bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomised clinical trial of long term glutathione supplementation offers protection from oxidative damage, improves HbA1c in elderly type 2 diabetic patients
Authors: Kalamkar Saurabh , Acharya Jhankar , Madathil Arjun Kolappurath , Gajjar Vijay , Divate Uma , Karandikar-Iyer Sucheta , Goel Pranay , Ghaskadbi Saroj
Published: April 2021

Sustained hyperglycemia in type 2 diabetes is associated with low levels of the endogenous antioxidant glutathione (GSH), which leads to oxidative stress and tissue damage. It is therefore important to investigate whether oral GSH supplementation would restore GSH levels, and also help improve redox state and glycaemia in diabetic individuals. We conducted a pragmatic clinical trial to assess effectiveness of oral GSH supplementation along with anti-diabetic treatment. 104 non-diabetic and 250 diabetic individuals were recruited. All the 250 diabetic individuals were on anti-diabetic therapy; of these 125 were given oral GSH supplementation additionally for a period of six months. Fasting and PP glucose and insulin, HbA1c, GSH and the oxidative DNA damage marker 8-OHdG were measured at the recruitment time and after three and six months of supplementation. GSH supplementation increased blood GSH and decreased 8-OHdG significantly within three months in diabetic individuals. It also reduced HbA1c within three months and stabilized it thereafter in diabetic population overall. Patients above 55 years benefited more as evidenced by a significant decrease in HbA1c and 8-OHdG and an increase in fasting insulin. Data suggest that GSH supplementation can be used as an adjunct therapy to anti-diabetic treatment to achieve better glycemic targets, especially in elderly population.

Trial registered

This study has been registered with Clinical Trials Registry-India (CTRI/2018/01/011257)

Novelty bullets

Oral GSH supplementation replenishes body stores of GSH and significantly reduces oxidative DNA damage in diabetic patients over six months.

HbA1c is lowered at three months and is stabilized thereafter.

A significant decrease in HbA1c and elevated fasting insulin was observed in people older than 55 years.
Laser speckle contrast imaging for visualizing blood flow during cerebral aneurysm surgery: A comparison with indocyanine green angiography
Authors: Miller David R. , Ashour Ramsey , Sullender Colin T. , Dunn Andrew K.
Published: April 2021

Laser speckle contrast imaging (LSCI) has emerged as a promising tool for intraoperative cerebral blood flow (CBF) monitoring because it produces real-time full-field blood flow maps non-invasively and label-free. In this study, we compare LSCI with indocyanine green angiography (ICGA) to assess CBF during aneurysm clipping surgery in humans. LSCI hardware was attached to the surgical microscope prior to the start of each surgery and did not interfere with the sterile draping of the microscope or normal operation of the microscope. LSCI and ICGA were performed simultaneously to visualize CBF inn=4 aneurysm clipping cases, and LSCI was performed throughout each surgery when the microscope was positioned over the patient. To more easily visualize CBF in real-time, LSCI images were overlaid on the built-in microscope white light camera images and displayed to the neurosurgeon in real-time. Blood flow changes before, during, and after an aneurysm clipping were visualized with LSCI and later verified with ICGA. LSCI was performed continuously throughout the aneurysm clipping process, providing the surgeon with immediate actionable information on the success of the clipping. The results demonstrate that LSCI and ICGA provide different, yet complementary information about vessel perfusion.
SARS-CoV-2 sculpts the immune system to induce sustained virus-specific naïve-like and memory B cell responses
Authors: de Campos-Mata Leire , Vaquero Sonia Tejedor , Tachó-Piñot Roser , Piñero Janet , Grasset Emilie K. , Aldea Itziar Arrieta , Melero Natalia Rodrigo , Carolis Carlo , Horcajada Juan P. , Cerutti Andrea , Villar-García Judit , Magri Giuliana
Published: April 2021

SARS-CoV-2 infection induces virus-reactive memory B cells expressing unmutated antibodies, which hints at their emergence from naïve B cells. Yet, the dynamics of virus-specific naïve B cells and their impact on immunity and immunopathology remain unclear. Here, we longitudinally studied moderate to severe COVID-19 patients to dissect SARS-CoV-2-specific B cell responses overtime. We found a broad virus-specific antibody response during acute infection, which evolved into an IgG1-dominated response during convalescence. Acute infection was associated with increased mature B cell progenitors in the circulation and the unexpected expansion of virus-targeting naïve-like B cells that further augmented during convalescence together with virus-specific memory B cells. In addition to a transitory increase in tissue-homing CXCR3+plasmablasts and extrafollicular memory B cells, most COVID-19 patients showed persistent activation of CD4+and CD8+T cells along with transient or long-lasting changes of key innate immune cells. Remarkably, virus-specific antibodies and the frequency of naïve B cells were among the major variables defining distinct immune signatures associated with disease severity and inflammation. Aside from providing new insights into the complexity of the immune response to SARS-CoV-2, our findings indicate that the de novo recruitment of mature B cell precursors into the periphery may be central to the induction of antiviral immunity.
Single-cell resolution of MET- and EMT-like programs in osteoblasts during zebrafish fin regeneration
Authors: Tang W. Joyce , Watson Claire J. , Olmstead Theresa , Allan Christopher H. , Kwon Ronald Y.
Published: April 2021

Zebrafish regenerate fin rays following amputation through epimorphic regeneration, a process that has been proposed to involve the epithelial-to-mesenchymal transition (EMT). We performed single-cell RNA-sequencing (scRNA-seq) to elucidate osteoblastic transcriptional programs during zebrafish caudal fin regeneration. We show that osteoprogenitors are enriched with components associated with EMT and its reverse, mesenchymal-to-epithelial transition (MET), and provide evidence that the EMT markerscdh11andtwist2are co-expressed in dedifferentiating cells at the amputation stump at 1 dpa, and in differentiating osteoblastic cells in the regenerate, the latter of which are enriched in EMT signatures. We also show thatesrp1, a regulator of alternative splicing in epithelial cells that is associated with MET, is expressed in a subset of osteoprogenitors during outgrowth. This study provides a single cell resource for the study of osteoblastic cells during zebrafish fin regeneration, and supports the contribution of MET- and EMT-associated components to this process.
Genome sequence ofPseudopithomyces chartarum, causal agent of facial eczema (pithomycotoxicosis) in ruminants, and identification of the putative sporidesmin toxin gene cluster
Authors: Sidhu Jaspreet Singh , Suresh Vinod , Baten Abdul , McCartney Ann M. , Lear Gavin , Sprosen Jan M. , Oliver Mark H. , Forester Natasha T. , Maclean Paul H. , Palevich Nikola , Jauregui Ruy , Voisey Christine R.
Published: April 2021

Facial eczema (FE) in grazing ruminants is a debilitating liver syndrome induced by ingestion of sporidesmin, a toxin belonging to the epipolythiodioxopiperazine class of compounds. Sporidesmin is produced in spores of the fungusPseudopithomyces chartarum, a microbe which colonises leaf litter in pastures. New Zealand has a high occurrence of FE in comparison to other countries as animals are fed predominantly on ryegrass, a species that supports high levels ofPse. chartarumspores. The climate is also particularly conducive forPse. chartarumgrowth. Here, we present the genome ofPse. chartarumand identify the putative sporidesmin gene cluster. ThePse. chartarumgenome was sequenced using single molecule real-time sequencing (PacBio) and gene models identified. Loci containing genes with homology to the aspirochlorine, sirodesmin PL and gliotoxin cluster genes ofAspergillus oryzae, Leptosphaeria maculansandAspergillus fumigatus, respectively, were identified by tBLASTn. We identified and annotated an epipolythiodioxopiperazine cluster at a single locus with all the functionality required to synthesise sporidesmin.

Highlights

The whole genome ofPseudopithomyces chartarumhas been sequenced and assembled.

The genome is 39.13 Mb, 99% complete, and contains 11,711 protein coding genes.

A putative sporidesmin A toxin (cause of facial eczema) gene cluster is described.

The genomes ofPse. chartarumand theLeptosphaerulina chartarumteleomorph differ.

Comparative genomics is required to further resolve thePseudopithomycesclade.
Factorization-based Imputation of Expression in Single-cell Transcriptomic Analysis (FIESTA) recovers Gene-Cell-State relationships
Authors: Mehrabad Elnaz Mirzaei , Bhaskara Aditya , Spike Benjamin T.
Published: April 2021

Single cell RNA sequencing (scRNA-seq) is a gene expression profiling technique that is presently revolutionizing the study of complex cellular systems in the biological sciences. Existing scRNA-seq methods suffer from sub-optimal target recovery leading to inaccurate measurements including many false negatives. The resulting ‘zero-inflated’ data may confound data interpretation and visualization. Since cells have coherent phenotypes defined by conserved molecular circuitries (i.e. multiple gene products working together) and since similar cells utilize similar circuits, information about each expression value or ‘node’ in a multi-cell, multi-gene scRNA-seq data set is expected to also be predictable from other nodes in the data set. Based on this logic, several approaches have been proposed to impute missing values in a data set by extracting information from its non-zero measurements. In this study, we apply non-negative matrix factorization to a selection of published scRNA-seq data sets followed by multiplication of the factor matrices to generate idealized ‘completed’ model versions of the data. From the model matrices, we recommend new values where original measurements are likely to be inaccurate and where ‘zero’ measurements are predicted to be false negatives. The resulting imputed data model predicts novel type markers and expression patterns that match orthogonal measurements and field literature better than those obtained from pre-imputation data or alternative imputation strategies.

Contact

benjamin.spike@hci.utah.edu

Availability and implementation

FIESTA is written in R and is available athttps://github.com/elnazmirzaei/FIESTAandhttps://github.com/TheSpikeLab/FIESTA.

Author summary

In this work, we develop FIESTA, a novel, unsupervised, mathematical approach to impute missing values in scRNA-seq data. For each dataset, we use parts-based, non-negative matrix factorization to break the cells-by-genes expression matrix into optimized component matrices and then multiply these component matrices to generate an idealized, ‘completed’ matrix. The completed matrix has many of the null values filled in because the optimized low rank factors from which it is generated, take multiple cells into account when estimating a particular component, including some cells with positive expression values for genes which are false negatives in other related cells. We also implement scaling and thresholding approaches based on intrinsic data topology for improved interpretability and graphical representation. Overall, FIESTA performs favorably relative to alternative imputation approaches and uncovers gene-gene and gene-cell relationships that are occluded in the raw data. The FIESTA computational pipeline is freely available for download and use by other researchers analyzing scRNA-seq data or other sparse data sets.
Widespread reorganisation of the regulatory chromatin landscape facilitates resistance to inhibition of oncogenic ERBB2 signalling
Authors: Ogden Samuel , Carys Kashmala , Bruce Jason ,   the OCCAMS consortium, Sharrocks Andrew D.
Published: April 2021

Oesophageal adenocarcinoma (OAC) patients show poor survival rates and there are few targeted molecular therapies available. However, components of the receptor tyrosine kinase (RTK) driven pathways are commonly mutated in OAC, typified by high frequency amplifications of the RTKERRB2. ERBB2 can be therapeutically targeted, but this has limited clinical benefit due to the acquisition of drug resistance. Here we examined how OAC cells respond to ERBB2 inhibition through altering their regulatory chromatin landscapes and rewiring their gene regulatory networks to acquire a reversible resistant state. ERBB2 inhibition triggers widespread remodelling of the accessible chromatin landscape. This remodelling is accompanied by the activation of the transcriptional regulators HNF4A and PPARGC1A. Initially, inhibition of cell cycle associated gene expression programmes is observed, with compensatory increases in the programmes driving changes in metabolic activity. PPARGC1A is instrumental in promoting a switch to dependency on oxidative phosphorylation and both PPARGC1A and HNF4A are required for the acquisition of resistance to ERBB2 inhibition. Our work therefore reveals the molecular pathways that support the acquisition of a resistant state and points to potential new therapeutic strategies to combat drug resistance.
Loss ofSmad4promotes aggressive lung cancer metastasis by de-repression of PAK3 via miRNA regulation
Authors: Tan Xiaohong , Tong Lu , Li Lin , Xu Jinjin , Xie Shaofang , Ji Lei , Fu Jujiang , Liu Qingwu , Shen Shihui , Liu Yun , Xiao Yanhui , Gao Feiran , Moses Robb E. , Bardeesy Nabeel , Wang Yanxiao , Zhang Jishuai , Wong Kwok-kin , Tang Longying , Li Lei , Song Dianwen , Yang Xiao , Liu Jian , Li Xiaotao
Published: April 2021

Over 85% of lung cancer patients harbor overt or subclinical metastases at diagnosis, and therefore most patients die of progressive metastatic disease despite aggressive local and systemic therapies. Somatic mutations in theSmad4gene have been found in non-small-cell lung cancer, but the underlying mechanism by which Smad4 loss-of-function (LOF) accelerates lung cancer metastasis is yet to be elucidated. Here, we generated a highly aggressive lung cancer mouse model bearing conditionalKrasG12D,p53fl/flLOF and/orSmad4fl/flLOF mutations. TheSmad4fl/fl;p53fl/fl; KrasG12D(SPK) mutant mice manifested a much higher incidence of tumor metastases than thep53fl/fl; KrasG12D(PK) mice. Molecularly, PAK3 was identified as a novel downstream effector of Smad4, mediating metastatic signal transduction via the PAK3-JNK-Jun pathway. Upregulation of PAK3 by Smad4 LOF in SPK mice was achieved by attenuating Smad4-dependent transcription of miR-495 and miR-543. These microRNAs (miRNAs) directly bind to the PAK3 3’UTR for blockade of PAK3 production, ultimately regulating lung cancer metastasis. An inverse correlation between Smad4 and PAK3 pathway components suggests clinical use of Smad4 LOF as a potential marker for prognosis in human lung cancer. Our study highlights the Smad4-PAK3 regulation as a point of potential therapy in metastatic lung cancer.
Why does Δ9-Tetrahydrocannabinol act as a partial agonist of cannabinoid receptors?
Authors: Dutta Soumajit , Selvam Balaji , Das Aditi , Shukla Diwakar
Published: April 2021

Cannabinoid receptor 1 (CB1) is a therapeutically relevant drug target for controlling pain, obesity, and other central nervous system disorders. However, full agonists and antagonists of CB1have been reported to cause serious side effects in patients. Therefore, partial agonists have emerged as a viable alternative to full agonists and antagonists as they avoid overstimulation and side effects. One of the key bottlenecks in the design of partial agonists is the lack of understanding of the molecular mechanism of partial agonism. In this study, we examine two mechanistic hypotheses for the origin of partial agonism in cannabinoid receptors and explain the mechanistic basis of partial agonism exhibited by Δ9-Tetrahydrocannabinol (THC). In particular, we inspect whether partial agonism emerges from the ability of THC to bind in both agonist and antagonist binding pose or from its ability to only partially activate the receptor. Extensive molecular dynamics simulations and the Markov state model capture the THC binding in both antagonist, and agonist binding poses in CB1receptor. Furthermore, we observe that binding of THC in the agonist binding pose leads to rotation of toggle switch residues and causes partial outward movement of intracellular transmembrane helix 6 (TM6). Our simulations also suggest that the alkyl side chain of THC plays a crucial role in determining partial agonism by stabilizing the ligand in the agonist and antagonist-like poses within the pocket. This study provides us fundamental insights into the mechanistic origin of the partial agonism of THC.
Metabolic adaptation to progressive mitochondrial dysfunction in aging POLGD257Amice
Authors: Lim Esther W. , Handzlik Michal K. , Trefts Elijah , Gengatharan Jivani M. , Shaw Reuben J. , Metallo Christian M.
Published: April 2021

A decline in mitochondrial function is associated with neurodegeneration and aging. Progressive mitochondrial defects have diverse metabolic consequences that could drive some of the pathophysiological changes that occur with aging. Here, we comprehensively characterized metabolic alterations in PolgD257Amitochondrial DNA mutator mice. Plasma alanine increased dramatically with time, with lactate and other organic acids accumulating to a lesser extent. These changes were reflective of increased glycolysis, rapid gluconeogenesis, and hypoglycemia. Tracing with [15N]ammonium revealed impairment of the urea cycle and diversion to purine catabolism. We also measured alterations in the lipidome, observing a general reduction in canonical lipids and the accumulation of 1-deoxysphingolipids, which are synthesized from alanine via promiscuous serine palmitoyltransferase activity. Consistent with 1-deoxysphingolipid’s association with peripheral neuropathy, PolgD257Amice exhibited thermal hypoalgesia. These results highlight the distinct changes that occur in carbon and nitrogen metabolism upon mitochondrial impairment and key metabolic mechanisms which can drive aging-associated neuropathy.
PTPRU, a quiescence-induced receptor tyrosine phosphatase negatively regulates osteogenic differentiation of human mesenchymal stem cells
Authors: Rumman Mohammad , Dhawan Jyotsna
Published: April 2021

Bone marrow mesenchymal stem cells (MSCs) are heterogeneous osteo-progenitors that are mainly responsible for bone regeneration and homeostasis. In vivo, a subpopulation of bone marrow MSCs persists in a quiescent state, providing a source of new cells for repair. Previously, we reported that induction of quiescence in hMSCs in vitro skews their differentiation potential in favour of osteogenesis while suppressing adipogenesis. Here, we uncover a new role for a protein tyrosine phosphatase, receptor type U (PTPRU) in repressing osteogenesis during quiescence. A 75 kD PTPRU protein isoform was found to be specifically induced during quiescence and down-regulated during cell cycle reactivation. Using siRNA-mediated knockdown, we report that in proliferating hMSC, PTPRU preserves self-renewal, while in quiescent hMSC, PTPRU not only maintains reversibility of cell cycle arrest but also suppresses expression of osteogenic lineage genes. Knockdown of PTPRU in proliferating or quiescent hMSC de-represses osteogenic markers, and enhances induced osteogenic differentiation. We also show that PTPRU positively regulates a β-catenin-TCF transcriptional reporter. Taken together, our study suggests a role for a quiescence-induced 75kD PTPRU isoform in modulating bone differentiation in hMSC, potentially involving the Wnt pathway.
Unraveling the stepwise maturation of the yeast telomerase
Authors: Hirsch Anna Greta , Becker Daniel , Lamping Jan-Philipp , Krebber Heike
Published: April 2021

Telomerases elongate the ends of chromosomes required for cell immortality through their reverse transcriptase activity. By using the model organismSaccharomyces cerevisiaewe defined the order in which the holoenzyme matures. First, a longer precursor of the telomerase RNA,TLC1is transcribed and exported into the cytoplasm, where it associates with the protecting Sm-ring, the Est- and the Pop-proteins. This partly matured telomerase is re-import into the nucleus via Mtr10 and a novelTLC1-import factor, the karyopherin Cse1. Remarkably, while mutations in all known transport factors result in short telomere ends, mutation inCSE1bypasses this defect and become Type I like survivors. Interestingly, both import receptors contact the Sm-ring for nuclear import, which therefore resembles a quality control step in the maturation process of the telomerase. The re-imported immatureTLC1is finally trimmed into the ~1150 nucleotide long mature form. TMG-capping ofTLC1finalizes maturation, leading to mature telomerase.
Evolution and function of nitrogen fixation gene clusters in sugarcane associated Bradyrhizobium strains
Authors: de Matos Gustavo Feitosa , Rouws Luc Felicianus Marie , Simões‐Araújo Jean Luiz , Baldani José Ivo
Published: April 2021

Bradyrhizobium spp. are well known to mediate biological nitrogen fixation (BNF) as microsymbionts inhabiting nodules on leguminous plants. However, they may also contribute to plant growth via free‐living N2 fixation (FLNF) in association with non‐legumes. Notably, several Bradyrhizobium strains from sugarcane roots display FLNF activity. Among them, Bradyrhizobium sacchari is a legume symbiotic species, whereas strains AG48 and M12 are non‐symbiotic. In the present study, a phylogenomic approach was applied to study peculiarities of these and other Bradyrhizobium strains with respect to N fixation (nif) gene content in order to reveal genetic features that enable FNLF in Bradyrhizobium spp. All FLNF strains carry an ancestral ‘non‐symbiotic’ nif‐gene cluster (NSC). B. sacchari also contains a second ‘symbiotic’ nif‐gene cluster (SC), a characteristic observed in only three of 156 evaluated genomes. B. sacchari stood out and presented a high level of sequence divergence between individual nif‐gene homologues and we discuss scenarios for the evolutionary origin of these clusters. The transcript level of NSC nifH gene increased during FLNF, when compared to symbiotic conditions. The data suggest that sugarcane roots harbor diverse Bradyrhizobium spp. that are genetically adapted to a dynamic environment where leguminous and non‐leguminous host plants are alternately available.
Environmental hazards: The microgeography of land‐use negative externalities
Authors: Somerville Tsur , Wetzel Jake
Published: April 2021

The decisions on the siting of hazardous facilities and compensation for nearby landowners depend on an accurate estimation of the negative externalities these facilities place on proximate land uses, primarily residential properties. In this paper, we highlight the sensitivity of these estimates to the treatment of distance from the hazard and to the presence of other nearby externality generating land uses identified at a highly granular geographic level. We find that estimated spillovers are quite sensitive to highly localized treatment of other land uses and that naive parametric specifications yield misleading results. Unlike previous work, we find proximity to a major oil pipeline results in lower house prices: properties adjacent to a property with a pipeline easement transact for 2.2% ($C 15.8k) less and those one property further away 1.6% ($C 11k) less than more distant residential properties. These effects vary by the type of land use on which the pipeline easement lies. Difference‐in‐differences tests indicate that the price effects of proximity respond to information shocks that remind potential buyers of pipeline risks but not those shocks that merely remind them of the presence of the pipeline. However, the effects of an information shock, in this case a nearby spill on the pipeline, dissipate within 18 months.
Development of a rapid colorimetric strip method for determination of volatile bases in mahi‐mahi and tuna
Authors: Bai Jing , Baker Shirley M. , Goodrich‐Schneider Renee M. , Montazeri Naim , Sarnoski Paul J.
Published: April 2021

Tuna (Thunnus albacares) and mahi‐mahi (Coryphaena hippurus) are two major fish species responsible for scombroid poisoning in the United States. The purpose of this research was to develop a low‐cost and easily operated colorimetric strip method for the rapid determination of spoilage degree via amine response in mahi‐mahi and tuna. The color strip method was developed by investigating different types of dyes, filter papers, sample volume, water bath temperature, and other parameters. Ultimately rose bengal and bromophenol blue (BPB) dyes were chosen. These two dyes produced standard curves with good linearity (0–50 mg/L for the total biogenic amines) and uniformity of color change. The r2 values for the standard curves of the rose Bengal and BPB were 0.9535 and 0.8883, respectively. Significant positive Pearson correlations coefficients (r) between the volatile biogenic amine levels detected by these two colorimetric strip methods with increasing spoilage grade of mahi‐mahi (rose bengal: r = 0.8907, p < 0.0001; BPB: r = 0.8711, p < 0.0001) and tuna (rose bengal: r = 0.8351, p < 0.0001; BPB: r = 0.7362, p = 0.0001) were observed. For mahi‐mahi, the volatile amines detected by the colorimetric strips correlated positively with increasing levels of eight biogenic amines, free alanine, four aldehydes, isoamyl alcohol, two ketones, and dimethyl disulfide. For tuna, the results determined by colorimetric strips positively correlated with three biogenic amines, three free amino acids, four aldehydes, and ethanol. The two validated colorimetric strips could rapidly monitor the spoilage degree of mahi‐mahi and tuna at low‐cost.

Practical Application

Rose bengal strips and BPB strips were developed as a rapid, objective, analytical method that can serve as an alternative to sensory grading methods. These two nonspecific colorimetric strip methods provided good linear response and uniformity of color change. Volatile amine levels in fish determined by these colorimetric strip methods were statistically significant and positively correlated with the spoilage grade of fish.
The serotonin 2C receptor agonist lorcaserin, alone and in combination with the opioid receptor antagonist naltrexone, attenuates binge‐like ethanol drinking
Authors: Tabbara Rayane I. , Li Zhaoxia , Fletcher Paul J. , Lê Anh D.
Published: April 2021

The serotonin (5‐HT) system has been implicated in the pathophysiology of alcohol (ethanol; EtOH) use disorders. Lorcaserin, a 5‐HT2C receptor agonist, attenuates drug self‐administration in animal models. We investigated the effects of lorcaserin on EtOH intake using the drinking‐in‐the‐dark (DID) procedure, an animal model of binge‐like drinking. We compared the effects of lorcaserin to those of the Food and Drug Administration (FDA)‐approved drug naltrexone and examined the effects of combining lorcaserin and naltrexone. To examine whether effects were specific for EtOH, we examined the effects of lorcaserin and naltrexone, administered alone and in combination, on saccharin intake. Adult male C57BL/6J mice received EtOH access (20% v/v) for 2 h in the home‐cage during the first 3 days of the DID procedure, beginning 3 h into the dark cycle. On day 4, mice were injected with lorcaserin, naltrexone, or a combination of lorcaserin and naltrexone prior to a 4‐h EtOH access. Intake was measured at 2 and 4 h. Lorcaserin reduced EtOH intake in a dose‐dependent fashion over the 2‐ and 4‐h measurement periods. Naltrexone also reduced EtOH intake when administered alone, with dose‐dependent effects being more pronounced over 2 h rather than the full 4‐h session. Combining lorcaserin and naltrexone reduced binge‐like EtOH drinking to a greater extent than either drug alone. A similar pattern of results was obtained for saccharin intake. These results suggest that lorcaserin and naltrexone can have additive effects on binge‐like EtOH drinking. They also support continued research into the therapeutic potential of lorcaserin for alcohol use disorders.
Vertical stratification and seasonal changes of the avian community in Mount Cameroon lowland rainforest
Authors: Chmel Kryštof , Kamga Solange Mekuate , Awa Taku , Ewome Francis Luma , Uceda‐Gómez Guillermo , Hořák David , Mlíkovský Jiří , Molua Lucas Lyonga , Riegert Jan , Janeček Štěpán
Published: April 2021

While birds are known to show preferences for distinct vertical strata in forests, detailed studies on the vertical distribution of whole communities are still scarce. Furthermore, of those conducted, most have used ground‐based methods, including in both tropical and temperate forest. Here, we utilised ground‐to‐canopy mist nets to explore the vertical distribution of birds within lowland forest of Mount Cameroon National Park in both dry and wet seasons. In total, 908 birds from 83 species were caught. Species richness was highest in the understory and decreased towards the canopy as did bird abundance. We sampled more species during the dry season, with some species showing substantial seasonal changes in overall abundance. No seasonally driven stratal shifts in abundance were observed, while species richness increased in denser strata in the wet season. Although frugivoro‐insectivorous birds represented the most species‐rich foraging guild, their total abundance was unrelated to height above the ground, season and vegetation cover. This was also applied to gleaning insectivores, the second most species‐rich foraging guild. Omnivores, insectivoro‐nectarivores, sallying insectivores and frugivores typically showed a preference for higher vertical strata, while ground‐foraging insectivores preferred low forest strata with dense vegetation. Seasonal variation was most profound in frugivores and sallying insectivores.
Ichthyosiform sarcoidosis: Report of a case and comprehensive review of the literature
Authors: Chen Henry W. , Vandergriff Travis
Published: April 2021

Sarcoidosis is a disease that can affect a multitude of organs and manifest as cutaneous disease. Cutaneous manifestations of sarcoidosis vary widely in morphology, earning the nickname of “great imitator,” and the diagnosis often requires clinicopathologic correlation and additional laboratory and radiographic workup. We present the case of a 42‐year‐old African American woman with ichthyosiform sarcoidosis on the bilateral lower extremities. As one of the rarest specific variants of cutaneous sarcoidosis, ichthyosiform is understudied and has been primarily documented in case reports and series. We undertake a comprehensive review of the literature to identify key clinicopathologic features including the characterization of sites of cutaneous and systemic involvement, as well as typical histopathological findings. Lower extremities were the most involved body site (85.7%). Extracutaneous organ involvement centered around pulmonary (65.7%), lymph node (57.1%), and ocular (31.4%) involvement. Of the histopathological features reported, hyperkeratosis (51.4%) and diminished stratum granulosum (62.9%) were most frequently reported in conjunction with dermal granulomas (100%). We hope that these findings will serve to aid clinicopathological correlation and accurate diagnosis of ichthyosiform sarcoidosis.
Perceptions of Using Multiple Mobile Health Devices to Support Self‐Management Among Adults With Type 2 Diabetes: A Qualitative Descriptive Study
Authors: Lewinski Allison A. , Vaughn Jacqueline , Diane Anna , Barnes Angel , Crowley Matthew J. , Steinberg Dori , Stevenson Janee , Yang Qing , Vorderstrasse Allison A. , Hatch Daniel , Jiang Meilin , Shaw Ryan J.
Published: April 2021

Purpose

This study identified facilitators and barriers pertaining to the use of multiple mobile health (mHealth) devices (Fitbit Alta® fitness tracker, iHealth® glucometer, BodyTrace® scale) that support self‐management behaviors in individuals with type 2 diabetes mellitus (T2DM).

Design

This qualitative descriptive study presents study participants’ perceptions of using multiple mobile devices to support T2DM self‐management. Additionally, this study assessed whether participants found visualizations, generated from each participant’s health data as obtained from the three separate devices, useful and easy to interpret.

Methods

Semistructured interviews were completed with a convenience sample of participants (n = 20) from a larger randomized control trial on T2DM self‐management. Interview questions focused on participants’ use of three devices to support T2DM self‐management. A study team member created data visualizations of each interview participant’s health data using RStudio.

Results

We identified two themes from descriptions of study participants: feasibility and usability. We identified one theme about visualizations created from data obtained from the mobile devices. Despite some challenges, individuals with T2DM found it feasible to use multiple mobile devices to facilitate engagement in T2DM self‐management behaviors.

Discussion

As mHealth devices become increasingly popular for diabetes self‐management and are integrated into care delivery, we must address issues associated with the use of multiple mHealth devices and the use of aggregate data to support T2DM self‐management.

Clinical Relevance

Real‐time patient‐generated health data that are easily accessible and readily available can assist T2DM self‐management and catalyze conversations, leading to better self‐management. Our findings lay an important groundwork for understanding how individuals with T2DM can use multiple mHealth devices simultaneously to support self‐management.
Bendy to the bone: Links between vertebral morphology and waterfall climbing in amphidromous gobioid fishes
Authors: Forker Grace K. , Schoenfuss Heiko L. , Blob Richard W. , Diamond Kelly M.
Published: April 2021

Locomotor force production imposes strong demands on organismal form. Thus, the evolution of novel locomotor modes is often associated with morphological adaptations that help to meet those demands. In the goby lineage of fishes, most species are marine and use their fused pelvic fins to facilitate station holding in wave‐swept environments. However, several groups of gobies have evolved an amphidromous lifecycle, in which larvae develop in the ocean but juveniles migrate to freshwater for their adult phase. In many of these species, the pelvic fins have been co‐opted to aid in climbing waterfalls during upstream migrations to adult habitats. During horizontal swimming, forces are produced by axial musculature pulling on the vertebral column. However, during vertical climbing, gravity also exerts forces along the length of the vertebral column. In this study, we searched for novel aspects of vertebral column form that might be associated with the distinctive locomotor strategies of climbing gobies. We predicted that stiffness would vary along the length of the vertebral column due to competing demands for stability of the suction disk anteriorly and flexibility for axial thrust production posteriorly. We also predicted that derived, climbing goby species would require stiffer backbones to aid in vertical thrust production compared to non‐climbing species. To test these predictions, we used microcomputed tomography scans to compare vertebral anatomy (centrum length, centrum width, and intervertebral space) along the vertebral column for five gobioid species that differ in climbing ability. Our results support our second prediction, that gobies are more flexible in the posterior portion of the body. However, the main variation in vertebral column form associated with climbing ability was the presence of larger intervertebral spaces in Sicyopterus stimpsoni, a species that uses a distinctive inching behavior to climb. These results build on past kinematic studies of goby climbing performance and lend insights into how the underlying vertebral structure of these fishes may enable their novel locomotion.
Subsequent meniscal tears following tibial tuberosity advancement and tibial plateau leveling osteotomy in dogs with cranial cruciate ligament deficiency: An in vivo experimental study
Authors: Jeong Jaemin , Jeong Seong Mok , Kim Stanley E. , Lewis Daniel D. , Lee Haebeom
Published: April 2021

Objective

To evaluate the short‐ and mid‐term effects of tibial tuberosity advancement (TTA) and tibial plateau leveling osteotomy (TPLO) on subsequent meniscal tears.

Study Design

Experimental in vivo study.

Animals

Purpose‐bred beagle dogs (n = 15).

Methods

For each dog, the cranial cruciate ligaments were transected; one limb underwent TTA and the other limb underwent TPLO. Orthopedic and radiographic examinations were performed preoperatively and at 12 and 32 weeks postoperatively. Gross evaluation of the stifle joint was performed after euthanasia at 12 (n = 10) and 32 (n = 5) weeks.

Results

Lameness scores were not different between TTA and TPLO limbs at any time point. Radiographic osteoarthritis scores of TTA stifles (1.33 ± 0.49) were higher than TPLO stifles (0.67 ± 0.49) (p = .002) at 12 weeks postoperatively, but there was no difference between groups at 32 weeks postoperatively. Subsequent medial meniscal tears occurred in 6/10 TTA stifles, and 0/10 TPLO stifles at 12 weeks postoperatively and in 5/5 TTA stifles, and 1/5 TPLO stifles at 32 weeks postoperatively. Subsequent lateral meniscal tears occurred in 4/5 TTA stifles at 32 weeks postoperatively. Medial meniscal total gross pathology score was higher in TTA than TPLO stifles. TTA stifles had more articular cartilage damage when compared with TPLO stifles at 32 weeks postoperatively.

Conclusion

In this within‐dog experimental comparison, subsequent medial meniscal tears and cartilage injury was more prevalent following TTA when compared to TPLO.

Clinical significance

In an experimental model, TPLO protects the medial meniscus and articular cartilage better than TTA in stifles with complete cranial cruciate ligament deficiency.
The new face of English in the Kyrgyz Republic
Authors: Ramsey‐Tyson Jill Marie , Abdysheva Chynara
Published: April 2021

After the collapse of the USSR in 1991, during the transition from a command to a market economy, the attitude in the Kyrgyz Republic toward competencies in the English language shifted significantly. This article briefly illustrates the priorities for general secondary education during the Soviet period from 1922 until 1991. In 1991, necessary transitions were made by the newly developed Ministry of Education and Science of the Kyrgyz Republic to meet the needs of the emerging global economy. The main aim of this article is to highlight how the challenges in current and ongoing reforms are being discussed and addressed in public secondary schools.
Service Sector as an Engine of Growth: Empirical Analysis of Rwanda
Authors: Harelimana Jean Bosco , Mukarwego Beline
Published: April 2021

This research was econometrically analyzing Service sector as an engine of growth: empirical analysis of Rwanda from 1995 to 2020. The data were collected from BNR and were analyzed using Eviews7. The study used different opinions of economists concerning the Philips curve, by constructing short-term and long-term Philips curves in Rwanda by making some conclusions about the results at the end. We pay special attention in our research to the study of Phillips curve made by some economists of the last period the findings of this study indicate the following results: *, ** and *** indicates rejection of the null hypothesis of unit root at 10, 5% and 1% significant level, respectively. The SERV, FDI, LR, GR series are not stationary at level, and then we should test the Stationarity at the first difference. (*), (**) & (***) represent respectively 10%, 5% and 1% level of significance.The results give an indication for the existence of long-run relationship between SERV and growth. The max and trace values statistic strongly reject the null hypothesis for “none “cointegration vector in favor of at least one cointegrating vectors at the 1 percent significance level. The cointegrating vector representing the long run relationship between service and growth. The above is endogenous because its probability of chi-square 0.000025 is less than 5% level of significance and it answers the second hypothesis of a Variable that can help national bank of Rwanda to control money supply in the short-run.The P- value of chi-square which is 0.0791 and this is greater than 0, 05 level of significant therefore, there is no short run causality between variables running from SERV, FDI, LR and GR at 5% level of significant. The results revealed out from the above table; LSERV, LFDI, LLR and LGR does Granger Cause LSERV at 10% level of significant due to their probability of 0.0284 which is less than 0.10 level of significance but LSERV does not Granger Cause LSERV, LFDI, LLR and LGR at 10% level of significant due to their probability of 0.1224 which is greater than 0.10 level of significance.
Fully vertical gallium nitride trench MOSFETs fabricated with metal-free gate first process
Authors: Dannecker Kevin , Baringhaus Jens
Published: April 2021

We report on the fabrication and characterization of fully vertical gallium nitride trench metal oxide semiconductor field effect transistors on native substrates with a metal-free gate first process and a chlorine-free trench etching method. Trenches were fabricated using sulfur hexafluoride and argon plasma etching in combination with alkaline wet etching posttreatment to create crystal oriented trenches along the a- and m-planes. Low pressure chemical vapor deposited silicon dioxide was used as gate dielectric with a poly-silicon gate contact. The metal-free gate structure was separated by a silicon dioxide passivation from any subsequent metal containing contact formation processing steps. The breakdown robustness of the gate structure was examined in the forward direction and no temperature dependence was observed up to 450 K. Fabricated trench MOSFETs showed only small hysteresis effects during transfer characterization but a positive threshold shift was observed. An inversion channel carrier field effect mobility of ≈10 cm2/V s was extracted. The area specific on resistance was calculated to be 5.8 mΩ cm2. Results for devices with differently oriented trenches were comparable and no significant performance difference was observed.
Hollywood Movie Physics to Personalize Assessments
Authors: Miller Kurtz K.
Published: April 2021

Have you ever taught “head on the table” physics students and wondered how to increase engagement? If so, I have two stories for you! Davon and Cynthia—both case study students—struggled with traditional physics but showed great promise with developing personalized physics problems.
What Physics Students Can Learn from the Wright Brothers
Authors: Page Brian R.
Published: April 2021

The Wright brothers, Wilbur and Orville, are often depicted as lone geniuses, secretly assembling the first successful powered aircraft far from civilization at Kitty Hawk on the Outer Banks of North Carolina. There is a germ of truth in the popular story, but only a germ. The brothers succeeded while so many other experimenters failed not because they possessed superhuman intelligence, but rather because they approached the problem of powered flight as engineers, using a step-by-step methodology to tackle the many different challenges while at the same time carefully measuring and logging each test case. Still, this wasn’t enough, and the brothers resorted to fundamental research in achieving their final breakthrough. Their approach to success remains a model of scientific research and applied technology, and is applicable today in the physics laboratory.
Beyond the Magnetic Field of a Finite Wire: A Teaching Approach Using the Superposition Principle
Authors: García-Farieta Jorge Enrique , Márquez Alejandro Hurtado
Published: April 2021

The traditional lecture-based scheme of teaching physics has shown to be ineffective in several aspects. It results in a lack of motivation, with low impact on students, to address more complex physical systems than the ones presented in textbooks. The electromagnetics course is a clear example at junior and senior university-level education, in particular when the magnetic field concept is introduced.
Sap Is Clever? Sap Ascent for Undergraduates Investigated with an Artificial Tree
Authors: González-Cámara Sergio , Sanz-Alférez Soledad , Orús Maria-Isabel , Ares Jose-Ramón
Published: April 2021

Water is the essential component in living and its role is particularly important in plants. In fact, the crucial photosynthesis process involves a huge loss of sap by transpiration (around 99% from the total amount recovered from the soil through the plant roots) from the stomas on the leaves. Therefore, a question arises: How could trees raise the sap to heights up to 100 m? In this article we present a simple experimental setup that provides a direct visualization and quantification of the water ascent process against gravity. Moreover, the artificial tree offers analogies with “real” ones that will help undergraduate science students from different areas to investigate the influence of environmental and morphological parameters on the variety of physics phenomena underlying the ascension mechanism.
New column on justice issues in physics and physics education
Authors: Iyer Deepak , Wachowski Shannon
Published: April 2021

Physics and physics education are famous for their acronyms and buzzwords, so much so that at times it feels like we just speak in code words and abbreviations. Sometimes the ideas that these buzzwords represent stick around and other times they get lost in the shuffle of trends. Recently one often hears, for good reason, the words diversity, equity, and inclusion (DEI). And while physics has come a long way in the conversation surrounding DEI, and in addressing these ever-prevalent issues, there are also some worrying signs that the conversation might be stagnating or, worse, becoming co-opted in ways antithetical to the original intent. We believe that in order to institute real change, a critical and nuanced discussion surrounding DEI must become embedded in and central to physics and physics education.
Shepard scale produced and analyzed with mobile devices
Authors: Ludwig-Petsch Kim , Kuhn Jochen
Published: April 2021

Contributions in this column describe how smartphones and tablets can be used to analyze experimental data in physics experiments. This is possible in nearly all areas of physics—from classical mechanics, to thermodynamics, electrics, and radioactivity. While many examples already showed the analysis of acoustic experiments with mobile devices, no psychoacoustic phenomenon has been studied with the smartphone yet. Nevertheless, acoustic illusions are great starting points for an intrinsic motivation of learners. One great acoustic illusion, often found in science centers, is the so-called Shepard scale illusion. This paper shows how to use mobile devices to analyze and produce Shepard tones to get a deeper understanding of the acoustic concepts like tone, sound, pitch and frequency.
Using Math in Physics: Overview
Authors: Redish Edward F.
Published: April 2021

The key difference between math as math and math in science is that in science we blend our physical knowledge with our knowledge of math. This blending changes the way we put meaning to math and even the way we interpret mathematical equations. Learning to think about physics with math instead of just calculating involves a number of general scientific thinking skills that are often taken for granted (and rarely taught) in physics classes. In this paper, I give an overview of my analysis of these additional skills. I propose specific tools for helping students develop these skills in subsequent papers.