bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Results of Acetabular Fracture Fixation Using a Focal Kocher–Langenbeck Approach Without a Specialty Traction Table
Authors: Shaath M. Kareem , Lim Philip K. , Andrews Reid , Gausden Elizabeth B. , Mitchell Phillip M. , Tissue Camden M. , “Chip” Routt Milton L.
Published: January 2020

Objectives:

To report the clinical result of a series of patients who underwent acetabular fracture fixation using a Kocher–Langenbeck approach without a specialty traction table.

Design:

Retrospective case series.

Setting:

Level 1 trauma center.

Patients/Participants:

All patients who sustained posterior wall or posterior wall associated acetabular fractures that were treated operatively with a Kocher–Langenbeck approach over a 5-year period.

Intervention:

Surgical fixation of acetabular fractures using a flat, radiolucent table.

Main Outcome Measurements:

Outcomes included reduction quality and complications such as infection, heterotopic ossification, loss of reduction or fixation, medical complications, and neurologic injury.

Results:

We identified 172 patients. No articular malreductions of greater than 2 mm were noted on postoperative CT scans. There were 13 surgical complications observed (8.1%). There was 1 death in our cohort (0.6%), and 3 patients had nonfatal pulmonary emboli (1.9%). There were no nerve injuries observed. There were 6 acute infections (3.1%) requiring surgical intervention. Three patients had symptomatic heterotopic bone that required excision (1.9%). Four patients (2.5%) required eventual total hip arthroplasty.

Conclusion:

Overall, we report on the largest cohort in the literature undergoing a prone Kocher–Langenbeck without a specialty table for acetabular fracture fixation. We found that limited extremity prepping and draping for a prone Kocher–Langenbeck on a flat, radiolucent table did not result in an increased rate of postoperative neurological complications or malreductions of acetabular fractures.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Sociodemographic patterns of pain in an urban community sample: an examination of intersectional effects of sex, race, age, and poverty status
Authors: Quiton Raimi L. , Leibel Daniel K. , Boyd Eryka L. , Waldstein Shari R. , Evans Michele K. , Zonderman Alan B.
Published: January 2020

Pain disparities based on race, sex, age, and socioeconomic status have been well documented. This study aimed to examine interactions among these sociodemographic factors on self-reported bodily pain in an urban community sample to assess whether membership in multiple at-risk groups confers greater risk for pain independent of depressive symptomatology. Participants (N = 1173) were enrolled in the epidemiological Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study, and reported experiences of pain in various body sites. Logistic regression was used to examine independent and interactive relations of sociodemographic factors on the likelihood of reporting pain in one or more sites. A significant three-way interaction was found for race, sex, and poverty status (odds ratio [OR] = 6.04, 95% confidence interval [CI] [1.26-28.97], P = 0.025). Specifically, among Whites living in poverty, women were more likely to report pain than men (P = 0.043), suggesting a double disadvantage of being both female and living in poverty. Among those above the poverty line, African American (AA) men were less likely to report pain than White men (P = 0.024) and AA women (P = 0.019), potentially due to greater stoicism or coping skills and sources of resilience. Consistent with prior research, significant main effects revealed that older age (OR = 2.16, 95% CI [1.28-3.64], P = 0.004) and higher depressive symptoms (OR = 1.03, 95% CI [1.02-1.04], P < 0.001) were associated independently with increased likelihood of reporting pain. This study demonstrates that in an urban population, intersecting sociodemographic factors create unique social identities that impact pain, and emphasizes the need for identification of relevant mediational pathways.
Measured Performance and Vaccine Administration After Decision Support and Office Workflow Changes for Influenza Vaccination
Authors: Persell Stephen D. , Lewin Nora , Yagci Banu , Lee Ji Young , Oberoi Sonali K. , Orelind Erik , Roemer Phillip , Schachter Michael A. , Thomas Kathryn
Published: January 2020

Influenza vaccination is underused. We examined changes in vaccination following decision support and workflow changes in a cross-sectional analysis of three vaccination seasons among adult primary care patients from 21 practices. Interventions included clinical decision support changes to facilitate documentation; changes to rooming workflow for medical assistants and licensed practical nurses to promote vaccination, prepare orders, document care done elsewhere; and record patient refusals. We measured rates for a national vaccination performance measure and receipt of onsite vaccination. Approximately 120,000 patients were eligible each season. Performance on the quality measure increased each year (40.6% to 62.5% to 76.4%). Corresponding rates of onsite vaccination were 27.7%, 28.8%, and 31.5%. The adjusted odds ratio for onsite vaccination in the second season compared with the first was 0.94 (95% confidence interval [CI] 0.92, 0.96). Onsite vaccination was more likely in the third season compared with either previous season—adjusted odds ratio for third versus second 1.14 (95% CI, 1.12, 1.16) or adjusted odds ratio for third versus first 1.07 (95% CI 1.05–1.09). Sequential changes in decision support and patient rooming process workflows were associated with large improvements in measured performance and with a significant increase in clinic-administered influenza vaccination by the third season.
Postmastectomy Breast Reconstruction: Exploring Plastic Surgeon Practice Patterns and Perspectives
Authors: Momoh Adeyiza O. , Griffith Kent A. , Hawley Sarah T. , Morrow Monica , Ward Kevin C. , Hamilton Ann S. , Shumway Dean , Katz Steven J. , Jagsi Reshma
Published: January 2020

Background:

Within the multidisciplinary management of breast cancer, variations exist in the reconstructive options offered and care provided. The authors evaluated plastic surgeon perspectives on important issues related to breast cancer management and reconstruction and provide some insight into factors that influence these perspectives.

Methods:

Women diagnosed with early-stage breast cancer (stages 0 to II) between July of 2013 and September of 2014 were identified through the Georgia and Los Angeles Surveillance, Epidemiology, and End Results registries. These women were surveyed and identified their treating plastic surgeons. Surveys were sent to the identified plastic surgeons to collect data on specific reconstruction practices.

Results:

Responses from 134 plastic surgeons (74.4 percent response rate) were received. Immediate reconstruction (79.7 percent) was the most common approach to timing, and expander/implant reconstruction (72.6 percent) was the most common technique reported. Nearly one-third of respondents (32.1 percent) reported that reimbursement influenced the proportion of autologous reconstructions performed. Most (82.8 percent) reported that discussions about contralateral prophylactic mastectomy were initiated by patients. Most surgeons (81.3 to 84.3 percent) felt that good symmetry is achieved with unilateral autologous reconstruction with contralateral symmetry procedures in patients with small or large breasts; a less pronounced majority (62.7 percent) favored unilateral implant reconstructions in patients with large breasts. In patients requiring postmastectomy radiation therapy, one-fourth of the surgeons (27.6 percent) reported that they seldom recommend delayed reconstruction, and 64.9 percent reported recommending immediate expander/implant reconstruction.

Conclusions:

Reconstructive practices in a modern cohort of plastic surgeons suggest that immediate and implant reconstructions are performed preferentially. Respondents perceived a number of factors, including surgeon training, time spent in the operating room, and insurance reimbursement, to negatively influence the performance of autologous reconstruction.
Decreased Length of Postoperative Drain Use, Parenteral Opioids, Length of Stay, and Complication Rates in Patients Receiving Meshed versus Unmeshed Acellular Dermal Matrix in 194 Submuscular Tissue Expander–Based Breast Reconstructions: A Single-Surgeon Cohort Study
Authors: Hagarty Sarah E. , Yen Lawrence L. , Luo Jessica , Fosco Christopher R. , Gomez Kayeromi , Khare Manorama
Published: January 2020

Background:

Studies have cited possible complications and increased fluid accumulation in implant-based breast reconstruction using acellular dermal matrix. The authors propose a novel approach, manually meshing acellular dermal matrix using a skin graft mesher before use in expander-based breast reconstruction. The authors investigated postoperative drain time, complication rates, pain, and length of hospital stay in meshed versus unmeshed acellular dermal matrix cohorts.

Methods:

One hundred fourteen patients and 194 reconstructed breasts were included overall. Of these, 99 patients were included in the pain and postoperative length of hospital stay analysis. Independent t test and chi-square analyses were used for bivariate comparisons. Multiple linear regression analyses were used to further delineate impact of meshing acellular dermal matrix on drain time, postoperative parenteral narcotic requirements, and length of stay between the two cohorts.

Results:

The meshed acellular dermal matrix cohort had lower overall complication rates compared with the unmeshed cohort. Multiple linear regression analyses showed meshing the acellular dermal matrix alone decreased drain time by 7.3 days, and decreased postoperative parenteral narcotic requirements by 77 percent (20 mg morphine). Furthermore, it was the only significant predictor for a decrease in length of stay.

Conclusions:

Meshing acellular dermal matrix significantly decreased the time needed for postoperative drains. Statistical analysis showed significantly decreased overall and minor complication rates in the meshed cohort. Meshing significantly decreased parenteral narcotic requirements and, importantly, also decreased length of stay. All of these factors have important implications regarding cost and quality of care in expander-based breast reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Calf Reduction by Partial Resection of Gastrocnemius Using a Suction-Assisted Cartilage Shaver
Authors: Jong Lih-Ren
Published: January 2020

Background:

Long-term aesthetic reduction of the legs in Asians is gaining increasing popularity among cosmetic patients. Current treatment options include botulinum toxin injection, radiofrequency, neurectomy, and total, subtotal, or partial muscle resection of the gastrocnemius. Partial resection using Kelly forceps was introduced in 2000. This article presents the use of a suction-assisted cartilage shaver to perform partial resection, describing the procedures and shaver modifications and evaluating its use.

Methods:

A retrospective review of 71 cases with a minimum 6-month follow-up (average, 36.5 months; range, 6 to 160 months) was performed. Twenty partial calf reductions were performed with a short shaver, 27 with a long shaver, and 24 with an endoscope-guided long shaver.

Results:

Mean reduction of calf circumference was 2 cm (range, –1 to 6 cm); the mean preoperative and postoperative calf circumferences were 35.8 cm and 33.8 cm, respectively. Mean tissue reduction per calf was 110 g (range, 25 to 300 g).Two patients developed larger calves after surgery, one because of weight gain and the other because of weight training. Complications included surface irregularity (n = 4, 5.6 percent), numbness over the lateral ankle or lateral foot (n = 9, 12.7 percent), hematoma clot requiring surgical evacuation (n = 11, 15.5 percent), prolonged seroma (n = 2, 2.8 percent), and left ankle plantar-flexion contracture due to tight, sustained postsurgery bandaging (n = 1, 1.5 percent). Scar-related complications were hyperpigmentation (n = 6, 8.5 percent), depressed scars (n = 5, 7 percent), and hypertrophic scars (n = 2, 2.8 percent).

Conclusions:

Short, long, and endoscope-guided long suction-assisted cartilage shavers for partial resection of calf muscles can be used effectively to reduce the calf. Several mostly treatable complications were noted.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Revisiting Anastomosis to the Retrograde Internal Mammary System in Stacked Free Flap Breast Reconstruction: An Algorithmic Approach to Recipient-Site Selection
Authors: Teotia Sumeet S. , Dumestre Danielle O. , Jayaraman Avinash P. , Sanniec Kyle J. , Haddock Nicholas T.
Published: January 2020

Background:

The authors present their stacked flap breast reconstruction experience to facilitate selection of either caudal internal mammary vessels or intraflap vessels for the second recipient anastomosis.

Methods:

A retrospective review was conducted of multiflap breast reconstructions (double-pedicled deep inferior epigastric perforator, stacked profunda artery perforator, and stacked profunda artery perforator/deep inferior epigastric perforator) performed at the authors’ institution from 2011 to 2018. Data collected included demographics, recipient vessels used, and intraoperative/postoperative flap complications. Complications were compared between cranial, caudal, and intraflap anastomoses.

Results:

Four hundred stacked flaps were performed in 153 patients. Of 400 arterial anastomoses, 200 (50 percent) were to cranial internal mammary vessels, 141 (35.3 percent) were to caudal internal mammary vessels, and 59 (14.8 percent) were to intraflap vessels. Of 435 venous anastomoses, 145 (33.3 percent) were to caudal internal mammary vessels, 201 (46.2 percent) were to cranial internal mammary vessels, and 89 (20.5 percent) were to intraflap vessels. Intraoperative revision for thrombosis occurred in 12 of 141 caudal (8.5 percent), 14 of 20 cranial (7 percent), and seven of 59 intraflap (11.9 percent) arterial anastomoses (p = 0.373), and in none of caudal, three of 201 cranial (1.5 percent), and two of 89 intraflap (2.2 percent) venous anastomoses (p = 0.559). Postoperative anastomotic complications occurred in 12 of 400 flaps (3 percent) and were exclusively attributable to venous compromise; seven of 12 (58.3 percent) were salvaged, and five of 12 (41.7 percent) were lost. More lost flaps were caused by caudal [four of five (80 percent)] versus cranial [one of five (20 percent)] or intraflap (zero of five) thrombosis (p = 0.020).

Conclusion:

If vessel features are equivalent between the caudal internal mammary vessels and intraflap vessels, intraflap vessels should be used for second site anastomosis in stacked flap reconstructions.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Inhibitory regulation of calcium transients in prefrontal dendritic spines is compromised by a nonsenseShank3mutation
Authors: Ali Farhan , Shao Ling-Xiao , Gerhard Danielle M. , Sweasy Katherine , Pothula Santosh , Pittenger Christopher , Duman Ronald S. , Kwan Alex C.
Published: January 2020

TheSHANK3gene encodes a postsynaptic scaffold protein in excitatory synapses, and its disruption is implicated in neurodevelopmental disorders such as Phelan-McDermid syndrome, autism spectrum disorder, and schizophrenia. Most studies of SHANK3 in the neocortex and hippocampus have focused on disturbances in pyramidal neurons. However, GABAergic interneurons likewise receive excitatory inputs and presumably would also be a target of constitutive SHANK3 perturbations. In this study, we characterize the prefrontal cortical microcircuit in awake mice using subcellular-resolution two-photon microscopy. We focused on a nonsense R1117X mutation, which leads to truncated SHANK3 and has been linked previously to cortical dysfunction. We find that R1117X mutants have abnormally elevated calcium transients in apical dendritic spines. The synaptic calcium dysregulation is due to a loss of dendritic inhibition via decreased NMDAR currents and reduced firing of dendrite-targeting somatostatin-expressing (SST) GABAergic interneurons. Notably, upregulation of the NMDAR subunit GluN2B in SST interneurons corrects the excessive synaptic calcium signals and ameliorates learning deficits in R1117X mutants. These findings reveal dendrite-targeting interneurons, and more broadly the inhibitory control of dendritic spines, as a key microcircuit mechanism compromised by the SHANK3 dysfunction.
Identification and antimicrobial properties of bacteria isolated from naturally decaying wood
Authors: Scheublin Tanja R. , Kielak Anna M. , van den Berg Marlies , van Veen Johannes A. , de Boer Wietse
Published: January 2020

Research on wood decay in forest ecosystems has traditionally focused on wood-rot fungi, which lead the decay process through attack of the lignocellulose complex. The role of bacteria, which can be highly abundant, is still unclear. Wood-inhabiting bacteria are thought to be nutritionally dependent on decay activities of wood-rot fungi. Therefore, we hypothesized that these bacteria are not antagonistic against wood-rot fungi whereas antagonistic activity against other bacteria may be high (resource competition). This was examined for decaying wood in temperate forests. We found that the abundance of cultivable bacteria in decaying wood can be highly variable. The general pattern is an increase of bacteria with progressive decay, but we also identified several fungi that were apparently able to exclude bacteria from their woody territory. We established a bacterial collection which is highly representative for decaying wood with typical wood-inhabiting taxa:Xanthomonadaceae,Acetobacteraceae,Caulobacteraceae,Methylovirgula,Sphingomonas,BurkholderiaandGranulicella.In vitroantagonistic activity against other bacteria and fungi was evaluated. In contrast to our hypothesis, we found surprisingly low antagonistic activity against bacteria (<2% of isolates), while antagonism against fungi was more prevalent. These results may point at a prominent role of mycophagy (growth at the expense of living fungi) among wood-inhabiting bacteria.
Geminin is required for Hox gene regulation to pattern the developing limb
Authors: Lewis Emily M.A. , Sankar Savita , Tong Caili , Patterson Ethan , Waller Laura E. , Gontarz Paul , Zhang Bo , Ornitz David M. , Kroll Kristen L.
Published: January 2020

Development of the complex structure of the vertebrate limb requires carefully orchestrated interactions between multiple regulatory pathways and proteins. Among these, precise regulation of 5’ Hox transcription factor expression is essential for proper limb bud patterning and elaboration of distinct limb skeletal elements. Here, we identified Geminin (Gmnn) as a novel regulator of this process. A conditional model of Gmnn deficiency resulted in loss or severe reduction of forelimb skeletal elements, while both the forelimb autopod and hindlimb were unaffected. 5’ Hox gene expression expanded into more proximal and anterior regions of the embryonic forelimb buds in this Gmnn-deficient model. A second conditional model of Gmnn deficiency instead caused a similar but less severe reduction of hindlimb skeletal elements and hindlimb polydactyly, while not affecting the forelimb. An ectopic posterior SHH signaling center was evident in the anterior hindlimb bud of Gmnn-deficient embryos in this model. This center ectopically expressed Hoxd13, the HOXD13 target Shh, and the SHH target Ptch1, while these mutant hindlimb buds also had reduced levels of the cleaved, repressor form of GLI3, a SHH pathway antagonist. Together, this work delineates a new role for Gmnn in modulating Hox expression to pattern the vertebrate limb.

This work identifies a new role for Geminin in mouse limb development. Geminin is a nuclear protein that regulates gene expression to control several other aspects of vertebrate development.
Brain-wide mapping of water flow perception in zebrafish
Authors: Vanwalleghem Gilles , Schuster Kevin , Taylor Michael A. , Favre-Bulle Itia A. , Scott Ethan K.
Published: January 2020

Information about water flow, detected by lateral line organs, is critical to the behavior and survival of fish and amphibians. While certain specific aspects of water flow processing have been revealed through electrophysiology, we lack a comprehensive description of the neurons that respond to water flow and the network that they form. Here, we use brain-wide calcium imaging in combination with microfluidic stimulation to map out, at cellular resolution, all neurons involved in perceiving and processing water flow information in larval zebrafish. We find a diverse array of neurons responding to forward flow, reverse flow, or both. Early in this pathway, in the lateral line ganglia, these are almost exclusively neurons responding to the simple presence of forward or reverse flow, but later processing includes neurons responding specifically to flow onset, representing the accumulated volume of flow during a stimulus, or encoding the speed of the flow. The neurons reporting on these more nuanced details are located across numerous brain regions, including some not previously implicated in water flow processing. A graph theory-based analysis of the brain-wide water flow network shows that a majority of this processing is dedicated to forward flow detection, and this is reinforced by our finding that details like flow velocity and the total volume of accumulated flow are only encoded for the simulated forward direction. The results represent the first brain-wide description of processing for this important modality, and provide a departure point for more detailed studies of the flow of information through this network.

Significance statement

In aquatic animals, the lateral line is important for detecting water flow stimuli, but the brain networks that interpret this information remain mysterious. Here, we have imaged the activity of individual neurons across the entire brains of larval zebrafish, revealing all response types and their brain locations as water flow processing occurs. We find some neurons that respond to the simple presence of water flow, and others that are attuned to the flow’s direction, speed, duration, or the accumulated volume of water that has passed during the stimulus. With this information, we modeled the underlying network, describing a system that is nuanced in its processing of water flow simulating forward motion but rudimentary in processing flow in the reverse direction.
The wild grape genome sequence provides insights into the transition from dioecy to hermaphroditism during grape domestication
Authors: Badouin Hélène , Velt Amandine , Gindraud François , Flutre Timothée , Dumas Vincent , Vautrin Sonia , Marande William , Corbi Jonathan , Sallet Erika , Ganofsky Jérémy , Santoni Sylvain , Guyot Dominique , Ricciardelli Eugenia , Jepsen Kristen , Käfer Jos , Berges Hélène , Duchêne Eric , Picard Franck , Hugueney Philippe , Tavares Raquel , Bacilieri Roberto , Rustenholz Camille , Marais Gabriel
Published: January 2020

Grapevine has a major economical and cultural importance since antiquity. A key step in domestication was the transition from separate sexes (dioecy) in wildVitis viniferassp.sylvestris(V. sylvestris) to hermaphroditism in cultivatedVitis viniferassp.vinifera. While the grapevine sex locus is known to be small, its precise boundaries, gene content and the sex-determining genes are unknown. Here we obtained a high-qualityde novoreference genome forV. sylvestrisand whole-genome resequencing data of a cross. Studying SNP segregation patterns, gene content and expression in wild and cultivated accessions allowed us to build a model for sex determination in grapevine. In this model, up- and down-regulation of a cytokinin regulator is sufficient to cause female sterility and reversal to hermaphroditism, respectively. This study highlights the importance of neo-functionalization of Y alleles in sex determination and provides a resource for studying genetic diversity inV. sylvestrisand the genomic processes of grapevine domestication.
Strigolactone defective mutants ofArabidopsisexhibit delayed sepal senescence
Authors: Xu Xi , Jibran Rubina , Wang Yanting , Dong Lemeng , Flokova Kristyna , Esfandiari Azadeh , McLachlan Andrew , Heiser Axel , Sutherland-Smith Andrew , Bouwmeester Harro , Dijkwel Paul , Hunter Donald
Published: January 2020

Flower sepals are critical for flower development and vary greatly in lifespan depending on their function postpollination. However, very little is known on what controls sepal longevity. Using a sepal senescence mutant screen, we directly connected strigolactones (SL) with sepal longevity. We identified twoArabidopsismutants that harbour novel mutations in the SL biosynthetic geneMORE AXILLARY GROWTH1(MAX1) and receptorDWARF14(AtD14). The mutation inAtD14caused a substitution of the catalytic Ser-97 to Phe in the enzyme active site. The lesion inMAX1changed a highly conserved Gly-469 to Arg in the haem-iron ligand signature of the cytochrome P450 protein, which caused loss-of-function of MAX1. nCounter-based transcriptional analysis suggested an interaction between SL and sugar signalling in controlling dark-induced inflorescence senescence. The results uncover an important function for SL in regulating floral organ senescence in addition to its other diverse functions in plant development and stress response.

One-sentence summary

Two novel mutants in the strigolactone pathway demonstrate a role for the hormone in sepal senescence, and transcriptional analysis highlights interaction between strigolactones and sugar signalling.
Genome wide association study pinpoints key agronomic QTLs in African riceOryza glaberrima
Authors: Cubry Philippe , Pidon Hélène , Ta Kim Nhung , Tranchant-Dubreuil Christine , Thuillet Anne-Céline , Holzinger Maria , Adam Hélène , Kam Honoré , Chrestin Harold , Ghesquière Alain , François Olivier , Sabot François , Vigouroux Yves , Albar Laurence , Jouannic Stefan
Published: January 2020

Background

African rice,Oryza glaberrima, is an invaluable resource for rice cultivation and for the improvement of biotic and abiotic resistance properties. Since its domestication in the inner Niger delta ca. 2500 years BP, African rice has colonized a variety of ecologically and climatically diverse regions. However, little is known about the genetic basis of quantitative traits and adaptive variation of agricultural interest for this species.

Results

Using a reference set of 163 fully re-sequenced accessions, we report the results of a Genome Wide Association Study carried out for African rice. We investigated a diverse panel of traits, including flowering date, panicle architecture and resistance toRice yellow mottle virus. For this, we devised a pipeline using complementary statistical association methods. First, using flowering time as a target trait, we demonstrated that we could successfully retrieve known genes from the rice flowering pathway, and identified new genomic regions that would deserve more study. Then we applied our pipeline to panicle- and resistance-related traits, highlighting some interesting QTLs and candidate genes (includingRymv1for resistance andSP1,Ghd7.1,APO1andOsMADS1for panicle architecture). Lastly, using a high-resolution climate database, we performed an association analysis based on climatic variables, searching for genomic regions that might be involved in adaptation to climatic variations.

Conclusion

Our results collectively provide insights into the extent to which adaptive variation is governed by sequence diversity within theO. glaberrimagenome, paving the way for in-depth studies of the genetic basis of traits of interest that might be useful to the rice breeding community.
Information theory tests critical predictions of plant defense theory for specialized metabolism
Authors: Li Dapeng , Halitschke Rayko , Baldwin Ian T. , Gaquerel Emmanuel
Published: January 2020

Different plant defense theories have provided important theoretical guidance in explaining patterns in plant specialized metabolism, but their critical predictions remain to be tested. Here, we systematically explored the metabolomes ofNicotiana attenuata, from single plants to populations, as well as of closely-related species, using unbiased MS/MS analyses and processed the abundances of compound-spectrum-based MS features within an information theory framework to test critical predictions of Optimal Defense (OD) and Moving Target (MT) theories. Information components of herbivory-elicited plant metabolomes were fully consistent with the OD theory predictions and contradicted the main prediction of the MT theory. From micro- to macro-evolutionary scales, jasmonate signaling was identified as the master determinant of OD while ethylene signaling provided fine-tuning for herbivore-specific responses annotated via MS/MS molecular networks.

One-sentence summary

Information theory tests defense theory predictions by providing a common currency for comparison of specialized metabolomes
Sharp wave-ripples in human amygdala and their coordination with hippocampus during NREM sleep
Authors: Cox Roy , Rüber Theodor , Staresina Bernhard P , Fell Juergen
Published: January 2020

Cooperative interactions between the amygdala and hippocampus are widely regarded as critical for overnight emotional processing of waking experiences, but direct support from the human brain for such a dialog is absent. Using intracranial recordings in four pre-surgical epilepsy patients (two male, two female), we discovered ripples within human amygdala during non-rapid eye movement (NREM) sleep. Like hippocampal ripples, amygdala ripples are strongly associated with sharp waves, are linked to sleep spindles, and tend to co-occur with their hippocampal counterparts. Moreover, sharp waves and ripples are temporally linked across the two brain structures, with amygdala ripples occurring during hippocampal sharp waves andvice versa. Combined with further evidence of interregional sharp wave and spindle synchronization, these findings offer a potential physiological substrate for the NREM-sleep-dependent consolidation and regulation of emotional experiences.
Basal-like and Classical cells coexistence in pancreatic cancer revealed by single cell analysis
Authors: Juiz Natalia , Elkaoutari Abdessamad , Bigonnet Martin , Gayet Odile , Roques Julie , Nicolle Rémy , Iovanna Juan , Dusetti Nelson
Published: January 2020

Pancreatic ductal adenocarcinoma (PDAC) is composed of stromal, immune and epithelial cells. Transcriptomic analysis of the epithelial compartment allows a binary classification into mainly two phenotypic subtypes, classical and basal-like. However, little is known about the intra-tumor heterogeneity of the epithelial component. Growing evidences suggest that this two side phenotypic segregation is not so clear and that both could coexist in a single tumor. In order to elucidate this hypothesis, we performed single-cell transcriptomic analyses using combinational barcoding on epithelial cells from 6 different classical PDAC obtained by Endoscopic Ultrasound (EUS) with Fine Needle Aspiration (FNA). In order to purify the epithelial compartment, PDAC were grown as Biopsy Derived Pancreatic Cancer Organoids. Single cell transcriptomic analysis allowed the identification of 4 main cell clusters present in different proportions in all tumors. Remarkably, although these tumors were classified as Classical, one of the clusters corresponded to a basal-like. These results depict the unanticipated high heterogeneity of pancreatic cancers and demonstrated that basal-like cells with a high aggressive phenotype are more widespread than expected.
Error correction enables use of Oxford Nanopore technology for reference-free transcriptome analysis
Authors: Sahlin Kristoffer , Sipos Botond , James Phillip L. , Medvedev Paul
Published: January 2020

The authors have withdrawn their manuscript as the author list was changed after publication of the paper. The listed authors wish that the published version should be considered/cited as a reference for the work reported, which has the correct author list. Please refer to and cite the published work. Besides the change in the author list, the only differences are in the Acknowledgements, Competing Interests, and Data Availability sections. If you have any questions, please contact the corresponding author.
Human papillomavirus 16 positive cervical cancer in Guatemala: The D2 and D3 sublineages differ in integration rate and age of diagnosis
Authors: Lou Hong , Boland Joseph F. , Torres-Gonzalez Edmundo , Albanez Anaseidy , Zhou Weiyin , Steinberg Mia , Diaw Lena , Mitchell Jason , Roberson David , Cullen Michael , Garland Lisa , Bass Sara , Burk Robert , Yeager Meredith , Wentzensen Nicolas , Schiffman Mark , Alvirez Enrique , Gharzouzi Eduardo , Mirabello Lisa , Dean Michael
Published: January 2020

Human papillomavirus (HPV) 16 displays substantial sequence variation; four HPV16 lineages (A, B, C, D) have been described, as well as multiple sub-lineages. To identify molecular events associated with HPV16 carcinogenesis we evaluated viral variation, the integration of HPV16, and somatic mutation in 96 cervical cancer samples from Guatemala. A total of 64% (60/94) of the samples had integrated HPV16 sequences, and integration was associated with an earlier age of diagnosis (P=0.0007) and pre-menopausal disease. HPV16 integration sites were broadly distributed in the genome but in one tumor, HPV16 integrated into the promoter of the interferon regulatory factor 4 (IRF4) gene, which plays an important role in the regulation of the interferon response to viral infection. The HPV16 D2 and D3 sub-lineages were found in 23% and 30% of the tumors, respectively and were significantly associated with adenocarcinoma. D2-positive tumors had a higher rate of integration (P=0.011), earlier age of diagnosis (P=0.012), and a lower rate of somatic mutation (P=0.03). Whereas D3-positive tumors are less likely to integrate, have later age-of-diagnosis, and a higher rate of somatic mutation. In conclusion, Guatemalan cervical tumors have a high frequency of the very high-risk HPV16 D2 and D3 sub-lineages and cervical cancer patients with these variants of HPV16 differ in histology, age of- diagnosis, integration, and somatic mutation frequency. In summary, related lineages of HPV16 have different features of oncogenicity.
SparkINFERNO: A scalable high-throughput pipeline for inferring molecular mechanisms of non-coding genetic variants
Authors: Kuksa Pavel P. , Lee Chien-Yueh , Amlie-Wolf Alexandre , Gangadharan Prabhakaran , Mlynarski Elizabeth E. , Chou Yi-Fan , Lin Han-Jen , Issen Heather , Greenfest-Allen Emily , Valladares Otto , Leung Yuk Yee , Wang Li-San
Published: January 2020

We report SparkINFERNO (Spark-based INFERence of the molecular mechanisms of NOn-coding genetic variants), a scalable bioinformatics pipeline characterizing noncoding GWAS association findings. SparkINFERNO prioritizes causal variants underlying GWAS association signals and reports relevant regulatory elements, tissue contexts, and plausible target genes they affect. To achieve this, the SparkINFERNO algorithm integrates GWAS summary statistics with large-scale collection of functional genomics datasets spanning enhancer activity, transcription factor binding, expression quantitative trait loci, and other functional datasets across more than 400 tissues and cell types. Scalability is achieved by an underlying API implemented using Apache Spark and Giggle-based genomic indexing. We evaluated SparkINFERNO on large GWAS studies and show that SparkINFERNO is more than 60-times efficient and scales with data size and amount of computational resources.

Availability

SparkINFERNO runs on clusters or a single server with Apache Spark environment, and is available athttps://bitbucket.org/wanglab-upenn/SparkINFERNOorhttps://hub.docker.com/r/wanglab/spark-inferno.

Contact

lswang@pennmedicine.upenn.edu
Role of Sulphate Transporter(PiSulT)of Endophytic FungusSerendipita indicain Plant Growth and Development
Authors: Narayan Om Prakash , Verma Nidhi , Jogawat Abhimanyu , Dua Meenakshi , Johri Atul Kumar
Published: January 2020

Sulfur is an important macronutrient required for the growth, development of plants and is a key component of many metabolic pathways. We have functionally characterized a high-affinity sulphate transporter (PiSulT) from an endophytic fungusSerendipita indica. ThePiSulTbelongs to the major facilitator superfamily (MFS) of membrane transporter. ThePiSulTfunctionally complements the yeast sulphate transporter mutant HK14.PiSulTis a high-affinity sulphate transporter, havingKm15μM. We found enhanced expression ofPiSulTin external fungal hyphae which helps the fungus in the acquisition of sulphate from the soil. When knockdown (KD)-PiSulT-P.indicacolonized with the plant, it results in an 8-fold reduction in the transfer of sulphate to the colonized plants as compared to the plants colonized with the WTS. indica, which suggests thatPiSulTis playing a role in sulphate transfer from soil to host plant. Further, plants colonized with the WTS. indicawere found to be healthy in comparison to the plants colonized with the KD-PiSulT-P.indica. Additionally,S. indicacolonization provides a positive effect on total sulfur content and on plant metabolites like sulfate ions and glutathione, particularly under low sulphate condition. We observed that the expression of sulfur assimilation pathway genes ofS. indicaand plant is dependent on the availability of sulphate and on the colonization with the plant. Our study highlights the importance ofPiSulTin the improvement of sulfur nutrition of host plant particularly under low sulphate condition and in plant growth development. This study will open new vistas to useS. indicaas a bio-fertilizer in the sulphate deficient field to improve crop production.

One-Sentence Summary

High-affinity sulphate transporter ofSerendipita indica(PiSulT) transfer sulphate from soil to plant under low sulphate condition and improve plant growth and development.
The copy-number and varied strengths of MELT motifs in Spc105 balance the strength and responsiveness the Spindle Assembly Checkpoint
Authors: Roy Babhrubahan , Han Simon JY , Fontan Adrienne N. , Joglekar Ajit P.
Published: January 2020

The Spindle Assembly Checkpoint (SAC) maintains genome stability while enabling timely anaphase onset. To maintain genome stability, the SAC must be strong so that it delays cell division even if one chromosome is unattached, but for timely anaphase onset, it must be responsive to silencing mechanisms. How it meets these potentially antagonistic requirements is unclear. Here we show that the balance between SAC strength and responsiveness is determined by the number of ‘MELT’ motifs in the kinetochore protein Spc105/KNL1 and their Bub3-Bub1 binding affinities. Spc105/KNL1 must contain many strong MELT motifs to prevent chromosome missegregation, but not too many, because this delays SAC silencing and anaphase onset. We demonstrate this by constructing a Spc105 variant that trades SAC responsiveness for significantly improved chromosome segregation accuracy. We propose that the necessity of balancing SAC strength with responsiveness drives the evolutionary trend of MELT motif number amplification and degeneration of their functionally optimal amino acid sequence.
The transcription regulatory code of a plant leaf
Authors: Tu Xiaoyu , Mejía-Guerra María Katherine , Franco Jose A Valdes , Tzeng David , Chu Po-Yu , Dai Xiuru , Li Pinghua , Buckler Edward S , Zhong Silin
Published: January 2020

The transcription regulatory network underlying essential and complex functionalities inside a eukaryotic cell is defined by the combinatorial actions of transcription factors (TFs). However, TF binding studies in plants are too few in number to produce a general picture of this complex regulatory netowrk. Here, we used ChIP-seq to determine the binding profiles of 104 TF expressed in the maize leaf. With this large dataset, we could reconstruct a transcription regulatory network that covers over 77% of the expressed genes, and reveal its scale-free topology and functional modularity like a real-world network. We found that TF binding occurs in clusters covering ∼2% of the genome, and shows enrichment for sequence variations associated with eQTLs and GWAS hits of complex agronomic traits. Machine-learning analyses were used to identify TF sequence preferences, and showed that co-binding is key for TF specificity. The trained models were used to predict and compare the regulatory networks in other species and showed that the core network is evolutionarily conserved. This study provided an extensive description of the architecture, organizing principle and evolution of the transcription regulatory network inside the plant leaf.
Development of the yeastSaccharomycescerevisiae as a biosensor for the toxicity detection of toxic substances
Authors: Gong Linlin , Yang Guang , Yang Bo , Gu Jihui
Published: January 2020

A whole-cell biosensor developed with yeastSaccharomycescerevisia to detect the toxicity of chlorothalonil has been developed. This biosensor relied on the inhibition effect for metabolism by toxicants to provide detection and the degree of toxicity to yeast cells. In order to further improve the toxic sensitivity of yeast cells biosensor, the effect of the action time, the initial pH value of the medium and the temperature on inhibiting cell growth were investigated. Response surface regression analysis was conducted to obtain optimal culture conditions. Th effects of treated yeast morphology, ROS, DNA, caspase 3 activity were analyzed. This optimized yeast as a biosensor was used to detect chlorothalonil and heavy metals. The results are as follows: at optimal culture conditions, EC50values of chlorothalonil to yeast biosensor determined at incubation time 4 h increased from 0.25 µg·mL-1in the control to 0.006 µg·mL-1, which increased by 41.67 times. Compared with the control yeast cells, the morphology of optimized yeast cells were more transparent, with significantly increased intracellular vesicle rate and cell membrane permeability, intracelluar ROS increased siginificantly, DNA bands extracted was ladder, and caspase 3 activity was stimulated. The yeast biosensor had a high sensitivity to heavy metals. After analysis, many treated cells were apoptosis which was the main reason for the increasing sensitivity to detect harmful substances. It was found that the method provides a new idea for the detection of harmful substances in the environment.

Yeast cells biosensor could be used to detect harmful substances in the environment, sunch as chlorothalonil, heavy metals. Even through chemical analysis methods, such as ICP-MS and High Performance Liquid Choromatography (HPLC), have strengths in accuracy and limit of detection, it is impossible to evaluate the cytotoxicity and the biological effect of waste water by chemical result alone, and it is also expensive, prolix and complicated. However, the yeast cell biosensor is easy to operate, is sensitive to various toxicants, comparable to the other totxicity detection methods, is cheap in cost, and has. Therefore, the method which used yeast cells as biosensor will have great potential in the detection of the cytotoxicity of waste water in the future.
Interval between two sequential arrays determines their storage state in visual working memory
Authors: Li Ziyuan , Zhang Jiafeng , Liang Tengfei , Ye Chaoxiong , Liu Qiang
Published: January 2020

The visual information can be stored as either “active” representations in the active state or “activity-silent” representations in the passive state during the retention period in visual working memory (VWM). Catering to the dynamic nature of visual world, we explored how the temporally dynamic visual input was stored in VWM. In the current study, the memory arrays were presented sequentially, and the contralateral delay activity (CDA), an electrophysiological measure, was used to identify whether the memory representations were transferred into the passive state. Participants were instructed to encode two sequential arrays and retrieve them respectively, with two conditions of interval across the two arrays: 400ms and 800ms. These results provided strong evidence for the state-separated storage of two sequential arrays in different neural states if the interval between them was long enough, and the concurrent storage of them in the active state if the interval was relatively short. This conclusion was valid only when the participants encountered the task for the first time. Once participants have formed their mindset, they would apply the same storage mode to the subsequently extended or shortened interval condition.
Gene replacement therapy provides benefit in an adult mouse model of Leigh syndrome
Authors: Dulaurier Robin Reynaud , Benegiamo Giorgia , Marrocco Elena , Al-Tannir Racha , Surace Enrico Maria , Auwerx Johan , Decressac Michael
Published: January 2020

Mutations in nuclear-encoded mitochondrial genes are responsible for a broad spectrum of disorders among which Leigh syndrome (LS) is the most common in infancy. No effective therapies are available for this severe disease mainly because of the limited capabilities of the standard adeno-associated viral (AAV) vectors to transduce both peripheral organs and the central nervous system (CNS) when injected systemically in adults.

Here, we used the brain-penetrating AAV-PHP.B vector to reinstate gene expression in theNdufs4KO mouse model of LS. Intravenous delivery of an AAV.PHP.B-Ndufs4 vector in 1-month old KO mice restored mitochondrial complex I activity in several organs including the CNS. This gene replacement strategy extended lifespan, rescued metabolic parameters, provided behavioral improvement, and corrected the pathological phenotype in the brain, retina, and heart ofNdufs4KO mice. These results provide a robust proof that gene therapy strategies targeting multiple organs can rescue fatal neurometabolic disorders with CNS involvement.
A Rainbow Reporter Tracks Single Cells and Reveals Heterogeneous Cellular Dynamics among Pluripotent Stem Cells and their Differentiated Derivatives
Authors: El-Nachef Danny , Shi Kevin , Beussman Kevin M. , Martinez Refugio , Regier Mary C. , Everett Guy W. , Murry Charles E. , Stevens Kelly R. , Young Jessica E. , Sniadecki Nathan J. , Davis Jennifer
Published: January 2020

Recent single cell analyses have found molecular heterogeneities within populations of pluripotent stem cells (PSCs). A tool that tracks single cell lineages and their phenotypes longitudinally would reveal whether heterogeneity extends beyond molecular identity. Hence, we generated a stable Cre-inducible rainbow reporter human PSC line that provides up to 18 unique membrane-targeted fluorescent barcodes. These barcodes enable repeated assessments of single cells as they clonally expand, change morphology, and migrate. Owing to the cellular resolution of this reporter, we identified subsets of PSCs with enhanced clonal expansion, synchronized cell divisions, and persistent localization to colony edges. Reporter expression was stably maintained throughout directed differentiation into cardiac myocytes, cortical neurons, and hepatoblasts. Repeated examination of neural differentiation revealed self-assembled cortical tissues derive from clonally dominant progenitors. Collectively, these findings demonstrate the broad utility and easy implementation of this reporter line for tracking single cell behavior.