bluuebunny/crossref_metadata_2025 huggingface dataset:
Obesity as protective against, rather than a risk factor for, postoperative Clostridium difficile infection: A nationwide retrospective analysis of 1,426,807 surgical patients
Authors: Meier Karien , Nordestgaard Ask T. , Eid Ahmed I. , Kongkaewpaisan Napaporn , Lee Jae M. , Kongwibulwut Manansun , Han Kelsey R. , Kokoroskos Nikolaos , Mendoza April E. , Saillant Noelle , King David R. , Velmahos George C. , Kaafarani Haytham M.A.
Published: March 2019

BACKGROUND

Recent studies suggest that obesity is a risk factor for Clostridium difficile infection, possibly due to disruptions in the intestinal microbiome composition. We hypothesized that body mass index (BMI) is associated with increased incidence of C. difficile infection in surgical patients.

METHODS

In this nationwide retrospective cohort study in 680 American College of Surgeons National Surgical Quality Improvement Program participating sites across the United States, the occurrence of C. difficile infection within 30 days postoperatively between different BMI groups was compared. All American College of Surgeons National Surgical Quality Improvement Program patients between 2015 and 2016 were classified as underweight, normal-weight, overweight, or obese class I-III if their BMI was less than 18.5, 18.5 to 25, 25 to 30, 30 to 35, 35 to 40 or greater than 40, respectively.

RESULTS

A total of 1,426,807 patients were included; median age was 58 years, 43.4% were male, and 82.9% were white. The postoperative incidence of C. difficile infection was 0.42% overall: 1.11%, 0.56%, 0.39%, 0.35%, 0.33% and 0.36% from the lowest to the highest BMI group, respectively (p < 0.001 for trend). In univariate then multivariable logistic regression analyses, adjusting for patient demographics (e.g., age, sex), comorbidities (e.g., diabetes, systemic sepsis, immunosuppression), preoperative laboratory values (e.g., albumin, white blood cell count), procedure complexity (work relative unit as a proxy) and procedure characteristics (e.g., emergency, type of surgery [general, vascular, other]), compared with patients with normal BMI, high BMI was inversely and incrementally correlated with the postoperative occurrence of C. difficile infection. The underweight were at increased risk (odds ratio, 1.15 [1.00–1.32]) while the class III obese were at the lowest risk (odds ratio, 0.73 [0.65–0.81]).

CONCLUSION

In this nationwide retrospective cohort study, obesity is independently and in a stepwise fashion associated with a decreased risk of postoperative C. difficile infection. Further studies are warranted to explore the potential and unexpected association.

LEVEL OF EVIDENCE

Prognostic/Epidemiologic, Level IV.
Artificial oxygen carriers and red blood cell substitutes: A historic overview and recent developments toward military and clinical relevance
Authors: Bialas Christopher , Moser Christopher , Sims Carrie A.
Published: March 2019

Packed red blood cells are a critical component in the resuscitation of hemorrhagic shock. The availability of donor-derived blood products, however, suffers from issues of supply, immunogenicity, and pathogenic contamination. Deployment in remote or austere environments, such as the battlefield, is further hindered by the inherent perishability of blood products. To address the significant limitations of allogenic packed red blood cells and the urgent medical need for better resuscitative therapies for both combat casualties and civilians, there has been significant research invested in developing safe, effective, and field deployable artificial oxygen carriers. This article provides a comprehensive review of the most important technologies in the field of artificial oxygen carriers including cell-free and encapsulated hemoglobin-based oxygen carriers, perfluorocarbon emulsions, natural hemoglobin alternatives, as well as other novel technologies. Their development status, clinical, and military relevance are discussed.

LEVEL OF EVIDENCE

Systematic review.
Identifying patients with time-sensitive injuries: Association of mortality with increasing prehospital time
Authors: Chen Xilin , Guyette Francis X. , Peitzman Andrew B. , Billiar Timothy R. , Sperry Jason L. , Brown Joshua B.
Published: March 2019

BACKGROUND

Trauma is a time-sensitive disease. However, recognizing which patients have time-critical injuries in the field is challenging. Many studies failed to identify an association between increasing prehospital time (PHT) and mortality due to evaluation of heterogenous trauma patients, as well as inherent survival bias from missed deaths in patients with long PHT. Our objective was to determine if a subset of existing trauma triage criteria can identify patients in whom mortality is associated with PHT.

METHODS

Trauma patients 16 years or older transported from the scene in the National Trauma Databank 2007 to 2015 were included. Cubic spline analysis used to identify an inflection where mortality increases to identify a marginal population in which PHT is more likely associated with mortality and exclude biased patients with long PHT. Logistic regression determined the association between mortality and PHT, adjusting for demographics, transport mode, vital signs, operative interventions, and complications. Interaction terms between existing trauma triage criteria and PHT were tested, with model stratification across triage criteria with a significant interaction to determine which criteria identify patients that have increased risk of mortality associated with increasing PHT.

RESULTS

Mortality risk increased in patients with total PHT of 30 minutes or less, comprising a study population of 517,863 patients. Median total PHT was 26 minutes (interquartile range, 22–28 minutes) with median Injury Severity Score of 9 (interquartile range, 4–14) and 7.4% mortality. Overall, PHT was not associated with mortality (adjusted odd ratio [AOR], 0.984 per 5-minute increase; 95% confidence interval [CI], 0.960–1.009; p = 0.20). Interaction analysis demonstrated increased mortality associated with increasing PHT for patients with systolic blood pressure less than 90 mm Hg (AOR, 1.039; 95% CI, 1.003–1.078, p = 0.04), Glasgow Coma Scale score of 8 or less (AOR, 1.047; 95% CI, 1.018–1.076; p < 0.01), or nonextremity firearm injury (AOR, 1.049; 95% CI, 1.010–1.089; p < 0.01).

CONCLUSION

Patients with prehospital hypotension, Glasgow Coma Scale score of 8 or less, and nonextremity firearm injury have higher mortality with increasing PHT. These patients may have time-sensitive injuries and benefit from rapid transport to definitive care.

LEVEL OF EVIDENCE

Prognostic/Epidemiologic III; Therapeutic/Care Management IV.
The associations between initial radiographic findings and interventions for renal hemorrhage after high-grade renal trauma: Results from the Multi-Institutional Genitourinary Trauma Study
Authors: Keihani Sorena , Putbrese Bryn E. , Rogers Douglas M. , Zhang Chong , Nirula Raminder , Luo-Owen Xian , Mukherjee Kaushik , Morris Bradley J. , Majercik Sarah , Piotrowski Joshua , Dodgion Christopher M. , Schwartz Ian , Elliott Sean P. , DeSoucy Erik S. , Zakaluzny Scott , Sherwood Brenton G. , Erickson Bradley A. , Baradaran Nima , Breyer Benjamin N. , Fick Cameron N. , Smith Brian P. , Okafor Barbara U. , Askari Reza , Miller Brandi , Santucci Richard A. , Carrick Matthew M. , Kocik Jurek F. , Hewitt Timothy , Burks Frank N. , Heilbrun Marta E. , Myers Jeremy B.
Published: March 2019

BACKGROUND

Indications for intervention after high-grade renal trauma (HGRT) remain poorly defined. Certain radiographic findings can be used to guide the management of HGRT. We aimed to assess the associations between initial radiographic findings and interventions for hemorrhage after HGRT and to determine hematoma and laceration sizes predicting interventions.

METHODS

The Genitourinary Trauma Study is a multicenter study including HGRT patients from 14 Level I trauma centers from 2014 to 2017. Admission computed tomography scans were categorized based on multiple variables, including vascular contrast extravasation (VCE), hematoma rim distance (HRD), and size of the deepest laceration. Renal bleeding interventions included angioembolization, surgical packing, renorrhaphy, partial nephrectomy, and nephrectomy. Mixed-effect Poisson regression was used to assess the associations. Receiver operating characteristic analysis was used to define optimal cutoffs for HRD and laceration size.

RESULTS

In the 326 patients, injury mechanism was blunt in 81%. Forty-seven (14%) patients underwent 51 bleeding interventions, including 19 renal angioembolizations, 16 nephrectomies, and 16 other procedures. In univariable analysis, presence of VCE was associated with a 5.9-fold increase in risk of interventions, and each centimeter increase in HRD was associated with 30% increase in risk of bleeding interventions. An HRD of 3.5 cm or greater and renal laceration depth of 2.5 cm or greater were most predictive of interventions. In multivariable models, VCE and HRD were significantly associated with bleeding interventions.

CONCLUSION

Our findings support the importance of certain radiographic findings in prediction of bleeding interventions after HGRT. These factors can be used as adjuncts to renal injury grading to guide clinical decision making.

LEVEL OF EVIDENCE

Prognostic and Epidemiological Study, Level III and Therapeutic/Care Management, Level IV.
Age-related mortality in abusive head trauma
Authors: Nuño Miriam , Ugiliweneza Beatrice , Bardini Renee L. , Ozturk Arzu , Stephenson Jacob T. , Magaña Julia N.
Published: March 2019

BACKGROUND

Abusive head trauma (AHT) peaks during early infancy and decreases in toddler years. Infants and toddlers experience different injuries, possibly impacting the risk of mortality. We aimed to evaluate the association of age with mortality.

METHODS

We conducted a retrospective study of AHT hospitalizations in 2000, 2003, 2006, 2009, and 2012 from the Kid's Inpatient Claims Database. An accidental head trauma cohort was included to hypothesize that the association between age and mortality is unique to abuse. A nested multivariable logistic regression was used to perform the analysis.

RESULTS

Children aged 2 years to 4 years experienced higher mortality than those younger than 2 years (22% vs. 10%, p < 0.0001; adjusted odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1–2.2). The presence of subarachnoid hemorrhage (OR, 1.9; 95% CI, 1.3–2.9), cerebral edema (OR, 4.0; 95% CI, 2.9–5.4), and retinal hemorrhage (OR, 1.9; 95% CI, 1.5–2.5) were associated with an increase risk in mortality. Children younger than 2 years experienced more fractures and hemorrhage (subdural, subarachnoid, retinal) while children aged 2 years to 4 years encountered more internal injuries and cerebral edema.

In children with accidental head trauma, those aged 2 years to 4 years have a lower mortality compared with those younger than 2 years (OR, 0.4; 95% CI, 0.3–0.6). Among children younger than 2 years, AHT and accidental trauma had comparable risk of mortality (OR, 0.9; 95% CI, 0.6–1.3). However, among those aged 22 years to 4 years, AHT had a higher risk of mortality than accidental trauma (OR, 3.3; 95% CI, 2.1–5.1).

CONCLUSION

There is a considerable risk of mortality associated with age at diagnosis in children with AHT.

Children younger than 2 years and those aged 2 years to 4 years present with different types of injuries. The high risk of mortality in the children aged 2 years to 4 years is unique to AHT. Efforts should be made to increase awareness about the risk of mortality and identify factors that can aide in a timely accurate diagnosis.

LEVEL OF EVIDENCE

Prognostic and epidemiological study, level III.
Computed tomography scans prior to transfer to a pediatric trauma center: Transfer time effects, neurosurgical interventions, and practice variability
Authors: Snyder Christopher W. , Danielson Paul D. , Gonzalez Raquel , Chandler Nicole M.
Published: March 2019

BACKGROUND

Many nontrauma centers perform computed tomography (CT) on injured children prior to transfer to a pediatric trauma center (PTC), but the institutional variability and clinical impact of this practice is unclear. This study evaluated the association of pretransfer CT with transfer delays, the likelihood of emergent neurosurgical intervention among patients who underwent pretransfer head CT, and the effects of transfer distance on prevalence and regional variability of pretransfer CT.

METHODS

All injured children transferred from outlying nontrauma centers to a single freestanding PTC from 2009 to 2017 were included. Patients were categorized by undergoing pretransfer CT head alone, CT of multiple/other areas, or no CT. Transfer time (referring hospital arrival to PTC arrival) was compared between CT groups, using multivariable modeling to adjust for covariates. Neurosurgical interventions were compared between patients with normal and abnormal Glasgow Coma Scale (GCS) scores. The prevalence of pretransfer CT among referring centers was compared, with stratification by transfer distance.

RESULTS

Of 2,947 transfer patients, 1,225 (42%) underwent pretransfer CT (29%, head CT alone; 13%, other/multiple CT). Transfer times were significantly longer for patients who underwent pretransfer head CT or multiple CT (287 or 298 minutes vs. 260 minutes, p < 0.0001) after adjustment for baseline characteristics, injury severity, and transfer distance. Among patients with normal pretransfer GCS who received a pretransfer head CT, the likelihood of urgent neurosurgical intervention was 1.3%. Prevalence rates of pretransfer CT by referring center varied from 15% to 94%; prevalence increased with increasing transfer distance but demonstrated wide variability among centers of similar distance.

CONCLUSION

Pretransfer CT, whether of the head alone or multiple areas, is associated with delays in transfer to definitive care. Among patients with pretransfer GCS 15, the risk of urgent neurosurgical intervention is very low. Wide variability in pretransfer CT use between referring centers suggests opportunity for development of standardized protocols.

LEVEL OF EVIDENCE

Economic/decision, level III.
Cardiac Allograft Vasculopathy: The Enduring Enemy of Cardiac Transplantation
Authors: Nikolova Andriana P. , Kobashigawa Jon A.
Published: March 2019

Cardiac allograft vasculopathy remains a major limiting factor in the long-term survival of the heart transplant recipient. Our understanding of its pathogenesis is continuously evolving as advances in imaging modalities have allowed a direct window into the natural history of the disease. Innovation in diagnostic modalities has spurred the proliferation of prognostic tools and biomarkers. And in parallel, pharmacological advances have emerged that have helped ameliorate the disease’s progressive course.
The endocannabinoid system in migraine: from bench to pharmacy and back
Authors: Tassorelli Cristina , Greco Rosaria , Silberstein Stephen D.
Published: March 2019

Purpose of review

Migraine is a common, highly disabling disorder. Its treatment involves acute and preventive therapy. Many of available preventive medications are not well tolerated, which results in poor compliance and limited effectiveness. Cannabinoids have been proposed for the treatment of migraine but their efficacy and tolerability are controversial.

Recent findings

Cannabinoids modulate functions and activity of signaling pathways that have a key role in pain control. Growing preclinical evidence and initial clinical findings suggest that modulation of the endocannabinoid system, via endogenous or exogenous cannabinoids may be relevant for migraine via multiple mechanisms.

The endocannabinoid system qualifies as an interesting area of research worth exploration in the quest for therapeutic targets for the treatment of migraine.
Telomere attrition: metabolic regulation and signalling function?
Authors: Casagrande Stefania , Hau Michaela
Published: March 2019

Stress exposure can leave long-term footprints within the organism, like in telomeres (TLs), protective chromosome caps that shorten during cell replication and following exposure to stressors. Short TLs are considered to indicate lower fitness prospects, but why TLs shorten under stressful conditions is not understood. Glucocorticoid hormones (GCs) increase upon stress exposure and are thought to promote TL shortening by increasing oxidative damage. However, evidence that GCs are pro-oxidants and oxidative stress is causally linked to TL attrition is mixed
.
Based on new biochemical findings, we propose the
metabolic telomere attrition
hypothesis: during times of substantially increased energy demands, TLs are shortened as part of the transition into an organismal ‘emergency state’, which prioritizes immediate survival functions over processes with longer-term benefits. TL attrition during energy shortages could serve multiple roles including amplified signalling of cellular energy debt to re-direct critical resources to immediately important processes. This new view of TL shortening as a strategy to resolve major energetic trade-offs can improve our understanding of TL dynamics. We suggest that TLs are master regulators of cell homeostasis and propose future research avenues to understand the interactions between energy homeostasis, metabolic regulators and TL.
Ian Read Gibbons. 30 October 1931—30 January 2018
Authors: Gibbons Wendy E. , Vale Ronald D. , Sale Winfield S.
Published: March 2019

Ian Read Gibbons is best known for discovering dynein, a molecular motor that powers the motion of cilia and flagella, is involved in assembling the mitotic spindle and moves chromosomes as well as other cargoes inside cells. Gibbons devoted his career in the lab of more than 50 years to understanding the mechanism of how dynein works in driving motility. In doing so, he built a life-long reputation as a creative, collaborative and tenacious researcher with an unusual gift for crafting innovative solutions to tricky experimental problems. His experimental methods spanned electron as well as light microscopy, biochemistry, molecular biology, crystallography and molecular modelling. He perceived the right set of experimental moves that would allow him to dissect and observe the physical underpinnings of minute biological processes such as the delicate movements of dynein. Gibbons traced his success to the ability to envision how pieces of a scientific puzzle might fit together to make a coherent story: ‘My own approach to research has always emphasized intuition over logic. Perhaps for that reason, I get attracted to questions with aesthetic appeal.’ Even though dynein holds much promise for helping to engineer ways to fight disease, Gibbons' focus was always on the intrinsic grace of understanding nature's workings.

Gibbons’ marriage to his biochemist wife Barbara played a particularly vital role in his life. Barbara and Ian worked frequently together as she built her own scientific career through their partnership in the study of dynein. Ian's many scientific accomplishments as well as his dedication to his friends and family represent enduring gifts to us all.
Flagellar ultrastructure suppresses buckling instabilities and enables mammalian sperm navigation in high-viscosity media
Authors: Gadêlha Hermes , Gaffney Eamonn A.
Published: March 2019

Eukaryotic flagellar swimming is driven by a slender motile unit, the axoneme, which possesses an internal structure that is essentially conserved in a tremendous diversity of sperm. Mammalian sperm, however, which are internal fertilizers, also exhibit distinctive accessory structures that further dress the axoneme and alter its mechanical response. This raises the following two fundamental questions. What is the functional significance of these structures? How do they affect the flagellar waveform and ultimately cell swimming? Hence we build on previous work to develop a mathematical mechanical model of a virtual human sperm to examine the impact of mammalian sperm accessory structures on flagellar dynamics and motility. Our findings demonstrate that the accessory structures reinforce the flagellum, preventing waveform compression and symmetry-breaking buckling instabilities when the viscosity of the surrounding medium is increased. This is in agreement with previous observations of internal and external fertilizers, such as human and sea urchin spermatozoa. In turn, possession of accessory structures entails that the progressive motion during a flagellar beat cycle can be enhanced as viscosity is increased within physiological bounds. Hence the flagella of internal fertilizers, complete with accessory structures, are predicted to be advantageous in viscous physiological media compared with watery media for the fundamental role of delivering a genetic payload to the egg.
Dynamic modelling of the killing mechanism of action by virus-infected yeasts
Authors: Sheppard Sean , Dikicioglu Duygu
Published: March 2019

Killer yeasts are microorganisms, which can produce and secrete proteinaceous toxins, a characteristic gained via infection by a virus. These toxins are able to kill sensitive cells of the same or a related species. From a biotechnological perspective, killer yeasts are beneficial due to their antifungal/antimicrobial activity, but also regarded as problematic for large-scale fermentation processes, whereby those yeasts would kill starter cultures species and lead to stuck fermentations. Here, we propose a mechanistic model of the toxin-binding kinetics pertaining to the killer population coupled with the toxin-induced death kinetics of the sensitive population to study toxic action. The dynamic model captured the transient toxic activity starting from the introduction of killer cells into the culture at the time of inoculation through to induced cell death. The kinetics of K1/K2 activity via its primary pathway of toxicity was 5.5 times faster than its activity at low concentration inducing the apoptotic pathway in sensitive cells. Conversely, we showed that the primary pathway for K28 was approximately three times slower than its equivalent apoptotic pathway, indicating the particular relevance of K28 in biotechnological applications where the toxin concentration is rarely above those limits to trigger the primary pathway of killer activity.
On the forces that cable webs under tension can support and how to design cable webs to channel stresses
Authors: Bouchitté Guy , Mattei Ornella , Milton Graeme W. , Seppecher Pierre
Published: March 2019

In many applications of structural engineering, the following question arises: given a set of forces

f

1
, 

f

2
, …, 

f

N

applied at prescribed points

x

1
, 

x

2
, …, 

x

N

, under what constraints on the forces does there exist a truss structure (or wire web) with all elements under tension that supports these forces? Here we provide answer to such a question for any configuration of the terminal points

x

1
, 

x

2
, …, 

x

N

in the two- and three-dimensional cases. Specifically, the existence of a web is guaranteed by a necessary and sufficient condition on the loading which corresponds to a finite dimensional linear programming problem. In two dimensions, we show that any such web can be replaced by one in which there are at most
P
elementary loops, where elementary means that the loop cannot be subdivided into subloops, and where
P
is the number of forces

f

1
, 

f

2
, …, 

f

N

applied at points strictly within the convex hull of

x

1
, 

x

2
, …, 

x

N

. In three dimensions, we show that, by slightly perturbing

f

1
, 

f

2
, …, 

f

N

, there exists a uniloadable web supporting this loading. Uniloadable means it supports this loading and all positive multiples of it, but not any other loading. Uniloadable webs provide a mechanism for channelling stress in desired ways.
Reactive learning strategies for iterated games
Authors: McAvoy Alex , Nowak Martin A.
Published: March 2019

In an iterated game between two players, there is much interest in characterizing the set of feasible pay-offs for both players when one player uses a fixed strategy and the other player is free to switch. Such characterizations have led to extortionists, equalizers, partners and rivals. Most of those studies use memory-one strategies, which specify the probabilities to take actions depending on the outcome of the previous round. Here, we consider ‘reactive learning strategies’, which gradually modify their propensity to take certain actions based on past actions of the opponent. Every linear reactive learning strategy,

p

*, corresponds to a memory one-strategy,

p

, and vice versa. We prove that for evaluating the region of feasible pay-offs against a memory-one strategy,

C

(

p

)

, we need to check its performance against at most 11 other strategies. Thus,

C

(

p

)

is the convex hull in

R

2

of at most 11 points. Furthermore, if

p

is a memory-one strategy, with feasible pay-off region

C

(

p

)

, and

p

* is the corresponding reactive learning strategy, with feasible pay-off region

C

(

p

∗

)

, then

C

(

p

∗

)

is a subset of

C

(

p

)

. Reactive learning strategies are therefore powerful tools in restricting the outcomes of iterated games.
Northern bottlenose whales in a pristine environment respond strongly to close and distant navy sonar signals
Authors: Wensveen Paul J. , Isojunno Saana , Hansen Rune R. , von Benda-Beckmann Alexander M. , Kleivane Lars , van IJsselmuide Sander , Lam Frans-Peter A. , Kvadsheim Petter H. , DeRuiter Stacy L. , Curé Charlotte , Narazaki Tomoko , Tyack Peter L. , Miller Patrick J. O.
Published: March 2019

Impact assessments for sonar operations typically use received sound levels to predict behavioural disturbance in marine mammals. However, there are indications that cetaceans may learn to associate exposures from distant sound sources with lower perceived risk. To investigate the roles of source distance and received level in an area without frequent sonar activity, we conducted multi-scale controlled exposure experiments (n= 3) with 12 northern bottlenose whales near Jan Mayen, Norway. Animals were tagged with high-resolution archival tags (n= 1 per experiment) or medium-resolution satellite tags (n= 9 in total) and subsequently exposed to sonar. We also deployed bottom-moored recorders to acoustically monitor for whales in the exposed area. Tagged whales initiated avoidance of the sound source over a wide range of distances (0.8–28 km), with responses characteristic of beaked whales. Both onset and intensity of response were better predicted by received sound pressure level (SPL) than by source distance. Avoidance threshold SPLs estimated for each whale ranged from 117–126 dB re 1 µPa, comparable to those of other tagged beaked whales. In this pristine underwater acoustic environment, we found no indication that the source distances tested in our experiments modulated the behavioural effects of sonar, as has been suggested for locations where whales are frequently exposed to sonar.
Phage-Encoded LuxR-Type Receptors Responsive to Host-Produced Bacterial Quorum-Sensing Autoinducers
Authors: Silpe Justin E. , Bassler Bonnie L.
Published: March 2019

Quorum sensing (QS) is a process of cell-to-cell communication that bacteria use to orchestrate collective behaviors. QS relies on the cell-density-dependent production, accumulation, and receptor-mediated detection of extracellular signaling molecules called autoinducers (AIs). Gram-negative bacteria commonly use N-acyl homoserine lactones (AHLs) as their AIs and they are detected by LuxR-type receptors. Often, LuxR-type receptors are insoluble when not bound to a cognate AI. In this report, we show that LuxR-type receptors are encoded on phage genomes and, in the cases we tested, the phage LuxR-type receptors bind to and are solubilized specifically by the AHL AI produced by the host bacterium. We do not yet know the viral activities that are controlled by these phage QS receptors, however, our observations, coupled with recent reports, suggest that their occurrence is more widespread than previously appreciated. Using receptor-mediated detection of QS AIs could enable phages to garner information concerning the population density status of their bacterial hosts. We speculate that such information can be exploited by phages to optimize the timing of execution of particular steps in viral infection.

Importance

Bacteria communicate with chemical signal molecules to regulate group behaviors in a process called quorum sensing (QS). In this report, we find that genes encoding receptors for Gram-negative bacterial QS communication molecules are present on genomes of viruses that infect these bacteria. These viruses are called phages. We show that two phage-encoded receptors, like their bacterial counterparts, bind to the communication molecule produced by the host bacterium, suggesting that phages can “listen in” on their bacterial hosts. Interfering with bacterial QS and using phages to kill pathogenic bacteria represent attractive possibilities for development of new antimicrobials to combat pathogens that are resistant to traditional antibiotics. Our findings of interactions between phages and QS bacteria need consideration as new antimicrobial therapies are developed.
‘Normal’ hearing thresholds and fundamental auditory grouping processes predict difficulties with speech-in-noise perception
Authors: Holmes Emma , Griffiths Timothy D.
Published: March 2019

Understanding speech when background noise is present is a critical everyday task that varies widely among people. A key challenge is to understand why some people struggle with speech-in-noise perception, despite having clinically normal hearing. Here, we developed new figure-ground tests that require participants to extract a coherent tone pattern from a stochastic background of tones. These tests dissociated variability in speech-in-noise perception related to mechanisms for detecting static (same-frequency) patterns and those for tracking patterns that change frequency over time. In addition, elevated hearing thresholds that are widely considered to be ‘normal’ explained significant variance in speech-in-noise perception, independent of figure-ground perception. Overall, our results demonstrate that successful speech-in-noise perception is related to audiometric thresholds, fundamental grouping of static acoustic patterns, and tracking of acoustic sources that change in frequency. Crucially, measuring both peripheral (audiometric thresholds) and central (grouping) processes is required to adequately assess speech-in-noise deficits.
REM negatively predicts statistical learning but not other forms of gist
Authors: Matorina Nelly , Poppenk Jordan
Published: March 2019

Human memory for recent events is believed to undergo reactivation during sleep. This process is thought to be relevant for the consolidation of both individual episodic memories and gist extraction, the formation of generalized memory representations from multiple, related memories. Which kinds of gist are actually enhanced, however, is the subject of less consensus. To address this question, we focused our design on four types of gist: inferential gist (relations extracted across non-contiguous events), statistical learning (regularities extracted from a series), summary gist (a theme abstracted from a temporally contiguous series of items), and category gist (characterization of a stimulus at a higher level in the semantic hierarchy). Sixty-nine participants (30 men, 38 women, and 1 other) completed memory encoding tasks addressing these types of gist and corresponding retrieval tasks the same evening, the morning after, and one week later. Inferential gist was retained over a week, whereas memory for category gist, summary gist, and statistical learning decayed. Higher proportions of REM were associated with worse performance in a statistical learning task controlling for time. Our results support that REM sleep is involved in schema disintegration, which works against participants’ ability to identify regularities within temporal series.

SIGNIFICANCE STATEMENT

To gain the most from our experiences, we extract from them the most important elements, or “gist”, with sleep believed to facilitate this process. However, what is referred to as gist varies considerably across studies. We report categorically different mnemonic trajectories of two classes of gist. In particular, we show that gist involving synthesis across relational memories is retained over time, whereas other gists were subject to substantial decay. Moreover, our evidence supports the idea that REM works to discretize, rather than synthesize experiences. Future research should test similar constructs in different tasks to determine whether these findings are generalizable. Our research suggests that patients with reduced REM sleep may experience more interference between similar memories.
Complete genome sequence and evolution analysis of Psychrobacter sp. YP14 from Gammaridea Gastrointestinal Microbiota of Yap Trench
Authors: Jiaqiang Wei , Zhiyuan Gao , Whenfeng Liu , Hao Chen
Published: March 2019

Psychrobacter sp. YP14, a moderately psychrophilic bacterium belonging to the class Gammaproteobacteria, was isolated from Gammaridea Gastrointestinal Microbiota of Yap Trench. The strain has one circular chromosome of 2,895,311 bp with a 44.66% GC content, consisting of 2333 protein-coding genes, 53 tRNA genes and 9 rRNA genes. Four plasmids were completely assembled and their sizes were 13,712 bp, 19711 bp, 36270 bp, 8194 bp, respectively. In particular, a putative open reading frame (ORF) for dienelactone hydrolase (DLH) related to degradation of chlorinated aromatic hydrocarbons. To get an better understanding of the evolution of Psychrobacter sp. YP14 in this genus, six Psychrobacter strains (G, PRwf-1, DAB_AL43B, AntiMn-1,P11G5, P2G3), with publicly available complete genome, were selected and comparative genomics analysis were performed among them. The closest phylogenetic relationship was identified between strains G and K5 based on 16s gene and ANI (average nucleotide identity) values. Analysis of the pan-genome structure found that YP14 has fewer COG clusters associated with transposons and prophage which indicates fewer sequence rearrangements compared with PRwf-1. Besides, stress response-related genes of strain YP14 demonstrates that it has less strategies to cope with extreme environment, which is consistent with its intestinal habitat. The difference of metabolism and strategies coped with stress response of YP14 are more conducive to the study of microbial survival and metabolic mechanisms in deep sea environment.
PlotsOfDifferences – a web app for the quantitative comparison of unpaired data
Authors: Goedhart Joachim
Published: March 2019

The quantitative comparison of data acquired under different conditions is an important aspect of experimental science. The most widely used statistic for quantitative comparisons is the p-value. However, p-values suffer from several shortcomings. The most prominent shortcoming that is relevant for quantitative comparisons is that p-values fail to convey the magnitude of differences. The differences between conditions are best quantified by the determination of effect size. To democratize the calculation of effect size, we have developed a web-based tool. The tool uses bootstrapping to resample mean or median values for each of the conditions and these values are used to calculate the effect size and their compatibility interval. The web tool generates a graphical output, showing the bootstrap distribution of the difference next to the actual data for optimal interpretation. A tabular output with statistics and effect sizes is also generated and the table can be supplemented with p-values that are calculated with a randomization test. The app that we report here is dubbed PlotsOfDifferences and is available at: https://huygens.science.uva.nl/PlotsOfDifferences
Embodiment is related to better performance on an immersive brain computer interface in head-mounted virtual reality: A pilot study
Authors: Juliano Julia M , Spicer Ryan P , Vourvopoulos Athanasios , Lefebvre Stephanie , Jann Kay , Ard Tyler , Santarnecchi Emiliano , Krum David M , Liew Sook-Lei
Published: March 2019

Brain computer interfaces (BCI) can be used to provide individuals with neurofeedback of their own brain activity and train them to learn how to control their brain activity. Neurofeedback-based BCIs used for motor rehabilitation aim to ‘close the loop’ between attempted motor commands and sensory feedback by providing supplemental sensory information when individuals successfully establish specific brain patterns. Existing neurofeedback-based BCIs have used a variety of displays to provide feedback, ranging from devices that provide a more immersive and compelling experience (e.g., head-mounted virtual reality (HMD-VR) or CAVE systems) to devices that are considered less immersive (e.g., computer screens). However, it is not clear whether more immersive systems (i.e., HMD-VR) improve neurofeedback performance compared to computer screens, and whether there are individual performance differences in HMD-VR versus screen-based neurofeedback. In this pilot experiment, we compared neurofeedback performance in HMD-VR versus on a computer screen in twelve healthy individuals. We also examined whether individual differences in presence or embodiment correlated with neurofeedback performance in either environment. Participants were asked to control a virtual right arm by imagining right hand movements. Real-time brain activity indicating motor imagery, which was measured via electroencephalography (EEG) as desynchronized sensorimotor rhythms (SMR; 8-24 Hz) in the left motor cortex, drove the movement of the virtual arm towards (increased SMR desynchronization) or away from (decreased SMR desynchronization) targets. Participants performed two blocks of 30 trials, one for each condition (Screen, HMD-VR), with the order of conditions counterbalanced across participants. After completing each block, participants were asked questions relating to their sense of presence and embodiment in each environment. We found that, while participants’ performance on the neurofeedback-based BCI task was similar between conditions, the participants’ reported levels of embodiment was significantly different between conditions. Specifically, participants experienced higher levels of embodiment in HMD-VR compared to the computer screen. We further found that reported levels of embodiment positively correlated with neurofeedback performance only in the HMD-VR condition. Overall, these preliminary results suggest that embodiment may improve performance on a neurofeedback-based BCI and that HMD-VR may increase embodiment during a neurofeedback-based BCI task compared to a standard computer screen.
Two ecotype-related long non-coding RNAs in the environmental control of root growth
Authors: Blein Thomas , Balzergue Coline , Roulé Thomas , Gabriel Marc , Scalisi Laetitia , Sorin Céline , Christ Aurélie , Delannoy Etienne , Martin-Magniette Marie-Laure , Nussaume Laurent , Hartmann Caroline , Gautheret Daniel , Desnos Thierry , Crespi Martin
Published: March 2019

Background

Root architecture varies widely between species and even between ecotypes of the same species despite the strong conservation of the protein-coding portion of their genomes. In contrast, non-coding RNAs evolved rapidly between ecotypes and may control their differential responses to the environment as several long non-coding RNAs (lncRNAs) can quantitatively regulate gene expression.

Results

Roots from Columbia (Col) and Landsbergerecta(Ler) ecotypes respond differently to phosphate starvation. We compared complete transcriptomes (mRNAs, lncRNAs and small RNAs) of root tips from these two ecotypes during early phosphate starvation. We identified thousands of new lncRNAs categorized as intergenic or antisense RNAs that were largely conserved at DNA level in these ecotypes. In contrast to coding genes, many lncRNAs were specifically transcribed in one ecotype and/or differentially expressed between ecotypes independently of the phosphate condition. These ecotype-related lncRNAs were characterized by analyzing their sequence variability among plants and their link with siRNAs. Our analysis identified 675 lncRNAs differentially expressed between the two ecotypes including specific antisense RNAs targeting key regulators of root growth responses. Mis-regulation of several intergenic lncRNAs showed that at least two ecotype-related lncRNAs regulate primary root growth in Col.

Conclusions

The in depth exploration of the non-coding transcriptome of two ecotypes identified thousands of new lncRNAs showing specific expression in root apexes. De-regulation of two ecotype-related lncRNAs revealed a new pathway involved in the regulation of primary root growth. The non-coding genome may reveal novel mechanisms involved in ecotype adaptation of roots to different soil environments.
Evidence of extensive intraspecific noncoding reshuffling in a 169-kb mitochondrial genome of a basidiomycetous fungus
Authors: Lee Hsin-Han , Ke Huei-Mien , Lin Chan-Yi Ivy , Lee Tracy J. , Chung Chia-Lin , Tsai Isheng J.
Published: March 2019

Comparative genomics of fungal mitochondrial genomes (mitogenomes) have revealed a remarkable pattern of rearrangement between and within major phyla owing to horizontal gene transfer (HGT) and recombination. The role of recombination was exemplified at a finer evolutionary time scale in basidiomycetes group of fungi as they display a diversity of mitochondrial DNA (mtDNA) inheritance patterns. Here, we assembled mitogenomes of six species from the Hymenochaetales order of basidiomycetes and examined 59 mitogenomes from two genetic lineages ofPyrrhoderma noxium. Gene order is largely colinear while intergene regions are major determinants of mitogenome size variation. Substantial sequence divergence was found in shared introns consistent with high HGT frequency observed in yeasts, but we also identified a rare case where an intron was retained in five species since speciation. In contrast to the hyperdiversity observed in nuclear genomes ofP. noxium, mitogenomes’ intraspecific polymorphisms at protein coding sequences are extremely low. Phylogeny based on introns revealed turnover as well as exchange of introns between two lineages. Strikingly, some strains harbor a mosaic origin of introns from both lineages. Analysis of intergenic sequence indicated substantial differences between and within lineages, and an expansion may be ongoing as a result of exchange between distal intergenes. These findings suggest that the evolution in mtDNAs is usually lineage specific but chimeric mitotypes are frequently observed, thus capturing the possible evolutionary processes shaping mitogenomes in a basidiomycete. The large mitogenome sizes reported in various basidiomycetes appear to be a result of interspecific reshuffling of intergenes.
Multiple Cross Displacement Amplification Coupled with Gold Nanoparticles-Based Lateral Flow Biosensor for Detection of the Mobilized Colistin Resistance Gene mcr-1
Authors: Gong Lin , Liu Ernan , Che Jie , Li Juan , Liu Xiaoli , Xu Huiqiong , Liang Jiansheng
Published: March 2019

Fast dissemination of the mobilized colistin resistance (mcr) gene mcr-1 in Enterobacteriaceae causes a huge threat to the treatment of severe infection. In the current report, a multiple cross displacement amplification (MCDA) coupled with the detection of amplified products by gold nanoparticles-based lateral flow biosensor (LFB) assay (MCDA-LFB) was established to identify the mcr-1 gene with simpleness, rapidity, specificity and sensitivity. The MCDA-LFB assay was performed at a isothermal temperature (63°C) for only 30 min during the amplification stage, and the reaction products were directly identified by using LFB which obtained the result with 2 min. The entire process of experiments, from templates extraction to result judging, was accomplished less than 60 min. For the analytical specificity of this method, all of the 16 mcr-1-producing strains were positive, and all of the non-mcr-1 isolates got the negative results. The sensitivity of mcr-1-MCDA-LFB assay was as little as 600 fg of plasmid DNA per reaction in pure culture, and approximately 4.5×103 CFU/mL (~4.5 CFU/reaction) in fecal samples spiked with 100 μl of strains. Therefore, this technique established in the present study is suitable for the surveillance of mcr-1 gene in clinic and livestock industry.
Pyridox(am)ine 5’-phosphate oxidase deficiency induces seizures inDrosophila melanogaster
Authors: Chi Wanhao , Iyengar Atulya , Albersen Monique , Bosma Marjolein , Verhoeven-Duif Nanda M. , Wu Chun-Fang , Zhuang Xiaoxi
Published: March 2019

Pyridox(am)ine 5’-phosphate oxidase (PNPO) is a rate-limiting enzyme in converting dietary vitamin B6 (VB6) to pyridoxal 5’-phosphate (PLP), the biologically active form of VB6, and involved in the synthesis of neuro-transmitters including GABA, dopamine, and serotonin. In humans, PNPO mutations have been increasingly identified in neonatal epileptic encephalopathy and more recently also in early-onset epilepsy. Till now, little is known about the neurobiological mechanisms underlying PNPO-deficiency-induced seizures due to the lack of animal models. Previously we identified a c.95 C > A missense mutation insgll- theDrosophilahomolog of humanPNPO(hPNPO) and found mutant (sgll95) flies exhibiting a lethal phenotype on a diet devoid of VB6. Here we report the establishment of bothsgll95and ubiquitoussgllknockdown (KD) flies as valid animal models of PNPO-deficiency-induced epilepsy. Bothsgll95andsgllKD flies exhibit spontaneous seizures before they die. Electrophysiological recordings reveal that seizures caused by PNPO deficiency have characteristics similar to that in flies treated with GABA antagonist picrotoxin. Both seizures and lethality are associated with low PLP levels and can be rescued by ubiquitous expression of wild-typesgllorhPNPO, suggesting the functional conservation of the PNPO enzyme between humans and flies. Results from cell type-specificsgllKD further demonstrate that PNPO in the brain is necessary for seizure prevention and survival. Our establishment of the first animal model of PNPO deficiency will lead to better understanding of VB6 biology, thePNPOgene and its mutations discovered in patients, and can be a cost-effective system to test therapeutic strategies.
Multiple genetic loci affect place learning and memory performance in Drosophila melanogaster
Authors: Williams-Simon P.A. , Posey C. , Mitchell S. , Ng’oma E. , Mrkvicka J.A. , Zars T. , King E.G.
Published: March 2019

Learning and memory are critical functions for all animals, giving individuals the ability to respond to changes in their environment. Within populations, individuals vary, however the mechanisms underlying this variation in performance are largely unknown. Thus, it remains to be determined what genetic factors cause an individual to have high learning ability, and what factors determine how well an individual will remember what they have learned. To genetically dissect learning and memory performance, we used the DSPR, a multiparent mapping resource in the model system Drosophila melanogaster, consisting of a large set of recombinant inbred lines (RILs) that naturally vary in these and other traits. Fruit flies can be trained in a “heat box” to learn to remain on one side of a chamber (place learning), and can remember this (place memory) over short timescales. Using this paradigm, we measured place learning and memory for ∼49,000 individual flies from over 700 DSPR RILs. We identified 16 different loci across the genome that significantly affect place learning and/or memory performance, with 5 of these loci affecting both traits. To identify transcriptomic differences associated with performance, we performed RNA-Seq on pooled samples of 7 high performing and 7 low performing RILs for both learning and memory and identified hundreds of genes with differences in expression in the two sets. Integrating our transcriptomic results with the mapping results allowed us to identify nine promising candidate genes, advancing our understanding of the genetic basis underlying natural variation in learning and memory performance.