Mismatch repair defects and Lynch syndrome: the role of the basic scientist in the battle against cancer

Publication date: Available online 2 December 2015
Source:DNA Repair
Author(s): Christopher D. Heinen
We have currently entered a genomic era of cancer research which may soon lead to a genomic era of cancer treatment. Patient DNA sequencing information may lead to a personalized approach to managing an individual's cancer as well as future cancer risk. The success of this approach, however, begins not necessarily in the clinician's office, but rather at the laboratory bench of the basic scientist. The basic scientist plays a critical role since the DNA sequencing information is of limited use unless one knows the function of the gene that is altered and the manner by which a sequence alteration affects that function. The role of basic science research in aiding the clinical management of a disease is perhaps best exemplified by considering the case of Lynch syndrome, a hereditary disease that predisposes patients to colorectal and other cancers. This review will examine how the diagnosis, treatment and even prevention of Lynch syndrome-associated cancers has benefitted from extensive basic science research on the DNA mismatch repair genes whose alteration underlies this condition.



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Antibody diversification caused by disrupted mismatch repair and promiscuous DNA polymerases

Publication date: Available online 2 December 2015
Source:DNA Repair
Author(s): Kimberly J. Zanotti, Patricia J. Gearhart
The enzyme activation-induced deaminase (AID) targets the immunoglobulin loci in activated B cells and creates DNA mutations in the antigen-binding variable region and DNA breaks in the switch region through processes known, respectively, as somatic hypermutation and class switch recombination. AID deaminates cytosine to uracil in DNA to create a U:G mismatch. During somatic hypermutation, the MutSα complex binds to the mismatch, and the error-prone DNA polymerase η generates mutations at A and T bases. During class switch recombination, both MutSα and MutLα complexes bind to the mismatch, resulting in double-strand break formation and end-joining. This review is centered on the mechanisms of how the MMR pathway is commandeered by B cells to generate antibody diversity.



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The conserved molecular machinery in DNA mismatch repair enzyme structures

Publication date: Available online 2 December 2015
Source:DNA Repair
Author(s): Flora S. Groothuizen, Titia K. Sixma
The machinery of DNA mismatch repair enzymes is highly conserved in evolution. The process is initiated by recognition of a DNA mismatch, and validated by ATP and the presence of a processivity clamp or a methylation mark. Several events in MMR promote conformational changes that lead to progression of the repair process. Here we discuss functional conformational changes in the MMR proteins and we compare the enzymes to paralogs in other systems.



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DNA[NdW1] Mismatch Repair and the DNA Damage Response[NdW2]

Publication date: Available online 2 December 2015
Source:DNA Repair
Author(s): Zhongdao Li, Alexander H. Pearlman, Peggy Hsieh
This review discusses the role of DNA mismatch repair (MMR) in the DNA damage response (DDR) that triggers cell cycle arrest and, in some cases, apoptosis. Although the focus is on findings from mammalian cells, much has been learned from studies in other organisms including bacteria and yeast [1,2]. MMR promotes a DDR mediated by a key signaling kinase, ATM and Rad3-related (ATR), in response to various types of DNA damage including some encountered in widely used chemotherapy regimes. An introduction to the DDR mediated by ATR reveals its immense complexity and highlights the many biological and mechanistic questions that remain. Recent findings and future directions are highlighted.



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Mismatch binding, ADP-ATP exchange and intramolecular signaling during mismatch repair

Publication date: Available online 2 December 2015
Source:DNA Repair
Author(s): Manju M. Hingorani
The focus of this article is on the DNA binding and ATPase activities of the mismatch repair (MMR) protein, MutS—our current understanding of how this protein uses ATP to fuel its actions on DNA and initiate repair via interactions with MutL, the next protein in the pathway. Structure-function and kinetic studies have yielded detailed views of the MutS mechanism of action in MMR. How MutS and MutL work together after mismatch recognition to enable strand-specific nicking, which leads to strand excision and synthesis, is less clear and remains an active area of investigation.



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Roles for mismatch repair family proteins in promoting meiotic crossing over

Publication date: Available online 2 December 2015
Source:DNA Repair
Author(s): Carol M. Manhart, Eric Alani
The mismatch repair (MMR) family complexes Msh4-Msh5 and Mlh1-Mlh3 act with Exo1 and Sgs1-Top3-Rmi1 in a meiotic double strand break repair pathway that results in the asymmetric cleavage of double Holliday junctions (dHJ) to form crossovers. This review discusses how meiotic roles for Msh4-Msh5 and Mlh1-Mlh3 do not fit paradigms established for post-replicative MMR. We also outline models used to explain how these factors promote the formation of meiotic crossovers required for the accurate segregation of chromosome homologs during the Meiosis I division.



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Evolution of the methyl directed mismatch repair system in Escherichia coli

Publication date: Available online 2 December 2015
Source:DNA Repair
Author(s): Christopher D. Putnam
DNA mismatch repair (MMR) repairs mispaired bases in DNA generated by replication errors. MutS or MutS homologs recognize mispairs and coordinate with MutL or MutL homologs to direct excision of the newly synthesized DNA strand. In most organisms, the signal that discriminates between the newly synthesized and template DNA strands has not been definitively identified. In contrast, Escherichia coli and some related gammaproteobacteria use a highly elaborated methyl-directed MMR system that recognizes Dam methyltransferase modification sites that are transiently unmethylated on the newly synthesized strand after DNA replication. Evolution of methyl-directed MMR is characterized by the acquisition of Dam and the MutH nuclease and by the loss of the MutL endonuclease activity. Methyl-directed MMR is present in a subset of Gammaproteobacteria belonging to the orders Enterobacteriales, Pasteurellales, Vibrionales, Aeromonadales, and a subset of the Alteromonadales (the EPVAA group) as well as in gammaproteobacteria that have obtained these genes by horizontal gene transfer, including the medically relevant bacteria Fluoribacter,Legionella, and Tatlockia and the marine bacteria Methylophaga and Nitrosococcus.



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Targeting Mismatch Repair defects: a novel strategy for personalized cancer treatment

Publication date: Available online 2 December 2015
Source:DNA Repair
Author(s): Rumena Begum, Sarah A. Martin
The DNA Mismatch Repair (MMR) pathway is a fundamental cellular process required to repair mispaired bases introduced routinely during DNA replication. Given this critical role in the maintenance of genome stability, it is not surprising that underlying defects in the MMR pathway occur in both hereditary and sporadic cancers. Furthermore, the MMR status greatly influences the sensitivity of cells to many common chemotherapeutic agents. Therefore, novel strategies are being investigated to exploit the loss of MMR in these cancers and to identify personalized therapeutic strategies to target MMR deficient tumours. In this review, we describe recent advances in strategies to target MMR deficient tumours using a synthetic lethal approach. We discuss new ways to target mutations secondary to MMR deficiency and suggest potential new therapies to optimize treatment outcome. We highlight ongoing clinical studies focussing on novel ways of preventing and treating MMR deficient cancers.



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Non-canonical actions of mismatch repair

Publication date: Available online 2 December 2015
Source:DNA Repair
Author(s): Gray F. Crouse
At the heart of the mismatch repair (MMR) system are proteins that recognize mismatches in DNA. Such mismatches can be mispairs involving normal or damaged bases or insertion/deletion loops due to strand misalignment. When such mispairs are generated during replication or recombination, MMR will direct removal of an incorrectly paired base or block recombination between nonidentical sequences. However, when mispairs are recognized outside the context of replication, proper strand discrimination between old and new DNA is lost, and MMR can act randomly and mutagenically on mispaired DNA. Such non-canonical actions of MMR are important in somatic hypermutation and class switch recombination, expansion of triplet repeats, and potentially in mutations arising in nondividing cells. MMR involvement in damage recognition and signaling is complex, with the end result likely dependent on the amount of DNA damage in a cell.



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Endonuclease activities of MutLα and its homologs in DNA mismatch repair

Publication date: Available online 2 December 2015
Source:DNA Repair
Author(s): Lyudmila Y. Kadyrova, Farid A. Kadyrov
MutLα is a key component of the DNA mismatch repair system in eukaryotes. The DNA mismatch repair system has several genetic stabilization functions. Of these functions, DNA mismatch repair is a major one. The loss of MutLα abolishes DNA mismatch repair, thereby predisposing humans to cancer. MutLα has an endonuclease activity that is required for DNA mismatch repair. The endonuclease activity of MutLα depends on the DQHA(X)2E(X)4E motif which is a part of the active site of the nuclease. This motif is also present in many bacterial MutL and eukaryotic MutLγ proteins, DNA mismatch repair system factors that are homologous to MutLα. Recent studies have shown that yeast MutLγ and several MutL proteins containing the DQHA(X)2E(X)4E motif possess endonuclease activities. Here, we review the endonuclease activities of MutLα and its homologs in the context of DNA mismatch repair.



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7,12-Dimethylbenz(a)Anthracene-Induced Genotoxicity on Bone Marrow Cells from Mice Phenotypically Selected for Low Acute Inflammatory Response

Publication date: Available online 2 December 2015
Source:DNA Repair
Author(s): Iana Suly Santos Katz, Layra Lucy Albuquerque, Alessandra Paes Suppa, Graziela Batista da Silva, José Ricardo Jensen, Andrea Borrego, Solange Massa, Nancy Starobinas, Wafa Hanna Koury Cabrera, Marcelo De Franco, Primavera Borelli, Olga Martinez Ibañez, Orlando Garcia Ribeiro
Exposure to Polycyclic aromatic hydrocarbon (PAH) environmental contaminants has been associated with the development of mutations and cancer. 7,12-Dimethylbenz(a)Anthracene ( DMBA), a genotoxic agent, reacts with DNA directly, inducing p53-dependent cytotoxicity resulting in cell death by apoptosis or giving rise to cancer. DMBA metabolism largely depends on activation of the aryl hydrocarbon receptor (AhR). Mice phenotypically selected for high (AIRmax) or low (AIRmin) acute inflammatory response present a complete segregation of Ahr alleles endowed with low (Ahr^d) or high (Ahr^b1) affinity to PAHs, respectively. To evaluate the role of AhR genetic polymorphism on the bone marrow susceptibility to DMBA, AIRmax and AIRmin mice were treated with a single intraperitoneal injection of DMBA (50mg/kg b.w.) in olive oil. Bone marrow cells (BMCs) were phenotyped by both flow cytometry and cytoslide preparations. Despite a significant decrease in total cell count in BM from AIRmin mice, there was an increase of blast cells and immature neutrophils at 1 and 50 days after DMBA treatment, probably due to a cell-cycle blockade at the G1/S transition leading to immature stage cell production. A panel of proteins related to cell cycle regulation was evaluated in immature BM cells (Lin⁻) by Western Blot, and DNA damage and repair were measured using an alkaline version of the Comet assay. In Lin⁻ cells isolated from AIRmin mice, high levels were found in both p53 and p21 protein contents in contrast with the low levels of CDK4 and Ciclin D1. Evaluation of DNA repair in DMBA-treated BMCs, indicated long-lasting genotoxicity and cytotoxicity in BMC from AIRmin mice and a blockade of cell cycle progression. On the other hand, AIRmax mice have a high capacity of DNA damage repair and protection. These mechanisms can be associated with the differential susceptibility to the toxic and carcinogenic effects of DMBA observed in these mice.



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Patient satisfaction and non-UK educated nurses: a cross-sectional observational study of English National Health Service Hospitals

Objectives

To examine whether patient satisfaction with nursing care in National Health Service (NHS) hospitals in England is associated with the proportion of non-UK educated nurses providing care.

Design

Cross-sectional analysis using data from the 2010 NHS Adult Inpatient Survey merged with data from nurse and hospital administrator surveys. Logistic regression models with corrections for clustering were used to determine whether the proportions of non-UK educated nurses were significantly related to patient satisfaction before and after taking account of other hospital, nursing and patient characteristics.

Setting

31 English NHS trusts.

Participants

12 506 patients 16 years of age and older with at least one overnight stay that completed a satisfaction survey; 2962 bedside care nurses who completed a nurse survey; and 31 NHS trusts.

Main outcome measure

Patient satisfaction.

Results

The percentage of non-UK educated nurses providing bedside hospital care, which ranged from 1% to 52% of nurses, was significantly associated with patient satisfaction. After controlling for potential confounding factors, each 10-point increase in the percentage of non-UK educated nurses diminished the odds of patients reporting good or excellent care by 12% (OR=0.88), and decreased the odds of patients agreeing that they always had confidence and trust in nurses by 13% (OR=0.87). Other indicators of patient satisfaction also revealed lower satisfaction in hospitals with higher percentages of non-UK educated nurses.

Conclusions

Use of non-UK educated nurses in English NHS hospitals is associated with lower patient satisfaction. Importing nurses from abroad to substitute for domestically educated nurses may negatively impact quality of care.

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Depression and risk of hospitalisations and rehospitalisations for ambulatory care-sensitive conditions in Denmark: a population-based cohort study

Objective

Hospitalisations for ambulatory care-sensitive conditions (ACSCs), a group of chronic and acute illnesses considered not to require inpatient treatment if timely and appropriate ambulatory care is received, and early rehospitalisations are common and costly. We sought to determine whether individuals with depression are at increased risk of hospitalisations for ACSCs, and rehospitalisation for the same or another ACSC, within 30 days.

Design

National, population-based cohort study.

Setting

Denmark.

Participants

5 049 353 individuals ≥18 years of age between 1 January 2005 and 31 December 2013.

Measurements

Depression was ascertained via psychiatrist diagnoses in the Danish Psychiatric Central Register or antidepressant prescription redemption from the Danish National Prescription Registry. Hospitalisations for ACSCs and rehospitalisations within 30 days were identified using the Danish National Patient Register.

Results

Overall, individuals with depression were 2.35 times more likely to be hospitalised for an ACSC (95% CI 2.32 to 2.37) versus those without depression after adjusting for age, sex and calendar period, and 1.45 times more likely after adjusting for socioeconomic factors, comorbidities and primary care utilisation (95% CI 1.43 to 1.46). After adjusting for ACSC-predisposing comorbidity, depression was associated with significantly greater risk of hospitalisations for all chronic (eg, angina, diabetes complications, congestive heart failure exacerbation) and acute ACSCs (eg, pneumonia) compared to those without depression. Compared to those without depression, persons with depression were 1.21 times more likely to be rehospitalised within 30 days for the same ACSC (95% CI 1.18 to 1.24) and 1.19 times more likely to be rehospitalised within 30 days for a different ACSC (95% CI 1.15 to 1.23).

Conclusions

Individuals with depression are at increased risk of hospitalisations for ACSCs, and once discharged are at elevated risk of rehospitalisations within 30 days for ACSCs.

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Risk factors for hospital admission in the 28 days following a community-acquired pneumonia diagnosis in older adults, and their contribution to increasing hospitalisation rates over time: a cohort study

Objectives

To determine factors associated with hospitalisation after community-acquired pneumonia (CAP) among older adults in England, and to investigate how these factors have contributed to increasing hospitalisations over time.

Design

Cohort study.

Setting

Primary and secondary care in England.

Population

39 211 individuals from the Clinical Practice Research Datalink, who were eligible for linkage to Hospital Episode Statistics and mortality data, were aged ≥65 and had at least 1 CAP episode between April 1998 and March 2011.

Main outcome measures

The association between hospitalisation within 28 days of CAP diagnosis (a 'post-CAP' hospitalisation) and a wide range of comorbidities, frailty factors, medications and vaccinations. We examined the role of these factors in post-CAP hospitalisation trends. We also looked at trends in post-CAP mortality and length of hospitalisation over the study period.

Results

14 comorbidities, 5 frailty factors and 4 medications/vaccinations were associated with hospitalisation (of 18, 12 and 7 considered, respectively). Factors such as chronic lung disease, severe renal disease and diabetes were associated with increased likelihood of hospitalisation, whereas factors such as recent influenza vaccination and a recent antibiotic prescription decreased the odds of hospitalisation. Despite adjusting for these and other factors, the average predicted probability of hospitalisation after CAP rose markedly from 57% (1998–2000) to 86% (2009–2010). Duration of hospitalisation and 28-day mortality decreased over the study period.

Conclusions

The risk factors we describe enable identification of patients at increased likelihood of post-CAP hospitalisation and thus in need of proactive case management. Our analyses also provide evidence that while comorbidities and frailty factors contributed to increasing post-CAP hospitalisations in recent years, the trend appears to be largely driven by changes in service provision and patient behaviour.

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Conformational dynamics of stem II of the U2 snRNA [ARTICLE]

The spliceosome undergoes dramatic changes in both small nuclear RNA (snRNA) composition and structure during assembly and pre-mRNA splicing. It has been previously proposed that the U2 snRNA adopts two conformations within the stem II region: stem IIa or stem IIc. Dynamic rearrangement of stem IIa into IIc and vice versa is necessary for proper progression of the spliceosome through assembly and catalysis. How this conformational transition is regulated is unclear; although, proteins such as Cus2p and the helicase Prp5p have been implicated in this process. We have used single-molecule Förster resonance energy transfer (smFRET) to study U2 stem II toggling between stem IIa and IIc. Structural interconversion of the RNA was spontaneous and did not require the presence of a helicase; however, both Mg²⁺ and Cus2p promote formation of stem IIa. Destabilization of stem IIa by a G53A mutation in the RNA promotes stem IIc formation and inhibits conformational switching of the RNA by both Mg²⁺ and Cus2p. Transitioning to stem IIa can be restored using Cus2p mutations that suppress G53A phenotypes in vivo. We propose that during spliceosome assembly, Cus2p and Mg²⁺ may work together to promote stem IIa formation. During catalysis the spliceosome could then toggle stem II with the aid of Mg²⁺ or with the use of functionally equivalent protein interactions. As noted in previous studies, the Mg²⁺ toggling we observe parallels previous observations of U2/U6 and Prp8p RNase H domain Mg²⁺-dependent conformational changes. Together these data suggest that multiple components of the spliceosome may have evolved to switch between conformations corresponding to open or closed active sites with the aid of metal and protein cofactors.

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Remote Sensing, Vol. 7, Pages 16108-16130: Correction of Interferometric and Vegetation Biases in the SRTMGL1 Spaceborne DEM with Hydrological Conditioning towards Improved Hydrodynamics Modeling in the Amazon Basin

In the Amazon basin, the recently released SRTM Global 1 arc-second (SRTMGL1) remains the best topographic information for hydrological and hydrodynamic modeling purposes. However, its accuracy is hindered by errors, partly due to vegetation, leading to erroneous simulations. Previous efforts to remove the vegetation signal either did not account for its spatial variability or relied on a single assumed percentage of penetration of the SRTM signal. Here, we propose a systematic approach over an Amazonian floodplain to remove the vegetation signal, addressing its heterogeneity by combining estimates of vegetation height and a land cover map. We improve this approach by interpolating the first results with drainage network, field and altimetry data to obtain a hydrological conditioned DEM. The averaged interferometric and vegetation biases over the forest zone were found to be −2.0 m and 7.4 m, respectively. Comparing the original and corrected DEM, vertical validation against Ground Control Points shows a RMSE reduction of 64%. Flood extent accuracy, controlled against Landsat and JERS-1 images, stresses improvements in low and high water periods (+24% and +18%, respectively). This study also highlights that a ground truth drainage network, as a unique input during the interpolation, achieves reasonable results in terms of flood extent and hydrological characteristics.

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Materials, Vol. 8, Pages 8279-8291: Polypropylene/Short Glass Fibers Composites: Effects of Coupling Agents on Mechanical Properties, Thermal Behaviors, and Morphology

This study uses the melt compounding method to produce polypropylene (PP)/short glass fibers (SGF) composites. PP serves as matrix while SGF serves as reinforcement. Two coupling agents, maleic anhydride grafted polypropylene, (PP-g-MA) and maleic anhydride grafted styrene-ethylene-butylene-styrene block copolymer (SEBS-g-MA) are incorporated in the PP/SGF composites during the compounding process, in order to improve the interfacial adhesion and create diverse desired properties of the composites. According to the mechanical property evaluations, increasing PP-g-MA as a coupling agent provides the composites with higher tensile, flexural, and impact properties. In contrast, increasing SEBS-g-MA as a coupling agent provides the composites with decreasing tensile and flexural strengths, but also increasing impact strength. The DSC results indicate that using either PP-g-MA or SEBS-g-MA as the coupling agent increases the crystallization temperature. However, the melting temperature of PP barely changes. The spherulitic morphology results show that PP has a smaller spherulite size when it is processed with PP-g-MA or SEBS-g-MA as the coupling agent. The SEM results indicate that SGF is evenly distributed in PP matrices, but there are distinct voids between these two materials, indicating a poor interfacial adhesion. After PP-g-MA or SEBS-g-MA is incorporated, SGF can be encapsulated by PP, and the voids between them are fewer and indistinctive. This indicates that the coupling agents can effectively improve the interfacial compatibility between PP and SGF, and as a result improves the diverse properties of PP/SGF composites.

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Nutrients, Vol. 7, Pages 10053-10064: Copper-2 Ingestion, Plus Increased Meat Eating Leading to Increased Copper Absorption, Are Major Factors Behind the Current Epidemic of Alzheimer’s Disease

It has become clear that copper toxicity is playing a major role in Alzheimer's disease; but why is the brain copper toxicity with cognition loss in Alzheimer's disease so much different clinically than brain copper toxicity in Wilson's disease, which results in a movement disorder? Furthermore, why is the inorganic copper of supplement pills and in drinking water so much more damaging to cognition than the organic copper in food? A recent paper, which shows that almost all food copper is copper-1, that is the copper-2 of foods reverts to the reduced copper-1 form at death or harvest, gives new insight into these questions. The body has an intestinal transport system for copper-1, Ctr1, which channels copper-1 through the liver and into safe channels. Ctr1 cannot absorb copper-2, and some copper-2 bypasses the liver, ends up in the blood quickly, and is toxic to cognition. Humans evolved to handle copper-1 safely, but not copper-2. Alzheimer's is at least in part, a copper-2 toxicity disease, while Wilson's is a general copper overload disease. In this review, we will show that the epidemiology of the Alzheimer's epidemic occurring in developed, but not undeveloped countries, fits with the epidemiology of exposure to copper-2 ingestion leached from copper plumbing and from copper supplement pill ingestion. Increased meat eating in developed countries is also a factor, because it increases copper absorption, and thus over all copper exposure.

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Materials, Vol. 8, Pages 8292-8303: Microstructural Changes Due to Alkali-Silica Reaction during Standard Mortar Test

The microstructural development of mortar bars with silica glass aggregate undergoing alkali-silica reaction (ASR) under the conditions of American Society for Testing and Materials (ASTM) Standard Test C1260 was analyzed using scanning electron microscopy and qualitative X-ray microanalysis. Cracking in the aggregate, the hydrated paste, and the paste-aggregate interface was important in the development of the microstructure. Cracks were characterized according to their location, their relationship to other cracks, and whether they are filled with ASR gel. Expansion of the bars was approximately 1% at 12 days and 2% at 53 days. They fell apart by 63 days. The bars contained two zones, an inner region that was undergoing ASR and an outer and much more highly damaged zone that extended further inward over time. Evidence of ASR was present even during the period when specimens were immersed in water, prior to immersion in NaOH solution.

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Nutrients, Vol. 7, Pages 10076-10088: Processed Food Contributions to Energy and Nutrient Intake Differ among US Children by Race/Ethnicity

This study determined and compared the mean daily intake of energy and nutrients from processed foods by level of processing (minimally processed; processed for preservation, nutrient enhancement, and freshness; mixtures of combined ingredients; ready-to-eat processed foods; and prepared foods/meals) among non-Hispanic white, non-Hispanic black, and Mexican American US children. Data from participants 2–18 years old (n = 10,298) of the nationally representative cross-sectional National Health and Nutrition Examination Survey 2003–2008 with a complete one day, 24-h dietary recall were used to determine mean intake of energy and nutrients recommended for increase and decrease, as per the 2010 Dietary Guidelines for Americans, among child race/ethnic groups by category of food processing. Regression analysis was used to estimate and compare covariate-adjusted (gender, age, and poverty-income-level) least square means (p < 0.05/3 race/ethnic groups). All children, regardless of race or ethnicity consumed processed foods. Approximately 66% to 84% of total daily energy, saturated fat, cholesterol, fiber, total sugar, added sugars, calcium, vitamin D, potassium, and sodium intake are contributed by one of the five categories of processed foods. Clinicians and policy should primarily advise consideration of the energy and nutrient composition of foods, rather than the processing level, when selecting a healthy diet for children.

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Sustainability, Vol. 7, Pages 15967-15981: AMF Inoculation Enhances Growth and Improves the Nutrient Uptake Rates of Transplanted, Salt-Stressed Tomato Seedlings

The study aimed to investigate the effects of commercially available AMF inoculate (Glomus sp. mixture) on the growth and the nutrient acquisition in tomato (Solanumlycopersicum L.) plants directly after transplanting and under different levels of salinity. Inoculated (AMF+) and non-inoculated (AMF−) tomato plants were subjected to three levels of NaCl salinity (0, 50, and 100 mM·NaCl). Seven days after transplanting, plants were analyzed for dry matter and RGR of whole plants and root systems. Leaf tissue was analyzed for mineral concentration before and after transplanting; leaf nutrient content and relative uptake rates (RUR) were calculated. AMF inoculation did not affect plant dry matter or RGR under fresh water-irrigation. The growth rate of AMF−plants did significantly decline under both moderate (77%) and severe (61%) salt stress compared to the fresh water-irrigated controls, while the decline was much less (88% and 75%,respectively)and statistically non-significant in salt-stressed AMF+ plants. Interestingly, root system dry matter of AMF+ plants (0.098 g plant–1) remained significantly greater under severe soil salinity compared to non-inoculated seedlings (0.082 g plant–1). The relative uptake rates of N, P, Mg, Ca, Mn, and Fe were enhanced in inoculated tomato seedlings and remained higher under (moderate) salt stress compared to AMF− plants This study suggests that inoculation with commercial AMF during nursery establishment contributes to alleviation of salt stress by maintaining a favorable nutrient profile. Therefore, nursery inoculation seems to be a viable solution to attenuate the effects of increasing soil salinity levels, especially in greenhouses with low natural abundance of AMF spores.

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Nutrients, Vol. 7, Pages 10032-10052: Concord Grape Juice Polyphenols and Cardiovascular Risk Factors: Dose-Response Relationships

Pure fruit juices provide nutritional value with evidence suggesting some of their benefits on biomarkers of cardiovascular disease risk may be derived from their constituent polyphenols, particularly flavonoids. However, few data from clinical trials are available on the dose-response relationship of fruit juice flavonoids to these outcomes. Utilizing the results of clinical trials testing single doses, we have analyzed data from studies of 100% Concord grape juice by placing its flavonoid content in the context of results from randomized clinical trials of other polyphenol-rich foods and beverages describing the same outcomes but covering a broader range of intake. We selected established biomarkers determined by similar methods for measuring flow-mediated vasodilation (FMD), blood pressure, platelet aggregation, and the resistance of low density lipoprotein cholesterol (LDL) to oxidation. Despite differences among the clinical trials in the treatment, subjects, and duration, correlations were observed between the dose and FMD. Inverse dose-response relationships, albeit with lower correlation coefficients, were also noted for the other outcomes. These results suggest a clear relationship between consumption of even modest serving sizes of Concord grape juice, flavonoid intake, and effects on risk factors for cardiovascular disease. This approach to dose-response relationships may prove useful for testing other individual foods and beverages.

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Nutrients, Vol. 7, Pages 9931-9945: A Randomized Controlled Trial Investigating the Effects of a Special Extract of Bacopa monnieri (CDRI 08) on Hyperactivity and Inattention in Male Children and Adolescents: BACHI Study Protocol (ANZCTRN12612000827831)

Clinical diagnoses of Attention Deficit Hyperactivity Disorder (ADHD) and the use of prescription medications for its treatment have increased in recent years. Current treatments may involve the administration of amphetamine-type substances, a treatment path many parents are apprehensive to take. Therefore, alternative pharmacological treatments are required. Few nutritional or pharmacological alternatives that reduce ADHD associated symptoms (hyperactivity and inattention) have been subjected to rigorous clinical trials. Bacopa monnieri is a perennial creeping herb. CDRI 08 is a special extract of Bacopa monnieri which has been subjected to hundreds of scientific studies and has been shown in human randomized controlled trials (RCTs) to improve memory, attention, and mood. It is hypothesised that chronic administration of CDRI 08 will improve attention, concentration and behaviour in children with high levels of hyperactivity and/or inattention. This paper reports the protocol for the first 16-week, randomized, placebo-controlled, double-blind, parallel groups trial examining the efficacy and safety of CDRI 08 in male children aged 6–14 years with high levels of inattention and hyperactivity. The primary outcome variable will be the level of hyperactivity and inattention measured by the Conners' Parent Rating Scale (CPRS). Secondary outcome variables include cognition, mood, sleep, and EEG. Trial registration: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000827831.

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Remote Sensing, Vol. 7, Pages 16091-16107: Object-Based Crop Classification with Landsat-MODIS Enhanced Time-Series Data

Cropland mapping via remote sensing can provide crucial information for agri-ecological studies. Time series of remote sensing imagery is particularly useful for agricultural land classification. This study investigated the synergistic use of feature selection, Object-Based Image Analysis (OBIA) segmentation and decision tree classification for cropland mapping using a finer temporal-resolution Landsat-MODIS Enhanced time series in 2007. The enhanced time series extracted 26 layers of Normalized Difference Vegetation Index (NDVI) and five NDVI Time Series Indices (TSI) in a subset of agricultural land of Southwest Missouri. A feature selection procedure using the Stepwise Discriminant Analysis (SDA) was performed, and 10 optimal features were selected as input data for OBIA segmentation, with an optimal scale parameter obtained by quantification assessment of topological and geometric object differences. Using the segmented metrics in a decision tree classifier, an overall classification accuracy of 90.87% was achieved. Our study highlights the advantage of OBIA segmentation and classification in reducing noise from in-field heterogeneity and spectral variation. The crop classification map produced at 30 m resolution provides spatial distributions of annual and perennial crops, which are valuable for agricultural monitoring and environmental assessment studies.

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Nutrients, Vol. 7, Pages 10020-10031: Gliadin-Specific T-Cells Mobilized in the Peripheral Blood of Coeliac Patients by Short Oral Gluten Challenge: Clinical Applications

Celiac disease (CD) is a common lifelong food intolerance triggered by dietary gluten affecting 1% of the general population. Gliadin-specific T-cell lines and T-cell clones obtained from intestinal biopsies have provided great support in the investigation of immuno-pathogenesis of CD. In the early 2000 a new in vivo, less invasive, approach was established aimed to evaluate the adaptive gliadin-specific T-cell response in peripheral blood of celiac patients on a gluten free diet. In fact, it has been demonstrated that three days of ingestion of wheat-containing food induces the mobilization of memory T lymphocytes reactive against gliadin from gut-associated lymphoid tissue into peripheral blood of CD patients. Such antigen-specific T-cells releasing interferon-γ can be transiently detected by using the enzyme-linked immunospot (ELISPOT) assays or by flow cytometry tetramer technology. This paper discusses the suitability of this in vivo tool to investigate the repertoire of gluten pathogenic peptides, to support CD diagnosis, and to assess the efficacy of novel therapeutic strategies. A systematic review of all potential applications of short oral gluten challenge is provided.

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Remote Sensing, Vol. 7, Pages 16062-16090: Building a Data Set over 12 Globally Distributed Sites to Support the Development of Agriculture Monitoring Applications with Sentinel-2

Developing better agricultural monitoring capabilities based on Earth Observation data is critical for strengthening food production information and market transparency. The Sentinel-2 mission has the optimal capacity for regional to global agriculture monitoring in terms of resolution (10–20 meter), revisit frequency (five days) and coverage (global). In this context, the European Space Agency launched in 2014 the "Sentinel­2 for Agriculture" project, which aims to prepare the exploitation of Sentinel-2 data for agriculture monitoring through the development of open source processing chains for relevant products. The project generated an unprecedented dataset, made of "Sentinel-2 like" time series and in situ data acquired in 2013 over 12 globally distributed sites. Earth Observation time series were mostly built on the SPOT4 (Take 5) data set, which was specifically designed to simulate Sentinel-2. They also included Landsat 8 and RapidEye imagery as complementary data sources. Images were pre-processed to Level 2A and the quality of the resulting time series was assessed. In situ data about cropland, crop type and biophysical variables were shared by site managers, most of them belonging to the "Joint Experiment for Crop Assessment and Monitoring" network. This data set allowed testing and comparing across sites the methodologies that will be at the core of the future "Sentinel­2 for Agriculture" system.

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Nutrients, Vol. 7, Pages 9972-9984: High Prevalence of Vitamin D Deficiency in Infertile Women Referring for Assisted Reproduction

A comprehensive analysis of the vitamin D status of infertile women is the first step in understanding hypovitaminosis impact on reproductive potential. We sought to determine vitamin D profiles of women attending an infertility center and to investigate non-dietary determinants of vitamin D status in this population. In this cross-sectional analysis, a cohort of 1072 women (mean age ± standard deviation 36.3 ± 4.4 years) attending an academic infertility center was used to examine serum 25-hydroxy-vitamin D (25(OH)D) levels in relation to demographic characteristics, seasons and general health risk factors. Both unadjusted and adjusted levels of serum 25(OH)D were examined. Median 25(OH)D concentration was below 30 ng/mL for 89% of the entire year. Over the whole year, 6.5% of patients had 25(OH)D levels ≤10 ng/mL, 40.1% ≤20 ng/mL, and 77.4% ≤30 ng/mL. Global solar radiation was weakly correlated with 25(OH)D levels. At multivariable analysis, 25(OH)D levels were inversely associated with BMI; conversely, 25(OH)D levels were positively associated with height and endometriosis history. Serum 25(OH)D levels are highly deficient in women seeking medical help for couple's infertility. Levels are significantly associated with body composition, seasonal modifications and causes of infertility. Importantly, this deficiency status may last during pregnancy with more severe consequences.

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Nutrients, Vol. 7, Pages 9960-9971: An Assessment of the Potential Impact of Fortification of Staples and Condiments on Micronutrient Intake of Young Children and Women of Reproductive Age in Bangladesh

Bangladesh has experienced rapid economic growth and achieved major health improvements in the past decade, but malnutrition rates remain high. A nationally representative study conducted in 2011 assessed the dietary habits of 841 children 24–59 months old; 1428 children 6–14 years old; and 1412 non-pregnant, non-lactating women. The study's objective was to assess dietary intakes of key micronutrients and the consumption pattern of potentially fortifiable foods, and then to model the potential impact of fortification of key staple foods. The current intakes of several micronutrients, namely, iron, zinc, folate, vitamin A and vitamin B12, were found to be insufficient to meet the needs of Bangladesh's children and women. The fortification of rice with iron and zinc and edible oil with vitamin A has the potential to fill a significant part of the nutrient gap, as these are consumed widely and in significant amounts. Wheat flour and sugar are not as promising food vehicles in the Bangladeshi context, as they were consumed by a smaller portion of the population and in smaller amounts. In conclusion, fortification of rice and oil is recommended to address the large gap in micronutrient intakes.

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Materials, Vol. 8, Pages 8169-8182: Electrical Properties and Interfacial Studies of HfxTi1–xO2 High Permittivity Gate Insulators Deposited on Germanium Substrates

In this research, the hafnium titanate oxide thin films, TixHf1–xO2, with titanium contents of x = 0, 0.25, 0.9, and 1 were deposited on germanium substrates by atomic layer deposition (ALD) at 300 °C. The approximate deposition rates of 0.2 Å and 0.17 Å per cycle were obtained for titanium oxide and hafnium oxide, respectively. X-ray Photoelectron Spectroscopy (XPS) indicates the formation of GeOx and germanate at the interface. X-ray diffraction (XRD) indicates that all the thin films remain amorphous for this deposition condition. The surface roughness was analyzed using an atomic force microscope (AFM) for each sample. The electrical characterization shows very low hysteresis between ramp up and ramp down of the Capacitance-Voltage (CV) and the curves are indicative of low trap densities. A relatively large leakage current is observed and the lowest leakage current among the four samples is about 1 mA/cm2 at a bias of 0.5 V for a Ti0.9Hf0.1O2 sample. The large leakage current is partially attributed to the deterioration of the interface between Ge and TixHf1–xO2 caused by the oxidation source from HfO2. Consideration of the energy band diagrams for the different materials systems also provides a possible explanation for the observed leakage current behavior.

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Materials, Vol. 8, Pages 8183-8194: The Effect of Niobium Doping on the Electrical Properties of 0.4(Bi0.5K0.5)TiO3-0.6BiFeO3 Lead-Free Piezoelectric Ceramics

Ceramics in the system (Bi0.5K0.5)TiO3-BiFeO3 have good electromechanical properties and temperature stability. However, the high conductivity inherent in BiFeO3-based ceramics complicates measurement of the ferroelectric properties. In the present work, doping with niobium (Nb) is carried out to reduce the conductivity of (Bi0.5K0.5)TiO3-BiFeO3. Powders of composition 0.4(K0.5Bi0.5)Ti1−xNbxO3-0.6BiFe1−xNbxO3 (x = 0, 0.01 and 0.03) are prepared by the mixed oxide method and sintered at 1050 °C for 1 h. The effect of Nb doping on the structure is examined by X-ray diffraction. The microstructure is examined by scanning electron microscopy. The variation in relative permittivity with temperature is measured using an impedance analyzer. Ferroelectric properties are measured at room temperature using a Sawyer Tower circuit. Piezoelectric properties are measured using a d33 meter and a contact type displacement sensor. All the samples have high density, a rhombohedral unit cell and equiaxed, micron-sized grains. All the samples show relaxor-like behavior. Nb doping causes a reduction in conductivity by one to two orders of magnitude at 200 °C. The samples have narrow P-E loops reminiscent of a linear dielectric. The samples all possess bipolar butterfly S-E loops characteristic of a classic ferroelectric material. Nb doping causes a decrease in d33 and Smax/Emax.

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Materials, Vol. 8, Pages 8195-8245: Elastic Properties and Enhanced Piezoelectric Response at Morphotropic Phase Boundaries

The search for improved piezoelectric materials is based on the morphotropic phase boundaries (MPB) between ferroelectric phases with different crystal symmetry and available directions for the spontaneous polarization. Such regions of the composition x − T phase diagrams provide the conditions for minimal anisotropy with respect to the direction of the polarization, so that the polarization can easily rotate maintaining a substantial magnitude, while the near verticality of the TMPB(x) boundary extends the temperature range of the resulting enhanced piezoelectricity. Another consequence of the quasi-isotropy of the free energy is a reduction of the domain walls energies, with consequent formation of domain structures down to nanoscale. Disentangling the extrinsic and intrinsic contributions to the piezoelectricity in such conditions requires a high level of sophistication from the techniques and analyses for studying the structural, ferroelectric and dielectric properties. The elastic characterization is extremely useful in clarifying the phenomenology and mechanisms related to ferroelectric MPBs. The relationship between dielectric, elastic and piezoelectric responses is introduced in terms of relaxation of defects with electric dipole and elastic quadrupole, and extended to the response near phase transitions in the framework of the Landau theory. An account is provided of the anelastic experiments, from torsional pendulum to Brillouin scattering, that provided new important information on ferroelectric MPBs, including PZT, PMN-PT, NBT-BT, BCTZ, and KNN-based systems.

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Materials, Vol. 8, Pages 8148-8168: Physical Characteristics of Medical Textile Prostheses Designed for Hernia Repair: A Comprehensive Analysis of Select Commercial Devices

Inguinal hernia repairs are among the most frequent operations performed worldwide. This study aims to provide further understanding of structural characteristics of hernia prostheses, and better comprehensive evaluation. Weight, porosity, pore size and other physical characteristics were evaluated; warp knitting structures were thoroughly discussed. Two methods referring to ISO 7198:1998, i.e., weight method and area method, were employed to calculate porosity. Porosity ranged from 37.3% to 69.7% measured by the area method, and 81.1% to 89.6% by the weight method. Devices with two-guide bar structures displayed both higher porosity (57.7%–69.7%) and effective porosity (30.8%–60.1%) than single-guide bar structure (37.3%–62.4% and 0%–5.9%, respectively). Filament diameter, stitch density and loop structure combined determined the thickness, weight and characteristics of pores. They must be well designed to avoid zero effective porosity regarding a single-bar structure. The area method was more effective in characterizing flat sheet meshes while the weight method was perhaps more accurate in describing stereoscopic void space for 3D structure devices. This article will give instructive clues for engineers to improve mesh structures, and better understanding of warp knitting meshes for surgeons.

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Development of a high-yield reassortant influenza vaccine virus derived from the A/Anhui/1/2013 (H7N9) strain

Publication date: Available online 1 December 2015
Source:Vaccine
Author(s): Kazuya Nakamura, Masayuki Shirakura, Yasushi Suzuki, Tadasuke Naito, Seiichiro Fujisaki, Masato Tashiro, Eri Nobusawa
In April 2013, the first three fatal cases of human infection with an avian influenza A virus (H7N9) were reported in China. Because of a pandemic threat by this virus, we have commenced to develop candidate vaccine viruses (CVVs). Three 6:2 genetic reassortant viruses with different hemagglutinin (HA) sequences, NIIDRG-10, -10.1 and -10.2, were generated by a reverse genetics technique between the high egg-growth master virus, A/Puerto Rico/8/34 (H1N1) and A/Anhui/1/2013 (H7N9), kindly provided by the Chinese Center for Disease Control and Prevention. The different HA gene sequences of the three CVVs were derived from the original virus stock. NIIDRG-10 possesses HA, whose sequence is identical to that of the original A/Anhui/1/2013 (H7N9) in the Global Initiative on Sharing Avian Influenza Data (EPI439507), while NIIDRG-10.1 and -10.2 possess amino acid differences, A125T and N123D/N149D, respectively, compared with NIIDRG-10. NIIDRG-10 replicated in embryonated chicken eggs with low hemagglutination titer 128, whereas NIIDRG-10.1 and -10.2 grew well with hemagglutination titer 1024. These viruses reacted well with a ferret antiserum raised against the original A/Anhui/1/2013 virus. Ferret antiserum against NIIDRG-10.1 reacted well with A/Anhui/1/2013 similar to the homologous virus NIIDRG-10.1. These results indicated that NIIDRG-10.1 passed the two-way test of antigenic identity. In contrast, the ferret antiserum against NIIDRG-10.2 reacted with A/Anhui/1/2013 at an 8-fold lower hemagglutination inhibition titer than with the homologous virus NIIDRG-10.2, indicating an antigenic change. The total and HA protein yields of NIIDRG-10.1 were 14.7 and 6.9μg/ml, respectively, similar to those levels of high-yield seed viruses of seasonal influenza vaccines. NIIDRG-10.1 was approved as one of the CVVs for H7N9 viruses by the WHO in 2013. The candidate vaccine derived from NIIDRG-10.1 is currently being evaluated in a phase II clinical study in Japan.



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Editorial Board/Aims and Scope

Publication date: 27 November 2015
Source:Vaccine, Volume 33, Issue 48





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What is the responsibility of national government with respect to vaccination?

Publication date: 27 November 2015
Source:Vaccine, Volume 33, Issue 48
Author(s): Ronald de Groot




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What is the responsibility of national government with respect to vaccination? Response of Marcel F. Verweij and Hans Houweling to Ronald de Groot

Publication date: 27 November 2015
Source:Vaccine, Volume 33, Issue 48
Author(s): Hans Houweling, Marcel F. Verweij




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The case for ILI surveillance

Publication date: 27 November 2015
Source:Vaccine, Volume 33, Issue 48
Author(s): Beverley J. Paterson, David N. Durrheim




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Usage of quadrivalent influenza vaccine among children in the United States, 2013–14

Publication date: 27 November 2015
Source:Vaccine, Volume 33, Issue 48
Author(s): Loren Rodgers, Laura J. Pabst, Liping Zhu, Sandra S. Chaves
Annual influenza vaccination is recommended for everyone ≥6 months in the U.S. During the 2013–14 influenza season, in addition to trivalent influenza vaccines, quadrivalent vaccines were available, protecting against two influenza A and two influenza B viruses. We analyzed 1,976,443 immunization records from six sentinel sites to compare influenza vaccine usage among children age 6 months–18 years. A total of 983,401 (49.8%) influenza vaccine doses administered were trivalent and 920,333 (46.6%) were quadrivalent (unknown type: 72,709). Quadrivalent vaccine administration varied by age and was least frequent among those <2 years of age.



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Canine distemper and endangered wildlife: Is it time for mandatory vaccination of dogs?

Publication date: 27 November 2015
Source:Vaccine, Volume 33, Issue 48
Author(s): Daria Di Sabatino, Giovanni Savini, Alessio Lorusso




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New diaphragms grown from stem cells offer hope of a cure for common birth defect and possibly future repairs of the heart

An international collaboration between scientists in Sweden, Russia, and the United States has resulted in the successful engineering of new diaphragm tissue in rats using a mixture of stem cells and a 3D scaffold. When transplanted, it has regrown with the same complex mechanical properties of diaphragm muscle. The study is published in the journal Biomaterials, and offers hope of a cure for a common birth defect and possible future heart muscle repairs. The multidisciplinary team behind the current study includes world-renowned researchers in the field of regenerative medicine and tissue engineering; Paolo Macchiarini, MD, PhD, Director of the Advanced Center for Regenerative Medicine and senior scientist at Karolinska Institutet; Doris Taylor, PhD, Regenerative Medicine Research Director at the Texas Heart Institute; and Mark Holterman, MD, PhD, Professor of Surgery and Pediatrics at the University of Illinois College of Medicine in Peoria, working in collaboration with a research team at the Kuban State Medical University in Russia.  The diaphragm is a sheet of muscle that has to contract and relax constantly to allow breathing. It is also important in swallowing, and acts as a barrier between the chest cavity and the abdomen. Malformations or holes in the diaphragm are found in 1 in 2,500 babies and can cause extreme, often fatal, symptoms.    At the moment, surgical repair of large defects like these involves using an artificial patch, which will not grow with the infant and does not provide any contraction to assist with breathing. The new technique presented in Biomaterials could instead allow such replacements to be grown especially for babies from their own cells, which would provide all the function of diaphragm tissue and would grow with them.   The success of this study also offers hope for the possibility of regenerating heart tissue, which undergoes similar pressure as it contracts and relaxes with every beat.    "So far, attempts to grow and transplant such new tissues have been conducted in the relatively simple organs of the bladder, windpipe and esophagus. The diaphragm, with its need for constant muscle contraction and relaxation puts complex demands on any 3D scaffold; until now, no one knew whether it would be possible to engineer," said Dr. Doris Taylor.  Dr. Paolo Macchiarini adds, "This bioengineered muscle tissue is a truly exciting step in our journey towards regenerating whole and complex organs. You can see the muscle contracting and doing its job as well as any naturally-grown tissue - there can be no argument that these replacements are truly regenerated, and the possibilities that this opens up for the future are enormous."  The field of tissue engineering involves 'growing' new tissues or organs from stem cells on three dimensional 'scaffolds,' which give both structural support and shape to the new tissue and guide the differentiation and proliferation of the stem cells.  Engineered new tissues can not only help patients avoid the need for an organ donation, but also the need for the recipient to take immunosuppressant drugs.  In the current study, the researchers took diaphragm tissue from donor rats and removed all the living cells from it using a series of chemical treatments. This process removes anything that might cause an immune response in the recipient animals, while keeping all the connective tissue – or extracellular matrix – which gives tissues their structure and mechanical properties. When tested in vitro, these diaphragm scaffolds at first appeared to have lost their important rubber-like ability to be continually stretched and contracted for long periods of time. However, once seeded with bone marrow derived alloegenic stem cells and then transplanted into the animals, the diaphragm scaffolds began to function as well as undamaged organs. The method must now be tested on larger animals before it can be tried in humans, but the hope is that tissue-engineered repairs for congenital diaphragm malformations will be at least as effective as current surgical options with the added benefit of growing with children throughout their lives.   The study was supported and financed by Bioengineering of Tracheal Tissue and the Government of the Russian Federation Grant. Publication Orthotopic transplantation of a tissue engineered diaphragm in rats. Gubareva E, Sjöqvist S, Gilevich I, Sotnichenko A, Kuevda E, Lim M, et al Biomaterials 2015 Nov;77():320-335 About the universities Kuban State Medical University Texas Heart® Institute University of Illinois College of Medicine in Peoria (UICOMP)

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PTSD reveals imbalance between signalling systems in the brain

Experiencing a traumatic event can cause life-long anxiety problems, called posttraumatic stress disorder. Researchers from Uppsala University and Karolinska Institutet now show that people with posttraumatic stress disorder, PTSD, have an imbalance between two neurochemical systems in the brain, serotonin and substance P. The greater the imbalance, the more serious the symptoms patients have. Many people experience traumatic events in life, e.g. robbery, warfare, a serious accident or sexual assault. Approximately 10 percent of people subjected to trauma suffer long-lasting symptoms in the form of disturbing flashbacks, insomnia, hyperarousal and anxiety. If these problems lead to impairment, the person is said to suffer from PTSD. It has previously been shown that people with PTSD have altered brain anatomy and function. The current study, which is being published in the journal Molecular Psychiatry, shows that shows that people with PTSD have an imbalance between two neurochemical signalling systems of the brain, serotonin and substance P. By using a PET scanner, researchers were able to measure the relationship between these systems. Design improved treatments The study also shows that it is the imbalance between the two signalling systems which determines the severity of the symptoms suffered by the individual rather than the degree of change in a single system. Others have previously speculated that the biological basis of psychiatric disorders such as PTSD includes a shift in the balance between different signalling systems in the brain but none has yet proved it. According to the research team, the study results are a great leap forward in our understanding of PTSD. It will contribute new knowledge which can be used to design improved treatments for traumatised individuals. The study was supervised by Mats Fredrikson, affiliated to both the Department of Psychology at Uppsala University and the Department of Clinical Neuroscience at Karolinska Institutet. The project was supported financially by the Swedish Research Council; the Swedish Brain Foundation; Riksbankens Jubileumsfond—the Swedish Foundation for Humanities and Social Sciences; and the Swedish Research Council for Health, Working Life and Welfare. Read more in a press release from Uppsala University Publikation Overlapping expression of serotonin transporters and neurokinin-1 receptors in posttraumatic stress disorder: a multi-tracer PET study Frick, A., Åhs, F., Michelgård Palmquist, Å., Pissiota, A., Wallenquist, U., Fernandez, M., Jonasson, M., Appel, L., Frans, Ö., Lubberink, M., Furmark, T., von Knorring, L., Fredrikson, M. Molecular Psychiatry advance online publication 1 December 2015; doi: 10.1038/mp.2015.180

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