bluuebunny/crossref_metadata_2025 huggingface dataset:
Biofabrication of in situ Self Assembled 3D Cell Cultures in a Weightlessness Environment Generated using Magnetic Levitation
Authors: Anil-Inevi Muge , Yaman Sena , Yildiz Ahu Arslan , Mese Gulistan , Yalcin-Ozuysal Ozden , Tekin H. Cumhur , Ozcivici Engin
Published: May 2018

Magnetic levitation though negative magnetophoresis is a novel technology to simulate weightlessness and has recently found applications in material and biological sciences. Yet little is known about the ability of the magnetic levitation system to facilitate biofabrication of in situ three dimensional (3D) cellular structures. Here, we optimized a magnetic levitation though negative magnetophoresis protocol appropriate for long term levitated cell culture and developed an in situ 3D cellular assembly model with controlled cluster size and cellular pattern under simulated weightlessness. The developed strategy outlines a potential basis for the study of weightlessness on 3D living structures and with the opportunity for real-time imaging that is not possible with current ground-based simulated weightlessness techniques. The low-cost technique presented here may offer a wide range of biomedical applications in several research fields, including mechanobiology, drug discovery and developmental biology.
Essential oil of Siparuna guianensis as an alternative tool for improved lepidopteran control and resistance management practices
Authors: Lourenço Adriano M. , Haddi Khalid , Ribeiro Bergman M. , Corrêia Roberto F. T. , Tomé Hudson V. V. , Santos-Amaya Oscar , Pereira Eliseu J. G. , Guedes Raul N. C. , Santos Gil R. , Oliveira Eugênio E. , Aguiar Raimundo W. S.
Published: May 2018

Although the cultivation of transgenic plants expressing toxins of Bacillus thuringiensis (Bt) represents a successful pest management strategy, the rapid evolution of resistance to Bt plants in several lepidopteran pests has threatened the sustainability of this practice. By exhibiting a favorable safety profile and allowing integration with pest management initiatives, plant essential oils have become relevant pest control alternatives. Here, we assessed the potential of essential oils extracted from a Neotropical plant, Siparuna guianensis Aublet, for improving the control and resistance management of key lepidopteran pests (i.e., Spodoptera frugiperda and Anticarsia gemmatalis). The essential oil exhibited high toxicity against both lepidopteran pest species (including an S. frugiperda strain resistant to Cry1A.105 and Cry2Ab Bt toxins). This high insecticidal activity was associated with necrotic and apoptotic effects revealed by in vitro assays with lepidopteran (but not human) cell lines. Furthermore, deficits in reproduction (e.g., egg-laying deterrence and decreased egg viability), larval development (e.g., feeding inhibition) and locomotion (e.g., individual and grouped larvae walking activities) were recorded for lepidopterans sublethally exposed to the essential oil. Thus, by similarly and efficiently controlling lepidopteran strains susceptible and resistant to Bt toxins, the S. guianensis essential oil represents a promising management tool against key lepidopteran pests.
The association between MTHFR polymorphism and cervical cancer
Authors: Gong Jiao-Mei , Shen Yong , Shan Wan-Wan , He Yan-Xia
Published: May 2018

Cervical cancer is an extremely prevalent disease worldwide. The purpose of this study was to illustrate the relationship between methylenetetrahydrofolate reductase (MTHFR) polymorphisms or methionine synthase reductase (MTRR) polymorphisms and cervical cancer. There were 372 women who performed genetic and folic acid assessments. For the MTHFR C677T, there was no significant difference in the distribution of C allele and T allele in the three groups. However, the mutant C allele of MTHFR A1298C was significantly higher in the cancer group than in the normal group. Similarly, the mutant G allele of MTRR A66G was also higher than the normal group. The serum folic acid levels were gradually decreased with the development of cervical lesions. Serum folate levels in 4–9 ng/ml and ≤4 ng/ml were both significantly associated with cervical cancer risk. However, the MTHFR C677T polymorphism was not associated with the risk of cervical cancer or CIN. In contrast, the MTHFR A1298C polymorphism could increase the risk of both cervical cancer and CIN. In addition, the MTRR A66G polymorphism was only associated with the risk of cervical cancer but not CIN.
Reduction/photo dual-responsive polymeric prodrug nanoparticles for programmed siRNA and doxorubicin delivery
Authors: Wu Ming , Li Jiong , Lin Xinyi , Wei Zuwu , Zhang Da , Zhao Bixing , Liu Xiaolong , Liu Jingfeng
Published: May 2018

A reduction/photo dual-responsive nanosystem for programmed P-gp siRNA and doxorubicin release was designed to optimize the efficacy of chemotherapy against multidrug resistance of cancer cells.
Biodegradable toughened nanohybrid shape memory polymer for smart biomedical applications
Authors: Biswas Arpan , Singh Akhand Pratap , Rana Dipak , Aswal Vinod K. , Maiti Pralay
Published: May 2018

Templated polyurethane is designed which shows superior shape memory behavior at ambient condition suitable for suture and stent application. Biodegradable and toughened nature add extra features of this hybrid material for versatile applications.
A nanoporous MXene film enables flexible supercapacitors with high energy storage
Authors: Fan Zhimin , Wang Youshan , Xie Zhimin , Xu Xueqing , Yuan Yin , Cheng Zhongjun , Liu Yuyan
Published: May 2018

A simple strategy is developed to prepare a nanoporous MXene film with high volumetric capacitance and good rate capability.
ACI/EG eutectic mixture mediated synthesis, characterization andin vitroosteoblast differentiation assessment of spiropyrrolo[1,2-b]isoquinoline analogues
Authors: Periyasami Govindasami , Arumugam Natarajan , Rahaman Mostafizur , Kumar Raju Suresh , Manikandan Muthurangan , Alfayez Musaad A. , Premnath Dhanaraj , Aldalbahi Ali
Published: May 2018

An eco-friendly acetylcholine iodide–ethylene glycol (ACI/EG) deep eutectic mixture mediated green protocol has been developed for the synthesis of unexplored multi-functionalized linear tricyclic spiropyrrolo[1,2-b]isoquinoline analogues.
Ultrahigh energy-storage potential under low electric field in bismuth sodium titanate-based perovskite ferroelectrics
Authors: Yin Jie , Zhang Yuxing , Lv Xiang , Wu Jiagang
Published: May 2018

Enhancement in energy-storage performance with a recoverable energy density of 2.42 J cm−3 in {Bi0.5[(Na0.8K0.2)0.90Li0.10]0.5}0.96Sr0.04(Ti0.975Ta0.025)O3 ceramics by a hot-pressed sintering (HPS) method.
Up-regulation of inflammation-related LncRNA-IL7R predicts poor clinical outcome in patients with cervical cancer
Authors: Fan Yangyang , Nan Yan , Huang Juanjuan , Zhong Hui , Zhou Weidong
Published: May 2018

The long-term chronic inflammation of cervical intraepithelial neoplasia (CIN) induces the initiation and progression of cervical cancer. Long non-coding RNAs (LncRNAs) are being identified to be involved into inflammation and carcinogenesis and could function as cancer biomarkers in clinical. However, the significance of inflammation-related LncRNA (e.g. LncRNA-IL7R) in cervical cancer is limited. We, here, investigated the clinical role of inflammation-related LncRNA-IL7R (Lnc-IL7R) in healthy cervical tissue (n=15), CIN 1/2/3 (n=35), cervical cancer (n=70), and clarified its function via knockdown in vitro and in vivo. The results showed that the expression of Lnc-IL7R was increased from normal tissues to neoplastic lesions and cervical cancer. Up-regulated Lnc-IL7R positively correlated to tumor size, International Federation of Gynaecology and Obstetrics (FIGO) stage, and lymph node metastasis (LNM). Patients with high expression of Lnc-IL7R had poor prognosis with short overall survival (OS) time, and Cox regression analysis revealed that Lnc-IL7R could be independent prognostic factor for cervical cancer. Moreover, knockdown of Lnc-IL7R by two different siRNAs in cervical cancer cell lines Hela and SiHa induced impaired cell vitality and caspase-3-dependent apoptosis in vitro. Furthermore, inhibition of Lnc-IL7R in vivo significantly restricted the tumor growth with decreased expressions of proliferation index Ki-67 and Lnc-IL7R. These data indicated that Lnc-IL7R predicts a poor clinical outcome of cervical cancer patients, and knockdown of Lnc-IL7R is amenable to the treatment of cervical cancer.
Gremlin activates the Notch pathway linked to renal inflammation
Authors: Lavoz Carolina , Poveda Jonay , Marquez-Exposito Laura , Rayego-Mateos Sandra , Rodrigues-Diez Raul R. , Ortiz Alberto , Egido Jesús , Mezzano Sergio , Ruiz-Ortega Marta
Published: May 2018

Preclinical studies suggest that Gremlin participates in renal damage and could be a potential therapeutic target for human chronic kidney diseases. Inflammation is a common characteristic of progressive renal disease, and therefore novel anti-inflammatory therapeutic targets should be investigated. The Notch signaling pathway is involved in kidney development and is activated in human chronic kidney disease, but whether Gremlin regulates the Notch pathway has not been investigated. In cultured tubular cells, Gremlin up-regulated gene expression of several Notch pathway components, increased the production of the canonical ligand Jagged-1, and caused the nuclear translocation of active Notch-1 (N1ICD). In vivo administration of Gremlin into murine kidneys elicited Jagged-1 production, increased N1ICD nuclear levels, and up-regulated the gene expression of the Notch effectors hes-1 and hey-1. All these data clearly demonstrate that Gremlin activates the Notch pathway in the kidney. Notch inhibition using the γ-secretase inhibitor DAPT impaired renal inflammatory cell infiltration and proinflammatory cytokines overexpression in Gremlin-injected mice and in experimental models of renal injury. Moreover, Notch inhibition blocked Gremlin-induced activation of the canonical and noncanonical nuclear factor-κB (NF-κB) pathway, identifying an important mechanism involved in the anti-inflammatory actions of Notch inhibition. In conclusion, Gremlin activates the Notch pathway in the kidney and this is linked to NF-κB-mediated inflammation, supporting the hypothesis that Notch inhibition could be a potential anti-inflammatory strategy for renal diseases.
Lineare IgA-Dermatose − interessanter Fall einer seltenen Erkrankung
Authors: Troyanova-Slavkova S. , Dumann K. , Esser M. , Kowalzick L.
Published: May 2018

Bullöse Autoimmundermatosen sind seltene, aber wichtige Hauterkrankungen mit relativ hoher Morbidität und Mortalität. Bei der Unterteilung dieser Hauterkrankungen ist es von Bedeutung, ob eine subepidermale oder intraepidermale Blasenbildung besteht. Subepidermale, autoimmune, bullöse Erkrankungen der Haut und der Schleimhäute umfassen eine große Gruppe chronischer Erkrankungen. Diese beinhaltet u. a. bullöses Pemphigoid, Pemphigoid gestationis, Schleimhautpemphigoid, lineare IgA-Dermatose, Anti-p200-Pemphigoid und Epidermolysis bullosa acquisita. Bei diesen Erkrankungen werden Auto-Antikörper gegen strukturelle Bestandteile der Desmosomen, Hemidesmosomen und der Basalmembranzone gebildet, wodurch sich die Blasen bilden. Die lineare IgA-Dermatose ist eine sehr seltene, v. a. bei Kindern und jungen Erwachsenen auftretende Hauterkrankung. Sie ist durch lineare Ablagerung von IgA entlang der Basalmembran und dadurch bedingte Störung der dermo-epidermalen Verbindung gekennzeichnet. Die Erkrankung kann sowohl medikamentös als auch idiopathisch auftreten. Hier berichten wir über den Fall eines 56-jährigen Patienten mit seit ca. 2 Monaten bestehenden, stark juckenden, prallen Blasen am Rumpf und an den Extremitäten, die mit klarer Flüssigkeit gefüllt waren. Aufgrund mangelhafter Compliance erfolgte ambulant noch keine Behandlung. Histologisch wurde eine subepidermal autoimmun-blasenbildende Dermatose beschrieben. Die genaue Diagnose konnte nur dank der indirekten Immunfluoreszenz-Untersuchung gestellt werden.
Behandlung und Prognose der ältesten Alten mit kolorektalem Karzinom
Authors: Denz Axel , Kohl Valerie , Weber Klaus , Langheinrich Melanie , Schellerer Vera , Merkel Susanne , Grützmann Robert
Published: May 2018

Einführung Epidemiologische Berechnungen prognostizieren, dass der Anteil der älteren Menschen bei steigender durchschnittlicher Lebenserwartung und einer abnehmenden Zahl jüngerer Menschen in Deutschland zukünftig weiter zunehmen wird. Es wird hierbei auch zu einer Zunahme älterer und sehr alter Menschen mit einem kolorektalen Karzinom kommen. Daher werden Studien über sehr alte Patienten eine zunehmende Bedeutung erfahren.

Material und Methodik Es wurden die prospektiv erhobenen Daten von 141 Patienten ≥ 85 Jahren („die ältesten Alten“) mit kolorektalem Karzinom, die zwischen 1995 und 2014 an unserer Klinik behandelt wurden, retrospektiv untersucht. Verglichen wurden die Behandlung, Komplikationen und onkologische Prognose dieser Kohorte mit einer gleichaltrigen historischen Patientengruppe (n = 57), deren Behandlung zwischen 1978 und 1994 erfolgte, und eines weniger alten Kollektivs im Alter von 75 bis 84 Jahren, das zwischen 1995 und 2014 (n = 726) behandelt wurde.

Ergebnisse Die untersuchte Patientengruppe bestand aus 64 Männern und 77 Frauen. 88 Patienten hatten ein Kolonkarzinom, 53 Patienten ein Rektumkarzinom. Bei 127 Patienten wurde eine Tumorresektion vorgenommen, davon wurden 112 als R0 klassifiziert. Der Vergleich mit der gleichaltrigen historischen Gruppe (1978 – 1994) zeigte, dass die Anzahl der Patienten und der Tumorresektionen gestiegen war (74 vs. 90%, p = 0,003) und seltener synchrone Fernmetastasen diagnostiziert wurden (28 vs. 14%, p = 0,015). Die 5-Jahres-Lokalrezidivraten nach R0-Resektion sanken von 11,5 auf 1,4% (p = 0,027). Im Vergleich mit der weniger alten Patientengruppe (75 – 84 Jahre) gab es im untersuchten Kollektiv mehr weibliche Patienten (55 vs. 42,3%, p = 0,007), mehr Notfalleingriffe (9,8 vs. 22%, p < 0,001) und seltener eine neoadjuvante Radio-/Chemotherapie (3 vs. 11%, p = 0,003). Sowohl die Morbidität als auch die Mortalität war in der Gruppe der ältesten Alten höher. Das beobachtete Überleben war nach R0-Resektion und Ausschluss der postoperativ Verstorbenen im Vergleich zum weniger alten Kollektiv kürzer (2-Jahres-Rate 66,4%, 5-Jahres-Rate 32,9%), wohingegen das krebsbezogene Überleben gleich war (2-Jahres-Rate 93,1%, 5-Jahres-Rate 86,7%).

Schlussfolgerung Der Anteil der ältesten alten Patienten mit kolorektalem Karzinom wird in Zukunft weiter zunehmen. Diese Patienten haben erwartungsgemäß ein höheres Risiko für postoperative Komplikationen. Allerdings ist nach der Rekonvaleszenz das krebsbezogene Überleben nicht schlechter als bei den weniger alten Patienten.
Increasing Body Mass Index Predicts Rapid Decline in Renal Function: A 5 Year Retrospective Study
Authors: Ma Xiaojing , Zhang Chengyin , Su Hong , Gong Xiaojie , Kong Xianglei
Published: May 2018

While obesity is a recognized risk factor for chronic kidney disease, it remains unclear whether change in body mass index (ΔBMI ) is independently associated with decline in renal function (evaluated by the change in estimated glomerular filtration rate, ΔeGFR) over time. Accordingly, to help clarify this we conducted a retrospective study to measure the association of ΔBMI with decline in renal function in Chinese adult population. A total of 4007 adults (aged 45.3±13.7 years, 68.6% male) without chronic kidney disease at baseline were enrolled between 2008 and 2013. Logistic regression models were applied to explore the relationships between baseline BMI and ΔBMI, and rapid decline in renal function (defined as the lowest quartile of ΔeGFR ). During 5 years of follow-up, the ΔBMI and ΔeGFR were 0.47±1.6 (kg/m2) and –3.0±8.8 (ml/min/1.73 m2), respectively. After adjusted for potential confounders, ΔBMI (per 1 kg/m2 increase) was independently associated with the rapid decline in renal function [with a fully adjusted OR of 1.12 (95% CI, 1.05 to 1.20). By contrast, the baseline BMI was not associated with rapid decline in renal function [OR=1.05 (95% CI, 0.98 to 1.13)]. The results were robust among 2948 hypertension-free and diabetes-free participants, the adjusted ORs of ΔBMI and baseline BMI were 1.14 (95% CI, 1.05 to 1.23) and 1.0 (95% CI, 0.96 to 1.04) for rapid decline in renal function, respectively. The study revealed that increasing ΔBMI predicts rapid decline in renal function.
Palsy of the Contralateral Abducens Nerve after Aneurysm Surgery and Temporal Meningioma in the Presence of Petroclival Meningioma: A Case Report
Authors: Moreira Pedro , Souza Anderson , Teixeira Manoel , Figueiredo Eberval
Published: May 2018

The sixth abducens nerve is subject to injury after rare complications of intracranial hypotension caused by procedures such as dural punctures and spinal surgeries. The purpose of this case report is to discuss the mechanism of nerve palsy in these situations. Therefore, we describe a case of onset of contralateral sixth cranial nerve palsy after intracranial aneurysm and temporal meningioma surgery. Moreover, in this case there is a singularity due to the presence of the petroclival meningioma that amplified the unfolding of the lesion.
Proper Choice of Vessels for Supermicrosurgery Training: An Experimental Animal study
Authors: Ha Yooseok , Song Seung , Kang Nak , Oh Sang-Ha
Published: May 2018

Background Reconstruction using supermicrosurgery, a technique of microneurovascular anastomosis for smaller vessels (< 0.8 mm), has become popular. Experimental animal studies for supermicrosurgery training have been reported; however, there have been few studies performed according to vessel diameter and pedicle length. In this study, the external diameters of four vessels (femoral, superficial epigastric, axillary, and common thoracic) and pedicle length of two flaps (superficial epigastric and common thoracic–long thoracic) were measured.

Methods The inguinal and pectoral regions of Sprague-Dawley rats (n = 19) were dissected anatomically, and the external diameters of the four vessels were measured (right and left, artery and vein measured separately). After elevating the superficial epigastric and common thoracic–long thoracic flaps, the pedicle length of the flaps was also measured.

Results Among the 16 vessels examined, the external diameters of 11 and 5 vessels were above and below 0.8 mm, respectively. The external diameters of the superficial epigastric vessel and common thoracic vessel (both arteries and veins) were below 0.8 mm. The external diameters of the femoral and axillary vessels (veins) were above 0.8 mm. The length of the common thoracic–long thoracic pedicle was approximately10 mm longer than that of the superficial epigastric pedicle.

Conclusions The external diameters of the superficial epigastric vessel and common thoracic vessel are small enough for supermicrosurgery training. The pedicle lengths of both the superficial epigastric and common thoracic–long thoracic flaps are sufficient to perform free flap experiments. Supermicrosurgical free flaps using these two vessels and a study of the physiology and pharmacology of the flaps will likely be possible in the future.
Prävention einer ersten psychotischen Episode
Authors: Schultz J. , Wasserthal S. , Kloss C. , Schmidt S. , Ruhrmann S. , Hurlemann R.
Published: May 2018

Gegenstand und Ziel: Psychotische Störungen gehören aufgrund ihres frühen Beginns und ihren langfristigen Konsequenzen zu den teuersten psychischen Erkrankungen in Europa. Prävention könnte die gesellschaftlichen Kosten und die immense Belastung für Patienten und Familien signifikant reduzieren. Neurobiologische Befunde deuten auf eine glutamaterge Dysfunktion und ein Redoxungleichgewicht in der Pathophysiologie der Schizophrenie. Wir vermuten, dass Interventionen, die auf soziale Funktionen und glutamaterge /oxidative Signalwege abzielen, die Übergangsraten signifikant reduzieren würden. Material und Methoden: Unsere Studie ist eine randomisierte, placebokontrollierte 18-monatige Studie (6-Monate Intervention; 12 Monate Nachuntersuchung) mit 200 Probanden, die ein klinisch erhöhtes Risiko für Psychosen haben. Wir werden in einem 2x2-faktoriellen Design die präventiven Effekte einer kognitiv-behavioralen und sozial-kognitiven Intervention (IPPI) mit einer pharmakologischen Intervention mit einem pro-glutamatergen, neuroprotektiven Medikament (N-Acetylcystein) vergleichen. Ergebnisse und klinische Relevanz: Die Ergebnisse dieser Studie sollen zu neuen, gut verträglichen präventiven Interventionen führen.
Verbesserung der kognitiven Leistungsfähigkeit von Patienten mit Schizophrenie durch transkranielle Gleichstromstimulation
Authors: Hasan A , Papazova I , Fallgatter A. J , Plewnia C , Schwippel T
Published: May 2018

Kognitive Störungen sind ein Kernaspekt der Schizophrenie und beeinflussen das Langzeitergebnis der Behandlung, die Mortalität und die Lebensqualität der Patienten. Medikamentöse Behandlungsversuche erbrachten wenig zufriedenstellende Resultate, wohingegen das Training kognitiver Leistungen durchaus wirksam sein kann. Eine noch unzureichende Effektstärke und Generalisierbarkeit der Trainingserfolge sowie der hoher Zeitaufwand limitieren den generellen klinischen Einsatz. In einem innovativen Ansatz soll untersucht werden, ob eine Augmentation des kognitiven Trainings mit transkranieller Gleichstromstimulation (tDCS) den Effekt des Trainings und damit die klinische Anwendbarkeit verbessern kann. Mit der tDCS steht ein nebenwirkungsarmes Verfahren zur Verfügung, mit welchem der Aktivitätszustand des Gehirns polaritätsabhängig moduliert werden kann. Hierbei wird über zwei Elektroden schwacher Gleichstrom appliziert, welcher zur Veränderung des Ruhemembranpotenzials kortikaler Neurone führt und es ermöglicht dadurch die Erregbarkeit neuronaler Netzwerke gezielt zu modulieren. Die Kombination von Training und tDCS kann synergistisch zur Unterstützung adaptiver neuroplastischer Prozesse eingesetzt werden und möglicherweise die Effektivität eines kognitiven Trainings bei Patienten mit Schizophrenie verbessern. Dies könnte dazu beitragen die Erholung von Beeinträchtigungen kognitiver Funktionen bei an Schizophrenie erkrankten Menschen wirkungsvoll zu unterstützen und ihre Lebensqualität zu steigern.
Morbus Menière – wie hilfreich ist die Magnetresonanztomografie?
Authors: Schaaf Helmut
Published: May 2018

Patel VA et al. Magnetic resonance imaging findings in Ménière‘s disease. J Laryngol Otol 2017; 131: 602–607

Ein amerikanisches Wissenschaftlerteam veranschaulichte MRT-Befunde, die im Zusammenhang mit der Menière-Krankheit stehen. Diese umfassten kongenitale
Malformationen, Schädigung der weißen Substanz, Veränderungen der hinteren Zirkulation und temporäre Abweichungen der Knochenstruktur.
Refractive index and temperature-sensing characteristics of a cladding-etched thin core fiber interferometer
Authors: Wang Weiying , Dong Xinran , Chu Dongkai , Hu Youwang , Sun Xiaoyan , Duan Ji-An
Published: May 2018

A high refractive index (RI) sensor based on an in-line Mach–Zehnder mode interferometer (MZI) is proposed. The sensor was realized by splicing a 2-cm length of cladding-etched thin core fiber (TCF) between two single mode fibers (SMFs). The TCF-structured MZI exhibited good fringe visibility as high as 15 dB in air and the high RI sensitivity attained a value of 1143.89 nm/RIU at a RI of 1.447. The experimental data revealed that the MZI has high RI sensitivity after HF etching realizing 2599.66 nm/RIU. Studies were performed on the temperature characteristics of the device. It is anticipated that this high RI sensor will be deployed in new and diverse applications in the chemical and biological fields.
Site-selective measurement of coupled spin pairs in an organic semiconductor
Authors: Bayliss S. L. , Weiss L. R. , Mitioglu A. , Galkowski K. , Yang Z. , Yunusova K. , Surrente A. , Thorley K. J. , Behrends J. , Bittl R. , Anthony J. E. , Rao A. , Friend R. H. , Plochocka P. , Christianen P. C. M. , Greenham N. C. , Chepelianskii A. D.
Published: May 2018

Significance

Pairs of spins in molecular materials have attracted significant interest as intermediates in photovoltaic devices and light-emitting diodes. However, isolating the local spin and electronic environments of such intermediates has proved challenging due to the complex structures in which they reside. Here we show how exchange coupling can be used to select and characterize multiple coexisting pairs, enabling joint measurement of their exchange interactions and optical profiles. We apply this to spin-1 pairs formed by photon absorption whose coupling gives rise to total-spin

S
=
0,1

and 2-pair configurations with drastically different properties. This presents a way of identifying the molecular conformations involved in spin-pair processes and generating design rules for more effective use of interacting spins.
The New Frontier Meets the White Revolution: The Peace Corps in Iran, 1962‒76
Authors: Rostam-Kolayi Jasamin
Published: May 2018

The Peace Corps brought an estimated 1,800 Americans to Iran from 1962 to 1976, coinciding with the unfolding of Mohammad-Reza Shah Pahlavi’sEnqelāb-e Sefid, or White Revolution. This article surveys Peace Corps Iran’s fourteen-year history by dividing it into three distinct moments defined by changing social and political conditions in Iran and shifting US‒Iranian relations. Initially, the Peace Corps Iran experiment built on earlier American foreign assistance programs, while coinciding with the roll-out of the White Revolution. Second, during its heyday in the mid-1960s, the Peace Corps inevitably became entangled with the White Revolution’s unfolding, both experiencing a phase of expansion and apparent success. Finally, as Iranian social and political conditions moved toward instability by the 1970s, Peace Corps Iran also seemed to have lost its direction and purpose, which ultimately led to a vote by volunteers to terminate the program. Based on accounts by US Peace Corps volunteers and the Iranians with whom they worked, the Peace Corps Agency, and the US State Department, this article argues that, ultimately, the Peace Corps Iran experience left a more lasting legacy on individuals than institutions.
Arrests and Deportations of Latvian Jews by the USSR During the Second World WAR
Authors: Levin Dov
Published: May 2018

Mass deportations of native populations (Jews included) from territories annexed by the USSR in 1939–40 in amicable division of spoils with Nazi Germany and its allies had everywhere the same historical background and followed roughly the same procedure. Territories in question included the states of Estonia, Latvia and Lithuania in their entirety, parts of Finland, nearly one-half of pre-1939 Poland, and the formerly Romanian regions of Bessarabia and Northern Bukovina.
Note on the absence of remainders in the Wiener-Ikehara theorem
Authors: Debruyne Gregory , Vindas Jasson
Published: May 2018

We show that it is impossible to get a better remainder than the classical one in the Wiener-Ikehara theorem even if one assumes analytic continuation of the Mellin transform after subtraction of the pole to a half-plane. We also prove a similar result for the Ingham-Karamata theorem.
Sorting cancer karyotypes using double-cut-and-joins, duplications and deletions
Authors: Zeira Ron , Shamir Ron
Published: May 2018

Motivation

Problems of genome rearrangement are central in both evolution and cancer research. Most genome rearrangement models assume that the genome contains a single copy of each gene and the only changes in the genome are structural, i.e. reordering of segments. In contrast, tumor genomes also undergo numerical changes such as deletions and duplications, and thus the number of copies of genes varies. Dealing with unequal gene content is a very challenging task, addressed by few algorithms to date. More realistic models are needed to help trace genome evolution during tumorigenesis.

Results

Here, we present a model for the evolution of genomes with multiple gene copies using the operation types double-cut-and-joins, duplications and deletions. The events supported by the model are reversals, translocations, tandem duplications, segmental deletions and chromosomal amplifications and deletions, covering most types of structural and numerical changes observed in tumor samples. Our goal is to find a series of operations of minimum length that transform one karyotype into the other. We show that the problem is NP-hard and give an integer linear programming formulation that solves the problem exactly under some mild assumptions. We test our method on simulated genomes and on ovarian cancer genomes. Our study advances the state of the art in two ways: It allows a broader set of operations than extant models, thus being more realistic and it is the first study attempting to re-construct the full sequence of structural and numerical events during cancer evolution.

Availability and implementation

Code and data are available in https://github.com/Shamir-Lab/Sorting-Cancer-Karyotypes.

Supplementary information

Supplementary data are available at Bioinformatics online.
Necklace: combining reference and assembled transcriptomes for more comprehensive RNA-Seq analysis
Authors: Davidson Nadia M , Oshlack Alicia
Published: May 2018

Background

RNA sequencing (RNA-seq) analyses can benefit from performing a genome-guided and de novo assembly, in particular for species where the reference genome or the annotation is incomplete. However, tools for integrating an assembled transcriptome with reference annotation are lacking.

Findings

Necklace is a software pipeline that runs genome-guided and de novo assembly and combines the resulting transcriptomes with reference genome annotations. Necklace constructs a compact but comprehensive superTranscriptome out of the assembled and reference data. Reads are subsequently aligned and counted in preparation for differential expression testing.

Conclusions

Necklace allows a comprehensive transcriptome to be built from a combination of assembled and annotated transcripts, which results in a more comprehensive transcriptome for the majority of organisms. In addition RNA-seq data are mapped back to this newly created superTranscript reference to enable differential expression testing with standard methods.
Outpatient Infection Prevention: A Practical Primer
Authors: Steinkuller Fozia , Harris Kristofer , Vigil Karen J , Ostrosky-Zeichner Luis
Published: May 2018

As more patients seek care in the outpatient setting, the opportunities for health care–acquired infections and associated outbreaks will increase. Without uptake of core infection prevention and control strategies through formal initiation of infection prevention programs, outbreaks and patient safety issues will surface. This review provides a step-wise approach for implementing an outpatient infection control program, highlighting some of the common pitfalls and high-priority areas.
Identification of the interaction of 2-aminosteroids with G-quadruplex in BCR/ABL gene promoter: An emerging potential target for treatment of human chronic myelogenous leukemia
Authors: He Qun , Yang Huihui
Published: May 2018

Our preliminary studies have verified that the small molecules aminosteroid could inhibit the mRNA expression of bcr/abl fusion gene in CML (Chronic Myelogenous Leukemia) cells, which may be effective in treating CML and that may have dramatically different mechanism underlying the effects by tyrosine kinase inhibitors (TKI) binding to the BCR/ABL protein. Therefore, the exact mechanism of how the aminosteroid inhibited the CML growth should be clarified and we pay our attention to the promoter domain of BCR/ABL gene to see if any interaction between aminosteroid and the promoter. First, it should be verified if G-quadruplex could be formed in BCR/ABL promoter region. Secondly, it is highly desirable to verify if aminoteroid could be interacted with the G-quadruplex structure. Here, we reported a novel therapeutic strategy based on the targeting of the G-quadruplex which formed in the promoter regions of BCR/ABL gene by aminosteroid compounds KH and BH, verified by using bioinformatics and computer simulation, UV-Vis absorption spectra, circular dichrosism(CD), fluorescence absorption spectra, fluorescence emission lifetime expenditure experiments and polymerase chain stop assays. It showed that G-quadruplex structures can be folded in BCR/ABL promoter regions and aminosteroid inhibits the mRNA expression of BCR/ABL fusion gene by stabilizing the structure of G-quadruplex, and then inhibiting the DNA replication and transcription. This demonstrates the theory that is the so-called “chemical gene therapy” by aminosteroid in the interaction with G-quadruplex is an emerging therapeutic protocol in treatment of chronic myeloid leukemia.
Quantifying spatiotemporal dynamics and noise in absolute microbiota abundances using replicate sampling
Authors: Ji Brian W. , Sheth Ravi U. , Dixit Purushottam D. , Wang Harris H. , Vitkup Dennis
Published: May 2018

Metagenomic sequencing has enabled detailed investigation of diverse microbial communities, but understanding their spatiotemporal dynamics remains an important challenge. Here we present DIVERS, a widely applicable method based on replicate sampling and spike-in sequencing that quantifies the contributions of temporal dynamics, spatial sampling variability and technical noise to the variances and covariances of absolute bacterial abundances. Using high resolution time series profiling, we apply DIVERS to the human gut microbiome. Our method reveals complex spatiotemporal dynamics of individual gut bacteria and unmasks key features of their behavior hidden from previous analyses.
A competitive binding model predicts nonlinear responses of olfactory receptors to complex mixtures
Authors: Singh Vijay , Murphy Nicolle R. , Balasubramanian Vijay , Mainland Joel D.
Published: May 2018

In color vision, the quantitative rules for mixing lights to make a target color are well understood. By contrast, the rules for mixing odorants to make a target odor remain elusive. A solution to this problem in vision relied on characterizing receptor responses to different wavelengths of light and subsequently relating these responses to perception. In olfaction, experimentally measuring receptor responses to a representative set of complex mixtures is intractable due to the vast number of possibilities. To meet this challenge, we develop a biophysical model that predicts mammalian receptor responses to complex mixtures using responses to single odorants. The dominant nonlinearity in our model is competitive binding (CB): only one odorant molecule can attach to a receptor binding site at a time. This simple framework predicts receptor responses to mixtures of up to twelve monomolecular odorants to within 15% of experimental observations and provides a powerful method for leveraging limited experimental data. Simple extensions of our model describe phenomena such as synergy, overshadowing, and inhibition. We demonstrate that the presence of such interactions can be identified via systematic deviations from the competitive binding model.
Basidiobolus haptosporus-likefungus as a causal agent of gastrointestinal basidiobolomycosis and its link to the common house gecko (Hemidactylus frenatus) as a potential risk factor
Authors: Al Bshabshe Ali , Joseph Martin R.P. , Al Hakami Ahmed M. , Al Azraqi Tarig , Al Humayed Sulieman , Hamid Mohamed E.
Published: May 2018

Basidiobolusspp. are a significant causal agent of infections in man and animals including gastrointestinal basidiobolomycosis (GIB). Little information is available on how these infections are acquired or transmitted, apart from the postulation that environmental sources are implicated. This study aimed to identifyBasidiobolusspp. from GIB patients and from the house gecko as a possible source of infection in Aseer, Saudi Arabia.Basidiobolusspp. were isolated from patient specimens (colonic mass biopsy) and from house gecko (gut contents) from Muhayil Aseer areas, in southern Saudi Arabia, using Sabouraud dextrose agar (SDA) which was incubated aerobically for up to three weeks at 30°C. Isolated fungi were initially identified using classical mycological tools and confirmed by sequence analysis of the large subunit ribosomal RNA gene. Cultured specimens from humans and geckos revealed phenotypically similar zygomycete-like fungi which conform to those ofBasidiobolusspecies. The strains formed a monophyletic clade in the 28S ribosomal RNA gene phylogenetic tree. They shared 99.97% similarity withB. haptosporusand 99.97% withB. haptosporusvar.minorbut have a relatively remote similarity toB. ranarum(99.925%). One isolates from a gecko (L3) fall within the sub-clade encompassingB. haptosporusstrain NRRL28635. The study strongly suggests a new and a serious causal agent of GIB related toBasidiobolus haptosporus. The isolation of identicalBasidiobolus haptosporus-likestrains from humans and lizards from one area is an important step towards identifying risk factors for GIB. Research is underway to screen more environmental niches and fully describe theBasidiobolusstrains.
Negative Cooperativity between Gemin2 and RNA provides Insights into RNA Selection and the SMN Complex’s Release in snRNP Assembly
Authors: Yi Hongfei , Mu Li , Shen Congcong , Kong Xi , Wang Yingzhi , Hou Yan , Zhang Rundong
Published: May 2018

The assembly of snRNP cores, in which seven Sm proteins, D1/D2/F/E/G/D3/B, form a ring around the nonameric Sm site of snRNAs, is the early step of spliceosome formation and essential to eukaryotes. It is mediated by the PMRT5 and SMN complexes sequentially in vivo. SMN deficiency causes neurodegenerative disease spinal muscular atrophy (SMA). How the SMN complex assembles snRNP cores is largely unknown, especially how the SMN complex achieves high RNA assembly specificity and how it is released. Here we show, using crystallographic and biochemical approaches, that Gemin2 of the SMN complex enhances RNA specificity of SmD1/D2/F/E/G via a negative cooperativity between Gemin2 and RNA in binding SmD1/D2/F/E/G. Gemin2, independent of its N-tail, constrains the horseshoe-shaped SmD1/D2/F/E/G from outside in a physiologically relevant, narrow state, enabling high RNA specificity. Moreover, the assembly of RNAs inside widens SmD1/D2/F/E/G, causes the release of Gemin2/SMN allosterically and allows SmD3/B to join. The assembly of SmD3/B further facilitates the release of Gemin2/SMN. This is the first to show negative cooperativity in snRNP assembly, which provides insights into RNA selection and the SMN complex’s release. These findings reveal a basic mechanism of snRNP core assembly and facilitate pathogenesis studies of SMA.
h-channels contribute to divergent electrophysiological properties of supragranular pyramidal neurons in human versus mouse cerebral cortex
Authors: Kalmbach Brian E , Buchin Anatoly , Miller Jeremy A , Bakken Trygve E , Hodge Rebecca D , Chong Peter , de Frates Rebecca , Dai Kael , Gwinn Ryder P. , Cobbs Charles , Ko Andrew L , Ojemann Jeffrey G , Silbergeld Daniel L , Koch Christof , Anastassiou Costas A. , Lein Ed , Ting Jonathan T
Published: May 2018

Gene expression studies suggest that differential ion channel expression contributes to differences in rodent versus human neuronal physiology. We tested whether h-channels more prominently contribute to the physiological properties of human compared to mouse supragranular pyramidal neurons. Single cell/nucleus RNA sequencing revealed ubiquitous HCN1-subunit expression in excitatory neurons in human, but not mouse supragranular layers. Using patch-clamp recordings, we found stronger h-channel-related membrane properties in supragranular pyramidal neurons in human temporal cortex, compared to mouse supragranular pyramidal neurons in temporal association area. The magnitude of these differences depended upon cortical depth and was largest in pyramidal neurons in deep L3. Additionally, pharmacologically blocking h-channels produced a larger change in membrane properties in human compared to mouse neurons. Finally, using biophysical modeling, we provided evidence that h-channels promote the transfer of theta frequencies from dendrite-to-soma in human L3 pyramidal neurons. Thus, h-channels contribute to between-species differences in a fundamental neuronal property.
Super-Resolution Tracking of Mitochondrial Dynamics with An Iridium(III) Luminophore
Authors: Chen Qixin , Jin Chengzhi , Shao Xintian , Guan Ruilin , Tian Zhiqi , Wang Chenran , Liu Fei , Ling Peixue , Guan Jun-Lin , Ji Liangnian , Wang Fengshan , Chao Hui , Diao Jiajie
Published: May 2018

Combining luminescent transition metal complex (LTMC) with super-resolution microscopy is an excellent strategy for the long-term visualization of the dynamics of subcellular structures in living cells. However, it remains unclear whether iridium(III) complexes are applicable for a particular type of super-resolution technique, structured illumination microscopy (SIM), to image subcellular structures.

As described herein, we developed an iridium(III) dye, to track mitochondrial dynamics in living cells under SIM. The dye demonstrated excellent specificity and photostability and satisfactory cell permeability. While using SIM to image mitochondria, we achieved an approximately 80-nm resolution that allowed the clear observation of the structure of mitochondrial cristae. We used the dye to monitor and quantify mitochondrial dynamics relative to lysosomes, including fusion involved in mitophagy, and newly discovered mitochondria-lysosome contact (MLC) under different conditions. MLC remained intact and fusion vanished when five receptors, p62, NDP52, OPTN, NBR1, and TAX1BP1, were knocked out, suggesting that these two processes are independence.
Internal Tensile Force and A2 Domain Unfolding of von Willebrand Factor Multimers in Shear Flow
Authors: Morabito Michael , Dong Chuqiao , Wei Wei , Cheng Xuanhong , Zhang Xiaohui F. , Oztekin Alparslan , Webb Edmund
Published: May 2018

Using Brownian molecular dynamics simulations, we examine the internal dynamics and biomechanical response of von Willebrand Factor (vWF) multimers subject to shear flow. The coarse grain multimer description employed here is based on a monomer model in which the A2 domain of vWF is explicitly represented by a non-linear elastic spring whose mechanical response was fit to experimental force/extension data from vWF monomers. This permits examination of the dynamic behavior of hydrodynamic forces acting on A2 domains as a function of shear rate and multimer length, as well as position of an A2 domain along the multimer contour. Force/position data reveal that collapsed multimers exhibit a force distribution with two peaks, one near each end of the chain; unraveled multimers, however, show a single peak in A2 domain force near the center of multimers. Guided further by experimental data, significant excursions of force acting on a domain are associated with an increasing probability for A2 domain unfolding. Our results suggest that the threshold shear rate required to induce A2 domain unfolding is inversely proportional to multimer length. By examining data for the duration and location of significant force excursions, convincing evidence is advanced that unfolding of A2 domains, and therefore scission of vWF multimers by the size-regulating blood enzyme ADAMTS13, happen preferentially near the center of unraveled multimers.
One-step assembly of large CRISPR arrays enables multi-functional targeting and reveals constraints on array design
Authors: Liao Chunyu , Ttofali Fani , Slotkowski Rebecca A. , Denny Steven R. , Cecil Taylor D. , Leenay Ryan T. , Keung Albert J. , Beisel Chase L.
Published: May 2018

CRISPR-Cas systems inherently multiplex through their CRISPR arrays--whether to confer immunity against multiple invaders or by mediating multi-target editing, regulation, imaging, and sensing. However, arrays remain difficult to generate due to their reoccurring repeat sequences. Here, we report an efficient, one-step scheme called CRATES to construct large CRISPR arrays through defined assembly junctions within the trimmed portion of array spacers. We show that the constructed arrays function with the single-effector nucleases Cas9, Cas12a, and Cas13a for multiplexed DNA/RNA cleavage and gene regulation in cell-free systems, bacteria, and yeast. We also applied CRATES to assemble composite arrays utilized by multiple Cas nucleases, where these arrays enhanced DNA targeting specificity by blocking off-target sites. Finally, array characterization revealed context-dependent loss of spacer activity and processing of unintended guide RNAs derived from Cas12a terminal repeats. CRATES thus can facilitate diverse applications requiring CRISPR multiplexing and help elucidate critical factors influencing array function.
Adaptive Partitioning of the tRNA Interaction Interface by Aminoacyl-tRNA-Synthetases
Authors: Collins-Hed Andy , Ardell David H.
Published: May 2018

We introduce rugged fitness landscapes called match landscapes for the coevolution of feature-based assortative interactions betweenP≥ 2 cognate pairs of tRNAs and aminoacyl-tRNA synthetases (aaRSs) in aaRS-tRNA interaction networks. Our genotype-phenotype-fitness maps assume additive feature-matching energies, a macroscopic theory of aminoacylation kinetics including proofreading, and selection for translational accuracy in multiple, perfectly encoded site-types. We compute the stationary genotype distributions of finite panmictic, asexual populations of haploid aaRs-tRNA interaction networks evolving under mutation, genetic drift, and selection for cognate matching and non-cognate mismatching of aaRS-tRNA pairs. We compared expected genotype frequencies under different matching rules and fitness functions, both with and without linked site-specific modifiers of interaction. Under selection for translational accuracy alone, our model predicts no selection on modifiers to eliminate non-cognate interactions, so long as they are compensated by tighter cognate interactions. Only under combined selection for both translational accuracy and rate do modifiers adaptively eliminate cross-matching in non-cognate aaRS/tRNA pairs. We theorize that the encoding of macromolecular interaction networks is a genetic language that symbolically maps identifying structural and dynamic features of genes and gene-products to functions within cells. Our theory helps explain 1) the remarkable divergence in how aaRSs bind tRNAs, 2) why interaction-informative features are phylogenetically informative, 3) why the Statistical Tree of Life became more tree-like after the Darwinian Transition, and 4) an approach towards computing the probability of the random origin of an interaction network.