bluuebunny/crossref_metadata_2025 huggingface dataset:
Consequences of climate-induced vegetation changes exceed those of human disturbance for wild impala in the Serengeti ecosystem
Authors: Hunninck L , May R , Jackson C R , Palme R , Røskaft E , Sheriff M J
Published: December 2019

In East Africa, climate change is predicted to reduce vegetation quality, and pervasive human disturbance has already resulted in significant declines in biodiversity. We studied the combined effects of reduced forage quality and human disturbance on faecal glucocorticoid metabolite (FGM) concentrations. We predicted that decreasing nutritional quality and increasing human disturbance would have an additive positive effect on FGM levels in wild impala (Aepyceros melampus). Employing a space-for-time approach, we used normalized difference vegetation index (NDVI) as a measure of forage quality, combined with spatially explicit proxies of human disturbance across areas of different protection management strategies in the Serengeti ecosystem. We collected 639 faecal samples, spread over 4 years, including both wet and dry seasons. Impala FGM levels increased significantly with declining NDVI and, to a lesser extent, with increasing proxies for human disturbance. However, we found no interaction between the two, such that impala had elevated FGM levels with low NDVI and low FGM levels with high NDVI regardless of human disturbance levels. This implies that impala will have high FGM levels if forage quality is poor, even with significant protection and reduced human disturbance. Understanding how animals respond to and cope with changes in forage quality and human land use across different protected areas is important for conservationists and managers to better protect species at risk and predict population viability.
Viral Hepatitis and Human Immunodeficiency Virus Testing and Linkage to Care for Individuals Enrolled in an Opioid Treatment Program
Authors: Rowan Sarah E , Kamis Kevin F , Beum Robert , Bryan Kimberly , Gawenus Lisa , Colon Sanchez Dayan , Hurley Hermione
Published: January 2020

Background

In the United States, many opioid treatment programs (OTPs) do not offer viral hepatitis (VH) or human immunodeficiency virus (HIV) testing despite high prevalence among OTP clients. We initiated an opt-out VH and HIV testing and linkage-to-care program within our OTP.

Methods

All OTP intakes are screened for VH and HIV and evaluated for rescreening annually. A patient navigator reviews laboratory results and provides counseling in the OTP clinic. The medical record is queried to identify individuals with previously diagnosed, untreated VH or HIV. Navigation support is provided for linkage or relinkage to VH or HIV care.

Results

Between March 2018 and Februrary 2019, 532 individuals were screened for hepatitis C virus (HCV), 180 tested HCV antibody positive (34%), and 108 were HCV-ribonucleic acid (RNA) positive (20%). Sixty individuals were identified with previously diagnosed, untreated HCV. Of all HCV RNA+, 49% reported current injection drug use (82 of 168). Ninety-five individuals were seen by an HCV specialist (57% of HCV RNA+), 72 started treatment (43%), and 69 (41%) completed treatment. Individuals with primary care providers were most likely to start treatment. Four individuals were diagnosed with hepatitis B; 0 were diagnosed with HIV.

Conclusions

The implementation of an OTP-based screening and navigation protocol has enabled significant gains in the identification and treatment of VH in this high prevalence setting.
Dosimetry of High-Energy Photon Beams Based on Standards of Absorbed Dose to Water: Abstract
Authors: Hohlfeld K. , Andreo P. , Mattsson O. , Simoen J. P.
Published: January 2020

This report examines the methods by which absorbed dose to water can be determined for photon radiations with maximum energies from approximately 1 MeV to 50 MeV, the beam qualities most commonly used for radiation therapy. The report is primarily concerned with methods of measurement for photon radiation, but many aspects are also relevant to the dosimetry of other therapeutic beams (high-energy electrons, protons, etc.). It deals with methods that are sufficiently precise and well established to be incorporated into the dosimetric measurement chain as primary standards (i.e., methods based on ionisation, radiation-induced chemical changes, and calorimetry using either graphite or water). The report discusses the primary dose standards used in several national standards laboratories and reviews the international comparisons that have been made. The report also describes the reference conditions that are suitable for establishing primary standards and provides a formalism for determining absorbed dose, including a discussion of correction factors needed under conditions other than those used to calibrate an instrument at the standards laboratory.
Absorbed-Dose Specification in Nuclear Medicine: Abstract
Authors: Adelstein S. J. , Green A. J. , Howell R. W. , Humm J. L. , Leichner P. K. , O'Donoghue J. A. , Strand S.-E. , Wessels B. W.
Published: January 2020

A number of reasons have led to a reappraisal of dose specification for nuclear medicine. These include an appreciation of non-uniformities in the distribution of radioactivity in the body, at all levels, for even the most common diagnostic and therapeutic agents; an increasing need to deal with the complexities of varying dose rates; the imperative to provide individual rather than standardised dose estimates as targeted radionuclide therapy becomes more sophisticated; as well as improvements in technology.

This Report deals first with biological considerations that inform the rational use of radionuclide dosimetry. Radiobiological factors in the selection of radionuclides and tumour and normal-tissue dose-responses are discussed. Then, the MIRD (medical internal radiation dose) approach to nuclear medical dosimetry, a robust method that has proven its clinical utility, is described. Following on is an elaboration of non-uniform distributions of radioactivity and of varying dose rates. Lastly, the Report deals with techniques and procedures for measuring time variant activity distributions, image fusion, patient specific dose computations, smallscale dosimetry, and the comparison of calculated and measured doses.
Unique bacterial assembly, composition, and interactions in a parasitic plant and its host
Authors: Fitzpatrick Connor R , Schneider Adam C
Published: January 2020

How plant-associated microbiota are shaped by, and potentially contribute to, the unique ecology and heterotrophic life history of parasitic plants is relatively unknown. Here, we investigate the leaf and root bacterial communities of the root holoparasite Orobanche hederae and its host Hedera spp. from natural populations. Root bacteria inhabiting Orobanche were less diverse, had fewer co-associations, and displayed increased compositional similarity to leaf bacteria relative to Hedera. Overall, Orobanche bacteria exhibited significant congruency with Hedera root bacteria across sites, but not the surrounding soil. Infection had localized and systemic effects on Hedera bacteria, which included effects on the abundance of individual taxa and root network properties. Collectively, our results indicate that the parasitic plant microbiome is derived but distinct from the host plant microbiota, exhibits increased homogenization between shoot and root tissues, and displays far fewer co-associations among individual bacterial members. Host plant infection is accompanied by modest changes of associated microbiota at both local and systemic scales compared with uninfected individuals. Our results are a first step towards extending the growing insight into the assembly and function of the plant microbiome to include the ecologically unique but often overlooked guild of heterotrophic plants.
The Correlative Strength of Objective Physical Assessment Against the ECOG Performance Status Assessment in Individuals Diagnosed With Cancer
Authors: Quinn Sarah E , Crandell Catherine E , Blake Morgan E , Bontrager Amy M , Dempsey Alexandra G , Lewis Derek J , Hamm John T , Flynn Joseph M , Smith Grant S , Wingard Christopher J
Published: January 2020

Background

Individuals with cancer experience loss of function and disability due to disease and cancer-related treatments. Physical fitness and frailty influence treatment plans and may predict cancer outcomes. Outcome measures currently used may not provide sufficiently comprehensive assessment of physical performance.

Objective

The objectives of this study are to: (1) describe the development of a functional measure, the Bellarmine Norton Assessment Tool (BNAT), for individuals with cancer; and (2) assess the relationship between the BNAT and the Eastern Cooperative Oncology Group (ECOG) Performance Status, a commonly used classification system by oncologists.

Design

This was a prospective cohort correlation study.

Methods

The BNAT encompasses 1 self-reported physical activity question and 4 objective tests: 2-Minute Step Test, 30-Second Sit to Stand, Timed Arm Curl, and Timed Up and Go. The BNAT score and its components were compared with ECOG Performance Status scores assigned by oncologists and analyzed for correlation and agreement.

Results

A total of 103 male and female individuals (ages 33–87 years) with various cancer diagnoses participated. The mean (SD) ECOG Performance Status score was 0.95 (0.87), range 0 to 3, and the mean BNAT score was 14.9 (4.3), range 5 to 24. Spearman agreement association of BNAT and ECOG Performance Status scores revealed a significant moderate negative relationship (r = −0.568).

Limitations

The BNAT was compared with the ECOG Performance Status, a commonly used but subjective measure. Additionally, a common data set was used for both deriving and evaluating the BNAT performance scale.

Conclusions

There was a moderate negative linear relationship of BNAT to ECOG Performance Status scores across all participants. Utilization of the BNAT may reflect overall physical performance and provide comprehensive and meaningful detail to influence therapeutic decisions.
MV v DSL & GV: arbitration, governing law and jurisdiction clauses
Authors: Simms Brian , Turnquest Marco
Published: January 2020

Two judgments, delivered by the Bahamian Supreme Court on 27 November 2018 and 7 August 2019 in ongoing litigation brought by MV against DSL and GV, provide useful guidance on changing a governing law and the efficacy of arbitration clauses. Courts are ready to construe arbitration clauses in deeds and statutes liberally to achieve their purposes. Sometimes, the best they can do is to highlight any statutory lacuna so that the law can be changed eg by Rules of Court.
Multifaced regulator: RNA binding proteins and their roles in hematopoiesis
Authors: Ren Yue , Huo Yue , Li Weiqian , Wang Fang , Yu Jia
Published: January 2020

Despite the conventional definition of RNA binding proteins (RBPs) as controlling the metabolism of their bound RNAs, more and more RBPs are found to function via distinct ways in complex biological processes. With the recent discovery of transcriptional regulation activity of some RBPs, a hypothesis that RBPs could be multilayered regulators orchestrating gene expression has emerged. Hematopoiesis is a stepwise process that needs to be fine-tuned to keep the subtle balance between hematopoietic stem cell (HSC) stemness maintenance and downstream lineage commitment. Although the classic RBPs account for the posttranscriptional regulation in hematopoiesis, the importance and multiple regulatory capacities of RBPs have not been well-characterized. In this review, we summarize the recent findings of large-scale screening of novel RBPs and their novel transcriptional regulation potentials. In hematopoietic system, this kind of multifaced regulators account for nearly a half of functional RBPs. Therefore, further studies on identifying this new kind of multifaced RBPs and clarifying their regulatory mechanisms would help us better understand the precise and complex regulatory networks of gene expression in hematopoiesis.
Tissue-resident macrophages: from zebrafish to mouse
Authors: Lin Xi , Wen Zilong , Xu Jin
Published: January 2020

Tissue-resident macrophages (TRMs), generally found in tissues under normal physiological conditions, play crucial roles not only in immunity but also in tissue development and homeostasis. Because of their diverse functions, dysregulation of their development and function has been implicated in many human disorders. In the past decade, a great deal of extensive studies have been conducted in various model organisms with cutting-edge technologies to explore the origin and function of TRMs. In this review, we summarize the recent findings on TRMs in mouse and zebrafish and compare the similarity/differences between these two species.
A chemotaxis model to explain WHIM neutrophil accumulation in the bone marrow of WHIM mouse model
Authors: Yip Ai Kia , Balachander Akhila , Tan Leonard D.L. , Liong Ka Hang , Tan Rui Zhen , Balabanian Karl , Bachelerie Francoise , Ng Lai Guan , Chiam Keng-Hwee
Published: January 2020

Neutrophils are essential immune cells that defend the host against pathogenic microbial agents. Neutrophils are produced in the bone marrow and are retained there through CXCR4–CXCL12 signaling. However, patients with the Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) syndrome are prone to infections due to increased accumulation of neutrophils in the bone marrow leading to low numbers of circulating neutrophils. How neutrophils accumulate in the bone marrow in this condition is poorly understood. To better understand factors involved in neutrophil accumulation in the bone marrow, neutrophils from wildtype and WHIM mouse models were characterized in their response to CXCL12 stimulation. WHIM neutrophils were found to exert stronger traction forces, formed significantly more lamellipodia-type protrusions and migrated with increased speed and displacement upon CXCL12 stimulation as compared to wildtype cells. Migration speed of WHIM neutrophils showed a larger initial increase upon CXCL12 stimulation, which decayed over a longer time period as compared to wildtype cells. We proposed a computational model based on the chemotactic behavior of neutrophils that indicated increased CXCL12 sensitivity and prolonged CXCR4 internalization adaptation time in WHIM neutrophils as being responsible for increased accumulation in the bone marrow. These findings provide a mechanistic understanding of bone marrow neutrophil accumulation in WHIM condition and novel insights into restoring neutrophil regulation in WHIM patients.
Wakanki Ewastepikte
Authors: Isaacson Mary J.
Published: January 2020

Many American Indian tribes' traditional philosophy of death is one of realism; death is a part of the cycle of life. Yet, health care professionals harbor misperceptions regarding beliefs about death and dying in American Indian tribes, fearing that it is inappropriate to broach the subject. These fears hamper end-of-life discussions, which are crucial for advance care planning and completion of advance directives. This community-based participatory project was conducted on an American Indian reservation in the Northern Plains, where American Indian elders and a nurse researcher developed and implemented a culturally specific advance directive program. At program completion, the 2 elders visited 11 different communities, conducted 270 face-to-face educational sessions, and traveled more than 1000 miles across the reservation. Of those attending the educational sessions, nearly 93% had never heard of a living will, with roughly 7% indicating some knowledge of living wills; 1 person reported having a living will. This community-based, American Indian, elder-led project demonstrates that this population is concerned about its care at end of life and wishes to receive more information. Improving American Indian awareness regarding palliative/end-of life care options and the need for advance directives can help to ensure that their end-of-life wishes will be honored.
Use of mobile health apps in low-income populations: a prospective study of facilitators and barriers
Authors: Liu Patrick , Astudillo Katia , Velez Damaris , Kelley Lauren , Cobbs-Lomax Darcey , Spatz Erica S.
Published: December 2019

Background

Mobile applications (apps) are increasingly popular in healthcare. For low-income populations, barriers exist, yet limited data are available about the challenges and catalysts for adoption.

Methods and Results

We partnered with a primary care center and a community organization and recruited patients to use a health app. A community health worker (CHW) consented participants, downloaded the app and instructed on its use, and provided ongoing technical support. Bi-weekly surveys for three months were sent via email/text to assess participant experiences and perceptions.

The majority (81 of 108 [75.0%] English language-preferred and 50 of 52 [96.2%] Spanish language-preferred) of patients approached were enrolled. Common reasons for declining were: did not own a smartphone (13.8%), did not have email (20.7%), and not interested (58.6%). Enrollment challenges included: insufficient storage, unfamiliarity with downloading apps, forgotten passwords to email accounts, and slow/absent WiFi connection – which the CHW and the app company were able to address. Most participants, English and Spanish language-preferred respectively, were interested in monitoring their health through an app (74.4%; 70.4%), connecting devices such as FitBits© and blood pressure cuffs (78.9%; 50.0%), and being the owner of their health records (83.6%; 95.6%). There were concerns about sharing health information with research teams (66.7%; 51.9%), and data being sold (83.0%; 70.4%). However, many (58.6%; 87.2%) reported being likely to share health data with a trusted research team. Compared with before the study, most felt more comfortable using health apps (67.4%; 82.1%) and more likely to participate in research using apps (76.2%; 72.4%).

Conclusions

The assistance of a CHW facilitated the enrollment of low-income individuals in a mobile health app by fostering trust and sustained engagement. Participants were interested in having several app features. Despite concerns about data privacy, they demonstrated greater interest in mobile health app use and research participation at study conclusion.
Simulation of closed-loop deep brain stimulation control schemes for suppression of pathological beta oscillations in Parkinson’s disease
Authors: Fleming John E. , Dunn Eleanor , Lowery Madeleine M.
Published: December 2019

This study presents a computational model of closed-loop control of deep brain stimulation (DBS) for Parkinson’s disease (PD) to investigate clinically-viable control schemes for suppressing pathological beta-band activity. Closed-loop DBS for PD has shown promising results in preliminary clinical studies and offers the potential to achieve better control of patient symptoms and side effects with lower power consumption than conventional open-loop DBS. However, extensive testing of algorithms in patients is difficult. The model presented provides a means to explore a range of control algorithmsin silicoand optimize control parameters before preclinical testing. The model incorporates (i) the extracellular DBS electric field, (ii) antidromic and orthodromic activation of STN afferent fibers, (iii) the LFP detected at non-stimulating contacts on the DBS electrode and (iv) temporal variation of network beta-band activity within the thalamo-cortico-basal ganglia loop. The performance of on-off and dual-threshold controllers for suppressing beta-band activity by modulating the DBS amplitude were first verified, showing levels of beta suppression and reductions in power consumption comparable with previous clinical studies. Proportional (P) and proportional-integral (PI) closed-loop controllers for amplitude and frequency modulation were then investigated. A simple tuning rule was derived for selecting effective PI controller parameters to target long duration beta bursts while respecting clinical constraints that limit the rate of change of stimulation parameters. Of the controllers tested, PI controllers displayed superior performance for regulating network beta-band activity whilst accounting for clinical considerations. Proportional controllers resulted in undesirable rapid fluctuations of the DBS parameters which may exceed clinically tolerable rate limits. Overall, the PI controller for modulating DBS frequency performed best, reducing the mean error by 83% compared to DBS off and the mean power consumed to 25% of that utilized by open-loop DBS. The network model presented captures sufficient physiological detail to act as a surrogate for preclinical testing of closed-loop DBS algorithms using a clinically accessible biomarker, providing a first step for deriving and testing novel, clinically-suitable closed-loop DBS controllers.
Neurophysiological Correlates of the Dunning-Kruger Effect
Authors: Muller Alana , Sirianni Lindsey A. , Addante Richard J.
Published: December 2019

The Dunning-Kruger Effect (DKE) is a metacognitive phenomenon of illusory superiority in which individuals who perform poorly on a task believe they performed better than others, yet individuals who performed very well believe they under-performed compared to others. This phenomenon has yet to be directly explored in episodic memory, nor explored for reaction times or physiological correlates. We designed a novel method to elicit the DKE via a test of item recognition while electroencephalography (EEG) was recorded. Throughout the task, participants were asked to estimate the percentile in which they performed compared to others. Results revealed participants in the bottom 25th percentile overestimated their percentile, while participants in the top 75th percentile underestimated their percentile, exhibiting the classic DKE. Reaction time measures revealed a condition x group interaction whereby over-estimators responded faster than under-estimators when estimating being in the top percentile and responded slower when estimating being in the bottom percentile.

Between-group EEG differences were evident between over-estimators and under-estimators during Dunning-Kruger responses, which revealed FN400-like effects of familiarity supporting differences for over-estimators from 400-600 ms, whereas ‘old-new’ memory ERP effects revealed a late parietal component (LPC) associated with recollection-based processing from 600-900 ms for under-estimators that was not evident for over-estimators. Findings suggest over- and under-estimators use differing cognitive processes when assessing their performance, such that under-estimators rely on recollection during memory and over-estimators draw upon excess familiarity when over-estimating their performance. Episodic memory thus appears to play a contributory role in metacognitive judgments of illusory superiority and inferiority.

Graphical Abstract

Event-related potentials (ERPS) were recorded for the Dunning-Kruger Effect as subjects made metacognitive judgments about performance on a memory task. Over- and Under-estimators exhibited a crossover interaction in response times when believing they did best and worst, respectively. A crossover pattern was also observed for ERPs: LPC signals of recollection were found for under-estimators, whereas familiarity-based FN400 effects were evident for over-estimators and correlated with estimates.
Game Theory Applications in Host-Microbe Interactions:Mycobacterium tuberculosisinfection as an example
Authors: Sharebiani H , Hajimiri S , Abbasnia S , Soleimanpour S , Asnaashari H , Valizadeh N , Derakhshan M , Pilpa R , Firouzeh A , Ghazvini K , Amel Jamehdar S , Rezaee SAR
Published: December 2019

The game theory describes the interactions between two players and the pay-off from wining, losing or compromising.Mycobacterium tuberculosis(Mtb)-host interactions were used as an example for the application of the game theory to describe and predict the possibilities of victory for any players. The gene expression for eight main markers of host response and threeMtbvirulence factors were assessed in broncho-alveolar lavage of TB+and TB−patients. The game theory showed that a variety of paths exist that players can use, in response to the behaviour of the counterpart. Briefly, according to the “Nash equilibrium”, Ag85B is the main virulence factor forMtbin active phase, however it is the most immunogenic factor if the host can respond by high expression of T-bet and iNOS. In this situation,Mtbcan express high levels of ESAT-6 and CFP10 and change the game to the latency, in which host responses by medium expression of T-bet and iNOS and medium level of TGF-β and IDO. Consistently, The IDO expression was 134-times higher in TB+s than the TB−s, and the T-bet expression, ~200-times higher in the TB−s than the TB+s. Furthermore,Mtb-Ag85B had a strong positive association with CCR2, T-bet and iNOS, but had a negative correlation with IDO.
Spontaneous and automatic processing of magnitude and parity information of Arabic digits: A frequency-tagging EEG study
Authors: Guillaume Mathieu , Poncin Alexandre , Schiltz Christine , Van Rinsveld Amandine
Published: December 2019

Arabic digits (1-9) are everywhere in our daily lives. These symbols convey various semantic information, and numerate adults can easily extract from them several numerical features such as magnitude and parity. Nonetheless, since most studies used active processing tasks to assess these properties, it remains unclear whether and to what degree the access to magnitude and especially to parity is automatic. Here we investigated with EEG whether spontaneous processing of magnitude or parity can be recorded in a frequency-tagging approach, in which participants are passively stimulated by fast visual sequences of Arabic digits. We assessed automatic magnitude processing by presenting a stream of frequentsmalldigit numbers mixed with deviantlargedigits (and the reverse) with a sinusoidal contrast modulation at the frequency of 10 Hz. We used the same paradigm to investigate numerical parity processing, contrastingodddigits toevendigits. We found significant brain responses at the frequency of the fluctuating change and its harmonics, recorded on electrodes encompassing right occipitoparietal regions, in both conditions. Our findings indicate that both magnitude and parity are spontaneously and unintentionally extracted from Arabic digits, which supports that they are salient semantic features deeply associated to digit symbols in long-term memory.
Mixture coding and segmentation in the anterior piriform cortex
Authors: Penker Sapir , Licht Tamar , Hofer Katharina T. , Rokni Dan
Published: December 2019

Coding of odorous stimuli has been mostly studied using single isolated stimuli. However, a single sniff of air in a natural environment is likely to introduce airborne chemicals emitted by multiple objects into the nose. The olfactory system is therefore faced with the task of segmenting odor mixtures to identify objects in the presence of rich and often unpredictable backgrounds. The piriform cortex is thought to be the site of object recognition and scene segmentation, yet the nature of its responses to odorant mixtures is largely unknown. In this study, we asked two related questions. 1) How are mixtures represented in the piriform cortex? And 2) Can the identity of individual mixture components be read out from mixture representations in the piriform cortex? To answer these questions, we recorded single unit activity in the piriform cortex of naïve mice while sequentially presenting single odorants and their mixtures. We find that a normalization model explains mixture responses well, both at the single neuron, and at the population level. Additionally, we show that mixture components can be identified from piriform cortical activity by pooling responses of a small population of neurons - in many cases a single neuron is sufficient. These results indicate that piriform cortical representations are well suited to perform figure-background segmentation without the need for learning.
“Campylobacter jejunimotility integrates specialized cell shape, flagellar filament, and motor, to coordinate action of its opposed flagella in viscous media”
Authors: Cohen Eli J. , Nakane Daisuke , Kabata Yoshiki , Hendrixson David R. , Nishizaka Takayuki , Beeby Morgan
Published: December 2019

Campylobacter jejunirotates a flagellum at each pole to swim through the viscous mucosa of its hosts’ gastrointestinal tracts. Despite their importance for host colonization, however, howC. jejunicoordinates rotation of these two opposing flagella is unclear. As well as their polar placement,C. jejuni’sflagella deviate from the Enterobacteriaceael norm in other ways: their flagellar motors produce much higher torque and their flagellar filament is made of two different zones of two different flagellins. To understand howC. jejuni’sopposed motors coordinate, and what contribution these factors play inC. jejunimotility, we developed strains with flagella that could be fluorescently labeled, and observed them by high-speed video microscopy. We found thatC. jejunicoordinates its dual flagella by wrapping the leading filament around the cell body during swimming in high-viscosity media and that its differentiated flagellar filament has evolved to facilitate this wrapped-mode swimming. Unexpectedly,C. jejuni’s helical body is important for facile unwrapping of the flagellar filament from the cell body during switching of swimming trajectory. Our findings demonstrate how multiple facets ofC. jejuni’sflagella and cell plan have co-evolved for optimal motility in high-viscosity environments.
Arginase Inhibition Supports Survival and Differentiation of Neuronal Precursors in Adult Alzheimer’s Disease Mice
Authors: Polis Baruh , Gurevich Vyacheslav , Bloch Naamah , Samson Abraham O.
Published: December 2019

Adult neurogenesis is a complex physiological process, which plays a central role in maintaining cognitive functions, and consists of progenitor cell proliferation, newborn cell migration, and cell maturation. Adult neurogenesis is susceptible to alterations under various physiological and pathological conditions. A substantial decay of neurogenesis has been documented in Alzheimer’s disease (AD) patients and animal AD models; however, several treatment strategies can halt any further decline and even induce neurogenesis.

Our previous results indicated a potential effect of arginase inhibition, with norvaline, on various aspects of neurogenesis in triple-transgenic mice. To better evaluate this effect, we chronically administer an arginase inhibitor, norvaline, to triple-transgenic and wild-type mice, and apply an advanced immunohistochemistry approach with several biomarkers and bright-field microscopy.

Remarkably, we evidence a significant reduction in the density of neuronal progenitors, which demonstrate a different phenotype in the hippocampi of triple-transgenic mice as compared to wild-type animals. However, norvaline shows no significant effect upon the progenitor cell number and constitution. We demonstrate that norvaline treatment leads to an escalation of the polysialylated neuronal cell adhesion molecule immunopositivity, which suggests an improvement in the newborn neuron survival rate. Additionally, we identify a significant increase in the hippocampal microtubule-associated protein 2 stain intensity. We also explore the molecular mechanisms underlying the effects of norvaline on adult mice neurogenesis and provide insights into their machinery.
Chemical transcription roadblocking for nascent RNA display
Authors: Strobel Eric J. , Lis John T. , Lucks Julius B.
Published: December 2019

Site-specific arrest of RNA polymerase is fundamental to several technologies that measure RNA structure and function. Currentin vitrotranscription ‘roadblocking’ approaches inhibit transcription elongation using a protein blockade bound to the DNA template. One limitation of protein-mediated transcription roadblocking is that it requires the inclusion of a protein factor that is extrinsic to the minimalin vitrotranscription reaction. In this work, we show that interrupting the transcribed DNA strand with an internal desthiobiotin-triethylene glycol modification efficiently and stably haltsEscherichia coliRNA polymerase transcription. To facilitate diverse applications of chemical transcription roadblocking, we establish a simple and sequence-independent method for the preparation of internally modified double-stranded DNA templates by sequential PCR and translesion synthesis. By encoding an intrinsic stall site within the template DNA, our chemical transcription roadblocking approach enables nascent RNA molecules to be displayed from RNA polymerase in a minimalin vitrotranscription reaction.
Mapping biology from mouse to man using transfer learning
Authors: Stumpf Patrick S. , Du Doris , Imanishi Haruka , Kunisaki Yuya , Semba Yuichiro , Noble Timothy , Smith Rosanna C.G. , Rose-Zerili Matthew , West Jonathan J. , Oreffo Richard O.C. , Niranjan Mahesan , Akashi Koichi , Arai Fumio , MacArthur Ben D.
Published: December 2019

Biomedical research often involves conducting experiments on model organisms in the anticipation that the biology learnt from these experiments will transfer to the human. Yet, it is commonly the case that biology does not transfer effectively, often for unknown reasons. Despite its importance to translational research this transfer process is not currently rigorously quantified. Here, we show that transfer learning – the branch of machine learning that concerns passing information from one domain to another – can be used to efficiently map biology from mouse to man, using the bone marrow (BM) as a representative example of a complex tissue. We first trained an artificial neural network (ANN) to accurately recognize various different cell types in mouse BM using data obtained from single-cell RNA-sequencing (scRNA-Seq) experiments. We found that this ANN, trained exclusively on mouse data, was able to identify individual human cells obtained from comparable scRNA-Seq experiments of human BM with 83% overall accuracy. However, while some human cell types were easily identified, others were not, indicating important differences in biology. To obtain a more accurate map of the human BM we then retrained the mouse ANN using scRNA-Seq data from a limited sample of human BM cells. Typically, less than 10 human cells of a given type were needed to accurately learn its representation in the updated model. In some cases, human cell identities could be inferred directly from the mouse ANN without retraining, via a process of biologically-guided zero-shot learning. These results show how machine learning can be used to reconstruct complex biology from limited data and have broad implications for biomedical research.
Selective and invariant features of neural response surfaces measured with principal curvature
Authors: Golden James R. , Vilankar Kedarnath P. , Field David J.
Published: December 2019

The responses of most visual cortical neurons are highly nonlinear functions of image stimuli. With the sparse coding network, a recurrent model of V1 computation, we apply techniques from differential geometry to these nonlinear responses and classify them as forms of selectivity or invariance. The selectivity and invariance of responses of individual neurons are quantified by measuring the principal curvatures of neural response surfaces in high-dimensional image space. An extended two-layer version of the network model that captures some properties of higher visual cortical areas is also characterized using this approach. We argue that this geometric view allows for the quantification of feature selectivity and invariance in network models in a way that provides insight into the computations necessary for object recognition.
Prolonged reaction times help to eliminate residual errors in visuomotor adaptation
Authors: Langsdorf Lisa , Maresch Jana , Hegele Mathias , McDougle Samuel D. , Schween Raphael
Published: December 2019

One persistent curiosity in visuomotor adaptation tasks is that participants often do not reach maximal performance. This incomplete asymptote has been explained as a consequence of obligatory computations within the implicit adaptation system, such as an equilibrium between learning and forgetting. A body of recent work has shown that in standard adaptation tasks, cognitive strategies operate alongside implicit learning. We reasoned that incomplete learning in adaptation tasks may primarily reflect a speed-accuracy trade-off on time-consuming motor planning. Across three experiments, we find evidence supporting this hypothesis, showing that hastened motor planning may primarily lead to under-compensation. When an obligatory waiting period was administered before movement start, participants were able to fully counteract imposed perturbations (experiment 1). Inserting the same delay between trials - rather than during movement planning - did not induce full compensation, suggesting that the motor planning interval predicts the learning asymptote (experiment 2). In the last experiment, we asked participants to continuously report their movement intent. We show that emphasizing explicit re-aiming strategies (and concomitantly increasing planning time) also lead to complete asymptotic learning. Findings from all experiments support the hypothesis that incomplete adaptation is, in part, the result of an intrinsic speed-accuracy trade-off, perhaps related to cognitive strategies that require parametric attentional reorienting from the visual target to the goal.
Oxygen consumption of drift-feeding rainbow trout: the energetic tradeoff between locomotion and feeding in flow
Authors: Johansen J.L. , Akanyeti O. , Liao J.C.
Published: December 2019

To forage in fast, turbulent flow environments where prey are abundant, predatory fishes must deal with the high associated costs of locomotion. Prevailing theory suggests that many species exploit hydrodynamic refuges to minimize the cost of locomotion while foraging. Here we challenge this theory based on direct oxygen consumption measurements of drift-feeding trout (Oncorhynchus mykiss)foraging in the freestream and from behind a flow refuge at velocities up to 100 cm s-1. We demonstrate that refuging is not energetically beneficial when foraging in fast flows due to a high attack cost and low prey capture success associated with leaving a station-holding refuge to intercept prey. By integrating optimum foraging theory with empirical data from respirometry and video imaging, we develop a mathematical model to predict when drift-feeding fishes should exploit or avoid refuges based on prey density, size and flow velocity. Our foraging and refuging model provides new mechanistic insights into the locomotor costs, habitat use, and prey selection of fishes foraging in current-swept habitats.
Benzaldehyde Synthases Are Encoded by Cinnamoyl-CoA Reductase Genes in Cucumber (Cucumis sativusL.)
Authors: Liu Baoxiu , Wei Guo , Hu Zhongyi , Wang Guodong
Published: December 2019

Benzaldedyde, commonly detected in plant VOC (volatile organic compounds) profiling, is derived from phenylalanine. However, the last enzymatic step for benzaldedyde formation, designated as benzaldehyde synthase, remains elusive for long time. Here, we demonstrated that cinnamoyl-CoA reductases are responsible for benzaldedyde production in cucumber (Cucumis sativusL.). Comprehensive tissue specificity of VOC profiling revealed that benzaldehyde was specifically accumulated in root and flower of cucumber plants. VOC-gene correlation analysis suggested that severalCCRs are candidate genes for benzaldehyde production:CsaCCR7had a root-specific expression pattern whileCsaCCR9andCsaCCR18showed a flower-specific expression pattern. Enzymatic assay demonstrated that CsaCCR7, CsaCCR9 and CsaCCR18 convert benzoyl-CoA to benzaldehyde. Subcellular localization experiments revealed that CsaCCR7 and CsaCCR18 are localized in cytosol, while CsaCCR9 was localized in peroxisome. In contrast to the long-standing view that CCR enzymes are involved in lignin biosynthesis in plants, it is the first time here to add a new biochemical role of CCR as benzaldehyde synthase in plants.

Highlights

Benzaldehyde is mainly produced in flower and root of cucumber plants.

14 genes encoding CCR enzyme from cucumber are comprehensively analyzed.

Three CsaCCRs, function as benzaldehyde synthases, utilize benzoyl-CoA as substrate to produce benzaldehydein vitro.
Transgenic mouse facial nerve model of synkinesis: Original Research
Authors: Ahmed Mostafa M , Deich Alexander , Balfour Grace , Laury Adrienne , Lorin Arkady , Silliman David , Williams Richard L.
Published: December 2019

Hypothesis

Our central hypothesis is that inhibition of Schwann cell de-differentiation, in the post-injury setting, will reduce synkinesis and improve facial muscle function

Background

No therapies exist to improve the accuracy of facial nerve regeneration. Following peripheral nerve injury, adult reactive Schwann cells de-differentiate and express glial fibrillary acidic protein (GFAP); suggesting that reactive Schwann cells impact axonal regeneration precision.

Methods

Transgenic GFAP-thymidine kinase (TK) mouse model was employed, allowing selective downregulation of reactive GFAP expressing Schwann cells on exposure of 7 day osmotic pump delivery of ganciclovir. Adult female transgenic GFAP-TK mice had right facial nerve transected and then immediately repaired with tissue glue, they then either were treated with saline or ganciclovir (GCV). At 6 weeks post-injury, mice were exposed to random air puffs events while high speed videography recorded whisker and eye movement. MatLab code video processing with publicly available BIOTACT algorithm automatically tracked whiskers.

Results

Whisker velocity was calculated using binning statistical analysis. Saline treated animals confirmed our model’s ability to detect aberrant movement such that intact (left) facial nerves caused whisker protraction, while repaired (right) facial nerves had retraction. Administration of GCV increased whisker retraction compared to saline. GCV did not impact intact animal whisker movement compared to repaired whiskers.

Conclusions

Inhibition of reactive Schwann cell proliferation appears to worse the degree of synkinesis, providing important insight into a potential therapeutic target for facial nerve injury.
Vineyard ecosystems are structured and distinguished by fungal communities impacting the flavour and quality of wine
Authors: Liu Di , Chen Qinglin , Zhang Pangzhen , Chen Deli , Howell Kate S.
Published: December 2019

The flavours of foods and beverages are formed by the agricultural environment where the plants are grown. In the case of wine, the location and environmental features of the vineyard site imprint the wine with distinctive aromas and flavours. Microbial growth and metabolism play an integral role in wine production from the vineyard to the winery, by influencing grapevine health, wine fermentation, and the flavour, aroma and quality of finished wines. The mechanism by which microbial distribution patterns drive wine metabolites is unclear and while flavour has been correlated with bacterial composition for red wines, bacterial activity provides a minor biochemical conversion in wine fermentation. Here, we collected samples across six distinct winegrowing areas in southern Australia to investigate regional distribution patterns of both fungi and bacteria and how this corresponds with wine aroma compounds. Results show that soil and must microbiota distinguish winegrowing regions and are related to wine chemical profiles. We found a strong relationship between microbial and wine metabolic profiles, and this relationship was maintained despite differing abiotic drivers (soil properties and weather/ climatic measures). Notably, fungal communities played the principal role in shaping wine aroma profiles and regional distinctiveness. We found that the soil microbiome is a potential source of grape- and must-associated fungi, and therefore the weather and soil conditions could influence the wine characteristics via shaping the soil fungal community compositions. Our study describes a comprehensive scenario of wine microbial biogeography in which microbial diversity responds to surrounding environments and ultimately sculpts wine aromatic characteristics. These findings provide perspectives for thoughtful human practices to optimise food and beverage flavour and composition through understanding of fungal activity and abundance.
iPromoter-BnCNN: a novel branched CNN based predictor for identifying and classifying sigma promoters
Authors: Amin Ruhul , Rahman Chowdhury Rafeed , Sifat Habibur Rahman , Liton Nazmul Khan , Rahman Moshiur , Ahmed Sajid , Shatabda Swakkhar
Published: December 2019

Motivation

Promoter is a short region of DNA which is responsible for initiating transcription of specific genes. Development of computational tools for automatic identification of promoters is in high demand. According to the difference of functions, promoters can be of different types. Promoters may have both intra and inter class variation and similarity in terms of consensus sequences. Accurate classification of various types of sigma promoters still remains a challenge.

Results

We presentiPromoter-BnCNNfor identification and accurate classification of six types of promoters -σ24,σ28,σ32,σ38,σ54,σ70. It is a CNN based classifier which combines local features related to monomer nucleotide sequence, trimer nucleotide sequence, dimer structural properties and trimer structural properties through the use of parallel branching. We conducted experiments on a benchmark dataset and compared with six state-of-the-art tools to show our supremacy on 5-fold cross-validation. Moreover, we tested our classifier on an independent test dataset.

Availability

Our proposed tool iPromoter-BnCNN web server is freely available athttp://103.109.52.8/iPromoter-BnCNN. The runnable source code can be found here.

Contact

rafeed@cse.uiu.ac.bd

Supplementary information

Supplementary data (benchmark dataset, independent test dataset, model files, structural property information, attention mechanism details and web server usage) are available atBioinformatics. online.
Dynamics of diffusive cell signaling relays
Authors: Dieterle Paul B. , Min Jiseon , Irimia Daniel , Amir Ariel
Published: December 2019

Cells can communicate with each other by emitting diffusible signaling molecules into the surrounding environment. However, simple diffusion is slow. Even small molecules take hours to diffuse millimeters away from their source, making it difficult for thousands of cells to coordinate their activity over millimeters, as happens routinely during development and immune response. Moreover, simple diffusion creates shallow, Gaussian-tailed concentration profiles. Attempting to move up or down such shallow gradients – to chemotax – is a difficult task for cells, as they see only small spatial and temporal concentration changes. Here, we demonstrate that cells utilizing diffusive relays, in which the presence of one type of diffusible signaling molecule triggers participation in the emission of the same type of molecule, can propagate fast-traveling diffusive waves that give rise to steep chemical gradients. Our methods are general and capture the effects of dimensionality, cell density, signaling molecule degradation, pulsed emission, and cellular chemotaxis on the diffusive wave dynamics. We show that system dimensionality – the size and shape of the extracellular medium and the distribution of the cells within it – can have a particularly dramatic effect on wave initiation and asymptotic propagation, and that these dynamics are insensitive to the details of cellular activation. As an example, we show that neutrophil swarming experiments exhibit dynamical signatures consistent with the proposed signaling motif. Interpreted in the context of these experiments, our results provide insight into the utility of signaling relays in immune response.