further, the relationship between dimension and TPL. Results showed that length (L), hollow radius (HR), hollow area (HA), hollow cylinder volume (HCV), total cylinder volume (TCV), density (De), and weight (W) all presented positive skewed distribution in varying degrees. For the basic one-dimensional parameters, the 9th internode was the longest, the 7th the heaviest, while thickness (T) decreased with internodes. Diameter (D) decreased in general but with an inconspicuous local mode at the 5–6th internodes, potentially due to the rapid height growth. The longest (9th) internode was the “turning point” for T-D and HR-D relationships. Scatter plot changing trends of W to the one-dimensional parameters after the heaviest (7th) internode were reversed, indicating a deceleration of growth speed. TPL was not holding well in one-dimensional parameters (R2: 0.5413–0.8125), but keep increasing as the parameter’s dimension increasing (R2 > 0.92 for two-dimensional, R2 > 0.97 for three-dimensional, and R2 > 0.99 for four-dimensional parameters.), suggesting an emergence mechanism of TPL related to both the physical dimensions of morphological measures and the allometric growth of bamboo. From the physical fundamental level, all existences are the expression of energy distribution in different dimensions, implying a more general rule that energy distribution holds better TPL in higher dimension level.National Natural Science Foundation of ChinaPAPD of Jiangsu ProvinceNational Research Foundation of South AfricaGVPR by the National Institute of Food and Agriculture, U.S. Department of Agriculture, Hatch projectPublishers versio