bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction Algorithm for Surgical Intervention in Neonatal Brachial Plexus Palsy
Authors: Wilson Thomas J , Chang Kate W C , Yang Lynda J S
Published: March 2017

BACKGROUND

Neonatal brachial plexus palsy (NBPP) results in reduced function of the affected arm with profound ramifications on quality of life. Advances in surgical technique have shown improvements in outcomes for appropriately selected patients. Patient selection, however, remains difficult.

OBJECTIVE

To develop a decision algorithm that could be applied at the individual patient level, early in life, to reliably predict persistent NBPP that would benefit from surgery.

METHODS

Retrospective review of NBPP patients was undertaken. Maternal and neonatal factors were entered into the C5.0 statistical package in R (The R Foundation). A 60/40 model was employed, whereby 60% of randomized data were used to train the decision tree, while the remaining 40% were used to test the decision tree. The outcome of interest for the decision tree was a severe lesion meeting requirements for surgical candidacy.

RESULTS

A decision tree prediction algorithm was generated from the entered variables. Variables utilized in the final decision tree included presence of Horner's syndrome, presence of a pseudomeningocele, Narakas grade, clavicle fracture at birth, birth weight >9 lbs, and induction or augmentation of labor. Sensitivity of the decision tree was 0.71, specificity 0.96, positive predictive value 0.94, negative predictive value 0.79, and F1 score 0.81.

CONCLUSION

We developed a decision tree prediction algorithm that can be applied shortly after birth to determine surgical candidacy of patients with NBPP, the first of its kind utilizing only maternal and neonatal factors. This conservative decision tree can be used to offer early surgical intervention for appropriate candidates.
Endoscopic-Assisted Median Aperture Approach for Resection of Fourth Ventricular Tumor and Confirmation of Patency of Cerebral Aqueduct Using an Adjustable-Angle Endoscope: Technical Case Report
Authors: Austerman Ryan , Lucas Joshua , Kammen Alexandra , Zada Gabriel
Published: March 2017

BACKGROUND AND IMPORTANCE: Open microsurgical approaches to the roof of the fourth ventricle via a telovelar approach typically require cerebellar retraction and/or splitting of the vermis and may be associated with postoperative neurological morbidities. In this case report and technical note, we describe the use of an adjustable-angle endoscope inserted into the median aperture via suboccipital craniotomy, resulting in enhanced visualization of the roof of the fourth ventricle and cerebral aqueduct and maximal safe tumor resection.

CLINICAL PRESENTATION: A 49-yr-old woman with obstructive hydrocephalus and a fourth ventricular mass that was not fully visible with the use of an operative microscope.

CONCLUSION: Direct visualization of the roof of the fourth ventricle, including the superior medullary velum and cerebral aqueduct, can be facilitated with an adjustable angle endoscope inserted into the median aperture via suboccipital craniotomy to minimize the degree of telovelar dissection and vermis splitting.
Surgical Approaches to the Temporal Horn: An Anatomic Analysis of White Matter Tract Interruption
Authors: Kadri Paulo A. S. , de Oliveira Jean G. , Krayenbühl Niklaus , Türe Uğur , de Oliveira Evandro P. L. , Al-Mefty Ossama , Ribas Guilherme C.
Published: March 2017

BACKGROUND: Surgical access to the temporal horn is necessary to treat tumors and vascular lesions, but is used mainly in patients with mediobasal temporal epilepsy. The surgical approaches to this cavity fall into 3 primary categories: lateral, inferior, and transsylvian. The current neurosurgical literature has underestimated the interruption of involved fiber bundles and the correlated clinical manifestations.

OBJECTIVE: To delineate the interruption of fiber bundles during the different approaches to the temporal horn.

METHODS: We simulated the lateral (trans-middle temporal gyrus), inferior (transparahippocampal gyrus), and transsylvian approaches in 20 previously frozen, formalin-fixed human brains (40 hemispheres). Fiber dissection was then done along the lateral and inferior aspects under the operating microscope. Each stage of dissection and its respective fiber tract interruption were defined.

RESULTS: The lateral (trans-middle temporal gyrus) approach interrupted “U” fibers, the superior longitudinal fasciculus (inferior arm), occipitofrontal fasciculus (ventral segment), uncinate fasciculus (dorsolateral segment), anterior commissure (posterior segment), temporopontine, inferior thalamic peduncle (posterior fibers), posterior thalamic peduncle (anterior portion), and tapetum fibers. The inferior (transparahippocampal gyrus) approach interrupted “U” fibers, the cingulum (inferior arm), and fimbria, and transected the hippocampal formation. The transsylvian approach interrupted “U” fibers (anterobasal region of the extreme capsule), the uncinate fasciculus (ventromedial segment), and anterior commissure (anterior segment), and transected the anterosuperior aspect of the amygdala.

CONCLUSION: White matter dissection improves our knowledge of the complex anatomy surrounding the temporal horn. Identifying the fiber bundles at risk during each surgical approach adds important information for choosing the appropriate surgical strategy.
Epidemiology and management of bacterial leaf spot on watermelon caused by Pseudomonas syringae
Authors: Newberry E. A. , Ritchie L. , Babu B. , Sanchez T. , Beckham K. A. , Jones J. B. , Freeman J. H. , Dufault N. S. , Paret M. L.
Published: March 2017

Bacterial leaf spot of watermelon caused by Pseudomonas syringae has been an emerging disease in the southeastern United States in recent years. Disease outbreaks in Florida were widespread from 2013 to 2014 and resulted in foliar blighting at the early stages of the crop and transplant losses. We conducted a series of field trials at two locations over the course of two years to examine the chemical control options that may be effective in management of this disease, and to investigate the environmental conditions conducive for bacterial leaf spot development. Weekly applications of acibenzolar-S-methyl (ASM) foliar, ASM drip, or copper hydroxide mixed with ethylene bis-dithiocarbamate were effective in reducing the standardized area under the disease progress curve (P < 0.05). Pearson’s correlation test demonstrated a negative relationship between the average weekly temperature and disease severity (–0.77, P = 0.0002). When incorporated into a multiple regression model with the square root transformed average weekly rainfall, these two variables accounted for 71% of the variability observed in the weekly disease severity (P < 0.0001). This information should be considered when choosing the planting date for watermelon seedlings as the cool conditions often encountered early in the spring season are conducive for bacterial leaf spot development.
Timing Fungicide Application Intervals Based on AirborneErysiphe necatorConcentrations
Authors: Thiessen L. D. , Neill T. M. , Mahaffee W. F.
Published: March 2017

Management of grape powdery mildew (Erysiphe necator) and other polycyclic diseases relies on numerous fungicide applications that follow calendar or model-based application intervals, both of which assume that inoculum is always present. Quantitative molecular assays have been previously developed to initiate fungicide applications, and could be used to optimize fungicide application intervals throughout the growing season based on inoculum concentration. Airborne inoculum samplers were placed at one research and six commercial vineyards in the Willamette Valley of Oregon. Fungicide applications in all plots were initiated at the first detection of E. necator inoculum, and all subsequent fungicide application intervals were made based the grower’ standard calendar program or based on inoculum concentration. In adjusted-interval plots, fungicides were applied at the shortest labeled application interval when >10 spores were detected and the longest labeled application interval when <10 spores were detected. Fungicide applications in control plots consisted of the growers’ standard management practice. An average of 2.3 fewer fungicide applications in 2013 and 1.6 fewer fungicide applications in 2014 were used in the adjusted fungicide application intervals treatment in grower fields without significant differences in berry or leaf disease incidence between treatments.
On Social and Political Effects of Plant Pest and Disease Epidemics
Authors: Zadoks J. C.
Published: March 2017

Selected historical pest and disease outbreaks in the Old World are discussed in view of their social and political consequences. Large-scale epidemics always caused social unrest, and often hunger, pestilence, and death. When coming on top of deeply rooted and widely spread social unrest such epidemics contributed to political change. Examples are the revolts following epidemics in 1789 and 1846. Epidemics, regardless of causal and target organisms, have elements in common. The notion of a common concept grew into a firmly established discipline: epidemiology.
Use of cardiovascular age for assessing risks and benefits of menopausal hormone therapy
Authors: Santen Richard J.
Published: March 2017

The Women's Health Initiative studies and others have suggested that menopausal hormone therapy may enhance the risk of new cardiovascular (CV) events in older women and diminish the development of coronary atherosclerosis in younger women. The underlying mechanisms to explain these findings are encapsulated in the term “Timing Hypothesis.” Extensive pathophysiologic studies have provided mechanistic evidence for the dichotomous effects of estrogen on coronary artery vasculature. Early in the atherosclerotic disease process, estrogen exerts protective effects on the endothelium and retards plaque formation. Late in the process, estrogen causes plaque erosion or rupture with subsequent thrombosis and acute coronary events. Analysis of the Timing Hypothesis in women examined in the Women's Health Initiative primarily used chronologic age to assess divergent effects of estrogen. The complexity of the data underlying coronary pathophysiology has resulted in controversy whether MHT can be used in older women or those with prior CV disease. In a debate of this issue at a recent International Menopause Society meeting, the concept of using CV age rather than chronologic age was discussed as a practical method of resolving this issue and facilitating therapeutic decisions in older women. This “Personal Perspective” will review the concepts underlying CV age, describe how it is determined, provide support for its utility, and propose future studies using this parameter.
Neuroprognostication after cardiac arrest in the light of targeted temperature management
Authors: Oddo Mauro , Friberg Hans
Published: March 2017

Purpose of review

Delayed awakening after targeted temperature management (TTM) and sedation is frequent among cardiac arrest patients. Differentiating between prolonged coma and irreversible cerebral damage can be challenging, therefore the utilization of a multimodal approach is recommended by international guidelines. Here, we discuss indications and advantages/disadvantages of available modalities for coma prognostication and describe new tools to improve our accuracy for outcome prediction.

Recent findings

Studies from the TTM era confirmed that combining neurological examination with electrophysiological assessment [electroencephalography (EEG) and somato-sensory evoked potentials (SSEP)] greatly improves coma prognostication. This combination is nowadays recognized as the most useful by many clinicians and appears widely applicable as part of initial patient assessment. Additional tests (serum neuron specific enolase and neuroimaging) may be most useful to orient clinical decisions in patients with prolonged coma. Advanced analysis of EEG and SSEP recordings and the emergence of quantitative pupillometry hold great promise.

Multimodal prognostication offers a comprehensive approach of anoxic–ischemic encephalopathy and is increasingly used in postresuscitation care. Worldwide implementation and future advancements of available modalities, together with the increasing use of novel automated devices for quantitative neurological examination, may further optimize prognostic accuracy in the early ICU phase following cardiac arrest.
Serum Aminotransferase Flares in Pregnant and Postpartum Women With Current or Prior Treatment for Chronic Hepatitis B
Authors: Chang Christine Y. , Aziz Natali , Poongkunran Mugilan , Javaid Asad , Trinh Huy N. , Lau Daryl T. , Nguyen Mindie H.
Published: March 2017

Background and Aims:

Antiviral therapy is recommended for pregnant women with chronic hepatitis B (CHB) and hepatitis B virus (HBV) DNA>200,000 IU/mL, but there is less consensus on management of women who discontinue therapy in anticipation of pregnancy or who become pregnant while on therapy. The goal of this study was to describe flares in alanine aminotransferase (ALT) during pregnancy and postpartum in CHB women with current and/or prior treatment.

Methods:

This was a multicenter, retrospective study of 67 pregnancies in 56 CHB women treated before and/or during pregnancy. Main outcomes were frequency, severity, and resolution of ALT flare (≥5× upper limit of normal or ≥3× baseline, whichever was higher).

Results:

During pregnancy, ALT flares (95 to 1064 U/L) were observed in 16% (7/43) of women who stopped treatment before pregnancy and 31% (4/13) of women who discontinued treatment during first trimester, many of whom had high HBV DNA levels (4.9 to 8.0 log IU/mL). No flares (0/11) were observed in women who continued treatment. Postpartum ALT flares (104 to 1584 U/L) were observed in 0% (0/15) of women who were completely untreated during pregnancy, 29% (2/7) of women who discontinued treatment in first trimester, 33% (3/9) of women who stopped treatment at delivery, and 22% (4/18) of women who continued treatment postpartum.

Conclusions:

In previously treated women with CHB, ALT flares were common during pregnancy and postpartum, especially if antiviral therapy was discontinued shortly before pregnancy, during first trimester, or at delivery. Thus, these pregnant women should be monitored closely throughout pregnancy and the early postpartum period; larger studies are needed to further characterize the natural history of HBV infection during pregnancy and postpartum.
Clinical implications of antimitochondrial antibody seropositivity in autoimmune hepatitis: a multicentre study
Authors: Muratori Paolo , Efe Cumali , Muratori Luigi , Ozaslan Ersan , Schiano Thomas , Yoshida Eric M. , Heurgué-Berlot Alexandra , Lalanne Claudine , Lenzi Marco , Wahlin Staffan
Published: March 2017

Background/aim

Antimitochondrial antibody (AMA) positivity is the serological marker of primary biliary cholangitis (PBC), but can also be sporadically detected in autoimmune hepatitis (AIH). Little is known about the clinical significance of AMA in AIH.

Patients and methods

We recruited 47 AMA-positive AIH cases from several centres and compared them with 264 well-characterized Italian AIH patients. Cases with any features of PBC were excluded.

Results

In univariate analysis, AMA-positive AIH patients were older (46 vs. 36, P=0.002) and more responsive to immunosuppression (74 vs. 59%, P=0.05), but no differences were observed between the two groups after logistic regression using AMA as a dependent variable. None of the AMA-positive AIH patients showed signs of evolving PBC features after a median follow-up of up 47 months. AMA was detected in combination with all serological AIH markers except antiliver kidney microsome type 1 and antiliver cytosol type 1. AMA was the only marker of autoimmunity in eight cases.

Conclusion

We found no differences between AIH with and without AMA. The groups had similar clinical, biochemical and histological features. AMA-positive AIH patients did not evolve towards PBC. In some cases, AMA was the only autoantibody.
The superiority of the two-thumb over the two-finger technique for single-rescuer infant cardiopulmonary resuscitation
Authors: Lee Sang Yoon , Hong Jun Young , Oh Je Hyeok , Son Sun-Han
Published: March 2017

Objectives

The two-finger technique (TFT) using the index-middle fingers of the right hand (TFT-R23) was recently confirmed to produce deeper chest compression depth (CCD) compared with the TFT using any other fingers. This study was carried out to confirm whether the TFT-R23 would be as effective as the two-thumb technique (TTT). In addition, individual finger strengths were measured to identify the reasons why the TTT and TFT-R23 produced deeper CCD than any other methods.

Methods

This prospective randomized cross-over trial compared TTT with TFT-R23. A total of 37 doctors conducted 2 min single-rescuer cardiopulmonary resuscitation using TTT and TFT-R23 in a random order using a 3-month-old sized infant manikin laid on the floor. The chest compression to ventilation ratio was set to 15 : 2. In addition, finger strengths were measured using a pinch meter.

Results

The actual CCD of the TTT was significantly deeper than that of the TFT-R23 (41.3±1.3 vs. 39.8±1.5 mm, P<0.001). Although the hands-off time of the TTT was significantly longer than that of the TFT-R23 (55.6±5.7 vs. 53.6±5.8 s, P=0.002), the mean difference was only 2.0±3.7 s (95% confidence interval: 0.755–3.245). The finger strength of the TTT was significantly higher than that of TFT-R23 (23.8±10.1 vs. 13.7±5.1 kg, P<0.001).

Conclusion

The TTT produced deeper CCD compared with that of the TFT-R23 because the finger strength of the TTT was significantly higher than that of the TFT-R23.
Partial occlusion, conversion from thoracotomy, undelayed but shorter occlusion: resuscitative endovascular balloon occlusion of the aorta strategy in Japan
Authors: Matsumura Yosuke , Matsumoto Junichi , Kondo Hiroshi , Idoguchi Koji , Funabiki Tomohiro
Published: March 2017

Introduction

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a viable alternative to resuscitative thoracotomy (RT) in refractory hemorrhagic patients. We evaluated REBOA strategies using Japanese multi-institutional data.

Patients and methods

The DIRECT-IABO investigators registered trauma patients requiring REBOA from 18 hospitals. Patients’ characteristics, outcomes, and time in initial treatment were collected and analyzed.

Results

From August 2011 to December 2015, 106 trauma patients were analyzed. The majority of patients were men (67%) (median BMI of 22 kg/m2, 96% blunt injured). REBOA occurred in the field (1.9%, all survived >30 days), emergency department (75%), angiography suite (17%), and operating room (1.9%). Initial deployment was at zone I in 93% and partial occlusion in 70% of cases. RT and REBOA were combined in 30 patients (RT+REBOA group) who showed significantly higher injury severity score (44 vs. 36, P=0.001) and chest abbreviated injury scale (4 vs. 3; P<0.001) than the REBOA-alone group (n=76). Frequent cardiopulmonary resuscitation (73%), longer prothrombin time-international normalised ratio, lower pH, and higher lactate were observed in the RT+REBOA. Among 24 h nonsurvivors (n=30) of the REBOA alone, preocclusion systolic blood pressure was lower (43 vs. 72 mmHg; P=0.002), indicating impending cardiac arrest, and duration of occlusion was longer (60 vs. 31 min; P=0.010). In the RT+REBOA (n=30), six survived beyond 24 h, three beyond 30 days, and achieved survival discharge.

Conclusion

Partial occlusion was performed in 70% of patients. Undelayed deployment of REBOA without presenting impending cardiac arrest with shorter balloon occlusion (<30 min at zone I with partial occlusion) might be related to successful hemodynamic stabilization and improved survival. Further evaluation should be performed prospectively.
Gas-phase reactivity of [Ca(formamide)]
2+
complex: an example of different dynamical behaviours
Authors: Martin-Somer Ana , Spezia Riccardo , Yáñez Manuel
Published: March 2017

In the present contribution, we have summarized our recent work on the comprehension of [Ca(formamide)]
2+
complex gas-phase unimolecular dissociation. By using different theoretical approaches, we were able to revise the original (and typical for such kind of problems) understanding given in terms of stationary points on the potential energy surface, which did not provide a satisfactory explanation of the experimentally observed reactivity. In particular, we point out how non-statistical and non-intrinsic reaction coordinate mechanisms are of fundamental importance.

This article is part of the themed issue ‘Theoretical and computational studies of non-equilibrium and non-statistical dynamics in the gas phase, in the condensed phase and at interfaces’.
Kinetics of low-temperature transitions and a reaction rate theory from non-equilibrium distributions
Authors: Aquilanti Vincenzo , Coutinho Nayara Dantas , Carvalho-Silva Valter Henrique
Published: March 2017

This article surveys the empirical information which originated both by laboratory experiments and by computational simulations, and expands previous understanding of the rates of chemical processes in the low-temperature range, where deviations from linearity of Arrhenius plots were revealed. The phenomenological two-parameter Arrhenius equation requires improvement for applications where interpolation or extrapolations are demanded in various areas of modern science. Based on Tolman's theorem, the dependence of the reciprocal of the apparent activation energy as a function of reciprocal absolute temperature permits the introduction of a deviation parameterdcovering uniformly a variety of rate processes, from those where quantum mechanical tunnelling is significant andd < 0, to those whered > 0, corresponding to the Pareto–Tsallis statistical weights: these generalize the Boltzmann–Gibbs weight, which is recovered ford = 0. It is shown here how the weights arise, relaxing the thermodynamic equilibrium limit, either for a binomial distribution ifd > 0 or for a negative binomial distribution ifd < 0, formally corresponding to Fermion-like or Boson-like statistics, respectively. The current status of the phenomenology is illustrated emphasizing case studies; specifically (i) thesuper-Arrhenius kinetics, where transport phenomena accelerate processes as the temperature increases; (ii) thesub-Arrhenius kinetics, where quantum mechanical tunnelling propitiates low-temperature reactivity; (iii) theanti-Arrhenius kinetics, where processes with no energetic obstacles are rate-limited by molecular reorientation requirements. Particular attention is given for case (i) to the treatment of diffusion and viscosity, for case (ii) to formulation of a transition rate theory for chemical kinetics including quantum mechanical tunnelling, and for case (iii) to the stereodirectional specificity of the dynamics of reactions strongly hindered by the increase of temperature.

This article is part of the themed issue ‘Theoretical and computational studies of non-equilibrium and non-statistical dynamics in the gas phase, in the condensed phase and at interfaces’.
A velocity-map imaging study of methyl non-resonant multiphoton ionization from the photodissociation of CH
3
I in the A-band
Authors: Poullain Sonia Marggi , Chicharro David V. , Rubio-Lago Luis , García-Vela Alberto , Bañares Luis
Published: March 2017

Chemical reaction dynamics and, particularly, photodissociation in the gas phase are generally studied using pump–probe schemes where a first laser pulse induces the process under study and a second one detects the produced fragments. Providing an efficient detection of ro-vibrationally state-selected photofragments, the resonance enhanced multiphoton ionization (REMPI) technique is, without question, the most popular approach used for the probe step, while non-resonant multiphoton ionization (NRMPI) detection of the products is scarce. The main goal of this work is to test the sensitivity of the NRMPI technique to fragment vibrational distributions arising from molecular photodissociation processes. We revisit the well-known process of methyl iodide photodissociation in the A-band at around 280 nm, using the velocity-map imaging technique in conjunction with NRMPI of the methyl fragment. The detection wavelength, carefully selected to avoid any REMPI transition, was scanned between 325 and 335 nm seeking correlations between the different observables—the product vibrational, translational and angular distributions—and the excitation wavelength of the probe laser pulse. The experimental results have been discussed on the base of quantum dynamics calculations of photofragment vibrational populations carried out on available
ab initio
potential-energy surfaces using a four-dimensional model.

This article is part of the themed issue ‘Theoretical and computational studies of non-equilibrium and non-statistical dynamics in the gas phase, in the condensed phase and at interfaces’.
Functional asymmetry in the central brain regions in boys with Attention Deficit Hyperactivity Disorder detected by Event Related Potentials during performance of the Attentional Network Test
Authors: Abramov Dimitri Marques , Mourão Carlos Alberto , Cunha Carla Quero , Pontes Monique Castro , Galhanone Paulo Ricardo , deAzevedo Leonardo C. , Lazarev Vladimir V.
Published: March 2017

Background

Various functional asymmetries detected by different neurophysiological and neuroimaging methods have been reported in the literature on the Attention Deficit Hyperactivity Disorder (ADHD), some of them pointing to the right hemisphere activity. In our attempt to discriminate the ADHD patients from normal subjects by hierarchical clustering of behavioural, psychological and event related potential (ERP) variables, the late P3 component of potentials from the right central region (C4) proved to be one of the most informative parameters (in preparation for publication). Here, we have studied the differences in ERPs between the left (C3) and right (C4) central leads and relation of this asymmetry to ADHD diagnosed using DSM.

Methods

20 typically developing (TD) boys and 19 boys diagnosed with ADHD according to DSM-IV-TR, aged 10-13 years, were examined by the Attentional Network Test (ANT), with simultaneous recording of the respective ERPs. The intergroup differences in the ERP amplitude parameters in the left (C3) and right (C4) central channels and in the difference in these parameters between the two channels (C3 minus C4) were accessed. These characteristics were compared to the subjects DSM scores and ANT performance.

Results

The target-related potentials late characteristics from the C4 and C3 did not shown significant difference between the groups. The difference between ERPs of the C3 and C4 channels inside the interval of 40-290 ms after target onset was larger in the ADHD group than in control, mainly for incongruent target condition. This asymmetry and right late component were correlated with DSM scores, mainly to hyperactive and impulsive criteria.

Conclusion

In ADHD patients, the results suggest ERP pattern of right-side functional predominance in the motor control, which correlates to DSM scores, mainly to hyperactive and impulsive criteria.
Decision-related signals in the presence of nonzero signal stimuli, internal bias, and feedback
Authors: Chicharro Daniel , Panzeri Stefano , Haefner Ralf M.
Published: March 2017

Understanding the nature of decision-related signals in sensory neurons promises to give insights into their role in perceptual decision-making. Those signals, traditionally quantified as choice probabilities (CP), are well-understood in a feedforward framework assuming zero-signal trials with no choice bias. Here, we extend this understanding by analytically solving models of choice-related signals that account for informative stimuli, choice bias, and importantly, feedback signals reflecting either internal states, such as attention or belief, or the outcome of the decision process. First, we relate CPs to Choice Triggered Averages (CTAs), which quantify choice-related average changes in neural responses, and show that both have general expressions valid for activity-choice covariations of both feedforward or feedback origin. These expressions allow a meaningful calculation of CPs across all trials, including non-zero signal trials. Second, we derive how CPs and CTAs depend on feedforward and feedback weights and on noise correlations under several plausible model architectures. Third, we examine different types of feedback signals, related to predictive coding, probabilistic inference, and attention, and we predict how CPs and CTAs depend in each case on the stimulus signal level and on the neural tuning properties. Finally, we show that measuring both CPs and CTAs offers complementary information about the origin of choice-related signals, especially when studying temporal changes of activity-choice covariations across the trial time. Overall, our work provides new analytical tools to better understand the link between sensory representations and perceptual decisions.
Mean-field equations for neuronal networks with arbitrary degree distributions
Authors: Nykamp Duane Q. , Friedman Daniel , Shaker Sammy , Shinn Maxwell , Vella Michael , Compte Albert , Roxin Alex
Published: March 2017

The emergent dynamics in networks of recurrently coupled spiking neurons depends on the interplay between single-cell dynamics and network topology. Most theoretical studies on network dynamics have assumed simple topologies, such as connections which are made randomly and independently with a fixed probability (Erdös-Rényi network) (ER), or all-to-all connected networks. However, recent findings from slice experiments suggest that the actual patterns of connectivity between cortical neurons are more structured than in the ER random network. Here we explore how introducing additional higher-order statistical structure into the connectivity can affect the dynamics in neuronal networks. Specifically, we consider networks in which the number of pre-synaptic and post-synaptic contacts for each neuron, the degrees, are drawn from a joint degree distribution. We derive mean-field equations for a single population of homogeneous neurons and for a network of excitatory and inhibitory neurons, where the neurons can have arbitrary degree distributions. Through analysis of the mean-field equations and simulation of networks of integrate-and-fire neurons, we show that such networks have potentially much richer dynamics than an equivalent ER network. Finally, we relate the degree distributions to so-called cortical motifs.
On the structure of cortical micro-circuits inferred from small sample sizes
Authors: Vegué Marina , Perin Rodrigo , Roxin Alex
Published: March 2017

The structure in cortical micro-circuits deviates from what would be expected in a purely random network, which has been seen as evidence of clustering. To address this issue we sought to reproduce the non-random features of cortical circuits by considering several distinct classes of network topology, including clustered networks, networks with distance-dependent connectivity and those with broad degree distributions. To our surprise we found that all these qualitatively distinct topologies could account equally well for all reported non-random features, despite being easily distinguishable from one another at the network level. This apparent paradox was a consequence of estimating network properties given only small sample sizes. In other words, networks which differ markedly in their global structure can look quite similar locally. This makes inferring network structure from small sample sizes, a necessity given the technical difficulty inherent in simultaneous intracellular recordings, problematic. We found that a network statistic called the sample degree correlation (SDC) overcomes this difficulty. The SDC depends only on parameters which can be reliably estimated given small sample sizes, and is an accurate fingerprint of every topological family. We applied the SDC criterion to data from rat visual and somatosensory cortex and discovered that the connectivity was not consistent with any of these main topological classes. However, we were able to fit the experimental data with a more general network class, of which all previous topologies were special cases. The resulting network topology could be interpreted as a combination of physical spatial dependence and non-spatial, hierarchical clustering.

Significance Statement

The connectivity of cortical micro-circuits exhibits features which are inconsistent with a simple random network. Here we show that several classes of network models can account for this non-random structure despite qualitative differences in their global properties. This apparent paradox is a consequence of the small numbers of simultaneously recorded neurons in experiment: when inferred via small sample sizes many networks may be indistinguishable, despite being globally distinct. We develop a connectivity measure which successfully classifies networks even when estimated locally, with a few neurons at a time. We show that data from rat cortex is consistent with a network in which the likelihood of a connection between neurons depends on spatial distance and on non-spatial, asymmetric clustering.
Theta-modulation drives the emergence of network-wide connectivity patterns underlying replay in a model of hippocampal place cells
Authors: Theodoni Panagiota , Rovira Bernat , Wang Yingxue , Roxin Alex
Published: March 2017

Place cells of the rodent hippocampus fire action potentials when the animal traverses a particular spatial location in a given environment. Therefore, for any given trajectory one will observe a repeatable sequence of place cell activations as the animal explores. Interestingly, when the animal is quiescent or sleeping, one can observe similar sequences of activation, although at a highly compressed rate, known as “replays”. It is hypothesized that this replay underlies the process of memory consolidation whereby memories are “transferred” from hippocampus to cortex. However, it remains unclear how the memory of a particular environment is actually encoded in the place cell activity and what the mechanism for replay is. Here we study how plasticity during spatial exploration shapes the patterns of synaptic connectivity in model networks of place cells. Specifically, we show how plasticity leads to the emergence of patterns of activity which represent the spatial environment learned. These states become spontaneously active when the animal is quiescent, reproducing the phenomenology of replays. Interestingly, replay emerges most rapidly when place cell activity is modulated by an ongoing oscillation. The optimal oscillation frequency can be calculated analytically, is directly related to the plasticity rule, and for experimentally determined values of the plasticity window in rodent slices gives values in the theta range. A major prediction of this model is that the pairwise correlation of place cells which encode for neighboring locations should increase during initial exploration, leading up to the critical transition. We find such an increase in a population of simultaneously recorded CA1 pyramidal cells from a rat exploring a novel track. Furthermore, in a rat in which hippocampal theta is reduced through inactivation of the medial septum we find no such increase. Our model is the first to show how theta-modulation can speed up learning by facilitating the emergence of environment-specific network-wide patterns of synaptic connectivity in hippocampal circuits.
Mapping protein interactions of sodium channel NaV1.7 using epitope-tagged gene targeted mice
Authors: Kanellopoulos Alexandros H. , Koenig Jennifer , Huang Honglei , Pyrski Martina , Millet Queensta , Lolignier Stephane , Morohashi Toru , Gossage Samuel J. , Jay Maude , Linley John , Baskozos Georgios , Kessler Benedikt , Cox James J. , Zufall Frank , Wood John N. , Zhao Jing
Published: March 2017

The voltage-gated sodium channel NaV1.7 plays a critical role in pain pathways. Besides action potential propagation, NaV1.7 regulates neurotransmitter release, integrates depolarizing inputs over long periods and regulates transcription. In order to better understand these functions, we generated an epitope-tagged NaV1.7 mouse that showed normal pain behavior. Analysis of NaV1.7 complexes affinity-purified under native conditions by mass spectrometry revealed 267 NaV1.7 associated proteins including known interactors, such as the sodium channel β3 subunit (Scn3b) and collapsin response mediator protein (Crmp2), and novel interactors. Selected novel NaV1.7 protein interactors membrane-trafficking protein synapototagmin-2 (Syt2), G protein-regulated inducer of neurite outgrowth 1 (Gprin1), L-type amino acid transporter 1 (Lat1) and transmembrane P24 trafficking protein 10 (Tmed10) together with Scn3b and Crmp2 were validated using co-immunoprecipitation and functional assays. The information provided with this physiologically normal epitope-tagged mouse should provide useful insights into the pain mechanisms associated with NaV1.7 channel function.
On the feasibility of mining CD8+ T-cell receptor patterns underlying immunogenic peptide recognition
Authors: De Neuter Nicolas , Bittremieux Wout , Beirnaert Charlie , Cuypers Bart , Mrzic Aida , Moris Pieter , Suls Arvid , Van Tendeloo Viggo , Ogunjimi Benson , Laukens Kris , Meysman Pieter
Published: March 2017

Current T-cell epitope prediction tools are a valuable resource in designing targeted immunogenicity experiments. They typically focus on, and are able to, accurately predict peptide binding and presentation by major histocompatibility complex (MHC) molecules on the surface of antigen-presenting cells. However, recognition of the peptide-MHC complex by a T-cell receptor is often not included in these tools. We developed a classification approach based on random forest classifiers to predict recognition of a peptide by a T-cell and discover patterns that contribute to recognition. We considered two approaches to solve this problem: (1) distinguishing between two sets of T-cell receptors that each bind to a known peptide and (2) retrieving T-cell receptors that bind to a given peptide from a large pool of T-cell receptors. Evaluation of the models on two HIV-1, B*08-restricted epitopes reveals good performance and hints towards structural CDR3 features that can determine peptide immunogenicity. These results are of particularly importance as they show that prediction of T-cell epitope and T-cell epitope recognition based on sequence data is a feasible approach. In addition, the validity of our models not only serves as a proof of concept for the prediction of immunogenic T-cell epitopes but also paves the way for more general and high performing models.
Long-Term Imaging of Cellular Forces with High Precision by Elastic Resonator Interference Stress Microscopy
Authors: Kronenberg Nils M. , Liehm Philipp , Steude Anja , Knipper Johanna A. , Borger Jessica G. , Scarcelli Giuliano , Franze Kristian , Powis Simon J. , Gather Malte C.
Published: March 2017

Cellular forces are crucial for many biological processes but current methods to image them have limitations with respect to online analysis, resolution and throughput. Here, we present a robust approach to measure mechanical cell-substrate interactions in diverse biological systems by interferometrically detecting deformations of an elastic micro-cavity. Elastic Resonator Interference Stress Microscopy (ERISM) yields stress maps with exceptional precision and large dynamic range (2 nm displacement resolution over a >1 μm range, translating into 1 pN force sensitivity). This enables investigation of minute vertical stresses (<1 Pa) involved in podosome protrusion, protein specific cell-substrate interaction and amoeboid migration through spatial confinement in real time. ERISM requires no zero-force reference and avoids phototoxic effects, which facilitates force monitoring over multiple days and at high frame rates and eliminates the need to detach cells after measurements. This allows observation of slow processes like differentiation and further investigation of cells, e.g. by immunostaining.
Neuronal patterning of the tubular collar cord is highly conserved among enteropneusts but dissimilar to the chordate neural tube
Authors: Kaul-Strehlow Sabrina , Urata Makoto , Praher Daniela , Wanninger Andreas
Published: March 2017

The dorsal neural tube of chordates and the ventral nerve cord of annelids exhibit a similar molecular mediolateral architecture. Accordingly, the presence of such a complex nervous system (CNS) has been proposed for their last common ancestor. Members of Enteropneusta, a group of non-chordate deuterostomes, possess a less complex CNS including a hollow neural tube, whereby homology to its chordate counterpart remains elusive. Since the majority of data on enteropneusts stem fromSaccoglossus kowalevskii,a derived direct-developer, we investigated expression of key neuronal patterning genes in the indirect-developerBalanoglossus misakiensis.

The collar cord ofB. misakiensisshows anteriorSix3/6and posteriorOtx+engrailedexpression, in a region corresponding to the chordate brain. NeuronalNk2.1/Nk2.2expression is absent. Interestingly, we found medianDlxand lateralPax6expression domains, i.e., a condition that is reversed compared to chordates.

Comparative analyses reveal that CNS patterning is highly conserved among enteropneusts.BmiDlxandBmiPax6have no corresponding expression domains in the chordate brain, which may be indicative of independent acquisition of a tubular CNS in Enteropneusta and Chordata. Moreover, mediolateral architecture varies considerably among chordates and enteropneusts, questioning the presence of a vertebrate-like patterned nervous system in the last common deuterostome ancestor.
Insect behavioral evidence of spatial memories during environmental reconfiguration
Authors: Santos-Pata Diogo , Escuredo Alex , Mathews Zenon , Verschure Paul F.M.J.
Published: March 2017

Insects are great explorers, able to navigate through long-distance trajectories and successfully find their way back. Their navigational routes cross dynamic environments suggesting adaptation to novel configurations. Arthropods and vertebrates share neural organizational principles and it has been shown that rodents modulate their neural spatial representation accordingly with environmental changes. However, it is unclear whether insects reflexively adapt to environmental changes or retain memory traces of previously explored situations. We sought to disambiguate between insect behavior at environmental novel situations and reconfiguration conditions. An immersive mixed-reality multi-sensory setup was built to replicate multi-sensory cues. We have designed an experimental setup where female crickets Gryllus Bimaculatus were trained to move towards paired auditory and visual cues during primarily phonotactic driven behavior. We hypothesized that insects were capable of identifying sensory modifications in known environments. Our results show that, regardless of the animals history, novel situation conditions did not compromise the animals performance and navigational directionality towards a novel target location. However, in trials where visual and auditory stimuli were spatially decoupled, the animals heading variability towards a previously known location significantly increased. Our findings showed that crickets are able to behaviorally manifest environmental reconfiguration, suggesting the encoding for spatial representation.
Causes and consequences of nuclear gene positioning
Authors: Shachar Sigal , Misteli Tom
Published: March 2017

The eukaryotic genome is organized in a manner that allows folding of the genetic material in the confined space of the cell nucleus, while at the same time enabling its physiological function. A major principle of spatial genome organization is the non-random position of genomic loci relative to other loci and to nuclear bodies. The mechanisms that determine the spatial position of a locus, and how position affects function, are just beginning to be characterized. Initial results suggest multiple, gene-specific mechanisms and the involvement of a wide range of cellular machineries. In this Commentary, we review recent findings from candidate approaches and unbiased screening methods that provide initial insight into the cellular mechanisms of positioning and their functional consequences. We highlight several specific mechanisms including tethering to the nuclear periphery, passage through replication and histone modifications that contribute to gene positioning in yeast, plants and mammals.
Temporal fitness fluctuations in experimentalArabidopsis thalianapopulations
Authors: Hu Jinyong , Lei Li , de Meaux Juliette
Published: March 2017

Understanding the genetics of lifetime fitness is crucial to understand a species’ ecological preferences and ultimately predict its ability to cope with novel environmental conditions. Yet, there is a dearth of information regarding the impact of the ecological variance experienced by natural populations on expressed phenotypic and fitness differences. Here, we follow the natural dynamics of experimentalA. thalianapopulations over 5 successive plantings whose timing was determined by the natural progression of the plant’s life cycle and disentangle the environmental and genetic factors that drive plant ecological performance at a given locality. We show that, at the intermediate latitude where the experiment was conducted, a given genotype can experience different life cycles across successive seasons. Lifetime fitness across these seasons varied strongly, with a fall planting yielding 36-fold higher fitness compared to a spring planting. In addition, the actual life-stage at which plant overwinter oscillated across years, depending on the timing of the end of the summer season. We observed a rare but severe fitness differential after inadequate early flowering in one of the five planting. Substrate variation played a comparatively minor role, but also contributed to modulate the magnitude of fitness differentials between genotypes. Finally, reciprocal introgressions on chromosome 4 demonstrated that the fitness effect of a specific chromosomal region is strongly contingent on micro-geographic and seasonal fluctuations. Our study contributes to emphasize the extent to which the fitness impact of phenotypic traits and the genes that encode them in the genome can fluctuate. Experiments aiming at dissecting the molecular basis of local adaptation must apprehend the complexity introduced by temporal fluctuations because they massively affect the expression of phenotype and fitness differences.
Intra- and Inter-individual genetic variation in human ribosomal RNAs
Authors: Babaian Artem
Published: March 2017

The ribosome is an ancient RNA-protein complex essential for translating DNA to protein. At its core are the ribosomal RNAs (rRNAs), the most abundant RNA in the cell. To support high levels of transcription, repetitive arrays of ribosomal DNA (rDNA) are necessary and the long-standing hypothesis is that they undergo sequence homogenization towards rDNA uniformity.

Here I present evidence of the rich genetic diversity in human rDNA, both within and between individuals. Using state-of-the-art genome sequencing data revealed an average of 192.7 intra-individual variants, including some deeply penetrating the rDNA copies, such as the bi-allelically expressed 28S.59A>G. From 104 diverse genomes, 947 high-confidence variants were identified and unmask a hidden genetic diversity of humans.

These findings support the emerging concept that ribosomes are heterogeneous within cells and extends the heterogeneity into the realm of population genetics. Fundamentally, do our ribosomal variants determine how our cells interpret the genome?