bluuebunny/crossref_metadata_2025_split huggingface dataset:
Organization of flexor–extensor interactions in the mammalian spinal cord: insights from computational modelling
Authors: Shevtsova Natalia A. , Rybak Ilya A. 
Published: June 2016

Key points
Alternation of flexor and extensor activity in the mammalian spinal cord is mediated by two classes of genetically identified inhibitory interneurons, V1 and V2b.
The V1 interneurons are essential for high‐speed locomotor activity. They secure flexor–extensor alternations in the intact cord but lose this function after hemisection, suggesting that they are activated by inputs from the contralateral side of the cord.
The V2b interneurons are involved in flexor–extensor alternations in both intact cord and hemicords.
We used a computational model of the spinal network, simulating the left and right rhythm‐generating circuits interacting via several commissural pathways, and extended this model by incorporating V1 and V2b neuron populations involved in flexor–extensor interactions on each cord side.
The model reproduces multiple experimental data on selective silencing and activation of V1 and/or V2b neurons and proposes the organization of their connectivity providing flexor–extensor alternation in the spinal cord.
AbstractAlternating flexor and extensor activity represents the fundamental property underlying many motor behaviours including locomotion. During locomotion this alternation appears to arise in rhythm‐generating circuits and transpires at all levels of the spinal cord including motoneurons. Recent studies in vitro and in vivo have shown that flexor–extensor alternation during locomotion involves two classes of genetically identified, inhibitory interneurons: V1 and V2b. Particularly, in the isolated mouse spinal cord, abrogation of neurotransmission derived by both V1 and V2b interneurons resulted in flexor–extensor synchronization, whereas selective inactivation of only one of these neuron types did not abolish flexor–extensor alternation. After hemisection, inactivation of only V2b interneurons led to the flexor–extensor synchronization, while inactivation of V1 interneurons did not affect flexor–extensor alternation. Moreover, optogenetic activation of V2b interneurons suppressed extensor‐related activity, while similar activation of V1 interneurons suppressed both flexor and extensor oscillations. Here, we address these issues using the previously published computational model of spinal circuitry simulating bilateral interactions between left and right rhythm‐generating circuits. In the present study, we incorporate V1 and V2b neuron populations on both sides of the cord to make them critically involved in flexor–extensor interactions. The model reproduces multiple experimental data on the effects of hemisection and selective silencing or activation of V1 and V2b neurons and suggests connectivity profiles of these neurons and their specific roles in left–right (V1) and flexor–extensor (both V2b and V1) interactions in the spinal cord that can be tested experimentally.
Functional adaptations of the coronary microcirculation to anaemia in fetal sheep
Authors: Jonker Sonnet S. , Davis Lowell , Soman Divya , Belcik J. Todd , Davidson Brian P. , Atkinson Tamara M. , Wilburn Adrienne , Louey Samantha , Giraud George D. , Lindner Jonathan R. 
Published: June 2016

Key points
In fetuses, chronic anaemia stimulates cardiac growth; simultaneously, blood flow to the heart muscle itself is increased, and reserve blood flow capacity of the coronary vascular bed is preserved.
Here we examined functional adaptations of the capillaries and small blood vessels responsible for delivering oxygen to the anaemic fetal heart muscle using contrast‐enhanced echocardiography.
We demonstrate that coronary microvascular flux rate doubled in anaemic fetuses compared to control fetuses, both at rest and during maximal flow, suggesting reduced microvascular resistance consistent with capillary widening.
Cardiac fractional microvascular blood volume was not greater in anaemic fetuses, suggesting that growth of new microvascular vessels does not contribute to the increased flow per volume of myocardium.
These unusual changes in microvascular function during anaemia may indicate novel adaptive strategies in the fetal heart.
AbstractFetal anaemia causes cardiac adaptations that have immediate and life‐long repercussions on heart function and health. It is known that resting and maximal coronary conductance both increase during chronic fetal anaemia, but the coronary microvascular changes responsible for the adaptive response are unknown. Until recently, technical limitations have prevented quantifying functional capillary‐level adaptations in the in vivo fetal heart. Our objective was to characterise functional microvascular adaptations in chronically anaemic fetal sheep. Chronically instrumented fetuses were randomized to a control group (n = 11) or were made anaemic by isovolumetric haemorrhage (n = 12) for 1 week prior to myocardial contrast echocardiography at 85% of gestation. Anaemia augmented cardiac mass by 23% without changing body weight. In anaemic fetuses, microvascular blood flow per volume of myocardium was twice that of control fetuses at rest, during vasodilatory hyperaemia, and during hyperaemia plus increased aortic pressure. The elevated blood flow was attributable almost entirely to an increase in microvascular blood flux rate whereas microvascular blood volumes were not different between groups at baseline, during hyperaemia, or with hyperaemia plus increased aortic pressure. Increased coronary microvascular flux rate in response to chronic fetal anaemia is consistent with expected reductions in capillary resistance from capillary diameter widening detected in earlier histological studies.
Technical Note: Image filtering to make computer‐aided detection robust to image reconstruction kernel choice in lung cancer CT screening
Authors: Ohkubo Masaki , Narita Akihiro , Wada Shinichi , Murao Kohei , Matsumoto Toru 
Published: June 2016

Purpose:In lung cancer computed tomography (CT) screening, the performance of a computer‐aided detection (CAD) system depends on the selection of the image reconstruction kernel. To reduce this dependence on reconstruction kernels, the authors propose a novel application of an image filtering method previously proposed by their group.Methods:The proposed filtering process uses the ratio of modulation transfer functions (MTFs) of two reconstruction kernels as a filtering function in the spatial‐frequency domain. This method is referred to as MTFratio filtering. Test image data were obtained from CT screening scans of 67 subjects who each had one nodule. Images were reconstructed using two kernels: fSTD (for standard lung imaging) and fSHARP (for sharp edge‐enhancement lung imaging). The MTFratio filtering was implemented using the MTFs measured for those kernels and was applied to the reconstructed fSHARP images to obtain images that were similar to the fSTD images. A mean filter and a median filter were applied (separately) for comparison. All reconstructed and filtered images were processed using their prototype CAD system.Results:The MTFratio filtered images showed excellent agreement with the fSTD images. The standard deviation for the difference between these images was very small, ∼6.0 Hounsfield units (HU). However, the mean and median filtered images showed larger differences of ∼48.1 and ∼57.9 HU from the fSTD images, respectively. The free‐response receiver operating characteristic (FROC) curve for the fSHARP images indicated poorer performance compared with the FROC curve for the fSTD images. The FROC curve for the MTFratio filtered images was equivalent to the curve for the fSTD images. However, this similarity was not achieved by using the mean filter or median filter.Conclusions:The accuracy of MTFratio image filtering was verified and the method was demonstrated to be effective for reducing the kernel dependence of CAD performance.
Effects of Mindfulness-Based Interventions in High School and College Athletes for Reducing Stress and Injury, and Improving Quality of Life
Authors: Petterson Haley , Olson Bernadette L. 
Published: June 2016

Clinical Scenario:Student athletes experience a variety of stressors from school and social activities, as well as the additional demands of sport participation. Mindfulness-based interventions can help increase mental awareness and acceptance, as well as mitigate negative thoughts and emotions. The use of mindfulness-based interventions may be beneficial for reducing thoughts of stress, injury reduction, and improving overall wellbeing.Clinical Question:Does the use of mindfulness-based interventions for student-athletes aged 13–24 years reduce stress and injury as well as improve overall quality of life?Summary of Findings:The literature was searched for studies that investigated the use of mindfulness-based strategies for student-athletes specifically for reducing stress and injury and/or improving quality of life. The literature search returned 8 possible studies related to the clinical question and 3 studies met the inclusion criteria (1 randomized control trial, 2 nonrandomized control cohort studies). All 3 included studies demonstrated overall improved levels of mindfulness among student-athletes after the use of a mindfulness-based intervention. Mindfulness-based interventions had positive effects for reducing negative thoughts and levels of perceived stress. The number of injury occurrences were found to decrease following the integration of a mindfulness-based intervention within an athletic population.Clinical Bottom Line:There is sufficient evidence supporting the use of mindfulness-based interventions with student-athletes for increasing mindfulness, managing negative emotions and perceived stress, as well as improving overall well-being. There is also current literature that advocates the use of mindfulness-based interventions for reducing injury, but further research is needed for support.Strength of Recommendation:Grade B evidence exists to support that the use of mindfulness-based interventions for student-athletes will reduce stress and improve overall well-being as well as support the possibility that if a student-athlete is more mindful, it may help decrease risk of injury incurred if the student-athlete is under mental stress.
Multicenter Study of the Emergence and Genetic Characteristics of Pyrazinamide-Resistant Tuberculosis in China
Authors: Li Dange , Hu Yi , Werngren Jim , Mansjö Mikael , Zheng Xubin , Drobniewski Francis , Hoffner Sven , Xu Biao 
Published: June 2016

ABSTRACT

The aim of this study was to investigate the epidemiology of pyrazinamide (PZA) resistance and the associated risk factors as well as to evaluate the
pncA
gene loci as a marker for PZA resistance in China. A population-based multicenter study of pulmonary tuberculosis (TB) cases was carried out from 2011 to 2013 in four Chinese districts/counties with different geographic and socioeconomic features. Testing for multidrug-resistant tuberculosis (MDR-TB) and susceptibility to PZA was done by the proportion method on Lowenstein-Jensen medium and Bactec MGIT 960, respectively. Mutations in the
pncA
gene were identified by sequencing. Among 878 culture-positive cases, 147 (16.7%) were resistant to PZA, with a significantly higher proportion among MDR isolates than among the first-line drug-susceptible isolates (30.2% versus 7.7%;
P
< 0.001). In total, 136 isolates had a nonsynonymous
pncA
mutation, with a comparable diagnostic performance between Beijing family and non-Beijing family as well as between MDR-TB and first-line drug-susceptible TB. Furthermore, the mutations in isolates with high-level PZA resistance (MIC > 500 mg/liter) were observed mainly in three regions of the
pncA
gene (codons 51 to 76, codons 130 to 142, and codons 163 to 180). Patients with prior treatment history had a significantly higher risk for PZA monoresistance (odds ratio [OR], 2.86; 95% confidence interval [CI], 1.363 to 6.015) and MDR PZA resistance (OR, 6.47; 95% CI, 3.186 to 13.15), while the additional factors associated with MDR PZA resistance were the patient's age (OR, 1.02; 95% CI, 1.003 to 1.042), lung cavity (OR, 2.64; 95% CI, 1.296 to 5.391). These findings suggest that it is a priority to identify PZA resistance in MDR-TB and that a rapid molecular diagnostic test based on
pncA
mutations in the Chinese settings where MDR-TB prevalence is high should be developed.
Murine Alveolar Macrophages Are Highly Susceptible to Replication of Coxiella burnetii Phase IIIn Vitro
Authors: Fernandes Talita D. , Cunha Larissa D. , Ribeiro Juliana M. , Massis Liliana M. , Lima-Junior Djalma S. , Newton Hayley J. , Zamboni Dario S. 
Published: June 2016

ABSTRACTCoxiella burnetiiis a Gram-negative bacterium that causes Q fever in humans. Q fever is an atypical pneumonia transmitted through inhalation of contaminated aerosols. In mammalian lungs,C. burnetiiinfects and replicates in several cell types, including alveolar macrophages (AMs). The innate immunity and signaling pathways operating during infection are still poorly understood, in part because of the lack of relevant host cell models for infectionin vitro. In the study described here, we investigated and characterized the infection of primary murine AMs byC. burnetiiphase IIin vitro. Our data reveal that AMs show a pronounced M2 polarization and are highly permissive toC. burnetiimultiplicationin vitro. Murine AMs present an increased susceptibility to infection in comparison to primary bone marrow-derived macrophages. AMs support more than 2 logs of bacterial replication during 12 days of infection in culture, similar to highly susceptible host cells, such as Vero and THP-1 cells. As a proof of principle that AMs are useful for investigation ofC. burnetiireplication, we performed experiments with AMs fromNos2−/−orIfng−/−mice. In the absence of gamma interferon and nitric oxide synthase 2 (NOS2), AMs were significantly more permissive than wild-type cells. In contrast, AMs fromIl4−/−mice were more restrictive toC. burnetiireplication, supporting the importance of M2 polarization for the permissiveness of AMs toC. burnetiireplication. Collectively, our data account for understanding the high susceptibility of alveolar macrophages to bacterial replication and support the use of AMs as a relevant model ofC. burnetiigrowth in primary macrophages.
The Conserved Tetratricopeptide Repeat-Containing C-Terminal Domain of Pseudomonas aeruginosa FimV Is Required for Its Cyclic AMP-Dependent and -Independent Functions
Authors: Buensuceso Ryan N. C. , Nguyen Ylan , Zhang Kun , Daniel-Ivad Martin , Sugiman-Marangos Seiji N. , Fleetwood Aaron D. , Zhulin Igor B. , Junop Murray S. , Howell P. Lynne , Burrows Lori L. 
Published: June 2016

ABSTRACT

FimV is a
Pseudomonas aeruginosa
inner membrane protein that regulates intracellular cyclic AMP (cAMP) levels—and thus type IV pilus (T4P)-mediated twitching motility and type II secretion (T2S)—by activating the adenylate cyclase CyaB. Its cytoplasmic domain contains three predicted tetratricopeptide repeat (TPR) motifs separated by an unstructured region: two proximal to the inner membrane and one within the “FimV C-terminal domain,” which is highly conserved across diverse homologs. Here, we present the crystal structure of the FimV C terminus, FimV
861–919
, containing a TPR motif decorated with solvent-exposed, charged side chains, plus a C-terminal capping helix. FimV
689
, a truncated form lacking this C-terminal motif, did not restore wild-type levels of twitching or surface piliation compared to the full-length protein. FimV
689
failed to restore wild-type levels of the T4P motor ATPase PilU or T2S, suggesting that it was unable to activate cAMP synthesis. Bacterial two-hybrid analysis showed that TPR3 interacts directly with the CyaB activator, FimL. However, FimV
689
failed to restore wild-type motility in a
fimV
mutant expressing a constitutively active CyaB (
fimV cyaB-R456L
), suggesting that the C-terminal motif is also involved in cAMP-independent functions of FimV. The data show that the highly conserved TPR-containing C-terminal domain of FimV is critical for its cAMP-dependent and -independent functions.

IMPORTANCE
FimV is important for twitching motility and cAMP-dependent virulence gene expression in
P. aeruginosa
. FimV homologs have been identified in several human pathogens, and their functions are not limited to T4P expression. The C terminus of FimV is remarkably conserved among otherwise very diverse family members, but its role is unknown. We provide here biological evidence for the importance of the C-terminal domain in both cAMP-dependent (through FimL) and -independent functions of FimV. We present X-ray crystal structures of the conserved C-terminal domain and identify a consensus sequence for the C-terminal TPR within the conserved domain. Our data extend our knowledge of FimV's functionally important domains, and the structures and consensus sequences provide a foundation for studies of FimV and its homologs.
Antimicrobial Resistance Expressed by
Neisseria gonorrhoeae
: A Major Global Public Health Problem in the 21st Century
Authors: Unemo Magnus , del Rio Carlos , Shafer William M. 
Published: June 2016

ABSTRACT

Neisseria gonorrhoeae
is a strictly human pathogen that is typically transmitted by sexual contact. The associated disease gonorrhea has plagued humankind for thousands of years, with a current estimated incidence of 78 million cases per year. Advances in antimicrobial discovery in the 1920s and 1930s leading to the discovery of sulfonamides and penicillin begun the era of effective antimicrobial treatment of gonorrhea. Unfortunately, the gonococcus developed decreased susceptibility or even resistance to these initially employed antibiotics, a trend that continued over subsequent decades with each new antibiotic that was brought into clinical practice. As this pattern of resistance has continued into the 21st century, there is now reason for great concern, especially in an era when few new antibiotics have prospects for use as treatment of gonorrhea. Here, we review the history of gonorrhea treatment regimens and gonococcal resistance to antibiotics, the mechanisms of resistance, resistance monitoring schemes that exist in different international settings, global responses to the challenge of resistance, and prospects for future treatment regimens in the 21st century.
Preparing for Serious Communicable Diseases in the United States: What the Ebola Virus Epidemic Has Taught Us
Authors: Varkey Jay B. , Ribner Bruce S. 
Published: June 2016

ABSTRACT
Ending the West Africa Ebola virus disease (EVD) outbreak required an unprecedented international response. For the United States, participation in the international response to the West Africa EVD outbreak provided an opportunity to learn important lessons in four key domains critical to preparing for future outbreaks of EVD and other serious communicable diseases: (i) safe and effective patient care, (ii) the role of experimental therapeutics and vaccines, (iii) infection control, and (iv) hospital and community preparedness.
Leisure activities are linked to mental health benefits by providing time structure: comparing employed, unemployed and homemakers
Authors: Goodman William K , Geiger Ashley M , Wolf Jutta M 
Published: June 2016

BackgroundUnemployment has consistently been linked to negative mental health outcomes, emphasising the need to characterise the underlying mechanisms. The current study aimed at testing whether compared with other employment groups, fewer leisure activities observed in unemployment may contribute to elevated risk for negative mental health via loss of time structure.MethodsDepressive symptoms (Center for Epidemiologic Studies Depression), leisure activities (exercise, self-focused, social), and time structure (Time Structure Questionnaire (TSQ)) were assessed cross-sectionally in 406 participants (unemployed=155, employed=140, homemakers=111) recruited through Amazon Mechanical Turk.ResultsControlling for gender and age, structural equation modelling revealed time structure partially (employed, homemakers) and fully (unemployed) mediated the relationship between leisure activities and depressive symptoms. With the exception of differential effects for structured routines, all other TSQ factors (sense of purpose, present orientation, effective organisation and persistence) contributed significantly to all models.ConclusionsThese findings support the idea that especially for the unemployed, leisure activities impose their mental health benefits through increasing individuals' perception of spending their time effectively. Social leisure activities that provide a sense of daily structure may thereby be a particularly promising low-cost intervention to improve mental health in this population.
Dynamic Process Migration Based on Block Access Patterns Occurring in Storage Servers
Authors: Liao Jianwei , Trahay François , Xiao Guoqiang 
Published: June 2016

An emerging trend in developing large and complex applications on today’s high-performance computers is to couple independent components into a comprehensive application. The components may employ the global file system to exchange their data when executing the application. In order to reduce the time required for input/output (I/O) data exchange and data transfer in the coupled systems or other applications, this article proposes a dynamic process migration mechanism on the basis of block access pattern similarity for utilizing the local file cache to exchange the data. We first introduce the scheme of the block access counting diagram to profile the process access pattern during a time period on the storage server. Next, we propose an algorithm that compares the access patterns of processes running on different computing nodes. Last, processes are migrated in order to group processes with similar access patterns. Consequently, the processes on the computing node can exchange their data by accessing the local file cache, instead of the global file system.
The experimental results show that the proposed process migration mechanism can reduce the execution time required by the application because of the shorter I/O time, as well as yield attractive I/O throughput. In summary, this dynamic process migration technique can work fairly well for distributed applications whose data dependency rely on distributed file systems.