bluuebunny/crossref_metadata_2025 huggingface dataset:
18F-Fluciclovine PET/CT Detection of Recurrent Prostate Carcinoma in Patients With Serum PSA ≤ 1 ng/mL After Definitive Primary Treatment
Authors: England Joseph R. , Paluch Jeremy , Ballas Leslie K. , Jadvar Hossein
Published: January 2019

Purpose

The aims of this study were to report on our initial experience using 18F-fluciclovine PET/CT to detect recurrent prostate carcinoma in patients with low serum prostate-specific antigen (PSA) after definitive treatment of primary disease and to conduct a preliminary investigation for factors associated with positive scan findings.

Patients and Methods

In this retrospective study, 18F-fluciclovine PET/CT scans from 28 men with suspected recurrence of prostate carcinoma and PSA values of 1 ng/mL or less were examined to identify the site(s) of disease recurrence. Differences in detection rate for Gleason scores of 7 and greater than 7, T2 and T3 disease, negative and positive surgical margins, and negative and positive seminal vesicle invasion were compared using the Fisher exact test. Mean PSA and mean PSA doubling time of patients with positive scans and negative scans were compared using the independent 2-group t test.

Results

At least one site of disease recurrence was identified in 13 (46.4%) of 28 patients. Disease detection rate was significantly higher in patients with history of Gleason score greater than 7 (Fisher exact test, P = 0.004). Mean PSA and PSA doubling time were not significantly different between patients with positive and negative 18F-fluciclovine PET/CT scans (P = 0.29 and 0.70, respectively).

Conclusions

Detection of recurrent prostate cancer using 18F-fluciclovine PET/CT is possible in patients with low but rising PSA levels of 1 ng/mL or less. In such patients, local and nodal recurrences are more common than distant metastasis, and Gleason score greater than 7 is associated with positive scan results.
Primary Common Iliac Artery Angiosarcoma With Multiple Bone Metastases Revealed by Dual-Time Point FDG PET/CT Imaging
Authors: Wang Renjie , Wang Xueju , Ji Bin , Guan Qingtao , Chen Bin
Published: January 2019

Iliac artery angiosarcoma is rare, and bone metastasis as its presenting initial symptom is extremely rare. A 67-year-old man with a history of low back pain presented with multiple MRI-identified lumbar and sacrum lesions highly suggestive of bone metastasis. On subsequent PET/CT scan, in addition to multiple vertebrae and pelvis hypermetabolism, a lesion with intense focal uptake was discovered within the lumen of left common iliac artery. Dual-time point quantitative analysis revealed that the lesion-to-liver ratio of SUVmax was significantly increased in the delayed phase. Biopsy confirmed the lesion as a primary iliac artery angiosarcoma.
A Case of Mediastinal Leiomyosarcoma Demonstrated on FDG PET/CT Imaging
Authors: Wu Xiaodong , Huang Yan , Li Yi , Wang Huoqiang , Jiang Lei
Published: January 2019

A 56-year-old man presented with persisting chest tightness over 1 month. A mediastinal mass was found by chest radiography. To further evaluate the mass, chest CT was performed and the malignancy was suspected. Staging FDG PET/CT demonstrated a hypermetabolic lesion located in the left middle mediastinum without extra-lesion involvement. The lesion pathologically confirmed mediastinal leiomyosarcoma after surgical resection.
The New Possibility of Lymphoscintigraphy to Guide a Clinical Treatment for Lymphedema in Patient With Breast Cancer
Authors: Seo Kwan Sik , Suh Minseok , Hong Sunmok , Cheon Gi Jeong , Lee Shi-Uk , Jung Gwang Pyo
Published: January 2019

Objectives

Lymphedema is a chronic disease that occurs frequently after breast cancer treatment. For the treatment of lymphedema, surgical approach such as vascularized lymph node transfer and super-microscopic lymphovenous anastomosis surgery is well established. Complex decongestive therapy (CDT) and sympathetic ganglion block (SGB) are two non-surgical therapeutic options. This study aimed to evaluate the effectiveness of lymphoscintigraphy in guiding the selection of the optimal non-surgical treatment in lymphedema.

Methods

A total of 81 lymphedema patients who underwent lymphoscintigraphy and were treated with CDT or SGB were retrospectively evaluated. The parameters for the lymphoscintigraphic findings included the extent of dermal backflow (small extent/large extent groups), the level of lymphatic flow (trunk flow pattern/upper arm-restricted pattern/forearm-restricted pattern groups), and the visualization of lymph nodes (visualized/non-visualized groups). The change in the circumferential difference between the two sides of the body at the upper arm and forearm was used as the clinical outcome variable. Paired comparison and group comparison analysis were conducted.

Results

Of 81 patients, 41 received CDT and 40 received SGB. There were no significant differences in demographic data between the CDT and SGB groups. Both CDT and SGB had a significant therapeutic effect. Upper arm edema was more significantly reduced after SGB than after CDT in the small extent group (P = 0.004), the forearm-restricted pattern group (P = 0.002), and the non-visualized group (P = 0.018). In the other groups, SGB and CDT showed comparable therapeutic effects without statistical differences.

Conclusion

SGB was found to have a better therapeutic effect in the lymphedema patients with specific lymphoscintigraphic findings compared with CDT. Lymphoscintigraphy may be helpful in selecting the appropriate approach to lymphedema treatment. Further well-designed prospective studies are warranted to validate the findings of this study.
Identification of Heterotopic Ossification Using 18F-NaF PET/CT
Authors: Seraj Siavash Mehdizadeh , Al-Zaghal Abdullah , Østergaard Brian , Høilund-Carlsen Poul F. , Alavi Abass
Published: January 2019

Heterotopic ossification (HO) is a benign condition characterized by the abnormal formation of mature lamellar bone in extraskeletal soft tissues. Most frequently, HO is observed around the hip joint after fractures or surgical procedures such as open reduction internal fixation or total hip arthroplasties. We are presenting a case of HO as detected by 18F-NaF PET/CT in a 68-year-old woman with multiple myeloma and a history of internal fixation of the right hip. Many previous publications have reported 18F-NaF uptake portraying calcification in soft tissue; the present report demonstrates the feasibility of 18F-NaF PET/CT to assess extraosseous calcification.
Odontogenic Cysts and Tumors
Authors: Rioux-Forker Dana , Deziel Allyson C. , Williams Larry S. , Muzaffar Arshad R.
Published: January 2019

Odontogenic cysts and tumors are mandibular and maxillary lesions that occur across all patient demographics across age, sex, race, and social economic status, as altered remnants of dental development. They may be incidental findings from routine imaging in any office or found through workup for craniofacial surgery or injury. Many of these patients present with asymptomatic lesions, whereas others may be symptomatic. In this article, we review the literature on the most common odontogenic tumors and cysts and discuss their presentation, their defining traits, and how to approach diagnosis and definitive management.
Advanced Age Impairs Intestinal Antimicrobial Peptide Response and Worsens Fecal Microbiome Dysbiosis Following Burn Injury in Mice
Authors: Wheatley Elizabeth G. , Curtis Brenda J. , Hulsebus Holly J. , Boe Devin M. , Najarro Kevin , Ir Diana , Robertson Charles E. , Choudhry Mashkoor A. , Frank Daniel N. , Kovacs Elizabeth J.
Published: January 2019

Maintenance of the commensal bacteria that comprise the gut microbiome is essential to both gut and systemic health. Traumatic injury, such as burn, elicits a number of changes in the gut, including a shift in the composition of the microbiome (dysbiosis), increased gut leakiness, and bacterial translocation into the lymphatic system and bloodstream. These effects are believed to contribute to devastating secondary complications following burn, including pneumonia, acute respiratory distress syndrome, multi-organ failure, and septic shock. Clinical studies demonstrate that advanced age causes a significant increase in mortality following burn, but the role of the gut in this age-dependent susceptibility has not been investigated. In this study, we combined our well-established murine model of scald burn injury with bacterial 16S-rRNA gene sequencing to investigate how burn injury affects the fecal microbiome in aged versus young mice. Of our treatment groups, the most substantial shift in gut microbial populations was observed in aged mice that underwent burn injury. We then profiled antimicrobial peptides (AMPs) in the ileum, and found that burn injury stimulated a 20-fold rise in levels of regenerating islet-derived protein 3 gamma (Reg3γ), a 16-fold rise in regenerating islet-derived protein 3 beta (Reg3β), and an 8-fold rise in Cathelicidin-related antimicrobial peptide (Cramp) in young, but not aged mice. Advanced age alone elicited 5-fold higher levels of alpha defensin-related sequence1 (Defa-rs1) in the ileum, but this increase was lost following burn. Comparison of bacterial genera abundance and AMP expression across treatment groups revealed distinct correlation patterns between AMPs and individual genera. Our results reveal that burn injury drives microbiome dysbiosis and altered AMP expression in an age-dependent fashion, and highlight potential mechanistic targets contributing to the increased morbidity and mortality observed in elderly burn patients.
The Primary Aldosteronism Surgical Outcome Score for the Prediction of Clinical Outcomes After Adrenalectomy for Unilateral Primary Aldosteronism
Authors: Burrello Jacopo , Burrello Alessio , Stowasser Michael , Nishikawa Tetsuo , Quinkler Marcus , Prejbisz Aleksander , Lenders Jacques W. M. , Satoh Fumitoshi , Mulatero Paolo , Reincke Martin , Williams Tracy Ann
Published: January 2019

Objective:

To develop a prediction model for clinical outcomes after unilateral adrenalectomy for unilateral primary aldosteronism.

Summary Background Data:

Unilateral primary aldosteronism is the most common surgically curable form of endocrine hypertension. Surgical resection of the dominant overactive adrenal in unilateral primary aldosteronism results in complete clinical success with resolution of hypertension without antihypertensive medication in less than half of patients with a wide between-center variability.

Methods:

A linear discriminant analysis model was built using data of 380 patients treated by adrenalectomy for unilateral primary aldosteronism to classify postsurgical clinical outcomes. The total cohort was then randomly divided into training (280 patients) and test (100 patients) datasets to create and validate a score system to predict clinical outcomes. An online tool (Primary Aldosteronism Surgical Outcome predictor) was developed to facilitate the use of the predictive score.

Results:

Six presurgical factors associated with complete clinical success (known duration of hypertension, sex, antihypertensive medication dosage, body mass index, target organ damage, and size of largest nodule at imaging) were selected based on classification performance in the linear discriminant analysis model. A 25-point predictive score was built with an optimal cut-off of greater than 16 points (accuracy of prediction = 79.2%; specificity = 84.4%; sensitivity = 71.3%) with an area under the curve of 0.839.

Conclusions:

The predictive score and the primary aldosteronism surgical outcome predictor can be used in a clinical setting to differentiate patients who are likely to be clinically cured after surgery from those who will need continuous surveillance after surgery due to persistent hypertension.
Local Referral of High-risk Patients to High-quality Hospitals
Authors: Smith Margaret E. , Shubeck Sarah P. , Nuliyalu Ushapoorna , Dimick Justin B. , Nathan Hari
Published: January 2019

Objective:

We sought to assess the potential changes in Medicare payments and clinical outcomes of referring high-risk surgical patients to local high-quality hospitals within small geographic areas.

Summary Background Data:

Previous studies have documented a benefit in referring high-risk patients to high-quality hospitals on a national basis, suggesting selective referral as a mechanism to improve the value of surgical care. Practically, referral of patients should be done within small geographic regions; however, the benefit of local selective referral has not been studied.

Methods:

We analyzed data on elderly Medicare beneficiaries undergoing any of 4 elective inpatient surgical procedures between 2012 and 2014. Hospitals were categorized into Metropolitan Statistical Areas by zip code and stratified into quintiles of quality based on rates of postoperative complications. Patient risk was calculated by modeling the predicted risk of a postoperative complication. Medicare payments for each surgical episode were calculated. Distances between patients’ home zip code and high- and low-quality hospitals were calculated.

Results:

One quarter of high-risk patients underwent surgery at a low-quality hospital despite the availability of a high-quality hospital in their small geographic area. Shifting these patients to a local high-quality hospital would decrease spending 12% to 37% ($2,500 for total knee and hip replacement, $6,700 for colectomy, and $11,400 for lung resection). Approximately 45% of high-risk patients treated at low-quality hospitals could travel a shorter distance to reach a high-quality hospital than the low-quality hospital they received care at.

Conclusions:

Complication rates and Medicare payments are significantly lower for high-risk patients treated at local high-quality hospitals. This suggests triaging high-risk patients to local high-quality hospitals within small geographic areas may serve as a template for improving the value of surgical care.
Australia and New Zealand Islet and Pancreas Transplant Registry Annual Report 2018—Islet Donations, Islet Isolations, and Islet Transplants
Authors: Webster Angela C. , Hedley James A. , Anderson Patricia F. , Hawthorne Wayne J. , Radford Toni , Drogemuller Chris , Rogers Natasha , Goodman David , Lee Melissa H. , Loudovaris Thomas , Kelly Patrick J.
Published: January 2019

Background

This is an excerpt from chapter 4 of the annual registry report from the Australia and New Zealand islet and pancreas transplant registry. The full report is available at http://anziptr.org/reports/.

Methods

We report data for all allogeneic islet isolation and transplant activity from 2002 to end 2017. Solid organ pancreas transplantation activity is reported separately. New Zealand does not have an islet transplant program. Data analysis was performed using Stata software version 14 (StataCorp, College Station, TX).

Results

From 2002 to 2017, a total of 104 allogeneic islet transplants were performed in 62 recipients.

Conclusions

The number of islet transplants performed in Australia was slightly lower in 2017 but continues to increase over time.
Are comorbidities compatible with a molecular pathological classification of neurodegenerative diseases?
Authors: Kovacs Gabor G.
Published: January 2019

Purpose of review

The purpose of this review is to provide an update on comorbidities in neurodegenerative conditions. The term comorbidity is used here to distinguish cases with overlapping pathogenic mechanisms, which includes combinations of neurodegenerative proteinopathies from cases with multimorbidity, which is defined as concomitant brain and systemic disorders with different pathogenic mechanisms.

Recent findings

Comorbid proteinopathies are more frequent in both sporadic and hereditary neurodegenerative diseases than previously assumed. The most frequent additional proteinopathies are related to Alzheimer's disease, Lewy body disorder, and limbic predominant transactive response DNA-binding protein 43 proteinopathy, however, different forms of tau pathologies are also increasingly recognized. In addition to ageing, synergistic interaction of proteins, common disease pathways, and the influence of genetic variations are discussed as possible pathogenic players.

Comorbid proteinopathies might influence the clinical course and have implications for biomarker and therapeutic development. As pure forms of proteinopathies are still observed, the notion of current molecular classification is justified. This corroborates elucidation of various pathogenic pathways leading to neurodegeneration. Assuming that single proteins and associated pathways are targeted in therapy trials, efforts are needed to better stratify patients and to select pure proteinopathy forms lacking unfavorable genetic constellations. Otherwise combined therapeutic strategies might be necessary for comorbid proteinopathies.
Collective ventilation in honeybee nests
Authors: Peters Jacob M. , Peleg Orit , Mahadevan L.
Published: January 2019

European honey bees (Apis mellifera) live in large congested nest cavities with a single opening that limits passive ventilation. When the local air temperature exceeds a threshold, the nests are actively ventilated by bees fanning their wings at the nest entrance. Here, we show that colonies with relatively large nest entrances use an emergent ventilation strategy where fanning bees self-organize to form groups, separating regions of continuous inflow and outflow. The observed spatio-temporal patterns correlate the air velocity and air temperature along the entrances to the distribution of fanning bees. A mathematical model that couples these variables to known fanning behaviour of individuals recapitulates their collective dynamics. Additionally, the model makes predictions about the temporal stability of the fanning group as a function of the temperature difference between the environment and the nest. Consistent with these predictions, we observe that the fanning groups drift, cling to the entrance boundaries, break-up and reform as the ambient temperature varies over a period of days. Overall, our study shows how honeybees use flow-mediated communication to self-organize into a steady state in fluctuating environments.
Assessing the airborne survival of bacteria in populations of aerosol droplets with a novel technology
Authors: Fernandez Mara Otero , Thomas Richard J. , Garton Natalie J. , Hudson Andrew , Haddrell Allen , Reid Jonathan P.
Published: January 2019

The airborne transmission of infection relies on the ability of pathogens to survive aerosol transport as they transit between hosts. Understanding the parameters that determine the survival of airborne microorganisms is critical to mitigating the impact of disease outbreaks. Conventional techniques for investigating bioaerosol longevity
in vitro
have systemic limitations that prevent the accurate representation of conditions that these particles would experience in the natural environment. Here, we report a new approach that enables the robust study of bioaerosol survival as a function of relevant environmental conditions. The methodology uses droplet-on-demand technology for the generation of bioaerosol droplets (1 to greater than 100 per trial) with tailored chemical and biological composition. These arrays of droplets are captured in an electrodynamic trap and levitated within a controlled environmental chamber. Droplets are then deposited on a substrate after a desired levitation period (less than 5 s to greater than 24 h). The response of bacteria to aerosolization can subsequently be determined by counting colony forming units, 24 h after deposition. In a first study, droplets formed from a suspension of
Escherichia coli
MRE162 cells (10
8
ml
−1
) with initial radii of 27.8 ± 0.08 µm were created and levitated for extended periods of time at 30% relative humidity. The time-dependence of the survival rate was measured over a time period extending to 1 h. We demonstrate that this approach can enable direct studies at the interface between aerobiology, atmospheric chemistry and aerosol physics to identify the factors that may affect the survival of airborne pathogens with the aim of developing infection control strategies for public health and biodefence applications.
Force-based three-dimensional model predicts mechanical drivers of cell sorting
Authors: Revell Christopher , Blumenfeld Raphael , Chalut Kevin J.
Published: January 2019

Many biological processes, including tissue morphogenesis, are driven by cell sorting. However, the primary mechanical drivers of sorting in multicellular aggregates (MCAs) remain controversial, in part because there is no appropriate computational model to probe mechanical interactions between cells. To address this important issue, we developed a three-dimensional, local force-based simulation based on the subcellular element method. In our method, cells are modelled as collections of locally interacting force-bearing elements. We use the method to investigate the effects of tension and cell–cell adhesion on MCA sorting. We predict a minimum level of adhesion to produce inside-out sorting of two cell types, which is in excellent agreement with observations in several developmental systems. We also predict the level of tension asymmetry needed for robust sorting. The generality and flexibility of the method make it applicable to tissue self-organization in a myriad of other biological processes, such as tumorigenesis and embryogenesis.
Infrastructure construction without information exchange: the trail clearing mechanism inAttaleafcutter ants
Authors: Bochynek Thomas , Burd Martin , Kleineidam Christoph , Meyer Bernd
Published: January 2019

A wide range of group-living animals construct tangible infrastructure networks, often of remarkable size and complexity. In ant colonies, infrastructure construction may require tens of thousands of work hours distributed among many thousand individuals. What are the individual behaviours involved in the construction and what level of complexity in inter-individual interaction is required to organize this effort? We investigate this question in one of the most sophisticated trail builders in the animal world: the leafcutter ants, which remove leaf litter, cut through overhangs and shift soil to level the path of trail networks that may cumulatively extend for kilometres. Based on obstruction experiments in the field and the laboratory, we identify and quantify different individual trail clearing behaviours. Via a computational model, we further investigate the presence of recruitment, which—through direct or indirect information transfer between individuals—is one of the main organizing mechanisms of many collective behaviours in ants. We show that large-scale transport networks can emerge purely from the stochastic process of workers encountering obstructions and subsequently engaging in removal behaviour with a fixed probability. In addition to such incidental removal, we describe a dedicated clearing behaviour in which workers remove additional obstructions independent of chance encounters. We show that to explain the dynamics observed in the experiments, no information exchange (e.g. via recruitment) is required, and propose that large-scale infrastructure construction of this type can be achieved without coordination between individuals.
Cellular transformation by combined lineage conversion and oncogene expression
Authors: Sahu Biswajyoti , Pihlajamaa Päivi , Zhang Kaiyang , Palin Kimmo , Ahonen Saija , Cervera Alejandra , Ristimäki Ari , Aaltonen Lauri A. , Hautaniemi Sampsa , Taipale Jussi
Published: January 2019

Cancer is the most complex genetic disease known, with mutations implicated in more than 250 genes. However, it is still elusive which specific mutations found in human patients lead to tumorigenesis. Here we show that a combination of oncogenes that is characteristic of liver cancer (CTNNB1, TERT, MYC) induces senescence in human fibroblasts and primary hepatocytes. However, reprogramming fibroblasts to a liver progenitor fate, induced hepatocytes (iHeps), makes them sensitive to transformation by the same oncogenes. The transformed iHeps are highly proliferative, tumorigenic in nude mice, and bear gene expression signatures of liver cancer. These results show that tumorigenesis is triggered by a combination of three elements: the set of driver mutations, the cellular lineage, and the state of differentiation of the cells along the lineage. Our results provide direct support for the role of cell identity as a key determinant in transformation, and establish a paradigm for studying the dynamic role of oncogenic drivers in human tumorigenesis.
Cell aggregation and aerobic respiration facilitate survival of Zymomonas mobilis ZM4 in an aerobic minimal medium
Authors: Jones-Burrage Sara E , Kremer Timothy A , McKinlay James B
Published: January 2019

Zymomonas mobilis produces ethanol from glucose near the theoretical maximum yield, making it a potential alternative to yeast for industrial ethanol production. A potentially useful industrial feature is the ability to form multicellular aggregates called flocs, which can settle quickly and exhibit higher resistance to harmful chemicals. While spontaneous floc-forming Z. mobilis mutants have been described, little is known about the natural conditions that induce Z. mobilis floc formation and the genetic factors involved. Here we found that wild-type Z. mobilis forms flocs in response to aerobic growth conditions but only in a minimal medium. We identified a cellulose synthase gene cluster and a single diguanylate cyclase that are essential for both floc formation and survival in an aerobic minimal medium. We also found that NADH dehydrogenase 2, a key component of the aerobic respiratory chain, is important for survival in an aerobic minimal medium, providing a physiological role for this enzyme which has previously been found to be disadvantageous in aerobic rich media. Supplementation of the minimal medium with vitamins also promoted survival but did not inhibit floc formation.
Maximum entropy models elucidate the contribution of metabolic traits to patterns of community assembly
Authors: Bertram Jason , Newman Erica A , Dewar Roderick
Published: January 2019

Aim: Maximum entropy (MaxEnt) models promise a novel approach for understanding community assembly and species abundance patterns. One of these models, the "Maximum Entropy Theory of Ecology" (METE) reproduces many observed species abundance patterns, but is based on an aggregated representation of community structure that does not resolve species identity or explicitly represent species-specific functional traits. In this paper, METE is compared to "Very Entropic Growth" (VEG), a MaxEnt model with a less aggregated representation of community structure that represents species (more correctly, functional types) in terms of their per capita metabolic rates. We examine the contribution of metabolic traits to the patterns of community assembly predicted by VEG and, through aggregation, compare the results with METE predictions in order to gain insight into the biological factors underlying observed patterns of community assembly. Innovation: We formally compare two MaxEnt-based community models, METE and VEG, that differ as to whether or not they represent species-specific functional traits. We empirically test and compare the metabolic predictions of both models, thereby elucidating the role of metabolic traits in patterns of community assembly. Main Conclusions: Our analysis reveals that a key determinant of community metabolic patterns is the "density of species" distribution, defined as the intrinsic number of species with metabolic rates in a given range that are available to a community prior to filtering by environmental constraints. Our analysis suggests that appropriate choice of of the density of species in VEG may lead to more realistic predictions than METE, for which this distribution is not defined, and thus opens up new ways to understanding the link between functional traits and patterns of community assembly.
Inferring tumor evolution from longitudinal samples
Authors: Myers Matthew A. , Satas Gryte , Raphael Benjamin J.
Published: January 2019

Background: Determining the clonal composition and somatic evolution of a tumor greatly aids in accurate prognosis and effective treatment for cancer. In order to understand how a tumor evolves over time and/or in response to treatment, multiple recent studies have performed longitudinal DNA sequencing of tumor samples from the same patient at several different time points. However, none of the existing algorithms that infer clonal composition and phylogeny using several bulk tumor samples from the same patient integrate the information that these samples were obtained from longitudinal observations. Results: We introduce a model for a longitudinally-observed phylogeny and derive constraints that longitudinal samples impose on the reconstruction of a phylogeny from bulk samples. These constraints form the basis for a new algorithm, Cancer Analysis of Longitudinal Data through Evolutionary Reconstruction (CALDER), which infers phylogenetic trees from longitudinal bulk DNA sequencing data. We show on simulated data that constraints from longitudinal sampling can substantially reduce ambiguity when deriving a phylogeny from multiple bulk tumor samples, each a mixture of tumor clones. On real data, where there is often considerable uncertainty in the clonal composition of a sample, longitudinal constraints yield more parsimonious phylogenies with fewer tumor clones per sample. We demonstrate that CALDER reconstructs more plausible phylogenies than existing methods on two longitudinal DNA sequencing datasets from chronic lymphocytic leukemia patients. These findings show the advantages of directly incorporating temporal information from longitudinal sampling into tumor evolution studies. Availability: CALDER is available at https://github.com/raphael-group.
A chromosome-level genome of black rockfish, Sebastes schlegelii, provides insights into the evolution of live birth
Authors: He Yan , Chang Yue , Bao Lisui , Yu Mengjun , Li Rui , Niu Jingjing , Fan Guangyi , Song Weihao , Seim Inge , Qin Yating , Li Xuemei , Liu Jinxiang , Kong Xiangfu , Peng Meiting , Sun Minmin , Wang Mengya , Qu Jiangbo , Wang Xuangang , Liu Xiaobing , Wu Xiaolong , Zhao Xi , Wang Xuliang , Zhao Yaolei , Guo Jiao , Liu Yang , Liu Kaiqiang , Wang Yilin , Zhang He , Liu Longqi , Wang Mingyue , Yu Haiyang , Wang Xubo , Cheng Jie , Wang Zhigang , Xu Xun , Wang Jian , Yang Huanming , Lee Simon Ming-Yuen , Liu Xin , Zhang Quanqi , Qi Jie
Published: January 2019

Black rockfish (Sebastes schlegelii) is a teleost species where eggs are fertilized internally and retained in the maternal reproductive system, where they undergo development until live birth (termed viviparity). In the present study, we report a chromosome-level black rockfish genome assembly. High-throughput transcriptome analysis (RNA-seq and ATAC-seq), coupled with in situ hybridization (ISH) and immunofluorescence, identify several candidate genes for maternal preparation, sperm storage and release, and hatching. We propose that zona pellucida (ZP) genes retain sperm at the oocyte envelope, while genes in two distinct astacin metalloproteinase subfamilies serve to release sperm from the ZP and free the embryo from chorion at pre-hatching stage. Finally, we present a model of black rockfish reproduction, and propose that the rockfish ovarian wall has a similar function to uterus of mammals. Taken together, these genomic data reveal unprecedented insights into the evolution of an unusual teleost life history strategy, and provide a sound foundation for studying viviparity in non-mammalian vertebrates and an invaluable resource for rockfish ecology and evolution research.
The response to the DNA damaging agent methyl methanesulfonate in a fungal plant pathogen
Authors: Milo Shira , Pareek Manish , Delulio Gregory , Almog Yael , Anand Gautam , Ma Li-Jun , Covo Shay
Published: January 2019

DNA damage can cause mutations that in fungal plant pathogens lead to hypervirulence and resistance to pesticides. Almost nothing is known about the response of these fungi to DNA damage. We performed transcriptomic and phosphoproteomic analyses of Fusarium oxysporum exposed to a DNA alkylating agent (MMS). At the RNA level we observe massive induction of DNA repair pathways; the most surprising is the global genome nucleotide excision repair. Cul3, Cul4, several Ubiquitin-like ligases and other components of the protein degradation machinery are significantly induced. In agreement, we observed drug synergism between a proteasome inhibitor and MMS. While our data suggest that Yap1 and Xbp1 networks are similarly activated in response to damage in yeast and Fusarium we were able to observe Fusarium specific MMS-responsive modules. These include transcription/splicing modules that are upregulated and respiration that is down-regulated. In agreement, MMS treated cells are much more sensitive to a respiration inhibitor. At the phosphoproteomic level, Adenylate cyclase, which generates cAMP, is phosphorylated by MMS and forms a network of phosphorylated proteins that include cell cycle regulators and several MAPK pathways. Recently, there are many attempts to re-sequence isolates of fungal plant pathogens. These attempts often reveal changes in the genomes that may be explained by DNA damage exposure. Our analysis provides an important starting point in understanding how these genomic changes occur.
Linking lineage and population observables in biological branching processes
Authors: García-García Reinaldo , Genthon Arthur , Lacoste David
Published: January 2019

Using a population dynamics inspired by an ensemble of growing cells, a set of fluctuation theorems linking observables measured at the lineage and population levels are derived. One of these relations implies inequalities comparing the population doubling time with the mean generation time at the lineage or population levels. We argue that testing these inequalities provides useful insights into the underlying mechanism controlling the division rate in such branching processes.
Oncogenic Notch promotes long-range regulatory interactions within hyperconnected 3D cliques
Authors: Petrovic Jelena , Zhou Yeqiao , Fasolino Maria , Goldman Naomi , Schwartz Gregory W. , Mumbach Maxwell R. , Nguyen Son C. , Rome Kelly S. , Sela Yogev , Zapataro Zachary , Blacklow Stephen C. , Kruhlak Michael J. , Shi Junwei , Aster Jon C. , Joyce Eric F. , Little Shawn C. , Vahedi Golnaz , Pear Warren S. , Faryabi Robert B.
Published: January 2019

Chromatin loops enable transcription factor-bound distal enhancers to interact with their target promoters to regulate transcriptional programs. Although developmental transcription factors, such as active forms of Notch, can directly stimulate transcription by activating enhancers, the effect of their oncogenic subversion on the 3-dimensional (3D) organization of the cancer genome is largely undetermined. By mapping chromatin looping genome-wide in Notch-dependent triple-negative breast cancer and B-cell lymphoma, we show that far beyond the well-characterized role of Notch as an activator of distal enhancers, Notch regulates its direct target genes through establishing new long-range regulatory interactions. Moreover, a large fraction of Notch-promoted regulatory loops forms highly interacting enhancer and promoter spatial clusters, termed “3D cliques”. Loss-and gain-of-function experiments show that Notch preferentially targets hyperconnected 3D cliques that regulate the expression of crucial proto-oncogenes. Our observations suggest that oncogenic hijacking of developmental transcription factors can dysregulate transcription through widespread effects on the spatial organization of cancer genomes.
Dynamical reorganization of transcriptional events governs robust Nanog heterogeneity
Authors: Samanta Tagari , Kar Sandip
Published: January 2019

Nanog maintains pluripotency of embryonic stem cells (ESC's), while demonstrating high expression heterogeneity within an ESC population. Intriguingly, in ESC's, the overall heterogeneity at the Nanog mRNA level under various culture conditions gets precisely partitioned into intrinsic (~45%) and extrinsic (~55%) fluctuations. However, the dynamical origin of such a robust transcriptional noise regulation, still remains illusive. Herein, we conceived a new stochastic simulation strategy centered around Gillespie's stochastic simulation algorithm to efficiently capture fluctuations of different origins that are operative within a simple Nanog transcriptional regulatory network. Our model simulations reconcile the strict apportioning of Nanog transcriptional fluctuation, while predicting possible experimental scenarios to avoid such an exact noise segregation. Importantly, model analyses reveal that different culture conditions essentially preserve the Nanog expression heterogeneity by altering the dynamics of transcriptional events. These insights will be essential to systematically maneuver cell-fate decision making events of ESC's for therapeutic applications.
A microfluidic device for inferring metabolic landscapes in yeast monolayer colonies
Authors: Marinkovic Zoran S , Vulin Clément , Acman Mislav , Song Xiaohu , Di Meglio Jean Marc , Lindner Ariel B. , Hersen Pascal
Published: January 2019

Microbial colonies are fascinating structures in which growth and internal organization reflect complex morphogenetic processes. Here, we generated a microfluidics device with arrays of long monolayer yeast colonies to further global understanding of how intercellular metabolic interactions affect the internal structure of colonies within defined boundary conditions. We observed the emergence of stable glucose gradients using fluorescently labelled hexose transporters and quantified the spatial correlations with intracolony growth rates and expression of other genes regulated by glucose availability. These landscapes depended on the external glucose concentration as well as secondary gradients, e.g., amino acid availability. This work demonstrates the regulatory genetic networks governing cellular physiological adaptation are the key to internal structuration of cellular assemblies. This approach could be used in the future to decipher the interplay between long-range metabolic interactions, cellular development and morphogenesis in more complex systems.
New modular assays for the quantitative study of skylight navigation in flying flies
Authors: Mathejczyk Thomas , Wernet Mathias F.
Published: January 2019

The quantitative study of visual behaviors using virtual flight arenas is complicated by the fact that an effective experimental setup needs to combine a rather complex set of custom-built mechanical, electronic, and software components. Assembling such an apparatus amounts to a major challenge when working in an environment without the support of a machine shop. Here we present detailed instructions for the assembly of virtual flight arenas optimized forDrosophilaskylight navigation, which can easily be modified towards other uses. This system consists entirely of off-the-shelf parts and 3D-printed components, combining a modular flight arena designed to reduce visual artifacts, swappable high-power LED light sources, polarization filters on a computer-controlled rotating filter wheel, all placed within a temperature and humidity controlled environment. Using this new assay, we show that individual flies choose arbitrary headings when flying under a uniform field of linear polarization. Furthermore, flies adjust their heading to both sudden and continuous changes in filter orientation and can keep their chosen heading for several minutes. Finally, flies show the tendency to maintain headings even after interruption with an unpolarized stimulus. Taken together, these findings demonstrate the usefulness of these assays for the study of skylight navigation in flies.
YAP/TAZ as a Novel Regulator of cell volume
Authors: Perez-Gonzalez Nicolas A. , Rochman Nash D. , Yao Kai , Tao Jiaxiang , Le Minh-Tam Tran , Flanary Shannon , Sablich Lucia , Toler Ben , Crentsil Eliana , Takaesu Felipe , Lambrus Bram , Huang Jessie , Fu Vivian , Holland Andrew J. , An Steven , Wirtz Denis , Guan Kun-Liang , Sun Sean X.
Published: January 2019

How mammalian cells regulate their physical size is currently poorly understood, in part due to the difficulty of accurately quantifying cell volume in a high throughput manner. Here, using the fluorescence exclusion method, we demonstrate that the mechanosensitive transcriptional regulators YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) are novel regulators of single cell volume. We report that the role of YAP/TAZ in cell volume regulation must go beyond its influence on total cell cycle duration or the cell shape to explain the observed changes in volume. Moreover, for our experimental conditions, volume regulation by YAP/TAZ is independent of mTOR. Instead, we find YAP/TAZ directly impacts the cell division volume. Based on the idea that YAP/TAZ is a mechanosensor, we find that inhibiting the assembly of myosin and cell tension slows cell cycle progression from G1 to S. These results suggest that YAP/TAZ and the Hippo pathway may be modulating cell volume in combination with cytoskeletal tension during cell cycle progression.
Insight from electron density and energy framework analysis on the structural features of F
x
-TCNQ (x = 0, 2, 4) family of molecules
Authors: Shukla Rahul , Ruzié Christian , Schweicher Guillaume , Kennedy Alan R. , Geerts Yves H. , Chopra Deepak , Chattopadhyay Basab
Published: January 2019

In this study, the nature and characteristics of the intramolecular and intermolecular interactions in crystal structures of the fluoro-substituted 7,7,8,8-tetracyanoquinodimethane (TCNQ) family of molecules, i.e. F
x
-TCNQ (x = 0, 2, 4), are explored. The molecular geometry of the reported crystal structures is directly dependent on the degree of fluorination in the molecule, which consequently also results in the presence of an intramolecular N[triple-bond]C...F—C π-hole tetrel bond. Apart from this, the energy framework analysis performed along the respective transport planes provides new insights into the energetic distribution in this class of molecules.
Three novel topologically different metal–organic frameworks built from 3-nitro-4-(pyridin-4-yl)benzoic acid
Authors: Qin Tao , Zhang Shunlin , Wang Yixiong , Hou Tianjiao , Zhu Dunru , Jing Su
Published: January 2019

The design and synthesis of metal–organic frameworks (MOFs) have attracted much interest due to the intriguing diversity of their architectures and topologies. However, building MOFs with different topological structures from the same ligand is still a challenge. Using 3-nitro-4-(pyridin-4-yl)benzoic acid (HL) as a new ligand, three novel MOFs, namely poly[[(N,N-dimethylformamide-κO)bis[μ2-3-nitro-4-(pyridin-4-yl)benzoato-κ3
O,O′:N]cadmium(II)] N,N-dimethylformamide monosolvate methanol monosolvate], {[Cd(C12H7N2O4)2(C3H7NO)]·C3H7NO·CH3OH}
n
, (1), poly[[(μ2-acetato-κ2
O:O′)[μ3-3-nitro-4-(pyridin-4-yl)benzoato-κ3
O:O′:N]bis[μ3-3-nitro-4-(pyridin-4-yl)benzoato-κ4
O,O′:O′:N]dicadmium(II)] N,N-dimethylacetamide disolvate monohydrate], {[Cd2(C12H7N2O4)3(CH3CO2)]·2C4H9NO·H2O}
n
, (2), and catena-poly[[[diaquanickel(II)]-bis[μ2-3-nitro-4-(pyridin-4-yl)benzoato-κ2
O:N]] N,N-dimethylacetamide disolvate], {[Ni(C12H7N2O4)2(H2O)2]·2C4H9NO}
n
, (3), have been prepared. Single-crystal structure analysis shows that the CdII atom in MOF (1) has a distorted pentagonal bipyramidal [CdN2O5] coordination geometry. The [CdN2O5] units as 4-connected nodes are interconnected by L
− ligands to form a fourfold interpenetrating three-dimensional (3D) framework with a dia topology. In MOF (2), there are two crystallographically different CdII ions showing a distorted pentagonal bipyramidal [CdNO6] and a distorted octahedral [CdN2O4] coordination geometry, respectively. Two CdII ions are connected by three carboxylate groups to form a binuclear [Cd2(COO)3] cluster. Each binuclear cluster as a 6-connected node is further linked by acetate groups and L
− ligands to produce a non-interpenetrating 3D framework with a pcu topology. MOF (3) contains two crystallographically distinct NiII ions on special positions. Each NiII ion adopts an elongated octahedral [NiN2O4] geometry. Each NiII ion as a 4-connected node is linked by L
− ligands to generate a two-dimensional network with an sql topology, which is further stabilized by two types of intermolecular OW—HW...O hydrogen bonds to form a 3D supramolecular framework. MOFs (1)–(3) were also characterized by powder X-ray diffraction, IR spectroscopy and thermogravimetic analysis. Furthermore, the solid-state photoluminescence of HL and MOFs (1) and (2) have been investigated. The photoluminescence of MOFs (1) and (2) are enhanced and red-shifted with respect to free HL. The gas adsorption investigation of MOF (2) indicates a good separation selectivity (71) of CO2/N2 at 273 K (i.e. the amount of CO2 adsorption is 71 times higher than N2 at the same pressure).
High-resolution structure of a Y27W mutant of the Dishevelled2 DIX domain
Authors: Yamanishi Kumpei , Sin Yooksil , Terawaki Shin-ichi , Higuchi Yoshiki , Shibata Naoki
Published: January 2019

Dishevelled (Dvl) is a positive regulator of the canonical Wnt pathway that downregulates the phosphorylation of β-catenin and its subsequent degradation. Dvl contains an N-terminal DIX domain, which is involved in its homooligomerization and interactions with regulators of the Wnt pathway. The crystal structure of a Y27W mutant of the Dishevelled2 DIX domain (DIX-Y27W) has been determined at 1.64 Å resolution. DIX-Y27W has a compact ubiquitin-like fold and self-associates with neighbouring molecules through β-bridges, resulting in a head-to-tail helical molecular arrangement similar to previously reported structures of DIX domains. Glu23 of DIX-Y27W forms a hydrogen bond to the side chain of Trp27, corresponding to the Glu762...Trp766 hydrogen bond of the rat Axin DIX domain, whereas Glu23 in the Y27D mutant of the Dishevelled2 DIX domain forms a salt bridge to Lys68 of the adjacent molecule. The high-resolution DIX-Y27W structure provides details of the head-to-tail interaction, including solvent molecules, and also the plausibly wild-type-like structure of the self-association surface compared with previously published Dvl DIX-domain mutants.
Synthesis, molecular and crystal structure of 1-(1,2-dihydrophthalazin-1-ylidene)-2-[1-(thiophen-2-yl)ethylidene]hydrazine
Authors: Majoumo-Mbe Felicite , Ngwang Nfor Emmanuel , Kenfack Tsobnang Patrice , Nguepmeni Eloundou Valoise Brenda , Ngwain Yong Joseph , Iris Efeti Ikome
Published: January 2019

The title compound, C14H12N4S, was synthesized by the condensation reaction of hydralazine and 2-acetylthiophene and during the reaction, a proton transfer from the imino nitrogen atom to one of the endocylic nitrogen atoms occurred. The compound crystallizes in the monoclinic crystal system with two independent molecules (molecules 1 and 2) in the asymmetric unit. In each molecule, there is a slight difference in the orientation of the thiophene ring with respect to phthalazine ring system, molecule 1 showing a dihedral angle of 42.51 (1)° compared to 8.48 (1)° in molecule 2. This implies an r.m.s deviation of 0.428 (1) Å between the two molecules for the 19 non-H atoms. The two independent molecules are connectedviatwo N—H...N hydrogen bonds, forming dimers which interact by two bifurcated π–π stacking interactions to build tetrameric motifs. The latter are packed in theacplaneviaweak C—H...π interactions and along thebaxisviaC—H ...N and C—H...π interactions. This results a three-dimensional architecture with a tilted herringbone packing mode.