bluuebunny/crossref_metadata_2025 huggingface dataset:
Background of couples undergoing non‐invasive prenatal testing in Japan
Authors: Takeda Eri , Suzumori Nobuhiro , Kumagai Kyoko , Oseto Kumiko , Ebara Takeshi , Yotsumoto Junko , Numabe Hironao , Sugiura‐Ogasawara Mayumi
Published: June 2016

Aim

Our purpose was to assess the background of couples who were undergoing non‐invasive prenatal testing (NIPT) in Japan.

Methods

The characteristics of 2486 women who had visited Nagoya City University Hospital for NIPT were compared with Japanese Demographic Trends as controls. The questionnaire included items regarding the maternal and paternal age, maternal age at marriage, age at first live birth, and conception mode.

Results

Compared with the controls, the percentage of women who were 4 or more years older than their partners was larger in the NIPT group (11.8% vs 6.5%). The maternal age at marriage, age at first live birth, and the duration between marriage and first birth tended to be greater in the NIPT group (32.6 years vs 29.3 years, 36.9 years vs 30.4 years, and 3.6 years vs 2.4 years, respectively), and the percentage of women who underwent assisted reproductive technology tended to be higher in the NIPT group (35–39 years: 21.2% vs 7.5%, 40–45 years: 36.2% vs 12.6%), compared with the controls.

Conclusion

Knowing the specific backgrounds of couples who have undergone NIPT may be important for improving the quality of genetic counseling for NIPT.
Genetics and epigenetics in small intestinal neuroendocrine tumours
Authors: Stålberg P. , Westin G. , Thirlwell C.
Published: June 2016

Neuroendocrine tumour of the small intestine (SI‐NET), formerly known as midgut carcinoid tumour, is the most common small intestinal malignancy. The incidence is rising, with recent reports of 0.67 per 100 000 in the USA and 1.12 per 100 000 in Sweden. SI‐NETs often present a challenge in terms of diagnosis and treatment, as patients often have widespread disease and are beyond cure by surgery. Somatostatin analogues provide the mainstay of medical treatment to control hormonal excess and increase the time to progression. Despite overall favourable prognosis (5‐year overall survival of 65%), there is a need to find markers to identify both patients with worse outcome and new targets for therapy. Loss on chromosome 18 has been reported in 60–90% of SI‐NETs, but mutated genes on this chromosome have failed detection. Recently, a putative tumour suppressor role has been suggested for TCEB3C occurring at 18q21 (encoding elongin A3), which may undergo epigenetic repression. CDKN1B has recently been revealed as the only recurrently mutated gene in SI‐NETs but, with a frequency as low as 8%, its role as a driver in SI‐NET development may be questioned. Integrated genomewide analysis including exome and whole‐genome sequencing, gene expression, DNA methylation and copy number analysis has identified three novel molecular subtypes of SI‐NET with differing clinical outcome. DNA methylation analysis has demonstrated that SI‐NETs have significant epigenetic dysregulation in 70–80% of tumours. In this review, we focus on understanding of the genetic, epigenetic and molecular events that lead to development and progression of SI‐NETs.
Systemic lupus erythematosus: still a challenge for physicians
Authors: Bengtsson A. A. , Rönnblom L.
Published: June 2016

Systemic lupus erythematosus (SLE) has a complex clinical picture, and a number of defects in the immune system have been described in patients with the disease. Most organs can be involved in SLE, and in addition to the typical major organ manifestations (e.g. from kidneys and the central nervous system), early cardiovascular disease is a major determinant of prognosis. Several important findings during the last decade have increased the understanding of the mechanisms behind the disease characteristics and the underlying autoimmune process. Amongst, these are defects in the handling of apoptotic cells, increased expression of type I interferon‐regulated genes and activation of autoreactive B cells, with both the type I interferon system and the B lymphocyte stimulator (BLyS) having key roles. In addition, a large number of genes have been identified that contribute to these abnormalities. It has also become clear that certain SLE risk genes are associated with some organ manifestations, such as STAT4 with nephritis and IRF8 with myocardial infarction. Furthermore, environmental factors that can induce SLE or trigger a disease flare have been identified. As a consequence of this increased knowledge, new treatments for SLE have been developed. The most recently approved drug for SLE is belimumab, which blocks BLyS, and several new therapies and therapeutic strategies are in the pipeline for clinical application.
Enhancing Mathematical Problem Solving for Secondary Students with or at Risk of Learning Disabilities: A Literature Review
Authors: Hwang Jiwon , Riccomini Paul J.
Published: June 2016

Requirements for reasoning, explaining, and generalizing mathematical concepts increase as students advance through the educational system; hence, improving overall mathematical proficiency is critical. Mathematical proficiency requires students to interpret quantities and their corresponding relationships during problem‐solving tasks as well as generalizing to different contexts; both requirements are particularly challenging for many students with learning disabilities. An in‐depth review of research was completed to (1) demonstrate how interventions targeting mathematical problem solving are categorized into heuristic, semantic, or authentic approaches; (2) explore the degree to which generalization is presented in each approach; and (3) determine the efficacy of each intervention approach. Experimental studies (n = 17) demonstrating the effects of interventions designed to enhance mathematical problem solving for secondary students with or at risk of learning disabilities were analyzed. Findings indicate that the efficacy of the three intervention approaches varies, and that the real‐world connections differ. Implications for research and practice are discussed.
The use of generic medications for hepatitis C
Authors: Freeman James A. D. , Hill Andrew
Published: June 2016

Hepatitis C, hepatitis B, HIV, TB and malaria are the five major causes of infectious disease death worldwide. In a breakthrough that rivals the invention of penicillin, drugs that cure hepatitis C, with minimal side effects and high success rates, have reached the market, but, in what must be one of the greatest tragedies of modern times, these life‐saving medications are not being deployed on a mass scale. Pharmaceutical patents are gifted to private corporations by governments for the dual purposes of protecting R&D expenditure and encouraging innovation. Unfortunately the monopoly pricing power these patents provision currently lacks adequate checks and balances, is open to abuse, and is quite clearly being abused. The sort of legislative changes required to deliver on the original goals of pharmaceutical patents will take years or even decades to eventuate. Parallel importation of generic medication offers hope to the millions of patients with HCV unable to afford access to vastly overpriced originator medications. Doctors prescribing and monitoring patients taking generics can take comfort from the fact that the REDEMPTION trial results show, like the HIV generics that came before them, that HCV generics deliver robust clinical results.
Don't bet against the natal homing abilities of marine fishes
Authors: Bentzen Paul , Bradbury Ian R.
Published: June 2016

Whether marine fishes are capable of homing to their natal areas has long been something of an enigma. For some estuarine species or sharks (which have extended nondispersal juvenile stages or are born as relatively large, fully formed juveniles), the answer is clearly ‘yes’ (Thorrold et al. ; Feldheim et al. ), but for most marine fishes, the issue is much more mysterious. Many species have free‐floating eggs, and most have pelagic, passively dispersing larvae. It is challenging to imagine how adult fish might navigate to a region of the ocean they experienced only as eggs or larvae, and easier to assume that such dispersal leads inexorably to high gene flow, and even panmixia. One way to resolve the conundrum would be to track fish from hatching to reproduction, but for marine fishes with tiny eggs and drifting larvae, this is notoriously difficult to do (Bradbury & Laurel ). In this issue of Molecular Ecology, Bonanomi et al. () use a creative approach to solve this challenge for Atlantic cod (Gadus morhua) populations that mingle in the vicinity of Greenland. They show that cod that disperse more than a 1000 km away from Iceland as eggs and larvae, then spend years growing on the far side of Greenland, while mixing with two local populations, return as adults to spawning areas near Iceland – and further, that this behaviour has remained stable over more than six decades. They manage this feat with a clever use of historical cod tracking data, modern genomic data and genetic analysis of decades‐old DNA obtained from archived materials. Their results have important implications for our view of the biocomplexity of marine fish populations, and how we should manage them.
Migraine comorbidity with cardiac, cardiovascular and cerebrovascular disease
Authors: Kato Yuji , Dodick David W , Schwedt Todd J
Published: June 2016

Migraine has complex relationships with disorders of the heart, the cardiovasculature and the cerebrovasculature. The purpose of this review was to summarize data regarding the relationship of migraine with structural cardiac disease, cardiovascular disease and stroke. There are low‐quality and/or conflicting data regarding a possible association between migraine with patent foramen ovale and other sources of right‐to‐left shunt. If these associations exist, migraine with aura, in contrast to migraine without aura, would likely account for the comorbidity. Although low‐quality evidence suggested that patent foramen ovale closure results in improved migraine patterns, higher‐quality evidence from prospective clinical trials of patent foramen ovale closure failed to achieve their primary end‐points. There are conflicting data regarding an increased risk of cardiovascular disease in people with migraine. Overall, data suggest that migraine with aura is probably associated with an increased risk for cardiovascular disease. Consistently, studies have shown migraine with aura to be associated with an increased risk for ischemic stroke. The explanation for the comorbidity between migraine with aura and cardiovascular and cerebrovascular diseases has yet to be adequately defined. Potential causal relationships and shared underlying risk factors are discussed. Migraine with aura is associated with an increased risk for ischemic stroke. Migraine with aura might be associated with an increased risk for cardiovascular disease and an increased likelihood for structural cardiac disease, such as patent foramen ovale. Further investigations will define the existence and nature of the relationship between migraine with aura and these disorders.
Hearing loss in lateral medullary syndrome
Authors: Sato Kenichiro , Hida Ayumi , Omori Aki , Arai Noritoshi , Takeuchi Sousuke
Published: June 2016

We report a case of lateral medullary syndrome with hemiparesis and hearing loss. A 69‐year‐old man was diagnosed with right‐sided lateral medullary syndrome and cerebellar vermis infarction with ipsilateral hemiparesis as a result of an upper cervical lesion. On the seventh hospital day, ipsilateral hearing loss suddenly emerged. The results of auditory and vestibular tests, including auditory brainstem responses, suggested a possible lesion in the vestibulocochlear nerve. Hearing loss could be attributed to a non‐anterior inferior cerebellar artery, vertebral artery and/or posterior inferior cerebellar artery infarction. The possibility of comorbidity of hearing loss with lateral medullary syndrome in this case suggests the possible usefulness of further intensive antithrombotic therapy in cases of lateral medullary syndrome with uncommon presentations.
Esophageal replacements in children
Authors: Reinberg Olivier
Published: June 2016

Replacement of the esophagus in children can be performed in cases of malformations, injuries, or acquired conditions. The new esophagus should allow normal oral feeding, with little or no gastroesophageal reflux, and be able to work well for the lifetime of the patient. For over a century, many substitutes have been used, such as segments of colon, the entire stomach, gastric tubes, or parts of the small bowel, but none are perfect or function like a normal esophagus. Esophageal replacements are demanding challenges for pediatric surgeons. Here, I review the different techniques and the pitfalls related to these procedures on the basis of our experience of more than 300 esophageal replacements in children performed since 1989.
Development of sulfanegen for mass cyanide casualties
Authors: Patterson Steven E. , Moeller Bryant , Nagasawa Herbert T. , Vince Robert , Crankshaw Daune L. , Briggs Jacquie , Stutelberg Michael W. , Vinnakota Chakravarthy V. , Logue Brian A.
Published: June 2016

Cyanide is a metabolic poison that inhibits the utilization of oxygen to form ATP. The consequences of acute cyanide exposure are severe; exposure results in loss of consciousness, cardiac and respiratory failure, hypoxic brain injury, and dose‐dependent death within minutes to hours. In a mass‐casualty scenario, such as an industrial accident or terrorist attack, currently available cyanide antidotes would leave many victims untreated in the short time available for successful administration of a medical countermeasure. This restricted therapeutic window reflects the rate‐limiting step of intravenous administration, which requires both time and trained medical personnel. Therefore, there is a need for rapidly acting antidotes that can be quickly administered to large numbers of people. To meet this need, our laboratory is developing sulfanegen, a potential antidote for cyanide poisoning with a novel mechanism based on 3‐mercaptopyruvate sulfurtransferase (3‐MST) for the detoxification of cyanide. Additionally, sulfanegen can be rapidly administered by intramuscular injection and has shown efficacy in many species of animal models. This article summarizes the journey from concept to clinical leads for this promising cyanide antidote.
Genetic enhancement of oil content in potato tuber (Solanum tuberosum L.) through an integrated metabolic engineering strategy
Authors: Liu Qing , Guo Qigao , Akbar Sehrish , Zhi Yao , El Tahchy Anna , Mitchell Madeline , Li Zhongyi , Shrestha Pushkar , Vanhercke Thomas , Ral Jean‐Philippe , Liang Guolu , Wang Ming‐Bo , White Rosemary , Larkin Philip , Singh Surinder , Petrie James
Published: June 2016

Potato tuber is a high yielding food crop known for its high levels of starch accumulation but only negligible levels of triacylglycerol (TAG). In this study, we evaluated the potential for lipid production in potato tubers by simultaneously introducing three transgenes, including WRINKLED 1 (WRI1), DIACYLGLYCEROL ACYLTRANSFERASE 1 (DGAT1) and OLEOSIN under the transcriptional control of tuber‐specific (patatin) and constitutive (CaMV‐35S) promoters. This coordinated metabolic engineering approach resulted in over a 100‐fold increase in TAG accumulation to levels up to 3.3% of tuber dry weight (DW). Phospholipids and galactolipids were also found to be significantly increased in the potato tuber. The increase of lipids in these transgenic tubers was accompanied by a significant reduction in starch content and an increase in soluble sugars. Microscopic examination revealed that starch granules in the transgenic tubers had more irregular shapes and surface indentations when compared with the relatively smooth surfaces of wild‐type starch granules. Ultrastructural examination of lipid droplets showed their close proximity to endoplasmic reticulum and mitochondria, which may indicate a dynamic interaction with these organelles during the processes of lipid biosynthesis and turnover. Increases in lipid levels were also observed in the transgenic potato leaves, likely due to the constitutive expression of DGAT1 and incomplete tuber specificity of the patatin promoter. This study represents an important proof‐of‐concept demonstration of oil increase in tubers and provides a model system to further study carbon reallocation during development of nonphotosynthetic underground storage organs.
Investigating the effect of cadmium and aluminium on growth and stress‐induced responses in the micropropagated medicinal plant Hypoxis hemerocallidea
Authors: Okem A. , Moyo M. , Stirk W. A. , Finnie J. F. , Van Staden J.
Published: June 2016

Hypoxis hemerocallidea is a highly utilized medicinal plant in South Africa. Its cultivation has received considerable attention in order to meet the high demand. High levels of cadmium (Cd) and aluminum (Al) in H. hemerocallidea plants sold in traditional medicinal markets was previously reported.

The present study used an in vitro propagation model to investigate the uptake of Cd and Al by H. hemerocallidea and their effect on plant growth, elemental uptake and some stress‐induced responses such as pigment, malondialdehyde (MDA), proline content and ultrastructural changes.

Shoot and root growth of plantlets exposed to Cd, Cd:Al and high concentrations of Al was significantly reduced. Highest concentrations of Cd accumulated in the corms of Cd‐treated plantlets while highest Al concentrations occurred in the leaves and roots. There was higher accumulation of Cd and Al when applied singularly compared to the Cd:Al combination treatments. Cd and Al also reduced accumulation of trace elements in micropropagted H. hemerocallidea with lowest concentrations in the Cd:Al combination treatments. Exposure to Cd, Al and Cd:Al significantly reduced the level of chlorophyll but increased the levels of carotenoids, MDA and proline. Ultrastructural changes were also observed in H. hemerocallidea exposed to Cd and Al.

All these factors contributed to the inhibition of plant growth and could potentially affect the ability of this important medicinal plant to synthesize bioactive compounds. It is thus necessary to understand heavy metal stress‐induced responses in this highly valued medicinal plant to ensure a high quality product for the consumer.
Use of formalin in intensive aquaculture: properties, application and effects on fish and water quality
Authors: Leal Joana F. , Neves Maria Graça P. M. S. , Santos Eduarda B. H. , Esteves Valdemar I.
Published: June 2016

Formalin (aqueous solution of formaldehyde stabilized with methanol) is one of the most used disinfectants in aquaculture. It is used to eliminate infectious agents but may be responsible for negative effects on fish and water quality. This work focuses on physical–chemical properties of formalin and on its reactions and its use in intensive aquaculture and in environment. The types of treatments and the action mode of formalin are also described. The main consequences of formalin exposure to fish are damage in gills and alterations in mucous cells. Formalin also interacts with some treatments adopted in aquaculture establishments, for example biological filter, where the nitrification process seems to be strongly affected. With respect to formalin inactivation, formaldehyde (effluent) may be diluted with water or specific treatments should be conducted to decrease the concentration levels before its discharge into the environment. The common methodologies applied to aquaculture are not completely efficient on formalin removal from water, and the advanced oxidation processes may be a good alternative.
Phylogenetic relationships within Diplotaxini Kirby (Coleoptera: Melolonthidae: Melolonthinae) with emphasis on LiogenysGuérin‐Méneville
Authors: CHERMAN MARIANA A. , MORÓN MIGUEL A. , ALMEIDA LÚCIA M.
Published: June 2016

Diplotaxini Kirby is one of the 29 tribes of Melolonthinae with Nearctic, Neotropical, Paleartic, Afrotropical and Oriental distribution. According to the current classification, Diplotaxini is composed of 706 species described in 21 genera. Neotropical Diplotaxini comprise 94 species, of which 78 are members of Liogenys Guérin Méneville, the largest Neotropical genus. Until now, no phylogenetic studies on Diplotaxini have tested whether the tribe is natural or artificial. This study tested the relationships among Diplotaxini genera, created hypotheses for better defining them, and assessed the monophyly of Liogenys. Cladistic analyses using 167 adult morphological characters were performed. The 83 included taxa represent three subfamilies of Melolonthidae, four tribes of Melolonthinae, and most genera of Diplotaxini, with emphasis on Liogenys. The data were analysed using parsimony under equal and implied weights. In both analyses, the traditional concept of Diplotaxini is shown to be a polyphyletic assemblage. Empecta Erichson and Clypeasta Fairmaire are closely related to Melolontha melolontha (Linnaeus) and Pseudoliogenys Moser close to Myloxenoides Martínez (Tanyproctini). Pachrodema Blanchard is identified as the sister group of Liogenys. The monophyly of both Pacuvia Curtis and Homalochilus Blanchard is confirmed and the paraphyly of Diplotaxis Kirby is suggested. The analyses strongly supported the polyphyly of Liogenys. To render this genus monophyletic, we transferred L. ferrugata Mannerheim (related to M. melolontha) to Phyllophaga Harris, and L. micropyga Burmeister to Diplotaxis, forming Diplotaxis micropyga (Burmeister, 1855) comb.n.; and included Homoliogenys tarsalis (Moser) and Hilarianus anguliceps Blanchard in Liogenys. As H. anguliceps is syn. junior of Liogenys punctaticollis, Hilarianus is synonymized with Liogenys. Hilarianus ovalis and Hilarianus rufinus are here assigned to Manonychus, and Hilarianus uniformis and Hilarianus suboblongus to Blepharotoma, forming: Blepharotoma uniformis comb.n., Blepharotoma suboblongus comb.n., Manonychus ovalis comb.n. and Manonychus rufinus comb.n.
An efficient method for measuring copy number variation applied to improvement of nematode resistance in soybean
Authors: Lee Tong Geon , Diers Brian W. , Hudson Matthew E.
Published: June 2016

Copy number variation (CNV) is implicated in important traits in multiple crop plants, but can be challenging to genotype using conventional methods. The Rhg1 locus of soybean, which confers resistance to soybean cyst nematode (SCN), is a CNV of multiple 31.2‐kb genomic units each containing four genes. Reliable, high‐throughput methods to quantify Rhg1 and other CNVs for selective breeding were developed. The CNV genotyping assay described here uses a homeologous gene copy within the paleopolyploid soybean genome to provide the internal control for a single‐tube TaqMan copy number assay. Using this assay, CNV in breeding populations can be tracked with high precision. We also show that extensive CNV exists within Fayette, a released, inbred SCN‐resistant soybean cultivar with a high copy number at Rhg1 derived from a single donor parent. Copy number at Rhg1 is therefore unstable within a released variety over a relatively small number of generations. Using this assay to select for individuals with altered copy number, plants were obtained with both increased copy number and increased SCN resistance relative to control plants. Thus, CNV genotyping technologies can be used as a new type of marker‐assisted selection to select for desirable traits in breeding populations, and to control for undesirable variation within cultivars.
Viral nucleic acids in human plasma pools
Authors: Zhang Wen , Li Linlin , Deng Xutao , Blümel Johannes , Nübling C. Micha , Hunfeld Andreas , Baylis Sally A. , Delwart Eric
Published: June 2016

BACKGROUND

The identification of viruses in human blood is required for epidemiologic surveillance and to detect potentially emerging threats to blood transfusion safety.

STUDY DESIGN AND METHODS

Viral nucleic acids in plasma fractionation pools assembled from blood donors in the United States and Europe were analyzed by viral metagenomics.

RESULTS

Anelloviruses were detected in each of the 10 plasma pools. Human pegivirus A (HPgV; GB virus type C) sequences were identified in eight of the 10 pools, more than 90% of which belong to Genotype 2. The recently described human HPgV2 in Flaviviridae was not detected. A small number of sequence reads of human papillomavirus were also detected in three pools. In one pool, two different gemycircularvirus genomes were identified and fully sequenced. The capsid protein of one gemycircularvirus shared 83% to 84% identity to those of genomes from human serum and sewage. The presence of the gemycircularvirus genomes in the plasma pool was independently confirmed and the viral concentration estimated by digital PCR at more than 106 copies/mL assuming their origin from single donors.

CONCLUSION

Further research is required to elucidate whether gemycircularviruses can infect humans or are indicative of contamination occurring during phlebotomy, plasma pool processing, or ongoing donor fungal infections.
A randomized, double‐blinded crossover trial testing the benefit of two hydrolysed poultry‐based commercial diets for dogs with spontaneous pruritic chicken allergy
Authors: Bizikova Petra , Olivry Thierry
Published: June 2016

Background

Hydrolysed protein diets are used to diagnose and treat dogs with cutaneous adverse food reactions (CAFR). Little is known about what proportion of dogs hypersensitive to the native protein would react to its hydrolysed form.

Objectives

To determine the clinical allergenicity of hydrolysed poultry feather (RCU) and chicken liver diets (HZD) in dogs with chicken induced CAFR.

Methods

In this randomized, double‐blinded, crossover trial, ten dogs with chicken induced CAFR were selected after a positive oral challenge to chicken meat and a negative one to corn. Test diets were fed for 14 days separated by a 14 day wash‐out period. Owners rated pruritus daily with a Visual Analog Scale (PVAS). The challenge was ended if a flare in pruritus occurred (i.e. PVAS ≥5/10).

Results

The median PVAS scores before feeding RCU and HZD were 0.9 and 1.7, respectively (Wilcoxon signed rank test, P = 0.46). Pruritus scores increased significantly after feeding HZD (Friedman's test, P < 0.001) but not after feeding RCU (P = 0.895). None of the dogs fed RCU, but four dogs fed HZD (40%), were withdrawn after a flare in pruritus developed (Fisher's test, P = 0.04). The maximal PVAS score was significantly higher after HZD (median: 4.7) compared to RCU (2.5) (Wilcoxon signed rank test, P = 0.01). One dog in each group was withdrawn due to diarrhoea.

Conclusions

The hydrolysed poultry feather diet did not induce pruritus flares in dogs allergic to chicken in contrast to the hydrolysed chicken liver diet that led to pruritus flares in 40% of these dogs.
Hyponatraemia alters the biophysical properties of neuronal cells independently of osmolarity: a study on Ni2+‐sensitive current involvement
Authors: Squecco Roberta , Luciani Paola , Idrizaj Eglantina , Deledda Cristiana , Benvenuti Susanna , Giuliani Corinna , Fibbi Benedetta , Peri Alessandro , Francini Fabio
Published: June 2016

New Findings

What is the central question of this study?

Hyponatraemia, an electrolyte disorder encountered in hospitalized patients, can cause neurological symptoms usually attributed to a reduction in plasma osmolarity. Here, we investigated whether low [Na+] per se can cause neuronal changes independent of osmolarity, focusing on involvement of the Na+–Ca2+ exchanger.

What is the main finding and its importance?

We show that hyponatraemia per se causes alterations of neuronal properties. The novel finding of Na+–Ca2+ exchanger involvement helps us to elucidate the volume regulation following hyponatraemia. This might have relevance in a translational perspective because Na+–Ca2+ exchanger could be a target for novel therapies.

Hyponatraemia is the most frequent electrolyte disorder encountered in hospitalized patients, and it can cause a wide variety of neurological symptoms. Most of the negative effects of this condition on neuronal cells are attributed to cell swelling because of the reduction of plasma osmolarity, although in hyponatraemia different membrane proteins are supposed to be involved in the conservation of neuronal volume. We have recently reported detrimental effects of hyponatraemia on two different neuronal cell lines, SK‐N‐AS and SH‐SY5Y, independent of osmotic alterations. In this study we investigated, in the same cell lines, whether hyponatraemic conditions per se can cause electrophysiological alterations and whether these effects vary over time. Accordingly, we carried out experiments in low‐sodium medium in either hyposmotic [Osm(−)] or isosmotic [Osm(+)] conditions, for a short (24 h) or long time (7 days). Using a patch pipette in voltage‐clamp conditions, we recorded possible modifications of cell capacitance (Cm) and membrane conductance (Gm). Our results indicate that in both Osm(−) and Osm(+) medium, Cm and Gm show a similar increase, but such effects are dependent on the time in culture in different ways. Notably, regarding the possible mechanisms involved in the maintenance of Cm, Gm and Gm/Cm in Osm(+) conditions, we observed a greater contribution of the Na+–Ca2+ exchanger compared with Osm(−) and control conditions. Overall, these novel electrophysiological results help us to understand the mechanisms of volume regulation after ionic perturbation. Our results might also have relevance in a translational perspective because the Na+–Ca2+ exchanger can be considered a target for planning novel therapies.
A Combined Experimental and Computational Approach to Subject-Specific Analysis of Knee Joint Laxity
Authors: Harris Michael D. , Cyr Adam J. , Ali Azhar A. , Fitzpatrick Clare K. , Rullkoetter Paul J. , Maletsky Lorin P. , Shelburne Kevin B.
Published: June 2016

Modeling complex knee biomechanics is a continual challenge, which has resulted in many models of varying levels of quality, complexity, and validation. Beyond modeling healthy knees, accurately mimicking pathologic knee mechanics, such as after cruciate rupture or meniscectomy, is difficult. Experimental tests of knee laxity can provide important information about ligament engagement and overall contributions to knee stability for development of subject-specific models to accurately simulate knee motion and loading. Our objective was to provide combined experimental tests and finite-element (FE) models of natural knee laxity that are subject-specific, have one-to-one experiment to model calibration, simulate ligament engagement in agreement with literature, and are adaptable for a variety of biomechanical investigations (e.g., cartilage contact, ligament strain, in vivo kinematics). Calibration involved perturbing ligament stiffness, initial ligament strain, and attachment location until model-predicted kinematics and ligament engagement matched experimental reports. Errors between model-predicted and experimental kinematics averaged <2 deg during varus–valgus (VV) rotations, <6 deg during internal–external (IE) rotations, and <3 mm of translation during anterior–posterior (AP) displacements. Engagement of the individual ligaments agreed with literature descriptions. These results demonstrate the ability of our constraint models to be customized for multiple individuals and simultaneously call attention to the need to verify that ligament engagement is in good general agreement with literature. To facilitate further investigations of subject-specific or population based knee joint biomechanics, data collected during the experimental and modeling phases of this study are available for download by the research community.
Excess Identification and Mapping in Engineered Systems
Authors: Cansler Ethan Z. , White Samantha B. , Ferguson Scott M. , Mattson Christopher A.
Published: June 2016

A system must continue to meet stakeholder needs throughout its service life to maintain value. Excess that is embedded into components during the design phase can enable in-service system evolution when new or changed requirements are introduced. However, while the concept of excess has been established in the literature, it is not clear how to identify and quantify the set of excesses in a particular design. This paper uses component properties and functional flow information to map and quantify the excess that exists within a system. Understanding the functional flow relationships between components allows for the bottlenecks at component interfaces to be identified. Those flows that do not limit the potential evolvability of a system can be removed from consideration, allowing for critical interface parameters to be highlighted and their capabilities quantified. The method is demonstrated on a consumer heat gun, where quantifying the excess within components allows for a reduced map to be created with irrelevant flows removed. Finally, changes to the system are explored to demonstrate how knowledge of component excess can be used to initially validate a proposed evolution.
Mechanical Response of Brain Stem in Compression and the Differential Scanning Calorimetry and FTIR Analyses
Authors: Zhang Wei , Zhang Run-run , Feng Liang-liang , Li Yang , Wu Fan , Wu Cheng-wei
Published: June 2016

The stress–strain curves of brain stem in uniaxial compression demonstrate strain rate dependency and can be characterized with three regions: initial toe region, transitional region, and high strain region, suggesting strong viscoelastic behavior. To investigate the origin of this viscoelasticity at microscale, differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectra of brain stem tissue were recorded and analyzed. The emergence of endotherm thermal domains in DSC indicates that the conformation change of biomolecules can absorb and dissipate energy, explaining the viscous behavior of the brain stem. FTIR analyses indicate that the presence of polar functional groups such as amide, phosphate, and carboxyl groups in the biomolecules takes responsibility for the viscous performance of brain stem. Ogden, Fung, and Gent models were adopted to fit the experimental data, and Ogden model is the most apt one in capturing the stiffening of the brain stem with the increasing strain rate.
Three‐dimensional quadratic modeling and quantitative evaluation of the diaphragm on a volumetric CT scan in patients with chronic obstructive pulmonary disease
Authors: Chang Yongjun , Bae Jangpyo , Kim Namkug , Park Joo‐Young , Lee Sang Min , Seo Joon Beom
Published: June 2016

Purpose:

In patients with chronic obstructive pulmonary disease (COPD), diaphragm function may deteriorate due to reduced muscle fiber length. Quantitative analysis of the morphology of the diaphragm is therefore important. In the authors current study, they propose a diaphragm segmentation method for COPD patients that uses volumetric chest computed tomography (CT) data, and they provide a quantitative analysis of the diaphragmatic dimensions.

Methods:

Volumetric CT data were obtained from 30 COPD patients and 10 normal control patients using a 16‐row multidetector CT scanner (Siemens Sensation 16) with 0.75‐mm collimation. Diaphragm segmentation using 3D ray projections on the lower surface of the lungs was performed to identify the draft diaphragmatic lung surface, which was modeled using quadratic 3D surface fitting and robust regression in order to minimize the effects of segmentation error and parameterize diaphragm morphology. This result was visually evaluated by an expert thoracic radiologist. To take into consideration the shape features of the diaphragm, several quantification parameters—including the shape index on the apex (SIA) (which was computed using gradient set to 0), principal curvatures on the apex on the fitted diaphragm surface (CA), the height between the apex and the base plane (H), the diaphragm lengths along the x‐, y‐, and z‐axes (XL, YL, ZL), quadratic‐fitted diaphragm lengths on the z‐axis (FZL), average curvature (C), and surface area (SA)—were measured using in‐house software and compared with the pulmonary function test (PFT) results.

Results:

The overall accuracy of the combined segmentation method was 97.22% ± 4.44% while the visual accuracy of the models for the segmented diaphragms was 95.28% ± 2.52% (mean ± SD). The quantitative parameters, including SIA, CA, H, XL, YL, ZL, FZL, C, and SA were 0.85 ± 0.05 (mm−1), 0.01 ± 0.00 (mm−1), 17.93 ± 10.78 (mm), 129.80 ± 11.66 (mm), 163.19 ± 13.45 (mm), 71.27 ± 17.52 (mm), 61.59 ± 16.98 (mm), 0.01 ± 0.00 (mm−1), and 34 380.75 ± 6680.06 (mm2), respectively. Several parameters were correlated with the PFT parameters.

Conclusions:

The authors propose an automatic method for quantitatively evaluating the morphological parameters of the diaphragm on volumetric chest CT in COPD patients. By measuring not only the conventional length and surface area but also the shape features of the diaphragm using quadratic 3D surface modeling, the proposed method is especially useful for quantifying diaphragm characteristics. Their method may be useful for assessing morphological diaphragmatic changes in COPD patients.
Sea ice retreat said to accelerate Greenland melting
Authors: Kintisch Eli
Published: June 2016

New claim intensifies “Arctic amplification” debate.
Biosensor reveals multiple sources for mitochondrial NAD
+
Authors: Cambronne Xiaolu A. , Stewart Melissa L. , Kim DongHo , Jones-Brunette Amber M. , Morgan Rory K. , Farrens David L. , Cohen Michael S. , Goodman Richard H.
Published: June 2016

A fluorescent sensor for NAD
+
in living cells

Roles of cellular nicotinamide adenine dinucleotide (NAD
+
) in metabolism, aging, and disease have garnered much interest, but methods have been lacking to measure the amounts of NAD
+
in living cells. Cambronne
et al.
developed a genetically encoded biosensor that can be used to monitor concentrations of free NAD
+
in various compartments of a cell (see the Perspective by Guarente). Such concentrations of NAD
+
appear to be important in regulating the activity of NAD
+
-consuming enzymes such as sirtuins and ADP-ribosyltransferases. The authors used the sensor to demonstrate that NAD
+
concentrations in mitochondria of cultured human cells can be controlled by multiple mechanisms.

Science
, this issue p.
1474
; see also p.
1396
From the RNA world to the clinic
Authors: Sullenger Bruce A. , Nair Smita
Published: June 2016

The study of RNA has continually emphasized the structural and functional versatility of RNA molecules. This versatility has inspired translational and clinical researchers to explore the utility of RNA-based therapeutic agents for a wide variety of medical applications. Several RNA therapeutics, with diverse modes of action, are being evaluated in large late-stage clinical trials, and many more are in early clinical development. Hundreds of patients are enrolled in large trials testing messenger RNAs to combat cancer, small interfering RNAs to treat renal and hepatic disorders, and aptamers to combat ocular and cardiovascular disease. Results from these studies are generating considerable interest among the biomedical community and the public and will be important for the future development of this emerging class of therapeutic agents.
Messenger RNA modifications: Form, distribution, and function
Authors: Gilbert Wendy V. , Bell Tristan A. , Schaening Cassandra
Published: June 2016

RNA contains more than 100 distinct modifications that promote the functions of stable noncoding RNAs in translation and splicing. Recent technical advances have revealed widespread and sparse modification of messenger RNAs with
N
6
-methyladenosine (m
6
A), 5-methylcytosine (m
5
C), and pseudouridine (Ψ). Here we discuss the rapidly evolving understanding of the location, regulation, and function of these dynamic mRNA marks, collectively termed the epitranscriptome. We highlight differences among modifications and between species that could instruct ongoing efforts to understand how specific mRNA target sites are selected and how their modification is regulated. Diverse molecular consequences of individual m
6
A modifications are beginning to be revealed, but the effects of m
5
C and Ψ remain largely unknown. Future work linking molecular effects to organismal phenotypes will broaden our understanding of mRNA modifications as cell and developmental regulators.
New online ecology of adversarial aggregates: ISIS and beyond
Authors: Johnson N. F. , Zheng M. , Vorobyeva Y. , Gabriel A. , Qi H. , Velasquez N. , Manrique P. , Johnson D. , Restrepo E. , Song C. , Wuchty S.
Published: June 2016

Tackling the advance of online threats

Online support for adversarial groups such as Islamic State (ISIS) can turn local into global threats and attract new recruits and funding. Johnson
et al.
analyzed data collected on ISIS-related websites involving 108,086 individual followers between 1 January 1 and 31 August 2015. They developed a statistical model aimed at identifying behavioral patterns among online supporters of ISIS and used this information to predict the onset of major violent events. Sudden escalation in the number of ISIS-supporting ad hoc web groups (“aggregates”) preceded the onset of violence in a way that would not have been detected by looking at social media references to ISIS alone. The model suggests how the development and evolution of such aggregates can be blocked.

Science
, this issue p.
1459
Improvements in ecosystem services from investments in natural capital
Authors: Ouyang Zhiyun , Zheng Hua , Xiao Yi , Polasky Stephen , Liu Jianguo , Xu Weihua , Wang Qiao , Zhang Lu , Xiao Yang , Rao Enming , Jiang Ling , Lu Fei , Wang Xiaoke , Yang Guangbin , Gong Shihan , Wu Bingfang , Zeng Yuan , Yang Wu , Daily Gretchen C.
Published: June 2016

China's national ecosystem assessment

China recently completed its first National Ecosystem Assessment covering the period 2000–2010. Ouyang
et al.
present the main findings of the assessment. Investment in the restoration and preservation of natural capital has resulted in improvements at the national level in most of the major ecosystem services measured. In particular, food production, carbon sequestration, and soil retention showed strong gains; on the other hand, habitat provision for biodiversity showed a gradual decline. Regional differences remain nonetheless, and there are serious environmental challenges still to be met in areas such as air quality and the wider global footprint of raw material imports.

Science
, this issue p.
1455
Carrots and sticks fail to change behavior in cocaine addiction
Authors: Ersche Karen D. , Gillan Claire M. , Jones P. Simon , Williams Guy B. , Ward Laetitia H. E. , Luijten Maartje , de Wit Sanne , Sahakian Barbara J. , Bullmore Edward T. , Robbins Trevor W.
Published: June 2016

Punishment doesn't work in cocaine addicts

Addiction is extremely difficult to treat, particularly cocaine use disorder. Animal experiments have led to the concept of drug addiction as abnormal goal-directed learning and habit formation. Ersche
et al.
found that overtraining with positive reinforcement such as rewards made cocaine-addicted patients less sensitive to the outcome of their actions. In contrast, overtraining on a punishment paradigm had no effect. Thus, habits may determine the behavior of cocaine users.

Science
, this issue p.
1468
Tuning organic band structures with Coulomb interactions
Authors: Ueno Nobuo
Published: June 2016

The smooth change of band gaps in blends of organic semiconductors arises from long-range electronic interactions
Designing a robust single-molecule switch
Authors: Frisbie C. Daniel
Published: June 2016

A single-molecule switch works at room temperature
Single-cell variability guided by microRNAs
Authors: Garg Salil , Sharp Phillip A.
Published: June 2016

Variability in miRNA activity, and therefore gene networks, may define cell state
Evaluation of a Multiplex Real-Time PCR Assay for Detecting Major Bacterial Enteric Pathogens in Fecal Specimens: Intestinal Inflammation and Bacterial Load Are Correlated in Campylobacter Infections
Authors: Wohlwend Nadia , Tiermann Sacha , Risch Lorenz , Risch Martin , Bodmer Thomas
Published: June 2016

A total of 1,056 native or Cary-Blair-preserved stool specimens were simultaneously tested by conventional stool culturing and by enteric bacterial panel (EBP) multiplex real-time PCR for
Campylobacter jejuni
,
Campylobacter coli
,
Salmonella
spp., and shigellosis disease-causing agents (
Shigella
spp. and enteroinvasive
Escherichia coli
[EIEC]). Overall, 143 (13.5%) specimens tested positive by PCR for the targets named above; 3 coinfections and 109 (10.4%)
Campylobacter
spp., 17 (1.6%)
Salmonella
spp., and 20 (1.9%)
Shigella
spp./EIEC infections were detected. The respective positive stool culture rates were 75 (7.1%), 14 (1.3%), and 7 (0.7%). The median threshold cycle (

C
T

) values of culture-positive specimens were significantly lower than those of culture-negative ones (

C
T

values, 24.3 versus 28.7;
P
< 0.001), indicating that the relative bacterial load per fecal specimen was significantly associated with the culture results. In
Campylobacter
infections, the respective median fecal calprotectin concentrations in PCR-negative/culture-negative (
n =
40), PCR-positive/culture-negative (
n =
14), and PCR-positive/culture-positive (
n =
15) specimens were 134 mg/kg (interquartile range [IQR], 30 to 1,374 mg/kg), 1,913 mg/kg (IQR, 165 to 3,813 mg/kg), and 5,327 mg/kg (IQR, 1,836 to 18,213 mg/kg). Significant differences were observed among the three groups (
P
< 0.001), and a significant linear trend was identified (
P
< 0.001). Furthermore, the fecal calprotectin concentrations and

C
T

values were found to be correlated (
r
= −0.658). Our results demonstrate that molecular screening of
Campylobacter
spp.,
Salmonella
spp., and
Shigella
spp./EIEC using the BD Max EBP assay will result in timely diagnosis and improved sensitivity. The determination of inflammatory markers, such as calprotectin, in fecal specimens may aid in the interpretation of PCR results, particularly for enteric pathogens associated with mucosal damage and colonic inflammation.
Rapid Detection of Polymyxin-Resistant Enterobacteriaceae from Blood Cultures
Authors: Jayol Aurélie , Dubois Véronique , Poirel Laurent , Nordmann Patrice
Published: June 2016

Enterobacterial strains resistant to polymyxins are being increasingly reported worldwide. The conventional methods for detection of colistin-resistant isolates such as broth microdilution remain time-consuming (24 to 48 h), and methods such as disc diffusion and Etest are not reliable. Recently, the rapid polymyxin NP test was developed for rapid identification of polymyxin-resistant
Enterobacteriaceae
. This test is based on the detection of glucose metabolism related to bacterial growth in the presence of a defined concentration of colistin (or polymyxin B). The formation of acid metabolites is evidenced by a color change of a pH indicator (red phenol) in less than 2 h. In this study, the polymyxin NP test was evaluated for detection of colistin-resistant
Enterobacteriaceae
directly from blood cultures. The test was performed with 73 blood culture sets (either spiked or clinical blood cultures) with various enterobacterial species. The test exhibited excellent discrimination between polymyxin-resistant and polymyxin-susceptible enterobacterial isolates, and results are obtained from blood cultures within 4 h. It is easy to perform and requires neither subculture nor a centrifugation step. This test is rapid, specific, and sensitive and allows early identification of polymyxin-resistant
Enterobacteriaceae
directly from blood cultures.
Evaluation of the Hologic Panther Transcription-Mediated Amplification Assay for Detection of Mycoplasma genitalium
Authors: Tabrizi S. N. , Costa A. M. , Su J. , Lowe P. , Bradshaw C. S. , Fairley C. K. , Garland S. M.
Published: June 2016

The detection of
Mycoplasma genitalium
was evaluated on 1,080 urine samples by the use of a Panther instrument. Overall sensitivity, specificity, positive predictive values, and negative predictive values were 100%, 99.4%, 93.6%, and 100%, respectively. Detection of
M. genitalium
by the use of the Panther transcription-mediated amplification assay offers a simple, accurate, and sensitive platform for diagnostic laboratories.