bluuebunny/crossref_metadata_2025 huggingface dataset:
Bureaucratic Policymaking on Natural Hazards
Authors: Taylor Kristin
Published: May 2018

Bureaucratic politics, discretion, and decision-making for natural hazards governance present an important challenge of the use of autonomous bureaucratic discretion in the absence of political accountability. Understanding how these factors influence discretion and policymaking is of critical importance for natural hazards because the extent to which bureaucrats are able to make decisions means that communities will be safer in the face of disaster. But the extent to which they are held accountable for their decisions has significant implications for public risk and safety. Bureaucrats are unelected and cannot be voted out of office.

There are two significant areas that remain regarding the use of bureaucratic discretion in natural hazards policy. One key area is to consider the increasing emphasis on networked disaster governance on bureaucratic discretion and decision-making. The conventional wisdom is that networks facilitate disaster management much better than command and control approaches. However, the extent to which the use of bureaucratic discretion is important in the implementation of natural hazard policy, particularly for mitigation and preparedness, remains an open area of research.

The other key area is the influence of bureaucratic discretion and decision-making when communities learn after a disaster. The political nature of disasters and the professional expertise of public service professionals imply that in order to make communities safer, bureaucrats will have to use discretion to push forward more aggressive mitigation and preparedness policies. Bureaucratic discretion would need to be used for both political and policy purposes in order to engage in policy learning after disasters that produces a substantive change.
History of Agriculture in the United States
Authors: Riney-Kehrberg Pamela
Published: May 2018

Agriculture is at the very center of the human enterprise; its trappings are in evidence all around, yet the agricultural past is an exceptionally distant place from modern America. While the majority of Americans once raised a significant portion of their own food, that ceased to be the case at the beginning of the 20th century. Only a very small portion of the American population today has a personal connection to agriculture. People still must eat, but the process by which food arrives on their plates is less evident than ever. The evolution of that process, with all of its many participants, is the stuff of agricultural history. The task of the agricultural historian is to make that past evident, and usable, for an audience that is divorced from the production of food. People need to know where their food comes from, past and present, and what has gone into the creation of the modern food system.
ProteomeVis: a web app for exploration of protein properties from structure to sequence evolution across organisms’ proteomes
Authors: Razban Rostam M , Gilson Amy I , Durfee Niamh , Strobelt Hendrik , Dinkla Kasper , Choi Jeong-Mo , Pfister Hanspeter , Shakhnovich Eugene I
Published: May 2018

Motivation

Protein evolution spans time scales and its effects span the length of an organism. A web app named ProteomeVis is developed to provide a comprehensive view of protein evolution in the Saccharomyces cerevisiae and Escherichia coli proteomes. ProteomeVis interactively creates protein chain graphs, where edges between nodes represent structure and sequence similarities within user-defined ranges, to study the long time scale effects of protein structure evolution. The short time scale effects of protein sequence evolution are studied by sequence evolutionary rate (ER) correlation analyses with protein properties that span from the molecular to the organismal level.

Results

We demonstrate the utility and versatility of ProteomeVis by investigating the distribution of edges per node in organismal protein chain universe graphs (oPCUGs) and putative ER determinants. S.cerevisiae and E.coli oPCUGs are scale-free with scaling constants of 1.79 and 1.56, respectively. Both scaling constants can be explained by a previously reported theoretical model describing protein structure evolution. Protein abundance most strongly correlates with ER among properties in ProteomeVis, with Spearman correlations of –0.49 (P-value < 10−10) and –0.46 (P-value < 10−10) for S.cerevisiae and E.coli, respectively. This result is consistent with previous reports that found protein expression to be the most important ER determinant.

Availability and implementation

ProteomeVis is freely accessible at http://proteomevis.chem.harvard.edu.

Supplementary information

Supplementary data are available at Bioinformatics online.
Persistent Plasmodium falciparum Infection in Women With an Intent to Become Pregnant as a Risk Factor for Pregnancy-associated Malaria
Authors: Tuikue Ndam Nicaise , Tornyigah Bernard , Dossou Akpéyédjé Yannelle , Escriou Guillaume , Nielsen Morten A , Salanti Ali , Issifou Saadou , Massougbodji Achille , Chippaux Jean-Philippe , Deloron Philippe
Published: May 2018

Background

Pregnant women are more susceptible to Plasmodium falciparum than before pregnancy, and infection has consequences for both mother and offspring. The World Health Organization recommends that pregnant woman in areas of transmission receive intermittent preventive treatment (IPTp) starting in the second trimester. Consequently, women are not protected during the first trimester, although P. falciparum infections are both frequent and harmful.

Methods

A cohort of nulligravid women was followed up during subsequent pregnancy. Malaria was diagnosed by means of microscopy and polymerase chain reaction. Parasites were genotyped at polymorphic loci.

Results

Among 275 nulligravidae enrolled, 68 women became pregnant and were followed up during pregnancy. Before pregnancy, P. falciparum prevalence rates were 15% by microscopy and 66% by polymerase chain reaction. Microscopic infection rates increased to 29% until IPTp administration, and their density increased by 20-fold. Conversely, submicroscopic infection rates decreased. After IPTp administration, all types of infections decreased, but they increased again late in pregnancy. The risk of infection during pregnancy was higher in women with a microscopic (odds ratio, 6.5; P = .047) or submicroscopic (3.06; P = .05) infection before pregnancy and was not related to the season of occurrence. Most infections during pregnancy were persistent infections acquired before pregnancy.

Conclusions

Microscopic and submicroscopic malaria infections were frequent in nulligravid women from south Benin. During the first trimester of pregnancy, microscopic infections were more frequent, with a higher parasite density, and mainly derived from parasites infecting the woman before conception. Preventive strategies targeting nonpregnant women with a desire for conception need to be designed.
Effects of sucroferric oxyhydroxide and sevelamer carbonate on chronic kidney disease–mineral bone disorder parameters in dialysis patients
Authors: Ketteler Markus , Sprague Stuart M , Covic Adrian C , Rastogi Anjay , Spinowitz Bruce , Rakov Viatcheslav , Walpen Sebastian , Floege Jürgen
Published: May 2018

Background

Treatment of hyperphosphataemia is the primary goal of chronic kidney disease–mineral and bone disorder (CKD-MBD) management. This post hoc analysis of a randomized, Phase 3 study evaluated the effects of 1-year treatment with the phosphate binders sucroferric oxyhydroxide or sevelamer carbonate (‘sevelamer’) on CKD-MBD indices among dialysis patients with hyperphosphataemia.

Methods

After a 2- to 4-week washout from previous phosphate binders, 1059 patients were randomized 2:1 to sucroferric oxyhydroxide 1.0–3.0 g/day (n = 710) or sevelamer 2.4–14.4 g/day (n = 349) for up to 24 weeks. Eligible patients enrolled in a 28-week extension. This post hoc analysis was performed for patients who completed ≥1 year of continuous treatment (n = 549). As the treatment groups showed similar CKD-MBD outcomes, the data were pooled for this analysis.

Results

Phosphate-binder therapy was associated with significant and sustained 30% reductions in serum phosphorus (P < 0.001). Median intact fibroblast growth factor-23 (FGF-23) also significantly decreased (P < 0.001) by 64% over 1 year. Intact parathyroid hormone decreased significantly after 24 weeks (P < 0.001), but levels returned to near baseline values by Week 52; minimal changes in serum calcium were observed. Of the bone resorption markers evaluated, tartrate-resistant acid phosphatase 5b (TRAP5b) decreased significantly (P < 0.001), whereas CTx increased transiently but returned to baseline levels by Week 52. The bone formation markers bone-specific alkaline phosphatase and osteocalcin both increased over 1 year of treatment.

Conclusions

Overall, 1 year of sucroferric oxyhydroxide or sevelamer treatment significantly reduced serum FGF-23, which has been associated with clinical benefit in patients with CKD. The trend towards increased bone formation marker levels indicates a beneficial effect on bone metabolism.
Transportation of cull sows-a descriptive study of the clinical condition of cull sows before transportation to slaughter
Authors: Fogsgaard Katrine K , Herskin Mette S , Thodberg Karen
Published: May 2018

Each year 500.000 sows, equal to 50% of Danish sows, are culled and transported to slaughter. However, the clinical condition, behavior, and welfare of cull sows have received almost no scientific attention. The aim of the current observational study was to describe the clinical condition of cull sows on the day of transportation to slaughter, including examination of possible differences between lactating and nonlactating sows. On the day of transportation, the participating farms were visited by trained technicians who conducted a thorough clinical examination of all sows selected by the farmer for slaughter. Four sows could not be transported because they were unfit according to the European Council Regulation regarding fitness for transportation, and they were not included in the present data. A total of 522 sows, with a median parity of 5 (range: 1–11), from 12 Danish farms were included in the study. Approximately, 10% showed signs of changed gait, and 0.8% were obvious lame. Wounds were observed in 54.6% of the sows, and 11% had decubital shoulder ulcers. Almost 40% of the cull sows were lactating. At culling, the lactating sows were of higher parity than the nonlactating sows, and lactating sows were at higher risk of having deviations from normal on clinical variables related to examination of the udder, such as udder swellings and inflammations. Nonlactating sows had 3.5 times more superficial skin lesions than lactating sows. Our findings warrant for further studies exploring different aspects of the life of cull sows in what is here defined as the The Cull Period, which is the interval from the culling decision is made until the sows are slaughtered
Characteristics and Prognostic Factors of Bone Metastasis in Patients With Colorectal Cancer
Authors: Kawamura Hidetaka , Yamaguchi Tatsuro , Yano Yuuta , Hozumi Takahiro , Takaki Yasunobu , Matsumoto Hiroshi , Nakano Daisuke , Takahashi Keiichi
Published: May 2018

BACKGROUND:

Because bone metastasis from colorectal cancer is rare, there are little available data regarding such cases.

OBJECTIVE:

The study aim was to identify the prognostic factors and characteristics associated with survival in colorectal cancer patients with bone metastasis.

DESIGN:

This was a retrospective study from a prospectively collected database.

SETTINGS:

The study took place in a multidisciplinary, high-volume tertiary cancer center in Japan.

PATIENTS:

Examined were records from 104 consecutive patients treated between 2004 and 2015 for bone metastasis from colorectal cancer.

MAIN OUTCOME MEASURES:

The primary outcome measure was overall survival.

RESULTS:

The spine was the most common site of bone metastasis from colorectal cancer. Right colon cancer correlated significantly with long bone metastasis (p = 0.046), whereas left colon cancer correlated significantly with spinal bone metastasis (p = 0.034). Liver metastasis was also significantly correlated with spinal bone metastasis (p = 0.036). The median interval between the primary therapy for colorectal cancer and the metachronous diagnosis of bone metastasis was 20.0 months (quartile 1 to quartile 3, 9.0–46.5 mo). The median survival time from diagnosis of bone metastasis from colorectal cancer was 5.0 months (95% CI, 4.0–9.0 mo), and the 1-year survival rate was 30.0% (95% CI, 21.1%–39.4%). Multivariate analysis revealed that ≥2 extra-bone metastatic organs, hypercalcemia, and pathologic fractures were independent poor prognostic factors (p < 0.001, 0.001, and 0.033). The number of extra-bone metastatic organs correlated with prognosis.

LIMITATIONS:

This study was limited by its retrospective, nonrandomized design, as well as selection bias and performance at a single institute.

CONCLUSIONS:

The location of colorectal cancer correlates significantly with the site of bone metastasis; the prognosis of patients with bone metastasis from colorectal cancer is very poor, and the significant prognostic factors are number of extra-bone metastatic organs, hypercalcemia, and pathologic fractures. See Video Abstract at http://links.lww.com/DCR/A589.
An Optimal Orthotopic Mouse Model for Human Colorectal Cancer Primary Tumor Growth and Spontaneous Metastasis
Authors: Hite Nathan , Klinger Aaron , Hellmers Linh , Maresh Grace A. , Miller Peter E. , Zhang Xin , Li Li , Margolin David A.
Published: May 2018

BACKGROUND:

Colorectal cancer is a leading cause of cancer-related death. Small animal models allow for the study of different metastatic patterns, but an optimal model for metastatic colorectal cancer has not been established.

OBJECTIVE:

The purpose of this study was to determine which orthotopic model most accurately emulates the patterns of primary tumor growth and spontaneous liver and lung metastases seen in patients with colorectal cancer.

DESIGN:

Using luciferase-tagged HT-29 cells coinoculated with lymph node stromal analog HK cells, 3 tumor cell delivery models were compared: intrarectal injection, intracecal injection, and acid enema followed by cancer cell instillation. Tumor growth was monitored weekly by bioluminescent imaging, and mice were sacrificed based on primary tumor size or signs of systemic decline. Liver and lungs were evaluated for metastases via bioluminescent imaging and histology.

SETTINGS:

The study was conducted at a single university center.

MAIN OUTCOME MEASURES:

Primary tumor and metastasis bioluminescent imaging were measured.

RESULTS:

Intrarectal injection had the lowest mortality at 4.0% (1/25) compared with the intracecal group at 17.4% (4/23) and the acid enema followed by cancer cell instillation group at 15.0% (3/20).The primary tumors in intrarectal mice had the highest average bioluminescence (3.78 × 1010 ± 4.94 × 1010 photons) compared with the mice in the intracecal (9.52 × 109 ± 1.92 × 1010 photons; p = 0.012) and acid enema followed by cancer cell instillation groups (6.23 × 108 ± 1.23 × 109 photons; p = 0.0016). A total of 100% of intrarectal and intracecal mice but only 35% of mice in the acid enema followed by cancer cell instillation group had positive bioluminescent imaging before necropsy. Sixty percent of intrarectal mice had liver metastases, and 56% had lung metastases. In the intracecal group, 39% of mice had liver metastases, and 35% had lung metastases. Only 2 acid enema followed by cancer cell instillation mice developed metastases.

LIMITATIONS:

Tumor injections were performed by multiple investigators. Distant metastases were confirmed, but local lymph node status was not evaluated.

CONCLUSIONS:

Intrarectal injection is the safest, most reproducible, and successful orthotopic mouse model for human colorectal cancer primary tumor growth and spontaneous metastasis.
Stimulus-Induced Rhythmic, Periodic, or Ictal Discharges (SIRPIDs)
Authors: Johnson Emily L. , Kaplan Peter W. , Ritzl Eva K.
Published: May 2018

Stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs) are a relatively common phenomenon found on prolonged electroencephalogram (EEG) monitoring that captures state changes and stimulation of critically ill patients. Common causes include hypoxic injury, traumatic brain injury, and hemorrhage, as well as toxic-metabolic disturbances. Some studies have shown an association between SIRPIDs and the presence of spontaneous electrographic seizures. Although the degree to which SIRPIDs should be treated with antiepileptic medications is unknown, the rare cases of functional imaging obtained in patients with SIRPIDs have not shown an increase in cerebral blood flow to suggest an active ictal process. Stimulus-induced rhythmic, periodic, or ictal discharges may reflect dysregulation of thalamo-cortical projections into abnormal or hyperexcitable cortex.
Lateralized Periodic Discharges: A Literature Review
Authors: Lin Lu , Drislane Frank W.
Published: May 2018

The purpose of this article is to provide a comprehensive review of the literature about a particular EEG pattern, lateralized periodic discharges (LPDs), or periodic lateralized epileptiform discharges (PLEDs). The review will discuss the history and terminology of LPDs and provide a detailed summary of the etiologies, pathophysiology, clinical symptoms, and imaging studies related to LPDs. Current controversies about the association of LPDs with seizures and their management will be reviewed. Finally, some unanswered questions and suggestions for future research on LPDs will be discussed.
Benchmarking cryo-EM single particle analysis workflow
Authors: Kim Laura Y. , Rice William J. , Eng Edward T. , Kopylov Mykhailo , Cheng Anchi , Raczkowski Ashleigh M. , Jordan Kelsey D. , Bobe Daija , Potter Clinton S. , Carragher Bridget
Published: May 2018

Cryo electron microscopy facilities running multiple instruments and serving users with varying skill levels need a robust and reliable method for benchmarking both the hardware and software components of their single particle analysis workflow. The workflow is complex, with many bottlenecks existing at the specimen preparation, data collection and image analysis steps; the samples and grid preparation can be of unpredictable quality, there are many different protocols for microscope and camera settings, and there is a myriad of software programs for analysis that can depend on dozens of settings chosen by the user. For this reason, we believe it is important to benchmark the entire workflow, using a standard sample and standard operating procedures, on a regular basis. This provides confidence that all aspects of the pipeline are capable of producing maps to high resolution. Here we describe benchmarking procedures using a test sample, rabbit muscle aldolase.
3D Shape Modeling for Cell Nuclear Morphological Analysis and Classification
Authors: Kalinin Alexandr A. , Allyn-Feuer Ari , Ade Alex , Fon Gordon-Victor , Meixner Walter , Dilworth David , Husain Syed S. , de Wet Jeffrey R. , Higgins Gerald A. , Zheng Gen , Creekmore Amy , Wiley John W. , Verdone James E. , Veltri Robert W. , Pienta Kenneth J. , Coffey Donald S. , Athey Brian D. , Dinov Ivo D.
Published: May 2018

Quantitative analysis of morphological changes in a cell nucleus is important for the understanding of nuclear architecture and its relationship with pathological conditions such as cancer. However, dimensionality of imaging data, together with a great variability of nuclear shapes, presents challenges for 3D morphological analysis. Thus, there is a compelling need for robust 3D nuclear morphometric techniques to carry out population-wide analysis. We propose a new approach that combines modeling, analysis, and interpretation of morphometric characteristics of cell nuclei and nucleoli in 3D. We used robust surface reconstruction that allows accurate approximation of 3D object boundary. Then, we computed geometric morphological measures characterizing the form of cell nuclei and nucleoli. Using these features, we compared over 450 nuclei with about 1,000 nucleoli of epithelial and mesenchymal prostate cancer cells, as well as 1,000 nuclei with over 2,000 nucleoli from serum-starved and proliferating fibroblast cells. Classification of sets of 9 and 15 cells achieved accuracy of 95.4% and 98%, respectively, for prostate cancer cells, and 95% and 98% for fibroblast cells. To our knowledge, this is the first attempt to combine these methods for 3D nuclear shape modeling and morphometry into a highly parallel pipeline workflow for morphometric analysis of thousands of nuclei and nucleoli in 3D.
A conserved glycine harboring disease-associated mutations is required for slow deactivation and high Ca2+ permeability in NMDA receptors
Authors: Amin Johansen B. , Leng Xiaoling , Gochman Aaron , Zhou Huan-Xiang , Wollmuth Lonnie P.
Published: May 2018

A variety of de novo and inherited missense mutations associated with neurological disorders are found in the NMDA receptor M4 transmembrane helices, which are peripheral to the pore domain in eukaryotic ionotropic glutamate receptors. Subsets of these mutations affect receptor gating with dramatic effects, including in one instance halting it, occurring at a conserved glycine near the extracellular end of M4. Functional experiments and molecular dynamic simulations of constructs with and without substitutions at this glycine indicate that it acts as a hinge, permitting the intracellular portion of the ion channel to laterally expand. This expansion stabilizes long-lived open states leading to slow deactivation and high Ca2+ permeability. Our studies provide a functional and structural framework for the effect of missense mutations on NMDARs at central synapses and highlight how the M4 segment may represent a pathway for intracellular modulation of NMDA receptor function.
An ancestral role of pericentrin in centriole formation through SAS-6 recruitment
Authors: Ito Daisuke , Zitouni Sihem , Jana Swadhin Chandra , Duarte Paulo , Surkont Jaroslaw , Carvalho-Santos Zita , Pereira-Leal Jose B. , Godinho Ferreira Miguel , Bettencourt-Dias Monica
Published: May 2018

The centrosome is composed of two centrioles surrounded by a microtubule-nucleating pericentriolar matrix (PCM). Centrioles regulate matrix assembly. Here we ask whether the matrix also regulates centriole assembly. To define the interaction between the matrix and individual centriole components, we take advantage of a heterologous expression system using fission yeast. Importantly, its centrosome, the spindle pole body (SPB), has matrix but no centrioles. Surprisingly, we observed that the SPB can recruit several animal centriole components. Pcp1/pericentrin, a conserved matrix component that is often upregulated in cancer, recruits a critical centriole constituent, SAS-6. We further show that this novel interaction is conserved and important for centriole biogenesis and elongation in animals. We speculate that the Pcp1/pericentrin-SAS-6 interaction surface was conserved for one billion years of evolution after centriole loss in yeasts, due to its conserved binding to calmodulin. This study reveals an ancestral relationship between pericentrin and the centriole, where both regulate each other assembly, ensuring mutual localisation.
Self-organization of Plk4 regulates symmetry breaking in centriole duplication
Authors: Yamamoto Shohei , Kitagawa Daiju
Published: May 2018

During centriole duplication, a single daughter centriole is formed near the mother centriole. The mechanism that determines a single duplication site is unknown. Here, we demonstrate that intrinsic self-organization of Plk4 underlies symmetry breaking in centriole duplication. We show that in its nonphosphorylated state, Plk4 preferentially self-assembles via a disordered linker and that this self-assembly is prevented by autophosphorylation. Consistently, the dissociation dynamics of centriolar Plk4 are controlled by autophosphorylation. We further found that autophophorylated Plk4 is localized as a single focus around the mother centriole before procentriole formation, and is subsequently targeted for STIL-HsSAS6 loading. Perturbing Plk4 self-organization affects the asymmetry of centriolar Plk4 distribution and centriole duplication. We propose that the spatial patterning of Plk4 directs a single duplication site per mother centriole.
Water motion as a transformation mechanism of algal communities structure in Lake Baikal
Authors: Kravtsova Lyubov S. , Mizandrontse Igor B. , Vorobyova Svetlana S. , Izhboldina Lyudmila A. , Mincheva Elena V. , Potyomkina Tatyana G. , Triboy Tatyana I. , Khanaev Igor V. , Sherbakovv Dmitry Yu. , Fedotov Andrey P.
Published: May 2018

The diversity of algal communities of phytoplankton and meio-and macrophytes was investigated in Lake Baikal. Fragments ofSpirogyrathallomes were recorded in the phytoplankton community of Southern Baikal, which had never been recorded before in its composition. It was also established that the structure of benthic algal communities changed in comparison with that in 2000 due to intense development of filamentous algae, particularlySpirogyra. Its lowest biomass was recorded in the surf zone and wave breaking, whereas the highest biomass was registered in the area of weakened effect of waves on the bottom. The cover percent of the bottom with filamentous algae in different areas of the coastal zone varied from 0 to 100%. Hydraulic characteristics ofSpirogyrawere the same as those of planktonic diatoms. The circulation currents and wave effect on the bottom favoured transfer and distribution ofSpirogyrafrom the location of its intense development into the coastal area of Lake Baikal.
Polymer translocation through nano-pores: influence of pore and polymer deformation
Authors: Shahzad M. A.
Published: May 2018

We have simulated polymer translocation across the a α-hemolysin nano-pore via a coarse grained computational model for both the polymer and the pore. We simulate the translocation process by allowing the protein cross a free-energy barrier from a metastable state, in the presence of thermal fluctuations. The deformation in the channel, which we model by making the radius of pore change from large to small size, can be originated by the random and non-random (systematic) cellular environment, drive out the polymer out of equilibrium during the transport dynamics. We expect that in more realistic conditions, effects originating on the translocation phenomena due to the deformability of the nano-pore can either decrease or increase the transport time of biomolecule passing through the channel. Deformation in channel can occurred because the structure of α-hemolysin channel is not completely immobile, hence a small pore deformation can be occurred during translocation process. We also discuss the effects of polymer deformation on the translocation process, which we achieve by varying the value of the empirical and dihedral potential constants. We investigate the dynamic and thermodynamical properties of the translocation process by revealing the statistics of translocation time as a function of the pulling inward force acting along the axis of the pore under the influence of small and large pore. We observed that a pore with small size can speed down the polymer translocation process, especially at the limit of small pulling force. A drastic increase in translocation time at the limit of low force for small pore clearly illustrate the strong interaction between the transport polymer and pore. Our results can be of fundamental importance for those experiments on DNA-RNA sorting and sequencing and drug delivery mechanism for anti-cancer therapy.
Genomic analysis of EuropeanDrosophila melanogasterpopulations reveals longitudinal structure, continent-wide selection, and previously unknown DNA viruses
Authors: Kapun Martin , Barrón Maite G. , Staubach Fabian , Obbard Darren J. , Wiberg R. Axel W. , Vieira Jorge , Goubert Clément , Rota-Stabelli Omar , Kankare Maaria , Bogaerts-Márquez María , Haudry Annabelle , Waidele Lena , Kozeretska Iryna , Pasyukova Elena G. , Loeschcke Volker , Pascual Marta , Vieira Cristina P. , Serga Svitlana , Montchamp-Moreau Catherine , Abbott Jessica , Gibert Patricia , Porcelli Damiano , Posnien Nico , Sánchez-Gracia Alejandro , Grath Sonja , Sucena Élio , Bergland Alan O. , Guerreiro Maria Pilar Garcia , Onder Banu Sebnem , Argyridou Eliza , Guio Lain , Schou Mads Fristrup , Deplancke Bart , Vieira Cristina , Ritchie Michael G. , Zwaan Bas J. , Tauber Eran , Orengo Dorcas J. , Puerma Eva , Aguadé Montserrat , Schmidt Paul S. , Parsch John , Betancourt Andrea J. , Flatt Thomas , González Josefa
Published: May 2018

Genetic variation is the fuel of evolution, with standing genetic variation especially important for short-term evolution and local adaptation. To date, studies of spatio-temporal patterns of genetic variation in natural populations have been challenging, as comprehensive sampling is logistically difficult, and sequencing of entire populations costly. Here, we address these issues using a collaborative approach, sequencing 48 pooled population samples from 32 locations, and perform the first continent-wide genomic analysis of genetic variation in EuropeanDrosophila melanogaster. Our analyses uncover longitudinal population structure, provide evidence for continent-wide selective sweeps, identify candidate genes for local climate adaptation, and document clines in chromosomal inversion and transposable element frequencies. We also characterise variation among populations in the composition of the fly microbiome, and identify five new DNA viruses in our samples.
Response to “No evidence of functional co-adaptation between clustered microRNAs”
Authors: Wang Yirong , Zhang Hong , Lu Jian
Published: May 2018

microRNAs (miRNAs) are a class of endogenously expressed small non-coding RNAs that regulate target genes at the post-transcriptional level. One significant feature of miRNA is that their genomic locations are often clustered together in the genome. In a previous study (Wang, et al. 2016), we proposed a “functional co-adaptation” model to explain how clustering helps new miRNAs survive and develop functions during long-term evolution. In a manuscript recently posted at bioRxiv (doi:10.1101/274811), Marco claimed that he re-analyzed our data and came to a different conclusion. However, we found his analyses were conducted in an inappropriate approach. He also claimed that the absence of substitution in highly conserved miRNAs does not support the “functional co-adaption” model based on the misunderstanding of our model. In summary, the analyses and claims of Marco, which are flawed, do not refute our model.
DUSP28 is a novel biomarker responsible for aggravating malignancy via the autocrine signaling pathways in metastatic pancreatic cancer
Authors: Lee Jungwhoi , Lee Jungsul , Choi Chulhee , Kim Jae Hoon
Published: May 2018

Pancreatic cancer remains one of the most dangerous cancers with a grave prognosis. We previously reported that pancreatic cancer cells can secrete dual specificity phosphatise 28 (DUSP28) to the cultured medium. However, its biological function is poorly understood. Here, we have identified the function of DUSP28 in human metastatic pancreatic cancer. Treatment with recombinant DUSP28 (rDUSP28) significantly increased the migration, invasion, and viability of metastatic pancreatic cancer cells through the activation of CREB, AKT, and ERK1/2 signaling pathways. Furthermore, rDUSP28 acted as an oncogenic reagent through the interaction with integrin α1 in metastatic pancreatic cancer cells. In addition, rDUSP28 induced pro-angiogenic effects in human umbilical vein endothelial cells (HUVECs). Administration of rDUSP28 also produced tumor growth in vivo. Notably, sDUSP28 can easily be detected by immunoassay. The results establish the rationale for sDUSP28 as a promising therapeutic target and biomarker for metastatic pancreatic cancer patients.
Automated cellular structure extraction in biological images with applications to calcium imaging data
Authors: Mishne Gal , Coifman Ronald R. , Lavzin Maria , Schiller Jackie
Published: May 2018

Recent advances in experimental methods in neuroscience enable measuring in-vivo activity of large populations of neurons at cellular level resolution. To leverage the full potential of these complex datasets and analyze the dynamics of individual neurons, it is essential to extract high-resolution regions of interest, while addressing demixing of overlapping spatial components and denoising of the temporal signal of each neuron. In this paper, we propose a data-driven solution to these challenges, by representing the spatiotemporal volume as a graph in the image plane. Based on the spectral embedding of this graph calculated across trials, we propose a new clustering method, Local Selective Spectral Clustering, capable of handling overlapping clusters and disregarding clutter. We also present a new nonlinear mapping which recovers the structural map of the neurons and dendrites, and global video denoising. We demonstrate our approach on in-vivo calcium imaging of neurons and apical dendrites, automatically extracting complex structures in the image domain, and denoising and demixing their time-traces.
Criticality in Tumor Evolution and Clinical Outcome
Authors: Persi Erez , Wolf Yuri I. , Leiserson Mark D.M. , Koonin Eugene V. , Ruppin Eytan
Published: May 2018

How mutation and selection determine the fitness landscape of tumors and hence clinical outcome is an open fundamental question in cancer biology, crucial for the assessment of therapeutic strategies and resistance to treatment. Here we explore the mutation-selection phase-diagram of 6721 primary tumors representing 23 cancer types, by quantifying the overall somatic point mutation load (ML) and selection (dN/dS) in the entire proteome of each tumor. We show thatMLstrongly correlates with patient survival, revealing two opposing regimes around a critical point. In lowMLcancers, high number of mutations indicates poor prognosis, whereas highMLcancers show the opposite trend, due to mutational meltdown. Although the majority of cancers evolve near neutrality, deviations are observed at extremeMLs. Cancers with the highestMLevolve under purifying selection, whereas those with the lowestMLshow signatures of positive selection, demonstrating how selection affects cancer fitness. Moreover, different cancers occupy specific positions on theML-dN/dSplane, revealing a diversity of evolutionary trajectories. These results support and expand the theory of tumor evolution and its non-linear effects on survival.

Significance Statement

It remains an open fundamental question how mutation and selection co-determine the course of cancer evolution. We construct a selection-mutation phase diagram, using tumor mutation load and selection strength as key variables, and assess their association with clinical outcome. We demonstrate the existence of a biphasic evolutionary regime, whereby beyond a criticalML, the fitness of tumors decreases with the number of mutations, while the proteome evolves near neutrality. Deviations from neutrality in extremeMLelucidate how positive and purifying selections maintain tumor fitness. These results empirically corroborate the existence of a critical state in cancer evolution predicted by theory, and have fundamental and likely clinical implications.
A mechanism-based computational model to capture the interconnections among epithelial-mesenchymal transition, cancer stem cells and Notch-Jagged signaling
Authors: Bocci Federico , Jolly Mohit K. , George Jason , Levine Herbert , Onuchic José N.
Published: May 2018

Epithelial-mesenchymal transition (EMT) and cancer stem cell formation (CSCs) are two fundamental and well-studied processes contributing to cancer metastasis and tumor relapse. Cells can undergo a partial EMT to attain a hybrid epithelial/mesenchymal (E/M) phenotype or a complete EMT to attain a mesenchymal one. Similarly, cells can reversibly gain or lose ‘stemness’. This plasticity in cell states is modulated by signaling pathways such as Notch. However, the interconnections among the cell states enabled by EMT, CSCs and Notch signaling remain elusive. Here, we devise a computational model to investigate the coupling among the core decision-making circuits for EMT, CSCs and the Notch pathway. Our model predicts that hybrid E/M cells are most likely to associate with stemness traits and exhibit enhanced Notch-Jagged signaling – a pathway that is implicated in therapeutic resistance. Further, we show that the position of the ‘stemness window’ on the ‘EMT axis’ is varied by altering the coupling strength between EMT and CSC circuits, and/or modulating Notch signaling. Finally, we analyze the gene expression profile of CSCs from several cancer types and observe a heterogeneous distribution along the ‘EMT axis’, suggesting that different subsets of CSCs may exist with varying phenotypes along the epithelial-mesenchymal plasticity axis. Our computational model offers insights into the complex EMT-stemness interplay and provides a platform to investigate the effects of therapeutic perturbations such as treatment with metformin, a common anti-diabetic drug that has been associated with decreased cancer incidence and increased lifespan of patients. Our mechanism-based model helps explain how metformin can both inhibit EMT and blunt the aggressive potential of CSCs simultaneously, by driving the cells out of a hybrid E/M stem-like state with enhanced Notch-Jagged signaling.
AFLOW-SYM: platform for the complete, automatic and self-consistent symmetry analysis of crystals
Authors: Hicks David , Oses Corey , Gossett Eric , Gomez Geena , Taylor Richard H. , Toher Cormac , Mehl Michael J. , Levy Ohad , Curtarolo Stefano
Published: May 2018

Determination of the symmetry profile of structures is a persistent challenge in materials science. Results often vary amongst standard packages, hindering autonomous materials development by requiring continuous user attention and educated guesses. This article presents a robust procedure for evaluating the complete suite of symmetry properties, featuring various representations for the point, factor and space groups, site symmetries and Wyckoff positions. The protocol determines a system-specific mapping tolerance that yields symmetry operations entirely commensurate with fundamental crystallographic principles. The self-consistent tolerance characterizes the effective spatial resolution of the reported atomic positions. The approach is compared with the most used programs and is successfully validated against the space-group information provided for over 54 000 entries in the Inorganic Crystal Structure Database (ICSD). Subsequently, a complete symmetry analysis is applied to all 1.7+ million entries of theAFLOWdata repository. TheAFLOW-SYMpackage has been implemented in, and made available for, public use through the automatedab initioframeworkAFLOW.
A method to estimate statistical errors of properties derived from charge-density modelling
Authors: Fournier Bertrand , Guillot Benoît , Lecomte Claude , Escudero-Adán Eduardo C. , Jelsch Christian
Published: May 2018

Estimating uncertainties of property values derived from a charge-density model is not straightforward. A methodology, based on calculation of sample standard deviations (SSD) of properties using randomly deviating charge-density models, is proposed with theMoProsoftware. The parameter shifts applied in the deviating models are generated in order to respect the variance–covariance matrix issued from the least-squares refinement. This `SSD methodology' procedure can be applied to estimate uncertainties ofanyproperty related to a charge-density model obtained by least-squares fitting. This includes topological properties such as critical point coordinates, electron density, Laplacian and ellipticity at critical points and charges integrated over atomic basins. Errors on electrostatic potentials and interaction energies are also available now through this procedure. The method is exemplified with the charge density of compound (E)-5-phenylpent-1-enylboronic acid, refined at 0.45 Å resolution. The procedure is implemented in the freely availableMoProprogram dedicated to charge-density refinement and modelling.
Strategic planning and performance of SMEs in Ghana
Authors: Donkor Jacob , Donkor George Nana Agyekum , Kwarteng Collins Kankam
Published: May 2018

Purpose

This paper aims to examine the interacting effect of market dynamism and strategic planning on the performance of small- and medium-scale enterprises (SMEs) in Ghana.

Design/methodology/approach

This study has used quantitative approach in dealing with the interacting effect of market dynamic on strategic planning and SMEs’ performance in Ghana. Purposive sampling is used to select 200 small- and medium-sized manufacturing and service firms in Ghana. The hierarchical multiple regression analysis is performed to test the hypotheses.

Findings

This study finds that a consistent application of strategic planning methodologies contributes to the advancement of SME performance in Ghana. In addition, it was ascertained that market dynamism has a significant positive relationship with firm performance, although its effect is not significant. Finally, the study reveals that market dynamism only influences SME performance when there is strategic planning.

Research limitations/implications

The findings are limited to the SMEs in Ghana. The study of market dynamism, strategic planning and performance is a very complex activity; therefore, to gather rich data on such research work may be best accomplished if the researchers adopt mixed method data gathering techniques. This will enrich the understanding on market dynamism, strategic planning and SMEs’ performance relationship.

Practical implications

The findings of this research work offer guidance to owners or managers considering how to develop market dynamics and strategic planning to enhance firm performance.

Originality/value

This study reports on an obvious gap in the prevailing literature that few empirical research works have explored on the possible impacts of market dynamism and strategic planning on performance of SMEs in a third world country.
Status and conditions of small- and medium-sized enterprises as predictors in empowering rural communities in Samar Island, Philippines
Authors: Miranda Asterio Tenedero , Miranda Juneth Lourdes Fiel
Published: May 2018

Purpose

This study aims to determine the status and conditions of small and medium enterprises (SMEs) as predictors in empowering the rural communities of Samar Island, Philippines. Specifically, it aimed to describe SMEs’ organizational variables, and assess their conditions in terms of membership/ownership structure; leadership; policies, systems and procedures; resource mobilization; linkages and networking; communication systems; and awards and recognition; determine the level of empowerment of rural communities with SMEs along the aspects of material, perceptual and relational changes; and find out whether significant relationship exist between the organizational variables and the level of empowerment.

Design/methodology/approach

The study is a descriptive survey that utilized structured survey questionnaires, personal interviews and dialogues with the respondents in the actual data collection. The survey involved 18 SMEs from the rural communities of the 12 municipalities from the 3 provinces of Samar Island, as study samples – 6 coming from each province with 2 SMEs in every sub-sector of trading, manufacturing and services. Out of 270 respondents, 256 (94.81 per cent) responded. All statistics were computed using the SPSS computer software.

Findings

The organizational variables of the SMEs such as membership and ownership structure, leadership, policies, systems and procedures, resource mobilization, linkages and networking, communication systems and awards and recognition were assessed to be all “good” and were found to have significant relationship with the level of empowerment of rural communities with SMEs.

Originality/value

The rural communities with SMEs were empowered along the aspects of material, perceptual and relational changes. The result of the study indicated that through SMEs, rural people experienced changes in their lives. The test about the relationship of the organizational variables such as nature and ownership of business enterprise, leadership, policies, systems and procedures, resource mobilization, linkages and networking, communication systems and awards and recognition and the level of empowerment of rural communities as determined by changes in the material, perceptual and relational aspects of rural life proved to have significant relationships.
Lean-green manufacturing: the enabling role of information technology resource
Authors: Ghobakhloo Morteza , Azar Adel , Fathi Masood
Published: May 2018

Purpose

The purpose of this paper is to contribute to the existing knowledge about the relationships between information technology (IT), lean manufacturing (LM), organizational environmental issues and business performance.

Design/methodology/approach

A questionnaire-based survey was conducted to collect data from 122 elite manufacturers, and the hypothesized relationships were tested using partial least squares structural equation modeling.

Findings

IT competence in LM acts as a lower-order organizational capability, and its business value should be recognized through the intermediate roles of LM effectiveness and environmental management capability. Findings recommend that the net benefits of LM are mainly materialized through waste and pollution reduction and simplified implementation of proactive environmental practices.

Research limitations/implications

Among other limitations, relying on a rather small sample size and cross-sectional data of this research, and lack of generalizability of findings, tends to have certain limitations. An interesting direction for future research would be to extend this research by assessing interaction of other types of IT resources with LM and organizational environmental issues.

Practical implications

Both LM and proactive environmental management are information-intensive. Investment in both technological and human aspects of IT resource aimed at increasing the effectiveness of LM activities and proactive environmental practices is imperative for contemporary manufacturers.

Originality/value

This study introduces the IT capability of IT competence in LM and two organizational capabilities of LM effectiveness and environmental management capability. By doing so, the study highlights the significant role of organizational environmental issues in devising firms’ IT and advanced manufacturing technology investment strategies in LM context.