bluuebunny/crossref_metadata_2025 huggingface dataset:
Type III Interferons in Systemic Lupus Erythematosus
Authors: Amezcua-Guerra Luis M. , Márquez-Velasco Ricardo , Chávez-Rueda Adriana K. , Castillo-Martínez Diana , Massó Felipe , Páez Araceli , Colín-Fuentes Juan , Bojalil Rafael
Published: September 2017

Objective

The aim of this study was to assess associations between serum type III (λ) interferons (IFN-λ) and disease activity in systemic lupus erythematosus (SLE).

Methods

Serum levels of IFN-λ1, IFN-λ2, and IFN-λ3 were measured in 93 SLE patients and 67 healthy individuals. The associations with overall disease activity, organ-specific damage, and SLE-related antibodies were assessed.

Results

Median IFN-λ1 levels were 0 pg/mL (range, 0–510 pg/mL) and 0 pg/mL (0–171 pg/mL; P = 0.814) in SLE patients and control subjects, respectively. These figures were 0 pg/mL (0–28 pg/mL) and 0 pg/mL (0–43 pg/mL; P = 0.659) for IFN-λ2, as well as 83 pg/mL (0–965 pg/mL) and 42 pg/mL (0–520 pg/mL; P = 0.002) for IFN-λ3, respectively. According to the Systemic Lupus Erythematosus Disease Activity Index categories, IFN-λ3 levels were 44 pg/mL (0–158 pg/mL) in quiescent, 117 pg/mL (0–344 pg/mL) in mild, 79 pg/mL (0–965 pg/mL) in moderate, and 78 pg/mL (0–329 pg/mL) in severe disease, with the highest levels found in patients with serosal or cutaneous involvement. In line with this, IFN-λ3 levels were inversely correlated with C3 (ρ = −0.44; 95% confidence interval, −0.62 to −0.20; P = 0.0003) and C4 (ρ = −0.40; 95% confidence interval, −0.59 to −0.15; P = 0.0001) complement proteins. In addition, higher IFN-λ3 levels were found in patients positive for anti-Ro/SSA antibodies than in those negative for that antibody (122 pg/mL [0–965 pg/mL] vs. 0 pg/mL [0–165 pg/mL]; P = 0.001). The concentration of IFN-λ3 also was higher in patients receiving glucocorticoids (104 pg/mL [0–965 pg/mL] vs. 30 pg/mL [0–165 pg/mL]; P = 0.009), and a dose-related effect was observed.

Conclusions

Interferon λ3, a subtype of type III IFNs, is associated with the extent of lupus activity, in particular with active serosal and cutaneous disease. This association could be mechanistically related to anti-Ro/SSA antibodies.
Prognostic Factors for Permanent Work Disability in Patients With Rheumatoid Arthritis Who Received Combination Therapy of Conventional Synthetic Disease-Modifying Antirheumatic Drugs
Authors: Vazquez-Villegas M. Luisa , Gamez-Nava Jorge I. , Celis Alfredo , Sanchez-Mosco Dalia , de la Cerda-Trujillo Liliana F. , Murillo-Vazquez Jessica D. , Saldaña-Cruz A. Miriam , Alcaraz-Lopez Miriam F. , Diaz-Rizo Valeria , Alvarez-Nemegyei Jose , Cardiel Mario H. , Gonzalez-Lopez Laura
Published: September 2017

Background

There is limited information about the factors related with the development of long-term permanent work disability (PWD) in rheumatoid arthritis (RA) treated with a combination of conventional synthetic disease-modifying antirheumatic drugs (cs-DMARDs).

Objective

The aim of this study was to evaluate incidence and factors associated with the development of PWD in RA treated with combination therapy using conventional synthetic cs-DMARDs.

Methods

We assessed in multivariate models the effect of clinical and demographic factors in the development of PWD in a long-term retrospective cohort of 180 workers with RA who were treated with a combination of cs-DMARDs.

Results

Incidence rates of PWD were 2.2% at 1 year, 7.7% at 5 years, 24.9% at 10 years, 34.9% at 15 years, and 45% at 20 years. In the adjusted Cox regression analysis, factors associated with PWD development were the first failure with combination of cs-DMARDs (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.05–5.46; P = 0.03), poor functioning at time of cohort onset (HR, 2.2; 95% CI, 1.05–4.70; P = 0.03), and requirement for joint replacement (HR, 3.3; 95% CI, 1.28–8.79; P = 0.01).

Conclusions

Around 25% of workers with combination therapy with cs-DMARDs developed PWD in 10 years following the diagnosis of RA. Some factors increase the risk of disability. Permanent work disability generates a relevant society burden and increases health care costs. Therefore, indicators predicting failure of combination therapies with cs-DMARDs might provide clinicians of useful tools for modifying treatments avoiding the disease progression.
Non contrast, Pseudo-Continuous Arterial Spin Labeling and Accelerated 3-Dimensional Radial Acquisition Intracranial 3-Dimensional Magnetic Resonance Angiography for the Detection and Classification of Intracranial Arteriovenous Shunts
Authors: Schubert Tilman , Clark Zachary , Sandoval-Garcia Carolina , Zea Ryan , Wieben Oliver , Wu Huimin , Turski Patrick A. , Johnson Kevin M.
Published: September 2017

Objectives

The aim of this study was to assess the sensitivity and specificity of pseudo-continuous arterial spin labeling (PCASL) magnetic resonance angiography (MRA) with 3-dimensional (3D) radial acquisition for the detection of intracranial arteriovenous (AV) shunts.

Materials and Methods

A total of 32 patients who underwent PCASL-MRA, clinical magnetic resonance imaging (MRI)/MRA exam, and digital subtraction angiography (DSA) were included in this retrospective analysis. Twelve patients presented with AV shunts. Among these were 8 patients with AV malformations (AVM) and 4 patients with AV fistulas (AVF). The clinical MRI/MRA included 3D time-of-flight MRA in all cases and time-resolved, contrast-enhanced MRA in 9 cases (6 cases with AV shunting). Research MRI and clinical MRI were independently evaluated by 2 neuroradiologists blinded to patient history. A third radiologist evaluated DSA imaging. A diagnostic confidence score was used for the presence of abnormalities associated with AV shunting (1–5). The AVMs were characterized using the Spetzler-Martin scale, whereas AVFs were characterized using the Borden classification. κ Statistics were applied to assess intermodality agreement.

Results

Compared with clinical MRA, noncontrast PCASL-MRA with 3D radial acquisition yielded excellent sensitivity and specificity for the detection of intracranial AV shunts (reader 1: 100%/100%, clinical MRA: 91.7%, 94.4%; reader 2: 91.7%/100%, clinical MRA: 91.7%/100%). Diagnostic confidence was 4.8/4.66 with PCASL-MRA and 4.25/4.66 with clinical MRA. For AVM characterization with PCASL-MRA, intermodality agreement with DSA showed κ values of 0.43 and 0.6 for readers 1 and 2, respectively. For AVF characterization, intermodality agreement showed κ values of 0.56 for both readers.

Conclusion

Noncontrast PCASL-MRA with 3D radial acquisition is a potential tool for the detection and characterization of intracranial AV shunts with a sensitivity and specificity equivalent or higher than routine clinical MRA.
Fractures of the Nasal Bones: Is External Splinting Really Warranted?
Authors: Schoinohoriti Ourania , Igoumenakis Dimosthenis , Rallis George
Published: September 2017

Background:

It has been advocated that reduction of nasal bone fractures should be followed by internal packing and/or external splinting. Despite the ample literature concerning the advantages and limitations of various splint types, the necessity and effectiveness of external splinting has not been well documented.

Objective:

To present the authors’ experience and review the literature on treatment of nasal bone fractures, focusing on the indications and effectiveness of external splinting following closed reduction.

Study Design:

Retrospective analysis and literature review.

Patients and Methods:

Medical records of all patients, treated at the Department of Oral and Maxillofacial Surgery of the “KAT” General Hospital of Attica between January 2010 and December 2016 for facial trauma including nasal bone fractures, were retrospectively reviewed. Patient demographic data, fracture type, applied treatment, complications, and final outcome were registered.

Results:

A total of 77 patients (58 males; 19 females) were included in the study. The age range was 18 to 65 years (mean, 37.8). Closed reduction without external splinting was performed in 63 patients and open reduction with internal fixation in 6; 8 severely comminuted fractures were treated with closed reduction and external splinting. The mean follow-up was 4.8 months. All severely comminuted fractures presented complications.

Conclusions:

External splinting following closed reduction of nasal bone fractures should not be used routinely but only in selected patients with severe comminution. Since the pertinent literature is inconclusive on the indications and effectiveness of external splinting, randomized controlled studies are warranted to fully elucidate the issue.
Multiple (Concomitant) Traumatic Pseudoaneurysms of the Superficial Temporal Artery
Authors: Gurkanlar Doga , Fahrioğlu Sevda Lafci
Published: September 2017

The authors present a case with a 22-year-old man suffering from a 2 pseudoaneurysms at the temporal region following trauma. The second pseudoaneurysm was diagnosed through an astute use of digital subtraction angiography along with ultrasound to the right external carotid artery which was preferred due to the presence of a vascular pathology at the region of the trauma. During surgery, the distal and proximal ends of both aneurysms were ligated and resected. The concomitant pseudoaneurysms and the use of digital subtraction angiography should be kept in mind in such trauma patients to prevent additional surgical interventions.
Evaluating the traditional day and night shift in an acute care surgery fellowship: Is the swing shift a better choice?
Authors: Chestovich Paul J. , McNicoll Christopher F. , Ingalls Nichole K. , Kuhls Deborah A. , Fraser Douglas R. , Morrissey Shawna L. , Fildes John J.
Published: September 2017

BACKGROUND

Fellowship trainees in acute care surgery require experience in the management of complex and operative trauma cases. Trauma center staffing usually follows standard 12-hour or 24-hour shifts, with resident and fellow trainees following a similar schedule. Although trauma admissions can be generally unpredictable, we analyzed temporal trends of trauma patient arrival times to determine the best time frame to maximize trainee experience during each day.

METHODS

We reviewed 10 years (2007–2016) of trauma registry data for blunt and penetrating trauma activations. Hourly volumetric trends were observed, and three specific events were chosen for detailed analysis: (1) trauma activation with Injury Severity Score (ISS) greater than 15, (2) laparotomy for trauma, and (3) thoracotomy for trauma. A retrospective shift log was created, which included day (7:00 am to 7:00 pm), night (7:00 pm to 7:00 am), and swing (noon to midnight) shifts. A swing shift was chosen because it captures the peak volume for all three events. Means and 95% confidence intervals were calculated, and comparisons were made between shifts using the Wilcoxon matched-pairs signed rank test with Bonferroni correction, and p less than 0.05 considered significant.

RESULTS

During the 10-year study period, 28,287 patients were treated at our trauma center. This included the evaluation and management of 7,874 patients with ISS greater than 15, performance of 1,766 laparotomies, and 392 thoracotomies for trauma. Swing shift was superior to both day and night shifts for ISS greater than 15 (p < 0.001). Both swing and night shifts were superior to day shift for laparotomies (p < 0.001). Swing shift was superior to both day shift (p < 0.001) and night shift (p = 0.031). Shifts with the highest yield of ISS greater than 15, laparotomies, and thoracotomies include night and swing shifts on Fridays and Saturdays.

CONCLUSION

Projected experience of acute care surgery fellows in managing complex trauma patients increases with the integration of swing shifts into the schedule. Daily trauma volume follows a temporal pattern which, when used correctly, can increase trainee exposure to complex and operative trauma cases. We encourage other centers to analyze their volume and adjust trainee schedules accordingly to maximize their educational experience.

Level of Evidence

Therapeutic study, level IV.
The “mortality ascent”: Hourly risk of death for hemodynamically unstable trauma patients at Level II versus Level I trauma centers
Authors: Herrera-Escobar Juan Pablo , Rios-Diaz Arturo J. , Zogg Cheryl K. , Wolf Lindsey L. , Harlow Alyssa , Schneider Eric B. , Cooper Zara , Ordonez Carlos Alberto , Salim Ali , Haider Adil H.
Published: September 2017

BACKGROUND

Severely injured trauma patients have higher in-hospital mortality at Level II versus Level I trauma centers (TCs). To better understand these differences, we sought to determine if there were any periods during which hemodynamically unstable trauma patients are at higher risk of death at Level II versus Level I TCs within the first 24 hours postadmission.

STUDY DESIGN

Trauma patients aged 18 years to 64 years, with Injury Severity Score of 15 or greater, systolic blood pressure less than 90 mm Hg at admission, and treated at Level II or Level I TCs, were identified using the 2007 to 2012 National Trauma Data Bank. Burn patients, transfers, and patients dead on arrival were excluded. Log-binomial regression models, adjusted for patient- and hospital-level confounders, were used to compare mortality at Level II versus Level I TCs over the first 24 hours postadmission.

RESULTS

Of 13,846 hemodynamically unstable patients, 4,212 (30.4%) were treated at 149 Level II TCs, and 9,634 (69.6%) at 116 Level I TCs. Within the first 24 hours, 3,059 (22.1%) patients died. In risk-adjusted models, mortality risk was significantly elevated at Level II versus Level I TCs during the 24 hours postadmission (relative risk, 1.08; 95% confidence interval, 1.01–1.16). Hourly mortality risk was significantly different between Level II and Level I TCs during 4 hours to 7 hours postadmission, with a maximal difference at 7 hours (relative risk, 1.70; 95% confidence interval, 1.23–2.36) and comparable mortality risk beyond 7 hours postadmission.

CONCLUSION

The 4-hour to 7-hour time window postadmission is critical for hemodynamically unstable trauma patients. Variations in available treatment modalities may account for higher relative mortality at Level II TCs during this time. Further investigation to elucidate specific risk factors for mortality during this period may lead to reductions in in-hospital mortality among hemodynamically unstable trauma patients.

Level of Evidence

Therapeutic/care management, level IV.
A Follow-up Study of Electroconvulsive Therapy in Children and Adolescents
Authors: Mitchell Shanti , Hassan Ehmer , Ghaziuddin Neera
Published: September 2017

Objectives

Electroconvulsive therapy (ECT) is an effective and a safe treatment for several severe psychiatric disorders across the age span. However, its use remains controversial and highly stigmatized especially among patients under 18 years. In this study, we examined current symptoms, attitudes, perception, and functioning of patients treated with ECT when they were less than 18 years old.

Methods

Participants had received ECT before age 18, between 1989 and 2015, at a tertiary medical center. Institutional review board–approval was obtained, and study documents (cover letter, consent, self-ratings scales for depression, anxiety, global functioning, and suicidality) were mailed.

Results

Based on self-rated depression, 59.1% (13/22) participants indicated mild or no depression; 65% (13/20) reported mild or no anxiety; the majority, 84.3% (16/19) perceived ECT as having improved their overall illness; and 27.3% (6/22) among the respondents reported no clinical impairment on a global functioning scale, whereas 72.7% (16/22) reported significant or severe impairment. Despite reports of ongoing impaired global functioning among some participants, adequate academic performance (83.3%, 5/6) and mild or no suicidality (78.3%, 18/23) were endorsed by the majority reported.

Conclusions

The majority of participants who had received ECT before age 18 years reported mild or absence of depression and anxiety on self-rated follow-up measures after treatment with ECT. Most notably, the majority reported absence of suicidality and adequate academic performance. A number of respondents, however, continued to endorse global impairment, which may be a reflection of their baseline severe illness, which had warranted treatment with ECT.
2016 Wilkins–Bernal–Medawar lecture The curious history of curiosity-driven research
Authors: Agar Jon
Published: September 2017

Curiosity has a curious place in the history of science. In the early modern period, curiosity was doubled-edged: it was both a virtue, the spring for a ‘love of truth’, but also the source of human error and even personal corruption. In the twentieth century, curiosity had become an apparently uncomplicated motivation. Successful scientists, for example Nobel Prize winners in their lectures and biographies, frequently attributed their first steps into science to a fundamental curiosity, an irrepressible desire to ask the question ‘why?’. The aside made by Albert Einstein in private correspondence in 1952—‘I have no special talents. I am only passionately curious’—has now become a meme. Yet in the twentieth century, science was shaped by many forces, and the practical utility of science in the real, messy problematic worlds of its formation seem far removed from the seeming innocence of curiosity-driven research. In my lecture and this paper, I ask why scientists say they ask ‘why?’, and trace the curious history of the idea of curiosity-driven science. In particular, I distinguish between a long and short history of curiosity in science, with the latter associated with the term ‘curiosity-driven science’ and the UK administration of Margaret Thatcher.
Quantifying the dynamic wing morphing of hovering hummingbird
Authors: Maeda Masateru , Nakata Toshiyuki , Kitamura Ikuo , Tanaka Hiroto , Liu Hao
Published: September 2017

Animal wings are lightweight and flexible; hence, during flapping flight their shapes change. It has been known that such dynamic wing morphing reduces aerodynamic cost in insects, but the consequences in vertebrate flyers, particularly birds, are not well understood. We have developed a method to reconstruct a three-dimensional wing model of a bird from the wing outline and the feather shafts (rachides). The morphological and kinematic parameters can be obtained using the wing model, and the numerical or mechanical simulations may also be carried out. To test the effectiveness of the method, we recorded the hovering flight of a hummingbird (Amazilia amazilia) using high-speed cameras and reconstructed the right wing. The wing shape varied substantially within a stroke cycle. Specifically, the maximum and minimum wing areas differed by 18%, presumably due to feather sliding; the wing was bent near the wrist joint, towards the upward direction and opposite to the stroke direction; positive upward camber and the ‘washout’ twist (monotonic decrease in the angle of incidence from the proximal to distal wing) were observed during both half-strokes; the spanwise distribution of the twist was uniform during downstroke, but an abrupt increase near the wrist joint was found during upstroke.
Familiarity affects collective motion in shoals of guppies (
Poecilia reticulata
)
Authors: Davis Scarlet , Lukeman Ryan , Schaerf Timothy M. , Ward Ashley J. W.
Published: September 2017

The coordinated and synchronized movement of animals in groups often referred to as collective motion emerges through the interactions between individual animals within the group. Factors which affect these interactions have the potential to shape collective movement. One such factor is familiarity, or the tendency to bias behaviour towards individuals as a result of social recognition. We examined the effect of familiarity on the expression of collective motion in small shoals of female guppies (
Poecilia reticulata
). Groups comprising familiar individuals were more strongly polarized than groups of unfamiliar individuals, particularly when in novel surroundings. The ability to form more strongly polarized shoals potentially promotes information transfer and enhances the anti-predator benefits of grouping.
Dielectric properties and carbothermic reduction of zinc oxide and zinc ferrite by microwave heating
Authors: Omran Mamdouh , Fabritius Timo , Heikkinen Eetu-Pekka , Chen Guo
Published: September 2017

This paper aims to study the dielectric properties and carbothermic reduction of zinc oxide (zincite, ZnO) and zinc ferrite (franklinite, ZnFe
2
O
4
) by microwave heating. To achieve this aim, the dielectric properties were measured with an open-ended coaxial method to understand the behaviour of the samples under microwave irradiation. The effects of microwave power, duration time and sample mass on the heating rate, and the effects of the stoichiometric amount of graphite on the reduction of ZnO and decomposition of ZnFe
2
O
4
were investigated. The results show that ZnFe
2
O
4
has significantly higher dielectric properties compared to ZnO. Generally, for both samples, the dielectric values at room temperature were quite low, indicating that both ZnO and ZnFe
2
O
4
are poor microwave absorbers. It was found that the temperatures have a more significant effect on the imaginary permittivities than on the real permittivities. The heating rate showed that the sample temperature increased with increase in microwave power and sample mass. Using 700 W of microwave power and two times the stoichiometric amount of graphite, almost complete reduction of ZnO was achieved in 12 min, while ZnFe
2
O
4
completely decomposed to zincite and wustite in 3 min.
Monarch butterfly population decline in North America: identifying the threatening processes
Authors: Thogmartin Wayne E. , Wiederholt Ruscena , Oberhauser Karen , Drum Ryan G. , Diffendorfer Jay E. , Altizer Sonia , Taylor Orley R. , Pleasants John , Semmens Darius , Semmens Brice , Erickson Richard , Libby Kaitlin , Lopez-Hoffman Laura
Published: September 2017

The monarch butterfly (Danaus plexippus) population in North America has sharply declined over the last two decades. Despite rising concern over the monarch butterfly's status, no comprehensive study of the factors driving this decline has been conducted. Using partial least-squares regressions and time-series analysis, we investigated climatic and habitat-related factors influencing monarch population size from 1993 to 2014. Potential threats included climatic factors, habitat loss (milkweed and overwinter forest), disease and agricultural insecticide use (neonicotinoids). While climatic factors, principally breeding season temperature, were important determinants of annual variation in abundance, our results indicated strong negative relationships between population size and habitat loss variables, principally glyphosate use, but also weaker negative effects from the loss of overwinter forest and breeding season use of neonicotinoids. Further declines in population size because of glyphosate application are not expected. Thus, if remaining threats to habitat are mitigated we expect climate-induced stochastic variation of the eastern migratory population of monarch butterfly around a relatively stationary population size.
Interaction between path integration and visual orientation during the homing run of fiddler crabs
Authors: Murakami Hisashi , Tomaru Takenori , Gunji Yukio-Pegio
Published: September 2017

Foraging fiddler crabs form a strict spatial relationship between their current positions and burrows, allowing them to run directly back to their burrows when startled even without visual contacts. Path integration (PI), the underlying mechanism, is a universal navigation strategy through which animals continuously integrate directions and distances of their movements. However, we report that fiddler crabs also use visual orientation during homing runs using burrow entrances as cues, with the prioritised mechanism (i.e. PI or visual) determined by the distance (which has a threshold value) between the goal, indicated by PI, and the visual cue. When we imposed homing errors using fake entrances (visual cue) and masking their true burrows (goal of PI), we found that frightened fiddler crabs initially ran towards the true burrow following PI, then altered their behaviour depending on the distance between the fake entrance and masked true burrow: if the distance was large, they kept running until they reached the true burrow, ignoring the visual cue; however, if the distance was small, they altered the homing path and ran until they reached the fake entrance. This suggests that PI and visual mechanism in fiddler crabs are mutually mediated to achieve their homing behaviour.
Loss of generalist plant species and functional diversity decreases the robustness of a seed dispersal network
Authors: Bastazini Vinicius A. G. , Debastiani Vanderlei J. , Azambuja Bethânia O. , Guimarães Paulo R. , Pillar Valério D.
Published: September 2017

Understanding cascading effects of species loss has become a major challenge for ecologists. Traditionally, the robustness of ecological networks has been evaluated based on simulation studies where primary extinctions occur at random or as a function of species specialization, ignoring other important biological factors. Here, we estimate the robustness of a seed dispersal network from a grassland–forest mosaic in southern Brazil, simulating distinct scenarios of woody plant species extinction, including scenarios where species are eliminated based on their evolutionary and functional distinctiveness. Our results suggest that the network is more robust when species are eliminated based on their evolutionary uniqueness, followed by random extinctions, the extinction of the most specialist species, functional distinctiveness and, at last, when the most generalist species are sequentially eliminated. Our results provide important information for grassland–forest mosaic management, as they indicate that loss of generalist species and functional diversity makes the system more likely to collapse.
Leaf shedding as a bacterial defense in Arabidopsis cauline leaves
Authors: Patharkar O. Rahul , Gassmann Walter , Walker John C.
Published: September 2017

Plants utilize an innate immune system to protect themselves from disease. While many molecular components of plant innate immunity resemble the innate immunity of animals, plants also have evolved a number of truly unique defense mechanisms, particularly at the physiological level. Plant’s flexible developmental program allows them the unique ability to simply produce new organs as needed, affording them the ability to replace damaged organs. Here we develop a system to study pathogen-triggered leaf abscission in Arabidopsis. Cauline leaves infected with the bacterial pathogenPseudomonas syringaeabscise as part of the defense mechanism.Pseudomonas syringaelacking a functional type III secretion system fail to elicit an abscission response, suggesting that the abscission response is a novel form of immunity triggered by effectors.HAESA/HAESA-like 2, INFLORESCENCE DEFICIENT IN ABSCISSION, andNEVERSHEDare all required for pathogen-triggered abscission to occur. Additionallyphytoalexin deficient 4, enhanced disease susceptibility 1, salicylic acid induction deficient 2, andsenescence-associated gene 101plants with mutations in genes necessary for bacterial defense and salicylic acid signaling, and NahG transgenic plants with low levels of salicylic acid fail to abscise cauline leaves normally. Bacteria that physically contact abscission zones trigger a strong abscission response; however, long distance signals are also sent from distal infected tissue to the abscission zone, alerting the abscission zone of looming danger. We propose a threshold model regulating cauline leaf defense where minor infections are handled by limiting bacterial growth, but when an infection is deemed out of control, cauline leaves are shed. Together with previous results our findings suggest that salicylic acid may regulate both pathogen‐ and drought-triggered leaf abscission.

Author Summary

Plants have a flexible development program that determine their form. We describe an organ level defense response in Arabidopsis to bacterial attack where plants simply shed heavily infected leaves. The genetics regulating this defense mechanism are comprised of both classical defense genes and floral organ abscission genes working together. Long distance signals are transmitted from infected areas to abscission zones which activate the abscission receptor. Salicylic acid, a defense hormone, signaling is necessary for cauline leaf abscission.
Sequences enriched in Alu repeats drive nuclear localization of long RNAs in human cells
Authors: Lubelsky Yoav , Ulitsky Igor
Published: September 2017

Long noncoding RNAs (lncRNAs) are emerging as key players in multiple cellular pathways, but their modes of action, and how those are dictated by sequence remain elusive. While lncRNAs share most molecular properties with mRNAs, they are more likely to be enriched in the nucleus, a feature that is likely to be crucial for function of many lncRNAs, but whose molecular underpinnings remain largely unclear. In order identify elements that can force nuclear localization we screened libraries of short fragments tiled across nuclear RNAs, which were cloned into the untranslated regions of an efficiently exported mRNA. The screen identified a short sequence derived from Alu elements and found in many mRNAs and lncRNAs that increases nuclear accumulation and reduces overall expression levels. Measurements of the contribution of individual bases and short motifs to the element functionality identified a combination of RCCTCCC motifs that are bound by the abundant nuclear protein HNRNPK. Increased HNRNPK binding and C-rich motifs are predictive of substantial nuclear enrichment in both lncRNAs and mRNAs, and this mechanism is conserved across species. Our results thus detail a novel pathway for regulation of RNA accumulation and subcellular localization that has been co-opted to regulate the fate of transcripts that integrated Alu elements.
Evolution and Engineering of Allosteric Regulation in Protein Kinases
Authors: Pincus David , Pandey Jai P. , Creixell Pau , Resnekov Orna , Reynolds Kimberly A.
Published: September 2017

Allosteric regulation – the control of protein function by sites far from the active site – is a common feature of proteins that enables dynamic cellular responses. Reversible modifications such as phosphorylation are well suited to mediate such regulatory dynamics, yet the evolution of new allosteric regulation demands explanation. To understand this, we mutationally scanned the surface of a prototypical kinase to identify readily evolvable phosphorylation sites. The data reveal a set of spatially distributed “hotspots” that coevolve with the active site and preferentially modulate kinase activity. By engineering simple consensus phosphorylation sites at these hotspots we successfully rewiredin vivocell signaling. Beyond synthetic biology, the hotspots are frequently used by the diversity of natural allosteric regulatory mechanisms in the kinase family and exploited in human disease.

ONE SENTENCE SUMMARY

Cell signaling is easily rewired by introducing new phosphoregulation at latent allosteric surface sites.
Large-Scale Analysis of Disease Pathways in the Human Interactome
Authors: Agrawal Monica , Zitnik Marinka , Leskovec Jure
Published: September 2017

Discovering disease pathways, which can be defined as sets of proteins associated with a given disease, is an important problem that has the potential to provide clinically actionable insights for disease diagnosis, prognosis, and treatment. Computational methods aid the discovery by relying on protein-protein interaction (PPI) networks. They start with a few known disease-associated proteins and aim to find the rest of the pathway by exploring the PPI network around the known disease proteins. However, the success of such methods has been limited, and failure cases have not been well understood. Here we study the PPI network structure of 519 disease pathways. We find that 90% of pathways do not correspond to single well-connected components in the PPI network. Instead, proteins associated with a single disease tend to form many separate connected components/regions in the network. We then evaluate state-of-the-art disease pathway discovery methods and show that their performance is especially poor on diseases with disconnected pathways. Thus, we conclude that network connectivity structure alone may not be sufficient for disease pathway discovery. However, we show that higher-order network structures, such as small subgraphs of the pathway, provide a promising direction for the development of new methods.
Post-fireQuercus albafitness in a stressed plant community
Authors: Milla Kevin
Published: September 2017

Prescribed burns are widely used for managing North American deciduous forests due to their ability to positively affect plant community structure and composition. This study examines the effects of neighboring herbaceous plants on the recruitment ofQuercus alba(white oak) seedlings in fire-managed parts of Shawnee National Forest (Illinois, USA). Herbs were clipped to induce plant community stress and relative growth rates (RGRs) of planted white oak seedlings were assessed to determine if a competitive or facilitative dynamic is present. In addition to RGR, we observed the mycorrhizal network via fungal colonization in mesh bags to quantify belowground activity for our experimental plots. Our results supported fire’s positive effects on tree recruitment and herbaceous growth. Clipping combined with fire management decreased RGR. This finding suggests that a facilitative dynamic is at play and herbaceous neighbors help white oak seedlings persist due to protection from environmental stressors (p = 0.017). Soil moisture played a large role in promoting tree fitness on each of our sites. Lower hyphal biomass was observed in areas where herbs were clipped. We further speculate that the stress caused by clipping may have suspended or eliminated the need for mycorrhizae to form, possibly due to herb mortality. Knowing how herbs and trees interact will lead to purposeful forest community planning especially in fire-managed forests where herbs are likely to dominate post-prescribed burn.
Generalised Complementarity Analysis: identifying the most precious places for the conservation of Species, Functional and Phylogenetic Diversity
Authors: Nipperess David Anthony
Published: September 2017

The most precious places for conservation are those that make the largest contribution to regional, national or global biodiversity. The two key concepts for determining the contribution of a specific site areComplementarity(the gain in diversity achieved when adding that site to a set of other sites) andIrreplaceability(here defined as the overall complementarity of that site when compared to a range of possible combinations of other sites).Generalised Complementarity Analysis(GCA) is a mathematical framework that provides an exact analytical solution for the expected complementarity (gain in diversity) of a focal site, when added to a set of other sites of a given size (m). Diversity is defined very generally to allow for complementarity to be calculated for species richness, Functional Diversity or Phylogenetic Diversity. The expected irreplaceability of a focal site is then defined in GCA as the area under the curve of expected complementarity values for all possible values ofm. GCA is much more computationally efficient than existing algorithmic approaches and is scalable to very large numbers of sites. Because complementarity and irreplaceability are calculated for all possible combinations of sites, GCA serves as a null model for systematic conservation planning algorithms that seek to optimise site selection. However, because truly irreplaceable sites remain so under all possible site selections, GCA is a powerful conservation planning tool in its own right, providing an efficient means of identifying the world’s most precious places for conservation.
Dynamic and Depth Dependent Nanomechanical Properties of Dorsal Ruffles in Live Cells and Biopolymeric Hydrogels
Authors: Vyas Varun , Solomon Melani , D’Souza Gerard G. M. , Huey Bryan D.
Published: September 2017

The nanomechanical properties of various biological and cellular surfaces are increasingly investigated with Scanning Probe Microscopy. Surface stiffness measurements are currently being used to define metastatic properties of various cancerous cell lines and other related biological tissues. Here we present a unique methodology to understand depth dependent nanomechanical variations in stiffness in biopolymers and live cells. In this study we have used A2780 & NIH3T3 cell lines and 0.5% & 1% Agarose to investigate depth dependent stiffness and porosity on nanomechanical properties in different biological systems. This analytical methodology can circumvent the issue associated with the contribution of substrates on cell stiffness. Here we demonstrate that by calculating ‘continuous-step-wise-modulus’ on force vs. distance curves one can observe minute variation as function of depth. Due to the presence of different kinds of cytoskeletal filament, dissipation of contact force might vary from one portion of a cell to another. On NIH3T3 cell lines, stiffness profile of Circular Dorsal Ruffles could be observed in form of large parabolic feature with changes in stiffness at different depth. In biopolymers like agarose, depending upon the extent of polymerization in there can be increase or decrease in stiffness due variations in pore size and extent to which crosslinking is taking place at different depths. 0.5% agarose showed gradual decrease in stiffness whereas with 1% agarose there was slight increase in stiffness as one indents deeper into its surface.
Recent African gene flow responsible for excess of old rare genetic variation in Great Britain
Authors: Platt Alexander , Hey Jody
Published: September 2017

Population genomic studies can reveal the allele frequencies at millions of SNPs, with the numbers of observed low frequency SNPs increasing as more genomes are sequenced. Rare alleles tend to be younger than common alleles and are especially useful for studying demographic history, selection and heritability1,2. However, allele frequency can be a poor proxy for allele age, as genetic drift and natural selection can lead to alleles that are both rare and old. In order to allow joint assessments of allele frequency and allele age, a new estimator of allele age was developed that can be applied to variants of the lowest observed frequencies (singletons). By examining the geographic and age distribution of very rare variants in a large genomic sample from the UK3, we identify new evidence of gene flow from Africa into the ancestors of the modern UK population. A substantial proportion of variants with observed frequencies as low as 1.4 × 10‒4are orders of magnitude older than can be explained without African gene flow and are found at much higher frequencies within modern African populations. We estimate that African populations contributed approximately 1.2% of the UK gene pool and did so approximately 400 years ago. These findings are relevant both to our understanding of human history and to the nature of rare variation segregating within populations: a variant that is rare because it is a recent mutation in the direct ancestor of the population will have had a very different evolutionary history than an ancient one that has persisted at high frequencies in a diverged population and only recently arrived through migration.
Structural Priming Is Supported By Different Components Of Non-Declarative Memory: Evidence From Priming Across The Lifespan
Authors: Heyselaar Evelien , Wheeldon Linda , Segaert Katrien
Published: September 2017

Structural priming is the tendency to repeat syntactic structure across sentences and can be divided into short-term (prime to immediately following target) and long-term (across an experimental session) components. This study investigates how non-declarative memory could support both the transient, short-term and the persistent, long-term structural priming effects commonly seen in the literature. We propose that these characteristics are supported by different subcomponents of non-declarative memory: Perceptual and conceptual non-declarative memory respectively. Previous studies have suggested that these subcomponents age differently, with only conceptual memory showing age-related decline. By investigating how different components of structural priming vary across the lifespan, we aim to elucidate how non-declarative memory supports two seemingly different components of structural priming. In 167 participants ranging between 20 and 85 years old, we find no change in short-term priming magnitude and performance on perceptual tasks, whereas both long-term priming and conceptual memory vary with age. We suggest therefore that the two seemingly different components of structural priming are supported by different components of non-declarative memory. These findings have important implications for theoretical accounts of structural priming.
The hidden spatial dimension of alpha: 10 Hz perceptual echoes propagate as periodic travelling waves in the human brain
Authors: Lozano-Soldevilla Diego , VanRullen Rufin
Published: September 2017

Alpha oscillations play a special role in vision. During sensory processing, reverse-correlation techniques revealed that white-noise luminance sequences elicit a robust occipital ∼10 Hz response that periodically reverberates the input sequence for up to 1 s. These perceptual echoes constitute the impulse response function of the visual system. However, the spatial dimension of perceptual echoes remains unknown: do they reverberate across the cortex simultaneously? Does stimulation over multiple visual coordinates evoke multiple synchronized echoes, or do they show consistent phase differences? Here, we tested the spatial dimension of perceptual echoes in two electroencephalogram (EEG) experiments manipulating the location of the visual stimulation. When a single disc flickered a white-noise luminance sequence in the upper visual field, we observed a single “echo wave” originating in posterior sensors and spatially propagating towards frontal ones (i.e. periodic travelling wave). The presentation of two independent flickering discs in separate visual hemifields produced two simultaneous and superimposed echo waves propagating in opposite directions, one in response to each stimulus. Strikingly, at many electrode sites, the phase of the two echoes differed, with a phase advance for the contralateral stimulus location. EEG source reconstruction tentatively located the waves within contralateral parieto-occipital cortex. In conclusion, the alpha rhythm processes stimulus information as a travelling wave that propagates across the cortical representation of retinotopic space in the human brain. In line with the “cortical scanning” hypothesis (Pitts & McCulloch, 1947), these results suggest the existence of an additional spatial dimension embedded in the phase of the alpha rhythm.

Significance statement:

How does the spatial dimension of sensory processing relate to the temporal dimension of brain rhythms? Using correlation techniques, we characterized perceptual echoes, the average electroencephalogram response induced by visual stimuli that change luminance randomly. We found that perceptual echoes are actually periodic waves that travel through human visual cortex. Strikingly these periodic waves show consistent phase differences across the visual field, processing screen locations sequentially across distinct phases of the cycle following basic retinotopy. These results suggest the existence of an additional “hidden” spatial dimension in sensory cortex, encoded in the phase of the alpha oscillatory cycle. This could mean that perceptual echoes behave like sweeps of a sonar, processing the visual field in cycles of ∼100 ms duration.
RNA-binding and HEPN-nuclease activation are decoupled in CRISPRCas13a
Authors: Tambe Akshay , East-Seletsky Alexandra , Knott Gavin J. , Doudna Jennifer A. , O’Connell Mitchell R.
Published: September 2017

CRISPR-Cas13a enzymes are RNA-guided, RNA-activated ribonucleases. Their properties have been exploited as powerful tools for RNA detection, RNA imaging and RNA regulation. However, the relationship between target RNA binding and HEPN (higher-eukaryotes-and-prokaryotes nucleotide-binding)- domain nuclease activation is not well understood. Using sequencing experiments coupled within vitrobiochemistry, we find that Cas13a’s target RNA binding affinity and HEPN-nuclease activity are differentially affected by the number of and position of mismatches between the guide and target. We identify a central ‘binding seed’ where perfect base pairing is absolutely required for target binding, and a separate ‘nuclease switch’ where imperfect base-pairing results in tight binding but no HEPN-nuclease activation. These results demonstrate that the binding and cleavage activities of Cas13a are decoupled, highlighting a complex specificity landscape. Our findings underscore a need to consider the range of effects off-target recognition has on Cas13a’s RNA binding and cleavage behavior for RNA-targeting tool development.
Biogenesis of a mitochondrial DNA inheritance machinery in the mitochondrial outer membrane
Authors: Käser Sandro , Willemin Mathilde , Schnarwiler Felix , Schimanski Bernd , Poveda-Huertes Daniel , Oeljeklaus Silke , Warscheid Bettina , Meisinger Chris , Schneider André
Published: September 2017

Mitochondria cannot form de novo but require mechanisms that mediate their inheritance to daughter cells. The parasitic protozoanTrypanosoma bruceihas a single mitochondrion with a single-unit genome that is physically connected across the mitochondrial membranes to the basal body of the flagellum. This connection, termed tripartite attachment complex (TAC), is essential for the segregation of the replicated mitochondrial genomes prior to cytokinesis. Here we identify a protein complex consisting of three integral mitochondrial outer membrane proteins - TAC60, TAC42 and TAC40 - which are essential subunits of the TAC. TAC60 contains separable mitochondrial import and TAC-sorting signals and its biogenesis depends on the main outer membrane protein translocase. TAC40 is a member of the mitochondrial porin family, whereas TAC42 represents a novel class of mitochondrial outer membrane β-barrel proteins. Consequently TAC40 and TAC42 contain C-terminal β-signals. Thus in trypanosomes the highly conserved β-barrel protein assembly machinery plays a major role in the biogenesis of its unique mitochondrial genome segregation system.
Evolutionary rate shifts suggest species-specific adaptation events in HIV-1 and SIV
Authors: Gelbart Maoz , Stern Adi
Published: September 2017

The process of molecular adaptation following a cross-species virus transmission event is currently poorly understood. Here, we identified 137 protein sites that experienced deceleration in their rate of evolution along the HIV-1/SIV phylogeny, likely indicating gain-of-function and consequent adaptation. The majority of such events occurred in parallel to cross-species transmission events and varied between HIV-1 groups, indicating independent adaptation strategies. The evolutionary rate decelerations we found were particularly prominent in accessory proteins that counteract host antiviral restriction factors, suggesting that these factors are a major barrier to viral adaptation to a new host. Surprisingly, we observed that the non-pandemic HIV-1 group O, derived from gorillas, exhibited more rate deceleration events than the pandemic group M, derived from chimpanzees. We suggest that the species barrier is higher when the genetic distance of the hosts increases. Our approach paves the way for subsequent studies on cross-species transfers in other major pathogens.