bluuebunny/crossref_metadata_2025 huggingface dataset:
Planes of Reference for Orbital Fractures: A Technique for Reproducible Measurements of the Orbit on Computed Tomography Scans
Authors: Cai Elijah Zhengyang , Chong Xin Tian , Ong Wan Li , Chan Lai San Felicia , Goh Jie Ying , Sundar Gangadhara , Lim Thiam Chye
Published: October 2018

Purpose:

Planes of reference for orbital fractures (PROF) was developed to standardize measurements made on orbital computed tomography scans. This study describes the use of PROF in determining the location along the orbital floor where the posterior ledge (PL) most commonly occurs. The transverse inclination and anterior-posterior inclination of the orbital floor will also be measured.

Methods:

This study evaluates 104 patients with unilateral orbital fracture. Fifty-two patients had intact infra-orbital margin (IM) and 52 had fractured IM. Facial computed tomography scans were analyzed using Osirix Lite Digital Imaging and Communications in Medicine Viewer version 7.0.1 (Geneva, Switzerland). All skull positions were standardized by orientation according to Frankfurt and mid-sagittal planes. Measurements of distance of PL from IM were determined in the sagittal view. Measurements of the inclination of the orbital floor in the transverse and anterior-posterior sections were done on the coronal and sagittal views respectively.

Results:

For patients with intact and fractured IM, the mean distances of PL from IM were 22.1 mm (95% CI: 21.2–23.0) and 21.1 mm (95% CI: 20.2–21.9) respectively. Mean transverse inclination was 19.4° (95% CI: 18.3–20.5). Mean anterior-posterior inclination was 15.5° (95% CI: 14.5–16.5).

Conclusion:

Planes of reference for orbital fractures is a simple and effective method to acquire standardized measurements of the orbital cavity on computed tomography scans. Understanding the commonest location of PL and the orientation of the orbital floor in 3-dimensional space allows surgeons to perform dissection with greater precision.
Effect of Prior Radiotherapy on the Outcome of Submental Island Flap in Head and Neck Reconstruction
Authors: Karimi Ebrahim , Badiei Reza , Aghazadeh Keivan , Sohrabpour Saeed , Yazdani Nasrin , Dabiri Sasan
Published: October 2018

The submental island flap is a new alternative to the reconstruction of various head and neck defects. But there has been a relative paucity of information about the use of this flap in irradiated patients. The authors present their preliminary experience in the use of this flap in irradiated and nonirradiated patients. Eighty-one patients (53 nonirradiated and 28 irradiated patients) underwent reconstruction with the submental island flap between March 2011 and August 2017. The authors have 13 patients of venous congestion (7 in nonirradiated and 6 in irradiated group), 7 patients of partial necrosis of the flap (4 in nonirradiated and 3 in irradiated group). The authors also have 3 patients of transient paralysis of marginal mandibular nerve (2 in the nonirradiated and 1 in irradiated group), and 2 patients of pharyngo-cutaneous fistula in nonirradiated group. The authors have no cases of total flap loss, permanent paralysis of marginal mandibular nerve but have dehiscence of the submental area after harvesting the flap in an irradiated patient. When combined with the reported experience of other surgeons, the authors’ preliminary experience showed that the submental island flap was an excellent alternative in the reconstruction of head and neck defects in both irradiated and nonirradiated patients because of its reliability, versatility, and relatively acceptable complications.
Circulating Monocyte Counts and its Impact on Outcomes in Patients With Severe Sepsis Including Septic Shock
Authors: Chung Hyunwoo , Lee Jae Hyuk , Jo You Hwan , Hwang Ji Eun , Kim Joonghee
Published: October 2018

This study was performed to evaluate the association of monocyte counts with mortality, the rate of bacteremia, and organ dysfunction and to evaluate whether the change in monocyte counts from the premorbid state to sepsis would differ between survivors and non-survivors in patients with severe sepsis including septic shock. A retrospective analysis of patients with severe sepsis including septic shock was performed. Monocyte counts were categorized into <250, 250–500, 500–750, and ≥750 cells/μL; in addition, 28-day mortality, the rate of bacteremia, and organ dysfunction were compared between the groups. Multivariate logistic regression analyses were performed to evaluate the independent association of initial blood cell counts with 28-day mortality. Subgroup analyses of patients who had premorbid data of blood cell counts were performed to evaluate the difference in the change in monocyte counts between survivors and non-survivors. During the study period, 2,012 patients were included. Neutrophil and monocyte counts were significantly different between survivors and non-survivors. However, only monocyte counts were independently associated with mortality in the multivariate logistic regression analyses. Patients with initial monocyte counts <250 cells/μL showed the highest mortality, rate of bacteremia, and organ dysfunction. In patients who had premorbid blood cell counts, the monocyte counts increased in survivors but decreased in non-survivors from the premorbid to sepsis. In conclusion, monocyte counts were associated with mortality, the rate of bacteremia, and organ dysfunction in patients with sepsis, possibly due to the relative lack of monocytopoiesis related to septic insults in non-survivors.
Performance of Patients with Early Parkinson Disease on an Executive and Social Cognition Battery
Authors: Esteves Sol , Gleichgerrcht Ezequiel , Torralva Teresa , Chade Anabel , Gómez Arévalo Gonzalo , Gershanik Oscar , Manes Facundo , Roca María
Published: October 2018

Objective:

To demonstrate the usefulness of incorporating the Executive and Social Cognition Battery (ESCB) to detect executive and social cognition deficits, which are otherwise not captured by more “classical” executive tests in early Parkinson disease (PD).

Background:

PD is a neurodegenerative disorder that includes executive and social cognition deficits. While cognitive assessment in PD still relies on classical executive tasks to detect frontal deficits, these traditional tests often fail to uncover subtle, yet relevant, frontal impairment.

Methods:

We evaluated 39 PD patients and 47 controls with a battery of classical executive tests and the ESCB. The ESCB includes a series of tasks that more closely resemble real-life activities and have been previously shown to be useful in detecting executive deficits in other neuropsychiatric disorders with frontal involvement.

Results:

We observed that both batteries used in a complementary way yielded better results, as 15 of the 39 patients presented deficits only on some of the ESCB tests, but not on the classical battery, while 5 patients presented deficits only on some tests of the classical battery, but not on the ESCB. Fourteen patients presented deficits on some tests of either battery, and 5 patients did not present deficits on any of the tests.

Conclusions:

We found that, used along with traditional neuropsychological tasks, the ESCB may be useful in providing a more comprehensive evaluation of frontal dysfunction among patients with PD, thus contributing to the early diagnosis of cognitive disorders in this patient population.
Testing of Verbal Fluency in Egyptians: Cultural and Educational Challenges
Authors: Farghaly Marwa , Hussein Mona , Hassan Amr , Hegazy Mohamed , Sabbah Asmaa
Published: October 2018

Background:

The importance of verbal fluency tasks as a cornerstone in cognitive assessment is now well acknowledged, as they provide fast, reliable tools for assessment of both verbal and executive function abilities.

Objectives:

To investigate the effect of age and education on verbal fluency and to develop a verbal fluency task that is culture-oriented and non-education-based to overcome the problem of illiteracy in Egypt.

Methods:

Two groups of participants were recruited, a normal cognition control group (n=79) and a clinically demented group (n=32). Phonemic verbal fluency was tested by asking participants to generate as many words as they could think of starting with the Arabic letter Haa; category fluency was evaluated using four semantic categories (animals, fruits, vegetables, and names).

Results:

Animal, vegetable, and name fluency tasks (unlike phonemic fluency and fruit) were not related to age and education, and they had better criterion validity (area under the receiver operating characteristic curve [AUC]=0.96, 0.91, and 0.92, respectively) than did letters and fruits (AUC=0.74 and 0.86, respectively). Our suggested cutoff points are 11 for the animal fluency task (sensitivity=94%, specificity=93%), 11 for vegetables (sensitivity=84%, specificity=88%), and 18 for names (sensitivity=91%, specificity=82%).

Conclusions:

Animals, vegetables, and names are reliable and appropriate categories to be used for culture-oriented and non-education-based verbal fluency tests.
The chemistry and pharmacology of putative synthetic cannabinoid receptor agonist (SCRA) new psychoactive substances (NPS) 5F-PY-PICA, 5F-PY-PINACA, and their analogues
Authors: Banister Samuel D. , Kevin Richard C. , Martin Lewis , Adams Axel , Macdonald Christa , Manning Jamie J. , Boyd Rochelle , Cunningham Michael , Stevens Marc Y. , McGregor Iain S. , Glass Michelle , Connor Mark , Gerona Roy R.
Published: October 2018

The structural diversity of synthetic cannabinoid receptor agonist (SCRA) new psychoactive substances (NPS) has increased since the first examples were reported a decade ago. 5F-PY-PICA and 5F-PY-PINACA were identified in 2015 as putative SCRA NPS, although nothing is known of their pharmacology. 5F-PY-PICA, 5F-PY-PINACA, and analogues intended to explore structure-activity relationships within this class of SCRAs were synthesized and characterized by nuclear magnetic resonance spectroscopy and liquid chromatography–quadrupole time-of-flight–mass spectrometry. Using competitive binding experiments and fluorescence-based plate reader membrane potential assays, the affinities and activities of all analogues at cannabinoid type 1 and type 2 receptors (CB1 and CB2) were evaluated. All ligands showed minimal affinity for CB1 (pKi < 5), although several demonstrated moderate CB2 binding (pKi = 5.45–6.99). At 10 μM none of the compounds produced an effect > 50% of CP55,950 at CB1, while several compounds showed a slightly higher relative efficacy at CB2. Unlike other SCRA NPS, 5F-PYPICA and 5F-PY-PINACA did not produce cannabimimetic effects in mice at doses up to 10 mg/kg.
Altered Gene Regulatory Networks are Associated with the Transition from C3 to Crassulacean Acid Metabolism in Erycina (Oncidiinae: Orchidaceae)
Authors: Heyduk Karolina , Hwang Michelle , Albert Victor A. , Silvera Katia , Lan Tianying , Farr Kimberly M. , Chang Tien-Hao , Chan Ming-Tsair , Winter Klaus , Leebens-Mack Jim
Published: October 2018

Crassulacean acid metabolism (CAM) photosynthesis is a modification of the core C3 photosynthetic pathway that improves the ability of plants to assimilate carbon in water-limited environments. CAM plants fix CO2 mostly at night, when transpiration rates are low. All of the CAM pathway genes exist in ancestral C3 species, but the timing and magnitude of expression are greatly altered between C3 and CAM species. Understanding these regulatory changes is key to elucidating the mechanism by which CAM evolved from C3. Here we use two closely related species in the Orchidaceae, Erycina pusilla (CAM) and Erycina crista-galli (C3), to conduct comparative transcriptomic analyses across multiple time points. Clustering of genes with expression variation across the diel cycle revealed some canonical CAM pathway genes similarly expressed in both species, regardless of photosynthetic pathway. However, gene network construction indicated that 149 gene families had significant differences in network connectivity and were further explored for these functional enrichments. Genes involved in light sensing and ABA signaling were some of the most differently connected genes between the C3 and CAM Erycina species, in agreement with the contrasting diel patterns of stomatal conductance in C3 and CAM plants. Our results suggest changes to transcriptional cascades are important for the transition from C3 to CAM photosynthesis in Erycina.
Functional diversity in a tritrophic system: Effects on biomass production, variability, and resilience of ecosystem functions
Authors: Ceulemans Ruben , Gaedke Ursula , Klauschies Toni , Guill Christian
Published: October 2018

Diverse communities can adjust their trait composition to altered environmental conditions, which may strongly influence their dynamics. Previous studies of trait-based models mainly considered only one or two trophic levels, whereas most natural system are at least tritrophic. Therefore, we investigated how the addition of trait variation to each trophic level influences population and community dynamics in a tritrophic model. Examining the phase relationships between species of adjacent trophic levels informs about the degree of top-down or bottom-up control in non-steady-state situations. Phase relationships within a trophic level highlight compensatory dynamical patterns between functionally different species, which are responsible for dampening the community temporal variability. Furthermore, even without trait variation, our tritrophic model always exhibits regions with two alternative states with either weak or strong nutrient exploitation, and correspondingly low or high biomass production at the top level. However, adding trait variation increased the basin of attraction of the high-production state, and decreased the likelihood of a critical transition from the high-to the low-production state with no apparent early warning signals. Hence, our study shows that trait variation enhances resource use efficiency, production, variability, and resilience of entire food webs.
Hetero-oligomeric CPN60 resembles highly symmetric group I chaperonin structure revealed by Cryo-EM
Authors: Zhao Qian , Zhang Xiang , Sommer Frederik , Ta Na , Wang Ning , Schroda Michael , Cong Yao , Liu Cuimin
Published: October 2018

The chloroplast chaperonin system is indispensable for the biogenesis of Rubisco, the key enzyme in photosynthesis. Using Chlamydomonas reinhardtii as the model system, we revealed that chloroplast chaperonin is consisted of CPN60α, CPN60β1, and CPN60β2, and co-chaperonin is composed of three subunits CPN20, CPN11 and CPN23 in vivo. CPN20 homo-oligomers and all possible other chloroplast co-chaperonin hetero-oligomers are functional, but only CPN11/20/23-CPN60αβ1β2 pair can fully replace GroES/GroEL in E. coli at stringent growth condition. Endogenous CPN60 was purified and its stoichiometry was determined to be 6:2:6 for CPN60α:CPN60β1:CPN60β2. The cryo-EM structures of endogenous CPN60αβ1β2/ADP and CPN60αβ1β2/co-chaperonin/ADP were solved at resolutions of 4.06 Å and 3.82Å, respectively. In both hetero-oligomeric complexes the chaperonin subunits within each ring are highly symmetric. The chloroplast co-chaperonin CPN11/20/23 formed seven GroES-like domains through hetero-oligomerization which symmetrically interact with CPN60αβ1β2. Our structures also reveal an uneven distribution of roof-like structures in the dome-shaped CPN11/20/23 and potentially diversified surface properties in the folding cavity of CPN60αβ1β2 that might enable the chloroplast chaperonin system to assist in the folding of specific substrates.
Genetic signatures of human cytomegalovirus variants acquired by seronegative glycoprotein B vaccinees
Authors: Nelson Cody S. , Cruz Diana Vera , Su Melody , Xie Guanhua , Vandergrift Nathan , Pass Robert F. , Forman Michael , Diener-West Marie , Koelle Katia , Arav-Boger Ravit , Permar Sallie R.
Published: October 2018

Human cytomegalovirus (HCMV) is the most common congenital infection worldwide, and a frequent cause of hearing loss or debilitating neurologic disease in newborn infants. Thus, a vaccine to prevent HCMV-associated congenital disease is a public health priority. One potential strategy is vaccination of women of child-bearing age to prevent maternal HCMV acquisition during pregnancy. The glycoprotein B (gB) + MF59 adjuvant subunit vaccine is the most efficacious tested clinically to date, demonstrating approximately 50% protection against HCMV infection of seronegative women in multiple phase 2 trials. Yet, the impact of gB/MF59-elicited immune responses on the population of viruses acquired by trial participants has not been assessed. In this analysis, we employed quantitative PCR as well as multiple sequencing methodologies to interrogate the magnitude and genetic composition of HCMV populations infecting gB/MF59 vaccinees and placebo recipients. We identified several differences between the viral dynamics of acutely-infected vaccinees and placebo recipients. First, there was reduced magnitude viral shedding in the saliva of gB vaccinees. Additionally, employing a panel of tests for genetic compartmentalization, we noted tissue-specific gB haplotypes in the majority of vaccinees though only in a single placebo recipient. Finally, we observed reduced acquisition of genetically-related gB1, gB2, and gB4 genotype “supergroup” HCMV variants among vaccine recipients, suggesting that the gB1 genotype vaccine construct may have elicited partial protection against HCMV viruses with antigenically-similar gB sequences. These findings indicate that gB immunization may have had a measurable impact on viral intrahost population dynamics and support future analysis of a larger cohort.

Author Summary

Though not a household name like Zika virus, human cytomegalovirus (HCMV) causes permanent neurologic disability in one newborn child every hour in the United States - more than Down syndrome, fetal alcohol syndrome, and neural tube defects combined. There are currently no established effective preventative measures to inhibit congenital HCMV transmission following acute or chronic HCMV infection of a pregnant mother. However, the glycoprotein B (gB) vaccine is the most effective HCMV vaccine tried clinically to date. Here, we utilized high-throughput, next-generation sequencing of viral DNA isolated from patients enrolled in a gB vaccine trial, and identified several impacts that this vaccine had on the size, distribution, and composition of thein vivoviral population. These results have increased our understanding of why the gB/MF59 vaccine was partially efficacious and will inform future rational design of a vaccine to prevent congenital HCMV.
Using a large-scale biodiversity monitoring dataset to test the effectiveness of protected areas at conserving North-American breeding birds
Authors: Cazalis Victor , Belghali Soumaya , Rodrigues Ana S.L.
Published: October 2018

Protected areas currently cover about 15% of the global land area, and constitute one of the main tools in biodiversity conservation. Quantifying their effectiveness at protecting species from local decline or extinction involves comparing protected with counterfactual unprotected sites representing “what would have happened to protected sites had they not been protected”. Most studies are based on pairwise comparisons, using neighbour sites to protected areas as counterfactuals, but this choice is often subjective and may be prone to biases. An alternative is to use large-scale biodiversity monitoring datasets, whereby the effect of protected areas is analysed statistically by controlling for landscape differences between protected and unprotected sites, allowing a more targeted and clearly defined measure of the protected areas effect. Here we use the North American Breeding Bird Survey dataset as a case study to investigate the effectiveness of protected areas at conserving bird assemblages. We analysed the effect of protected areas on species richness, on assemblage-level abundance, and on the abundance of individual species by modelling how these metrics relate to the proportion of each site that is protected, while controlling for local habitat, altitude, productivity and for spatial autocorrelation. At the assemblage level, we found almost no relationship between protection and species richness or overall abundance. At the species level, we found that forest species are present in significantly higher abundances within protected forest sites, compared with unprotected forests, with the opposite effect for species that favour open habitats. Hence, even though protected forest assemblages are not richer than those of unprotected forests, they are more typical of this habitat. We also found some evidence that species that avoid human activities tend to be favoured by protection, but found no such effect for regionally declining species. Our results highlight the complexity of assessing protected areas effectiveness, and the necessity of clearly defining the metrics of effectiveness and the controls used in such assessments.
Selective sweep and phylogenetic models for the emergence and spread of pyrimethamine resistance mutations inPlasmodium vivax
Authors: Shaukat Ayaz , Ali Qasim , Connelley Timothy , Azmat Ullah Khan Muhammad , Saleem Mushtaq A. , Rashid Imran , Sargison Neil D. , Chaudhry Umer
Published: October 2018

Pyrimethamine resistance is a major concern for the control of human haemoprotozoa, especiallyPlasmodiumspecies. Currently, there is little understanding of how pyrimethamine resistance developed inPlasmodium vivaxin the natural field conditions. Here, we present first time the evidence of positive selection pressure on a dihydrofolate reductase locus and its consequences on the emergence and the spread of pyrimethamine resistance inP. vivaxin the Punjab province of Pakistan. First, we examined the pyrimethamine resistance locus in 38P. vivaxpopulations to look for evidence of positive selection pressure in human patients. The S58R (AGA)/S117N (AAC) double mutation was most common, being detected in 10/38 populations. Single mutation S117N (AAC), I173L (CTT) and S58R (AGA) SNPs were detected in 8/38, 2/38 and 1/38 populations, respectively. The F57L/I (TTA/ATA) and T61M (ATG) SNPs were not detected in any population examined. Although both soft and hard selective sweeps have occurred with striking differences between populations, there was a predominance of hard sweeps. A single resistance haplotype was present at high frequency in 9/14 populations, providing a strong evidence for the single emergence of these mutations. In contrast, 5/14 populations carried multiple resistance haplotypes at high frequencies, providing an evidence of the emergence of resistance by recurrent mutations, characteristics of soft selective sweeps. Our phylogenetic relationship analysis suggests that S58R (AGA)/S117N (AAC) and S117N (AAC) mutations arose multiple times from a single origin and spread to multiple different cities in the Punjab province through gene flow. Interestingly, the I173L (CTT) mutation was present on a single haplotype, suggesting that it arises rarely and has not spread between cities. Our work shows the need for responsible use of exiting and new antimicrobial drugs and their combinations, control the movement of infected patients and mosquito vector control strategies.
Structural and proteomic changes in viable but non-culturableVibrio cholerae
Authors: Brenzinger Susanne , van der Aart Lizah T. , van Wezel Gilles P. , Lacroix Jean-Marie , Glatter Timo , Briegel Ariane
Published: October 2018

Aquatic environments are reservoirs of the human pathogenVibrio choleraeO1, which causes the acute diarrheal disease cholera. Upon low temperature or limited nutrient availability, the cells enter a viable but non-culturable (VBNC) state. Characteristic of this state are an altered morphology, low metabolic activity and lack of growth under standard laboratory conditions. Here, for the first time, the cellular ultrastructure ofV. choleraeVBNC cells raised in natural waters was investigated using electron cryo-tomography complemented by comparison of the proteomes and the peptidoglycan composition of LB overnight culture and VBNC cells. The extensive remodeling of the VBNC cells was most obvious in the passive dehiscence of the cell envelope, resulting in improper embedment of flagella and pili. Only minor changes of the peptidoglycan and osmoregulated periplasmic glucans were observed. Active changes in VBNC cells included the production of cluster I chemosensory arrays and change of abundance of cluster II array proteins. Components involved in iron acquisition and storage, peptide import and arginine biosynthesis were overrepresented in VBNC cells, while enzymes of the central carbon metabolism were found at lower levels. Finally, several pathogenicity factors ofV. choleraewere less abundant in the VBNC state, potentially limiting their infectious potential.
Neurons remap to represent memories in the human entorhinal cortex
Authors: Qasim Salman , Miller Jonathan , Inman Cory S. , Gross Robert E. , Willie Jon T. , Lega Bradley , Lin Jui-Jui , Sharan Ashwini , Wu Chengyuan , Sperling Michael R. , Sheth Sameer A. , McKhann Guy M. , Smith Elliot H. , Schevon Catherine , Stein Joel , Jacobs Joshua
Published: October 2018

The entorhinal cortex (EC) is known to play a key role in both memory and spatial navigation. Despite this overlap in spatial and mnemonic circuits, it is unknown how spatially responsive neurons contribute to our ability to represent and distinguish past experiences. Recording from medial temporal lobe (MTL) neurons in subjects performing cued recall of object–location memories in a virtual-reality environment, we identified “trace cells” in the EC that remap their spatial fields to locations subjects were cued to recall on each trial. In addition to shifting its firing field according to the memory cue, this neuronal activity exhibited a firing rate predictive of the cued memory’s content. Critically, this memory-specific neuronal activity re-emerged when subjects were cued for recall without entering the environment, indicating that trace-cell memory representations generalized beyond navigation. These findings suggest a general mechanism for memory retrieval via trace-cell activity and remapping in the EC.
The genetic relationship between female reproductive traits and six psychiatric disorders
Authors: Ni Guiyan , Amare Azmeraw , Zhou Xuan , Mills Natalie , Gratten Jacob , Hong Lee Sang
Published: October 2018

Female reproductive behaviors have an important implication in evolutionary fitness and health of offspring. Previous studies have shown that age at first birth of women (AFB) is genetically associated with schizophrenia (SCZ). However, for most other psychiatric disorders and reproductive traits, the latent shared genetic architecture is largely unknown. Here we used the second wave of UK Biobank data (N=220,685) to evaluate the association between five female reproductive traits and polygenetic risk scores (PRS) projected from genome-wide association study summary statistics of six psychiatric disorders (N=429,178). We found that the PRS of attention-deficit/hyperactivity disorder (ADHD) were strongly associated with AFB (genetic correlation of −0.68 ± 0.03 with p-value = 1.86E-89), age at first sexual intercourse (AFS) (−0.56 ± 0.03 with p-value = 3.42E-60), number of live births (NLB) (0.36 ± 0.04 with p-value = 4.01E-17) and age at menopause (−0.27 ± 0.04 with p-value = 5.71E-13). There were also robustly significant associations between the PRS of eating disorder (ED) and AFB (genetic correlation of 0.35 ± 0.06), ED and AFS (0.19 0.06), Major depressive disorder (MDD) and AFB (−0.27 ± 0.07), MDD and AFS (− 0.27 ± 0.03) and SCZ and AFS (−0.10 ± 0.03). Our findings reveal the shared genetic architecture between the five reproductive traits in women and six psychiatric disorders, which have a potential implication that helps to improve reproductive health in women, hence better child outcomes. Our findings may also explain, at least in part, an evolutionary hypothesis that causal mutations underlying psychiatric disorders have positive effects on reproductive success.
Wide and Deep Imaging of Neuronal Activities by a Wearable NeuroImager Reveals Premotor Activity in the Whole Motor Cortex
Authors: Kobayashi Takuma , Islam Tanvir , Sato Masaaki , Ohkura Masamichi , Nakai Junichi , Hayashi Yasunori , Okamoto Hitoshi
Published: October 2018

Wearable technologies for functional whole brain imaging in freely moving animals would advance our understanding of cognitive processing and adaptive behavior. Fluorescence imaging can visualize the activity of individual neurons in real time, but conventional microscopes have limited sample coverage in both the width and depth of view. Here we developed a novel head-mounted laser camera (HLC) with macro and deep-focus lenses that enable fluorescence imaging at cellular resolution for comprehensive imaging in mice expressing a layer- and cell type-specific calcium probe. We visualized orientation selectivity in individual excitatory neurons across the whole visual cortex of one hemisphere, and cell assembly expressing the premotor activity that precedes voluntary movement across the motor cortex of both hemispheres. Including options for multiplex and wireless interfaces, our wearable, wide- and deep-imaging HLC technology could enable simple and economical mapping of neuronal populations underlying cognition and behavior.
Blood flow-mediated gene transfer and siRNA-knockdown in the developing vasculature in a spatio-temporally controlled manner in chicken embryos
Authors: Takase Yuta , Takahashi Yoshiko
Published: October 2018

We describe a method by which early developing vasculature can be gene-manipulated independently of the heart in a spatio-temporally controlled manner. Lipofectamine 2000 or 3000, an easy-to-use lipid reagent, has been found to yield a high efficiency of transfection when co-injected withGFPDNA within a critical range of lipid concentration. By exploiting developmentally changing patterns of vasculature and blood flow, we have succeed in controlling the site of transfection: injection with a lipid-DNA cocktail into the heart before or after the blood circulation starts results in a limited and widely spread patterns of transfection, respectively. Furthermore, a cocktail injection into the right dorsal aorta leads to transgenesis of the right half of embryonic vasculature. In addition, this method combined with the siRNA technique has allowed, for the first time, to knockdown the endogenous expression ofVE-cadherin(also calledCdh5), which has been implicated in assembly of nasant blood vessels: whenCah5siRNA is injected into the right dorsal aorta, pronounced defects in the right half of vasculature are observed without heart defects. Whereas infusion-mediated gene transfection method has previously been reported using lipid reagents that were elaborately prepared on their own, Lipofectamine is an easy-use reagent with no requirement of special expertise. The methods reported here would overcome shortcomings of conventional vascular-transgenic animals, such as mice and zebrafish, in which pan-endothelial enhancer-driven transgenesis often leads to the heart malformation, which, in turn, indirectly affects peripheral vasculature due to flow defects. Since a variety of subtypes in vasculature have increasingly been appreciated, the spatio-temporally controllable gene manipulation described in this study offers a powerful tool.

Research Highlights

Blood flow-mediated transfection enables site-specific transgenesis in vessels.

This transfection technique allows local knockdown of endogenous gene(s) by siRNA.

Knockdown of endogenousVE-cadherincauses vascular defects without heart failure.
Structural variants identified by Oxford Nanopore PromethION sequencing of the human genome
Authors: Wouter De Coster , Arne De Roeck , Tim De Pooter , Svenn D’Hert , Peter De Rijk , Mojca Strazisar , Sleegers Kristel , Christine Van Broeckhoven
Published: October 2018

We sequenced the Yoruban NA19240 genome on the long read sequencing platform Oxford Nanopore PromethION for benchmarking and evaluation of recently published aligners and structural variant calling tools. In this work, we determined the precision and recall, present high confidence and high sensitivity call sets of variants and discuss optimal parameters. The aligner Minimap2 and structural variant caller Sniffles are both the most accurate and the most computationally efficient tools in our study. We describe our scalable workflow for identification, annotation, and characterization of tens of thousands of structural variants from long read genome sequencing of an individual or population. By discussing the results of this genome we provide an approximation of what can be expected in future long read sequencing studies aiming for structural variant identification.
Brg1 controls neurosensory cell fate commitment and differentiation in the mammalian inner ear
Authors: Xu Jinshu , Li Jun , Eddie Loh Yong-Hwee , Zhang Ting , Jiang Huihui , Fritzsch Bernd , Ramakrishnan Aarthi , Shen Li , Xu Pin-Xian
Published: October 2018

Otic ectoderm gives rise to almost all cell types of the inner ear; however, the mechanisms that link transcription factors, chromatin, lineage commitment and differentiation capacity are largely unknown. Here we show that Brg1 chromatin-remodeling factor is required for specifying neurosensory lineage in the otocyst and for inducing hair and supporting cell fates in the cochlear sensory epithelium. Brg1 interacts with the critical neurosensory-specific transcription factors Eya1/Six1, both of which simultaneously interact with BAF60a or BAF60c. Chromatin immunoprecipitation-sequencing (ChIP-seq) and ChIP assays demonstrate Brg1 association with discrete regulatory elements at theEya1andSix1loci.Brg1-deficiency leads to markedly decreased Brg1 binding at these elements and loss ofEya1andSix1expression. Furthermore, ChIP-seq reveals Brg1-bound promoter-proximal and distal regions near genes essential for inner ear morphogenesis and cochlear sensory epithelium development. These findings uncover essential functions for chromatin-remodeling in the activation of neurosensory fates during inner ear development.
pyPhotometry: Open source Python based hardware and software for fiber photometry data acquisition
Authors: Akam Thomas , Walton Mark E.
Published: October 2018

Fiber photometry is the process of recording bulk neural activity by measuring fluorescence changes in activity sensitive indicators (e.g. GCaMP) through an optical fiber. We present a system of open source hardware and software for fiber photometry data acquisition consisting of a compact, low cost, data acquisition board built around the Micropython microcontroller, and a cross platform graphical user interface (GUI) for controlling acquisition and visualising signals. The system can acquire two analog and two digital signals, and control two external LEDs via built in LED drivers. Time-division multiplexed illumination allows independent readout of fluorescence evoked by different excitation wavelengths from a single photoreceiver signal. Validation experiments indicate this approach offers better signal to noise for a given average excitation light intensity than sinusoidally-modulated illumination. pyPhotometry is substantially cheaper than commercial hardware filling the same role, and we anticipate, as an open source and comparatively simple tool, it will be easily adaptable and therefore of broad interest to a wide range of users.
High-performance GFP-based calcium indicators for imaging activity in neuronal populations and microcompartments
Authors: Dana Hod , Sun Yi , Mohar Boaz , Hulse Brad , Hasseman Jeremy P. , Tsegaye Getahun , Tsang Arthur , Wong Allan , Patel Ronak , Macklin John J. , Chen Yang , Konnerth Arthur , Jayaraman Vivek , Looger Loren L. , Schreiter Eric R. , Svoboda Karel , Kim Douglas S.
Published: October 2018

Calcium imaging with genetically encoded calcium indicators (GECIs) is routinely used to measure neural activity in intact nervous systems. GECIs are frequently used in one of two different modes: to track activity in large populations of neuronal cell bodies, or to follow dynamics in subcellular compartments such as axons, dendrites and individual synaptic compartments. Despite major advances, calcium imaging is still limited by the biophysical properties of existing GECIs, including affinity, signal-to-noise ratio, rise and decay kinetics, and dynamic range. Using structure-guided mutagenesis and neuron-based screening, we optimized the green fluorescent protein-based GECI GCaMP6 for different modes of in vivo imaging. The jGCaMP7 sensors provide improved detection of individual spikes (jGCaMP7s,f), imaging in neurites and neuropil (jGCaMP7b), and tracking large populations of neurons using 2-photon (jGCaMP7s,f) or wide-field (jGCaMP7c) imaging.
Chronic aromatase inhibition increases ventral hippocampal neurogenesis in middle-aged female mice
Authors: Chaiton Jessica A , Wong Sarah J , Galea Liisa AM
Published: October 2018

Letrozole, a third-generation aromatase inhibitor, prevents the production of estrogens in the final step in conversion from androgens. Due to its efficacy at suppressing estrogens, letrozole has recently taken favor as a first-line adjuvant treatment for hormone-responsive breast cancer in middle-aged women. Though patient response to letrozole has generally been positive, there is conflicting evidence surrounding its effects on the development of depression. It is possible that the potential adverse effects of letrozole on mood are a result of the impact of hormonal fluctuations on neurogenesis in the hippocampus. Thus, to clarify the effects of letrozole on the hippocampus and behavior, we examined how chronic administration affects hippocampal neurogenesis and depressive-like behavior in middle-aged, intact female mice. Mice were given either letrozole (1mg/kg) or vehicle by injection (i.p.) daily for 3 weeks. Depressive-like behavior was assessed during the last 3 days of treatment using the forced swim test, tail suspension test, and sucrose preference test. The production of new neurons was quantified using the immature neuronal marker doublecortin (DCX), and cell proliferation was quantified using the endogenous marker Ki67. We found that letrozole increased DCX and Ki67 expression and maturation in the dentate gyrus, but had no significant effect on depressive-like behavior. Our findings suggest that a reduction in estrogens in middle-aged females increases hippocampal neurogenesis without any adverse impact on depressive-like behavior; as such, this furthers our understanding of how estrogens modulate neurogenesis, and to the rationale for the utilization of letrozole in the clinical management of breast cancer.
Intestinal Serum Amyloid A suppresses systemic neutrophil activation and bactericidal activity in response to microbiota colonization
Authors: Murdoch Caitlin C. , Espenschied Scott T. , Matty Molly A. , Mueller Olaf , Tobin David M. , Rawls John F.
Published: October 2018

The intestinal microbiota influence diverse aspects of host physiology, including the development and function of myeloid lineages. Numerous host and microbial factors are known to poise neutrophils and other granulocytes for response to pathogens and danger signals, yet the mechanisms by which the intestinal microbiota regulate this process are largely unknown. Using gnotobiotic zebrafish, we identified the immune effector Serum amyloid A (Saa) as one of the most highly induced transcripts in digestive tissues following microbiota colonization. Saa is a conserved secreted protein produced in the intestine and liver with described effects on neutrophilsin vitro, however itsin vivofunctions are poorly defined. We engineered saa mutant zebrafish to test requirements for Saa on innate immunityin vivo. Zebrafish mutant for saa displayed impaired neutrophil responses to wounding but augmented clearance of pathogenic bacteria. At baseline, saa mutants exhibited moderate neutrophilia and altered neutrophil tissue distribution. Molecular and functional analyses of isolated neutrophils revealed that Saa suppresses expression of pro-inflammatory mRNAs and bactericidal activity. Saa’s effects on neutrophils depends on microbiota colonization, suggesting this protein mediates the microbiota’s influence on host innate immunity. To test tissue-specific roles of Saa on neutrophil function, we generated transgenic zebrafish over-expressingsaain the intestine. Transgenic intestinal saa expression was sufficient to partially complement the neutrophil phenotypes insaamutants. These results indicate Saa produced by the intestine in response to microbiota serves as a systemic signal to neutrophils to restrict aberrant activation, decreasing inflammatory tone and bacterial killing potential while simultaneously enhancing their ability to migrate to wounds.
High-salt–recovered sequences are associated with the active chromosomal compartment and with large ribonucleoprotein complexes including nuclear bodies
Authors: Baudement Marie-Odile , Cournac Axel , Court Franck , Seveno Marie , Parrinello Hugues , Reynes Christelle , Sabatier Robert , Bouschet Tristan , Yi Zhou , Sallis Sephora , Tancelin Mathilde , Rebouissou Cosette , Cathala Guy , Lesne Annick , Mozziconacci Julien , Journot Laurent , Forné Thierry
Published: October 2018

The mammalian cell nucleus contains numerous discrete suborganelles named nuclear bodies. While recruitment of specific genomic regions into these large ribonucleoprotein (RNP) complexes critically contributes to higher-order functional chromatin organization, such regions remain ill-defined. We have developed the high-salt–recovered sequences-sequencing (HRS-seq) method, a straightforward genome-wide approach whereby we isolated and sequenced genomic regions associated with large high-salt insoluble RNP complexes. By using mouse embryonic stem cells (ESCs), we showed that these regions essentially correspond to the most highly expressed genes, and to cis-regulatory sequences like super-enhancers, that belong to the active A chromosomal compartment. They include both cell-type–specific genes, such as pluripotency genes in ESCs, and housekeeping genes associated with nuclear bodies, such as histone and snRNA genes that are central components of Histone Locus Bodies and Cajal bodies. We conclude that HRSs are associated with the active chromosomal compartment and with large RNP complexes including nuclear bodies. Association of such chromosomal regions with nuclear bodies is in agreement with the recently proposed phase separation model for transcription control and might thus play a central role in organizing the active chromosomal compartment in mammals.
Not your typical “historian”
Authors: Lefevre Adrienne , Walter-Garcia Madison , Hanson Kimberly , Smith-Easley Julia
Published: October 2018

Purpose

In the incident command system (ICS) structure, response documentation is formally found within the planning section. However, longer term emergency responses have demonstrated the need for a flexible and innovative role that encompasses a variety of activities, including response documentation, communications science, real-time evaluation of major themes, and information management. The paper aims to discuss this issue.

Design/methodology/approach

This need can be universally met through the functional role of “Historian,” a term specific to ICS, or in the case of public health response, incident management system (IMS). It should be noted that the Historian role discussed is not related to the academic study of history, but to archiving key successes and challenges during a response. Ideally the Historian should be activated at the start of an emergency response and remain active to capture the overall picture of the response, including internal information, such as lessons learned, response activities, and decision-making processes.

Findings

The Historian compiles details of response activities that inform leadership, donors and external communications products while alleviating pressures on the planning section. The primary, minimum output of an IMS Historian is a response timeline, which notes major internal and external events during a response with emphasis on major themes, lessons learned, and creating a user-friendly interface to display this information (see the list “Abbreviated Example of Hurricane Matthew Response Timeline” in the text).

Originality/value

In a world with competing priorities and ongoing emergencies, the Historian’s role of archiving details of response efforts can help the international public health community to share lessons learned and contribute to lower morbidity and mortality among those affected by emergencies.
Integration of materialism with shopping motivations: motivations based profile of Indian mall shoppers
Authors: Singh Devinder Pal
Published: October 2018

Purpose

The paper aims to investigate materialism as one of the retail shopping motives along with utilitarian/hedonic motivations in the Indian context. It aims to identify the key shopping motivations, which explain the shopping value in the context of malls. Furthermore, it intends to develop a shopping motivations-based typology of Indian mall shoppers, and to profile the motivational and demographic characteristics of the discerned segments.

Design/methodology/approach

The data were collected through a mall intercept survey. The shopping motivations were identified through literature, and established scales were utilised to collect data. Exploratory factor analysis was used to understand the underlying structure of mall shopping motives. Hierarchical and K-means clustering were used to cluster the consumers. Additionally, ANOVA along withpost hoctests were used to explore the mean differences between the various clusters. Cross-tabulation along with the chi-square statistic was used to understand the demographic characteristics of the clusters.

Findings

Indian mall shoppers are motivated by hedonistic, materialistic and utilitarian motives. They can be primarily classified into four clusters, namely, balanced shoppers, materialist shoppers, hedonistic shoppers and value shoppers.

Research limitations/implications

Knowledge of distinct consumer segments will aid marketers in formulating marketing and promotional strategies for augmenting mall footfalls.

Originality/value

Although past research has accentuated hedonic and utilitarian motivations as the primary shopping motives, little research has been conducted to examine materialism as a shopping motive. Rise of materialism in the emerging Indian market has metamorphosed the consumer behaviour. The study examines the utilitarian, hedonistic and materialistic dimensions of shopping and unfolds a typology of mall shoppers. It contributes to the repository of cross-national research on shopping behaviour by unravelling the shopping motivations of Indian consumers.