bluuebunny/crossref_metadata_2025 huggingface dataset:
From Separation to Interaction
Authors: Nordqvist Kerkko
Published: December 2016

Up until recent years, Corded Ware has remained poorly studied in the eastern part of the Gulf of Finland, located in north-eastern Europe. Traditionally, this region has been considered marginal in terms of Corded Ware, but new research has started to change this view. This paper presents the Corded Ware material known up to the current date (2016) from the eastern area of the Gulf of Finland, i.e. the Karelian Isthmus and Ingria (western Leningrad oblast, Russia); currently ca. 30 sites and ca. 60 stray finds are known in the research area. Based on this and previously published data from the adjoining regions, features related to the material culture, the contact networks, and the chronology of Corded Ware are discussed. Even though focusing the research may skew the picture, there are good grounds to propose, that there was a distinctive Corded Ware sphere of interaction in the eastern area of the Gulf of Finland, also including areas in north-eastern Estonia and south-eastern Finland. Due to its particular cultural background, local preferences, and consequently, development trajectories, the area had a clear regional character. Further, populations inhabiting it also maintained active contacts with other Corded Ware groups in the sphere of Baltic Sea and further to the east, as well as with non-Corded Ware settlers of north-eastern Europe.
Language Use in Real‐Time Interactions During Early Elementary Science Lessons: The Bidirectional Dynamics of the Language Complexity of Teachers and Students
Authors: Menninga Astrid , van Dijk Marijn , Steenbeek Henderien , van Geert Paul
Published: December 2016

This study used a dynamic approach to explore bidirectional sequential relations between the real‐time language use of teachers and students in naturalistic early elementary science lessons. It also compared experienced teachers (n = 22) with novice teachers (n = 8) with respect to such relations. Verbal interactions were transcribed and coded at the utterance level for syntactic complexity, lexical density of content word use, and open‐ended teacher questions. Sequential analyses provided evidence for the existence of a bidirectional relationship, meaning that both teachers and students were sensitive to each other's use of complex and dense language. In addition, the use of open‐ended teacher questions was related to complex and dense student utterances. Comparisons between experienced teachers and novice teachers revealed that sequential patterns were stronger in the case of experienced teachers, suggesting that there were more flexible adaptation processes in this group.
Radioembolization for hepatocellular carcinoma: gaining insight on a personalized approach
Authors: Sangro Bruno , Rodriguez Macarena
Published: December 2016

See Article on Page 101
Changing survival of people with myeloma and end stage kidney disease: A cohort study using Australian and New Zealand dialysis and transplant registry 1963–2013
Authors: Webster Angela C , Irish Ashley B , Kelly Patrick J
Published: December 2016

Background

It is unclear whether recent advances in myeloma therapy have improved survival for all those with myeloma and end stage kidney disease (ESKD).

Methods

Population‐based registry cohort study using Australia and New Zealand Dialysis and Transplant Registry data 1963–2013. We measured survival of people with myeloma and other plasma cell dyscrasias and ESKD over time, and investigated prognostic factors for improved survival using survival analysis (results expressed as hazard ratios (HR) with 95% confidence intervals).

Results

We included 65 940 people (207 595 person‐years); 1067 people (1.6%) with myeloma and 572 (0.9%) with other plasma cell dyscrasia. Myeloma ESKD rose from 0.8% before 1994 to 2.2% in 2004 and remained stable. People with myeloma were older, and age increased over time, from 62.5 before 1994 to 70.1 years from 2010, but the non‐myeloma group age increased more steeply (52.0 before 1994; 62.2 from 2010). In myeloma patients, survival improved (P < 0.001) with recent predicted 5 year survival of 27.5% aged <55, 32.2% aged 55–64, 16.3% for 65–74 and 12.7% aged ≥75 years. Survival did not improve for plasma cell dyscrasia patients (P = 0.70). Myeloma patients on peritoneal dialysis had improved survival compared with those on haemodialysis (HR 0.7, CI 0.6–0.9), but those aged ≥65 had poorer survival (65–74 years HR 1.5, CI1.2–1.9; ≥75 HR 1.7, CI1.3–2.1), as did diabetics (HR 1.3, CI1.1–1.6).

Conclusions

The proportion of people with myeloma and ESKD remains stable, but their survival has progressively improved in Australia and New Zealand. On starting ESKD treatment with myeloma, a 59 year old without diabetes on peritoneal dialysis can expect a 45% 5 year survival, where a 75‐year‐old diabetic on haemodialysis has 9% 5 year survival.
Biopsy‐proven case of Epstein–Barr virus (EBV)‐associated vasculitis of the central nervous system
Authors: Kano Kohei , Katayama Takayuki , Takeguchi Shiori , Asanome Asuka , Takahashi Kae , Saito Tsukasa , Sawada Jun , Saito Masato , Anei Ryogo , Kamada Kyousuke , Miyokawa Naoyuki , Nishihara Hiroshi , Hasebe Naoyuki
Published: December 2016

A 75‐year‐old woman was admitted to our hospital with rapidly deteriorating consciousness disturbance. She had a 7‐year history of rheumatoid arthritis (RA), which had been treated with methotrexate (MTX) and prednisolone. Brain T2‐weighted MRI showed diffuse high‐intensity lesions in the cerebral subcortical and deep white matter, bilateral basal ganglia and thalamus. A cerebrospinal fluid examination revealed elevated protein levels and positive Epstein–Barr virus (EBV) DNA. Human immunodeficiency virus was negative. Brain biopsy showed perivascular lymphocytic infiltration in the parenchyma and meninx with EBV‐encoded small RNA (EBER). Since this case did not fulfill the criteria for chronic active EBV infection (CAEBV), she was diagnosed with Epstein–Barr virus (EBV)‐associated vasculitis of the central nervous system. High‐dose methylprednisolone, acyclovir, ganciclovir and foscarnet were not effective. Although EBV is a causative agent of infectious mononucleosis (IM), lymphomas and nasopharyngeal carcinomas, vasculitic pathology of the central nervous system with EBV reactivation in the elderly is rare. Immunosuppressive drugs such as steroids and MTX are widely used to treat autoimmune disorders, but may exacerbate the reactivation of EBV. This is the first case of biopsy‐proven EBV‐positive/HIV‐negative vasculitis during the treatment of RA with MTX and steroids. This case indicates that EBV‐associated vasculitis needs to be considered as a differential diagnosis of CNS vasculitis.
Duty and dilemma: Perioperative nurses hiding an objection to participate in organ procurement surgery
Authors: Smith Zaneta
Published: December 2016

Perioperative nurses assist in organ procurement surgery; however, there is a dearth of information of how they encounter making conscientious objection requests or refusals to participate in organ procurement surgery. Organ procurement surgical procedures can present to the operating room ad hoc and can catch a nurse who may not desire to participate by surprise with little opportunity to refuse as a result of staffing, skill mix or organizational work demands. This paper that stems from a larger doctoral research study exploring the experiences of perioperative nurses participating in multi‐organ procurement surgery used a grounded theory method to develop a substantive theory of the nurses’ experiences. This current paper aimed to highlight the experiences of perioperative nurses when confronted with expressing a conscientious objection towards their participation in these procedures. A number of organizational and cultural barriers within the healthcare organization were seen to hamper their ability in expressing a conscience‐based refusal, which lead to their reluctant participation. Perioperative nurses must feel safe to express a conscientious objection towards these types of surgical procedures and feel supported in doing so by their respective hospital organizations and not be forced to participate unwillingly.
Hedging, Strategic Partnership, and Taiwan's Relations with Japan Under the Ma Ying‐jeou Administration
Authors: Leng Tse‐Kang , Chang Liao Nien‐chung
Published: December 2016

This article examines Taiwan's new hedging policy toward China and its evolving relations with Japan. Taiwan under President Ma Ying‐jeou focused on hedging its bets against China's rise through engagement, accommodation, and soft balancing. Meanwhile, Taipei and Tokyo are also forging a strategic partnership as they cautiously achieve low‐commitment agreements for deeper cooperation, including signing an important fisheries agreement. Nevertheless, both international and domestic challenges may constrain the flexibility of Taipei's hedging strategy. Given the uncertainty and complexity in East Asia, Taipei will continue its hedging strategy as a way to expand its external cooperation in the region.
Multidimensional cognitive impairment in unipolar and bipolar depression and the moderator effect of adverse childhood experiences
Authors: Poletti Sara , Aggio Veronica , Brioschi Silvia , Dallaspezia Sara , Colombo Cristina , Benedetti Francesco
Published: December 2016

Aim

Studies have demonstrated neuropsychological deficits across a variety of cognitive domains in depression. These deficits are observable both in major depressive disorder (MDD) and in bipolar disorder (BD) and are present in each phase of the illness, including euthymia. Adverse childhood experiences (ACE) have been associated with an increased risk of developing psychiatric disorders and cognitive deficits. The aim of this study was to assess neuropsychological performances in a sample of MDD and BD patients during a depressive episode compared to healthy controls (HC) and, to investigate if ACE affect the cognitive profiles in the three groups.

Methods

Seventy‐six BD patients, 57 MDD patients, and 57 HC underwent neuropsychological assessment for cognitive performances through the Brief Assessment of Cognition in Schizophrenia and Wisconsin Card Sorting Test.

Results

Both BD and MDD patients obtained significantly lower domain scores across the entire battery compared to HC. Splitting the sample according to exposure to ACE (high and low), the differences observed in the whole sample persisted only in the subsample of those patients exposed to high ACE.

Conclusion

This study confirms that cognitive impairment is present both in MDD and BD, albeit in different degrees of severity, and highlights the importance of early stress as a moderator factor when investigating cognitive functions in mood disorders.
Genomic pathobiology of gastric carcinoma
Authors: Katoh Hiroto , Ishikawa Shumpei
Published: December 2016

With the recent advances in genome sequencing technologies, comprehensive cancer genomic profiling has revealed the in‐depth molecular mechanisms of gastric malignancies. New insights into the carcinogenesis pathways of gastric cancers have been acquired, not only by DNA sequencing, but also by the expression profiling of the transcriptome, the identification of chimeric genes, and epi‐genetic profiling (such as DNA hypermethylation). Global genomic profiling of gastric cancers, in combination with histopathology, etiology, and cancer biology, has clarified that gastric cancers can be categorized into four subtypes with specific genomic characteristics. Here, we summarize recent knowledge concerning the clinically relevant genomic classifications of gastric cancers and discuss the therapeutic implications for such genomic subtypes, including future perspectives for immune‐checkpoint blockade therapies against gastric malignancies.
Leveraging Nonprofit and Voluntary Action Research to Inform Public Policy
Authors: Bushouse Brenda K.
Published: December 2016

The field of nonprofit and voluntary action (NVA) studies in the United States originates in the 1970s and has since grown to encompass multiple scholarly associations around the world and graduate degree programs producing faculty with NVA as their primary scholarly focus. This article introduces readers to the NVA field by describing the development of the field, its scholarly associations and publication venues, and education programs. The second section discusses three areas of foundational research: why nonprofit organizations exist, why people give, and nonprofit relations with government. Each of these areas can be drawn upon by public policy scholars to more fully understand how individuals and nonprofit organizations participate in the policy process. The final section identifies three nexuses with policy process: policy design, advocacy, and the role of foundations. These are three areas that have significant potential for research collaborations to connect NVA with policy process literature.
Public/Private Pension Mix, Income Inequality and Poverty among the Elderly in Europe: An Empirical Analysis Using New and Revised OECD Data
Authors: Been Jim , Caminada Koen , Goudswaard Kees , van Vliet Olaf
Published: December 2016

Prior studies have suggested that higher public pensions are associated with lower income inequality among the elderly, whereas the reverse is true for private pensions. Van Vliet et al. () empirically test whether relative shifts from public to private pension schemes entail higher levels of income inequality among the elderly using panel data from the OECD SOCX and the EU‐SILC databases. Contrasting earlier empirical studies using either cross‐sectional or time‐series data, they do not find evidence that shifts from public to private pension provision are associated with higher levels of income inequality or poverty among the elderly. The aim of the current article is to extend the analysis of Van Vliet et al. by: (1) adding additional countries; (2) adding additionally available years; and (3) using revised OECD SOCX data. In contrast to Van Vliet et al., we find that a greater relative importance of private pensions is associated with higher levels of income inequality and poverty among the elderly. A central explanation of the difference in conclusions stems from the revision of OECD SOCX data.
Geographically weighted regression‐based determinants of malaria incidences in northern China
Authors: Ge Yong , Song Yongze , Wang Jinfeng , Liu Wei , Ren Zhoupeng , Peng Junhuan , Lu Binbin
Published: December 2016

Geographically weighted regression (GWR) is an important local method to explore spatial non‐stationarity in data relationships. It has been repeatedly used to examine spatially varying relationships between epidemic diseases and predictors. Malaria, a serious parasitic disease around the world, shows spatial clustering in areas at risk. In this article, we used GWR to explore the local determinants of malaria incidences over a 7‐year period in northern China, a typical mid‐latitude, high‐risk malaria area. Normalized difference vegetation index (NDVI), land surface temperature (LST), temperature difference, elevation, water density index (WDI) and gross domestic product (GDP) were selected as predictors. Results showed that both positively and negatively local effects on malaria incidences appeared for all predictors except for WDI and GDP. The GWR model calibrations successfully depicted spatial variations in the effect sizes and levels of parameters, and also showed substantially improvements in terms of goodness of fits in contrast to the corresponding non‐spatial ordinary least squares (OLS) model fits. For example, the diagnostic information of the OLS fit for the 7‐year average case is R2 = 0.243 and AICc = 837.99, while significant improvement has been made by the GWR calibration with R2 = 0.800 and AICc = 618.54.
Nonhuman labour, encounter value, spectacular accumulation: the geographies of a lively commodity
Authors: Barua Maan
Published: December 2016

This paper maps into geographies of ‘lively commodities’, commodities whose value derives from their status as living beings. In an era where life itself has become a locus of capitalist accumulation, picking apart the category of ‘liveliness’ underpinning commodification has important analytical and geographical stakes. To this end, by tracking historical geographies of commodifying lions in political economies of ecotourism in India, this paper shows how more‐than‐human labour and lively potentials affect commodification and influence accumulation, not simply through recalcitrance, but as active participants within political economic organisation. The paper advances and develops a triad of relational concepts – nonhuman labour, encounter value, spectacular accumulation – through which the political economic potency of lively commodities might be articulated and grasped. It concludes by discussing the analytical potential of this approach and its future purchase for rethinking commodity geographies.
Enhanced efficiencies of sludge dewatering and domestic wastewater treatment by using the bioflocculant from rice stover
Authors: Guo Junyuan , Du Jiali , Chen Peilan , Tan Xiandong , Huang Xinyi , Gan Pengfei , Fu Lin
Published: December 2016

Potential of a bioflocculant from rice stover was studied in sludge dewatering and domestic wastewater treatment. Production of this bioflocculant showed good correspondence to cell growth, after fermentation for 60 h, the fermentation liquor was obtained, from 1.0 L of which a value of 2.37 g bioflocculant can be extracted, and the main backbone of this bioflocculant was polysaccharides. Without adjusting the sludge's initial pH value of 6.5, when incubated with 18 mg/L of this bioflocculant, dry solids (DS) and specific resistance to filtration (SRF) of the typical wastewater activated sludge reached 18.5% and 4.7 × 1012 m/kg, respectively, which was better than the ones achieved by Al2(SO4)3 and FeCl3 flocculants. For domestic wastewater treatment, after treated by 12 mg/L of this bioflocculant at pH value of 7.5, removal efficiencies of chemical oxygen demand (COD) and turbidity can reach 91.8 and 89.7%, respectively, which were better than the ones achieved by the traditional flocculants such as Al2(SO4)3, FeCl3, and polyaluminum chloride (PAC). This study suggested that the bioflocculant from rice stover has great potentials as an alternative flocculant to conventional flocculants in sludge dewatering and domestic wastewater treatment.
Effects of early and delayed initiation of exercise training on cardiac and haemodynamic function after spinal cord injury
Authors: Popok David W. , West Christopher R. , McCracken Laura , Krassioukov Andrei V.
Published: December 2016

New Findings

What is the central question of this study?

How does early versus delayed initiation of passive hindlimb cycling, as well as detraining, affect cardiac function and blood pressure control in a rodent model of spinal cord injury?

What is the main finding and its importance?

Early or delayed initiation of hindlimb cycling improves cardiac and haemodynamic function in spinal cord injury, although the benefits of early administration are more pronounced. We also demonstrate the need for exercise to be maintained, because detraining rapidly reverses the cardiac and haemodynamic benefits.

Spinal cord injury (SCI) reduces physical activity and alters descending supraspinal cardiovascular control, predisposing this population to early onset of cardiovascular disease. We used a T3 SCI rodent model to investigate the effect of early versus delayed passive hindlimb cycling (PHLC), as well as the effect of detraining on cardiac dysfunction and blood pressure control, including autonomic dysreflexia (AD). Twenty male Wistar rats were divided into an early PHLC initiation group followed by a period of detraining (PHLC starting day 6 post‐SCI, for 4 weeks, followed by 4 weeks of detraining; ‘early PHLC/detraining’ group) and a delayed PHLC intervention group (no PHLC for first 5 weeks post‐SCI, followed by PHLC for 4 weeks; ‘no PHLC/delayed PHLC’ group). At 5 weeks post‐SCI, the no PHLC/delayed PHLC group exhibited a decline in almost all cardiac indices (all P < 0.029), which was maintained in the early PHLC/detraining group. Also, the severity of induced AD was reduced in the early PHLC/detraining versus no PHLC/delayed PHLC group (all P < 0.0279). At 9 weeks post‐SCI, no PHLC/delayed PHLC animals exhibited a reversal of cardiac dysfunction such that all indices were not different from pre‐SCI, whereas early PHLC/detraining rats exhibited a reduction in all cardiac indices relative to pre‐SCI (all P < 0.049), except ejection fraction. Between weeks 7 and 9 post‐SCI, the no PHLC/delayed PHLC rats exhibited fewer spontaneous AD events than the early PHLC/detraining rats (P < 0.01). We show, for the first time, that delayed exercise promotes similar improvements in cardiac and haemodynamic function to those observed with early initiation. Furthermore, exercise needs to be maintained, because detraining reduces these cardiohaemodynamic benefits.
Ultrasonic Welding of Magnesium–Titanium Dissimilar Metals: A Study on Influences of Welding Parameters on Mechanical Property by Experimentation and Artificial Neural Network
Authors: Zhao Dewang , Zhao Kunmin , Ren Daxin , Guo Xinglin
Published: December 2016

The advancement in the application of light alloys such as magnesium and titanium is closely related to the state of the art of joining them. As a new type of solid-phase welding, ultrasonic spot welding is an effective way to achieve joints of high strength. In this paper, ultrasonic welding was carried out on magnesium–titanium dissimilar alloys to investigate the influences of welding parameters on joint strength. The analysis of variance was adopted to study the weight of each welding parameter and their interactions. The artificial neural network (ANN) was used to predict joint strength. Results show that in ultrasonic welding of magnesium and titanium alloys, clamping force is the most significant factor, followed by vibration time and vibration amplitude; the interactions between vibration time and vibration amplitude, and between vibration amplitude and clamping force also significantly impact the strength. By using the artificial neural network, test data were trained to obtain a high precision network, which was used to predict the variations of joint strength under different parameters. The analytical model predicts that with the increase in vibration time, the increase in optimal joint strength is limited, but the range of welding parameters to obtain a higher joint strength increases significantly; the minimum joint strength increases as well; and the optimal vibration amplitude expands gradually and reaches the maximum when the vibration time is 1000 ms, then shifts toward the low end gradually.
Engineered feature used to enhance gardening at a 3800-year-old site on the Pacific Northwest Coast
Authors: Hoffmann Tanja , Lyons Natasha , Miller Debbie , Diaz Alejandra , Homan Amy , Huddlestan Stephanie , Leon Roma
Published: December 2016

Ancient complex hunter-gatherers constructed a rock pavement to enhance the predictability and availability of wetland plant resources.
Reactive nitrogen chemistry in aerosol water as a source of sulfate during haze events in China
Authors: Cheng Yafang , Zheng Guangjie , Wei Chao , Mu Qing , Zheng Bo , Wang Zhibin , Gao Meng , Zhang Qiang , He Kebin , Carmichael Gregory , Pöschl Ulrich , Su Hang
Published: December 2016

Multiphase chemistry of NO
2
and alkaline matter in aerosol water explains rapid sulfate formation and severe haze in China.
XPrize finalists mull payloads to the moon
Authors: Clery Daniel
Published: December 2016

Science experiments take a back seat to commercial aims for five teams planning launches.
In India, elite institutes in shady journals
Authors: Pulla Priyanka
Published: December 2016

Predatory publishers draw papers from faculty at top research centers.
Comment on “Structural basis of histone H3K27 trimethylation by an active polycomb repressive complex 2”
Authors: Zhang Ying , Justin Neil , Wilson Jon R. , Gamblin Steven J.
Published: December 2016

Jiao and Liu (Research Articles, 16 October 2015, aac4383) reported the crystal structure of the protein complex polycomb repressive complex 2 from
Chaetomium thermophilum
. This landmark structure has brought invaluable insights into the activation mechanism of this essential methyltransferase. However, the analysis of the x-ray data discussed below suggests that the description of oncogenic H3K27M peptide binding to the active site is incorrect.
A three-dimensional movie of structural changes in bacteriorhodopsin
Authors: Nango Eriko , Royant Antoine , Kubo Minoru , Nakane Takanori , Wickstrand Cecilia , Kimura Tetsunari , Tanaka Tomoyuki , Tono Kensuke , Song Changyong , Tanaka Rie , Arima Toshi , Yamashita Ayumi , Kobayashi Jun , Hosaka Toshiaki , Mizohata Eiichi , Nogly Przemyslaw , Sugahara Michihiro , Nam Daewoong , Nomura Takashi , Shimamura Tatsuro , Im Dohyun , Fujiwara Takaaki , Yamanaka Yasuaki , Jeon Byeonghyun , Nishizawa Tomohiro , Oda Kazumasa , Fukuda Masahiro , Andersson Rebecka , Båth Petra , Dods Robert , Davidsson Jan , Matsuoka Shigeru , Kawatake Satoshi , Murata Michio , Nureki Osamu , Owada Shigeki , Kameshima Takashi , Hatsui Takaki , Joti Yasumasa , Schertler Gebhard , Yabashi Makina , Bondar Ana-Nicoleta , Standfuss Jörg , Neutze Richard , Iwata So
Published: December 2016

Snapshots of bacteriorhodopsin

Bacteriorhodopsin is a membrane protein that harvests the energy content from light to transport protons out of the cell against a transmembrane potential. Nango
et al.
used timeresolved serial femtosecond crystallography at an x-ray free electron laser to provide 13 structural snapshots of the conformational changes that occur in the nanoseconds to milliseconds after photoactivation. These changes begin at the active site, propagate toward the extracellular side of the protein, and mediate internal protonation exchanges that achieve proton transport.

Science
, this issue p.
1552
Oceans on the edge of anoxia
Authors: Watson Andrew J.
Published: December 2016

Environmental crises can tip the ocean into O
2
depletion
Divining science
Before Nature Cuneiform Knowledge and the History of Science
Francesca Rochberg
University of Chicago Press, 2016. 379 pp.
Authors: Robinson Andrew
Published: December 2016

A new tome argues that the ancient Babylonians deserve greater recognition in scientific histories
Optical circulators reach the quantum level
Authors: Munro William J. , Nemoto Kae
Published: December 2016

The spin state of a single atom can route light signals in different directions
Fermentative Production of Cysteine by Pantoea ananatis
Authors: Takumi Kazuhiro , Ziyatdinov Mikhail Kharisovich , Samsonov Viktor , Nonaka Gen
Published: December 2016

Cysteine is a commercially important amino acid; however, it lacks an efficient fermentative production method. Due to its cytotoxicity, intracellular cysteine levels are stringently controlled via several regulatory modes. Managing its toxic effects as well as understanding and deregulating the complexities of regulation are crucial for establishing the fermentative production of cysteine. The regulatory modes include feedback inhibition of key metabolic enzymes, degradation, efflux pumps, and the transcriptional regulation of biosynthetic genes by a master cysteine regulator, CysB. These processes have been extensively studied using
Escherichia coli
for overproducing cysteine by fermentation. In this study, we genetically engineered
Pantoea ananatis
, an emerging host for the fermentative production of bio-based materials, to identify key factors required for cysteine production. According to this and our previous studies, we identified a major cysteine desulfhydrase gene,
ccdA
(formerly PAJ_0331), involved in cysteine degradation, and the cysteine efflux pump genes
cefA
and
cefB
(formerly PAJ_3026 and PAJ_p0018, respectively), which may be responsible for downregulating the intracellular cysteine level. Our findings revealed that
ccdA
deletion and
cefA
and
cefB
overexpression are crucial factors for establishing fermentative cysteine production in
P. ananatis
and for obtaining a higher cysteine yield when combined with genes in the cysteine biosynthetic pathway. To our knowledge, this is the first demonstration of cysteine production in
P. ananatis
, which has fundamental implications for establishing overproduction in this microbe.

IMPORTANCE
The efficient production of cysteine is a major challenge in the amino acid fermentation industry. In this study, we identified cysteine efflux pumps and degradation pathways as essential elements and genetically engineered
Pantoea ananatis
, an emerging host for the fermentative production of bio-based materials, to establish the fermentative production of cysteine. This study provides crucial insights into the design and construction of cysteine-producing strains, which may play central roles in realizing commercial basis production.
Antibacterial Mechanism of 405-Nanometer Light-Emitting Diode against Salmonella at Refrigeration Temperature
Authors: Kim Min-Jeong , Yuk Hyun-Gyun
Published: December 2016

The aim of this study was to elucidate the antibacterial mechanism of 405 ± 5-nm light-emitting diode (LED) illumination against
Salmonella
at 4°C in phosphate-buffered saline (PBS) by determining endogenous coproporphyrin content, DNA oxidation, damage to membrane function, and morphological change. Gene expression levels, including of
oxyR
,
recA
,
rpoS
,
sodA
, and
soxR
, were also examined to understand the response of
Salmonella
to LED illumination. The results showed that
Salmonella
strains responded differently to LED illumination, revealing that
S. enterica
serovar Enteritidis (ATCC 13076) and
S. enterica
subsp.
enterica
serovar Saintpaul (ATCC 9712) were more susceptible and resistant, respectively, than the 16 other strains tested. There was no difference in the amounts of endogenous coproporphyrin in the two strains. Compared with that in nonilluminated cells, the DNA oxidation levels in illuminated cells increased. In illuminated cells, we observed a loss of efflux pump activity, damage to the glucose uptake system, and changes in membrane potential and integrity. Transmission electron microscopy revealed a disorganization of chromosomes and ribosomes due to LED illumination. The levels of the five genes measured in the nonilluminated and illuminated
S
. Saintpaul cells were upregulated in PBS at a set temperature of 4°C, indicating that increased gene expression levels might be due to a temperature shift and nutrient deficiency rather than to LED illumination. In contrast, only
oxyR
in
S
. Enteritidis cells was upregulated. Thus, different sensitivities of the two strains to LED illumination were attributed to differences in gene regulation.

IMPORTANCE
Bacterial inactivation using visible light has recently received attention as a safe and environmentally friendly technology, in contrast with UV light, which has detrimental effects on human health and the environment. This study was designed to understand how 405 ± 5-nm light-emitting diode (LED) illumination kills
Salmonella
strains at refrigeration temperature. The data clearly demonstrated that the effectiveness of LED illumination on
Salmonella
strains depended highly on the serotype and strain. Our findings also revealed that its antibacterial mechanism was mainly attributed to DNA oxidation and a loss of membrane functions rather than membrane lipid peroxidation, which has been proposed by other researchers who studied the antibacterial effect of LED illumination by adding exogenous photosensitizers, such as chlorophyllin and hypericin. Therefore, this study suggests that the detailed antibacterial mechanisms of 405-nm LED illumination without additional photosensitizers may differ from that by exogenous photosensitizers. Furthermore, a change in stress-related gene regulation may alter the susceptibility of
Salmonella
cells to LED illumination at refrigeration temperature. Thus, our study provides new insights into the antibacterial mechanism of 405 ± 5-nm LED illumination on
Salmonella
cells.
Four Inserts within the Catalytic Domain Confer Extra Stability and Activity to Hyperthermostable Pyrolysin from Pyrococcus furiosus
Authors: Gao Xiaowei , Zeng Jing , Yi Huawei , Zhang Fang , Tang Bing , Tang Xiao-Feng
Published: December 2016

Pyrolysin from the hyperthermophilic archaeon
Pyrococcus furiosus
is the prototype of the pyrolysin family of the subtilisin-like serine protease superfamily (subtilases). It contains four inserts (IS
147
, IS
29
, IS
27
, and IS
8
) of unknown function in the catalytic domain. We performed domain deletions and showed that three inserts are either essential (IS
147
and IS
27
) or important (IS
8
) for efficient maturation of pyrolysin at high temperatures, whereas IS
29
is dispensable. The large insert IS
147
contains Ca3 and Ca4, two calcium-binding Dx[DN]xDG motifs that are conserved in many pyrolysin-like proteases. Mutagenesis revealed that the Ca3 site contributes to enzyme thermostability and the Ca4 site is necessary for pyrolysin to fold into a maturation-competent conformation. Mature insert-deletion variants were characterized and showed that IS
29
and IS
8
contribute to enzyme activity and stability, respectively. In the presence of NaCl, pyrolysin undergoes autocleavage at two sites: one within IS
29
and the other in IS
27
. Disrupting the ion pairs in IS
27
and IS
8
induces autocleavage in the absence of salts. Interestingly, autocleavage products combine noncovalently to form an active, nicked enzyme that is resistant to SDS and urea denaturation. Additionally, a single mutation in IS
29
increases resistance to salt-induced autocleavage and further increases enzyme thermostability. Our results suggest that these extra structural elements play a crucial role in adapting pyrolysin to hyperthermal environments.

IMPORTANCE
Pyrolysin-like proteases belong to the subtilase superfamily and are characterized by large inserts and long C-terminal extensions; however, the role of the inserts in enzyme function is unclear. Our results demonstrate that four inserts in the catalytic domain of hyperthermostable pyrolysin contribute to the folding, maturation, stability, and activity of the enzyme at high temperatures. The modification of extra structural elements in pyrolysin-like proteases is a promising strategy for modulating global structure stability and enzymatic activity of this class of protease.
Characterization of Metarhizium viride Mycosis in Veiled Chameleons (Chamaeleo calyptratus), Panther Chameleons (Furcifer pardalis), and Inland Bearded Dragons (Pogona vitticeps)
Authors: Schmidt Volker , Klasen Linus , Schneider Juliane , Hübel Jens , Pees Michael
Published: December 2016

Metarhizium viride
has been associated with fatal systemic mycoses in chameleons, but subsequent data on mycoses caused by this fungus in reptiles are lacking. The aim of this investigation was therefore to obtain information on the presence of
M. viride
in reptiles kept as pets in captivity and its association with clinical signs and pathological findings as well as improvement of diagnostic procedures. Beside 18S ribosomal DNA (rDNA) (small subunit [SSU]) and internal transcribed spacer region 1 (ITS-1), a fragment of the large subunit (LSU) of 28S rDNA, including domain 1 (D1) and D2, was sequenced for the identification of the fungus and phylogenetic analysis. Cultural isolation and histopathological examinations as well as the pattern of antifungal drug resistance, determined by using agar diffusion testing, were additionally used for comparison of the isolates. In total, 20 isolates from eight inland bearded dragons (
Pogona vitticeps
), six veiled chameleons (
Chamaeleo calyptratus
), and six panther chameleons (
Furcifer pardalis
) were examined. Most of the lizards suffered from fungal glossitis, stomatitis, and pharyngitis or died due to visceral mycosis. Treatment with different antifungal drugs according to resistance patterns in all three different lizard species was unsuccessful. Sequence analysis resulted in four different genotypes of
M. viride
based on differences in the LSU fragment, whereas the SSU and ITS-1 were identical in all isolates. Sequence analysis of the SSU fragment revealed the first presentation of a valid large fragment of the SSU of
M. viride
. According to statistical analysis, genotypes did not correlate with differences in pathogenicity, antifungal susceptibility, or species specificity.
NS1 Protein Amino Acid Changes D189N and V194I Affect Interferon Responses, Thermosensitivity, and Virulence of Circulating H3N2 Human Influenza A Viruses
Authors: Nogales Aitor , Martinez-Sobrido Luis , Topham David J. , DeDiego Marta L.
Published: December 2016

Influenza virus NS1 protein is a nonstructural, multifunctional protein that counteracts host innate immune responses, modulating virus pathogenesis. NS1 protein variability in subjects infected with H3N2 influenza A viruses (IAVs) during the 2010/2011 season was analyzed, and amino acid changes in residues 86, 189, and 194 were found. The consequences of these mutations for the NS1-mediated inhibition of IFN responses and the pathogenesis of the virus were evaluated, showing that NS1 mutations D189N and V194I impaired the ability of the NS1 protein to inhibit general gene expression, most probably because these mutations decreased the binding of NS1 to the cleavage and polyadenylation specificity factor 30 (CPSF30). A recombinant A/Puerto Rico/8/34 (PR8) H1N1 virus encoding the H3N2 NS1-D189N protein was slightly attenuated, whereas the virus encoding the H3N2 NS1-V194I protein was further attenuated in mice. The higher attenuation of this virus could not be explained by differences in the ability of the two NS1 proteins to counteract host innate immune responses, indicating that another factor must be responsible. In fact, we showed that the virus encoding the H3N2 NS1-V194I protein demonstrated a temperature-sensitive (ts) phenotype, providing a most likely explanation for the stronger attenuation observed. As far as we know, this is the first description of a mutation in NS1 residue 194 conferring a ts phenotype. These studies are relevant in order to identify new residues important for NS1 functions and in human influenza virus surveillance to assess mutations affecting the pathogenicity of circulating viruses.

IMPORTANCE
Influenza viral infections represent a serious public health problem, with influenza virus causing a contagious respiratory disease that is most effectively prevented through vaccination. The multifunctional nonstructural protein 1 (NS1) is the main viral factor counteracting the host antiviral response. Therefore, influenza virus surveillance to identify new mutations in the NS1 protein affecting the pathogenicity of the circulating viruses is highly important. In this work, we evaluated amino acid variability in the NS1 proteins from H3N2 human seasonal viruses and the effect of the mutations on innate immune responses and virus pathogenesis. NS1 mutations D189N and V194I impaired the ability of the NS1 protein to inhibit general gene expression, and recombinant viruses harboring these mutations were attenuated in a mouse model of influenza infection. Interestingly, a virus encoding the H3N2 NS1-V194I protein demonstrated a temperature-sensitive phenotype, further attenuating the virus
in vivo
.
Mildly Acidic pH Triggers an Irreversible Conformational Change in the Fusion Domain of Herpes Simplex Virus 1 Glycoprotein B and Inactivation of Viral Entry
Authors: Weed Darin J. , Pritchard Suzanne M. , Gonzalez Floricel , Aguilar Hector C. , Nicola Anthony V.
Published: December 2016

Herpes simplex virus (HSV) entry into a subset of cells requires endocytosis and endosomal low pH. Preexposure of isolated virions to mildly acidic pH of 5 to 6 partially inactivates HSV infectivity in an irreversible manner. Acid inactivation is a hallmark of viruses that enter via low-pH pathways; this occurs by pretriggering conformational changes essential for fusion. The target and mechanism(s) of low-pH inactivation of HSV are unclear. Here, low-pH-treated HSV-1 was defective in fusion activity and yet retained normal levels of attachment to cell surface heparan sulfate and binding to nectin-1 receptor. Low-pH-triggered conformational changes in gB reported to date are reversible, despite irreversible low-pH inactivation. gB conformational changes and their reversibility were measured by antigenic analysis with a panel of monoclonal antibodies and by detecting changes in oligomeric conformation. Three-hour treatment of HSV-1 virions with pH 5 or multiple sequential treatments at pH 5 followed by neutral pH caused an irreversible >2.5 log infectivity reduction. While changes in several gB antigenic sites were reversible, alteration of the H126 epitope was irreversible. gB oligomeric conformational change remained reversible under all conditions tested. Altogether, our results reveal that oligomeric alterations and fusion domain changes represent distinct conformational changes in gB, and the latter correlates with irreversible low-pH inactivation of HSV. We propose that conformational change in the gB fusion domain is important for activation of membrane fusion during viral entry and that in the absence of a host target membrane, this change results in irreversible inactivation of virions.

IMPORTANCE
HSV-1 is an important pathogen with a high seroprevalence throughout the human population. HSV infects cells via multiple pathways, including a low-pH route into epithelial cells, the primary portal into the host. HSV is inactivated by low-pH preexposure, and gB, a class III fusion protein, undergoes reversible conformational changes in response to low-pH exposure. Here, we show that low-pH inactivation of HSV is irreversible and due to a defect in virion fusion activity. We identified an irreversible change in the fusion domain of gB following multiple sequential low-pH exposures or following prolonged low-pH treatment. This change appears to be separable from the alteration in gB quaternary structure. Together, the results are consistent with a model by which low pH can have an activating or inactivating effect on HSV depending on the presence of a target membrane.
Characterization of the Candida albicans Amino Acid Permease Family: Gap2 Is the Only General Amino Acid Permease and Gap4 Is an
S
-Adenosylmethionine (SAM) Transporter Required for SAM-Induced Morphogenesis
Authors: Kraidlova Lucie , Schrevens Sanne , Tournu Hélène , Van Zeebroeck Griet , Sychrova Hana , Van Dijck Patrick
Published: December 2016

Candida albicans
is a commensal organism that can thrive in many niches in its human host. The environmental conditions at these different niches differ quite a bit, and this fungus must be able to sense these changes and adapt its metabolism to them. Apart from glucose and other sugars, the uptake of amino acids is very important. This is underscored by the fact that the
C. albicans
genome encodes 6 orthologues of the
Saccharomyces. cerevisiae
general amino acid permease Gap1 and many other amino acid transporters. In this work, we characterize these six permeases and we show that
C. albicans
Gap2 is the functional orthologue of
Sc
Gap1 and that
C. albicans
Gap4 is an orthologue of
Sc
Sam3, an
S
-adenosylmethionine (SAM) transporter. Furthermore, we show that Gap4 is required for SAM-induced morphogenesis, an important virulence factor of
C. albicans
.
Identification and Characterization of Novel Rat Polyomavirus 2 in a Colony of X-SCID Rats by P-PIT assay
Authors: Rigatti Lora H. , Toptan Tuna , Newsome Joseph T. , Moore Patrick S. , Chang Yuan
Published: December 2016

Although P-PIT was developed to detect diseases associated with known human polyomaviruses, the identification of a new polyomavirus in rats suggests that it may have utility as a broad-based screen for new, as well as known polyomaviruses. Our findings suggest that RatPyV2 may be a commensal infection of laboratory rats that can lead to disseminated disease in T cell immune-deficient rats. Infection of the X-SCID rats with RatPyV2 and
Pneumocystis carinii
is a potential model for coinfection pathogenesis and treatment options during transplant preclinical studies.
A systematic review on the effect of the organisation of hospital discharge on patient health outcomes
Authors: Couturier Bérengère , Carrat Fabrice , Hejblum Gilles
Published: December 2016

Objective

The transition from hospital to home represents a key step in the management of patients and several problems related to this transition may arise, with potential adverse effects on patient health after discharge. The purpose of our study was to explore the association between components of the hospital discharge process including subsequent continuity of care and patient outcomes in the post-discharge period.

Design

Systematic review of observational and interventional studies.

Setting

We conducted a combined search in the Medline and Web of Science databases. Additional studies were identified by screening the bibliographies of the included studies. The data collection process was conducted using a standardised predefined grid that included quality criteria.

Participants

A standard patient population returning home after hospitalisation.

Primary and secondary outcomes

Adverse health outcomes occurring after hospital discharge.

Results

In the 20 studies fulfilling our eligibility criteria, the main discharge-process components explored were: discharge summary (n=2), discharge instructions (n=2), drug-related problems at discharge (n=4), transition from hospital to home (n=5) and continuity of care after hospital discharge (n=7). The major subsequent patient health outcomes measured were: rehospitalisations (n=18), emergency department visits (n=8) and mortality (n=5). Eight of the 18 studies exploring rehospitalisations and two of the eight studies examining emergency department visits reported at least one significant association between the discharge process and these outcomes. None of the studies investigating patient mortality reported any significant such associations between the discharge process and these outcomes.

Conclusions

Irrespective of the component of the discharge process explored, the outcome considered (composite or not), the sample size and the study design, no consistent statistical association between hospital discharge and patient health outcome was identified. This systematic review highlights a wide heterogeneity between studies, especially in terms of the component(s) of the hospital discharge process investigated, study designs, outcomes and follow-up durations.