bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening Breast Ultrasound Using Handheld or Automated Technique in Women with Dense Breasts
Authors: Berg Wendie A , Vourtsis Athina
Published: October 2019

In women with dense breasts (heterogeneously or extremely dense), adding screening ultrasound to mammography increases detection of node-negative invasive breast cancer. Similar incremental cancer detection rates averaging 2.1–2.7 per 1000 have been observed for physician- and technologist-performed handheld ultrasound (HHUS) and automated ultrasound (AUS). Adding screening ultrasound (US) for women with dense breasts significantly reduces interval cancer rates. Training is critical before interpreting examinations for both modalities, and a learning curve to achieve optimal performance has been observed. On average, about 3% of women will be recommended for biopsy on the prevalence round because of screening US, with a wide range of 2%–30% malignancy rates for suspicious findings seen only on US. Breast Imaging Reporting and Data System 3 lesions identified only on screening HHUS can be safely followed at 1 year rather than 6 months. Computer-aided detection and diagnosis software can augment performance of AUS and HHUS; ongoing research on machine learning and deep learning algorithms will likely improve outcomes and workflow with screening US.
Educated and Engaged Communicators Are Critical to Successful Integrated Pest Management Adoption
Authors: Gott Ryan C , Coyle David R
Published: October 2019

Integrated pest management (IPM) programs combining multiple compatible pest control tactics can result in effective commodity protection, pesticide use reduction, and cost savings – yet establishment of IPM programs is still low in many areas of the United States. While several potential causes of and solutions to low adoption rates exist, our focus is on the often-neglected human aspect of IPM. IPM educators who serve as the conduit of IPM research and advice to IPM practitioners often face challenges in areas that are less scientific and more social, such as communication and teaching. The skills needed in these areas (e.g., conflict management and resolution, needs assessment, negotiation, training, and informal education) are sometimes neglected in the professional development of future IPM educators, to the detriment of their ability to work with practitioners to encourage adoption of IPM programs. We explore these challenges, including a survey of current IPM educators, and propose areas of communication skills that could be included in the professional development of future or early-career IPM educators.
Learning Core Leadership: Seeing the Problem We Do Not See
Authors: Edwards Calvin , Woo Jason
Published: October 2019

Uniformed health care professionals operate in complex environments. We presume our partners’ mission perspective mirrors our own; they share and support our goals. This case demonstrates how this “self-deception” blinds and limits us. Seeing this self-deceit enables us to adjust our efforts to better accomplish our mission.
Anterior Cervical Discectomy and Fusion in the Outpatient Ambulatory Surgery Setting: Analysis of 2000 Consecutive Cases
Authors: McGirt Matthew J , Rossi Vincent , Peters David , Dyer Hunter , Coric Domagoj , Asher Anthony L , Pfortmiller Deborah , Adamson Tim
Published: October 2019

BACKGROUND

In an effort to improve efficiency of care, ambulatory surgery centers (ASCs) have emerged as lower-cost options. Anterior cervical discectomy and fusion (ACDF) is one of the most prevalent spine surgeries performed and rarely requires overnight stays in the hospital, supporting its migration to the ASC. Recent analyses have called into question the safety of outpatient ACDF, potentially slowing its adoption. ASC-ACDF studies have largely been limited to small series, precluding an accurate assessment of safety.

OBJECTIVE

To analyze 2000 ASC-ACDF cases, describe patient selection and perioperative protocol, and report associated safety profile.

METHODS

A total of 2000 patients who underwent 1 to 3 level ACDF in a single ASC from 2006 to 2018 were included in this retrospective analysis. Patients were observed in a 4-h postanesthesia care unit (PACU) with a multimodal pain management regiment. Data were collected on patient demographics, comorbidities, operative details, and 30- and 90-d morbidity.

RESULTS

Of the 2000 patients, 10 (0.5%) required transfer to an inpatient setting within the 4-h observation. Reasons for transfer included hematoma (2), pain control (2), cerebrospinal fluid leak (1), and medical complications (5). Six patients (0.3%) underwent reoperation within 30 d. All-cause 30-d readmission was 1.9%.

CONCLUSION

An analysis of 2000 ACDF patients in an ASC setting with a standardized perioperative protocol demonstrates that surgical complications occur at a low rate (<1%) and can be appropriately diagnosed and managed in a 4-h PACU. In an effort to decrease healthcare costs, surgeons can safely perform ACDFs in an ASC utilizing patient selection criteria and perioperative management protocols similar to those reported here.
Treatment of HER2+ metastatic salivary ductal carcinoma in a pregnant woman: a case report
Authors: Bergamini Cristiana , Cavalieri Stefano , Sanguineti Giuseppe , Farneti Alessia , Licitra Lisa
Published: October 2019

Salivary duct carcinoma (SDC) is a rare and aggressive malignancy with a high mortality and poor response to treatment in the advanced setting. Human epidermal growth factor 2 (HER2) can be amplified in a fraction of SDC. We describe the case of HER2+ metastatic SDC of the submandibular gland in a young pregnant woman treated by multimodal treatment (chemotherapy, radiotherapy and targeted therapy). During pregnancy, a 27-year-old woman developed SDC of the left submandibular gland with lung and bone metastases. Given the HER2 overexpression, she was treated with trastuzumab, paclitaxel and cisplatin. Since the tumor had arisen during pregnancy, triptorelin was administered after delivery. A complete remission was observed, and after eight cycles of chemotherapy, radiotherapy was started in association with trastuzumab and triptorelin. A prolonged disease control and complete visceral remission were observed. Multimodal therapy based on patient’s tumor characteristics showed good clinical efficacy in the treatment of metastatic SDC.
Successful limb salvage by endovascular treatment for critical limb ischemia subsequent to acute limb ischemia
Authors: Nomura Tetsuya , Tasaka Satoshi , Ono Kenshi , Sakaue Yu , Wada Naotoshi , Keira Natsuya , Tatsumi Tetsuya
Published: October 2019

Recently, there have been increasing opportunities to treat patients with peripheral arterial disease. Of those patients, both pathological conditions, such as acute limb ischemia (ALI) and chronic critical limb ischemia (CLI), are closely associated with high risks of major amputation, disability and death. We encountered a very rare case of CLI subsequent to ALI. An 83-year-old male showed the sudden onset of ALI, probably due to thromboembolism from an abdominal aortic aneurysm during an operation for gastric cancer. The patient was referred to another hospital for Fogarty thrombectomy. About 1 month after ALI onset, necrosis of the left first toe gradually progressed. On angiography of the left lower limb, we noted occlusions of both anterior and posterior tibial arteries. Then, we successfully conducted balloon angioplasty for the below-the-knee arteries. Thereby, favorable blood flow was achieved, which led to successful wound healing without amputations.
Comparing Kinetics of Xylem Ion Loading and Its Regulation in Halophytes and Glycophytes
Authors: Zarei Mahvash , Shabala Sergey , Zeng Fanrong , Chen Xiaohui , Zhang Shuo , Azizi Majid , Rahemi Majid , Davarpanah Sohrab , Yu Min , Shabala Lana
Published: October 2019

Although control of xylem ion loading is essential to confer salinity stress tolerance, specific details behind this process remain elusive. In this work, we compared the kinetics of xylem Na+ and K+ loading between two halophytes (Atriplex lentiformis and quinoa) and two glycophyte (pea and beans) species, to understand the mechanistic basis of the above process. Halophyte plants had high initial amounts of Na+ in the leaf, even when grown in the absence of the salt stress. This was matched by 7-fold higher xylem sap Na+ concentration compared with glycophyte plants. Upon salinity exposure, the xylem sap Na+ concentration increased rapidly but transiently in halophytes, while in glycophytes this increase was much delayed. Electrophysiological experiments using the microelectrode ion flux measuring technique showed that glycophyte plants tend to re-absorb Na+ back into the stele, thus reducing xylem Na+ load at the early stages of salinity exposure. The halophyte plants, however, were capable to release Na+ even in the presence of high Na+ concentrations in the xylem. The presence of hydrogen peroxide (H2O2) [mimicking NaCl stress-induced reactive oxygen species (ROS) accumulation in the root] caused a massive Na+ and Ca2+ uptake into the root stele, while triggering a substantial K+ efflux from the cytosol into apoplast in glycophyte but not halophytes species. The peak in H2O2 production was achieved faster in halophytes (30 min vs 4 h) and was attributed to the increased transcript levels of RbohE. Pharmacological data suggested that non-selective cation channels are unlikely to play a major role in ROS-mediated xylem Na+ loading.
Epigenetic Flexibility Underlies Somaclonal Sex Conversions in Hexaploid Persimmon
Authors: Masuda Kanae , Akagi Takashi , Esumi Tomoya , Tao Ryutaro
Published: October 2019

Epigenetic regulation adds a flexible layer to genetic variations, potentially enabling long-term, but reversible, changes to a trait, while maintaining genetic information. In the hexaploid Oriental persimmon (Diospyros kaki), genetically monoecious cultivars bearing male flowers require the Y-encoded small RNA (smRNA) gene, OGI. This gene represses the expression of its autosomal counterpart gene, MeGI, as part of the canonical male production system. However, a D. kaki cultivar, Saijo, which lacks the OGI gene and originally bears only female flowers, occasionally produces somaclonal mutant male and revertant female (RF) branches. In this study, we investigated the mechanisms underlying these somaclonal sex conversions in persimmon. Specifically, we aimed to unravel how a genetically female tree without the OGI gene can produce male flowers and RF flowers. Applying multi-omics approaches, we revealed that this noncanonical male production system is basically consistent with the canonical system, in which the accumulation of smRNA targeting MeGI and the considerable DNA methylation of MeGI are involved. The epigenetic status of MeGI on CGN and CHG was synchronized to the genome-wide methylation patterns, both in transition to and from the male production system. These results suggest that the somaclonal sex conversions in persimmon are driven by the genome-wide epigenetic regulatory activities. Moreover, flexibility in the epigenetic layers of long-lived plant species (e.g. trees) is important for overcoming genetic robustness.
Striatal histamine mechanism in the pathogenesis of restless legs syndrome
Authors: Lai Yuan-Yang , Hsieh Kung-Chiao , Cheng Yu-Hsuan , Chew Keng-Tee , Nguyen Darian , Ramanathan Lalini , Siegel Jerome M
Published: October 2019

Study Objectives

Restless legs syndrome (RLS) has been hypothesized to be generated by abnormal striatal dopamine transmission. Dopaminergic drugs are effective for the treatment of RLS. However, long-term use of dopaminergic drugs causes adverse effects. We used iron-deficient (ID) and iron-replacement (IR) rats to address the neuropathology of RLS and to determine if a histamine H3 receptor (H3R) antagonist might be a useful treatment. Histamine H3R antagonists have been shown to decrease motor activity.

Methods

Control and ID rats were surgically implanted with electrodes for polysomnographic recording. After 3 days of baseline polysomnographic recordings, rats were systemically injected with the H3R agonist, α-methylhistamine, and antagonist, thioperamide. Recordings were continued after drug injection. Striatal H3R levels from control, ID, and IR rats were determined by western blots. Blood from control, ID, and IR rats was collected for the measurement of hematocrit levels.

Results

α-Methylhistamine and thioperamide increased and decreased motor activity, respectively, in control rats. In ID rats, α-methylhistamine had no effect on motor activity, whereas thioperamide decreased periodic leg movement (PLM) in sleep. Sleep–wake states were not significantly altered under any conditions. Striatal H3R levels were highest in ID rats, moderate to low in IR rats, and lowest in control rats. Striatal H3R levels were also found to positively and negatively correlate with PLM in sleep and hematocrit levels, respectively.

Conclusions

A striatal histamine mechanism may be involved in ID anemia-induced RLS. Histamine H3R antagonists may be useful for the treatment of RLS.
Origin and adaptive radiation of the exceptional and threatened bembidiine beetle fauna of St Helena (Coleoptera: Carabidae)
Authors: Maddison David R , Sproul John S , Mendel Howard
Published: October 2019

The central peaks of the isolated island of St Helena (south Atlantic Ocean) are home to an extraordinary set of ground beetles of the tribe Bembidiini, which belong to three endemic genus-group taxa. These beetles are strikingly different in overall body form from the many bembidiines found elsewhere in the world. At least some of the St Helena species are likely to be extinct, and all are threatened by habitat destruction and invasive species. Through next-generation sequencing of historical museum specimens, we examine the phylogenetic relationships of the St Helena fauna. We find that, in spite of their morphological disparities, the endemic bembidiines of St Helena form a clade of genetically similar species, with their sister group being Bembidion alsium from the Indian Ocean island of La Réunion, and the sister group of this pair being the African subgenus Omotaphus. We propose that the St Helena Peaks Bembidion are an adaptive radiation that arose from a single dispersal event to St Helena from a now-extinct African lineage (sister to Omotaphus) and that this extinct lineage also served as the ancestral source of B. alsium. Given that the St Helena Peaks Bembidion are deeply nested in the genus Bembidion, we move the three taxa back in that genus as subgenera and provide a new name (Bembidion shepherdae) for the now-homonymous Bembidion wollastoni.
Revision of the Ropalopus ungaricus/insubricus group (Coleoptera: Cerambycidae: Callidiini) from the western Palaearctic region
Authors: Karpiński Lech , Szczepański Wojciech T , Kruszelnicki Lech
Published: October 2019

This paper revises the taxonomy and phylogeny of Ropalopus (Coleoptera: Cerambycidae: Callidiini) species belonging to the taxonomically intricate Ropalopus ungaricus/insubricus group from the western Palaearctic. Specimens from all taxa were studied and compared. The key characters, including the male terminalia, were examined by means of scanning electron microscopy. High-quality stacked photographs of the habitus of the specimens (dorsal, ventral) are presented. The phylogenetic analyses were based on 34 adult morphological characters. Both the strict and majority consensus trees revealed the monophyly of the revised group. Identification keys are provided for every taxon from this group, and their geographical distributions are also mapped. All European populations are reduced to subspecies of Ropalopus ungaricus. Additionally, a new subspecies from Greece, Ropalopus ungaricus ossae subsp. nov., is described and illustrated. A new synonymy for Ropalopus insubricus fischeri is proposed: Callidium insubricum = Callidium fischeri. Ropalopus nataliyae, which was described based on only a single female, is herein redescribed owing to the collection of abundant new material. Apart from geographical barriers, the main differentiating factor in this group is proved to be the elevation above sea level. Taxa of the R. ungaricus/insubricus group are therefore allopatric or, when parapatric, are isolated by elevation.
SPAM1/HYAL5 double deficiency in male mice leads to severe male subfertility caused by a cumulus‐oocyte complex penetration defect
Authors: Park Soojin , Kim Young‐Hyun , Jeong Pil‐Soo , Park Chaeri , Lee Jeong‐Woong , Kim Ju‐Sung , Wee Gabin , Song Bong‐Seok , Park Boon‐Joo , Kim Sang‐Hyun , Sim Bo‐Woong , Kim Sun‐Uk , Triggs‐Raine Barbara , Baba Tadashi , Lee Sang‐Rae , Kim Ekyune
Published: October 2019

The glycosylphosphatidylinositol‐anchored sperm hyaluronidases (Hyals), sperm adhesion molecule 1 (SPAM1) and HYAL5, have long been believed to assist in sperm penetration through the cumulus‐oocyte complex (COC), but their role in mammalian fertilization remains unclear. Previously, we have shown that mouse sperm devoid of either Spam1 or Hyal5 are still capable of penetrating the COC and that the loss of either Spam1 or Hyal5 alone does not cause male infertility in mice. In the present study, we found that Spam1/Hyal5 double knockout (dKO) mice produced significantly fewer offspring compared with wild‐type (WT) mice, and this was due to defective COC dispersal. A comparative analysis between WT and Spam1/Hyal5 dKO epididymal sperm revealed that the absence of these 2 sperm Hyals resulted in a marked accumulation of sperm on the outside of the COC. This impaired sperm activity is likely due to the deficiency in the sperm Hyals, even though other somatic Hyals are expressed normally in the dKO mice. The fertilization ability of the Spam1/Hyal5 dKO sperm was restored by adding purified human sperm Hyal to the in vitro fertilization medium. Our results suggest that Hyal deficiency in sperm may be a significant risk factor for male sterility.—Park, S., Kim, Y.‐H., Jeong, P.‐S., Park, C., Lee, J.‐W., Kim, J.‐S., Wee, G., Song, B.‐S., Park, B.‐J., Kim, S.‐H., Sim, B.‐W., Kim, S.‐U., Triggs‐Raine, B., Baba, T., Lee, S.‐R., Kim, E. SPAM1/HYAL5 double deficiency in male mice leads to severe male subfertility caused by a cumulus‐oocyte complex penetration defect. FASEB J. 33, 14440‐14449 (2019). www.fasebj.org
Actinomadura harenae sp. nov., a novel actinomycete isolated from sea sand in Sanya
Authors: Hu Jiangmeihui , Han Chuanyu , Yu Bing , Zhao Junwei , Guo Xiaowei , Shen Yue , Wang Xiangjing , Xiang Wensheng
Published: October 2019

A novel actinomycete, designated strain NEAU-Ht49T, was isolated from sea sand sampled in Sanya and characterized by using a polyphasic approach. The 16S rRNA gene sequence analysis showed that strain NEAU-Ht49T was most closely related to

Actinomadura rhizosphaerae

SDA37T (98.8 %),

Actinomadura logoneensis

NEAU-G17T (98.6 %),

Actinomadura oligospora

ATCC 43269T (98.6 %) and

Actinomadura gamaensis

NEAU-Gz5T (98.6 %). The results of phylogenetic analysis based on the 16S rRNA gene sequences indicated that strain NEAU-Ht49T formed a cluster with

A. rhizosphaerae

SDA37T,

A. logoneensis

NEAU-G17T,

A. oligospora

ATCC 43269T,

A. gamaensis

NEAU-Gz5T and

Actinomadura rupiterrae

CS5-AC15T (96.4 %). Meso-diaminopimelic acid was detected in its cell walls and glucose, madurose, mannose and ribose were detected in whole-cell hydrolysate. The polar lipids were found to consist of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositolmannoside and two unidentified lipids. The majoy menaquinone was MK-10(H6) and the minor menaquinones were MK-9(H4) and MK-9(H8). The major fatty acids were C16 : 0, C18 : 1ω9c, 10-methyl C18 : 0 and iso-C16 : 0. Moreover, morphological and chemotaxonomic characteristics of properties of strain NEAU-Ht49T also confirmed the affiliation of the isolate to the genus

Actinomadura

. However, DNA–DNA relatedness, physiological and biochemical data showed that strain NEAU-Ht49T could be distinguished from its closest relatives. Therefore, strain NEAU-Ht49T represents a novel species of the genus

Actinomadura

, for which the name Actinomadura harenae sp. nov. is proposed, with strain NEAU-Ht49T (=CGMCC 4.7499T=JCM 32659T) as the type strain.
Kocuria coralli sp. nov., a novel actinobacterium isolated from coral reef seawater
Authors: Li Jie , Zhang Si
Published: October 2019

An actinobacterial strain, SCSIO 13007T, was isolated from seawater collected from the Luhuitou fringing reef at a depth of 4.2 m. Phylogenetic and phenotypic properties of the organism supported the hypothesis that it represented a member of the genus

Kocuria

. Phylogenetic analysis indicated that the levels of 16S rRNA gene sequence similarity between SCSIO 13007T and type strains of other recognized members of the genus

Kocuria

were lower than 96.99 %. Growth in the presence of up to 15 % (w/v) NaCl was a distinctive characteristic of SCSIO 13007T. Other biochemical and physiological properties and the major fatty acids also differentiated the isolate from its phylogenetically closest relative

Kocuria subflava

YIM 13062T. The menaquinone types were MK-7(H2) and MK-8(H2). Major cellular fatty acids were anteiso-C15 : 0, iso-C15 : 0 and anteiso-C17 : 0. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, an unidentified lipid and an unidentified aminolipid. The DNA G+C content was 73.7 mol%. The combined genotypic and phenotypic data indicated that strain SCSIO 13007T represents a novel species of the genus

Kocuria

, for which the name Kocuria coralli sp. nov. is proposed; the type strain is SCSIO 13007T (=DSM 27811T=NBRC 109942T).
Primary visual cortex excitability is not atypical in acquired synaesthesia
Authors: Lungu Laura , Stewart Ryan , Luke David P. , Terhune Devin B.
Published: October 2019

A wealth of data suggests that psychedelic drugs elicit spontaneous perceptual states that resemble synaesthesia although it is unclear whether these different forms of synaesthesia share overlapping neural mechanisms. Multiple studies have shown that developmental and trained synaesthesia is characterized by selective hyperexcitability in primary visual cortex and it has been proposed that cortical hyperexcitability may contribute to induced and acquired synaesthesia. This study tested the prediction that a case of acquired synaesthesia (LW) would display selectively elevated primary visual cortex excitability, as reflected in lower transcranial magnetic stimulation (TMS) phosphene thresholds, but no difference in motor thresholds, relative to controls. In contrast to this prediction, LW’s phosphene threshold was well within the threshold range of controls. These results suggest that acquired synaesthesia is not characterized by atypical visual cortex excitability.
Biophysical mechanisms governing large-scale brain network dynamics underlying individual-specific variability of perception
Authors: Vinodh Kumar G. , Dutta Shrey , Talwar Siddharth , Roy Dipanjan , Banerjee Arpan
Published: October 2019

Perception necessitates interaction amongst neuronal ensembles, the dynamics of which can be conceptualized as the emergent behavior of coupled dynamical systems. Here, we propose a detailed neurobiologically realistic model that captures the neural mechanisms of inter-individual variability observed in cross-modal speech perception. From raw EEG signals recorded from human participants when they were presented with speech vocalizations of McGurk-incongruent and congruent audio-visual (AV) stimuli, we computed the global coherence metric to capture the neural variability of large-scale networks. We identified that participants’ McGurk susceptibility was negatively correlated to their alpha-band global coherence. The proposed biophysical model conceptualized the global coherence dynamics emerge from coupling between the interacting neural masses - representing the sensory specific auditory/visual areas and modality non-specific associative/integrative regions. Subsequently, we could predict that an extremely weak direct AV coupling result in a decrease in alpha band global coherence - mimicking the cortical dynamics of participants with higher McGurk susceptibility. Source connectivity analysis also showed decreased connectivity between sensory specific regions in participants more susceptible to McGurk effect, thus establishing an empirical validation to the prediction. Overall, our study provides an outline to link variability in structural and functional connectivity metrics to variability of performance that can be useful for several perception & action task paradigms.
On islands, evolutionary but not functional originality is rare
Authors: Veron S. , Pellens R. , Kondratyeva A. , Grandcolas P. , Govaerts Rafaël , Robuchon M. , Haevermans T. , Mouchet M.
Published: October 2019

Functionally and evolutionary original species are those whose traits or evolutionary history are shared by few others in a given set. These original species promote ecosystem multifunctionality, the ability to cope with an uncertain future, future benefits to society and therefore have a high conservation value. A potential signal of their extinction risks is their rarity (stating for geographic range-restriction in this study). On islands, life in isolation conducted to the rise of a multitude of original forms and functions as well as to high rates of endemism. Not only patterns and processes of insular originality are unexplained but the relationship between originality and rarity is still unknown. The aim of this study is to assess how original insular species are, to explore whether original species are rare or not and to investigate the factors that may explain the rarity of original species. We first compared the functional and evolutionary originality of monocotyledon species and whether continental or insular species were more original. We found that species restricted to islands were more original than continental species and, although functionally and evolutionary original species were dissimilar, many occurred on similar territories so that regional conservation strategies may allow to conserve these distinct forms. Yet, evolutionary original species were significantly more range-restricted than those which were distinct in their traits. Reflecting their rarity, evolutionary original species had low dispersal abilities and were found on islands where settlement may have been facilitated. On the opposite, functionally original species could reach a wider set of islands by being transported on long-distances. While some mechanisms may both explain rarity and originality such as extinctions, others may be specific to each of these biodiversity facets, in particular diversification, niche shift and expansion, and dispersal power. Implications for conservation are huge: original species are range-restricted and mostly found in the most threatened systems of the world, i.e. islands, endangering the reservoir of features against an uncertain future.
In planta bacterial multi-omics analysis illuminates regulatory principles underlying plant-pathogen interactions
Authors: Nobori Tatsuya , Wang Yiming , Wu Jingni , Stolze Sara Christina , Tsuda Yayoi , Finkemeier Iris , Nakagami Hirofumi , Tsuda Kenichi
Published: October 2019

Understanding how gene expression is regulated in plant pathogens is crucial for pest control and thus global food security. An integrated understanding of bacterial gene regulation in the host is dependent on multi-omic datasets, but these are largely lacking. Here, we simultaneously characterized the transcriptome and proteome of a foliar bacterial pathogen, Pseudomonas syringae, in Arabidopsis thaliana and identified a number of bacterial processes influenced by plant immunity at the mRNA and the protein level. We found instances of both concordant and discordant regulation of bacterial mRNAs and proteins. Notably, the tip component of bacterial type III secretion system was selectively suppressed by the plant salicylic acid pathway at the protein level, suggesting protein-level targeting of the bacterial virulence system by plant immunity. Furthermore, gene co-expression analysis illuminated previously unknown gene regulatory modules underlying bacterial virulence and their regulatory hierarchy. Collectively, the integrated in planta bacterial omics approach provides molecular insights into multiple layers of bacterial gene regulation that contribute to bacterial growth in planta and elucidate the role of plant immunity in controlling pathogens.
Predominance of positive epistasis among drug resistance-associated mutations in HIV-1 protease
Authors: Zhang Tian-hao , Dai Lei , Barton John P. , Du Yushen , Tan Yuxiang , Pang Wenwen , Chakraborty Arup K. , Lloyd-Smith James O. , Sun Ren
Published: October 2019

Drug-resistant mutations often have deleterious impacts on replication fitness, posing a fitness cost that can only be overcome by compensatory mutations. However, the role of fitness cost in the evolution of drug resistance has often been overlooked in clinical studies orin vitroselection experiments, as these observations only capture the outcome of drug selection. In this study, we systematically profile the fitness landscape of resistance-associated sites in HIV-1 protease using deep mutational scanning. We construct a mutant library covering combinations of mutations at 11 sites in HIV-1 protease, all of which are associated with resistance to protease inhibitors in clinic. Using deep sequencing, we quantify the fitness of thousands of HIV-1 protease mutants after multiple cycles of replication in human T cells. Although the majority of resistance-associated mutations have deleterious effects on viral replication, we find that epistasis among resistance-associated mutations is predominantly positive. Furthermore, our fitness data are consistent with genetic interactions inferred directly from HIV sequence data of patients. Fitness valleys formed by strong positive epistasis reduce the likelihood of reversal of drug resistance mutations. Overall, our results support the view that strong compensatory effects are involved in the emergence of clinically observed resistance mutations and provide insights to understanding fitness barriers in the evolution and reversion of drug resistance.
Mathematical modeling of the protective coloration of animals with usage of parameters of diversity and evenness
Authors: Bespalov Yu. , Nosov K. , Levchenko O. , Grigoriev O. , Hnoievyi I. , Kabalyants P.
Published: October 2019

Adaptive mechanisms performing at different levels of organization of living matter play an important role in theoretical biology. One of the important cases of such mechanisms is the protective coloration of animals, that masks them on the ground.

The article aims at building mathematical models of the performance of the protective coloration of animals, depending on the specific situations of their adaptation to a particular area. The results of the study can be used to create remote technologies for detecting animals of certain species at a considerable distance.
Structural basis of UCUU RNA motif recognition by splicing factor RBM20
Authors: Upadhyay Santosh Kumar , Mackereth Cameron D.
Published: October 2019

The vertebrate splicing factor RBM20 (RNA Binding Motif protein 20) regulates protein isoforms important for heart development and function, with mutations in the gene linked to cardiomyopathy. Previous studies have identified the four base RNA motif UCUU as a common element in pre-mRNA targeted by RBM20. Here, we have determined the structure of the RNA Recognition Motif (RRM) domain from mouse RBM20 bound to RNA containing a UCUU sequence. The atomic details show that the RRM domain spans a larger region than initially proposed in order to interact with the complete UCUU motif, with a well-folded C-terminal helix encoded by exon 8 critical for high affinity binding. This helix only forms upon binding RNA with the final uracil, and removing the helix reduces affinity as well as specificity. We therefore find that RBM20 uses a coupled folding-binding mechanism by the C-terminal helix to specifically recognize the UCUU RNA motif.
RNA polymerase I passage through nucleosomes depends on its lobe binding subunits
Authors: Merkl Philipp E. , Pilsl Michael , Fremter Tobias , Schwank Katrin , Engel Christoph , Längst Gernot , Milkereit Philipp , Griesenbeck Joachim , Tschochner Herbert
Published: October 2019

RNA polymerase I (Pol I) is a highly efficient enzyme specialized to synthesize most of the ribosomal RNA. After nucleosome deposition at each round of replication the Pol I transcription machinery has to deal with nucleosomal barriers. It was suggested that Pol I-associated factors facilitate chromatin transcription, but it is not known whether Pol I has an intrinsic capacity to transcribe through nucleosomes. Here we used in vitro transcription assays to study purified Pol I of the yeast S. cerevisiae and Pol I mutants in comparison to Pol II and Pol III to pass a nucleosome. Under identical conditions, purified Pol I and Pol III, but not Pol II, were able to transcribe nucleosomal templates. Pol I mutants lacking either the heterodimeric subunit Rpa34.5/Rpa49 or the C-terminal part of the specific subunit Rpa12.2 showed a lower processivity on naked DNA templates, which was even more reduced in the presence of a nucleosome. The contribution of Pol I specific subunit domains to efficient passage through nucleosomes in context with transcription rate and processivity is discussed.
Extensive functional repertoire underpins complex behaviours: insights from Parkinson’s disease
Authors: Sorrentino Pierpaolo , Rucco Rosaria , Baselice Fabio , De Micco Rosa , Tessitore Alessandro , Hillebrand Arjan , Mandolesi Laura , Breakspear Michael , Gollo Leonardo L. , Sorrentino Giuseppe
Published: October 2019

Rapid reconfigurations of brain activity support efficient neuronal communication and flexible behaviour. Suboptimal brain dynamics impair this adaptability, possibly leading to functional deficiencies. We hypothesize that impaired flexibility in brain activity can lead to motor and cognitive symptoms of Parkinson’s disease (PD). To test this hypothesis, we studied the ‘functional repertoire’ – the number of distinct configurations of neural activity – using source-reconstructed magnetoencephalography in PD patients and controls. We found stereotyped brain dynamics and reduced flexibility in PD. The intensity of this reduction was proportional to symptoms severity, which can be explained by beta-band hyper-synchronization. Moreover, the basal ganglia were prominently involved in the abnormal patterns of brain activity. Our findings support the hypotheses that: symptoms in PD reflect impaired brain flexibility, this impairment preferentially involves the basal ganglia, and beta-band hypersynchronization is associated with reduced brain flexibility. These findings highlight the importance of extensive functional repertoires for behaviour and motor.
A multidimensional framework for measuring biotic novelty: How novel is a community?
Authors: Schittko Conrad , Bernard-Verdier Maud , Heger Tina , Buchholz Sascha , Kowarik Ingo , von der Lippe Moritz , Seitz Birgit , Joshi Jasmin , Jeschke Jonathan M.
Published: October 2019

Anthropogenic changes in climate, land use and disturbance regimes, as well as introductions of non-native species can lead to the transformation of many ecosystems. The resulting novel ecosystems are usually characterized by species assemblages that have not occurred previously in a given area. Quantifying the ecological novelty of communities (i.e. biotic novelty) would enhance the understanding of environmental change. However, quantification remains challenging since current novelty metrics, such as the number and/or proportion of non-native species in a community, fall short of considering both functional and evolutionary aspects of biotic novelty. Here, we propose the Biotic Novelty Index (BNI), an intuitive and flexible multidimensional measure that combines (1) functional differences between native and non-native introduced species with (2) temporal dynamics of species introductions. We show that the BNI is an additive partition of Rao’s quadratic entropy, capturing the novel interaction component of the community’s functional diversity. Simulations show that the index varies predictably with the relative amount of functional novelty added by recently arrived species, and they illustrate the need to provide an additional standardized version of the index. We present a detailed R-code and two applications of the BNI by (1) measuring changes of biotic novelty of dry grassland plant communities along an urbanization gradient in a metropolitan region and (2) determining the biotic novelty of plant species assemblages at a national scale. Results illustrate the applicability of the index across scales and its flexibility in the use of data of different quality. Both case studies revealed strong connections between biotic novelty and increasing urbanization, a measure of abiotic novelty. We conclude that the BNI framework may help in building a basis for a better understanding of the ecological and evolutionary consequences of global change.
Dissociation between Frontal and Temporal-Parietal Contributions to Connected Speech in Acute Stroke
Authors: Ding Junhua , Martin Randi , Hamilton A. Cris , Schnur Tatiana T.
Published: October 2019

Humans are uniquely able to retrieve and combine words into syntactic structure to produce connected speech. Previous identification of focal brain regions necessary for production focused primarily on associations with the content produced by speakers with chronic stroke, where function may have shifted to other regions after reorganization occurred. Here, we relate patterns of brain damage with deficits to the content and structure of spontaneous connected speech in 52 speakers during the acute stage of a left hemisphere stroke. Multivariate lesion behavior mapping demonstrated that damage to temporal-parietal regions impacted the ability to retrieve words and produce them within increasingly complex combinations. Damage primarily to inferior frontal cortex affected the production of syntactically accurate structure. In contrast to previous work, functional-anatomical dissociations did not depend on lesion size likely because acute lesions were smaller than typically found in chronic stroke. These results are consistent with predictions from theoretical models based primarily on evidence from language comprehension and highlight the importance of investigating individual differences in brain-language relationships in speakers with acute stroke.
TSA-Seq reveals a largely “hardwired” genome organization relative to nuclear speckles with small position changes tightly correlated with gene expression changes
Authors: Zhang Liguo , Zhang Yang , Chen Yu , Gholamalamdari Omid , Wang Yuchuan , Ma Jian , Belmont Andrew S.
Published: October 2019

Genome-wide mapping of chromosomal distances relative to nuclear compartments using TSA-Seq suggests a more deterministic relationship between intranuclear gene position and expression as a function of nuclear speckle distance than radial position. Gene activity increases overall with decreasing distance to nuclear speckles, with active chromosomal regions forming the apex of chromosome loops protruding from the nuclear periphery into the interior. Interestingly, genomic distances to the nearest lamina-associated domain are larger for loop apexes mapping very close to nuclear speckles, suggesting the possibility of genomic “hardwiring” and conservation of speckle-associated regions. To facilitate comparison of genome organization relative to nuclear speckles in human K562, HCT116, HFFc6, and H1 cell lines, here we describe reducing the required cell number 10-20-fold for TSA-Seq by deliberately saturating protein-labeling while preserving distance mapping by the still unsaturated DNA-labeling. Surprisingly, in pair-wise cell line comparisons, only ∼10% of the genome shows a statistically significant shift in relative nuclear speckle distances. These modest shifts in nuclear speckle distance, however, tightly correlate with changes in cell-type specific gene expression. Similarly, half of all loci that contain induced heat-shock protein genes appear pre-positioned close to nuclear speckles, with the remaining showing small shifts towards speckles with transcriptional induction. Speckle association together with chromatin decondensation correlates with expression amplification upon HSPH1 activation. Our results demonstrate a largely “hardwired” genome organization and specific genes moving small mean distances relative to speckles during cell differentiation or physiological transition, suggesting an important role of nuclear speckles in gene expression regulation.
Computational and experimental investigation of biofilm disruption dynamics induced by high velocity gas jet impingement
Authors: Prades Lledó , Fabbri Stefania , Dorado Antonio D. , Gamisans Xavier , Stoodley Paul , Picioreanu Cristian
Published: October 2019

Experimental data showed that high-speed micro-sprays can effectively disrupt biofilms on their support substratum, producing a variety of dynamic reactions such as elongation, displacement, ripples formation and fluidization. However, the mechanics underlying the impact of high-speed turbulent flows on biofilm structure is complex in such extreme conditions, since direct measurements of viscosity at these high shear rates are not possible using dynamic testing instruments. Here we used computational fluid dynamics simulations to assess the complex fluid interactions of ripple patterning produced by high-speed turbulent air jets impacting perpendicular to the surface of Streptococcus mutans biofilms, a dental pathogen causing caries, captured by high speed imaging. The numerical model involved a two-phase flow of air over a non-Newtonian biofilm, whose viscosity as a function of shear rate was estimated using the Herschel-Bulkley model. The simulation suggested that inertial, shear and interfacial tension forces governed biofilm disruption by the air jet. Additionally, the high shear rates generated by the jet impacts coupled with shear-thinning biofilm property resulted in rapid liquefaction (within milliseconds) of the biofilm, followed by surface instability and travelling waves from the impact site. Our findings suggest that rapid shear-thinning in the biofilm reproduces dynamics under very high shear flows that elasticity can be neglected under these conditions, behaving the biofilm as a Newtonian fluid. A parametric sensitivity study confirmed that both applied force intensity (i.e. high jet-nozzle air velocity) and biofilm properties (i.e. low viscosity, low air-biofilm surface tension and thickness) intensify biofilm disruption, by generating large interfacial instabilities.

IMPORTANCE

Knowledge of mechanisms promoting disruption though mechanical forces is essential in optimizing biofilm control strategies which rely on fluid shear. Our results provide insight into how biofilm disruption dynamics is governed by applied forces and fluid properties, revealing a mechanism for ripples formation and fluid-biofilm mixing. These findings have important implications for the rational design of new biofilms cleaning strategies with fluid jets, such as determining optimal parameters (e.g. jet velocity and position) to remove the biofilm from a certain zone (e.g. in dental hygiene or debridement of surgical site infections), or using antimicrobial agents which could increase the interfacial area available for exchange, as well as causing internal mixing within the biofilm matrix, thus disrupting the localized microenvironment which is associated with antimicrobial tolerance. The developed model also has potential application in predicting drag and pressure drop caused by biofilms on bioreactor, pipeline and ship hull surfaces.
Ecological character displacement destabilizes food webs
Authors: Barbour Matthew A.
Published: October 2019

Ecological character displacement is an adaptive process that generally increases phenotypic diversity. Despite the fact that this diversification is due to an eco-evolutionary feedback between consumers competing for shared resources, its consequences for food-web dynamics have received little attention. Here, I study a model of two consumers competing for two shared resources to examine how character displacement in consumer attack rates affects resource abundances and the resilience of food webs to perturbations. I found that character displacement always strengthened consumer-resource interactions whenever consumers competed for resources that occurred in different habitats. This increase in interaction strength resulted in lower resource abundances and less resilient food webs. This occurred under different evolutionary tradeoffs and in both simple and more realistic foraging scenarios. Taken together, my results show that the adaptive process of character displacement may come with the ecological cost of decreasing food-web resilience.
The co-chaperone Fkbp5 shapes the acute stress response in the paraventricular nucleus of the hypothalamus
Authors: Häusl Alexander S. , Hartmann Jakob , Pöhlmann Max L. , Brix Lea M. , Lopez Juan-Pablo , Brivio Elena , Engelhardt Clara , Roeh Simone , Rudolph Lisa , Stoffel Rainer , Hafner Kathrin , Goss Hannah M. , Reul Johannes M.H.M. , Deussing Jan M. , Ressler Kerry J. , Gassen Nils C. , Chen Alon , Schmidt Mathias V.
Published: October 2019

Disturbed activation or regulation of the stress response through the hypothalamic-pituitary-adrenal (HPA) axis is a fundamental component of multiple stress-related diseases, including psychiatric, metabolic and immune disorders. The FK506 binding protein 51 (FKBP5) is a negative regulator of the glucocorticoid receptor (GR), a main driver of HPA axis regulation, andFKBP5polymorphisms have been repeatedly linked to stress-related disorders in humans. However, the specific role ofFkbp5in the paraventricular nucleus of the hypothalamus (PVN) in shaping HPA axis (re)activity remains to be elucidated. Using deletion, overexpression, and rescue ofFkbp5exclusively in the PVN, we establish the fundamental importance ofFkbp5in the HPA axis stress response. Furthermore, we show thatFkbp5manipulation alters GR activation and elucidate the cellular complexity in the PVN, in whichFkbp5operates.
Harmonization of diffusion MRI datasets with adaptive dictionary learning
Authors: St-Jean Samuel , Viergever Max A. , Leemans Alexander
Published: October 2019

Diffusion magnetic resonance imaging can indirectly infer the microstructure of tissues and provide metrics subject to normal variability in a population. Potentially abnormal values may yield essential information to support analysis of controls and patients cohorts, but subtle confounds could be mistaken for purely biologically driven variations amongst subjects. In this work, we propose a new harmonization algorithm based on adaptive dictionary learning to mitigate the unwanted variability caused by different scanner hardware while preserving the natural biological variability of the data. Our harmonization algorithm does not require paired training datasets, nor spatial registration or matching spatial resolution. Overcomplete dictionaries are learned iteratively from all datasets at the same time with an adaptive regularization criterion. removing variability attributable to the scanners in the process. The obtained mapping is applied directly in the native space of each subject towards a scanner-space. The method is evaluated with a public database which consists of two different protocols acquired on three different scanners. Results show that the effect size of the four studied diffusion metrics is preserved while removing variability attributable to the scanner. Experiments with alterations using a free water compartment, which is not simulated in the training data, shows that the modifications applied to the diffusion weighted images are preserved in the diffusion metrics after harmonization, while still reducing global variability at the same time. The algorithm could help multicenter studies pooling their data by removing scanner specific confounds, and increase statistical power in the process.