bluuebunny/crossref_metadata_2025 huggingface dataset:
Endogenous but not sensory-driven activity controls migration, morphogenesis and survival of adult-born neurons in the mouse olfactory bulb
Authors: Li Kaizhen , Figarella Katherine , Su Xin , Kovalchuk Yury , Gorzolka Jessika , Neher Jonas J. , Mojtahedi Nima , Casadei Nicolas , Hedrich Ulrike B. S. , Garaschuk Olga
Published: April 2021

The development and survival of adult-born neurons is believed to be driven by sensory signaling. By genetically manipulating excitability of adult-born cells (via cell-specific overexpression of either Kv1.2 or Kir2.1 K+channels), longitudinalin vivomonitoring of their Ca2+signaling and transcriptome analyses, we show that endogenous but not sensory-driven activity governs migration, morphogenesis, survival, and functional integration of adult-born juxtaglomerular neurons in the mouse olfactory bulb. The proper development of these cells required fluctuations of cytosolic Ca2+levels, phosphorylation of CREB, and pCREB-mediated gene expression. Attenuating Ca2+fluctuations via K+channel overexpression strongly downregulated genes involved in neuronal migration, differentiation, and morphogenesis and upregulated apoptosis-related genes, thus locking adult-born cells in the vulnerable and immature state. Together, the data reveal signaling pathways connecting the endogenous intermittent neuronal activity/Ca2+fluctuations as well as proper Kv1.2/Kir2.1 K+channel function to migration, maturation, and survival of adult-born neurons.
RTL8 promotes nuclear localization of UBQLN2 to subnuclear compartments associated with protein quality control
Authors: Mohan Harihar Milaganur , Pithadia Amit , Trzeciakiewicz Hanna , Crowley Emily V. , Pacitto Regina , Safren Nathaniel , Zhang Chengxin , Zhou Xiaogen , Zhang Yang , Basrur Venkatesha , Paulson Henry L. , Sharkey Lisa M.
Published: April 2021

The brain expressed ubiquilins (UBQLNs) 1, 2 and 4 are a family of ubiquitin adaptor proteins that participate broadly in protein quality control (PQC) pathways, including the ubiquitin proteasome system (UPS). One family member, UBQLN2, has been implicated in numerous neurodegenerative diseases including ALS/FTD. UBQLN2 typically resides in the cytoplasm but in disease can translocate to the nucleus, as in Huntington’s disease where it promotes the clearance of mutant Huntingtin protein. How UBQLN2 translocates to the nucleus and clears aberrant nuclear proteins, however, is not well understood. In a mass spectrometry screen to discover UBQLN2 interactors, we identified a family of small (13 kDa), highly homologous uncharacterized proteins, RTL8, and confirmed the interaction between UBQLN2 and RTL8 bothin vitrousing recombinant proteins andin vivousing mouse brain tissue. Under endogenous and overexpressed conditions, RTL8 localizes to nucleoli. When co-expressed with UBQLN2, RTL8 promotes nuclear translocation of UBQLN2. UBQLN2 and RTL8 colocalize within ubiquitin-enriched subnuclear structures containing PQC components. The robust effect of RTL8 on the nuclear translocation and subnuclear localization of UBQLN2 does not extend to the other brain-expressed ubiquilins, UBQLN1 and UBQLN4. Moreover, compared to UBQLN1 and UBQLN4, UBQLN2 preferentially stabilizes RTL8 levels in human cell lines and in mouse brain, supporting functional heterogeneity among UBQLNs. As a novel UBQLN2 interactor that recruits UBQLN2 to specific nuclear compartments, RTL8 may regulate UBQLN2 function in nuclear protein quality control.
Dynamic interplay between a TonB dependent heme transporter and a TonB protein in a membrane environment
Authors: Somboon Kamolrat , Melling Oliver , Lejeune Maylis , Pinheiro Glaucia M.S. , Paquelin Annick , Bardiaux Benjamin , Nilges Michael , Delepelaire Philippe , Khalid Syma , Izadi-Pruneyre Nadia
Published: April 2021

The envelope of Gram-negative bacteria is composed of a double membrane separated by the periplasmic space. This organization imposes geometrical and distance constraints that are key for the mechanism of action of multicomponent systems spanning the envelope. However, consideration of all three compartments by experimental approaches is still elusive. Here we used the state-of-the-art molecular dynamics simulation in anEscherichia colienvelope model to obtain a dynamic view of molecular interactions between the outer membrane heme transporter HasR and the inner membrane TonB-like protein HasB. Their interaction allows the transfer of the inner membrane proton motive force derived energy to the transporter for heme internalization. The simulations which incorporate both membranes show the key role of periplasmic domains of both proteins, and their dynamics in the complex formation and stability. They revealed a previously unidentified atomic network of interactions, as well as the sequences of the interactions and their variations with the presence of external substrates. Experimental validation (mutations, phenotypic andin vitroassays) confirms the robustness of our approach and provides verification of the simulation-predicted interactions. Based on structural and sequence conservation, the network of interaction revealed in this study is expected to occur in other nutrient import systems. The integrative approach presented here is highly useful to study the dynamic interplay between components of any other bacterial transmembrane systems.
Physical Characterization of Triolein and Implications for Its Role in Lipid Droplet Biogenesis
Authors: Kim Siyoung , Voth Gregory A.
Published: April 2021

Lipid droplets (LDs) are neutral lipid storing organelles surrounded by a phospholipid (PL) monolayer. At present, how LDs are formed in the endoplasmic reticulum (ER) bilayer is poorly understood. In this study, we present a revised all-atom (AA) triolein (TG) model, the main constituent of the LD core, and characterize its properties in a bilayer membrane to demonstrate the implications of its behavior in LD biogenesis. In bilayer simulations, TG resides at the surface, adopting PL-like conformations (denoted in this work as SURF-TG). Free energy sampling simulation results estimate the barrier for TG relocating from the bilayer surface to the bilayer center to be ∼2 kcal/mol in the absence of an oil lens. SURF-TG is able to modulate membrane properties by increasing PL ordering, decreasing bending modulus, and creating local negative curvature. The other neutral lipid, dioleoyl-glycerol (DAG), also reduces the membrane bending modulus and populates the negative curvature regions. A phenomenological coarse-grained (CG) model is also developed to observe larger scale SURF-TG-mediated membrane deformation. The CG simulations confirm that TG nucleates between the bilayer leaflets at a critical concentration when SURF-TG is evenly distributed. However, when one monolayer contains more SURF-TG, the membrane bends toward the other leaflet, followed by TG nucleation if a concentration is higher than the critical threshold. The central conclusion of this study is that SURF-TG is a negative curvature inducer, as well as a membrane modulator. To this end, a model is proposed in which the accumulation of SURF-TG in the luminal leaflet bends the ER bilayer toward the cytosolic side, followed by TG nucleation.
Structural and molecular determinants for the interaction of ExbB fromSerratia marcescensand HasB, a TonB paralog
Authors: Biou Valérie , Adaixo Ricardo Jorge Diogo , Chami Mohamed , Coureux Pierre-Damien , Laurent Benoist , Ntsogo Enguéné Véronique Yvette , de Amorim Gisele Cardoso , Izadi-Pruneyre Nadia , Malosse Christian , Chamot-Rooke Julia , Stahlberg Henning , Delepelaire Philippe
Published: April 2021

ExbB and ExbD are cytoplasmic membrane proteins that associate with TonB to convey the energy of the proton-motive force to outer membrane receptors in Gram-negative bacteria for iron uptake. The opportunistic pathogenSerratia marcescens(Sm) possesses both TonB and a heme-specific TonB paralog, HasB. ExbBSmhas a long periplasmic extension absent in other bacteria such asE. coli (Ec). Long ExbB’s are found in several genera of Alphaproteobacteria, most often in correlation with ahasBgene. We investigated specificity determinants of ExbBSmand HasB. We determined the cryo-EM structures of ExbBSmand of the ExbB-ExbDSmcomplex fromS. marcescens. ExbBSmalone is a stable pentamer, and its complex includes two ExbD monomers. We showed that ExbBSmextension interacts with HasB and is involved in heme acquisition and we identified key residues in the membrane domain of ExbBSmand ExbBEc, essential for function and likely involved in the interaction with TonB/HasB. Our results shed light on the new class of inner membrane energy machinery formed by ExbB,ExbD and HasB.
Chemoenzymatic Generation of Phospholipid Membranes Mediated by Type I Fatty Acid Synthase
Authors: Khanal Satyam , Brea Roberto J. , Burkart Michael D. , Devaraj Neal K.
Published: April 2021

Thede novoformation of lipid membranes from minimal reactive precursors is a major goal in synthetic cell research. In nature, the synthesis of membrane phospholipids is orchestrated by numerous enzymes, including fatty acid synthases and membrane-bound acyltransferases. However, these enzymatic pathways are difficult to fully reproducein vitro. As such, the reconstitution of phospholipid membrane synthesis from simple metabolic building blocks remains a challenge. Here, we describe a chemoenzymatic strategy for lipid membrane generation that utilizes a soluble bacterial fatty acid synthase (cgFAS I) to synthesize palmitoyl-CoAin situfrom acetyl-CoA and malonyl-CoA. The fatty acid derivative spontaneously reacts with a cysteine-modified lysophospholipid by native chemical ligation (NCL), affording a non-canonical amidophospholipid that self-assembles into micron-sized membrane-bound vesicles. To our knowledge, this is the first example of reconstituting phospholipid membrane formation directly from acetyl-CoA and malonyl-CoA precursors. Our results demonstrate that combining the specificity and efficiency of a type I fatty acid synthase with a highly selective bioconjugation reaction provides a biomimetic route for thede novoformation of membrane-bound vesicles.
Spontaneous Isomerization of Asp387 in Tau is Diagnostic for Alzheimer’s Disease: An Endogenous Indicator of Reduced Autophagic Flux
Authors: Hubbard Evan E. , Heil Lilian , Merrihew Gennifer E. , Chhatwal Jasmeer P. , Farlow Martin R. , McLean Catriona A. , Ghetti Bernardino , Newell Kathy L. , Frosch Matthew P. , Bateman Randall J. , Larson Eric B. , Keene C. Dirk , Montine Thomas J. , MacCoss Michael , Julian Ryan R.
Published: April 2021

Amino acid isomerization is a spontaneous chemical modification potentially related to the underlying causes of Alzheimer’s disease (AD). We demonstrate that data-independent acquisition mass spectrometry can be used to characterize isomerization in complex protein mixtures. Examination of a large cohort of brain tissue samples revealed a striking relationship between isomerization of tau and AD status. Surprisingly, isomerization was found to be more abundant in both autosomal dominant and sporadic AD samples relative to controls. We hypothesize that lower autophagic flux in AD brains accounts for these results. Additional data, including quantitative analysis of proteins related to autophagy, strongly support this hypothesis. For example, isomerization of tau is positively correlated with levels of p62, a recognized indicator of autophagic inhibition. In sum, the data suggest strong ties between isomerization and autophagic flux, which may therefore represent a promising target for future investigations into the therapy and prevention of AD.
Evidence for continent-wide convergent evolution and stasis throughout 150 years of a biological invasion
Authors: Wu Yihan , Colautti Robert I.
Published: April 2021

The extent to which evolution can rescue a species from extinction, or facilitate range expansion, depends critically on the rate, duration, and geographical extent of the evolutionary response to natural selection. Adaptive evolution can occur quickly, but the duration and geographical extent of contemporary evolution in natural systems remains poorly studied. This is particularly true for species with large geographical ranges and for timescales that lie between ‘long-term’ field experiments and the fossil record. Here, we introduce the Virtual Common Garden (VCG) to investigate phenotypic evolution in natural history collections while controlling for phenotypic plasticity in response to local growing conditions. Reconstructing 150 years of evolution inLythrum salicaria(purple loosestrife) as it invaded North America, we analyze phenology measurements of 3,429 herbarium records, reconstruct growing conditions from more than 12 million local temperature records, and validate predictions across three common gardens spanning 10 degrees of latitude. We find that phenology clines have evolved along parallel climatic gradients, repeatedly throughout the range, during the first century of evolution. Thereafter, the rate of microevolution stalls, recapitulating macroevolutionary stasis observed in the fossil record. Our study demonstrates that preserved specimens are a critical resource for investigating limits to evolution in natural populations. Our results show how natural selection and trade-offs measured in field studies predict adaptive divergence observable in herbarium specimens over 15 decades at a continental scale.
Virulent but not temperate bacteriophages display hallmarks of rapid translation initiation
Authors: Hockenberry Adam J. , Weaver David C. , Wilke Claus O.
Published: April 2021

Bacteriophages rely almost exclusively on host-cell machinery to produce their proteins, and their mRNAs must therefore compete with host mRNAs for valuable translational resources. In many bacterial species, highly translated mRNAs are characterized by the presence of a Shine-Dalgarno sequence motif upstream of the start codon and weak secondary structure within the start codon region. However, the general constraints and principles underlying the translation of phage mRNAs are largely unknown. Here, we show that phage mRNAs are highly enriched in strong Shine-Dalgarno sequences and have comparatively weaker secondary structures in the start codon region than host-cell mRNAs. Phage mRNAs appear statistically similar to the most highly expressed host genes inE. coliaccording to both features, strongly suggesting that they initiate translation at particularly high rates. Interestingly, we find that these observations are driven largely by virulent phages and that temperate phages encode mRNAs with similar start codon features to their host genes. These findings apply broadly across a wide-diversity of host-species and phage genomes. Further study of phage translational regulation—with a particular emphasis on virulent phages—may provide new strategies for engineering phage genomes and recombinant expression systems more generally.
Mining Thousands of Genomes to Classify Somatic and Pathogenic Structural Variants
Authors: Layer Ryan M. , Sedlazeck Fritz J. , Pedersen Brent S. , Quinlan Aaron R.
Published: April 2021

Structural variants (SVs) are associated with cancer progression and Mendelian disorders, but challenges with estimating SV frequency remain a barrier to somatic and de novo classification. In particular, variability in filtering and variant calling heuristics limit our ability to use SV catalogs from large cohorts. We present a method to index and search the raw alignments from thousands of samples that overcomes these limitations and supports robust SV analysis.
Reflectance spectroscopy allows rapid, accurate, and non-destructive estimates of functional traits from pressed leaves
Authors: Kothari Shan , Beauchamp-Rioux Rosalie , Laliberté Etienne , Cavender-Bares Jeannine
Published: April 2021

More than ever, ecologists seek to employ herbarium collections to estimate plant functional traits from the past and across biomes. However, many trait measurements are destructive, which may preclude their use on valuable specimens. Researchers increasingly use reflectance spectroscopy to estimate traits from fresh or ground leaves, and to delimit or identify taxa. Here, we extend this body of work to non-destructive measurements on pressed, intact leaves, like those in herbarium collections.

Using 618 samples from 68 species, we used partial least-squares regression to build models linking pressed-leaf reflectance spectra to a broad suite of traits, including leaf mass per area (LMA), leaf dry matter content (LDMC), equivalent water thickness, carbon fractions, pigments, and twelve elements. We compared these models to those trained on fresh- or ground-leaf spectra of the same samples.

Our pressed-leaf models were best at estimating LMA (R2= 0.932; %RMSE = 6.56), C (R2= 0.855; %RMSE = 9.03), and cellulose (R2= 0.803; %RMSE = 12.2), followed by water-related traits, certain nutrients (Ca, Mg, N, and P), other carbon fractions, and pigments (allR2= 0.514-0.790; %RMSE = 12.8-19.6). Remaining elements were predicted poorly (R2< 0.5, %RMSE > 20). For most chemical traits, pressed-leaf models performed better than fresh-leaf models, but worse than ground-leaf models. Pressed-leaf models were worse than fresh-leaf models for estimating LMA and LDMC, but better than ground-leaf models for LMA. Finally, in a subset of samples, we used partial least-squares discriminant analysis to classify specimens among 10 species with near-perfect accuracy (>97%) from pressed- and ground-leaf spectra, and slightly lower accuracy (>93%) from fresh-leaf spectra.

These results show that applying spectroscopy to pressed leaves is a promising way to estimate leaf functional traits and identify species without destructive analysis. Pressed-leaf spectra might combine advantages of fresh and ground leaves: like fresh leaves, they retain some of the spectral expression of leaf structure; but like ground leaves, they circumvent the masking effect of water absorption. Our study has far-reaching implications for capturing the wide range of functional and taxonomic information in the world’s preserved plant collections.
Transfer Learning for Inference of Metastatic Origin from Whole Slide Histology
Authors: Schau Geoffrey F. , Ghani Hassan , Burlingame Erik A. , Thibault Guillaume , Gray Joe W. , Corless Christopher , Chang Young Hwan
Published: April 2021

Accurate diagnosis of metastatic cancer is essential for prescribing optimal control strategies to halt further spread of metastasizing disease. While pathological inspection aided by immunohistochemistry staining provides a valuable gold standard for clinical diagnostics, deep learning methods have emerged as powerful tools for identifying clinically relevant features of whole slide histology relevant to a tumor’s metastatic origin. Although deep learning models require significant training data to learn effectively, transfer learning paradigms provide mechanisms to circumvent limited training data by first training a model on related data prior to fine-tuning on smaller data sets of interest. In this work we propose a transfer learning approach that trains a convolutional neural network to infer the metastatic origin of tumor tissue from whole slide images of hematoxylin and eosin (H&E) stained tissue sections and illustrate the advantages of pre-training network on whole slide images of primary tumor morphology. We further characterize statistical dissimilarity between primary and metastatic tumors of various indications on patch-level images to highlight limitations of our indication-specific transfer learning approach. Using a primary-to-metastatic transfer learning approach, we achieved mean class-specific areas under receiver operator characteristics curve (AUROC) of 0.779, which outperformed comparable models trained on only images of primary tumor (mean AUROC of 0.691) or trained on only images of metastatic tumor (mean AUROC of 0.675), supporting the use of large scale primary tumor imaging data in developing computer vision models to characterize metastatic origin of tumor lesions.
SKAP2 as a new regulator of oligodendroglial migration and myelin sheath formation
Authors: Ghelman Julia , Grewing Laureen , Windener Farina , Albrecht Stefanie , Zarbock Alexander , Kuhlmann Tanja
Published: April 2021

Oligodendroglial progenitor cells (OPC) are highly proliferative and migratory bipolar cells, which differentiate into complex myelin forming and axon ensheathing mature oligodendrocytes during myelination. Recent studies indicate that the oligodendroglial cell population is heterogeneous on transcriptional and functional level depending on the location in the CNS. Here, we compared intrinsic properties of OPC from spinal cord and brain on functional and transcriptional level. Spinal cord OPC demonstrated increased migration as well as differentiation capacity. Moreover, transcriptome analysis revealed differential expression of several genes between both OPC populations. In spinal cord OPC we confirmed upregulation of SKAP2, a cytoplasmatic adaptor protein known for its implication in cytoskeletal remodelling and migration in other cell types. Recent findings suggest that actin dynamics determine not only oligodendroglial migration, but also differentiation: Whereas actin polymerization is important for process extension, actin destabilization and depolymerization is required for myelin sheath formation. Downregulation or complete lack of SKAP2 in OPC resulted in reduced migration and impaired morphological maturation in oligodendrocytes. In contrast, overexpression of SKAP2 as well as constitutively active SKAP2 increased OPC migration suggesting that SKAP2 function is dependent on activation by phosphorylation. Furthermore, lack of SKAP2 enhanced the positive effect on OPC migration after integrin activation suggesting that SKAP2 acts as modulator of integrin dependent migration. In summary, we demonstrate the presence of intrinsic differences between spinal cord and brain OPC and identified SKAP2 as a new regulator of oligodendroglial migration and sheath formation.

Significance statement

OPC play an important role in many still incurable diseases, such as multiple sclerosis, leukodystrophies or neurodegenerative diseases. Their heterogeneity in different CNS regions has recently been identified. Here, we observed increased migration and differentiation capabilities of OPC isolated from the spinal cord compared to brain OPC and confirmed differences in the transcriptome between these two cell populations. Furthermore, we identified SKAP2 as potential modulator of actin dynamics in oligodendrocytes. Whereas knockdown or lack of SKAP2 impairs migration and myelin sheath formation in mouse and human oligodendrocytes, overexpression of wildtype or constitutively active SKAP2 enhances the migratory capacity of murine oligodendrocytes. In summary, we present SKAP2 as modulator of cytoskeletal dynamics regulating OPC migration, differentiation and myelin sheath formation.
Non-canonical mitochondrial STAT3 signaling mediates exercise-induced insulin secretion down-regulation
Authors: Leite Nayara C. , de Paula Flávia , Lubaczeuski Camila , Borck Patricia C. , Juan-Mateu Jonàs , Souza Jane C. , Eizirik Decio L. , Boschero Antonio C. , Jonas Jean-Christophe , Carneiro Everardo M. , Zoppi Claudio C.
Published: April 2021

Chronic exercise protects pancreatic beta cells from diabetogenic stress, reducing insulin secretion through unknown mechanisms. We tested the hypothesis that the IL-6/mitochondrial STAT3 (pS-STAT3) axis plays a role in this protective effect. C57BL/6N mice were subjected to endurance training ahead of pancreatic islet isolation and functional analysis. Similar in vitro experiments were performed using insulin-producing INS-1E cells and islets from untrained mice, cultured with serum from trained animals and treated with or without an IL-6 receptor (IL-6R) inhibitor. Then, IL-6R/pS-STAT3 pathway activation and its effects on mitochondrial function and insulin secretion were assessed. Exercise-induced down-regulation of insulin secretion was prevented by inhibition of IL-6R signaling and following STAT3 knockdown. IL-6R activation promoted STAT3 phosphorylation and translocation to the mitochondria, increasing oxygen consumption. Accordingly, lower H2O2 content was reported in islets from trained mice and beta cells exposed to exercise-conditioned serum, while exposure to exogenous H2O2 blocked the down-regulatory effect of training on insulin secretion. Similar findings were observed in islets from obese-trained mice. Together, these findings suggest that the IL-6R/pS-STAT3 axis mediates exercise-induced down-regulation of insulin secretion through modulation of the mitochondrial redox state.
Repurposing statin and L-glutamine: replenishing β-cells in hyperlipidemic T2D mouse model
Authors: Palit Sayantani Pramanik , Patel Roma , Parmar Nishant , Rathwa Nirali , Dalvi Nilay , Ramachandran A. V. , Begum Rasheedunnisa
Published: April 2021

While cases of obesity-induced type 2 diabetes (T2D) are on the upswing, current therapies help only manage the symptoms. Of late, L-glutamine has been implicated in the amelioration of T2D by virtue of its glucagon like peptide-1 (GLP-1) secretagogue property. Alongside, there are mixed reports on adiponectin (insulin sensitizer) potentiating property of statins. We aimed to investigate the effect of pitavastatin (P) and L-glutamine (LG) combination on glycemic control and pancreatic β-cell regeneration in a high-fat diet (HFD)+Streptozotocin (STZ) induced T2D mouse model. C57BL6/J mice treated with HFD+STZ were randomly assigned into four groups: Diabetic control, L-glutamine, Pitavastatin and P+LG. Control group was fed with the chow diet. Significant amelioration in insulin resistance along with plasma glucose, lipid profile, adiponectin levels, and mitochondrial complexes I, II, III activities were observed in P+LG group as compared to HFD+STZ treated group. Phosphoenolpyruvate carboxykinase, glucose 6-phophatase, glycogen phosphorylase, and GLUT2 transcript levels were reduced with increased glycogen synthase transcript levels in liver. Further, the protein levels of Insulin receptor 1-β, pAkt/Akt, and AdipoR1 were restored in the skeletal muscle and a significant increase in islet number as a result of β-cell regeneration and reduced β-cell death were also observed in the combination drug treated group. Thus, L-glutamine and pitavastatin in combination can induce β-cell regeneration and regulate glucose homeostasis to bring about amelioration of HFD+STZ induced T2D.
Critical roles of transcriptional coactivator MED1 in the formation and function of mouse adipose tissues
Authors: Ito Keiichi , Schneeberger Marc , Gerber Alan , Jishage Miki , Marchildon Francois , Maganti Aarthi V. , Cohen Paul , Friedman Jeffrey M. , Roeder Robert G.
Published: April 2021

The MED1 subunit has been shown to mediate ligand-dependent binding of the Mediator coactivator complex to multiple nuclear receptors, including the adipogenic PPARγ, and to play an essential role in ectopic PPARγ-induced adipogenesis of mouse embryonic fibroblasts. However, the precise roles of MED1, and its various domains, at various stages of adipogenesis and in adipose tissue have been unclear. Here, after establishing requirements for MED1, including specific domains, for differentiation of 3T3L1 cells and both primary white and brown preadipocytes, we used multiple genetic approaches to assess requirements for MED1 in adipocyte formation, maintenance, and function in mice. We show that MED1 is indeed essential for the differentiation and/or function of both brown and white adipocytes, as its absence in these cells leads to, respectively, defective brown fat function and lipodystrophy. This work establishes MED1 as an essential transcriptional coactivator that ensures homeostatic functions of adipocytes.
Building a circuit through correlated spontaneous neuronal activity in the developing vertebrate and invertebrate visual systems
Authors: Choi Ben Jiwon , Chen Yu-Chieh David , Desplan Claude
Published: April 2021

During the development of the vertebrate nervous systems, genetic programs assemble an immature circuit that is subsequently refined by neuronal activity evoked by external stimuli. However, prior to sensory experience, the intrinsic property of the developing nervous system also triggers correlated network-level neuronal activity, with retinal waves in the developing vertebrate retina being the best documented example. Spontaneous activity has also been found in the visual system of Drosophila. Here, we compare the spontaneous activity of the developing visual system between mammalian and Drosophila and suggest that Drosophila is an emerging model for mechanistic and functional studies of correlated spontaneous activity.
Pathophysiology of psoriasis: A review
Authors: Yamanaka Keiichi , Yamamoto Osamu , Honda Tetsuya
Published: April 2021

Psoriasis is a complex chronic inflammatory skin disease caused by the dynamic interplay between multiple genetic risk foci, environmental risk factors, and excessive immunological abnormalities. Psoriasis affects approximately 2% of the population worldwide, and dramatic advances have been achieved in the understanding and treatment options for psoriasis. Recent progress in biological therapies has revealed the fundamental roles of tumor necrosis factor‐α, interleukin (IL)‐23p19, and the IL‐17A axis together with skin‐resident immune cells and major signal transduction pathways in the pathogenesis of psoriasis. In addition to IL‐17‐producing T helper17 cells, innate lymphoid cell (ILC)3 induces psoriasis rashes directly without T‐cell/antigen interaction in response to the released antimicrobial peptides from activated keratinocytes and inflammatory cytokines. ILC3 typically expresses retinoic acid receptor‐related orphan receptor gamma t in the nucleus, matures in the presence of IL‐7 and IL‐23, and produces IL‐17 and IL‐22. The number of ILC3s is increased in the blood, psoriasis rash, and even in nonrash areas of psoriatic skin. Psoriasis is significantly associated with cardiovascular disease, metabolic syndrome, and inflammatory disorders, particularly the severe type. The similarity of enterobacteria in the psoriasis gut to that in diabetic patients may be related to its pathogenesis. In the current review, we focus on the pathophysiology of psoriasis in the accelerated immunological inflammatory loop, danger signal from keratinocytes, and cytokines, particularly IL‐17 and IL‐23p19. In addition, pathophysiological speculation with regard to morphology has been supplemented. Finally, the differences and similarities between psoriasis and atopic dermatitis are discussed.
Energetic constraints on mammalian distribution areas
Authors: Boratyński Zbyszek
Published: April 2021

Energy is a universal resource essential for all life functions. The rate of transformation of energy into an organism, and the energetic investment into reproduction, determines population and ecological‐level processes.

Several hypotheses predicted that the ecological expansion and size of the geographic distribution of a species are shaped by, among other factors, metabolic performance. However, how organismal energetic characteristics contribute to species geographic range size is poorly understood.

With phylogenetic comparative methods whether energetic maintenance costs (basal metabolic rate, BMR), aerobic capacity (maximum exercise metabolic rate, VO2max), summit thermoregulation (summit metabolic rate, VO2sum) and the ability to sustain energy provisioning (daily energy expenditure, DEE) determine the distribution of mammalian species range sizes was tested.

Both basal and maximum exercise metabolic rates (accounting for body mass), but not summit thermogenic metabolic rate, were positively associated with species range sizes. Furthermore, daily energy expenditure (accounting for body mass) was positively associated with species ranges. Body mass (accounting for energetic maintenance) was negatively related to range sizes.

High aerobic exercise capacity, aiding mobility such as running and dispersal, and high sustained energy provisioning, aiding reproductive effort such as pregnancy, lactation and natal dispersal, can facilitate the establishment of large mammalian geographic ranges. Consequently, the pace of organismal physiological processes can shape important ecological and biodiversity patterns by setting limits to species’ range sizes.
Race/ethnicity, gender and the SES gradient in BMI: The diminishing returns of SES for racial/ethnic minorities
Authors: Ciciurkaite Gabriele
Published: April 2021

Using the 2013–2016 data from the National Health and Nutrition Examination Survey (NHANES), this study uses the case of obesity to examine whether and to what extent racial and ethnic minorities experience fewer benefits from higher SES relative to their white counterparts. Study results provide support for the diminishing returns in health hypothesis and add an intersectional dimension to this perspective by uncovering stark gendered racial/ethnic disparities in BMI. Specifically, research findings demonstrate that higher income and education is associated with lower BMI among white but not black or Mexican American adults. The most substantial decrease in BMI associated with increase in individual‐level SES was observed among white women. Taken together, empirical evidence from this study underscores difficulty in overcoming adverse health effects of lower ascribed status (i.e. gender or race/ethnicity) even with attainment of higher achieved social status (i.e. educational attainment or income) and offers promising avenues for future research on identifying complex hierarchies that shape population health outcomes.
Managing (im) patience of nurses and nurse's aides: Emotional labour and normalizing practices at geriatric facilities
Authors: Roitenberg Neta
Published: April 2021

Nurses and nurse's aides at geriatric facilities face demanding patients and challenging situations that trigger undesired emotions. The psychological implications of care workers' emotional labour have been extensively researched, but not so their emotional experiences and the regulation of these emotions aimed at normalizing the extraordinary situations that arise in the course of geriatric care. The present study is based on data collected in interviews with 36 nurses and nurse's aides, and nine health professionals and management‐level employees, on participant observations, and on field notes collected over a period of 14 months at two geriatric institutions in Israel. The data reveal the construction of patience and impatience as the pivotal emotional experience that needs regulation to cope successfully with extraordinary situations. The findings suggest that strict patience‐display rules were constructed as an occupational impetus that exacts a price by increasing emotional load. Patience was regulated continually by normalizing practices that were culturally embedded in the organizations, by reframing patients' abusive behaviours, and by diffusing undesired emotions using detachment and disengagement practices. The findings contribute to the scarce empirical research on emotional labour of nurse's aides, and to the conceptualization and empirical study of nurses' normalizing regulation practices as cultural‐organizational artefacts.
What is the best way to characterise the contributions of oral language to reading comprehension: listening comprehension or individual oral language skills?
Authors: Metsala Jamie L. , Sparks Erin , David Margaret , Conrad Nicole , Deacon S. Hélène
Published: April 2021

Educators and researchers agree that oral language is fundamental to students' reading acquisition. It is not clear how best to conceptualise oral language within models of reading – as one's overall understanding of spoken language, or as individual skills, each with unique contributions to children's reading comprehension. In our longitudinal study of children in Grades 2 and 3, we examined the unique contributions of three oral language skills – vocabulary, syntactic awareness, and morphological awareness – to gains in reading comprehension assessed later that academic year (N = 116) and in the spring of the following academic year (N = 87). In our most conservative analyses, we controlled for children's listening comprehension in addition to prior reading achievement. Each language skill predicted variance in later reading comprehension beyond that accounted for by initial word reading and reading comprehension. In analyses with listening comprehension also controlled, each of syntactic awareness and morphological awareness retained their predictive power. Morphological awareness emerged as the most robust predictor and was associated with greater increases in reading comprehension for students in third versus second grade. Results support theoretical models that identify and differentiate contributions from individual oral language skills to reading comprehension. Our findings suggest that increasing each of these oral language skills within the elementary classroom may lead to advances in children's reading comprehension.
Voice of the Customers: Local Trust Culture and Consumer Complaints to the CFPB
Authors: HAYES RACHEL M. , JIANG FENG , PAN YIHUI
Published: April 2021

We use complaints filed with the Consumer Financial Protection Bureau (CFPB) to study the interplay between social norms and the effectiveness of consumer protection laws. We find that a higher level of trust in a given location is associated with a lower number of complaints filed against financial institutions in that location. Employing a difference‐in‐differences approach, we further find that, after the establishment of the CFPB, banks in low‐trust areas reduce fees charged to consumers more compared to banks in high‐trust areas. Our results suggest that the threat of consumer complaints to a government agency affects how banks treat their customers, and they shed light on the interaction between informal culture and formal institutions, as well as on stakeholders’ influence in corporate policies.
Insights into chemometric algorithms for quality attributes and hazards detection in foodstuffs using Raman/surface enhanced Raman spectroscopy
Authors: Wang Jingjing , Chen Quansheng , Belwal Tarun , Lin Xingyu , Luo Zisheng
Published: April 2021

Raman spectroscopy and surface‐enhanced Raman spectroscopy (SERS) have been extensively explored in the design of accurate, transparent, and conclusive food safety and quality control assays. Its hyphenation with chemometric algorithms is instrumental in securing safe food campaigns. To provide valuable recommendations and meet the growing demands for food screening, the current study begins with a brief description of the Raman spectroscopy and SERS theory followed by a comprehensive overview of spectral preprocessing, qualitative algorithms, variable selection methods, and quantitative algorithms. The review emphasizes on the importance of food monitoring practices using multivariate regression models. The applicability of the distinct chemometrics modes toward monitoring pesticide, food and illicit additives, heavy metals, pathogens, and its metabolites in Raman spectroscopy and SERS is covered in dairy, poultry, oil, honey, beverages, and other selected food matrices. Its pertinence toward classification and/or discrimination in food quality and safety monitoring and authentication is examined. Finally, it also complies with the limitations, key challenges, and prospects. The chemometrics processing spectra implemented with simpler or no complicated sample pretreatment step make Raman spectroscopy/SERS technique a potential approach that is expected to achieve simultaneous and fast detection of multiple analytes in food matrices.
Testing for anabolic steroids in human nail clippings
Authors: Kintz Pascal , Gheddar Laurie , Raul Jean‐Sébastien
Published: April 2021

Anabolic steroids are synthetic derivatives of testosterone, and their abuse can have numerous health consequences. Identification of this group of drugs has found applications in forensic toxicology, clinical situations, psychiatric disorders, and of course, anti‐doping violations. Although anabolic steroids are generally tested in urine and very occasionally in head hair, collectors can face the lack of standard specimens, and therefore, nail clippings can be the unique alternative choice. Although there is no possibility to perform segmental analyses using nail clippings, the window of drug detection is generally much longer in nail when compared to head hair (particularly in male subjects), that is, 3–8 months and 4–12 months for finger and toenail clippings, respectively. A new method was developed, including nail pulverization in a ball mill, sonication for 90 min in methanol, and a combination of liquid–liquid and solid‐phase extractions, followed by gas and liquid chromatography coupled to tandem mass spectrometry. To document the application of steroid testing in nail clippings, the authors present 6 authentic cases of abuse, involving stanozolol (7 and 24 pg/mg), nandrolone (6 pg/mg), trenbolone (26, 67, 81, and 89 pg/mg), drostanolone (8 and 11 pg/mg), and testosterone enanthate (14 pg/mg). Given concentrations were always in the low pg/mg range, the use of tandem mass spectrometry appears as a prerequisite.
Comparison of myoglobin clearance in three types of blood purification modalities
Authors: Suzuki Shinya , Moriyama Kazuhiro , Hara Yoshitaka , Hinoue Takuya , Kato Yu , Hasegawa Daisuke , Kuriyama Naohide , Nakamura Tomoyuki , Komatsu Satoshi , Yamashita Chizuru , Komura Hidefumi , Nishida Osamu
Published: April 2021

Myoglobin, which can cause acute kidney injury, has a relatively high molecular weight and is poorly cleared by diffusion. We compared and examined myoglobin clearance by changing the blood purification membrane and modality in patients with a myoglobin blood concentration ≥ 1000 ng/ml. We retrospectively analyzed three patient groups based on the following three types of continuous hemofiltration (CHF): AN69ST membrane, polymethylmethacrylate (PMMA) membrane, and high‐flow hemodiafiltration (HDF) with increased dialysate flow rate using the PMMA membrane. There was no significant difference in clearance in CHF between AN69ST and PMMA membranes. However, the high‐flow HDF group showed the highest myoglobin clearance (p = 0.003). In the PMMA membrane, changing the treatment modality to high‐flow HDF increased clearance above the theoretical value, possibly due to internal filtration. To remove myoglobin by kidney replacement therapy from patients with hypermyoglobinemia, a modality such as high‐flow HDF would be desirable.
Adjustment by hematocrit level in calculation of removal rate in therapeutic apheresis
Authors: Sakurasawa Takatoshi , Ohkubo Atsushi , Hoshikawa Yuki , Yamauchi Daisuke , Yamamoto Hiroko , Seshima Hiroshi , Kurashima Naoki , Iimori Soichiro , Rai Tatemitsu , Uchida Shinichi , Naito Shotaro
Published: April 2021

Plasma volume (PV) variation during therapeutic apheresis (TA) (such as plasma exchange [PE] and selective PE using albumin solution as replacement solution or immunoadsorption plasmapheresis) has been considered to be unignorable. It changes the concentration of the target molecule and might impact its removal rate (RR.) This study aimed to evaluate the effects of PV variation on the calculation of the RR of fibrinogen and immunoglobulin by categorizing the hematocrit (Ht) change during TA into two patterns, that is, increased group and decreased group. In all modalities of TA, the Ht level frequently changed during apheresis sessions. In calculating RR, RR calculated with Ht adjustment was significantly higher than that calculated without adjustment in the increased group and significantly lower than it in the decreased group. Therefore, RR might have been underestimated in the increased group and overestimated in the decreased group when RR was calculated without Ht adjustment. Ht adjustment is suggested to be crucial in calculating RR in TA.
Synergistic gelation in the hybrid gel of scallop (Patinopecten yessoensis) male gonad hydrolysates and xanthan gum
Authors: Xue Shan , Yan Jia‐Nan , Du Yi‐Nan , Jiang Xin‐Yu , Xu Shi‐Qi , Wu Hai‐Tao
Published: April 2021

This study evaluated the gel and microstructure properties of scallop (Patinopecten yessoensis) male gonads hydrolysates (SMGHs) combined with xanthan gum (XG). SMGHs/XG hydrogel matrix properties and structures were elucidated via different analysis tools such as rheometry, LF‐NMR, FTIR, AFM, and Cryo‐SEM. The addition of XG significantly improved the rheological properties of SMGHs, as indicated by 3.1‐fold G′ and 1.3‐fold melting temperature with increasing the XG dose to 5.6 mg/ml. The corresponding decrease in the T23 relaxation time from 450.3 to 365.6 ms also signified the strong binding between SMGHs and XG. SMGHs/XG also had a higher proton density (T1 and T2 weighted images) due to the higher bound and free water content of the hybrid gel systems, respectively. Additionally, the blueshift in the amide I and II bands in SMGHs/XG further indicated stronger electrostatic interactions between SMGHs and XG. Such scenarios resulted in a well‐distributed and compact network with a rougher surface of SMGHs/XG in comparison to pure SMGHs and XG, as assessed by AFM and SEM. These results suggest that SMGHs/XG gel could be a potential hybrid gel applied in the food industry.

Practical Application

Scallop (Patinopecten yessoensis) male gonads are edible, but are usually discarded during processing of scallop adductor. Because of its rich nutrition and gelation properties, scallop male gonads have a potential role in developing marine source‐protein as a functional food base. The SMGHs/XG binary gel would be potentially applied in delivery system in food and biological fields. Further study is undergoing to apply SMGHs/XG binary gel to embed bioactive compounds, such as curcumin and β‐carotene.
Effect of dexmedetomidine on evoked‐potential monitoring in patients undergoing brain stem and supratentorial cranial surgery
Authors: Pacreu Susana , Vilà Esther , Moltó Luis , Fernández‐Candil Juan , Fort Beatriz , Lin Yiyang , León Alba
Published: April 2021

Background

Dexmedetomidine is used as adjuvant in total intravenous anaesthesia (TIVA), but there have been few studies concerning its effect on intraoperative neurophysiological monitoring (IONM) during cranial surgery. Our aim was to study the effect of dexmedetomidine on IONM in patients undergoing brain stem and supratentorial cranial surgery.

Methods

Two prospective, randomized, double‐blind substudies were conducted. In substudy 1, during TIVA with an infusion of propofol and remifentanil, 10 patients received saline solution (SS) (PR group) and another 10 (PRD group) received dexmedetomidine (0.5 mcg/kg/h). Total dosage of propofol and remifentanil, intensity, latency and amplitude of motor‐evoked potentials following transcranial electrical stimulation (tcMEPs) as well as somatosensory‐evoked potentials (SSEP) were recorded at baseline, 15, 30, 45 minutes, and at the end of surgery. In order to identify differences in the same patient after dexmedetomidine administration, we designed substudy 2 with 20 new patients randomized to two groups. After 30 minutes with TIVA, 10 patients received dexmedetomidine (0.5 mcg/kg/h) and 10 patients SS. The same variables were recorded.

Results

In substudy 1, propofol requirements were significantly lower (P = .004) and tcMEP intensity at the end of surgery was significantly higher in PRD group, but no statistically significant differences were observed for remifentanil requirements, SSEP and tcMEP latency or amplitude. In substudy 2, no differences in any of the variables were identified.

Conclusions

The administration of dexmedetomidine at a dosage of 0.5 mg/kg/h may reduce propofol requirements and adversely affect some neuromonitoring variables. However, it can be an alternative on IONM during cranial surgeries.

REDEX

EudraCT: 2014‐000962‐23