bluuebunny/crossref_metadata_2025 huggingface dataset:
The Pseudomonas putida CsrA/RsmA homologues negatively affect c‐di‐GMP pools and biofilm formation through the GGDEF/EAL response regulator CfcR
Authors: Huertas‐Rosales Óscar , Romero Manuel , Heeb Stephan , Espinosa‐Urgel Manuel , Cámara Miguel , Ramos‐González María Isabel
Published: July 2017

Expression of cfcR, encoding the only GGDEF/EAL response regulator in Pseudomonas putida, is transcriptionally regulated by RpoS, ANR and FleQ, and the functionality of CfcR as a diguanylate cyclase requires the multisensor CHASE3/GAF hybrid histidine kinase named CfcA. Here an additional level of cfcR control, operating post‐transcriptionally via the RNA‐binding proteins RsmA, RsmE and RsmI, is unraveled. Specific binding of the three proteins to an Rsm‐binding motif (5′CANGGANG3′) encompassing the translational start codon of cfcR was confirmed. Although RsmA exhibited the highest binding affinity to the cfcR transcript, single deletions of rsmA, rsmE or rsmI caused minor derepression in CfcR translation compared to a ΔrsmIEA triple mutant. RsmA also showed a negative impact on c‐di‐GMP levels in a double mutant ΔrsmIE through the control of cfcR, which is responsible for most of the free c‐di‐GMP during stationary phase in static conditions. In addition, a CfcR‐dependent c‐di‐GMP boost was observed during this stage in ΔrsmIEA confirming the negative effect of Rsm proteins on CfcR translation and explaining the increased biofilm formation in this mutant compared to the wild type. Overall, these results suggest that CfcR is a key player in biofilm formation regulation by the Rsm proteins in P. putida.
Two histidine kinases can sense different stress cues for activation of the MAPK Hog1 in a fungal insect pathogen
Authors: Liu Jing , Tong Sen‐Miao , Qiu Lei , Ying Sheng‐Hua , Feng Ming‐Guang
Published: July 2017

Filamentous fungi possess a large family of histidine kinases (HKs) classified to 11 distinct groups. Of those, only Group III (HK3) homologues in some fungi can sense osmotic, fungicidal and/or oxidative cues upstream of the signalling MAPK Hog1 cascade that usually governs two hallmark phenotypes, i.e., osmotolerance and dicarboximide/phenylpyrrole fungicide resistance. Here we examined functions of all eight HK groups with each possessing a single member in Beauveria bassiana. HK3 and HK8 (Group VIII) were evidently localized at hyphal cell periphery and had more functions in aerial conidiation and multiple stress responses than six other HKs. Increased osmosensitivity occurred uniquely in Δhk8 while high resistance to fludioxonil (phenylpyrrole) or iprodione (dicarboximide) fungicide appeared only in Δhk3. Phosphorylation of Hog1 was inhibited only in the Δhk3 cells triggered with fludioxonil cue and reduced only in the Δhk8 cells triggered with osmotic cue. However, an oxidative cue resulted in no signal change of phosphorylated Hog1 in either Δhk3 or Δhk8. Other Δhk mutants showed minor changes in some non‐hallmark phenotypes. Altogether, HK3 and HK8 act as unique sensors of fungicidal and hyperosmotic cues respectively, upstream of the Hog1 cascade that regulates fungicidal resistance negatively and osmotolerance positively in B. bassiana.
Microbial community structure and soil pH correspond to methane production in Arctic Alaska soils
Authors: Wagner Robert , Zona Donatella , Oechel Walter , Lipson David
Published: July 2017

While there is no doubt that biogenic methane production in the Arctic is an important aspect of global methane emissions, the relative roles of microbial community characteristics and soil environmental conditions in controlling Arctic methane emissions remains uncertain. Here, relevant methane‐cycling microbial groups were investigated at two remote Arctic sites with respect to soil potential methane production (PMP). Percent abundances of methanogens and iron‐reducing bacteria correlated with increased PMP, while methanotrophs correlated with decreased PMP. Interestingly, α‐diversity of the methanogens was positively correlated with PMP, while β‐diversity was unrelated to PMP. The β‐diversity of the entire microbial community, however, was related to PMP. Shannon diversity was a better correlate of PMP than Simpson diversity across analyses, while rarefied species richness was a weak correlate of PMP. These results demonstrate the following: first, soil pH and microbial community structure both probably control methane production in Arctic soils. Second, there may be high functional redundancy in the methanogens with regard to methane production. Third, iron‐reducing bacteria co‐occur with methanogens in Arctic soils, and iron‐reduction‐mediated effects on methanogenesis may be controlled by α‐ and β‐diversity. And finally, species evenness and rare species abundances may be driving relationships between microbial groups, influencing Arctic methane production.
Cascading Bias of Initial Exposure to Information at the Crime Scene to the Subsequent Evaluation of Skeletal Remains,
Authors: Nakhaeizadeh Sherry , Morgan Ruth M. , Rando Carolyn , Dror Itiel E.
Published: July 2017

Thirty‐eight participants took part in a study that investigated the potential cascading effects of initial exposure to extraneous context upon subsequent decision‐making. Participants investigated a mock crime scene, which included the excavation of clandestine burials that had a male skeletal cast dressed either in female or gender neutral clothing. This was followed by a forensic anthropological assessment of the skeletal remains, with a control group assessing the same male skeletal cast without any clothing context. The results indicated that the sex assessment was highly dependent upon the context in which participants were exposed to prior to the analysis. This was especially noticeable in the female clothing context where only one participant determined the male skeletal cast to be male. The results demonstrate the importance of understanding the role of context in forensic anthropology at an early stage of an investigation and its potential cascading effect on subsequent assessments.
Disseminated Neonatal Herpes Simplex Virus Infection with Escherichia Coli Coinfection
Authors: Krehbiel Kacy , Singh Veena
Published: July 2017

Neonatal herpes simplex virus (HSV) infection is an uncommon disease that rarely presents as sudden unexpected death of a previously healthy newborn. Clinical manifestations are variable; signs and symptoms may be subtle and nonspecific. Neonatal infection may present with mucocutaneous (skin, eye, and/or mouth), disseminated, or central nervous system disease. Morbidity and mortality are dependent upon disease presentation and treatment. The infection is most frequently transmitted during the peripartum period, although the majority of mothers have no known history of HSV infection at the time of delivery. Findings at autopsy include gastrointestinal or mucocutaneous ulcers, diffuse hepatic necrosis, adrenal necrosis, pneumonitis, and splenic necrosis. Characteristic intranuclear viral inclusions are identified on microscopic examination. Coinfection with bacterial organisms may contribute to death. Autopsy examination with appropriate ancillary studies, including cultures, is critical given that many infants lack cutaneous manifestations of disease and remain undiagnosed prior to death.
Whitefly feeding behavior and retention of a foregut‐borne crinivirus exposed to artificial diets with different pH values
Authors: Zhou Jaclyn S. , Chen Angel Y. S. , Drucker Martin , Lopez Nicole H. , Carpenter Alyssa , Ng James C. K.
Published: July 2017

Transmission of plant viruses by phytophagous hemipteran insects encompasses complex interactions underlying a continuum of processes involved in virus acquisition, retention and inoculation combined with vector feeding behavior. Here, we investigated the effects of dietary pH on whitefly (Bemisia tabaci) feeding behavior and release of Lettuce infectious yellows virus (LIYV) virions retained in the vector's foregut. Electrical penetration graph analysis revealed that variables associated with whitefly probing and ingestion did not differ significantly in pH (4, 7.4, and 9) adjusted artificial diets. To investigate virus retention and release, whiteflies allowed to acquire LIYV virions in a pH 7.4 artificial diet were fed pH 4, 7.4, or 9 virion‐free artificial (clearing) diets. Immunofluorescent localization analyses indicated that virions remained bound to the foreguts of approximately 20%–24% of vectors after they fed on each of the 3 pH‐adjusted clearing diets. When RNA preparations from the clearing diets were analyzed by reverse transcription (RT) nested‐PCR and, in some cases, real‐time qPCR, successful amplification of LIYV‐specific sequence was infrequent but consistently repeatable for the pH 7.4 diet but never observed for the pH 4 and 9 diets, suggesting a weak pH‐dependent effect for virion release. Viruliferous vectors that fed on each of the 3 pH‐adjusted clearing diets transmitted LIYV to virus‐free plants. These results suggest that changes in pH values alone in artificial diet do not result in observable changes in whitefly feeding behaviors, an observation that marks a first in the feeding of artificial diet by whitefly vectors; and that there is a potential causal and contingent relationship between the pH in artificial diet and the release/inoculation of foregut bound virions.
Prebiotic Potential and Chemical Composition of Seven Culinary Spice Extracts
Authors: Lu Qing‐Yi , Summanen Paula H. , Lee Ru‐Po , Huang Jianjun , Henning Susanne M. , Heber David , Finegold Sydney M. , Li Zhaoping
Published: July 2017

The objective of this study was to investigate prebiotic potential, chemical composition, and antioxidant capacity of spice extracts. Seven culinary spices including black pepper, cayenne pepper, cinnamon, ginger, Mediterranean oregano, rosemary, and turmeric were extracted with boiling water. Major chemical constituents were characterized by RP‐HPLC‐DAD method and antioxidant capacity was determined by measuring colorimetrically the extent to scavenge ABTS radical cations. Effects of spice extracts on the viability of 88 anaerobic and facultative isolates from intestinal microbiota were determined by using Brucella agar plates containing serial dilutions of extracts. A total of 14 phenolic compounds, a piperine, cinnamic acid, and cinnamaldehyde were identified and quantitated. Spice extracts exhibited high antioxidant capacity that correlated with the total amount of major chemicals. All spice extracts, with the exception of turmeric, enhanced the growth of Bifidobacterium spp. and Lactobacillus spp. All spices exhibited inhibitory activity against selected Ruminococcus species. Cinnamon, oregano, and rosemary were active against selected Fusobacterium strains and cinnamon, rosemary, and turmeric were active against selected Clostridium spp. Some spices displayed prebiotic‐like activity by promoting the growth of beneficial bacteria and suppressing the growth of pathogenic bacteria, suggesting their potential role in the regulation of intestinal microbiota and the enhancement of gastrointestinal health. The identification and quantification of spice‐specific phytochemicals provided insight into the potential influence of these chemicals on the gut microbial communities and activities. Future research on the connections between spice‐induced changes in gut microbiota and host metabolism and disease preventive effect in animal models and humans is needed.
Use of Laser‐Etched Pouches to Control the Volume Expansion of Kimchi Packages During Distribution: Impact of Packaging and Storage on Quality Characteristics
Authors: Lee Hyun‐Gyu , Yoo SeungRan
Published: July 2017

Use of laser‐etched pouches was investigated to develop kimchi packages with gas control functions. According to the degree of laser processing, the headspace pressure, atmospheric composition, and water vapor transmission rate of the kimchi packages were measured to investigate the potential use of laser‐etched packages for kimchi. In addition, the pH, titratable acidity, organic acid, and microbial population of the packaged kimchi were examined to study the effect of packaging and storage conditions on its quality characteristics. The concentration of carbon dioxide in the pouches with a high gas transmission rate was less than that in other pouches (P < 0.05), indicating that low a carbon dioxide concentration resulted in less volume expansion. During the storage period (P < 0.05), the gas pressure in some pouches started to increase after the 15th d at 10 °C. Few differences were observed between the quality characteristics of kimchi (for example, pH, titratable acidity, organic acid, and microbial count). In addition, this study indicated that the higher the storage temperature, the more rapid the fermentation. Consequently, laser‐etched pouches demonstrate the potential for controlling the gas, which in turn maintains the quality of kimchi. The use of laser‐etched films could exert marked effects on alleviating the volume expansion or pressure build‐up in kimchi packages.
Using Preferred Attribute Elicitation to Determine How Males and Females Evaluate Beer
Authors: Muggah Elizabeth M. , McSweeney Matthew B.
Published: July 2017

The variety of beers available for consumption has increased due to the recent emergence of many craft brewing operations and it has been suggested that this is affecting how consumers evaluate beer. Currently, beer consumers are mostly male and only 20% of women are primarily beer drinkers. The main objective of this project is to compare and contrast descriptions of beer products created by males and females. The preferred attribute elicitation (PAE) method was used to create a description of 4 beers common to residents of Nova Scotia, Canada. Four PAE sessions were held: 2 sessions consisted of females (n = 16 and 15) and 2 sessions of males (n = 11 and 17). Four beer samples were chosen from locally available commercial beers, 2 of these samples were considered to be craft‐brewed beer and the other samples were nationally available brands (macrobrewed). Both the males and females generated descriptions that included 5 identical terms; however, they differed in the importance they assigned to each attribute. Notably, bitterness was perceived to be of more importance to female panelists. Throughout all PAE sessions, the craft‐brewed beers were associated with considerably more sensory attributes than the macrobrewed beers. It can be concluded that both the female and male groups found discernible differences between the craft and macrobrewed beers; however, they place importance on different sensory attributes.
The fitness costs and benefits of antibiotic resistance in drug‐free microenvironments encountered in the human body
Authors: Maharjan Ram , Ferenci Thomas
Published: July 2017

The relationship between bacterial drug resistance and growth fitness is a contentious topic, but some antibiotic resistance mutations clearly have a fitness cost in the laboratory. Whether these costs translate into deleterious effects in natural habitats is less certain however. Previously, fitness effects of resistance mutations were mostly characterized in nutrient‐rich, fast‐growth conditions, which bacteria rarely encounter in natural habitats. Carbon, phosphate, iron or oxygen limitations are conditions met by bacterial pathogens in various compartments of the human body. Here, we measured the fitness of four different rpoB mutations commonly found in rifampicin‐resistant bacterial isolates. The fitness properties and the emergence of these and other alleles were studied in Escherichia coli populations growing under nutrient excess and in four different nutrient‐limited states. Consistent with previous findings, all four mutations exhibited deleterious fitness effects under nutrient‐rich conditions. In stark contrast, we found positive or neutral fitness effects under nutrient‐limited conditions. Two particular rpoB alleles had a remarkable fitness increase under phosphate limitation and these alleles arose to high frequencies specifically under phosphate limitation. These findings suggest that it is not meaningful to draw general conclusions on fitness costs without considering bacterial microenvironments in humans and other animals.
Anti‐aging pharmacology in cutaneous wound healing: effects of metformin, resveratrol, and rapamycin by local application
Authors: Zhao Pan , Sui Bing‐Dong , Liu Nu , Lv Ya‐Jie , Zheng Chen‐Xi , Lu Yong‐Bo , Huang Wen‐Tao , Zhou Cui‐Hong , Chen Ji , Pang Dan‐Lin , Fei Dong‐Dong , Xuan Kun , Hu Cheng‐Hu , Jin Yan
Published: July 2017

Cutaneous wounds are among the most common soft tissue injuries and are particularly hard to heal in aging. Caloric restriction (CR) is well documented to extend longevity; pharmacologically, profound rejuvenative effects of CR mimetics have been uncovered, especially metformin (MET), resveratrol (RSV), and rapamycin (RAPA). However, locally applied impacts and functional differences of these agents on wound healing remain to be established. Here, we discovered that chronic topical administration of MET and RSV, but not RAPA, accelerated wound healing with improved epidermis, hair follicles, and collagen deposition in young rodents, and MET exerted more profound effects. Furthermore, locally applied MET and RSV improved vascularization of the wound beds, which were attributed to stimulation of adenosine monophosphate‐activated protein kinase (AMPK) pathway, the key mediator of wound healing. Notably, in aged skin, AMPK pathway was inhibited, correlated with impaired vasculature and reduced healing ability. As therapeutic approaches, local treatments of MET and RSV prevented age‐related AMPK suppression and angiogenic inhibition in wound beds. Moreover, in aged rats, rejuvenative effects of topically applied MET and RSV on cell viability of wound beds were confirmed, of which MET showed more prominent anti‐aging effects. We further verified that only MET promoted wound healing and cutaneous integrity in aged skin. These findings clarified differential effects of CR‐based anti‐aging pharmacology in wound healing, identified critical angiogenic and rejuvenative mechanisms through AMPK pathway in both young and aged skin, and unraveled chronic local application of MET as the optimal and promising regenerative agent in treating cutaneous wound defects.
The Boom and Bust of the RMB's Internationalization: A Perspective from Cross‐Border Arbitrage
Authors: Zhang Ming , Zhang Bin
Published: July 2017

The RMB's internationalization developed very quickly from 2010 to 2015H1, but it slowed down significantly since 2015H2. This paper argues that cross‐border arbitraging activities played a significant role in both the boom and the bust of the RMB's internationalization. A slower pace of the RMB's internationalization based more on real demand might become a new norm in the future. To pursue a more sustainable RMB internationalization in the next decade, the Chinese government should maintain a relatively high economic growth rate, avoid the burst of systemic financial crisis, continue to liberalize the capital account in a gradual and cautious way, accelerate the reform and opening up of the domestic financial market, and integrate the RMB's internationalization with Asian monetary cooperation.
Delirium in a residential care facility: An exploratory study of staff knowledge
Authors: Buettel Amy , Cleary Michelle , Bramble Marguerite
Published: July 2017

Objective

To explore staff knowledge of delirium by eliciting meaning through descriptions of their experiences within a residential aged care facility (RACF).

Methods

Six staff from one RACF in Australia participated in this qualitative study. Semi‐structured individual interviews were conducted and analysed using Colaizzi's analytical framework.

Results

The analysis revealed four themes: (i) absence of the word delirium; (ii) care based on intuition and automated actions; (iii) reliance on teamwork; and (iv) confusing delirium, depression and dementia.

Conclusion

Delirium was absent from clinical discourse in the RACF. Although participants concluded that delirium was common, lack of knowledge led to under‐assessment. Findings emphasise the need for staff education, informed assessment and clinical guidelines to better support staff care for residents.
Analysis of KERA in four families with cornea plana identifies two novel mutations
Authors: Dudakova Lubica , Vercruyssen Jang Hee J. , Balikova Irina , Postolache Lavina , Leroy Bart P. , Skalicka Pavlina , Liskova Petra
Published: July 2017

Purpose

To identify the molecular genetic cause in four families of various ethnic backgrounds with cornea plana.

Methods

Detailed ophthalmological examination and direct sequencing of the KERA coding region in five patients of Czech and Turkish origin and their available family members.

Results

Compound heterozygosity for a novel missense mutation c.209C>T; p.(Pro70Leu) and a novel splice site mutation c.887‐1G>A in KERA were detected in two affected siblings of Czech origin. In silico analysis supported the pathogenicity of both variants. The second proband of Czech origin harboured c.835C>T; p.(Arg279*) in a homozygous state. Homozygous mutations c.740A>G; p.(Asn247Ser) and c.674C>T; p.(Ile225Thr) were identified in the Turkish probands, both born out of consanguineous marriages. Observed ocular phenotypes were typical of cornea plana with the exception of one Czech patient who also had marked thinning and protrusion in the superior part of the left cornea (mean keratometry 47.2 D). No corneal endothelial cell pathology was found by specular microscopy in seven eyes, in three eyes visualization of the posterior corneal surface was unsuccessful.

Conclusion

KERA mutation c.740A>G has been identified to date in three different populations, which makes it the most frequently occurring mutation in patients with cornea plana. Marked corneal thinning and ectasia are a very rare finding in this disorder and longitudinal follow‐up needs to be performed to determine its potential progressive nature.
Vitrectomy with a modified temporal inverted limiting membrane flap to reconstruct the foveolar architecture for macular hole retinal detachment in highly myopic eyes
Authors: Ho Tzyy‐Chang , Ho Allen , Chen Muh‐Shy
Published: July 2017

Purpose

We investigated the surgical results of macular hole retinal detachment (MHRD) with a modified C‐shaped temporal inverted internal limiting membrane (ILM) flap to reconstruct the foveolar architecture in highly myopic eyes.

Methods

Eighteen highly myopic eyes with MHRD in 17 patients who underwent a vitrectomy with a modified C‐shaped temporal inverted ILM flap were followed for 12 months. Anatomic outcomes were evaluated by fundus examinations and optical coherence tomography. The preoperative and postoperative best‐corrected visual acuities (BCVAs) were compared as functional outcomes.

Results

Women accounted for 88% of the MHRD patients. The mean age was 60.2 ± 8.2 years. The mean axial length was 29.25 ± 2.10 mm. Type 1 and type 2 MHRD was present in four eyes and 14 eyes, respectively. After a single surgery, the hole was closed in 18 eyes (100%). Retinal attachment was achieved in 95%. Persistent shallow subretinal fluid (SRF) was noted in one case, which was resolved at follow‐up. The surgery significantly improved BCVAs (from 1.7 ± 0.6 to 0.72 ± 0.4 logarithm of the minimum angle of resolution units [p < 0.001]) at the last visit. In total, 94.4% of the eyes had restored foveolar architecture. Ellipsoid zone recovery within the foveola was found in 77.8% of the eyes.

Conclusion

A vitrectomy and modified C‐shaped inverted temporal ILM flap is effective for closing MHs, reattaching the retina, restoring the foveolar architecture and significantly improving the postoperative BCVA in MHRD patients. This technique is feasible, and we propose ‘presumed’ Müller cell cone repair in MHRD surgery.
Editorial: gut selective immunosuppression—is it a double edged sword?
Authors: Sheridan J. , Doherty G. A.
Published: July 2017

Linked Content

This article is linked to Bye et al papers. To view these articles visit https://doi.org/10.1111/apt.14075 and https://doi.org/10.1111/apt.14166.
Editorial: volatile organic compounds in breath for monitoring IBD—longitudinal studies are essential. Authors’ reply
Authors: Smolinska A. , van Schooten F. J.
Published: July 2017

Linked Content

This article is linked to Williams and Orchard, and Smolinska et al papers. To view these articles visit https://doi.org/10.1111/apt.14135 and https://doi.org/10.1111/apt.14004.
Editorial: gut selective immunosuppression—is it a double edged sword? Authors’ reply
Authors: Bye W. A. , Jairath V. , Travis S. P. L.
Published: July 2017

Linked Content

This article is linked to Bye et al, and Sheridan and Doherty papers. To view these articles visit https://doi.org/10.1111/apt.14075 and https://doi.org/10.1111/apt.14149.
Editorial: hepatitis C direct acting antiviral agents and the kidney—authors’ reply
Authors: Maan R. , Feld J. J. , Duarte‐Rojo A.
Published: July 2017

Linked Content

This article is linked to Maan et al, and Hussaini and Yoshida papers. To view these articles visit https://doi.org/10.1111/apt.14117 and https://doi.org/10.1111/apt.14161.
An epidemiological profile of bipolar disorder among older adults with complex needs: A national cross‐sectional study
Authors: Schluter Philip J , Lacey Cameron , Porter Richard J , Jamieson Hamish A
Published: July 2017

Objectives

Research on bipolar disorder (BD) among community‐living older adults is scant and often suffers from important methodological limitations. Using a national database, this study presents an epidemiological profile of BD in older community residents within New Zealand.

Methods

Since 2012, all New Zealand community care recipients have undergone a standardized needs assessment using the Home Care International Residential Assessment Instrument (interRAI‐HC). The interRAI‐HC elicits information using 236 questions over 20 domains, including BD diagnosis. Those who were assessed between 1 September 2012 and 31 January 2016, who were aged ≥65 years, and who provided consent were included. Statistical investigations employed bivariable and multivariable logistic regression models.

Results

Overall, 71 859 people were eligible; their average age was 82.7 years (range 65‐105 years), with 43 802 (61.0%) being female and 798 (1.1%) having a BD diagnosis. Participants' sex, age and ethnic identification were significantly related to BD (all P<.001). Participants with a higher number of comorbidities had greater odds of BD; for those with at least six comorbidities, the adjusted odds ratio (AOR) was 2.32 (95% confidence interval [CI] 1.37‐3.92). Almost all considered social and environmental variables were significantly and detrimentally associated with BD, such as living in squalid conditions (2.7% for those with DB vs 1.1% for those without DB; AOR=1.60 [95% CI 1.06‐2.42]).

Conclusions

BD among older adults is not uncommon, and numbers will increase as populations age. Increasingly, health services are moving to home‐based integrated models of care. Clinicians and decision‐makers need to be aware in their planning and service delivery that significant deficits in environment quality and exposure to stressful living circumstances remain for older adults with BD.
Overall survival in lower IPSS risk MDS by receipt of iron chelation therapy, adjusting for patient‐related factors and measuring from time of first red blood cell transfusion dependence: an MDS‐CAN analysis
Authors: Leitch Heather A. , Parmar Ambica , Wells Richard A. , Chodirker Lisa , Zhu Nancy , Nevill Thomas J. , Yee Karen W. L. , Leber Brian , Keating Mary‐Margaret , Sabloff Mitchell , St. Hilaire Eve , Kumar Rajat , Delage Robert , Geddes Michelle , Storring John M. , Kew Andrea , Shamy April , Elemary Mohamed , Lenis Martha , Mamedov Alexandre , Ivo Jessica , Francis Janika , Zhang Liying , Buckstein Rena
Published: July 2017

Analyses suggest iron overload in red blood cell (RBC) transfusion‐dependent (TD) patients with myleodysplastic syndrome (MDS) portends inferior overall survival (OS) that is attenuated by iron chelation therapy (ICT) but may be biassed by unbalanced patient‐related factors. The Canadian MDS Registry prospectively measures frailty, comorbidity and disability. We analysed OS by receipt of ICT, adjusting for these patient‐related factors. TD International Prognostic Scoring System (IPSS) low and intermediate‐1 risk MDS, at RBC TD, were included. Predictive factors for OS were determined. A matched pair analysis considering age, revised IPSS, TD severity, time from MDS diagnosis to TD, and receipt of disease‐modifying agents was conducted. Of 239 patients, 83 received ICT; frailty, comorbidity and disability did not differ from non‐ICT patients. Median OS from TD was superior in ICT patients (5·2 vs. 2·1 years; P < 0·0001). By multivariate analysis, not receiving ICT independently predicted inferior OS, (hazard ratio for death 2·0, P = 0·03). In matched pair analysis, OS remained superior for ICT patients (P = 0·02). In this prospective, non‐randomized analysis, receiving ICT was associated with superior OS in lower IPSS risk MDS, adjusting for age, frailty, comorbidity, disability, revised IPSS, TD severity, time to TD and receiving disease‐modifying agents. This provides additional evidence that ICT may confer clinical benefit.
Comparative outcomes of immunochemotherapy regimens in Waldenström macroglobulinaemia
Authors: Olszewski Adam J. , Chen Chang , Gutman Roee , Treon Steven P. , Castillo Jorge J.
Published: July 2017

Comparative data on immunochemotherapy regimens for Waldenström macroglobulinaemia/lymphoplasmacytic lymphoma (WM/LPL) are lacking. We analysed overall survival (OS), risk of hospitalizations, transfusions and plasmapheresis in a population‐based cohort of patients ≥65 years old initiating WM/LPL therapy in 1999–2013. To minimize bias, we applied a propensity score‐based causal inference method. We conducted three analyses of: patients treated with or without rituximab, patients treated with rituximab monotherapy or with combination immunochemotherapy, and regimens based on classic purine analogues or alkylators. Among 1310 patients, 78·5% received rituximab. Patients who received rituximab had significantly better OS [hazard ratio (HR) 0·62, 95% confidence interval (CI) 0·55–0·71] and lower risk of transfusions (risk difference −3·3%, 95% CI −6·3 to −0·3) than those who did not, without a significant difference in hospitalizations or plasmapheresis. We observed no significant difference in OS (HR 0·91, 95% CI 0·79–1·04) between rituximab monotherapy and combination immunochemotherapy, but toxicity outcomes were lower with rituximab alone. Neither survival (HR 1·10, 95%CI 0·92–1·32) nor toxicity outcomes differed significantly between regimens based on purine analogues or alkylators. The survival advantage strongly supports rituximab as part of upfront therapy for WM/LPL, whereas regimens with either purine analogues or alkylating agents result in similar outcomes.
Big conductance calcium‐activated potassium channel openers control spasticity without sedation
Authors: Baker David , Pryce Gareth , Visintin Cristina , Sisay Sofia , Bondarenko Alexander I , Vanessa Ho W S , Jackson Samuel J , Williams Thomas E , Al‐Izki Sarah , Sevastou Ioanna , Okuyama Masahiro , Graier Wolfgang F , Stevenson Lesley A , Tanner Carolyn , Ross Ruth , Pertwee Roger G , Henstridge Christopher M , Irving Andrew J , Schulman Jesse , Powell Keith , Baker Mark D , Giovannoni Gavin , Selwood David L
Published: July 2017

Background and Purpose

Our initial aim was to generate cannabinoid agents that control spasticity, occurring as a consequence of multiple sclerosis (MS), whilst avoiding the sedative side effects associated with cannabis. VSN16R was synthesized as an anandamide (endocannabinoid) analogue in an anti‐metabolite approach to identify drugs that target spasticity.

Experimental Approach

Following the initial chemistry, a variety of biochemical, pharmacological and electrophysiological approaches, using isolated cells, tissue‐based assays and in vivo animal models, were used to demonstrate the activity, efficacy, pharmacokinetics and mechanism of action of VSN16R. Toxicological and safety studies were performed in animals and humans.

Key Results

VSN16R had nanomolar activity in tissue‐based, functional assays and dose‐dependently inhibited spasticity in a mouse experimental encephalomyelitis model of MS. This effect occurred with over 1000‐fold therapeutic window, without affecting normal muscle tone. Efficacy was achieved at plasma levels that are feasible and safe in humans. VSN16R did not bind to known CB1/CB2/GPPR55 cannabinoid‐related receptors in receptor‐based assays but acted on a vascular cannabinoid target. This was identified as the major neuronal form of the big conductance, calcium‐activated potassium (BKCa) channel. Drug‐induced opening of neuronal BKCa channels induced membrane hyperpolarization, limiting excessive neural‐excitability and controlling spasticity.

Conclusions and Implications

We identified the neuronal form of the BKCa channel as the target for VSN16R and demonstrated that its activation alleviates neuronal excitability and spasticity in an experimental model of MS, revealing a novel mechanism to control spasticity. VSN16R is a potential, safe and selective ligand for controlling neural hyper‐excitability in spasticity.
Misuse of bird digital distribution maps creates reversed spatial diversity patterns in the Amazon
Authors: Vale Mariana M. , Marques Tamires L. , Cohn‐Haft Mario , Vieira Marcus Vinícius
Published: July 2017

It is well known that bird richness in the Amazon is greater in upland forests and that seasonally flooded forest is particularly species poor. However, the misleading pattern of greater bird richness in seasonally flooded forest has emerged seemingly unnoticed numerous times in richness maps in the literature. We hypothesize that commission errors in digital distribution maps (DDMs) are the cause behind the misleading richness pattern. In the Amazon, commission errors are a consequence of the different methodological treatment given to large‐ranged versus small‐ranged habitat specialists when mapping distributions.DDMs of 1007 Amazonian birds were examined, and maps that had commission errors were corrected. We generated two richness maps, one from the overlay of originalDDMs and another from the overlay of the corrected ones. We identified 291 species whose distribution maps had errors. In the original data, seasonally flooded forests showed higher species richness than upland forest, but this pattern was reverted in the corrected richness map. Commission errors were 35 times more likely in the seasonally flooded forest. We conclude thatDDMs accurately portray the distribution of single species in the Amazon. Commission errors in individual maps, however, accumulate when they are overlaid, explaining the misleading pattern for birds in the Amazon.DDMs can continue to be used mapping richness, as long as, at a regional scale: (1) basic map refinements are carried, or (2) only small‐range species are used for mapping species richness.
Downregulation of ULK1 by microRNA‐372 inhibits the survival of human pancreatic adenocarcinoma cells
Authors: Chen Hongxi , Zhang Zhipeng , Lu Yebin , Song Kun , Liu Xiwu , Xia Fada , Sun Weijia
Published: July 2017

Dysregulation of microRNA (miRNA) expression in various cancers and their role in cancer progression is well documented. The purpose of this study was to investigate the biological role of miR‐372 in human pancreatic adenocarcinoma (HPAC). We collected 20 pairs of HPAC tissues and adjacent non‐cancerous tissues to detect miR‐372 expression levels. We transfected BXPC‐3 and PANC‐1 cells with miR‐372 inhibitor/mimics to study their effect on cell proliferation, apoptosis, invasion, migration and autophagy. In addition, miR‐372 mimics and a tumor protein UNC51‐like kinase 1 (ULK1) siRNA were co‐transfected into BXPC‐3 and PANC‐1 cells to explore the mechanism of miR‐372 and ULK1 on HPAC tumorigenesis. We found that the expression of miR‐372 was markedly downregulated in HPAC cells compared to adjacent normal tissues. Furthermore, functional assays showed that miR‐372 inhibited cell proliferation, invasion, migration and autophagy in BXPC‐3 and PANC‐1 cells. An inverse correlation between miR‐372 expression and ULK1 expression was observed in HPAC tissues. Downregulation of ULK1 inhibited the overexpression effects of miR‐372, and upregulation of ULK1 reversed the effects of overexpressed miR‐372. Finally, we found that silencing ULK1 or inhibiting autophagy partly rescued the effects of miR‐372 knockdown in HPAC cells, which may explain the influence of miR‐372/ULK1 in HPAC development. Taken together, these results revealed a significant role of the miR‐372/ULK1 axis in suppressing HPAC cell proliferation, migration, invasion and autophagy.
Decomposing Single Images for Layered Photo Retouching
Authors: Innamorati Carlo , Ritschel Tobias , Weyrich Tim , Mitra Niloy J.
Published: July 2017

Photographers routinely compose multiple manipulated photos of the same scene into a single image, producing a fidelity difficult to achieve using any individual photo. Alternately, 3D artists set up rendering systems to produce layered images to isolate individual aspects of the light transport, which are composed into the final result in post‐production. Regrettably, these approaches either take considerable time and effort to capture, or remain limited to synthetic scenes. In this paper, we suggest a method to decompose a single image into multiple layers that approximates effects such as shadow, diffuse illumination, albedo, and specular shading. To this end, we extend the idea of intrinsic images along two axes: first, by complementing shading and reflectance with specularity and occlusion, and second, by introducing directional dependence. We do so by training a convolutional neural network (CNN) with synthetic data. Such decompositions can then be manipulated in any off‐the‐shelf image manipulation software and composited back. We demonstrate the effectiveness of our decomposition on synthetic (i. e., rendered) and real data (i. e., photographs), and use them for photo manipulations, which are otherwise impossible to perform based on single images. We provide comparisons with state‐of‐the‐art methods and also evaluate the quality of our decompositions via a user study measuring the effectiveness of the resultant photo retouching setup. Supplementary material and code are available for research use at geometry.cs.ucl.ac.uk/projects/2017/layered-retouching.
Cost‐effectiveness of a lifestyle modification program in long‐term survivors of hemopoietic stem cell transplantation
Authors: Gao Lan , Moodie Marj , Brown Victoria , Avery Sharon
Published: July 2017

To evaluate the cost‐effectiveness of a lifestyle modification program targeting long‐term survivors of hematological malignancy treated with hemopoietic stem cell transplantation, a multistate life table Markov model was used to calculate health outcomes for both the intervention and no intervention. Cost per health‐adjusted life year (HALY) saved was reported for four scenarios: all participants with/without standard weight regain, and participants who at baseline were overweight with/without standard weight regain. The program recruited 53 participants and was associated with reductions in body weight of 2.2 kg and BMI 0.8 units on intervention completion (12 months) at a cost of $1233/participant. These adipose reductions were sustained and remained significant at 24 months. The incremental cost‐effectiveness ratios varied from $118 418 per HALY to dominant, depending on the weight regain assumption. The program may be cost‐effective in transplant survivors, with the results most sensitive to the weight regain assumption and intervention cost.
S1‐Leitlinie Lipödem
Authors: Reich‐Schupke Stefanie , Schmeller Wilfried , Brauer Wolfgang Justus , Cornely Manuel E. , Faerber Gabriele , Ludwig Malte , Lulay Gerd , Miller Anya , Rapprich Stefan , Richter Dirk Frank , Schacht Vivien , Schrader Klaus , Stücker Markus , Ure Christian
Published: July 2017

Die vorliegende überarbeitete Leitlinie zum Lipödem wurde unter der Federführung der Deutschen Gesellschaft für Phlebologie (DGP) erstellt und finanziert. Die Inhalte beruhen auf einer systematischen Literaturrecherche und dem Konsens von acht medizinischen Fachgesellschaften und Berufsverbänden. Die Leitlinie beinhaltet Empfehlungen zu Diagnostik und Therapie des Lipödems.

Die Diagnose ist dabei auf der Basis von Anamnese und klinischem Befund zu stellen. Charakteristisch ist eine umschriebene, symmetrisch lokalisierte Vermehrung des Unterhautfettgewebes an den Extremitäten mit deutlicher Disproportion zum Stamm. Zusätzlich finden sich Ödeme, Hämatomneigung und eine gesteigerte Schmerzhaftigkeit der betroffenen Körperabschnitte. Weitere apparative Untersuchungen sind bisher besonderen Fragestellungen vorbehalten. Die Erkrankung ist chronisch progredient mit individuell unterschiedlichem und nicht vorhersehbarem Verlauf.

Die Therapie besteht aus vier Säulen, die individuell kombiniert und an das aktuelle Beschwerdebild angepasst werden sollten: komplexe physikalische Entstauungstherapie (manuelle Lymphdrainage, Kompressionstherapie, Bewegungstherapie, Hautpflege), Liposuktion und plastisch‐chirurgische Interventionen, Ernährung und körperliche Aktivität sowie ggf. additive Psychotherapie. Operative Maßnahmen sind insbesondere dann angezeigt, wenn trotz konsequent durchgeführter konservativer Therapie noch Beschwerden bestehen bzw. eine Progredienz des Befundes und/oder der Beschwerden auftritt. Eine begleitend zum Lipödem bestehende morbide Adipositas sollte vor einer Liposuktion therapeutisch angegangen werden.
Knowledge Integration and Team Effectiveness: A Team Goal Orientation Approach
Authors: Mehta Anju , Mehta Nikhil
Published: July 2017

Knowledge integration is critical to achieving both objective and subjective team effectiveness goals. Integrating knowledge resources, however, is a challenging activity for teams. Converging the theories of team goal orientation and knowledge integration, in this study we examine how team goal orientation impacts a team's internal knowledge integration, and how knowledge integration, in turn, affects multiple dimensions of team effectiveness. Data were collected from 90 self‐directed teams engaged in an extended business simulation, where each team acted as a top management team of a business firm. Results indicated that both learning and performance‐prove goal orientations positively influenced team knowledge integration, and knowledge integration impacted both objective and subjective dimensions of team effectiveness. We also found partial support for a mediating role of internal knowledge integration. The study recommends a goal orientation approach to integrating knowledge in teams and proposes that this approach has significant implications for both research and practice.
THE PROTESTANT FISCAL ETHIC: RELIGIOUS CONFESSION AND EURO SKEPTICISM IN GERMANY
Authors: Chadi Adrian , Krapf Matthias
Published: July 2017

During the European sovereign debt crisis, most countries that ran into fiscal trouble had Catholic majorities, whereas countries with Protestant majorities were able to avoid fiscal problems. We find that Christian‐conservative members of the German parliament from constituencies with higher shares of Protestants were more likely to vote against a third bailout for Greece. Survey data show that views on the euro differ between German Protestants and non‐Protestants at the individual level, too. Among Protestants, concerns about the euro have, compared to non‐Protestants, increased during the crisis. We show that this increase in concern is linked to a reduction of Protestants' subjective well‐being. We use the timing of survey interviews and news events in 2011 to account for the endogeneity of euro concerns. Emphasis on moral hazard concerns in Protestant theology may, thus, still shape economic preferences. (JEL D72, E00, I31, Z12)
DREADD‐induced silencing of the medial amygdala reduces the preference for male pheromones and the expression of lordosis in estrous female mice
Authors: McCarthy Elizabeth A. , Maqsudlu Arman , Bass Matthew , Georghiou Sofia , Cherry James A. , Baum Michael J.
Published: July 2017

Sexually naïve estrous female mice seek out male urinary pheromones; however, they initially display little receptive (lordosis) behavior in response to male mounts. Vomeronasal–accessory olfactory bulb inputs to the medial amygdala (Me) regulate courtship in female rodents. We used a reversible inhibitory chemogenetic technique (Designer Receptors Exclusively Activated by Designer Drugs; DREADDs) to assess the contribution of Me signaling to females’ preference for male pheromones and improvement in receptivity normally seen with repeated testing. Sexually naïve females received bilateral Me injections of an adeno‐associated virus carrying an inhibitory DREADD. Females were later ovariectomized, treated with ovarian hormones, and given behavioral tests following intraperitoneal injections of saline or clozapine‐N‐oxide (CNO; which hyperpolarizes infected Me neurons). CNO attenuated females’ preference to investigate male vs. female urinary odors. Repeated CNO treatment also slowed the increase in lordosis otherwise seen in females given saline. However, when saline was given to females previously treated with CNO, their lordosis quotients were as high as other females repeatedly given saline. No disruptive behavioral effects of CNO were seen in estrous females lacking DREADD infections of the Me. Finally, CNO attenuated the ability of male pheromones to stimulate Fos expression in the Me of DREADD‐infected mice but not in non‐infected females. Our results affirm the importance of Me signaling in females’ chemosensory preferences and in the acute expression of lordosis. However, they provide no indication that Me signaling is required for the increase in receptivity normally seen after repeated hormone priming and testing with a male.
Striatal cholinergic interneurons and Parkinson's disease
Authors: Tanimura Asami , Pancani Tristano , Lim Sean Austin O. , Tubert Cecilia , Melendez Alexandra E. , Shen Weixing , Surmeier Dalton James
Published: July 2017

Giant, aspiny cholinergic interneurons (ChIs) have long been known to be key nodes in the striatal circuitry controlling goal‐directed actions and habits. In recent years, new experimental approaches, like optogenetics and monosynaptic rabies virus mapping, have expanded our understanding of how ChIs contribute to the striatal activity underlying action selection and the interplay of dopaminergic and cholinergic signaling. These approaches also have begun to reveal how ChI function is distorted in disease states affecting the basal ganglia, like Parkinson's disease (PD). This review gives a brief overview of our current understanding of the functional role played by ChIs in striatal physiology and how this changes in PD. The translational implications of these discoveries, as well as the gaps that remain to be bridged, are discussed as well.