Desert Farming Benefits from Microbial Potential in Arid Soils and Promotes Diversity and Plant Health

BACKGROUND: To convert deserts into arable, green landscapes is a global vision, and desert farming is a strong growing area of agriculture world-wide. However, its effect on diversity of soil microbial communities, which are responsible for important ecosystem services like plant health, is still not known. METHODOLOGY/PRINCIPAL FINDINGS: We studied the impact of long-term agriculture on desert soil in one of the most prominent examples for organic desert farming in Sekem (Egypt). Using a polyphasic methodological approach to analyse microbial communities in soil as well as associated with cultivated plants, drastic effects caused by 30 years of agriculture were detected. Analysing bacterial fingerprints, we found statistically significant differences between agricultural and native desert soil of about 60%. A pyrosequencing-based analysis of the 16S rRNA gene regions showed higher diversity in agricultural than in desert soil (Shannon diversity indices: 11.21/7.90), and displayed structural differences. The proportion of Firmicutes in field soil was significantly higher (37%) than in the desert (11%). Bacillus and Paenibacillus play the key role: they represented 96% of the antagonists towards phytopathogens, and identical 16S rRNA sequences in the amplicon library and for isolates were detected. The proportion of antagonistic strains was doubled in field in comparison to desert soil (21.6%/12.4%); disease-suppressive bacteria were especially enriched in plant roots. On the opposite, several extremophilic bacterial groups, e.g., Acidimicrobium, Rubellimicrobium and Deinococcus-Thermus, disappeared from soil after agricultural use. The N-fixing Herbaspirillum group only occurred in desert soil. Soil bacterial communities were strongly driven by the a-biotic factors water supply and pH. CONCLUSIONS/SIGNIFICANCE: After long-term farming, a drastic shift in the bacterial communities in desert soil was observed. Bacterial communities in agricultural soil showed a higher diversity and a better ecosystem function for plant health but a loss of extremophilic bacteria. Interestingly, we detected that indigenous desert microorganisms promoted plant health in desert agro-ecosystems

Pharmacokinetics and pharmacodynamics of medication in asphyxiated newborns during controlled hypothermia. The PharmaCool multicenter study

<p>Abstract</p> <p>Background</p> <p>In the Netherlands, perinatal asphyxia (severe perinatal oxygen shortage) necessitating newborn resuscitation occurs in at least 200 of the 180–185.000 newly born infants per year. International randomized controlled trials have demonstrated an improved neurological outcome with therapeutic hypothermia. During hypothermia neonates receive sedative, analgesic, anti-epileptic and antibiotic drugs. So far little information is available how the pharmacokinetics (PK) and pharmacodynamics (PD) of these drugs are influenced by post resuscitation multi organ failure and the metabolic effects of the cooling treatment itself. As a result, evidence based dosing guidelines are lacking. This multicenter observational cohort study was designed to answer the question how hypothermia influences the distribution, metabolism and elimination of commonly used drugs in neonatal intensive care.</p> <p>Methods/Design</p> <p>Multicenter cohort study. All term neonates treated with hypothermia for Hypoxic Ischemic Encephalopathy (HIE) resulting from perinatal asphyxia in all ten Dutch Neonatal Intensive Care Units (NICUs) will be eligible for this study. During hypothermia and rewarming blood samples will be taken from indwelling catheters to investigate blood concentrations of several antibiotics, analgesics, sedatives and anti-epileptic drugs. For each individual drug the population PK will be characterized using Nonlinear Mixed Effects Modelling (NONMEM). It will be investigated how clearance and volume of distribution are influenced by hypothermia also taking maturation of neonate into account. Similarly, integrated PK-PD models will be developed relating the time course of drug concentration to pharmacodynamic parameters such as successful seizure treatment; pain assessment and infection clearance.</p> <p>Discussion</p> <p>On basis of the derived population PK-PD models dosing guidelines will be developed for the application of drugs during neonatal hypothermia treatment. The results of this study will lead to an evidence based drug treatment of hypothermic neonatal patients. Results will be published in a national web based evidence based paediatric formulary, peer reviewed journals and international paediatric drug references.</p> <p>Trial registration</p> <p>NTR2529.</p

Antenatal allopurinol for reduction of birth asphyxia induced brain damage (ALLO-Trial); a randomized double blind placebo controlled multicenter study

<p>Abstract</p> <p>Background</p> <p>Hypoxic-ischaemic encephalopathy is associated with development of cerebral palsy and cognitive disability later in life and is therefore one of the fundamental problems in perinatal medicine. The xanthine-oxidase inhibitor allopurinol reduces the formation of free radicals, thereby limiting the amount of hypoxia-reperfusion damage. In case of suspected intra-uterine hypoxia, both animal and human studies suggest that maternal administration of allopurinol immediately prior to delivery reduces hypoxic-ischaemic encephalopathy.</p> <p>Methods/Design</p> <p>The proposed trial is a randomized double blind placebo controlled multicenter study in pregnant women at term in whom the foetus is suspected of intra-uterine hypoxia.</p> <p>Allopurinol 500 mg IV or placebo will be administered antenatally to the pregnant woman when foetal hypoxia is suspected. Foetal distress is being diagnosed by the clinician as an abnormal or non-reassuring foetal heart rate trace, preferably accompanied by either significant ST-wave abnormalities (as detected by the STAN-monitor) or an abnormal foetal blood scalp sampling (pH < 7.20).</p> <p>Primary outcome measures are the amount of S100B (a marker for brain tissue damage) and the severity of oxidative stress (measured by isoprostane, neuroprostane, non protein bound iron and hypoxanthine), both measured in umbilical cord blood. Secondary outcome measures are neonatal mortality, serious composite neonatal morbidity and long-term neurological outcome. Furthermore pharmacokinetics and pharmacodynamics will be investigated.</p> <p>We expect an inclusion of 220 patients (110 per group) to be feasible in an inclusion period of two years. Given a suspected mean value of S100B of 1.05 ug/L (SD 0.37 ug/L) in the placebo group this trial has a power of 90% (alpha 0.05) to detect a mean value of S100B of 0.89 ug/L (SD 0.37 ug/L) in the 'allopurinol-treated' group (z-test_2-sided). Analysis will be by intention to treat and it allows for one interim analysis.</p> <p>Discussion</p> <p>In this trial we aim to answer the question whether antenatal allopurinol administration reduces hypoxic-ischaemic encephalopathy in neonates exposed to foetal hypoxia.</p> <p>Trial registration number</p> <p>Clinical Trials, protocol registration system: NCT00189007</p

Salmonella Strains Isolated from Galápagos Iguanas Show Spatial Structuring of Serovar and Genomic Diversity

It is thought that dispersal limitation primarily structures host-associated bacterial populations because host distributions inherently limit transmission opportunities. However, enteric bacteria may disperse great distances during food-borne outbreaks. It is unclear if such rapid long-distance dispersal events happen regularly in natural systems or if these events represent an anthropogenic exception. We characterized Salmonella enterica isolates from the feces of free-living Galápagos land and marine iguanas from five sites on four islands using serotyping and genomic fingerprinting. Each site hosted unique and nearly exclusive serovar assemblages. Genomic fingerprint analysis offered a more complex model of S. enterica biogeography, with evidence of both unique strain pools and of spatial population structuring along a geographic gradient. These findings suggest that even relatively generalist enteric bacteria may be strongly dispersal limited in a natural system with strong barriers, such as oceanic divides. Yet, these differing results seen on two typing methods also suggests that genomic variation is less dispersal limited, allowing for different ecological processes to shape biogeographical patterns of the core and flexible portions of this bacterial species' genome

Developmental malformation of the corpus callosum: a review of typical callosal development and examples of developmental disorders with callosal involvement

This review provides an overview of the involvement of the corpus callosum (CC) in a variety of developmental disorders that are currently defined exclusively by genetics, developmental insult, and/or behavior. I begin with a general review of CC development, connectivity, and function, followed by discussion of the research methods typically utilized to study the callosum. The bulk of the review concentrates on specific developmental disorders, beginning with agenesis of the corpus callosum (AgCC)—the only condition diagnosed exclusively by callosal anatomy. This is followed by a review of several genetic disorders that commonly result in social impairments and/or psychopathology similar to AgCC (neurofibromatosis-1, Turner syndrome, 22q11.2 deletion syndrome, Williams yndrome, and fragile X) and two forms of prenatal injury (premature birth, fetal alcohol syndrome) known to impact callosal development. Finally, I examine callosal involvement in several common developmental disorders defined exclusively by behavioral patterns (developmental language delay, dyslexia, attention-deficit hyperactive disorder, autism spectrum disorders, and Tourette syndrome)

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease