bluuebunny/crossref_metadata_2025 huggingface dataset:
Chia (Salvia hispanica) gene expression atlas elucidates dynamic spatio-temporal changes associated with plant growth and development
Authors: Gupta Parul , Geniza Matthew , Naithani Sushma , Phillips Jeremy , Haq Ebaad , Jaiswal Pankaj
Published: October 2020

Chia (Salvia hispanicaL.), now a popular superfood, is one of the richest sources of dietary nutrients such as protein, fiber, and polyunsaturated fatty acids. At present, the genomic and genetic information available in the public domain for this crop is scanty, which hinders understanding its growth and developmental processes and impedes genetic improvement through genomics-assisted methods. We report RNA-seq based comprehensive transcriptome atlas of Chia across 13 different tissue types covering vegetative and reproductive growth stages. We generated ∼394 million raw reads from transcriptome sequencing, of which ∼355 million high-quality reads were used to generatede novoreference transcriptome assembly and the tissue-specific transcript assemblies. After quality assessment of merged assemblies and using redundancy reduction methods, 82,663 reference transcripts were identified. Of these, 53,200 transcripts show differential expression in at least one sample and provide information on spatio-temporal modulation of gene expression in Chia. We identified genes involved in the biosynthesis of omega-3 and omega-6 polyunsaturated fatty acids, and various terpenoid compounds. The study also led to the identification of 633 differentially expressed transcription factors from 53 gene families. The coexpression analysis suggested that members of the B3, bZIP, ERF, WOX, AP2, MYB, C3H, EIL, LBD, DBB, Nin-like, and HSF transcription factor gene families play key roles in the regulation of target gene expression across various developmental stages. This study also identified 2,411 simple sequence repeat (SSRs) as potential genetic markers residing in the transcribed regions. The transcriptome atlas provides essential genomic resources for basic research, applications in plant breeding, and annotation of the Chia genome.
Long-term soil fungal community recovery after fire is impacted by climate change
Authors: McGee Spencer , Tidwell Alyssa , Riggs Erin , Veltkamp Hannah , Zahn Geoffrey
Published: October 2020

Though much is known about fungal importance to forest health, there is very little information about factors that impact soil fungal community recovery time after a fire. Soil samples were taken from burn sites within one ecotype of temperate coniferous forest in Utah over a 20-year chronosequence. Sites were selected from available historic burns and were similar in plant community structure, elevation, slope, and aspect. Fungal DNA from these samples was compared to soil from paired unburned sites nearby to measure community similarity and estimate soil fungal recovery rates. Differences between paired burned and unburned sites remained fairly stable over a decadal time scale overall, but fungal community structure was found to recover more quickly in areas with a higher average annual temperatures. A significant positive correlation in community recovery was seen in areas with a difference of as little as two degrees celsius per year. The only other environmental variable that significantly interacted with time since burn was annual mean precipitation. As global temperatures increase, alpine fires are increasing as well, but these results suggest that fungal community recovery time will be shortened under new climate scenarios.
CELL ATLAS OF THE CHICK RETINA: SINGLE CELL PROFILING IDENTIFIES 136 CELL TYPES
Authors: Yamagata Masahito , Yan Wenjun , Sanes Joshua R.
Published: October 2020

Retinal structure and function have been studied in many vertebrate orders, but molecular characterization has been largely confined to mammals. We used single-cell RNA sequencing (scRNA-seq) to generate a cell atlas of the chick retina. From ∼40,000 single cell transcriptomes, we identified 136 cell types distributed among the six classes conserved across vertebrates – photoreceptor, horizontal, bipolar, amacrine, retinal ganglion and glial cells. To match molecular profiles to morphology, we adapted a method for CRISPR-based integration of reporters into selectively expressed genes. For Müller glia, we found that transcriptionally distinct cells were regionally localized along the anterior-posterior, dorsal-ventral and central-peripheral retinal axes. We also identified immature photoreceptor, horizontal cell and oligodendrocyte types that persist into late embryonic stages. Finally, we analyzed relationships among chick, mouse and primate retinal cell classes and types. Taken together, our results provide a foundation for anatomical, physiological, evolutionary, and developmental studies of the avian visual system.
Misoprostol Treatment Prevents Hypoxia-Induced Cardiac Dysfunction Through a 14-3-3 and PKA regulatory motif on Bnip3
Authors: Martens Matthew D. , Seshadri Nivedita , Nguyen Lucas , Chapman Donald , Henson Elizabeth S. , Xiang Bo , Falk Landon , Mendoza Arielys , Rattan Sunil , Gibson Spencer B. , Keijzer Richard , Saleem Ayesha , Hatch Grant M. , Doucette Christine A. , Karch Jason M. , Dolinsky Vernon W. , Dixon Ian M. , West Adrian R. , Rampitsch Christof , Gordon Joseph W.
Published: October 2020

Systemic hypoxia is a common element in most perinatal emergencies and is a known driver of Bnip3 expression in the neonatal heart. Bnip3 plays a prominent role in the evolution of necrotic cell death, disrupting ER calcium homeostasis and initiating mitochondrial permeability transition (MPT). Emerging evidence suggests a cardioprotective role for the prostaglandin E1 analogue misoprostol during periods of hypoxia, but the mechanisms for this protection are not completely understood. Using a combination of mouse and cell models, we tested if misoprostol is cardioprotective during neonatal hypoxic injury by altering Bnip3 function. Here we report that hypoxia elicits mitochondrial-fragmentation, MPT, reduced ejection fraction, and evidence of necroinflammation, which were abrogated with misoprostol treatment or Bnip3 knockout. Through molecular studies we show that misoprostol leads to PKA-dependent Bnip3 phosphorylation at threonine-181, and subsequent redistribution of Bnip3 from mitochondrial Opa1 and the ER through an interaction with 14-3-3 proteins. Taken together, our results demonstrate a role for Bnip3 phosphorylation in the regulation of cardiomyocyte contractile/metabolic dysfunction, and necroinflammation. Furthermore, we identify a potential pharmacological mechanism to prevent neonatal hypoxic injury.
Identification of key immune regulatory genes in HIV–1 Progression
Authors: Hossain Sk Md Mosaddek , Khatun Lutfunnesa , Ray Sumanta , Mukhopadhyay Anirban
Published: October 2020

In the last few decades, application of DNA microarray technology has sprung up as a powerful technique for discovering stage specific changes in expression pattern of a disease progression. Human Immunodeficiency Virus (HIV) infection causes Acquired Immunodeficiency Syndrome (AIDS) which is one of the most devastating diseases affecting humankind. Here, we have proposed a framework to examine the difference among microarray gene expression data of uninfected and three different HIV–1 infection stages using module preservation statistics. Initially, we detected differentially expressed genes among all the stages and identified coexpression modules by using topological overlap as a dissimilarity measure. To examine relationship among co-expression modules, we have compiled a module eigenegene network for each sample category which models similarity among all coexpression modules. To further examine the network, we have found clusters in it which are termed as ‘meta-modules’. Different module preservation statistics with two composite statistics: “Zsummary” and “MedianRank” are utilized to examine changes in structure of coexpression modules. We have applied our proposed methodology to discover modular changes between uninfected and acute samples, acute and chronic samples, chronic and AIDS samples. We have found several interesting results on preservation characteristics of gene modules across different stages. Some genes are identified to be preserved in a pair of stages while alter their characteristics across other stages. We further validated the obtained results using permutation test and classification techniques. Biological significance of the obtained modules have been examined using gene ontology and pathway based analysis. Additionally, we have detected key immune regulatory hub genes in the associated protein-protein interaction networks (PPINs) of the differentially expressed genes (DEGs) using twelve topological and centrality analysis methods. Moreover, we have analyzed the key immune regulatory genes which interacts with HIV-1 proteins inside the preserved and perturbed meta-modules across different HIV-1 stages and thus likely to act as potential biomarkers in HIV–1 progression.
Clock proteins regulate spatiotemporal organization of clock genes to control circadian rhythms
Authors: Xiao Yangbo , Yuan Ye , Jimenez Mariana , Soni Neeraj , Yadlapalli Swathi
Published: October 2020

Circadian clocks regulate ∼24 hour oscillations in gene expression, behavior, and physiology. While the molecular and neural mechanisms of circadian rhythms are well characterized, how cellular organization of clock components controls circadian clock regulation remains poorly understood. Here, we elucidate how clock proteins regulate circadian rhythms by controlling the spatiotemporal organization of clock genes. Using high-resolution live imaging techniques we demonstrate thatDrosophilaclock proteins are concentrated in a few discrete foci and are organized at the nuclear envelope; these results are in contrast to longstanding expectations that clock proteins are diffusely distributed in the nucleus. We also show that clock protein foci are highly dynamic and change in number, size, and localization over the circadian cycle. Further, we demonstrate that clock genes are positioned at the nuclear periphery by the clock proteins precisely during the circadian repression phase, suggesting that subnuclear localization of clock genes plays an important role in the control of rhythmic gene expression. Finally, we show that Lamin B receptor, a nuclear envelope protein, is required for peripheral localization of clock protein foci and clock genes and for normal circadian rhythms. These results reveal that clock proteins form dynamic nuclear foci and play a hitherto unexpected role in the subnuclear reorganization of clock genes to control circadian rhythms, identifying a novel mechanism of circadian regulation. Our results further suggest a new role for clock protein foci in the clustering of clock-regulated genes during the repression phase to control gene co-regulation and circadian rhythms.

SIGNIFICANCE

Almost all living organisms have evolved circadian clocks to tell time. Circadian clocks regulate ∼24-hour oscillations in gene expression, behavior and physiology. Here, we reveal the surprisingly sophisticated spatiotemporal organization of clock proteins and clock genes and its critical role in circadian clock function. We show, in contrast to current expectations, that clock proteins are concentrated in a few discrete, dynamic nuclear foci at the nuclear envelope during the repression phase. Further, we uncovered several unexpected features of clock protein foci, including their role in positioning the clock genes at the nuclear envelope precisely during the repression phase to enable circadian rhythms. These studies provide fundamental new insights into the cellular mechanisms of circadian rhythms and establish direct links between nuclear organization and circadian clocks.
Increased light availability enhances tolerance against ocean acidification stress inHalimeda opuntia
Authors: Wei Zhangliang , Long Chao , Zhang Yating , Huo Yuanzi , Yang Fangfang , Long Lijuan
Published: October 2020

Although the adverse impacts of ocean acidification (OA) on marine calcifiers have been investigated substantially, the anti-stress abilities regulated by increased light availability are unclear. Herein, the interactive effects of three light levels combined with twopCO2concentrations on the physiological acclimation of the calcifying macroalgaHalimeda opuntiawere investigated using apCO2–light coupling experiment. The results indicate that OA exhibits an adverse role in influencing algal growth, calcification, photosynthesis and other physiological performances inH. opuntia.The relative growth rate in elevatedpCO2significantly declined by 13.14%–41.29%, while net calcification rates decreased by nearly three-fold under OA. Notably, increased light availability could enhance stress resistance by the accumulation of soluble organic molecules, especially soluble carbohydrate, soluble protein and free amino acids, and in combination with metabolic enzyme-driven activities alleviated OA stress. Carotenoid content in low light conditions accumulated remarkably and rapid light curves for relative electron transport rate was significantly enhanced by increasing light intensities, indicating that this new organization of the photosynthetic machinery inH. opuntiaaccommodated light variations and elevatedpCO2conditions. Taken together, the results describe stress resistance by the enhancement of metabolic performance in marine calcifiers to mitigate OA stress.

One sentence summary

Increased light availability enhances stress resistance inHalimeda opuntiaby the accumulation of soluble organic molecules and enzyme-driven activities to alleviate ocean acidification stress.

Credit authorship contribution statement

Fangfang Yang and Lijuan Long conceived and designed the experiments. Zhangliang Wei performed the experiments and wrote the paper. Yuanzi Huo analyzed the data, while Chao Long and Yating Zhang contributed materials and analysis tools. Lijuan Long agrees to serve as the author responsible for contact and communication.

Highlights

ElevatedpCO2adversely affects the physiological performance ofHalimeda.

Moderately high light increases soluble organic molecules and enzymatic-driven activities.

Increased light availability enablesH. opuntiato alleviate the negative effects of ocean acidification.
A Chinese hamster transcription start site atlas that enables targeted editing of CHO cells
Authors: Shamie Isaac , Duttke Sascha H. , la Cour Karottki Karen J. , Han Claudia Z. , Hansen Anders H. , Hefzi Hooman , Xiong Kai , Li Shangzhong , Roth Sam , Tao Jenhan , Lee Gyun Min , Glass Christopher K. , Kildegaard Helene Faustrup , Benner Christopher , Lewis Nathan E.
Published: October 2020

Chinese hamster ovary (CHO) cells, with their human-compatible glycosylation and high protein titers, are the most widely used cells for producing biopharmaceuticals. Engineering gene expression in CHO is key to improving drug quality and affordability. However, engineering gene expression or activating silent genes requires accurate annotation of the underlying regulatory elements and transcription start sites (TSSs). Unfortunately, most TSSs in the Chinese hamster genome were computationally predicted and are frequently inaccurate. Here, we revised TSS annotations for 15,308 Chinese hamster genes and 4,478 non-coding RNAs based on experimental data from CHO-K1 cells and 10 hamster tissues. The experimental realignment and discovery of TSSs now expose previously hidden motifs, such as the TATA box. We further demonstrate, by targeting the glycosyltransferase geneMgat3, how accurate annotations readily facilitate activating silent genes by CRISPRa to obtain more human-like glycosylation. Together, we envision our annotation and data will provide a rich resource for the CHO community, improve genome engineering efforts and aid comparative and evolutionary studies.
HectoSTAR microLED optoelectrodes for large-scale, high-precisionin invoopto-electrophysiology
Authors: Kim Kanghwan , Vöröslakos Mihály , Fernández-Ruiz Antonio , Parizi Saman S. , Ko Eunah , Hendrix Blake , Seymour John P. , Wise Kensall D. , Buzsáki György , Yoon Euisik
Published: October 2020

We present a device that can be utilized for a large-scale in vivo extracellular recording, from more than 250 electrodes, with the capability to optically modulate activities of neurons located at more than a hundred individual stimulation targets at the anatomical resolution.
LyticBacteroides uniformisbacteriophages exhibiting host tropism congruent with diversity generating retroelement
Authors: Hedzet Stina , Accetto Tomaž , Rupnik Maja
Published: October 2020

Intestinal phages are abundant and important component of gut microbiota, but our knowledge remains limited to only a few isolated and characterized representatives targeting numerically dominant gut bacteria. Here we describe isolation of human intestinal phages infectingBacteroides uniformis. Bacteroidesis one of the most common bacterial groups in the global human gut microbiota, however, to date not manyBacteroidesspecific phages are known. Phages isolated in this study belong to a novel viral genus, Bacuni, withinSiphoviridaefamily and represent the first lytic phages, genomes of which encode diversity generating retroelements (DGR). This region is assumed to promote phage adaptation to the rapidly changing environmental conditions and to broaden its host range. Three isolated phages showed 99,83% genome identity but infected distinctB. uniformisstrains. The tropism of Bacuni phages appeared to be dependent on the interplay of DGR mediated sequence variations of phage fimbrial tip proteins and mutations in host genes coding for outer-membrane proteins. We found prophages with up to 85% aa similarity to Bacuni phages in the genomes ofB. acidifaciensandPrevotellasp.. Despite the abundance ofBacteroideswithin human microbiome, we found Bacuni phages only in a limited subset of published gut metagenomes.

Importance

The lack of common marker gene in viruses require a precise characterization of diverse isolated phages to enhance metagenomic analyses and to understand their role in gut microbiota. Here we report the isolation of phages representing a new genus with characteristics so far not known or rarely described in intestinal phages. They are the first lytic phages specific forBacteroides uniformis, a bacterial representative of the prevalent genus in the gut of humans and animals. Additionally, they are the first lytic phages containing specific regions (diversity generating retroelement) that putatively influence host tropism. The ability to switch constantly the targeted populations of the host species could provide an evolutionary advantage to these bacteriophages and may affect intra species diversity.
Gastruloids generated without exogenous Wnt activation develop anterior neural tissues
Authors: Girgin Mehmet U. , Lutolf Matthias P.
Published: October 2020

When stimulated with a pulse from an exogenous WNT pathway activator, small aggregates of mouse embryonic stem cells (ESCs) can undergo embryo-like axial morphogenesis and patterning along the three major body axes. However, these structures, called gastruloids, currently lack the anterior embryonic regions, such as those belonging to the brain. Here we describe an approach to generate gastruloids that have a more complete antero-posterior development. We used bioengineered hydrogel microwell arrays to promote the robust derivation of mouse ESCs into post-implantation epiblast-like (EPI) aggregates in a reproducible and scalable manner. These EPI aggregates break symmetry and axially elongate without external chemical stimulation. Inhibition of WNT signaling in early stages of development leads to the formation of gastruloids with anterior neural tissues. Thus, we provide a new tool to study the development of the mouse after implantationin vitro, especially the formation of anterior neural regions.
Circulating adipokines in non-obese PCOS patients: a systematic review and meta-analysis
Authors: Lin Kainan , Sun Xiaoting , Wang Xiao , Wang Hanchu , Chen Xia
Published: October 2020

Concentrations of circulating adipokines in non-obese polycystic ovary syndrome (PCOS) patients had been reported in many researches, however, these results were conflicting. The aim of this meta-analysis was to assess whether the levels of circulating adipokines were changed in non-obese PCOS. To identify eligible studies, literature research was performed in the database of PubMed, Embase, Web of Science without the restriction of region, publication or language. Of the total studies found, only 81 met the inclusion criteria. The meta-analysis showed that circulating levels of adiponectin [-0.95 (95% CI, −1.36 to −0.53)] decreased statistically in non-obese PCOS women. On the contrary, circulating levels of chemerin [1.13 (95% CI, 0.08 to 2.18)], leptin [0.47 (95% CI, 0.13 to 0.81)], resistin [0.45 (95% CI, 0.03 to 0.88)] and visfatin [1.38 (95% CI, 0.68 to 2.09)] increased significantly in non-obese PCOS females. Besides, there was no statistically significant change in the circulating levels of apelin [0.32 (95% CI, −1.34 to 1.99), irisin [1.01(95% CI, −0.68 to 2.70), omentin [-0.37(95% CI, −1.05 to 0.31)] and vaspin [0.09(95% CI, −0.14 to 0.32)] in non-obese PCOS patients. Scientific evidence suggested that the levels of circulating adipokines altered in non-obese PCOS patients compared with controls. Independent of the degree of obesity, the abnormal change of circulating adipokines levels might play an important role in the occurrence and development of PCOS.
SPLICE-q: a Python tool for genome-wide quantification of splicing efficiency
Authors: Costa Verônica R Melo , Pfeuffer Julianus , Louloupi Annita , Ørom Ulf A V , Piro Rosario M
Published: October 2020

Background

Introns are generally removed from primary transcripts to form mature RNA molecules in a post-transcriptional process called splicing. An efficient splicing of primary transcripts is an essential step in gene expression and its misregulation is related to numerous human diseases. Thus, to better understand the dynamics of this process and the perturbations that might be caused by aberrant transcript processing it is important to quantify splicing efficiency.

Results

Here, we introduce SPLICE-q, a fast and user-friendly Python tool for genome-wideSPLICingEfficiencyquantification. It supports studies focusing on the implications of splicing efficiency in transcript processing dynamics. SPLICE-q uses aligned reads from strand-specific RNA-seq to quantify splicing efficiency for each intron individually and allows the user to select different levels of restrictiveness concerning the introns’ overlap with other genomic elements such as exons of other genes. We applied SPLICE-q to globally assess the dynamics of intron excision in yeast and human nascent RNA-seq. We also show its application using total RNA-seq from a patient-matched prostate cancer sample.

Conclusions

Our analyses illustrate that SPLICE-q is suitable to detect a progressive increase of splicing efficiency throughout a time course of nascent RNA-seq and it might be useful when it comes to understanding cancer progression beyond mere gene expression levels. SPLICE-q is available at:https://github.com/vrmelo/SPLICE-q
Sequences in the cytoplasmic tail of SARS-CoV-2 Spike facilitate expression at the cell surface and syncytia formation
Authors: Cattin-Ortolá Jerome , Welch Lawrence , Maslen Sarah L. , Skehel J. Mark , Papa Guido , James Leo C. , Munro Sean
Published: October 2020

The Spike (S) protein of SARS-CoV-2 binds ACE2 to direct fusion with host cells. S comprises a large external domain, a transmembrane domain (TMD) and a short cytoplasmic tail. Understanding the intracellular trafficking of S is relevant to SARS-CoV-2 infection, and to vaccines expressing full-length S from mRNA or adenovirus vectors. We have applied proteomics to identify cellular factors that interact with the cytoplasmic tail of S. We confirmed interactions with the COPI and COPII vesicle coats, ERM family actin regulators, and the WIPI3 autophagy component. The COPII binding-site promotes exit from the endoplasmic reticulum (ER), and although COPI-binding should retain S in the early Golgi where viral budding occurs, there is a suboptimal histidine residue in the recognition motif. As a result, S leaks to the surface where it accumulates and can direct the formation of multinucleate syncytia. Thus, the trafficking signals in the tail of S indicate that syncytia play a role in the SARS-CoV-2 lifecycle.
TRAF4 inhibits bladder cancer progression by promoting BMP/SMAD signalling pathway
Authors: Iyengar Prasanna Vasudevan , Marvin Dieuwke Louise , Lama Dilraj , Tan Tuan Zea , Suriyamurthy Sudha , Xie Feng , van Dinther Maarten , Mei Hailiang , Verma Chandra Shekhar , Zhang Long , Ritsma Laila , ten Dijke Peter
Published: October 2020

Bladder cancer is one of the most prevalent cancer types in the world, frequently exhibiting invasion and metastasis and therefore associated with poor prognosis. It is a progressive disease with high recurrence rates even after surgery, which calls for the urgent need for early intervention and diagnosis. The E3 ubiquitin ligase TNF Receptor Associated Factor 4 (TRAF4) has been largely implicated as a tumour-promoting element in a wide range of cancers. Over-expression and amplification of this gene product has been a common observation in breast and other metastatic tumours. In contrast, we observed that expression of TRAF4 negatively correlated with overall patient survival. Moreover, its expression was repressed at epigenetic levels in aggressive bladder cancer cells. We also describe an ERK kinase phosphorylation site on TRAF4 that inhibits its stability and localization to plasma membrane in such cells. Furthermore, knockdown of TRAF4 in epithelial bladder cancer cell lines leads to gain of mesenchymal genes and a loss of epithelial integrity. Reciprocally, stable over-expression of TRAF4 in mesenchymal cells leads to decreased migratory and invasive properties. Transcriptomic analysis upon TRAF4 mis-expression in bladder cancer cell lines revealed that higher TRAF4 expression enhanced BMP/SMAD and dampened NF-κB signalling pathways. Importantly, this notion was confirmed in bladder cancer patient material. Mechanistically, we showed that TRAF4 targets the E3 ubiquitin ligase SMURF1, a negative regulator of BMP/SMAD signalling, for proteasomal degradation in bladder cancer cells. We show that genetic and pharmacological inhibition of SMURF1 or its function inhibited migration of aggressive (mesenchymal) bladder cancer cells.
Imaging stable isotope labelling kinetics (iSILK) for following spatial Aβ plaque aggregation dynamics in evolving Alzheimer’s disease pathology
Authors: Michno Wojciech , Stringer Katie , Enzlein Thomas , Passarelli Melissa K. , Escrig Stephane , Blennow Kaj , Zetterberg Henrik , Meibom Anders , Hopf Carsten , Edwards Frances A. , Hanrieder Jörg
Published: October 2020

For our understanding of Alzheimer’s disease (AD) pathophysiology, it is of critical importance to determine how key pathological factors, specifically amyloid β (Aβ) plaque formation, are interconnected and implicated in neurodegeneration, disease progression and the development of clinical symptoms. Exactly how Aβ plaque formation is initiated and how the ongoing plaque deposition proceeds is not well understood. This is partly because we can only examine details of the molecular pathology after death in humans, and in mice, we can only examine a particular point in time without any longitudinal information on the fate of individually formed deposits. Herein, we used metabolic labelling of proteins with stable isotopes, together with multimodal imaging mass spectrometry (IMS) for imaging stable isotope labelling kinetics (iSILK) in the APPNL-G-Fknock-in mouse model of AD. The aim was to monitor the earliest seeds of Aβ deposition through ongoing plaque development and track the deposition of Aβ that is produced later in relation to already deposited plaques. This allowed us to visualize Aβ peptide aggregation dynamics within individual deposits across different brain regions. We identified the cortex as a primary site of deposition in precipitating plaque pathology. Further, our data show that structural plaque heterogeneity is associated with differential peptide deposition. Specifically, Aβ1-42 is forming an initial core seed followed by radial outgrowth and late secretion and deposition of Aβ1-38.

Together these data prove the potential of iSILK for probing amyloid protein secretion, processing and aggregation dynamics in AD pathology.
Everything Under Control? Comparing Knepp Estate rewilding project with ‘traditional’ nature conservation
Authors: Dempsey Benedict Edward
Published: October 2020

‘Rewilding’ is an increasingly prominent concept in conservation, but one that has attracted controversy. Debate frequently focuses on ‘control,’ with rewilding presented as reducing human control of nature. Opposition to rewilding often stems from a perceived lack of control – and associated perception of increased risk and uncertainty.

I explore the concept of control in conservation. I identify that control is not a simple, linear concept, but consists of multiple dimensions. Using a lens of control, I compare two ethnographic case studies: the Sussex Wildlife Trust’s Old Lodge nature reserve; and Knepp Estate, one of the most influential rewilding projects in the UK. These sites ostensibly represent ‘high-control’ and ‘low-control’ examples of conservation.

I outline how Old Lodge does not exert precise control in all respects, but rather involves elements of uncertainty and negotiation. I describe how Knepp’s model of rewilding reduces control in some dimensions but increases it in others. I conclude that, while Knepp’s ‘rewilding’ does represent a significant conceptual departure from ‘traditional’ conservation, it should not be characterised simplistically as an approach that reduces control.

Based on this analysis, I argue that reduction of control should not be assumed to underpin the concept of rewilding. Rather, there is interplay between different control dimensions that combine to form different configurations of control. With this understanding, debate about rewilding – and conservation more broadly – can avoid simplistic characterisations of ‘reducing control’ and become instead an active discussion of what configuration of control is desired.

This analysis could be seen negatively by those who argue that Knepp’s version of rewilding does not sufficiently reduce human control of nature. In contrast, Knepp’s approach can be seen positively as opening new conceptual space while retaining human involvement. It supports the argument that versions of rewilding can be legitimate, innovative components of plural conservation strategies.
Differential gene expression in the interactome of the Human Dopamine transporter in the context of Parkinson’s disease
Authors: Quiroz Roberto Navarro , Scott Ana Ligia , Philot Eric Allison , Atencio Linda , Ponce Cecilia Fernandez , Martinez Gustavo Aroca , Bonfanti Andres Cadena , Escorcia Lorena Gomez , Quiroz Elkin Navarro
Published: October 2020

Background

The human dopamine transporter is the main regulator of dopamine tone and an intricate network exists to regulate the expression, conformation, and kinetics of the hDAT. hDAT dysfunction is directly related to Parkinson’s disease. The objective of this work is to evaluate the differential gene expression in the interactome of the Dopamine transporter in the context of Parkinson’s disease.

Methods

To do this, we evaluated hDAT interaction data in string-db, mint.bio, IntAct, reactome, hprd and BioGRID, subsequently, data was obtained from the differential gene expression of mRNA and miRNAs for this hDAT interactome in the context of PD.

Results

The analysis of the differential expression changes of genes of the hDAT interactome in tissues of patients with PD compared with tissues of individuals without PD, allowed to identify an expression pattern of 32 components of the hDAT interactome, of which 31 presented a negative change proportion in PD.

Conclusions

We found a total of 90 miRNAs that could regulate the expression of 27 components of the hDAT interactome, at the same time, 39 components of the hDAT interactome may participate in 40 metabolic pathways. Together, these findings show a systematic effect on the hDAT-mediated dopamine internalization process in patients with Parkinson’s, which would contribute to a greater susceptibility to neuronal oxidative stress in PD patients.
Spleen glia are a transcriptionally unique glial subtype interposed between immune cells and sympathetic axons
Authors: Lucas Tawaun A. , Zhu Li , Buckwalter Marion S.
Published: October 2020

Glia are known to play important roles in the brain, the gut, and around the sciatic nerve. While the gut has its own specialized nervous system, other viscera are innervated solely by autonomic nerves. The functions of glia that accompany autonomic innervation are not well known, even though they are one of the most abundant cell types in the peripheral nervous system. Here, we focused on non-myelinating Schwann Cells in the spleen, spleen glia. The spleen is a major immune organ innervated by the sympathetic nervous system, which modulates immune function. This interaction is known as neuroimmune communication. We establish that spleen glia can be visualized using both immunohistochemistry for S100B and GFAP and with a reporter mouse. Spleen glia ensheath sympathetic axons and are localized to the lymphocyte-rich white pulp areas of the spleen. We sequenced the spleen glia transcriptome and identified genes that are likely involved in axonal ensheathment and communication with both nerves and immune cells. Spleen glia express receptors for neurotransmitters made by sympathetic axons (adrenergic, purinergic, and Neuropeptide Y), and also cytokines, chemokines, and their receptors that may communicate with immune cells in the spleen. We also established similarities and differences between spleen glia and other glial types. While all glia share many genes in common, spleen glia differentially express immune genes, including genes involved in cytokine-cytokine receptor interactions, phagocytosis, and the complement cascade. Thus, spleen glia are a unique glial type, physically and transcriptionally poised to participate in neuroimmune communication in the spleen.

Table of Contents

Main Points

Spleen glia maintain tight associations with splenic nerves and come in close contact with immune cells

Spleen glia express genes required for communication with nerves and immune cells

Spleen glia are a transcriptionally unique glial type
Genome-enabled inference of functional genetic variants in the face, brain and behavior
Authors: Patil Chinar , Sylvester Jonathan B. , Abdilleh Kawther , Norsworthy Michael W. , Pottin Karen , Malinsky Milan , Bloomquist Ryan F. , Johnson Zachary V. , McGrath Patrick T. , Streelman Jeffrey T.
Published: October 2020

Lake Malawi cichlid fishes exhibit extensive divergence in form and function among closely related species separated by a relatively small number of genetic changes. During the past million years, hundreds of species have diversified along an ecological axis in rock vs. sand habitats. We compared the genomes of rock- and sand-dwelling species and asked which genetic variants in which genes differed among the groups. We found that 96% of differentiated variants reside in non-coding sequence but these non-coding diverged variants are evolutionarily conserved. The majority of divergent coding variants are missense and/or loss of function. Regions near differentiated variants are enriched for craniofacial, neural and behavioral functional categories. To follow up experimentally, we used rock- vs. sand-species and their hybrids to (i) clarify the push-pull roles of BMP signaling andirx1bin the specification of forebrain territories during gastrulation and (ii) reveal striking context-dependent brain gene expression during adult social behavior. Our results suggest compelling ties between early brain development and adult behavior and highlight the promise of evolutionary reverse genetics – the identification of functional variants from genome sequencing in natural populations.
A high-throughput amplicon sequencing approach for population-wide species diversity and composition survey
Authors: Tay WT , Court LN , Macfadyen S , Jacomb F , Vyskočilová S , Colvin J , De Barro PJ
Published: October 2020

Management of agricultural pests requires an understanding of pest species diversity, their interactions with beneficial insects and spatial-temporal patterns of pest abundance. Invasive and agriculturally important insect pests can build up very high populations, especially in cropping landscapes. Traditionally, sampling effort for species identification involves small sample sizes and is labour intensive. Here, we describe a multi-primer high throughput sequencing (HTS) metabarcoding method and associated analytical workflow for a rapid, intensive, high-volume survey of pest species compositions. We demonstrate our method using the taxonomically challenging Bemisia pest cryptic species complex as examples. The whiteflies Bemisia including the ‘tabaci’ species are agriculturally important capable of vectoring diverse plant viruses that cause diseases and crop losses. Our multi-primer metabarcoding HTS amplicon approach simultaneously process high volumes of whitefly individuals, with efficiency to detect rare (i.e., 1%) test-species, while our improved whitefly primers for metabarcoding also detected beneficial hymenopteran parasitoid species from whitefly nymphs. Field-testing our redesigned Bemisia metabarcoding primer sets across the Tanzania, Uganda and Malawi cassava cultivation landscapes, we identified the sub-Saharan Africa 1 Bemisia putative species as the dominant pest species, with other cryptic Bemisia species being detected at various abundances. We also provide evidence that Bemisia species compositions can be affected by host crops and sampling techniques that target either nymphs or adults. Our multi-primer HTS metabarcoding method incorporated two over-lapping amplicons of 472bp and 518bp that spanned the entire 657bp 3’ barcoding region for Bemisia, and is particularly suitable to molecular diagnostic surveys of this highly cryptic insect pest species complex that also typically exhibited high population densities in heavy crop infestation episodes. Our approach can be adopted to understand species biodiversity across landscapes, with broad implications for improving trans-boundary biosecurity preparedness, thus contributing to molecular ecological knowledge and the development of control strategies for high-density, cryptic, pest-species complexes.
Shared developmental gait disruptions across two mouse models of neurodevelopmental disorders
Authors: Rahn Rachel M. , Weichselbaum Claire T. , Gutmann David H. , Dougherty Joseph D. , Maloney Susan E.
Published: October 2020

Motor deficits such as abnormal gait are an underappreciated yet characteristic phenotype of many neurodevelopmental disorders (NDDs), including Williams Syndrome (WS) and Neurofibromatosis Type 1 (NF1). Compared to cognitive phenotypes, gait phenotypes are readily and comparably assessed in both humans and model organisms, and are controlled by well-defined CNS circuits. Discovery of a common gait phenotype between NDDs might suggest shared cellular and molecular deficits and highlight simple outcome variables to potentially quantify longitudinal treatment efficacy in NDDs. We therefore characterized gait using the DigiGait assay in two different NDD models: the complete deletion (CD) mouse, which models hemizygous loss of the complete WS locus, and theNf1+/R681Xmouse, which models a patient-derived heterozygous germlineNF1mutation. We collected longitudinal data across five developmental time points (postnatal days 21-30) and one early adulthood time point. Compared to wild type littermate controls, both models displayed markedly similar spatial, temporal, and postural gait abnormalities during development. Developing CD mice also displayed significant decreases in variability metrics. Multiple gait abnormalities observed acrossNf1+/R681Xmouse development persisted into early adulthood, including increased stride length and decreased stride frequency, while developmental abnormalities in CD mice largely resolved by adulthood. These findings suggest that gait subcomponents affected in NDDs show overlap between disorders as well as some disorder-specific features, which may change over the course of development. Our incorporation of spatial, temporal, and postural gait measures also provides a template for gait characterization in other NDD models, and a platform to examining circuits or longitudinal therapeutics.

Lay Summary

Gait changes have been reported in Williams Syndrome and Neurofibromatosis Type 1, but how these changes develop over time has not been explored. We therefore studied gait in mouse models of these two disorders across time. We found multiple shared differences in gait as compared to healthy controls at the younger ages in both models. However, those differences were resolved in the Williams Syndrome model by adulthood, yet persisted in the Neurofibromatosis Type 1 model.
Highly sensitive quantification of carbon monoxide (CO)in vivoreveals a protective role of circulating hemoglobin in CO intoxication
Authors: Mao Qiyue , Kawaguchi Akira T. , Mizobata Shun , Motterlini Roberto , Foresti Roberta , Kitagishi Hiroaki
Published: October 2020

Carbon monoxide (CO) is a gaseous molecule known as the silent killer. It is widely believed that an increase in blood carboxyhemoglobin (CO-Hb) is the best biomarker to define CO intoxication, neglecting the important fact that CO accumulation in tissues is the most likely direct cause of mortality. There is no reliable method other than gas chromatography to accurately determine CO content in tissues. Here we report the properties and usage of hemoCD1, a synthetic supramolecular compound composed of an iron(II)porphyrin and a cyclodextrin dimer, as an accessible reagent for a simple colorimetric assay to quantify CO in biological samples. The assay was validated in various organ tissues collected from rats under normal conditions and after exposure to CO by inhalation. The kinetic profile of CO in blood and tissues after CO treatment suggested that CO accumulation in tissues is prevented by circulating Hb, revealing a protective role of Hb in CO intoxication. Furthermore, hemoCD1 was usedin vivoas a CO removal agent, showing that it acts as effective adjuvant to O2ventilation to eliminate residual CO accumulated in organs, including the brain. These findings open new therapeutic perspectives to counteract the toxicity associated with CO poisoning.
Does well banking performance attract FDI? Empirical evidence from the SAARC economies
Authors: Tahir Muhammad , Alam Md Badrul
Published: October 2020

Purpose

This paper empirically examines the perceived relationship between banking sector performance and FDI inflows, thereby highlighting an underexplored area in the existing literature.

Design/methodology/approach

To provide evidence from the South Asian context, this study selected five economies of the same region based on the data availability. A panel dataset, collected from the internationally reliable sources for the period 1998–2017, is analyzed with the help of different econometric techniques, including pooled least squares, fixed effects, generalized least square and two stages least squares.

Findings

The results indicate a significant negative relationship between banking sector performance and FDI inflows while demonstrating a significant positive association of inflation and trade openness with FDI inflows Moreover, higher per capita income, which is one of the indicators of a growing economy, exerts a statistically significant positive impact on FDI inflows. Finally, institutional factors have not played a significant role in attracting FDI in the sampled countries.

Practical implications

The results demonstrate a unique outcome from the perspective of the relationship between banking sector performance and FDI inflows, and hence policymakers of the developing countries in general and South Asian countries in particular would benefit from the current study significantly.

Originality/value

The obtained results are original as we have provided comprehensive evidence on the relationship between FDI and banking sector performance in the SAARC context for the first time.
Electrical energy prediction using a surface fitting model for an on-farm direct expansion bulk milk cooler (DXBMC) in South Africa
Authors: Mhundwa Russel , Simon Michael
Published: October 2020

Purpose

This paper aims to show that a simplified surface fitting model can be efficient in determining the energy consumption during milk cooling by an on-farm direct expansion bulk milk cooler (DXBMC). The study reveals that milk volume and the temperature gradient between the room and the final milk temperature can effectively be used for predicting the energy consumption within 95% confidence bounds.

Design/methodology/approach

A data acquisition system comprised a Landis and Gyr E650 power meter, TMC6-HE temperature sensors, and HOBO UX120-006M 4-channel analog data logger was designed and built for monitoring of the DXBMC. The room temperature where the DXBMC is housed was measured using a TMC6-HE temperature sensor, connected to a Hobo UX120-006M four-channel analog data logger which was configured to log at one-minute intervals. The electrical energy consumed by the DXBMC was measured using a Landis and Gyr E650 meter while the volume of milk was extracted from on the farm records.

Findings

The results showed that the developed model can predict the electrical energy consumption of the DXBMC within an acceptable accuracy since 80% of the variation in the electrical energy consumption by the DXBMC was explained by the mathematical model. Also, milk volume and the temperature gradient between the room and final milk temperature in the BMC are primary and secondary contributors, respectively, to electrical energy consumption by the DXBMC. Based on the system that has been monitored the findings reveal that the DXBMC was operating within the expected efficiency level as evidenced by the optimized electrical energy consumption (EEC) closely mirroring the modelled EEC with a determination coefficient of 0.95.

Research limitations/implications

Only one system was monitored due to unavailability of funding to deploy several data acquisition systems across the country. The milk blending temperatures, effects of the insulation of the DXBMC, were not taken into account in this study.

Practical implications

The developed model is simple to use, cost effective and can be applied in real-time on the dairy farm which will enable the farmer to quickly identify an increase in the cooling energy per unit of milk cooled.

Social implications

The developed easy to use model can be used by dairy farmers on similar on-farm DXBMC; hence, they can devise ways to manage their energy consumption on the farm during the cooling of milk and foster some energy efficiency initiatives.

Originality/value

The implementation of the developed model can be useful to dairy farmers in South Africa. Through energy optimization, the maintenance of the DXBMC can be determined and scheduled accordingly.