bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic potential and in situ activity of marine Marinimicrobia bacteria in an anoxic water column
Authors: Bertagnolli Anthony D. , Padilla Cory C. , Glass Jennifer B. , Thamdrup Bo , Stewart Frank J.
Published: August 2017

Marinimicrobia bacteria are widespread in subeuphotic areas of the oceans and particularly abundant in oxygen minimum zones (OMZs). Information on Marinimicrobia metabolism is sparse, making the biogeochemical influence of this group challenging to predict. Here, metagenome‐assembled genomes representing Marinimicrobia subgroups PN262000N21 and ARCTIC96B‐7 were retrieved to near completion (97% and 94%) from OMZ metagenomes, with contamination (14.1%) observed only in ARCTIC96B‐7. Genes for aerobic carbon monoxide (CO) oxidation, polysulfide metabolism and hydrogen utilization were identified only in PN262000N21, while genes for partial denitrification occurred in both genomes. Transcripts mapping to these genomes increased from <0.3% of total mRNA from the oxic zone to a max of 22% under anoxia. ARCTIC96B‐7 transcript representation decreased an order of magnitude from non‐sulfidic to sulfidic depths. In contrast, PN262000N21 representation was relatively constant throughout the OMZ, although transcripts encoding sulfur‐utilizing proteins, including sulfur transferases, were enriched at sulfidic depths. PN262000N21 transcripts encoding a protein with fibronectin domains similar to those in cellulosome‐producing bacteria were also abundant, suggesting a potential for high molecular weight carbon cycling. These data provide omic‐level descriptions of metabolic potential and activity in OMZ‐associated Marinimicrobia, suggesting differentiation between subgroups with roles in carbon and dissimilatory inorganic nitrogen and sulfur cycling.
Evidence for H2 consumption by uncultured Desulfobacterales in coastal sediments
Authors: Dyksma Stefan , Pjevac Petra , Ovanesov Kin , Mussmann Marc
Published: August 2017

Molecular hydrogen (H2) is the key intermediate in the anaerobic degradation of organic matter. Its removal by H2‐oxidizing microorganisms is essential to keep anaerobic degradation energetically favourable. Sulfate‐reducing microorganisms (SRM) are known as the main H2 scavengers in anoxic marine sediments. Although the community of marine SRM has been extensively studied, those consuming H2 in situ are completely unknown. We combined metagenomics, PCR‐based clone libraries, single‐amplified genomes (SAGs) and metatranscriptomics to identify potentially H2‐consuming SRM in anoxic coastal sediments. The vast majority of SRM‐related H2ase sequences were assigned to group 1b and 1c [NiFe]‐H2ases of the deltaproteobacterial order Desulfobacterales. Surprisingly, the same sequence types were similarly highly expressed in spring and summer, suggesting that these are stable and integral members of the H2‐consuming community. Notably, one sequence cluster from the SRM group 1 consistently accounted for around half of all [NiFe]‐H2ase transcripts. Using SAGs, we could link this cluster with the 16S rRNA genes of the uncultured Sva0081‐group of the family Desulfobacteraceae. Sequencing of 16S rRNA gene amplicons and H2ase gene libraries suggested consistently high in situ abundance of the Sva0081 group also in other marine sediments. Together with other Desulfobacterales these likely are important H2‐scavengers in marine sediments.
Multifunctional Curcumin Mediate Multitherapeutic Effects
Authors: Shehzad Adeeb , Qureshi Munibah , Anwar Muhammad Nabeel , Lee Young Sup
Published: August 2017

Inflammation can promote the development of arthritis, obesity, cardiovascular, type II diabetes, pancreatitis, metabolic and neurodegenerative diseases, and certain types of cancer. Compounds isolated from plants have been practiced since ancient times for curing various ailments including inflammatory disorders and to support normal physiological functions. Curcumin (diferuloylmethane) is a yellow coloring agent, extracted from turmeric that has been used for the prevention and treatment of various inflammatory diseases. Numerous studies have shown that curcumin modulate multiple molecular targets and can be translated to the clinics for multiple therapeutic processes. There is compelling evidence that curcumin can block cell proliferation, invasion, and angiogenesis as well as reduced the prolonged survival of cancer cells. Curcumin mediates anti‐inflammatory effect through downregulation of inflammatory cytokines, transcription factors, protein kinases, and enzymes that promote inflammation and development of chronic diseases. In addition, curcumin induces apoptosis through mitochondrial and receptor‐mediated pathways by activating caspase cascades. Curcumin is a safe and nontoxic drug that has been reported to be well tolerated. Available clinical trials support the potential role of curcumin for treatment of various inflammatory disorders. However, curcumin's efficacy is hindered by poor absorption and low bioavailability, which limit its translation into clinics. This review outlines the potential pharmacological and clinical role of curcumin, which provide a gateway for the beneficial role of plant isolated compounds in treatment of various inflammatory diseases and cancer.
Seven microbial bio‐processes to help the planet
Authors: de Lorenzo Víctor
Published: August 2017

There is a number of global environmental problems that could be tackled through advanced Microbial Biotechnology.
Methanotroph‐derived bacteriohopanepolyol signatures as a function of temperature related growth, survival, cell death and preservation in the geological record
Authors: Osborne Kate A. , Gray Neil D. , Sherry Angela , Leary Peter , Mejeha Obioma , Bischoff Juliane , Rush Darci , Sidgwick Frances R. , Birgel Daniel , Kalyuzhnaya Marina G. , Talbot Helen M.
Published: August 2017

Interpretation of bacteriohopanepolyol (BHP) biomarkers tracing microbiological processes in modern and ancient sediments relies on understanding environmental controls of production and preservation. BHPs from methanotrophs (35‐aminoBHPs) were studied in methane‐amended aerobic river‐sediment incubations at different temperatures. It was found that: (i) With increasing temperature (4°C–40°C) a 10‐fold increase in aminopentol (associated with Crenothrix and Methylobacter spp. growth) occurred with only marginal increases in aminotriol and aminotetrol; (ii) A further increase in temperature (50°C) saw selection for the thermophile Methylocaldum and mixtures of aminopentol and C‐3 methylated aminopentol, again, with no increase in aminotriol and aminotetrol. (iii) At 30°C, more aminopentol and an aminopentol isomer and unsaturated aminopentol were produced after methanotroph growth and the onset of substrate starvation/oxygen depletion. (iv) At 50°C, aminopentol and C‐3 methylated aminopentol, only accumulated during growth but were clearly resistant to remineralization despite cell death. These results have profound implications for the interpretation of aminoBHP distributions and abundances in modern and past environments. For instance, a temperature regulation of aminopentol production but not aminotetrol or aminotriol is consistent with and, corroborative of, observed aminopentol sensitivity to climate warming recorded in a stratigraphic sequence deposited during the Paleocene‐Eocene thermal maximum (PETM).
Epac1, PDE4, and PKC protein expression and their correlation with AKAP95 and Cx43 in esophagus cancer tissues
Authors: Guan Zhiyu , Zhuang Winxin , Lei Hui , Wang Dai , Yao Youliang , Guo Dongbei , Sun Qian , Chen Yun , Chen Xiaoyi , Lin Hongyan , Teng Bogang , Zhang Yongxing
Published: August 2017

Background

This study examined the expression of exchange protein directly activated by cAMP1 (Epac1), PDE4, and PKC in esophageal cancer tissues, and analyzed the association of each protein with the pathological parameters of the samples.

Methods

Epac1, PDE4, and PKC protein expression was evaluated by PV‐9000 two‐step immunohistochemical techniques in 51 esophageal cancer specimens and 10 para‐carcinoma tissues.

Results

The positive expression rates of Epac1 and PKC in esophageal cancer tissues (62.7% and 68.6%, respectively) were higher compared to those in para‐carcinoma tissues (20% and 20%, respectively) (P < 0.05). The positive expression rate of PDE4 in esophageal cancer tissues (54.1%) was higher than in para‐carcinoma tissues (30%), (P > 0.05). Epac1, PDE4, and PKC protein expression levels were not associated with the extent of tumor differentiation and/or lymph node metastasis (P > 0.05). Epac1 protein expression levels correlated with PDE4, PKC, and AKAP95 protein expression levels. In addition, there was a correlation between PKC and Cx43 protein levels (P < 0.05).

Conclusion

The expression rates of Epac1, PDE4, and PKC protein in esophageal cancer tissues were significantly higher compared to the rates in para‐carcinoma tissues, suggesting an association between these proteins and the development and progression of esophageal cancer. The correlations between these proteins also revealed that they may exert a synergistic effect during the development of esophageal cancer.
Phase I study of pemetrexed and concurrent radiotherapy for previously untreated elderly patients with locally advanced non‐squamous non‐small cell lung cancer
Authors: Takemoto Shinnosuke , Nakamura Yoichi , Fukuda Minoru , Senju Hiroaki , Gyotoku Hiroshi , Taniguchi Hirokazu , Shimada Midori , Ikeda Takaya , Yamaguchi Hiroyuki , Nakatomi Katsumi , Hayashi Nobuyuki , Soda Hiroshi , Mukae Hiroshi
Published: August 2017

Background

Chemoradiotherapy is the standard treatment for locally advanced non‐small cell lung cancer (NSCLC); however, it is disputed whether this treatment is suitable for patients aged ≥75. This study was conducted to determine the maximum tolerated dose (MTD) of pemetrexed for use in concurrent radiotherapy for elderly patients with locally advanced non‐squamous NSCLC.

Methods

The eligibility criteria were as follows: aged ≥75 with inoperable stage IIIA or IIIB non‐squamous NSCLC, no history of chemotherapy or radiotherapy, a performance status of 0 or 1, and adequate organ function. The patients were scheduled to receive pemetrexed on days 1, 22, 43, and 64 with concurrent once daily thoracic radiotherapy (60 Gy). The initial pemetrexed dose was 400 (level 1), and it was planned to increase the dose to 500 mg/m2 (level 2).

Results

Two patients were enrolled in this trial. In the first case, the patient suffered prolonged leukocytopenia, and treatment was discontinued on day 35. In the second case, febrile neutropenia occurred on day 32, and the patient developed drug‐induced pneumonitis and acute respiratory distress syndrome. Both patients experienced dose‐limiting toxicities; therefore, the level 1 dose was considered to be the MTD.

Conclusions

During combined treatment with pemetrexed and concurrent radiotherapy, a pemetrexed dose of 400 mg/m2 was the MTD; we did not set up a phase II study. Concurrent chemoradiotherapy might be too toxic for elderly patients aged ≥75 with locally advanced NSCLC.
HDAC3 negatively regulates spatial memory in a mouse model of Alzheimer's disease
Authors: Zhu Xiaolei , Wang Sulei , Yu Linjie , Jin Jiali , Ye Xing , Liu Yi , Xu Yun
Published: August 2017

The accumulation and deposition of beta‐amyloid (Aβ) is a key neuropathological hallmark of Alzheimer's disease (AD). Histone deacetylases (HDACs) are promising therapeutic targets for the treatment of AD, while the specific HDAC isoforms associated with cognitive improvement are poorly understood. In this study, we investigate the role of HDAC3 in the pathogenesis of AD. Nuclear HDAC3 is significantly increased in the hippocampus of 6‐ and 9‐month‐old APPswe/PS1dE9 (APP/PS1) mice compared with that in age‐matched wild‐type C57BL/6 (B6) mice. Lentivirus ‐mediated inhibition or overexpression of HDAC3 was used in the hippocampus of APP/PS1 mice to investigate the role of HDAC3 in spatial memory, amyloid burden, dendritic spine density, glial activation and tau phosphorylation. Inhibition of HDAC3 in the hippocampus attenuates spatial memory deficits, as indicated in the Morris water maze test, and decreases amyloid plaque load and Aβ levels in the brains of APP/PS1 mice. Dendritic spine density is increased, while microglial activation is alleviated after HDAC3 inhibition in the hippocampus of 9‐month‐old APP/PS1 mice. Furthermore, HDAC3 overexpression in the hippocampus increases Aβ levels, activates microglia, and decreases dendritic spine density in 6‐month‐old APP/PS1 mice. In conclusion, our results indicate that HDAC3 negatively regulates spatial memory in APP/PS1 mice and HDAC3 inhibition might represent a potential therapy for the treatment of AD.
American exceptionalism and the failure to learn from mistakes of the past
Authors: Pardo Bryce
Published: August 2017

Commentary to: The diverging trajectories of cannabis and tobacco policies in the United States: reasons and possible implications
Lymphocytic hidradenitis: A distinctive histopathological finding of annular erythema of Sjögren syndrome
Authors: Hsu Hsiu‐cheng , Lin Chien‐Yio , Shih I‐Hsin , Shen Su‐Chin
Published: August 2017

Background/Objectives

Lymphocytic hidradenitis is a non‐specific histopathological feature observed in many dermatoses such as lupus erythematosus, morphea or scleroderma. When it occurs it is usually accompanied by the other distinctive histological features of those conditions. Isolated lymphocytic hidradenitis is uncommon and its clinical features and associated underlying medical conditions are still undetermined.

Methods

We performed a retrospective review of patients who clinically presented with annular erythema between 2000 and 2016. Altogether, 30 patients with a histopathological presentation of isolated lymphocytic hidradenitis were identified. Their following characteristics were recorded: clinical features, number and localisation of lesions, serology and other associated medical conditions.

Results

Isolated lymphocytic hidradenitis was found most frequently in middle‐aged women. Most patients (n = 28, 93%) presented with many annular erythematous patches and plaques with mild pruritus; 22 (73%) had the SS‐A antibody and 17 (57%) met the diagnostic criteria of Sjögren syndrome. Among these patients, 11 had primary and six had secondary Sjögren syndrome associated with systemic lupus erythematosus. Altogether 15 (50%) patients tested positive for a high titre of the antinuclear autoantibody. Other underlying diseases identified during the follow‐up period include cryoglobulinaemia, angioimmunoblastic T‐cell lymphoma, autoimmune hepatitis, hepatitis C infection and toxic thyroid goitre.

Conclusions

Lymphocytic hidradenitis is a microscopic finding associated with annular erythemas of Sjögren syndrome. Systemic survey for sicca symptoms and work up for autoimmune diseases, including antinuclear antibodies, SS‐A, SS‐B antibodies, cryoglobulin, lymphoma, viral and autoimmune hepatitis should be performed to facilitate the correct diagnosis.
Challenges in the implementation of EAACI guidelines on allergen immunotherapy: A global perspective on the regulation of allergen products
Authors: Bonertz A. , Roberts G. C. , Hoefnagel M. , Timon M. , Slater J. E. , Rabin R. L. , Bridgewater J. , Pini C. , Pfaar O. , Akdis C. , Goldstein J. , Poulsen L. K. , van Ree R. , Rhyner C. , Barber D. , Palomares O. , Sheikh A. , Pawankar R. , Hamerlijnk D. , Klimek L. , Agache I. , Angier E. , Casale T. , Fernandez‐Rivas M. , Halken S. , Jutel M. , Lau S. , Pajno G. , Sturm G. , Varga E. M. , Gerth van Wijk R. , Bonini S. , Muraro A. , Vieths S.
Published: August 2017

Regulatory approaches for allergen immunotherapy (AIT) products and the availability of high‐quality AIT products are inherently linked to each other. While allergen products are available in many countries across the globe, their regulation is very heterogeneous. First, we describe the regulatory systems applicable for AIT products in the European Union (EU) and in the United States (US). For Europe, a depiction of the different types of relevant procedures, as well as the committees involved, is provided and the fundamental role of national agencies of the EU member states in this complex and unique network is highlighted. Furthermore, the regulatory agencies from Australia, Canada, Japan, Russia, and Switzerland provided information on the system implemented in their countries for the regulation of allergen products. While AIT products are commonly classified as biological medicinal products, they are made available by varying types of procedures, most commonly either by obtaining a marketing authorization or by being distributed as named patient products. Exemptions from marketing authorizations in exceptional cases, as well as import of allergen products from other countries, are additional tools applied by countries to ensure availability of needed AIT products. Several challenges for AIT products are apparent from this analysis and will require further consideration.
Safety and efficacy of rescue flexible bronchoscopic intubation using the Bentson floppy‐tip guidewire via a supraglottic airway in critically ill children
Authors: Cross D. , Nyman A. , James P. , Durward A.
Published: August 2017

Difficulty in tracheal intubation in paediatric intensive care patients is associated with increased morbidity and mortality. Delays to intubation and interruption to oxygenation and ventilation are poorly tolerated. We developed a safe and atraumatic tracheal intubation technique. A floppy‐tipped guidewire and airway exchange catheter were placed to a pre‐determined length under bronchoscopic guidance while oxygenation and ventilation was maintained via a supraglottic airway device (SAD). We performed a retrospective review of this technique on patients who were either known to have or who had an unexpected difficultly in intubation. We describe the safety and experience of this in a broad range of critically ill children. Thirteen patients, median (IQR [range]) (9.0 (5.0–10.0 [4.0–12.0]) kg and 15.4 (12.1–23.2 [3.3–49.7]) months) underwent emergency tracheal intubation using this technique, after unsuccessful attempts at intubation using standard laryngoscopy blades. All intubations were successful at the first attempt using this technique and no airway trauma or significant clinical deteriorations were recorded.
Intraoperative ultrasound for the colorectal surgeon: current trends and barriers
Authors: Walker Thomas L. J. , Bamford Richard , Finch‐Jones Margaret
Published: August 2017

Up to two thirds of patients diagnosed with colorectal cancer (CRC) develop colorectal liver metastases (CRLMs) and one quarter of patients present with synchronous metastases. Early detection of CRLM widens the scope of potential treatment. Surgery for CRLM offers the best chance of a cure. Current preoperative staging of CRC relies on computerized tomography and magnetic resonance imaging. Intraoperative ultrasound (IOUS) scans and contrast‐enhanced IOUS (CE‐IOUS) have been demonstrated to detect additional metastases not seen on routine preoperative imaging. IOUS is not widely used by colorectal surgeons during primary resection for CRC. Confident use of IOUS/CE‐IOUS during primary resection of CRC may improve decision‐making by providing the most sensitive form of liver staging even when compared with magnetic resonance imaging. This may be particularly important in the era of laparoscopic resections, where the colorectal surgeon loses the opportunity to palpate the liver. There are several implied barriers to the routine use of IOUS/CE‐IOUS by colorectal surgeons. These include time pressure, familiarity with techniques, a perceived learning curve, cost implications and limitation of the modality due to operator variations. Inclusion of IOUS in the training of colorectal surgeons and further investigation of potential benefits of IOUS/CE‐IOUS could potentially reduce these barriers, enabling usage during primary resection for CRC to become more widespread.
Neurotoxic side effects in children with refractory or relapsed T‐cell malignancies treated with nelarabine based therapy
Authors: Kuhlen Michaela , Bleckmann Kirsten , Möricke Anja , Schrappe Martin , Vieth Simon , Escherich Gabriele , Bronsema Annika , Vonalt Annika , Queudeville Manon , Zwaan C. Michel , Ebinger Martin , Debatin Klaus‐Michael , Klingebiel Thomas , Koscielniak Ewa , Rossig Claudia , Burkhardt Birgit , Kolb Reinhard , Eckert Cornelia , Borkhardt Arndt , von Stackelberg Arend , Chen‐Santel Christiane
Published: August 2017

The prognosis in children with refractory or relapsed (r/r) T‐cell acute lymphoblastic leukaemia (T‐ALL) or lymphoblastic lymphoma (T‐LBL) is poor. Nelarabine (Ara‐G) has successfully been used as salvage therapy in these children, but has been associated with significant, even fatal, neurotoxicities. We retrospectively analysed 52 patients with r/r T‐ALL/T‐LBL aged ≤19 years who were treated with Ara‐G alone (n = 25) or in combination with cyclophosphamide and etoposide (n = 27). The majority of patients (45/52) received 1–2 cycles of Ara‐G. Seventeen patients (32·7%) had refractory disease, 28 (53·8%) were in first relapse and 7 (13·5%) were in second relapse. A response to Ara‐G was achieved in 20 patients and 15 (28·8%) were in remission at last follow‐up. Twelve patients (23·1%) had neurotoxic adverse effects (neuro‐AE) of any grade, of whom 7 (13·5%) developed neurotoxicity ≥ grade III. The most frequent neuro‐AEs were peripheral motor neuropathy (19·2%), peripheral sensory neuropathy (11·5%) and seizures (9·6%). Three patients died of central neuro‐AE after 1–2 cycles of combination therapy. Patients with neurotoxicity were significantly older (median 15·17 years) than those without (10·34 years, P = 0·017). No differences were observed between mono‐ and combination therapy concerning outcome and neuro‐AE. The incidence of neuro‐AE was not associated with concurrent intrathecal therapy or prior central nervous system irradiation.
Transformed Waldenström macroglobulinaemia: clinical presentation and outcome. A multi‐institutional retrospective study of 77 cases from the French Innovative Leukemia Organization (FILO)
Authors: Durot Eric , Tomowiak Cécile , Michallet Anne‐Sophie , Dupuis Jehan , Hivert Bénédicte , Leprêtre Stéphane , Toussaint Elise , Godet Sophie , Merabet Fatiha , Van Den Neste Eric , Ivanoff Sarah , Roussel Xavier , Zini Jean‐Marc , Regny Caroline , Lemal Richard , Sutton Laurent , Perrot Aurore , Le Dû Katell , Kanagaratnam Lukshe , Morel Pierre , Leblond Véronique , Delmer Alain
Published: August 2017

Histological transformation (HT) to diffuse large B‐cell lymphoma (DLBCL) is a rare and poorly reported complication of Waldenström macroglobulinaemia (WM). We performed a retrospective study of 77 WM patients with biopsy‐proven transformation to DLBCL. The median time from WM diagnosis to HT was 4·6 years and 16 patients (21%) had never been treated for WM. At HT, extranodal sites were observed in 91% of patients with a rather high incidence of central nervous system, cutaneous or testicular involvement. Fluorodeoxyglucose‐positron emission tomography was performed in half of the patients and the median maximum standardized uptake value was 15 for transformed disease. More than 80% of cases with available data for assessment by the Hans’ algorithm harboured a non‐germinal centre B‐cell phenotype. First‐line treatment for transformation consisted of R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)‐like regimen in 85% of patients. The overall response rate after first‐line treatment was 61% and the median overall survival was only 16 months for the entire cohort. Time to transformation above 5 years (P = 0·0004) and elevated LDH (P = 0·02) were associated with worse outcome. Based on these findings, HT should be considered and lead to a biopsy in WM patients presenting with extranodal involvement, elevated LDH and constitutional symptoms. The optimal therapeutic approaches remain to be defined.
Long non‐coding RNA MALAT1 is an inducible stress response gene associated with extramedullary spread and poor prognosis of multiple myeloma
Authors: Handa Hiroshi , Kuroda Yuko , Kimura Kei , Masuda Yuta , Hattori Hikaru , Alkebsi Lobna , Matsumoto Morio , Kasamatsu Tetsuhiro , Kobayashi Nobuhiko , Tahara Ken‐ichi , Takizawa Makiko , Koiso Hiromi , Ishizaki Takuma , Shimizu Hiroaki , Yokohama Akihiko , Tsukamoto Norifumi , Saito Takayuki , Murakami Hirokazu
Published: August 2017

Extramedullary myeloma (EMM) occurs when myeloma develops outside the bone marrow; it often develops after chemotherapy and is associated with the acquisition of chemo‐resistance and a fatal course. The mechanisms underlying extramedullary spread have not yet been fully elucidated. MALAT1 is a highly abundantly and ubiquitously expressed long non‐coding RNA that plays important roles in cancer metastasis. The aims of this study were to clarify the association of MALAT1 with EMM and to elucidate the underlying mechanism of EMM formation under chemotherapeutic pressure. MALAT1 expression was significantly higher in multiple myeloma (MM) than in monoclonal gammopathy of undetermined significance. Furthermore, MALAT1 expression was markedly higher in EMM compared with that in corresponding intramedullary myeloma cells. A higher MALAT1 level was associated with shorter overall and progression‐free survival. MALAT1 expression level was positively correlated with expression of HSP90AA1, HSP90AB1 and HSP90B1 but not with TP53 expression. MALAT1 was significantly upregulated by bortezomib and doxorubicin. Considering the known functions of MALAT1, our results suggest that it acts as a stress response gene that is upregulated by chemotherapy, thereby linking chemotherapy to EMM formation. Elucidating the biological implication of long non‐coding RNA contributes to deeper understanding concerning the pathogenesis and investigation of novel therapeutic targets for MM.
Comparison of lesions detected and undetected by template‐guided transperineal saturation prostate biopsy
Authors: Mai Zhipeng , Xiao Yu , Yan Weigang , Zhou Yi , Zhou Zhien , Liang Zhiyong , Ji Zhigang , Li Hanzhong
Published: August 2017

Objectives

To compare the characteristics of lesions detected or undetected by template‐guided transperineal saturation prostate biopsy and to evaluate the potential impact of undetected lesions.

Materials and Methods

We evaluated the characteristics of lesions in radical prostatectomy (RP) specimens, compared the differences between lesions detected and undetected by systematic transperineal ultrasonography‐guided 11‐region biopsy with regard to tumour volume, Gleason score, surgical margin, spatial location and clinical significance, and assessed the potential impact of undetected clinically significant lesions.

Results

The median number of biopsy cores was 24. Sixty‐four percent of the clinically significant lesions (170/264) were detected. There were significant differences between the detected and undetected lesions in tumour volume, Gleason score and clinical significance. Inconsistencies found in lesion position between biopsy and RP specimens in the anterior and posterior zones and the left and right sides was 3.4% (7/203) and 5.4% (11/203), respectively. Of the 129 patients, 13 (10.1%) were found to have undetected clinically significant lesions in the biopsy lying on the same side but in a different zone from the detected clinically significant lesions, whereas 23 patients (17.8%) had undetected clinically significant lesions in the biopsy lying on the opposite side from the detected clinically significant lesions.

Conclusions

Template‐guided transperineal saturation prostate biopsy detected approximately two‐thirds of clinically significant lesions. Most of the undetected lesions were those with small tumour volume. Approximately 20–30% of patients had clinically significant undetected lesions in a different lobe or different quadrant from the detected lesions in the biopsy.
Effects of centrally administered endocannabinoids and opioids on orofacial pain perception in rats
Authors: Zubrzycki Marek , Janecka Anna , Liebold Andreas , Ziegler Mechthild , Zubrzycka Maria
Published: August 2017

Background and Purpose

Endocannabinoids and opioids play a vital role in mediating pain‐induced analgesia. The specific effects of these compounds within the orofacial region are largely unknown. In this study, we tried to determine whether an increase in cannabinoid and opioid concentration in the CSF affects impulse transmission between the motor centres localized in the vicinity of the third and fourth cerebral ventricles.

Experimental Approach

The study objectives were realized on rats using a method that allows the recording of the amplitude of evoked tongue jerks (ETJ) in response to noxious tooth pulp stimulation. The amplitude of ETJ was a measure of the effect of neurotransmitters on neural structures.

Key Results

Perfusion of cerebral ventricles with anandamide (AEA), endomorphin‐2 (EM‐2), URB597, an inhibitor of fatty acid amide hydrolase (FAAH) and JZL195, a dual inhibitor of FAAH and monoacylglycerol lipase (MAGL) reduced the ETJ amplitude. The antinociceptive effect of AEA, EM‐2, URB597 and JZL195 was blocked by CB1receptor antagonist, AM251 and by μ receptor‐antagonist, β‐funaltrexamine. In contrast to AEA, 2‐arachidonoylglycerol alone did not decrease ETJ amplitude.

Conclusions and Implications

We demonstrated that in the orofacial area, analgesic activity is modulated by AEA and that EM‐2‐induced antinociception was mediated by μ and CB1receptors. The action of AEA and EM‐2 is tightly regulated by FAAH and FAAH/MAGL, by preventing the breakdown of endogenous cannabinoids in regions where they are produced on demand. Therefore, the current findings support the therapeutic potential of FAAH and FAAH/MAGL inhibitors as novel pharmacotherapeutic agents for orofacial pain.
microRNA‐219‐5p inhibits epithelial‐mesenchymal transition and metastasis of colorectal cancer by targeting lymphoid enhancer‐binding factor 1
Authors: Huang Lan‐xuan , Hu Chun‐yan , Jing Li , Wang Min‐cong , Xu Meng , Wang Jing , Wang Yu , Nan Ke‐jun , Wang Shu‐hong
Published: August 2017

Aberrant expression of microRNAs (miRs) has been shown to play a critical role in the pathogenesis and progression of tumors. microRNA‐219‐5p (miR‐219‐5p) has been reported to be abnormally expressed in some types of human tumors. However, the mechanism between miR‐219‐5p and colorectal cancer (CRC) metastasis remains unclear. In the present study, miR‐219‐5p was found to be downregulated in CRC tissue compared with matched normal tissue. Through luciferase reporter assay, we demonstrated lymphoid enhancer‐binding factor 1 (LEF1) as a direct target of miR‐219‐5p. Overexpression of miR‐219‐5p could inhibit motility, migration and invasion of CRC cells, and inhibit epithelial‐mesenchymal transition (EMT). Furthermore, silencing LEF1 phenocopied this metastasis‐suppressive function. The recovery experiment showed that re‐expression of LEF1 rescued this suppressive effect on tumor metastasis and reversed the expression of EMT markers caused by miR‐219‐5p. Additionally, we demonstrated that miR‐219‐5p exerted this tumor‐suppressive function by blocking activation of the AKT and ERK pathways. Finally, a nude mice experiment showed that miR‐219‐5p reduced the lung metastasis ability of CRC cells. Taken together, our findings indicate that miR‐219‐5p inhibits metastasis and EMT of CRC by targeting LEF1 and suppressing the AKT and ERK pathways, which may provide a new antitumor strategy to delay CRC metastasis.
Cognitive impairment in adolescents and adults with congenital adrenal hyperplasia
Authors: Karlsson Leif , Gezelius Anton , Nordenström Anna , Hirvikoski Tatja , Lajic Svetlana
Published: August 2017

Objective

Impaired cognition has been reported in patients with congenital adrenal hyperplasia (CAH), although the findings have been conflicting. It has been hypothesized that the major causes of the deficits are prenatal hormonal imbalances and/or excessive glucocorticoid treatment.

Design

An observational study investigating cognition in patients with CAH.

Patients

A total of 55 patients with CAH and 58 control subjects from the general population, aged 16–33 years. Nine CAH subjects had been treated prenatally with dexamethasone.

Setting

Singel research institute.

Measurements

Standardized neuropsychological tests (Wechsler Scales and Stroop Interference Test) and questionnaires (Barkley Deficit in Executive Functioning Scale) were used.

Results

Compared to controls, patients with CAH had impaired performance in tests measuring verbal working memory (P = .024), visual‐spatial working memory (P = .005 and P = .003) and inhibition (P = .002). In measures of fluid intelligence/nonverbal logical reasoning, males with CAH performed poorer than control males (P = .033). Patients with salt‐wasting CAH performed equally compared to patients with simple virilizing CAH. However, patients with a null genotype performed poorer than patients with a non‐null genotype and significantly worse on fluid intelligence/nonverbal logical reasoning (P = .042). Prenatally‐treated women performed worse on most cognitive measures than women with CAH not treated prenatally.

Conclusions

Patients with CAH had normal psychometric intelligence but impaired executive functions compared with population controls. A null CAH genotype was associated with poorer general cognitive capacity.
Hospitality and Immigration in a Greek Urban Neighborhood: An Ethnography of Mimesis
Authors: ANDRIKOPOULOS APOSTOLOS
Published: August 2017

This article uses the concept of hospitality to examine the relations between native‐born Greeks and recently arrived immigrants in a Greek urban neighborhood. Beyond romanticized notions of hospitality as a moral obligation or national virtue, this article considers hospitality as a power relation and a control mechanism of social behavior and cultural production. Although relations between hosts and guests are interpersonal, their (perceived) statuses are often enmeshed in macro hierarchical structures. The concept of hospitality helps us to shift scales and examine host‐guest relations at the micro‐level of a neighborhood in relation to wider political and economic constellations. However, the scalar dimensions of hospitality have limitations. This ethnographic study shows that ethnic Greek ‘repatriates’ from the former Soviet Union, despite their ideological incorporation in the home of the Greek nation, are treated by native‐born Greeks, at the neighborhood level, as guests who must comply with the rules of hospitality. At the same time, regardless of their legal exclusion and stigmatization in official discourses, Albanian immigrants, who have accepted the role of guests and imitate the socio‐cultural patterns of their native‐Greek neighbors, are received better than Greek ‘repatriates’.
German “National Cancer Aid Monitoring” 2015–2019 – study protocol and initial results
Authors: Schneider Sven , Görig Tatiana , Schilling Laura , Breitbart Eckhard W. , Greinert Rüdiger , Diehl Katharina
Published: August 2017

Background and objectives

The National Cancer Aid Monitoring of Tanning Bed Use (NCAM) project is a major German study that aims to observe the most significant risk factors for skin cancer: natural sunlight and artificial UV radiation.

Participants and methods

NCAM is a nationwide cross‐sectional survey that will initially involve four rounds of data collection (so‐called waves) between 2015 and 2018. Every year, a representative nationwide sample consisting of 3,000 individuals aged between 14 and 45 years will be surveyed. The cross‐sectional survey will be complemented by a panel of n  =  450 current tanning bed users.

Results

The initial wave in 2015 shows an overall prevalence of tanning bed use of 29.5 %. Eleven percent of all participants had used a tanning bed within the past twelve months. Determinants of current tanning bed use included younger age, female gender, and full‐time/part‐time employment. The main motivations for tanning bed use reported were relaxation and increased attractiveness.

Conclusions

NCAM is the first study worldwide to monitor skin cancer risk factors at one‐year intervals using a large, nationally representative sample. Initial results indicate that, despite WHO warnings, millions of Germans use tanning beds, and that many of these users are adolescents despite legal restrictions aimed at preventing minors from using tanning beds.
Season length, body size, and social polymorphism: size clines but not saw tooth clines in sweat bees
Authors: DAVISON PAUL J. , FIELD JEREMY
Published: August 2017

1. Annual insects are predicted to grow larger where the growing season is longer. However, transitions from one to two generations per year can occur when the season becomes sufficiently long, and are predicted to result in a sharp decrease in body size because available development time is halved. The potential for resulting saw‐tooth clines has been investigated only in solitary taxa with free‐living larvae.

2. Size clines were investigated in two socially polymorphic sweat bees (Halictidae): transitions between solitary and social nesting occur along gradients of increasing season length, characterised by the absence or presence of workers and offspring that are individually mass provisioned by adults. How the body size changes with season length was examined, and whether transitions in social phenotype generate saw‐tooth size clines. We measured Lasioglossum calceatum and Halictus rubicundus nest foundresses originating from more than 1000 km of latitude, encompassing the transition between social and solitary nesting.

3. Using satellite‐collected temperature data to estimate season length, it was shown that both species were largest where the season was longest. Body size increased linearly with season length in L. calceatum and non‐linearly in H. rubicundus but the existence of saw‐tooth clines was not supported.

4. The present results suggest that because the amount of food consumed by offspring during development is determined by adults, environmental and social influences on the provisioning strategies of adult bees may be more important factors than available feeding time in determining offspring body size in socially polymorphic sweat bees.
Plant and insect genetic variation mediate the impact of arbuscular mycorrhizal fungi on a natural plant–herbivore interaction
Authors: RASMUSSEN PIL U. , AMIN TARIQUE , BENNETT ALISON E. , KARLSSON GREEN KRISTINA , TIMONEN SARI , VAN NOUHUYS SASKYA , TACK AYCO J. M.
Published: August 2017

1. While both arbuscular mycorrhizal (AM) fungi and plant and insect genotype are well known to influence plant and herbivore growth and performance, information is lacking on how these factors jointly influence the relationship between plants and their natural herbivores.

2. The aim of the present study was to investigate how a natural community of arbuscular mycorrhizal fungi affects the growth of the perennial herbPlantago lanceolataL. (Plantaginaceae), as well as its interaction with theGlanville fritillary butterfly [Melitaea cinxiaL. (Nymphalidae)]. For this, a multifactorial experiment was conducted using plant lines originating from multiple plant populations in theÅlandIslands,Finland, grown either with or without mycorrhizal fungi. For a subset of plant lines, the impact of mycorrhizal inoculation, plant line, and larval family on the performance ofM. cinxialarvae were tested.

3. Arbuscular mycorrhizal inoculation did not have a consistently positive or negative impact on plant growth or herbivore performance. Instead, plant genetic variation mediated the impact of arbuscular mycorrhizal fungi on plant growth, and both plant genetic variation and herbivore genetic variation mediated the response of the herbivore. For both the plant and insect, the impact of the arbuscular mycorrhizal community ranged from mutualistic to antagonistic. Overall, the present findings illustrate that genetic variation in response to mycorrhizal fungi may play a key role in the ecology and evolution of plant–insect interactions.
Justice without Solidarity? Collective Identity and the Fate of the ‘Ethical’ in Habermas' Recent Political Theory
Authors: Pierce Andrew J.
Published: August 2017

In past work, Habermas has claimed that justice and solidarity stand in a complementary relationship—that ‘ethical’ relations of solidarity are the ‘reverse side’ of justice. Yet in a recent address to the World Congress of Philosophy, he rejects this idea. This paper argues against this rejection. After explaining the idea, arguing for its centrality to Habermas' thought, and evaluating Habermas' scant reflections on this major transformation, I argue that his rejection of the idea is a result of a newfound skepticism about the power of secular reason, and should thus be understood in terms of his corresponding turn to religious traditions as alternative sources of solidarity. I argue against this ‘religious turn’ by developing an alternative advocated by Habermas himself in earlier reflections—attention to real sociopolitical movements. In particular, I analyze feminist and black liberation movements to demonstrate that Habermas' pessimism about secular sources of justice‐producing solidarity is unwarranted, and that, while ‘postsecular’ sources may provide one avenue for actionable solidarity, they are not the only one. I conclude by identifying a conceptual commonality in these two alternatives: an inclusive conception of what it means to be human.
Clinical and mutational spectrum of Charcot–Marie–Tooth disease type 2Z caused by MORC2 variants in Japan
Authors: Ando M. , Okamoto Y. , Yoshimura A. , Yuan J.‐H. , Hiramatsu Y. , Higuchi Y. , Hashiguchi A. , Mitsui J. , Ishiura H. , Fukumura S. , Matsushima M. , Ochi N. , Tsugawa J. , Morishita S. , Tsuji S. , Takashima H.
Published: August 2017

Background and purpose

The microrchidia family CW‐type zinc finger 2 gene (MORC2) was newly identified as a causative gene of Charcot–Marie–Tooth disease (CMT) type 2Z in 2016. We aimed to describe the clinical and mutational spectrum of patients with CMT harboring MORC2 mutations in Japan.

Methods

We analyzed samples from 781 unrelated patients clinically diagnosed with CMT using deoxyribonucleic acid microarray or targeted resequencing by next‐generation sequencing, and samples from 434 mutation‐negative patients were subjected to whole‐exome sequencing. We extracted MORC2 variants from these whole‐exome sequencing data and classified them according to American College of Medical Genetics standards and guidelines.

Results

We identified MORC2 variants in 13 patients. As the second most common causative gene of CMT type 2 after MFN2, MORC2 variants were detected in 2.7% of patients with CMT type 2. The mean age of onset was 10.3 ± 8.7 years, and the inheritance pattern was mostly sporadic (11/13 patients, 84.6%). The clinical phenotype was typically length‐dependent polyneuropathy, and electrophysiological studies revealed sensory‐dominant axonal neuropathy. Mental retardation was identified in 4/13 patients (30.8%). p.Arg190Trp, as a mutational hotspot, was observed in eight unrelated families. We also identified two novel probably pathogenic variants, p.Cys345Tyr and p.Ala369Val, and one novel uncertain significance variant, p.Tyr332Cys.

Conclusions

Our study is the largest report of patients harboring MORC2 variants. We revealed a clinical and mutational spectrum of Japanese patients with MORC2 variants. More attention should be paid to cognitive impairment, and the responsible mechanism requires further research for elucidation.
Glucocorticoids: The mode of action in bullous pemphigoid
Authors: Kubin Minna E. , Hellberg Lars , Palatsi Riitta
Published: August 2017

Bullous pemphigoid (BP) is the most common of pemphigoid diseases caused by autoantibodies against the structures of dermoepidermal junction followed by complement activation, innate immune cell infiltration, neutrophil proteinase secretion and subepidermal blister formation. The first‐line treatment of BP is topical and systemic glucocorticoids (GC). Regulation of the immune system and inflammatory cells is the main target of GC actions. GCs act through genomic and non‐genomic mechanisms. The human glucocorticoid receptor (GR) mediates most of the biologic effects of GC: cytosolic GR binds GCs and is capable to bind to glucocorticoid response elements in DNA and either transactivate or transrepress genes depending on the tissue and cell type. In addition, GR exerts rapid, non‐genomic effects possibly mediated by membrane‐localized receptors or by translocation to mitochondria. GCs can also interact directly with several enzymes and cytokines. As a target treatment for BP, the production of autoantibodies should be discontinued. GCs, in spite of their wide immunosuppressive actions, are weak to stop immunoglobulin G (IgG) autoantibody formation. However, both systemic and topical GCs are able to reduce the clinical symptoms of BP. GCs are used to inhibit the secondary inflammation and symptoms, such as blistering and pruritus, and it is shown that GC treatment will gradually decrease also the autoantibody formation. Our review article analyses the mode of action of GC treatment in BP, as far it is possible due to paucity of modern immunological studies.
Bacteriohopanepolyols along redox gradients in the Humboldt Current System off northern Chile
Authors: Matys E. D. , Sepúlveda J. , Pantoja S. , Lange C. B. , Caniupán M. , Lamy F. , Summons R. E.
Published: August 2017

Marine oxygen minimum zones (OMZs) are characterized by the presence of subsurface suboxic or anoxic waters where diverse microbial processes are responsible for the removal of fixed nitrogen. OMZs have expanded over past decades and are expected to continue expanding in response to the changing climate. The implications for marine biogeochemistry, particularly nitrogen cycling, are uncertain. Cell membrane lipids (biomarkers), such as bacterial bacteriohopanepolyols (BHPs) and their degradation products (hopanoids), have distinctive structural attributes that convey information about their biological sources. Since the discovery of fossil hopanoids in ancient sediments, the study of BHPs has been of great biogeochemical interest due to their potential to serve as proxies for bacteria in the geological record. A stereoisomer of bacteriohopanetetrol (BHT), BHT II, has been previously identified in OMZ waters and has as been unequivocally identified in culture enrichments of anammox bacteria, a key group contributing to nitrogen loss in marine OMZs. We tested BHT II as a proxy for suboxia/anoxia and anammox bacteria in suspended organic matter across OMZ waters of the Humboldt Current System off northern Chile, as well as in surface and deeply buried sediments (125–150 ky). The BHT II ratio (BHT II/total BHT) increases as oxygen content decreases through the water column, consistent with previous results from Perú, the Cariaco Basin and the Arabian Sea, and in line with microbiological evidence indicating intense anammox activity in the Chilean OMZ. Notably, BHT II is transported from the water column to surface sediments, and preserved in deeply buried sediments, where the BHT II ratio correlates with changes in δ15N sediment values during glacial–interglacial transitions. This study suggests that BHT II offers a proxy for past changes in the relative importance of anammox, and fluctuations in nitrogen cycling in response to ocean redox changes through the geological record.