bluuebunny/crossref_metadata_2025 huggingface dataset:
Revisionist Just War Theory and the Concept of War Crimes
Authors: CHEHTMAN ALEJANDRO
Published: November 2017

Under contemporary international law, war crimes are conceived as particularly serious violations of the laws of armed conflict. Mere participation of rank-and-file soldiers in an unjust or unlawful war is generally not considered to warrant legal punishment. This position is based on the principle of equality between belligerents. During the last 20 years, this principle has been challenged by the so-called revisionist position in just war theory, as well as by certain scholars in international law. According to them, unjust or unlawful participants in armed conflict perpetrate serious wrongs. This article argues that their conduct is not only morally wrongful, but also that it should be criminalized under certain circumstances. On the basis of empirical research on cognitive biases, and on one of the leading accounts of legitimate authority in political philosophy, it argues that participation in war warrants criminalization only when the war is knowingly or manifestly unlawful. Furthermore, it claims that this position is not only sound at the level of deep moral principles, but that in fact it provides a persuasive reinterpretation of existing international law.
Epidemiology and genetic diversity of human parechoviruses circulating among children hospitalised with acute gastroenteritis in Pune, Western India: a 5-years study
Authors: PATIL P. R. , GANORKAR N. N. , GOPALKRISHNA V.
Published: November 2017

Human parechoviruses (HPeVs) are known to cause various clinical manifestations including acute gastroenteritis. Although HPeV infections and their genotypes have been detected in human patients worldwide, no such reports are available from India to ascertain the association of HPeVs in acute gastroenteritis. The present study was conducted to determine the clinical features and genetic diversity of HPeVs detected in children hospitalised for acute gastroenteritis. Stool specimens (n= 979) collected from children aged ⩽5 years hospitalised for acute gastroenteritis in Pune, western India during January 2006–December 2010 were included. HPeV RNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) (5′UTR) followed by genotyping using VP1 gene-based PCR and phylogenetic analysis. HPeV was detected in 13·9% (136/979) of the cases, co-infections with other enteric viruses were found in 43·4%. HPeV was more frequent in children ⩽1 year age with infections reported throughout the year. A total of 102/136 (75%) HPeV strains were genotyped, which comprised 13 different HPeV genotypes. Of these, HPeV1 was the most predominant genotype detected and phylogenetically clustered with the Harris strain which is rarely reported. The study documents circulation of heterogeneous HPeV genotypes. Two variant strains of HPeV4 and ‘RGD absent’ HPeV5 and 6 strains were also detected. This is the first report of HPeV with diversified genotypes identified in acute gastroenteritis patients from India.
Drug addiction and alcoholism as predictors for tuberculosis treatment default in Brazil: a prospective cohort study
Authors: SILVA M. R. , PEREIRA J. C. , COSTA R. R. , DIAS J. A. , GUIMARÃES M. D. C. , LEITE I. C. G.
Published: November 2017

This study aimed to evaluate the risk factors for tuberculosis (TB) treatment default in a priority city for disease control in Brazil. A cohort of TB cases diagnosed from 2008 to 2009 was followed up from patients’ entry into three outpatient sites, in Juiz de Fora, Minas Gerais (Brazil), until the recording of the outcomes. Drug addiction, alcoholism and treatment site appeared to be independently associated with default. Current users of crack as the hardest drug (odds ratio (OR) 12·25, 95% confidence interval (CI) 3·04–49·26) were more likely to default than other hard drug users (OR 5·67, 95% CI 1·34–24·03), former users (OR 4·12, 95% CI 1·11–15·20) and those not known to use drugs (reference group). Consumers at high risk of alcoholism (OR 2·94, 95% CI 1·08–7·99) and those treated in an outpatient hospital unit (OR 8·22, 95% CI 2·79–24·21%) also were more likely to default. Our results establish that substance abuse was independently associated with default. National TB programmes might be more likely to achieve their control targets if they include interventions aimed at improving adherence and cure rates, by diagnosing and treating substance abuse concurrently with standard TB therapy.
Impact of an intervention programme on knowledge, attitudes and practices of population regarding severe fever with thrombocytopenia syndrome in endemic areas of Lu'an, China
Authors: LYU Y. , HU C.-Y. , SUN L. , QIN W. , XU P.-P. , SUN J. , HU J.-Y. , YANG Y. , LI F.-L. , CHANG H.-W. , LI X.-D. , XIE S.-Y. , LI K.-C. , HUANG X.-X. , DING F. , ZHANG X.-J.
Published: November 2017

Knowledge, attitudes and practices (KAP) of the population regarding severe fever with thrombocytopenia syndrome (SFTS) in endemic areas of Lu'an in China were assessed before and after an intervention programme. The pre-intervention phase was conducted using a sample of 425 participants from the 12 selected villages with the highest rates of endemic SFTS infection. A predesigned interview questionnaire was used to assess KAP. Subsequently, an intervention programme was designed and applied in the selected villages. KAP was re-assessed for each population in the selected villages using the same interview questionnaire. Following 2 months of the programme, 339 participants had completed the re-assessed survey. The impact of the intervention programme was evaluated using suitable statistical methods. A significant increase in the KAP and total KAP scores was noted following the intervention programme, whereas the proportion of correct knowledge, the positive attitudes and the effective practices toward SFTS of respondents increased significantly. The intervention programme was effective in improving KAP level of SFTS in populations that were resident in endemic areas.
Overweight negatively affects outcome of superovulation treatment in female mice
Authors: Fabian Dušan , Babeľová Janka , Čikoš Štefan , Šefčíková Zuzana
Published: November 2017

Superovulatory response is characterized by a high degree of variability and unpredictability. The aim of the present experimental study was to examine whether the amount of maternal body fat can influence the efficiency of ovarian stimulation with gonadotropins. Female mice of two body condition types, normal and obese, produced in a standardized two-generation model, were subjected to ovarian stimulation using eCG and hCG followed by natural mating. Produced ova and embryos were recovered on day 1 and day 4 of pregnancy respectively, and several quantitative, qualitative and developmental parameters were evaluated in them. The overall response of mouse females with normal and elevated amounts of body fat to superovulation was similar: They produced almost the same numbers of ova and embryos on average. Conversely, a higher number of immature oocytes, non-fertilized mature oocytes and lower-stage zygotes were collected from fat females. In both groups, the majority of fertilized oocytes was able to cleave and reach the higher stages of development. However, in the group of fat mice, a lower number of blastocysts was collected, and these blastocysts showed increased incidence of apoptotic cell death. In conclusion, although the response of normal and fat mice to superovulatory treatment was similar, the quality and developmental capacities of produced ova were lower in the group of fat donors.
Prevalence of breast-feeding and exclusive breast-feeding at 48 h after birth and up to the sixth month in Cyprus: the BrEaST start in life project
Authors: Economou Mary , Kolokotroni Ourania , Paphiti-Demetriou Irene , Kouta Christiana , Lambrinou Ekaterini , Hadjigeorgiou Eleni , Hadjiona Vasiliki , Tryfonos Froso , Philippou Elena , Middleton Nicos
Published: November 2017

Objective

To assess the prevalence and sociodemographic determinants of breast-feeding (BF) and exclusive breast-feeding (EBF) in Cyprus up to the sixth month.

Design

Cross-sectional and longitudinal descriptive study. BF and EBF were estimated based on mothers’ self-reported BF status in line with Step 7 of the WHO/UNICEF Baby-Friendly Hospital Initiative questionnaire and based on 24 h recall.

Setting

Maternity wards in all public hospitals and twenty-nine (of thirty-five) private maternity clinics nationwide.

Subjects

Consecutive sample of 586 mothers recruited within 48 h from birth, followed up by telephone interview at the first, fourth and sixth month.

Results

Although 84·3 % of mothers initiated BF before discharge, prevalence of BF at the sixth month was 32·4 %, with the highest reduction observed between the first and fourth months. Prevalence of EBF at 48 h was 18·8 % and fell gradually to 5·0 % at the sixth month. Mothers with higher educational attainment or higher family income were more likely to breast-feed until the sixth month. In terms of EBF, an association was observed only with education, which persisted until the sixth month. Other than social gradient, mode of delivery was the strongest determinant of BF initiation, exclusivity and continuation. Mothers who gave birth vaginally were three to four times more likely to initiate BF (OR=3·1; 95 % CI 1·7, 5·4) and EBF (OR=4·3; 95 % CI 2·7, 6·8).

Conclusions

The low prevalence of BF and EBF in Cyprus, together with the fact that caesarean section rates are currently among the highest in Europe, suggest the need for further research to understand this multidimensional phenomenon and for interdisciplinary policy action to protect, promote and support BF.
Improving the implementation of nutrition guidelines in childcare centres improves child dietary intake: findings of a randomised trial of an implementation intervention
Authors: Seward Kirsty , Wolfenden Luke , Finch Meghan , Wiggers John , Wyse Rebecca , Jones Jannah , Yoong Sze Lin
Published: November 2017

Objective

Evidence suggests that improvements to the childcare nutrition environment can have a positive impact on child dietary intake. The primary aim of the present study was to assess, relative to usual care, the effectiveness of a multi-strategy implementation intervention in improving childcare compliance with nutrition guidelines. As a secondary aim, the impact on child dietary intake was assessed.

Design

Parallel-group, randomised controlled trial design. The 6-month intervention was designed to overcome barriers to implementation of the nutrition guidelines that had been identified by applying the theoretical domains framework.

Setting

Hunter New England region, New South Wales, Australia.

Subjects

Forty-five centre-based childcare services.

Results

There were no differences between groups in the proportion of services providing food servings (per child) compliant with nutrition guideline recommendations for all five (5/5) food groups at follow-up (i.e. full compliance). Relative to control services, intervention services were more likely to be compliant with guidelines (OR; 95 % CI) in provision of fruit (10·84; 1·19, 551·20;P=0·0024), meat and meat alternatives (8·83; 1·55, –;P=0·023), dairy (8·41; 1·60, 63·62;P=0·006) and discretionary foods (17·83; 2·15, 853·73;P=0·002). Children in intervention services consumed greater servings (adjusted difference; 95 % CI) of fruit (0·41; 0·09, 0·73;P=0·014) and vegetables (0·70; 0·33, 1·08;P<0·001).

Conclusions

Findings indicate that service-level changes to menus in line with dietary guidelines can result in improvements to children’s dietary intake. The study provides evidence to advance implementation research in the setting as a means of enhancing child public health nutrition.
X-Ray Excited Optical Luminescence and Portable Electron Probe Microanalyzer–Cathodoluminescence (EPMA–CL) Analyzers for On-Line and On-Site Analysis of Nonmetallic Inclusions in Steel
Authors: Imashuku Susumu , Ono Koichiro , Wagatsuma Kazuaki
Published: November 2017

The potential of the application of an X-ray excited optical luminescence (XEOL) analyzer and portable analyzers, composed of a cathodoluminescence (CL) spectrometer and electron probe microanalyzer (EPMA), to the on-line and on-site analysis of nonmetallic inclusions in steel is investigated as the first step leading to their practical use. MgAl2O4 spinel and Al2O3 particles were identified by capturing the luminescence as a result of irradiating X-rays in air on a model sample containing MgAl2O4 spinel and Al2O3 particles in the size range from 20 to 50 μm. We were able to identify the MgAl2O4 spinel and Al2O3 particles in the same sample using the portable CL spectrometer. In both cases, not all of the particles in the sample were identified because the luminescence intensities of the smaller Al2O3 in particular were too low to detect. These problems could be solved by using an X-ray tube with a higher power and increasing the beam current of the portable CL spectrometer. The portable EPMA distinguished between the MgAl2O4 spinel and Al2O3 particles whose luminescent colors were detected using the portable CL spectrometer. Therefore, XEOL analysis has potential for the on-line analysis of nonmetallic inclusions in steel if we have information on the luminescence colors of the nonmetallic inclusions. In addition, a portable EPMA–CL analyzer would be able to perform on-site analysis of nonmetallic inclusions in steel.
A cognitive approach to persistent complex bereavement disorder (PCBD)
Authors: Duffy Michael , Wild Jennifer
Published: November 2017

Persistent complex bereavement disorder (PCBD) has been included in the appendix of the fifth edition of the Diagnostic and Statistical Manual for Mental Disorders as a condition for further study, and a new diagnostic category of prolonged grief disorder (PGD) is likely to be added to the International Statistical Classification of Diseases and Related Health Problems (ICD-11) (Maercker et al., 2013). Whilst there is increasing evidence that prolonged grief has distinct characteristics (Bryant, 2012), there are clinical features that overlap with post-traumatic stress disorder (PTSD), such as intrusive memories, emotional numbing, and avoidance of trauma or loss reminders. Here we describe how the cognitive model for persistent PTSD (Ehlers and Clark, 2000) and trauma-focused cognitive therapy for PTSD (Ehlers et al., 2005) have been helpful in treating persistent complex grief.
Global Risks, Divergent Pandemics: Contrasting Responses to Bubonic Plague and Smallpox in 1901 Cape Town
Authors: White Alexandre I. R.
Published: November 2017

This article explores two simultaneous epidemics that, despite similar pathologies, prompted significantly varying responses from public health actors in 1901 Cape Town: the bubonic plague and smallpox. The Cape Colony responded to the plague with racialized quarantining, forcibly removing all black Africans from certain poor neighborhoods and transferring them to a camp on the outskirts of the city. It was the most significant segregationist act in Cape Town's history to date and foreshadowed the actions of governments in postunification and apartheid South Africa. Conversely, smallpox, though highly contagious and deadly, did not prompt similar aggression. Drawing from archival material, I argue that this differential treatment was the result of a global medical concern for the spread of plague to Europe that imposed external demands upon any region affected by plague that were nonexistent for smallpox. These demands aligned with local ideologies that equated state control with racial discipline to produce the first urban township in South Africa. This article addresses the global processes at work within seemingly localized epidemics and contributes to existing scholarship by exploring the role of medical experts and scientific knowledge in the framing of early pandemic threats.
Influence of Broadcast Spray Nozzle on the Deposition, Absorption, and Efficacy of Dicamba plus Glyphosate on Four Glyphosate-Resistant Dicot Weed Species
Authors: Legleiter Travis R. , Young Bryan G. , Johnson William G.
Published: November 2017

Dicamba-resistant soybean technology provides an additional site of action for POST control of herbicide-resistant broadleaf weeds in soybean but also raises concern of off-site movement and damage to sensitive crops in adjacent fields. Dicamba formulations approved for use on dicamba-resistant soybean require applicators to use nozzles producing large droplets to reduce the risk of spray-particle drift. The use of nozzles with relatively larger droplet spectra can reduce herbicide deposition on target weeds, especially if a filtering effect from the crop canopy occurs. Experiments were conducted to evaluate the influence of broadcast nozzle design on the deposition and efficacy of 280 g ha−1glyphosate plus 140 g ha−1dicamba applied POST to four herbicide-resistant weed species. The TTI11004 nozzle, the original nozzle labeled for dicamba applications on dicamba-resistant soybean, reduced deposition coverage and density on spray cards compared with the TT11004 and XR11004 nozzle. The AIXR11004 nozzle produces a very coarse droplet spectrum and did not reduce coverage on spray cards, though it did reduce deposition density. Herbicide solution deposition onto Palmer amaranth, tall waterhemp, giant ragweed, and horseweed ranged from 0.41 to 0.52, 0.55 to 0.87, 0.49 to 0.58, and 0.38 to 0.41 µl cm−2, respectively. Nozzle design and droplet spectrum did not influence the deposition of herbicide solution onto the target weed, as all nozzles were equivalent for all species and site-years. Herbicide efficacy was not influenced by nozzle design, as weed control and plant height reduction were similar for all species. The results of this experiment show that the use of the TTI11004 nozzle for dicamba applications to dicamba-resistant soybean will provide acceptable herbicide deposition and efficacy when applied under the label requirements of weed height and carrier volume.
Too Tasty to Be Ignored
Authors: Dummel Sebastian , Hübner Ronald
Published: November 2017

Abstract. Recent research has shown that even non-salient stimuli (colored circles) can gain attentional weight, when they have been loaded with some value through previous reward learning. The present study examined such value-based attentional weighting with intrinsically rewarding food stimuli. Different snacks were assumed to have different values for people due to individual food preferences. Participants indicated their preferences toward various snacks and then performed a flanker task with these snacks: they had to categorize a target snack as either sweet or salty; irrelevant flanker snacks were either compatible or incompatible with the target category. Results of a linear mixed-effects model show that the effect of flanker compatibility on participants’ performance (response times) increased with the participants’ preference toward the flanking snacks. This shows, for the first time, that attentional weightings in a flanker task with naturalistic stimuli (snacks) are modulated by participants’ preferences toward the flankers.
Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility
Authors: Sud Amit , Thomsen Hauke , Law Philip J. , Försti Asta , Filho Miguel Inacio da Silva , Holroyd Amy , Broderick Peter , Orlando Giulia , Lenive Oleg , Wright Lauren , Cooke Rosie , Easton Douglas , Pharoah Paul , Dunning Alison , Peto Julian , Canzian Federico , Eeles Rosalind , Kote-Jarai ZSofia , Muir Kenneth , Pashayan Nora ,   The PRACTICAL consortium, Henderson Brian E. , Haiman Christopher A. , Benlloch Sara , Schumacher Fredrick R. , Olama Ali Amin Al , Berndt Sonja I. , Conti David V. , Wiklund Fredrik , Chanock Stephen , Stevens Victoria L. , Tangen Catherine M. , Batra Jyotsna , Clements Judith , Gronberg Henrik , Schleutker Johanna , Albanes Demetrius , Weinstein Stephanie , Wolk Alicja , West Catharine , Mucci Lorelei , Cancel-Tassin Géraldine , Koutros Stella , Sorensen Karina Dalsgaard , Maehle Lovise , Neal David E. , Travis Ruth C. , Hamilton Robert J. , Ingles Sue Ann , Rosenstein Barry , Lu Yong-Jie , Giles Graham G. , Kibel Adam S. , Vega Ana , Kogevinas Manolis , Penney Kathryn L. , Park Jong Y. , Stanford Janet L. , Cybulski Cezary , Nordestgaard Børge G. , Brenner Hermann , Maier Christiane , Kim Jeri , John Esther M. , Teixeira Manuel R. , Neuhausen Susan L. , De Ruyck Kim , Razack Azad , Newcomb Lisa F. , Lessel Davor , Kaneva Radka , Usmani Nawaid , Claessens Frank , Townsend Paul A. , Gago-Dominguez Manuela , Roobol Monique J. , Menegaux Florence , Hoffmann Per , Nöthen Markus M. , Jöckel Karl-Heinz , Strandmann Elke Pogge von , Lightfoot Tracy , Kane Eleanor , Roman Eve , Lake Annette , Montgomery Dorothy , Jarrett Ruth F. , Swerdlow Anthony J. , Engert Andreas , Orr Nick , Hemminki Kari , Houlston Richard S.
Published: November 2017

Several susceptibility loci for classical Hodgkin lymphoma have been reported. However, much of the heritable risk is unknown. Here, we perform a meta-analysis of two existing genome-wide association studies, a new genome-wide association study, and replication totalling 5,314 cases and 16,749 controls. We identify risk loci for all classical Hodgkin lymphoma at 6q22.33 (rs9482849, P = 1.52 × 10−8) and for nodular sclerosis Hodgkin lymphoma at 3q28 (rs4459895,P = 9.43 × 10−17), 6q23.3 (rs6928977,P = 4.62 × 10−11), 10p14 (rs3781093,P = 9.49 × 10−13), 13q34 (rs112998813,P = 4.58 × 10−8) and 16p13.13 (rs34972832, P = 2.12 × 10−8). Additionally, independent loci within the HLA region are observed for nodular sclerosis Hodgkin lymphoma (rs9269081, HLA-DPB1*03:01, Val86 in HLA-DRB1) and mixed cellularity Hodgkin lymphoma (rs1633096, rs13196329, Val86 in HLA-DRB1). The new and established risk loci localise to areas of active chromatin and show an over-representation of transcription factor binding for determinants of B-cell development and immune response.
Evidence for single metal two electron oxidative addition and reductive elimination at uranium
Authors: Gardner Benedict M. , Kefalidis Christos E. , Lu Erli , Patel Dipti , McInnes Eric J. L. , Tuna Floriana , Wooles Ashley J. , Maron Laurent , Liddle Stephen T.
Published: November 2017

Reversible single-metal two-electron oxidative addition and reductive elimination are common fundamental reactions for transition metals that underpin major catalytic transformations. However, these reactions have never been observed together in the f-block because these metals exhibit irreversible one- or multi-electron oxidation or reduction reactions. Here we report that azobenzene oxidises sterically and electronically unsaturated uranium(III) complexes to afford a uranium(V)-imido complex in a reaction that satisfies all criteria of a single-metal two-electron oxidative addition. Thermolysis of this complex promotes extrusion of azobenzene, where H-/D-isotopic labelling finds no isotopomer cross-over and the non-reactivity of a nitrene-trap suggests that nitrenes are not generated and thus a reductive elimination has occurred. Though not optimally balanced in this case, this work presents evidence that classical d-block redox chemistry can be performed reversibly by f-block metals, and that uranium can thus mimic elementary transition metal reactivity, which may lead to the discovery of new f-block catalysis.
Multiplex single-cell visualization of nucleic acids and protein during HIV infection
Authors: Puray-Chavez Maritza , Tedbury Philip R. , Huber Andrew D. , Ukah Obiaara B. , Yapo Vincent , Liu Dandan , Ji Juan , Wolf Jennifer J. , Engelman Alan N. , Sarafianos Stefan G.
Published: November 2017

Technical limitations in simultaneous microscopic visualization of RNA, DNA, and proteins of HIV have curtailed progress in this field. To address this need we develop a microscopy approach, multiplex immunofluorescent cell-based detection of DNA, RNA and Protein (MICDDRP), which is based on branched DNA in situ hybridization technology. MICDDRP enables simultaneous single-cell visualization of HIV (a) spliced and unspliced RNA, (b) cytoplasmic and nuclear DNA, and (c) Gag. We use MICDDRP to visualize incoming capsid cores containing RNA and/or nascent DNA and follow reverse transcription kinetics. We also report transcriptional “bursts” of nascent RNA from integrated proviral DNA, and concomitant HIV-1, HIV-2 transcription in co-infected cells. MICDDRP can be used to simultaneously detect multiple viral nucleic acid intermediates, characterize the effects of host factors or drugs on steps of the HIV life cycle, or its reactivation from the latent state, thus facilitating the development of antivirals and latency reactivating agents.
Remodelling of the gut microbiota by hyperactive NLRP3 induces regulatory T cells to maintain homeostasis
Authors: Yao Xiaomin , Zhang Chenhong , Xing Yue , Xue Guang , Zhang Qianpeng , Pan Fengwei , Wu Guojun , Hu Yingxin , Guo Qiuhong , Lu Ailing , Zhang Xiaoming , Zhou Rongbin , Tian Zhigang , Zeng Benhua , Wei Hong , Strober Warren , Zhao Liping , Meng Guangxun
Published: November 2017

Inflammasomes are involved in gut homeostasis and inflammatory pathologies, but the role of NLRP3 inflammasome in these processes is not well understood. Cryopyrin-associated periodic syndrome (CAPS) patients with NLRP3 mutations have autoinflammation in skin, joints, and eyes, but not in the intestine. Here we show that the intestines of CAPS model mice carrying anNlrp3R258Wmutation maintain homeostasis in the gut. Additionally, such mice are strongly resistant to experimental colitis and colorectal cancer; this is mainly through a remodelled gut microbiota with enhanced anti-inflammatory capacity due to increased induction of regulatory T cells (Tregs). Mechanistically, NLRP3R258Wfunctions exclusively in the lamina propria mononuclear phagocytes to directly enhance IL-1β but not IL-18 secretion. Increased IL-1β boosts local antimicrobial peptides to facilitate microbiota remodelling. Our data show that NLRP3R258W-induced remodelling of the gut microbiota, induces local Tregsto maintain homeostasis and compensate for otherwise-detrimental intestinal inflammation.
Magnesium uptake by connecting fluid-phase endocytosis to an intracellular inorganic cation filter
Authors: Klompmaker Sandra H. , Kohl Kid , Fasel Nicolas , Mayer Andreas
Published: November 2017

Cells acquire free metals through plasma membrane transporters. But, in natural settings, sequestering agents often render metals inaccessible to transporters, limiting metal bioavailability. Here we identify a pathway for metal acquisition, allowing cells to cope with this situation. Under limited bioavailability of Mg2+, yeast cells upregulate fluid-phase endocytosis and transfer solutes from the environment into their vacuole, an acidocalcisome-like compartment loaded with highly concentrated polyphosphate. We propose that this anionic inorganic polymer, which is an avid chelator of Mg2+, serves as an immobilized cation filter that accumulates Mg2+ inside these organelles. It thus allows the vacuolar exporter Mnr2 to efficiently transfer Mg2+ into the cytosol. Leishmania parasites also employ acidocalcisomal polyphosphate to multiply in their Mg2+-limited habitat, the phagolysosomes of inflammatory macrophages. This suggests that the pathway for metal uptake via endocytosis, acidocalcisomal polyphosphates and export into the cytosol, which we term EAPEC, is conserved.
Directed self-assembly of fluorescence responsive nanoparticles and their use for real-time surface and cellular imaging
Authors: Cheung Shane , O’Shea Donal F.
Published: November 2017

Directed self-assemblies in water are known as the most efficient means of forming complex higher ordered structures in nature. Here we show a straightforward and robust method for particle assembly which utilises the amphiphilic tri-block co-polymer poloxamer-188 and a hydrophobic fluorophore as the two designer components, which have a built-in ability to convey spatial and temporal information about their surroundings to an observer. Templating of particle self-assembly is attributed to interactions between the fluorophore and hydrophobic segment of the poloxamer. Particle fluorescence in water is quenched but can be induced to selectively switch on in response to temperature, surface adsorption and cellular uptake. The ability of the particles to dynamically modulate emission intensity can be exploited for selective labelling and real-time imaging of drug crystal surfaces, natural fibres and insulin fibrils, and cellular delivery. As particle solutions are easily prepared, further applications for this water-based NIR-fluorescent paint are anticipated.
Autonomous calibration of single spin qubit operations
Authors: Frank Florian , Unden Thomas , Zoller Jonathan , Said Ressa S. , Calarco Tommaso , Montangero Simone , Naydenov Boris , Jelezko Fedor
Published: November 2017

Fully autonomous precise control of qubits is crucial for quantum information processing, quantum communication, and quantum sensing applications. It requires minimal human intervention on the ability to model, to predict, and to anticipate the quantum dynamics, as well as to precisely control and calibrate single qubit operations. Here, we demonstrate single qubit autonomous calibrations via closed-loop optimisations of electron spin quantum operations in diamond. The operations are examined by quantum state and process tomographic measurements at room temperature, and their performances against systematic errors are iteratively rectified by an optimal pulse engineering algorithm. We achieve an autonomous calibrated fidelity up to 1.00 on a time scale of minutes for a spin population inversion and up to 0.98 on a time scale of hours for a single qubit $$\frac{\pi }{2}$$

π

2

-rotation within the experimental error of 2%. These results manifest a full potential for versatile quantum technologies.
De novo transcriptome assembly of Zanthoxylum bungeanum using Illumina sequencing for evolutionary analysis and simple sequence repeat marker development
Authors: Feng Shijing , Zhao Lili , Liu Zhenshan , Liu Yulin , Yang Tuxi , Wei Anzhi
Published: November 2017

Zanthoxylum, an ancient economic crop in Asia, has a satisfying aromatic taste and immense medicinal values. A lack of genomic information and genetic markers has limited the evolutionary analysis and genetic improvement of Zanthoxylum species and their close relatives. To better understand the evolution, domestication, and divergence of Zanthoxylum, we present a de novo transcriptome analysis of an elite cultivar of Z. bungeanum using Illumina sequencing; we then developed simple sequence repeat markers for identification of Zanthoxylum. In total, we predicted 45,057 unigenes and 22,212 protein coding sequences, approximately 90% of which showed significant similarities to known proteins in databases. Phylogenetic analysis indicated that Zanthoxylum is relatively recent and estimated to have diverged from Citrus ca. 36.5–37.7 million years ago. We also detected a whole-genome duplication event in Zanthoxylum that occurred 14 million years ago. We found no protein coding sequences that were significantly under positive selection by Ka/Ks. Simple sequence repeat analysis divided 31 Zanthoxylum cultivars and landraces into three major groups. This Zanthoxylum reference transcriptome provides crucial information for the evolutionary study of the Zanthoxylum genus and the Rutaceae family, and facilitates the establishment of more effective Zanthoxylum breeding programs.
Emphatic visualization of sphingomyelin-rich domains by inter-lipid FRET imaging using fluorescent sphingomyelins
Authors: Kinoshita Masanao , Ano Hikaru , Murata Michio , Shigetomi Kenta , Ikenouchi Junichi , Matsumori Nobuaki
Published: November 2017

Imaging the distribution of sphingomyelin (SM) in membranes is an important issue in lipid-raft research. Recently we developed novel fluorescent SM analogs that exhibit partition and dynamic behaviors similar to native SM, and succeeded in visualizing lateral domain-segregation between SM-rich liquid-ordered (Lo) and SM-poor liquid-disordered (Ld) domains. However, because the fluorescent contrast between these two domains depends directly on their partition ratio for the fluorescent SMs, domain-separation becomes indeterminate when the distribution difference is not great enough. In this study, we propose the use of inter-lipid Förster resonance energy transfer (FRET) imaging between fluorescent SMs to enhance the contrast of the two domains in cases in which the inter-domain difference in SM distribution is inadequate for conventional monochromic imaging. Our results demonstrate that inter-lipid FRET intensity was significantly higher in the Lo domain than in the Ld domain, resulting in a clear and distinguishable contrast between the two domains even in poorly phase-separated giant unilamellar vesicles. In addition, we show that inter-lipid FRET imaging is useful for selective visualization of highly condensed assemblies and/or clusters of SM molecules in living cell membranes. Thus, the inter-lipid FRET imaging technique can selectively emphasize the SM-condensed domains in both artificial and biological membranes.
3D photogrammetry quantifies growth and external erosion of individual coral colonies and skeletons
Authors: Ferrari Renata , Figueira Will F. , Pratchett Morgan S. , Boube Tatiana , Adam Arne , Kobelkowsky-Vidrio Tania , Doo Steve S. , Atwood Trisha Brooke , Byrne Maria
Published: November 2017

Growth and contraction of ecosystem engineers, such as trees, influence ecosystem structure and function. On coral reefs, methods to measure small changes in the structure of microhabitats, driven by growth of coral colonies and contraction of skeletons, are extremely limited. We used 3D reconstructions to quantify changes in the external structure of coral colonies of tabular Acropora spp., the dominant habitat-forming corals in shallow exposed reefs across the Pacific. The volume and surface area of live colonies increased by 21% and 22%, respectively, in 12 months, corresponding to a mean annual linear extension of 5.62 cm yr−1 (±1.81 SE). The volume and surface area of dead skeletons decreased by 52% and 47%, respectively, corresponding to a mean decline in linear extension of −29.56 cm yr−1 (±7.08 SE), which accounted for both erosion and fragmentation of dead colonies. This is the first study to use 3D photogrammetry to assess fine-scale structural changes of entire individual colonies in situ, quantifying coral growth and contraction. The high-resolution of the technique allows for detection of changes on reef structure faster than other non-intrusive approaches. These results improve our capacity to measure the drivers underpinning ecosystem biodiversity, status and trajectory.
A polar bundle of flagella can drive bacterial swimming by pushing, pulling, or coiling around the cell body
Authors: Hintsche Marius , Waljor Veronika , Großmann Robert , Kühn Marco J. , Thormann Kai M. , Peruani Fernando , Beta Carsten
Published: November 2017

Bacteria swim in sequences of straight runs that are interrupted by turning events. They drive their swimming locomotion with the help of rotating helical flagella. Depending on the number of flagella and their arrangement across the cell body, different run-and-turn patterns can be observed. Here, we present fluorescence microscopy recordings showing that cells of the soil bacterium Pseudomonas putida that are decorated with a polar tuft of helical flagella, can alternate between two distinct swimming patterns. On the one hand, they can undergo a classical push-pull-push cycle that is well known from monopolarly flagellated bacteria but has not been reported for species with a polar bundle of multiple flagella. Alternatively, upon leaving the pulling mode, they can enter a third slow swimming phase, where they propel themselves with their helical bundle wrapped around the cell body. A theoretical estimate based on a random-walk model shows that the spreading of a population of swimmers is strongly enhanced when cycling through a sequence of pushing, pulling, and wrapped flagellar configurations as compared to the simple push-pull-push pattern.
Spatial statistical modelling of capillary non-perfusion in the retina
Authors: MacCormick Ian J. C. , Zheng Yalin , Czanner Silvester , Zhao Yitian , Diggle Peter J. , Harding Simon P. , Czanner Gabriela
Published: November 2017

Manual grading of lesions in retinal images is relevant to clinical management and clinical trials, but it is time-consuming and expensive. Furthermore, it collects only limited information - such as lesion size or frequency. The spatial distribution of lesions is ignored, even though it may contribute to the overall clinical assessment of disease severity, and correspond to microvascular and physiological topography. Capillary non-perfusion (CNP) lesions are central to the pathogenesis of major causes of vision loss. Here we propose a novel method to analyse CNP using spatial statistical modelling. This quantifies the percentage of CNP-pixels in each of 48 sectors and then characterises the spatial distribution with goniometric functions. We applied our spatial approach to a set of images from patients with malarial retinopathy, and found it compares favourably with the raw percentage of CNP-pixels and also with manual grading. Furthermore, we were able to quantify a biological characteristic of macular CNP in malaria that had previously only been described subjectively: clustering at the temporal raphe. Microvascular location is likely to be biologically relevant to many diseases, and so our spatial approach may be applicable to a diverse range of pathological features in the retina and other organs.
Pathologic N0 Status in Clinical T1N0M0 Lung Adenocarcinoma is Predictable by the Solid Component Proportion with Quantitative CT Number Analysis
Authors: Li Meng , Wu Ning , Zhang Li , Sun Wei , Wang Jianwei , Lv Lv , Ren Jiansong , Lin Dongmei
Published: November 2017

Correctly predicting pathologic regional node-negative (pN0) disease in patients with lung cancer before operation may avoid unnecessary mediastinal lymph node dissection (MLND). In this study, we analyze the value of the radiographic and histopathological features of primary tumors for predicting pN0 status in cT1N0M0 lung adenocarcinoma and to establish an optimal surgical strategy for avoiding MLND in cT1N0M0 lung adenocarcinoma patients. We retrospectively investigated the histopathological and radiographic data of 348 surgically resected cT1N0M0 lung adenocarcinoma patients with systematic lymph node dissection from January 2005 to December 2012. Histopathological features and radiographic features were analyzed. Multivariable analysis was used to identify significant predictors of pN0 disease. Our results showed that pN0 disease was detected in 306 patients (87.9%) among the 348 patients with cT1N0M0 lung adenocarcinoma. A decreasing trend of the pN0 disease proportion was observed with both increasing histological grade and decreased differentiation (P < 0.001). In multivariable analysis, the solid component proportion was a significant predictor of pN0 disease. Among 110 patients with a solid component proportion of no more than 21.3%, mediastinal lymph node involvement was not observed. Patients who meet this criterion may be successfully managed with lung resection without MLND.
A hybrid strain and thermal energy harvester based on an infra-red sensitive Er3+ modified poly(vinylidene fluoride) ferroelectret structure
Authors: Ghosh Sujoy Kumar , Xie Mengying , Bowen Christopher Rhys , Davies Philip R. , Morgan David J. , Mandal Dipankar
Published: November 2017

In this paper, a novel infra-red (IR) sensitive Er3+ modified poly(vinylidene fluoride) (PVDF) (Er-PVDF) film is developed for converting both mechanical and thermal energies into useful electrical power. The addition of Er3+ to PVDF is shown to improve piezoelectric properties due to the formation of a self-polarized ferroelectric β-phase and the creation of an electret-like porous structure. In addition, we demonstrate that Er3+ acts to enhance heat transfer into the Er-PVDF film due to its excellent infrared absorbance, which, leads to rapid and large temperature fluctuations and improved pyroelectric energy transformation. We demonstrate the potential of this novel material for mechanical energy harvesting by creating a durable ferroelectret energy harvester/nanogenerator (FTNG). The high thermal stability of the β-phase enables the FTNG to harvest large temperature fluctuations (ΔT ~ 24 K). Moreover, the superior mechanosensitivity, SM ~ 3.4 VPa−1 of the FTNG enables the design of a wearable self-powered health-care monitoring system by human-machine integration. The combination of rare-earth ion, Er3+ with the ferroelectricity of PVDF provides a new and robust approach for delivering smart materials and structures for self-powered wireless technologies, sensors and Internet of Things (IoT) devices.
An engineered opsin monomer scrambles phospholipids
Authors: Pandey Kalpana , Ploier Birgit , Goren Michael A. , Levitz Joshua , Khelashvili George , Menon Anant K.
Published: November 2017

The G protein-coupled receptor opsin is a phospholipid scramblase that facilitates rapid transbilayer phospholipid exchange in liposomes. The mechanism by which opsin scrambles lipids is unknown. It has been proposed that lipid translocation may occur at protein-protein interfaces of opsin dimers. To test this possibility, we rationally engineered QUAD opsin by tryptophan substitution of four lipid-facing residues in transmembrane helix 4 (TM4) that is known to be important for dimerization. Atomistic molecular dynamics simulations of wild type and QUAD opsins combined with continuum modeling revealed that the tryptophan substitutions lower the energetically unfavorable residual hydrophobic mismatch between TM4 and the membrane, reducing the drive of QUAD opsin to dimerize. We purified thermostable wild type and QUAD opsins, with or without a SNAP tag for fluorescence labeling. Single molecule fluorescence measurements of purified SNAP-tagged constructs revealed that both proteins are monomers. Fluorescence-based activity assays indicated that QUAD opsin is a fully functional scramblase. However, unlike wild type opsin which dimerizes en route to insertion into phospholipid vesicles, QUAD opsin reconstitutes as a monomer. We conclude that an engineered opsin monomer can scramble phospholipids, and that the lipid-exposed face of TM4 is unlikely to contribute to transbilayer phospholipid exchange.
Adrenergic receptor agonists induce the differentiation of pluripotent stem cell-derived hepatoblasts into hepatocyte-like cells
Authors: Kotaka Maki , Toyoda Taro , Yasuda Katsutaro , Kitano Yuko , Okada Chihiro , Ohta Akira , Watanabe Akira , Uesugi Motonari , Osafune Kenji
Published: November 2017

Current induction methods of hepatocytes from human induced pluripotent stem cells (hiPSCs) are neither low cost nor stable. By screening a chemical library of 1,120 bioactive compounds and known drugs, we identified the α1-adrenergic receptor agonist methoxamine hydrochloride as a small molecule that promotes the differentiation of hiPSC-derived hepatoblasts into ALBUMIN+ hepatocyte-like cells. Other α1-adrenergic receptor agonists also induced the differentiation of hepatocyte-like cells, and an α1-receptor antagonist blocked the hepatic-inducing activity of methoxamine hydrochloride and that of the combination of hepatocyte growth factor (HGF) and Oncostatin M (OsM), two growth factors often used for the induction of hepatoblasts into hepatocyte-like cells. We also confirmed that treatment with methoxamine hydrochloride activates the signal transducer and activator of transcription 3 (STAT3) pathway downstream of IL-6 family cytokines including OsM. These findings allowed us to establish hepatic differentiation protocols for both mouse embryonic stem cells (mESCs) and hiPSCs using small molecules at the step from hepatoblasts into hepatocyte-like cells. The results of the present study suggest that α1-adrenergic agonists induce hepatocyte-like cells by working downstream of HGF and OsM to activate STAT3.
Toehold-enhanced LNA probes for selective pull down and single-molecule analysis of native chromatin
Authors: Hermans Nicolaas , Huisman Juriën Jori , Brouwer Thomas Bauke , Schächner Christopher , van Heusden G. Paul H. , Griesenbeck Joachim , van Noort John
Published: November 2017

The organization of DNA into chromatin is thought to regulate gene expression in eukaryotes. To study its structure in vitro, there is a need for techniques that can isolate specific chromosomal loci of natively assembled chromatin. Current purification methods often involve chemical cross-linking to preserve the chromatin composition. However, such cross-linking may affect the native structure. It also impedes single molecule force spectroscopy experiments, which have been instrumental to probe chromatin folding. Here we present a method for the incorporation of affinity tags, such as biotin, into native nucleoprotein fragments based on their DNA sequence, and subsequent single molecule analysis by magnetic tweezers. DNA oligos with several Locked Nucleic Acid (LNA) nucleotides are shown to selectively bind to target DNA at room temperature, mediated by a toehold end in the target, allowing for selective purification of DNA fragments. The stability of the probe-target hybrid is sufficient to withstand over 65 pN of force. We employ these probes to obtain force-extension curves of native chromatin fragments of the 18S ribosomal DNA from the yeast Saccharomyces cerevisiae. These experiments yield valuable insights in the heterogeneity in structure and composition of natively assembled chromatin at the single-molecule level.
A Ser75-to-Asp phospho-mimicking mutation in Src accelerates ageing-related loss of retinal ganglion cells in mice
Authors: Kashiwagi Kenji , Ito Sadahiro , Maeda Shuichiro , Kato Goro
Published: November 2017

Src knockout mice show no detectable abnormalities in central nervous system (CNS) post-mitotic neurons, likely reflecting functional compensation by other Src family kinases. Cdk1- or Cdk5-dependent Ser75 phosphorylation in the amino-terminal Unique domain of Src, which shares no homology with other Src family kinases, regulates the stability of active Src. To clarify the roles of Src Ser75 phosphorylation in CNS neurons, we established two types of mutant mice with mutations in Src: phospho-mimicking Ser75Asp (SD) and non-phosphorylatable Ser75Ala (SA). In ageing SD/SD mice, retinal ganglion cell (RGC) number in whole retinas was significantly lower than that in young SD/SD mice in the absence of inflammation and elevated intraocular pressure, resembling the pathogenesis of progressive optic neuropathy. By contrast, SA/SA mice and wild-type (WT) mice exhibited no age-related RGC loss. The age-related retinal RGC number reduction was greater in the peripheral rather than the mid-peripheral region of the retina in SD/SD mice. Furthermore, Rho-associated kinase activity in whole retinas of ageing SD/SD mice was significantly higher than that in young SD/SD mice. These results suggest that Src regulates RGC survival during ageing in a manner that depends on Ser75 phosphorylation.