bluuebunny/crossref_metadata_2025 huggingface dataset:
Rupturing the hemi-fission intermediate in membrane fission under tension: Reaction coordinates, kinetic pathways, and free-energy barriers
Authors: Zhang Guojie , Müller Marcus
Published: August 2017

Membrane fission is a fundamental process in cells, involved inter alia in endocytosis, intracellular trafficking, and virus infection. Its underlying molecular mechanism, however, is only incompletely understood. Recently, experiments and computer simulation studies have revealed that dynamin-mediated membrane fission is a two-step process that proceeds via a metastable hemi-fission intermediate (or wormlike micelle) formed by dynamin’s constriction. Importantly, this hemi-fission intermediate is remarkably metastable, i.e., its subsequent rupture that completes the fission process does not occur spontaneously but requires additional, external effects, e.g., dynamin’s (unknown) conformational changes or membrane tension. Using simulations of a coarse-grained, implicit-solvent model of lipid membranes, we investigate the molecular mechanism of rupturing the hemi-fission intermediate, such as its pathway, the concomitant transition states, and barriers, as well as the role of membrane tension. The membrane tension is controlled by the chemical potential of the lipids, and the free-energy landscape as a function of two reaction coordinates is obtained by grand canonical Wang-Landau sampling. Our results show that, in the course of rupturing, the hemi-fission intermediate undergoes a “thinning → local pinching → rupture/fission” pathway, with a bottle-neck-shaped cylindrical micelle as a transition state. Although an increase of membrane tension facilitates the fission process by reducing the corresponding free-energy barrier, for biologically relevant tensions, the free-energy barriers still significantly exceed the thermal energy scale kBT.
Magnetic X points disturbed by the in-plane electric fields
Authors: Xu Z. , Qiao B. , Yao W. P. , Chang H. X. , Zhou C. T. , Zhu S. P. , He X. T.
Published: August 2017

As an efficient mechanism of energy release, magnetic reconnection is popular to explain many explosive events in extreme environments. In some cases, however, we show the key concept of the magnetic X and O points is ambiguous, due to its non-covariant definition. A simple model is constructed to study the case when the magnetic X point is disturbed by the in-plane electric field. The dynamics of the charged particle is investigated near the magnetic X point, where there is a localized attractive or repulsive electric potential. We find that the orbits of the particles are chaotic, which are induced by the X-type magnetic field outside the disturbed region. The chaotic motion helps the charged particles to enter into the reconnection region, though the in-plane electric field may affect the trajectory of the particle. Therefore, the particles that can approach the X point will get accelerated by the out-of-plane electric field, so long as there is an X-type magnetic field outside the disturbed region. Our results may help to clarify the concepts of X and O points in the reconnection process.
Electronic structures at the interface between CuPc and black phosphorus
Authors: Wang Can , Niu Dongmei , Xie Haipeng , Liu Baoxing , Wang Shitan , Zhu Menglong , Gao Yongli
Published: August 2017

The electronic structure at the organic-inorganic semiconductor interface of π-conjugated copper phthalocyanine (CuPc) on a black phosphorus (BP) crystal surface is studied with photoemission spectroscopy and density functional theory calculations. From the photoemission spectra, we observe a shift of about 0.7 eV for the highest occupied molecular orbital, which originates from the transition of phase in the organic molecular thin film (from the interface phase to the bulk phase). On the other hand, we find 0.2 eV band bending at the CuPc/BP interface while the formation of an interface dipole is very small. According to our photoemission spectrum and theoretical simulation, we also define that the interaction between CuPc and BP is physisorption via van der Waals forces, rather than chemisorption. Our results provide a fundamental understanding of CuPc/BP interfacial interactions that could be important for future two-dimensional organic/inorganic heterostructure devices.
Comment on “Photothermal radiometry parametric identifiability theory for reliable and unique nondestructive coating thickness and thermophysical measurements” [J. Appl. Phys. 121, 095101 (2017)]
Authors: Krapez J.-C. , Rigollet F.
Published: August 2017

A recent paper [Guo et al., J. Appl. Phys. 121, 095101 (2017)] intends to demonstrate that from the photothermal radiometry signal obtained on a coated opaque sample in 1D transfer, one should be able to identify separately the following three parameters of the coating: thermal diffusivity, thermal conductivity, and thickness. In this comment, it is shown that, in the considered experiment arrangement, these three parameters are correlated, the identifiability criterion is in error, and the thickness inferred therefrom is not trustable.
High performance organic nonvolatile memory transistors based on HfO2 and poly(α-methylstyrene) electret hybrid charge-trapping layers
Authors: Xu W. C. , He H. X. , Jing X. S. , Wu S. J. , Zhang Z. , Gao J. W. , Gao X. S. , Zhou G. F. , Lu X. B. , Liu J.-M.
Published: August 2017

In this work, we fabricated a high performance flash-type organic nonvolatile memory transistor, which adopted polymer-electret poly(α-methylstyrene) (PαMS) and HfO2 films as hybrid charge trapping layer (CTL). Compared with a single HfO2 or PαMS CTL structure, the hybrid HfO2/PαMS CTL structure can provide enhanced charge trapping efficiency to increase the device operation speed and reduce the leakage current to boost the device reliability. The fabricated nonvolatile organic memory transistors with the hybrid CTL shows excellent electrical properties, including low operation voltage (8 V), high speed (<10 ms), excellent data retention (on-off current ratio of 2.6 × 104 after 104 s), and good endurance (more than 2000 program/erase cycles). The present work provides useful idea for the design of future low-power consumption and highly reliable organic nonvolatile memories.
Electronic structure of Ba (Zn0.875Mn0.125)2As2
Authors: Zhu Fengfeng , Jiang W. X. , Li P. , Yang Z. Q. , Man H. Y. , Li Y. Y. , Liu Canhua , Guan Dandan , Jia Jin-Feng , Ning F. L. , Luo Weidong , Qian Dong
Published: August 2017

The electronic structure of single-crystalline Ba(Zn0.875Mn0.125)2As2, the parent compound of the recently found high-temperature ferromagnetic semiconductor–(Ba,K)(Zn,Mn)2As2, was studied by high-resolution angle-resolved photoemission spectroscopy. A flat band related to the 3d states of the doped Mn atoms was observed at the binding energy of ∼ −1.6 eV besides the previously reported feature at about −3.3 eV. The spectral weight of this feature is much stronger than that obtained from density functional theory calculations. We proposed that the large spectral weight could originate from the hybridization between Mn and As orbitals. The overall band dispersions agree well with the first-principles calculations of undoped BaZn2As2 except that the total bandwidth of the valence band is larger than that calculated. The increased bandwidth after Mn doping is compatible with the proposed theoretical model.
Epitaxial VO2 thin film-based radio-frequency switches with thermal activation
Authors: Lee Jaeseong , Lee Daesu , Cho Sang June , Seo Jung-Hun , Liu Dong , Eom Chang-Beom , Ma Zhenqiang
Published: August 2017

In this paper, we report on the demonstration of thermally triggered “normally ON” radio-frequency (RF) switches based on epitaxial vanadium dioxide (VO2) thin films with a SnO2 template on (001) TiO2 substrates. Fast insulator-to-metal phase transition of the epitaxial VO2 at a relatively low temperature allowed RF switches made of the VO2 to exhibit sharp changes in the RF insertion loss during cooling and heating at 60 °C and 66 °C, respectively. The change of RF insertion loss due to phase transition is greater than 15 dB. The VO2 RF switches also completed the transition of S21 within less than 3 °C and showed a low-loss operation frequency of up to 24.2 GHz with a low insertion loss of −1.36 dB and isolation of 17.56 dB at 12.03 GHz, respectively. The demonstration suggests that epitaxial VO2-based RF switches can be used in switching elements up to Ku-band RF circuits.
Genotype by environment interactions in cowpea (Vigna unguiculata L. Walp.) grown in the Iberian Peninsula
Authors: Martos-Fuentes Marina , Fernández Juan A. , Ochoa Jesús , Carvalho Márcia , Carnide Valdemar , Rosa Eduardo , Pereira Graça , Barcelos Carina , Bebeli Penelope J. , Egea-Gilabert Catalina
Published: August 2017

The aim of this work was to determine the variance components and genetic and environmental stability of 12 cowpea genotypes at three locations (South-east of Spain: Cartagena, South and North of Portugal: Elvas and Vila Real, respectively) in the Iberian Peninsula in two consecutive years (2015 and 2016). The genotype, the environment and the genotype × environment interaction significantly influenced all the morphological and agronomical parameters evaluated. For both years, the highest yields were observed at Elvas, whereas Cartagena and Vila real were the most suitable places to obtain crop precocity. Cartagena was the place where the filling of the seed was the fastest, probably due to the higher temperatures and radiation. The thermal time model (effective degree-days) could be used to predict the period of cowpea development, therefore predict flowering and pod maturity date. Correlation analysis showed that days to flowering, days to maturity and the seed yield vs protein content exhibited negative correlations. The highest heritability was found for plant height and pod length at Cartagena and for 100-seed weight at Elvas and Vila Real. In conclusion, the variations that exist in the studied accessions could give rise to a breeding program to develop cowpea cultivars with interesting agronomic traits.
Patterns of herders’ adaptation to changes in social–ecological systems across northern China’s grasslands over the past three decades
Authors: Li Xiliang , Ding Yong , Yin Yanting , Yang Tingting , Liu Zhiying , Ren Weibo , Zhang JiangLi , Sarula  , Li Yuanheng , Hou Xiangyang
Published: August 2017

Understanding the changes in herders’ adaptation to environmental change can provide insight into humans’ adaptive mechanisms to different social–ecological systems, and is also important for the optimal management of grasslands. However, the existing and emerging patterns of herders’ adaptation to changes in social–ecological systems across different types of grasslands are poorly understood. This paper presents a systematic participatory investigation that was conducted to comprehensively understand herders’ adaptation in this context over the past three decades. Three counties in Inner Mongolia grasslands were selected as the case study sites, located in meadow steppe, typical steppe and desert steppe respectively. Our results indicate that herders’ perceptions partly fit with the reality of the actual changes. The majority of herders attributed their pasture’s quality degradation to reduced precipitation rather than overgrazing, a contradictory perception to previous scientific observations (overgrazing > climate change). Moreover, herders’ behaviour in relation to herbage storage and livestock structure had dramatically changed in terms of spatial and temporal patterns in Inner Mongolia, which benefited herders in production efficiency. Lambing time of sheep and goats occurred earlier than it did several decades ago across the three grassland types. This was attributed to a rise in temperature, increasing marketisation and developing infrastructure. In addition, there became evident a transformation in the animal husbandry production cycle from a two-year to one-year cycle. Our results highlighted that the transformation of herders’ behavioural strategies resulted from variations in spatial and temporal patterns of climate change, pasture degradation, new policies and marketisation in pastoral areas. These strategies can be seen as key mechanisms in long-term adaptation to changes in social–ecological systems, which benefit herders’ efficiency in grassland management.
Marine reserves solve an important bycatch problem in fisheries
Authors: Hastings Alan , Gaines Steven D. , Costello Christopher
Published: August 2017

Significance

Bycatch, where one species is unintentionally caught in pursuit of another species, is one of the most ubiquitous and crippling challenges in global fisheries. The usual solution is to dramatically reduce take of the target species to allow “weak stock” persistence. Using a general strategic model, we show that establishing areas closed to fishing can alleviate, or even completely eliminate, this problem. If the weak stock is long-lived, but slow to reproduce, significantly higher yields can be obtained by using reserves than by using fishing effort controls alone. We emphasize that this is the problem plaguing the US West Coast groundfish fishery, suggesting that in that fishery, marine reserves may be a solution that simultaneously benefits fishermen and conservation.
Comparison of American Fisheries Society (AFS) Standard Fish Sampling Techniques and Environmental DNA for Characterizing Fish Communities in a Large Reservoir
Authors: Perez Christina R. , Bonar Scott A. , Amberg Jon J. , Ladell Bridget , Rees Chris , Stewart William T. , Gill Curtis J. , Cantrell Chris , Robinson Anthony T.
Published: August 2017

Recently, methods involving examination of environmental DNA (eDNA) have shown promise for characterizing fish species presence and distribution in waterbodies. We evaluated the use of eDNA for standard fish monitoring surveys in a large reservoir. Specifically, we compared the presence, relative abundance, biomass, and relative percent composition of Largemouth Bass Micropterus salmoides and Gizzard Shad Dorosoma cepedianum measured through eDNA methods and established American Fisheries Society standard sampling methods for Theodore Roosevelt Lake, Arizona. Catches at electrofishing and gillnetting sites were compared with eDNA water samples at sites, within spatial strata, and over the entire reservoir. Gizzard Shad were detected at a higher percentage of sites with eDNA methods than with boat electrofishing in both spring and fall. In contrast, spring and fall gillnetting detected Gizzard Shad at more sites than eDNA. Boat electrofishing and gillnetting detected Largemouth Bass at more sites than eDNA; the exception was fall gillnetting, for which the number of sites of Largemouth Bass detection was equal to that for eDNA. We observed no relationship between relative abundance and biomass of Largemouth Bass and Gizzard Shad measured by established methods and eDNA copies at individual sites or lake sections. Reservoirwide catch composition for Largemouth Bass and Gizzard Shad (numbers and total weight [g] of fish) as determined through a combination of gear types (boat electrofishing plus gillnetting) was similar to the proportion of total eDNA copies from each species in spring and fall field sampling. However, no similarity existed between proportions of fish caught via spring and fall boat electrofishing and the proportion of total eDNA copies from each species. Our study suggests that eDNA field sampling protocols, filtration, DNA extraction, primer design, and DNA sequencing methods need further refinement and testing before incorporation into standard fish sampling surveys.

Received October 26, 2016; accepted June 9, 2017Published online August 10, 2017
The intricacies of atrial calcium cycling during excitation-contraction coupling
Authors: Blatter Lothar A.
Published: August 2017

Blatter discusses the initiation and spread of Ca release, Ca store depletion, and release termination in atrial myocytes.
Perspectives on “Control of Ca release from within the cardiac sarcoplasmic reticulum”
Authors: Ríos Eduardo
Published: August 2017

Five groups of experts unravel the complex modulation of a function crucial for the beating heart.
Coi1 is a novel assembly factor of the yeast complex III–complex IV supercomplex
Authors: Singhal Ravi K. , Kruse Christine , Heidler Juliana , Strecker Valentina , Zwicker Klaus , Düsterwald Lea , Westermann Benedikt , Herrmann Johannes M. , Wittig Ilka , Rapaport Doron
Published: August 2017

The yeast bc1 complex (complex III) and cytochrome oxidase (complex IV) are mosaics of core subunits encoded by the mitochondrial genome and additional nuclear-encoded proteins imported from the cytosol. Both complexes build various supramolecular assemblies in the mitochondrial inner membrane. The formation of the individual complexes and their supercomplexes depends on the activity of dedicated assembly factors. We identified a so far uncharacterized mitochondrial protein (open reading frame YDR381C-A) as an important assembly factor for complex III, complex IV, and their supercomplexes. Therefore we named this protein Cox interacting (Coi) 1. Deletion of COI1 results in decreased respiratory growth, reduced membrane potential, and hampered respiration, as well as slow fermentative growth at low temperature. In addition, coi1Δ cells harbor reduced steady-state levels of subunits of complexes III and IV and of the assembled complexes and supercomplexes. Interaction of Coi1 with respiratory chain subunits seems transient, as it appears to be a stoichiometric subunit neither of complex III nor of complex IV. Collectively this work identifies a novel protein that plays a role in the assembly of the mitochondrial respiratory chain.
HaploForge: a comprehensive pedigree drawing and haplotype visualization web application
Authors: Tekman Mehmet , Medlar Alan , Mozere Monika , Kleta Robert , Stanescu Horia
Published: August 2017

Motivation

Haplotype reconstruction is an important tool for understanding the aetiology of human disease. Haplotyping infers the most likely phase of observed genotypes conditional on constraints imposed by the genotypes of other pedigree members. The results of haplotype reconstruction, when visualized appropriately, show which alleles are identical by descent despite the presence of untyped individuals. When used in concert with linkage analysis, haplotyping can help delineate a locus of interest and provide a succinct explanation for the transmission of the trait locus. Unfortunately, the design choices made by existing haplotype visualization programs do not scale to large numbers of markers. Indeed, following haplotypes from generation to generation requires excessive scrolling back and forth. In addition, the most widely used program for haplotype visualization produces inconsistent recombination artefacts for the X chromosome.

Results

To resolve these issues, we developed HaploForge, a novel web application for haplotype visualization and pedigree drawing. HaploForge takes advantage of HTML5 to be fast, portable and avoid the need for local installation. It can accurately visualize autosomal and X-linked haplotypes from both outbred and consanguineous pedigrees. Haplotypes are coloured based on identity by descent using a novel A* search algorithm and we provide a flexible viewing mode to aid visual inspection. HaploForge can currently process haplotype reconstruction output from Allegro, GeneHunter, Merlin and Simwalk.

Availability and implementation

HaploForge is licensed under GPLv3 and is hosted and maintained via GitHub. https://github.com/mtekman/haploforge

Supplementary information

Supplementary data are available at Bioinformatics online.
Long-Term Follow-up Study of MRI-Guided Bilateral Anterior Capsulotomy in Patients With Refractory Anorexia Nervosa
Authors: Liu Wei , Li Dianyou , Sun Fafa , Zhang Xiaoxiao , Wang Tao , Zhan Shikun , Pan Yixin , Huang Peng , Jin Haiyan , Li Yongchao , Sun Bomin
Published: August 2017

BACKGROUND

Anorexia nervosa (AN) is one of the most challenging psychiatric disorders to treat. The poor clinical outcomes warrant novel treatments for AN, especially in severe and persistent cases.

OBJECTIVE

To explore the feasibility of magnetic resonance imaging-guided bilateral anterior capsulotomy in the treatment of refractory AN.

METHODS

Seventy-four patients diagnosed with refractory AN who underwent capsulotomy completed this 3-yr follow-up study. Outcomes included body mass index (BMI) and results from a series of psychiatric scales (for obsessive, depressive, and anxious symptoms) that were implemented at baseline (presurgery), and 1 mo, 1 yr, and 3 yr after surgery.

RESULTS

Compared to presurgical levels, BMI increased significantly at 1-yr and 3-yr follow-ups. Compared to presurgery scores, psychiatric scale scores were significantly improved at 1-mo postsurgery, and continued to remain low at the 1-yr and 3-yr follow-ups. In addition, Mini-Mental State Examination (MMSE) scores were in the normal range during the long-term follow-up. The most common short-term side effects included urinary incontinence (n = 7), sleep disorders (n = 8), and fatigue (n = 6). Long-term complications included disinhibition (n = 6), memory loss (n = 3), and lethargy (n = 4). No patient in this study experienced death or disability.

CONCLUSION

Capsulotomy enabled patients with refractory AN to normalize their weight, especially those in life-threatening conditions. While it appears to be an acceptable life-saving treatment, it is indicated only when fulfilling strict criteria given its complications and irreversibility.
Frozen Convenience Noodles: Use of Ultrasound to Study the Influence of Preparation Methods on Their Rheological Parameters
Authors: Daugelaite Daiva , Strybulevych Anatoliy , Norisuye Tomohisa , Hatcher David W. , Scanlon Martin G. , Page John H.
Published: August 2017

Longitudinal ultrasonic waves were used to investigate effects of preparation and frozen storage time on the rheological properties of noodles. Noodles prepared with and without glucose oxidase (GOx) were flash frozen either immediately after production (raw), after blanching, or after being optimally cooked. From measurements of attenuation, phase velocity, loss and storage moduli (M″ and M′), and tanδL (M″/M′), it was found that raw noodles, prepared with or without GOx, were most similar overall to fresh noodles when stored frozen for one week. However, blanched noodles were closest to fresh noodles in terms of firmness, as measured by storage modulus, after one week of storage. Frozen storage for four weeks resulted in a significant loss in noodle quality. Stress relaxation measurements of Peleg's K1 and K2 parameters showed a significant effect of GOx addition on raw noodles after one week of frozen storage. As shown by K1 and K2 parameters, GOx addition delayed noodle texture deterioration associated with frozen aging for blanched and cooked treatments. The combined texture assessment of stress relaxation coupled with simultaneous ultrasonic measurements exhibits good potential for examining how formulation and pretreatment can mitigate the textural quality impairments associated with freezing of convenience noodles.
Learning Curve of Small Incision Lenticule Extraction: Challenges and Complications
Authors: Titiyal Jeewan S. , Kaur Manpreet , Rathi Anubha , Falera Ruchita , Chaniyara Manthan , Sharma Namrata
Published: August 2017

Purpose:

To describe the intraoperative complications observed during the initial learning curve of small incision lenticule extraction (SMILE) and their management.

Methods:

Prospective evaluation of 100 consecutive eyes (50 patients) undergoing SMILE was performed at an apex tertiary care ophthalmic center. Patients older than 18 years with a stable refractive error ranging from −1.0 to −10.0 D myopia and up to 3.0 D astigmatism were included. Any intraoperative complications and their management were noted. Postoperative examination including visual acuity was performed on day 1, 1 week, and 1 month.

Results:

Intraoperative difficulties observed in the initial 100 eyes included suction loss (2%), black spots (11%), opaque bubble layer (19%), epithelial defect (2%), and difficult lenticule extraction (9%). Difficult lenticule dissection and extraction was the most surgically challenging step and resulted in posterior stromal damage, anterior cap tear (1%), side-cut tears (4%), partially retained lenticule (1%), and completely retained lenticule (2%). Its incidence decreased from 16% (8/50) in the initial 50 cases to 2% (1/50) in the next 50 cases. Two eyes with completely retained lenticule were re-treated with flap-based excimer laser ablation after 3 months. Optimal visual and anatomical outcomes could be achieved, and no sight-threatening complication was observed in any case.

Conclusions:

The learning curve of SMILE is surgically challenging. Lenticule dissection and extraction is the most difficult step and leads to a multitude of complications. Most complications that result in delayed visual recovery are observed in the initial 50 cases.
Inflammation-Related Pancreatic Carcinogenesis
Authors: Dai Juan-juan , Jiang Ming-jie , Wang Xing-Peng , Tian Ling
Published: August 2017

Chronic inflammation has long been considered critical in pancreatic carcinogenesis, and recently studies showed that some anti-inflammatory agents such as aspirin could potentially be used to attenuate pancreatic carcinogenesis. Several inflammation-related critical transcription factors and pathways such as NF-κB (nuclear factor κ-light-chain enhancer of activated B cells) and reactive oxygen species have been confirmed to be involved in carcinogenesis. However, its underlying mechanisms are far from clear, which largely limits further development of potential anticarcinogenesis drugs. As a result, it is of great importance for us to better understand and gain a better perspective in inflammation-related pancreatic carcinogenesis. In this review, we systematically analyzed recent advances concerning inflammation-related pancreatic carcinogenesis and brought out the possible underlying mechanisms. Potential preventive and therapeutic strategies based on anti-inflammatory agents have also been further discussed.
Effects of exercise training on exercise capacity, cardiac function, BMI, and quality of life in patients with atrial fibrillation: a meta-analysis of randomized-controlled trials
Authors: Kato Michitaka , Kubo Akira , Nihei Fumi , Ogano Michio , Takagi Hisato
Published: August 2017

Exercise training has become part of the standard care for patients with cardiovascular disease. We investigated the effects of exercise training on exercise capacity, cardiac function, BMI, and quality of life in patients with atrial fibrillation (AF). We searched for randomized-controlled trials of supervised exercise training versus care without exercise training (the control) in patients with permanent or nonpermanent AF published up to November 2016. Standard mean differences (SMD) or mean differences (MD), and 95% confidence intervals (CIs) were calculated using random-effect models. We identified 259 trials, and after an assessment of relevance, five trials with a combined total of 379 participants were analyzed. In AF patients, exercise training significantly improved exercise capacity and left ventricular ejection fraction compared with the control (SMD: 0.91, 95% CI: 0.70 to 1.12; MD: 4.8%, 95% CIs: 1.56 to 8.03, respectively). Compared with the control, exercise training also significantly reduced BMI (MD: −0.47 kg/m2, 95% CIs: −0.89 to −0.06) and significantly improved scores in the ‘general health’ and ‘vitality’ sections of the 36-item Short Form Health Status Survey (SMD: 0.71, 95% CIs: 0.30 to 1.12; SMD: 0.81, 95% CIs: 0.40 to 1.23, respectively). Exercise training improved exercise capacity, left ventricular ejection fraction, and some the 36-item Short Form Health Status Survey scores, and reduced BMI in AF patients.
Toxic Myocarditis Caused by Acetaminophen in a Multidrug Overdose
Authors: Gosselin Maxime , Dazé Yann , Mireault Pascal , Crahes Marie
Published: August 2017

We report the case of an 18-year-old woman with personality disorders who was hospitalized a few hours after suicidal ingestion of acetaminophen, quetiapine, acetylsalicylic acid, and ethanol. Twelve hours after admission, severe liver damage was evident, but the patient was stable and awaiting hepatic transplantation. Electrolytes were successfully controlled. The condition of the liver stabilized. Cardiac biomarkers then deteriorated unexpectedly. Localized ST-segment elevations were noted on electrocardiogram, but angiography ruled out myocardial infarction. A computed tomographic scan ruled out cerebral edema. The patient died of irreversible cardiac arrest 40 hours after admission. Heart failure remained unexplained, and the body underwent forensic autopsy.

At autopsy, histologic findings were indicative of acute toxic myocarditis and were concluded to be caused by acetaminophen intoxication. Acetaminophen overdose is common and typically leads to liver failure requiring supportive treatment and emergency liver transplantation. Toxic myocarditis is an extremely rare complication of acetaminophen overdose. It has only been reported 4 times in the literature despite the widespread use and misuse of acetaminophen. Toxic myocarditis remains a possibility in many cases of overdose but can be overlooked in a clinical picture dominated by hepatorenal failure and encephalopathy. Clinicians and forensic pathologists should be aware of this rare potential complication.
Cell Polarity Reversal Distinguishes True Micropapillary Growth From Retraction Artifact in Invasive Urothelial Carcinoma
Authors: Hui Yiang , Lombardo Kara A. , Quddus M. Ruhul , Matoso Andres
Published: August 2017

Focal micropapillary features in invasive urothelial carcinoma is sometimes difficult to distinguish from retraction artifact morphologically. Cell polarity reversal has been demonstrated in micropapillary tumors by epithelial membrane antigen (EMA) immunostaining. We have previously described the use of E-cadherin as a cell polarity marker in ovarian micropapillary serous borderline tumors. The aim of this study was to evaluate the utility of immunohistochemistry for EMA and E-cadherin in differentiating micropapillary urothelial carcinoma from retraction artifact. We identified 29 invasive urothelial carcinomas with micropapillary features and 30 invasive urothelial carcinomas without reported micropapillary features but with areas of retraction artifact. Cell polarity reversal was considered present if E-cadherin showed membranous apical cup-like staining or if EMA demonstrated a well-defined basal staining towards the stroma. Twenty-seven of 29 cases (93%) of urothelial carcinoma with micropapillary features demonstrated EMA or E-cadherin staining patterns consistent with cell polarity reversal. Staining consistent with micropapillary architecture was identified with both markers in 20 of these 27 cases (74%). Six cases showed reversal of polarity by E-cadherin alone, whereas 1 case showed polarity reversal by EMA alone. Retraction artifacts showed circumferential staining by E-cadherin and lacked well-defined basal staining by EMA. Three cases originally classified as with retraction artifact showed reversal of cell polarity by both EMA and E-cadherin and were reclassified as micropapillary. Our data show that pathologists can reliably make this distinction in most cases. However, in some cases with ambiguous features, EMA and E-cadherin immunostaining may aid in resolving this diagnostic dilemma.
Large Tumefactive IgG4-related Disease: Histologic, Cytologic, and Immunohistochemical Features of a Very Unusual Case
Authors: Akhtar Israh , Shenoy Veena , Khan Majid , Saad Ali G.
Published: August 2017

Immunoglobulin G4-related disease (IgG4-RD) is a regional or systemic multiorgan lymphoplasmacytic inflammatory disease of unknown etiology. It has been described in numerous organs and anatomic locations. Review of the literature shows that when the disease involves the retroperitoneum it causes retroperitoneal fibrosis. Tumefactive IgG4-RD of the retroperitoneum has not been previously reported. In this report, we describe the first case of a large retroperitoneal tumefactive IgG4-RD along with its histologic, cytologic, and immunohistochemical characteristics.
Bringing plants and soils to life through a simple role-playing activity
Authors: Van Nuland Michael E. , Chen Miranda , England Benjamin J.
Published: August 2017

Interactions are at the core of many ecological and evolutionary forces in nature. Plant-soil interactions provide a rich example of the interconnectedness of living systems, but are hidden from everyday view and overshadowed in the classroom by more popular teaching examples involving animals, reptiles, or invertebrates. To highlight the importance and relevance of plant-soil relationships, we devised a simple role-playing activity suitable for college students. Specifically, the activity simulates how feedbacks between plants and soil environments influence plant species abundance and community richness. With this activity, students will gain a better understanding of these prolific, but overlooked, forms of biological interactions that impact the diversity and functioning of ecosystems.
Evolution of exploitative interactions during diversification inBacillus subtilisbiofilms
Authors: Dragoš Anna , Lakshmanan Nivedha , Martin Marivic , Horváth Balázs , Maróti Gergely , Falcón García Carolina , Lieleg Oliver , Kovács Ákos T.
Published: August 2017

Microbial biofilms are tightly packed, heterogeneous structures that serve as arenas for social interactions. Studies on Gram negative models reveal that during evolution in structured environments like biofilms, isogenic populations commonly diversify into phenotypically and genetically distinct variants. These variants can settle in alternative biofilm niches and develop new types of interactions that greatly influence population productivity. Here, we explore the evolutionary diversification of pellicle biofilms of the Gram positive, spore-forming bacteriumBacillus subtilis. We discover that - similarly to other species -B. subtilisdiversifies into distinct colony variants. These variants dramatically differ in biofilm formation abilities and expression of biofilm-related genes. In addition, using a quantitative approach, we reveal striking differences in surface complexity and hydrophobicity of the evolved colony types. Interestingly, one of the morphotypes completely lost the ability of independent biofilm formation and evolved to hitchhike with other morphotypes with improved biofilm forming abilities. Genome comparison suggests that major phenotypic transformations between the morphotypes can be triggered by subtle genetic differences. Our work demonstrates how positive complementarity effects and exploitative interactions intertwine during evolutionary diversification in biofilms.
Rapid degradation and 3D CLEM of condensin reveal chromatin compaction uncoupled from chromosome architecture in mitosis
Authors: Samejima Kumiko , Booth Daniel G. , Ogawa Hiromi , Paulson James R. , Xie Linfeng , Watson Cara A. , Platani Melpomeni , Kanemaki Masato T. , Earnshaw William C.
Published: August 2017

The requirement for condensin in chromosome formation in somatic cells remains unclear as imperfectly condensed chromosomes do form in conventional condensindepleted cells. Here we have dissected the role of condensin at different stages of vertebrate mitosis by combining auxin-mediated rapid depletion of condensin subunit SMC2 with chemical genetics to obtain near-synchronous mitotic entry of chicken DT40 cells. We analysed the outcomes by live and fixed-cell microscopy methods, including 3D correlative light and serial block face scanning electron microscopy. Following rapid depletion of condensin, chromosomal defects were obvious. The chromatin was compacted normally, but formed a single mass of mitotic chromosomes clustered at one side of a bent mitotic spindle. Cultures arrest at prometaphase, eventually exiting mitosis without segregating chromosomes. Experiments titrating the auxin concentration suggest a previously unsuspected dual role of condensin, as different condensin levels are required for anaphase chromosome segregation and formation of a normal chromosome architecture.
Can CRISPR-based gene drive be confined in the wild? A question for molecular and population biology
Authors: Marshall John M. , Akbari Omar S.
Published: August 2017

The recent discovery of CRISPR and its application as a gene editing tool has enabled a range of gene drive systems to be engineered with much greater ease. In order for the benefits of this technology to be realized, drive systems must be developed that are capable of both spreading into populations to achieve their desired impact, and being recalled in the event of unwanted consequences or public disfavor. We review the performance of three broad categories of drive systems at achieving these goals - threshold-dependent drives, homing-based drive and remediation systems, and temporally self-limiting systems such as daisy-chain drives.
Genome-Wide SNPs Reveal the Drivers of Gene Flow In An Urban Population of the Asian Tiger Mosquito,Aedes albopictus
Authors: Schmidt Thomas L. , Rašić Gordana , Zhang Dongjing , Zheng Xiaoying , Xi Zhiyong , Hoffmann Ary A.
Published: August 2017

Aedes albopictusis a highly invasive disease vector with an expanding worldwide distribution. Genetic assays using low to medium resolution markers have found little evidence of spatial genetic structure even at broad geographic scales, suggesting frequent passive movement along human transportation networks. Here we analysed genetic structure ofAe. albopictuscollected from 12 sample sites in Guangzhou, China, using thousands of genome-wide single nucleotide polymorphisms (SNPs). We found evidence for passive gene flow, with distance from shipping terminals being the strongest predictor of genetic distance among mosquitoes. As further evidence of passive dispersal, we found multiple pairs of full-siblings distributed between two sample sites 3.7 km apart. After accounting for geographical variability, we also found evidence for isolation by distance, previously undetectable inAe. albopictus. These findings demonstrate how large SNP datasets and spatially-explicit hypothesis testing can be used to decipher processes at finer geographic scales than formerly possible. Our approach can be used to help predict new invasion pathways ofAe. albopictusand to refine strategies for vector control that involve the transformation or suppression of mosquito populations.

Author Summary

Aedes albopictus, the Asian Tiger Mosquito, is a highly invasive disease vector with a growing global distribution. Designing strategies to prevent invasion and to controlAe. albopictuspopulations in invaded regions requires knowledge of howAe. albopictusdisperses. Studies comparingAe. albopictuspopulations have found little evidence of genetic structure even between distant populations, suggesting that dispersal along human transportation networks is common. However, a more specific understanding of dispersal processes has been unavailable due to an absence of studies using high-resolution genetic markers. Here we present a study using high-resolution markers, which investigates genetic structure among 152Ae. albopictusfrom Guangzhou, China. We found that human transportation networks, particularly shipping terminals, had an influence on genetic structure. We also found genetic distance was correlated with geographical distance, the first such observation in this species. This study demonstrates how high-resolution markers can be used to investigate ecological processes that may otherwise escape detection. We conclude that strategies for controllingAe. albopictuswill have to consider both passive reinvasion along human transportation networks and active reinvasion from neighbouring regions.
Scanpy for analysis of large-scale single-cell gene expression data
Authors: Wolf F. Alexander , Angerer Philipp , Theis Fabian J.
Published: August 2017

We present Scanpy, a scalable toolkit for analyzing single-cell gene expression data. It includes preprocessing, visualization, clustering, pseudotime and trajectory inference, differential expression testing and simulation of gene regulatory networks. The Python-based implementation efficiently deals with datasets of more than one million cells and enables easy interfacing of advanced machine learning packages. Code is available fromhttps://github.com/theislab/scanpy.
Autocatalytic microtubule nucleation determines the size and mass of spindles
Authors: Decker Franziska , Oriola David , Dalton Benjamin , Brugués Jan
Published: August 2017

Regulation of size and growth is a fundamental problem in biology. A prominent example is the formation of the mitotic spindle, where protein concentration gradients around chromosomes are thought to regulate spindle growth by controlling microtubule nucleation (1,2). Previous evidence suggests that microtubules nucleate throughout the spindle structure (3-5). However, the mechanisms underlying microtubule nucleation and its spatial regulation are still unclear. Here, we developed an assay based on laser ablation to directly probe microtubule nucleation events inXenopus laevisegg extracts. Combining this method with theory and quantitative microscopy, we show that the size of a spindle is controlled by autocatalytic growth of microtubules, driven by microtubule-stimulated microtubule nucleation. The autocatalytic activity of this nucleation system is spatially regulated by the limiting amounts of active microtubule nucleators, which decrease with distance from the chromosomes. Thus, the size of spindles is determined by the distance where one microtubule nucleates on average less than one new microtubule. This mechanism provides an upper limit to spindle size even when resources are not limiting and may have implications for spindle scaling during development (6,7).
YAP and TAZ regulate adherens junction dynamics and endothelial cell distribution during vascular development
Authors: Neto Filipa , Klaus-Bergmann Alexandra , Ong Yu-Ting , Alt Silvanus , Vion Anne-Clémence , Szymborska Anna , Carvalho Joana R. , Hollfinger Irene , Bartels-Klein Eireen , Franco Claudio A. , Potente Michael , Gerhardt Holger
Published: August 2017

Formation of a hierarchically organized blood vessel network by sprouting angiogenesis is critical for tissue growth, homeostasis and regeneration. How in this process endothelial cells arise in adequate numbers and arrange suitably to shape a functional vascular network is poorly understood. Here we show that YAP and TAZ promote stretch-induced proliferation and rearrangements of endothelial cells whilst preventing bleeding in developing vessels. Mechanistically, YAP and TAZ increase VE-cadherin turnover at junctions and suppress endothelial Notch and BMP signaling, two key pathways that limit sprouting and endothelial dynamics. Consequently, the loss of YAP and TAZ leads to stunted sprouting with local aggregation as well as scarcity of endothelial cells, branching irregularities and junction defects. Forced nuclear activity of TAZ instead drives hypersprouting and vascular hyperplasia. We propose a new model in which YAP and TAZ integrate mechanical signals with Notch and BMP signaling to balance endothelial cell distribution in angiogenic vessels.
A subgroup of mitochondrial extracellular vesicles discovered in human melanoma tissues are detectable in patient blood
Authors: Jang Su Chul , Crescitelli Rossella , Cvjetkovic Aleksander , Belgrano Valerio , Bagge Roger Olofsson , Höög Johanna L. , Sundfeldt Karin , Ochiya Takahiro , Kalluri Raghu , Lötvall Jan
Published: August 2017

Extracellular vesicles (EVs), including exosomes and microvesicles, are secreted from all cells, and convey messages between cells in health and disease. However, the diversity of EV subpopulations are only beginning to be explored. Since EVs have been implicated in tumor microenvironmental communication, we started to determine the diversity of EVs specifically in this tissue. To do this, we isolated EVs directly from patient melanoma metastatic tissues. Using EV membrane isolation and mass spectrometry analysis, we discovered enrichment of mitochondrial membrane proteins in the melanoma tissue-derived EVs, compared to non-melanoma-derived EVs. Specifically, EVs positive for a combination of the two mitochondrial inner membrane proteins MT-CO2 (mitochondrial genome) and COX6c (nuclear genome) were detected in the plasma of melanoma patients, and in ovarian and breast cancer patients. Furthermore, this subpopulation of EVs, contains active mitochondrial enzymes. Our findings show that tumor tissues are enriched in EVs with mitochondrial proteins and enzymatic activity, and these EVs can be detected in blood.
Characterization of a replicating mammalian orthoreovirus with tetracysteine tagged μNS for live cell visualization of viral factories
Authors: Bussiere Luke D. , Choudhury Promisree , Bellaire Bryan , Miller Cathy L.
Published: August 2017

Within infected host cells, mammalian orthoreovirus (MRV) forms viral factories (VFs) which are sites of viral transcription, translation, assembly, and replication. MRV non-structural protein, μNS, comprises the structural matrix of VFs and is involved in recruiting other viral proteins to VF structures. Previous attempts have been made to visualize VF dynamics in live cells but due to current limitations in recovery of replicating reoviruses carrying large fluorescent protein tags, researchers have been unable to directly assess VF dynamics from virus-produced μNS. We set out to develop a method to overcome this obstacle by utilizing the 6 amino-acid (CCPGCC) tetracysteine (TC)-tag and FlAsH-EDT2 reagent. The TC-tag was introduced into eight sites throughout μNS, and the capacity of the TC-μNS fusion proteins to form virus factory-like (VFL) structures and colocalize with virus proteins was characterized. Insertion of the TC-tag interfered with recombinant virus rescue in six of the eight mutants, likely as a result of loss of VF formation or important virus protein interactions. However, two recombinant (r)TC-μNS viruses were rescued and VF formation, colocalization with associating virus proteins, and characterization of virus replication were subsequently examined. Furthermore the rTC-μNS viruses were utilized to infect cells and examine VF dynamics using live cell microscopy. These experiments demonstrate active VF movement with fusion events as well as transient interactions between individual VFs, and demonstrate the importance of microtubule stability for VF fusion during MRV infection. This work provides important groundwork for future in depth studies of VF dynamics and host cell interactions.

Importance

MRV has historically been used as a model to study the double-stranded RNA (dsRNA)Reoviridaefamily, which infect and cause disease in humans, animals, and plants. During infection, MRV forms VFs that play a critical role in virus infection, but remain to be fully characterized. To study VFs, researchers have focused on visualizing the non-structural protein μNS which forms the VF matrix. This work provides the first evidence of recovery of replicating reoviruses in which VFs can be labeled in live cells via introduction of a TC-tag into the μNS open reading frame. Characterization of each recombinant reovirus sheds light on μNS interactions with viral proteins. Moreover, utilizing the TC labeling FlAsH-EDT2 biarsenical reagent to visualize VFs, evidence is provided of dynamic VF movement and interactions at least partially dependent on intact microtubules.