bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue Expander Followed by Autogenous Bone Graft Versus Autogenous Bone Graft Alone for Mandibular Reconstruction: Quantitative Assessment
Authors: Tawfik Bahaa Eldin Abdrabbo , El-Sayed Amany Khalifa , Mohamed Raafat Elghetany , Elsayed Shadia A. , Hosny Mostafa Mohamed
Published: August 2022

Background:

The use of a tissue expander in maxillofacial intraoral tissue reconstruction is a developing approach, which provide adequate tissue coverage and aesthetics.

Objectives:

The purpose of this study was to quantitatively compare the use of a soft tissue expander in conjunction with autogenous bone graft with bone graft alone for the repair of the mandible’s anterior region.

Methods:

The study comprised 24 patients with bone defects in the anterior mandibular region. Patients were divided into 2 groups at random. In group I, expander with bone graft was used, whereas in group II, bone graft was used alone. Volumetric measures of the grafted area was performed using CBCT, and cephalometric evaluations of the anteroposterior and vertical skeletal relationship, as well as the soft tissue profile were recoded. A comparison was made between the 2 groups 6 and 24 months after surgery with P≤ 0.05 considered significant.

Results:

The mean difference in grafted bone volume between the 2 groups was 1.95 cm3, indicating a significant difference between the 2 groups (P= 0.05) with superior group I results. The soft tissue profile of group I demonstrated a considerable improvement and stability of the lower lip, the labiomental sulcus, and the thickness of the soft tissue Pogonion compared with group II.

Conclusion:

The use of a tissue expander in conjunction with a bone graft resulted in a better soft tissue profile, making it a favored approach in maxillofacial reconstruction.
Comparative Safety of Sleeve Gastrectomy and Gastric Bypass up to 5 Years After Surgery in Patients With Medicaid
Authors: Howard Ryan , Yang Jie , Thumma Jyothi , Ehlers Anne , O’Neill Sean , Arterburn David , Ryan Andrew , Telem Dana , Dimick Justin B.
Published: August 2022

Objective:

Compare adverse outcomes up to 5 years after sleeve gastrectomy and gastric bypass in patients with Medicaid.

Background:

Sleeve gastrectomy is the most common bariatric operation among patients with Medicaid; however, its long-term safety in this population is unknown.

Methods:

Using Medicaid claims, we performed a retrospective cohort study of adult patients who underwent sleeve gastrectomy or gastric bypass from January 1, 2012, to December 31, 2018. Instrumental variables survival analysis was used to estimate the cumulative incidence and heterogeneity of outcomes up to 5 years after surgery.

Results:

Among 132,788 patients with Medicaid, 84,717 (63.8%) underwent sleeve gastrectomy and 48,071 (36.2%) underwent gastric bypass. A total of 69,225 (52.1%) patients were White, 33,833 (25.5%) were Black, and 29,730 (22.4%) were Hispanic. Compared with gastric bypass, sleeve gastrectomy was associated with a lower 5-year cumulative incidence of mortality (1.29% vs 2.15%), complications (11.5% vs 16.2%), hospitalization (43.7% vs 53.7%), emergency department (ED) use (61.6% vs 68.2%), and reoperation (18.5% vs 22.8%), but a higher cumulative incidence of revision (3.3% vs 2.0%). Compared with White patients, the magnitude of the difference between sleeve and bypass was smaller among Black patients for ED use [5-y adjusted hazard ratios: 1.01; 95% confidence interval (CI), 0.94–1.08 vs 0.94 (95% CI, 0.88–1.00), P<0.001] and Hispanic patients for reoperation [5-y adjusted hazard ratios: 0.95 (95% CI, 0.86–1.05) vs 0.76 (95% CI, 0.69–0.83), P<0.001].

Conclusions:

Among patients with Medicaid undergoing bariatric surgery, sleeve gastrectomy was associated with a lower risk of mortality, complications, hospitalization, ED use, and reoperations, but a higher risk of revision compared with gastric bypass. Although the difference between sleeve and bypass was generally similar among White, Black, and Hispanic patients, the magnitude of this difference was smaller among Black patients for ED use and Hispanic patients for reoperation.
Vagal paraganglioma extending to the brain: a case report with literature review
Authors: Kakamad Fahmi H. , Mohammed Shvan H. , Fatah Mariwan L. , Hattam Azad S. , Qaradakhy Aras J. , Abdullah Ari M. , Mustafa Umed M. , Naqar Sharo
Published: August 2022

Introduction:

Vagal paraganglioma (VP) is a rare tumor of the vagus nerve (VII). This study aims to present a rare case of VP extending to the brain.

Case report:

A 35-year-old woman presents with neck swelling for 1 year. On examination, there was an ill-defined hard mass involving the left side of the anterior neck, fixed in all directions. A neck ultrasound revealed an irregular mass attached to both carotid arteries. A computed tomography scan showed a large lobulated, intensely enhanced mass encasing left carotid carotid vessels. Total resection under general anesthesia was done. Histopathologic examination revealed VP.

Discussion:

VP is the rarest form of paraganglioma and accounts for <5% of all head and neck paragangliomas. The average age of diagnosis for these patients is reported to be 45 years. VP poses a therapeutic challenge due to its anatomic location, and surgery is often associated with a significant rate of postoperative morbidities, particularly loss or impaired vagus nerve function.

Conclusion:

VP is a rare tumor of the head and neck, even rarer in young adults. A standard management approach is absent for these cases.
Cellular schwannoma of the posterior tongue: a rare case report with a literature review
Authors: Hammood Zuhair D. , Baba Hiwa O. , Saeed Yadgar A. , Salih Abdulwahid M. , Noori Savo Sh. , Abdullah Hiwa O. , Tahir Soran H. , Kakamad Fahmi H.
Published: August 2022

Introduction:

Schwannoma is a gradually growing encapsulated benign tumor arising from the Schwan cells of the peripheral nerve sheath. This study aims to report a rare case of tongue cellular schwannoma.

Case presentation:

A 15-year-old boy presented with a swelling of the posterior part of the tongue that had started 2 years prior. On examination, a large mass was seen in the posterior part of the tongue. It was smooth, mobile, and nontender on palpation. A contrast computed tomography scan of the neck revealed an irregular, ill-defined, thick-walled cystic lesion. Magnetic resonance imaging demonstrated a well-circumscribed, enhancing mass measuring about 5×4.56×4.59 cm and causing compression upon the oropharyngeal airway. Histopathologic examination revealed a cellular schwannoma.

Discussion:

Histologically, all schwannoma tumors are encapsulated. Under the capsule, there are 2 specific patterns associated together, but they can be easily differentiated from each other. The first one is made up of firmly aggregated Schwan cells arranged in rows with palisade and enlarged nuclei which are known as Antoni type-A. The second one is the Antoni type-B that consists of weakly packed Schwann cells.

Conclusion:

Tongue schwannoma is regarded as a solitary encapsulated benign tumor that may cause complications like difficulty in phonation. The primary treatment modality usually is transoral excision.
Variations on Ogden’s model: close and distant relatives
Authors: Ehret A. E. , Stracuzzi A.
Published: August 2022

The power law in terms of stretch, the truncated series representation and the Valanis–Landel hypothesis are distinguished features of Ogden’s strain-energy density function. While they represent a set of special constitutive choices, they have also been shown recently to allow a particular molecular statistical interpretation of the model, where each of these ingredients can be associated with a step in the development of the strain-energy density of the polymer network from the statistical mechanics of long-chain molecules. The schematic of this perspective brings us into a position to vary these steps individually. By this means, Ogden’s theory can be embedded in a certain family of models within the large class of isotropic hyperelastic materials, whose members can be identified as close and distant ‘relatives’.

This article is part of the theme issue ‘The Ogden model of rubber mechanics: Fifty years of impact on nonlinear elasticity’.
Bifurcation analysis of residually stressed neo-Hookean and Ogden electroelastic tubes
Authors: Melnikov Andrey , Merodio Jose , Bustamante Roger , Dorfmann Luis
Published: August 2022

The conditions for bifurcation of a circular cylindrical tube of elastic material subjected to combined axial loading and internal pressure are well known and are frequently used as a reference in related works. The present paper takes the theory further by considering a residually stressed circular cylindrical dielectric tube subjected to a combination of internal or external pressure, axial load and radial electric field. We examine axisymmetric incremental deformations and increments in the electric displacement superimposed on a known finitely deformed and residually stressed configuration in the presence of an electric field. The governing equations and boundary conditions are first obtained in general form and then specialized for the neo-Hookean and Ogden electroelastic models. The system of equations is solved numerically for different values of charge density and radial and circumferential residual stresses, and the results are compared with the purely elastic case. The bifurcation curves are presented as the azimuthal stretch on the inner surface versus the axial stretch together with the corresponding zero pressure curves.

This article is part of the theme issue ‘The Ogden model of rubber mechanics: Fifty years of impact on nonlinear elasticity’.
An adaptable, monobody-based biosensor scaffold with FRET output
Authors: Presti Maria F. , Ha Jeung-Hoi , Loh Stewart N.
Published: August 2022

Protein-based fluorescent biosensors are powerful tools for analyte recognition in vitro and in cells. Numerous proteinaceous binding scaffolds have been developed that recognize ligands with affinity and specificity comparable to those of conventional antibodies, but are smaller, readily overexpressed, and more amenable to engineering. Like antibodies, these binding domains are useful as recognition modules in protein switches and biosensors, but they are not capable of reporting on the binding event by themselves. Here, we engineer a small binding scaffold—a consensus-designed fibronectin 3 monobody—such that it undergoes a conformational change upon ligand binding. This change is detected by Förster resonance energy transfer using chemical dyes or cyan and yellow fluorescent proteins as donor/acceptor groups. By grafting substrate recognition residues from different monobodies onto this scaffold, we create fluorescent biosensors for c-Abl Src homology 2 (SH2) domain, WD40-repeat protein 5 (WDR5), small ubiquitin-like modifier-1 (SUMO), and h-Ras. The biosensors bind their cognate ligands reversibly, with affinities consistent with those of the parent monobodies, and with half times of seconds to minutes. This design serves as generalizable platform for creating a genetically-encoded, ratiometric biosensors by swapping binding residues from known monobodies, with minimal modification.
CD8+T-cell memory induced by successive SARS-CoV-2 mRNA vaccinations is characterized by clonal replacement
Authors: Aoki Hiroyasu , Kitabatake Masahiro , Abe Haruka , Xu Peng , Tsunoda Mikiya , Shichino Shigeyuki , Hara Atsushi , Ouji-Sageshima Noriko , Motozono Chihiro , Ito Toshihiro , Matsushima Kouji , Ueha Satoshi
Published: August 2022

mRNA vaccines against the Spike glycoprotein of severe acute respiratory syndrome type 2 coronavirus (SARS-CoV-2) elicit strong T-cell responses. However, it’s not known whether T cell clonotypes responding to the first vaccination repeatedly expand with booster vaccinations. Here, we temporally tracked the CD8+T-cell repertoire in individuals who received three shots of the BNT162b2 mRNA vaccine. By analyzing the kinetic profile of CD8+T-cell clonotypes responding to the first, second, or third shot, we demonstrated that newly expanded clonotypes elicited by the second shot replaced many of those that responded to the first shot. Although these 2ndresponder clonotypes expanded after the third shot, their clonal diversity was skewed, and they were partially replaced by newly elicited the 3rdresponders. Furthermore, this replacement of vaccine-responding clonotypes occurred within the same Spike epitope. These results suggest that CD8+T-cell memory induced by repetitive mRNA vaccination is characterized by the emergence of new dominant clones.
Wounding promotes root regeneration through a cell wall integrity sensor, the receptor kinase FERONIA
Authors: Xie Qijun , Chen Weijun , Xu Fan , Ouyang Shiling , Chen Jia , Wang Xuening , Wang Yirong , Mao Longfer , Zhou Wenkun , Yu Feng
Published: August 2022

Wounding caused by various stresses is the initial event of plant regeneration. However, the mechanisms underlying the early wounding responses to promote plant regeneration remain largely unknown. Here, we report that the receptor kinase FERONIA (FER) interacts with Topless/Topless-related proteins (TPL/TPRs) to regulate the expression of regeneration-related genes to modulate root tip regeneration. One ligand of FER, rapid alkalinization factor 33 (RALF33), is stimulated by wounding and functions together with FER to promote regeneration. Single-cell sequencing data showed that the low-differentiation cell types in the stele may account for the enhanced regeneration ability in the fer mutant, especially in the columella and quiescent center (QC). Further interaction assays and analysis of the gene expression patterns in low-differentiation cell types confirmed that FER interacts with TPL/TPRs to regulate the expression of downstream regeneration-related genes. One of their downstream targets, an essential transcription factor (TF) in root regeneration, ERF115, acts downstream of FER-TPL/TPRs to control regeneration. Our results suggested a signaling pathway between the early wounding response and regeneration processes in roots.

One-sentence summary

RALF33-FER serves as an early signaling module between wounding and regeneration by functioning with TPL/TPRs in roots.
Chemotaxonomy supports morphology in the identification of Vepris hemp (Rutaceae) a new species of Critically Endangered deciduous forest shrub from Usambara Mts, Tanzania
Authors: Langat Moses , Hemp Andreas , Cheek Martin
Published: August 2022

Hemp 7152, a sterile herbarium plot voucher of a shrub from a rare type of deciduous forest in the Usambara Mts, Tanzania was tentatively identified using morphology as a new species of Vepris (Rutaceae). To gain further support for its placement its chemistry was investigated. The compounds isolated from Hemp 7152 were four quinoline alkaloids, kokusaginine (1), N-methylplaty-desminium ion (9), ribalinium ion (10), and isoplatydesmine (11), and seven acridone alkaloids, arborinine (2) 1,2,3-trimethoxy-N-methylacridone (3), 1,2,3,5-tetramethoxy-N-methylacridone (4), 1,3-dimethoxy-N-methylacridone (5) and toddaliopsis A (6), evoxanthine (7) and tecleanthine (8). In addition, lupeol and ferulic acid were isolated from this plant. The combination of quinoline and acridone alkaloids is restricted to the Rutaceae family, confirming beyond reasonable doubt the placement of this material in the Rutaceae. Within Rutaceae in tropical Africa, only the genus Vepris is unarmed, with trifoliolate leaves. Using an identification key, and herbarium specimen matching, Hemp 7152 was morphologically placed as close to Vepris uguenensis, sharing xerophytic characters unusual in the genus. The species are geographically close, occurring in adjoining mountains in northern Tanzania. However, Vepris uguenensis contains 13 alkaloids which are not present in Hemp 7152, nor in any other species of Vepris that has been studied, supporting species recognition for Hemp 7152 which is formally named as Vepris hemp, morphologically characterised, illustrated and assessed as Critically Endangered using the IUCN 2012 standard. The new species appears restricted to an almost extinct type of deciduous forest, characterised in this paper.
Parallel CRISPR-Cas9 screens reveal mechanisms of PLIN2 and lipid droplet regulation
Authors: Roberts Melissa A. , Deol Kirandeep K. , Lange Mike , Leto Dara E. , Mathiowetz Alyssa J. , Stevenson Julian , Hashemi Sayed Hadi , Morgens David W. , Easter Emilee , Heydari Kartoosh , Nalls Mike A. , Bassik Michael C. , Kampmann Martin , Kopito Ron R. , Faghri Faraz , Olzmann James A.
Published: August 2022

Lipid droplets (LDs) are lipid storage organelles that consist of a central core of neutral lipids surrounded by a phospholipid monolayer decorated with a unique set of integral and peripheral proteins. Invariably, at least one member of the perilipin family of proteins (PLIN1-5) associates with LDs in all cell types. Despite key roles of PLIN2 in governing hepatic lipid metabolism, the mechanisms that regulate PLIN2 levels remain incompletely understood. Here, we develop a set of genome-edited PLIN2 reporter cell lines that facilitate the analysis of genes that regulate PLIN2 and LD abundance. Leveraging these reporter cells in a series of CRISPR-Cas9 loss-of-function screens, we generate a comprehensive inventory of genes that influence PLIN2 levels under different metabolic conditions. Moreover, we uncouple their effects on PLIN2 expression and post-translational stability. Identified genetic modifiers include canonical genes that control LD metabolism (e.g., ACSL3, DGAT2, PNPLA2, ABHD5) as well as genes with less characterized roles in PLIN2 and LD regulation such as ubiquitination machinery (e.g., MARCH6, UBE2J2), transcription regulators (e.g., HNF4A, HDAC3), mitochondrial pathways (e.g., electron transport chain and mitochondrial fatty acid synthesis), and others. These CRISPR screens, and several published screens that focus on different aspects of lipid metabolism, provide the foundation for CRISPRlipid (http://crisprlipid.org), a versatile, online data commons for lipid-related functional genomics data. Together, our study uncovers new mechanisms of PLIN2 regulation and provides an extensive, phenotype-rich resource for the exploration of LD biology and lipid metabolism.
Short-term high fat diet feeding of mice suppresses catecholamine-stimulated Ca2+ signalling in hepatocytes and intact liver
Authors: Brumer Robert P. , Corrêa-Velloso Juliana C. , Thomas Samantha J. , Sandiford Oleta A. , Thomas Andrew P. , Bartlett Paula J.
Published: August 2022

Excess consumption of carbohydrates, fat, and calories leads to non-alcoholic fatty liver disease (NAFLD) and hepatic insulin resistance; major factors in the pathogenesis of type II diabetes. Hormones and catecholamines acting through G-protein coupled receptors (GPCRs) linked to phospholipase C (PLC) and increases in cytosolic Ca2+ ([Ca2+]c) regulate many metabolic functions of the liver. In the intact liver, catabolic hormones such as glucagon, catecholamines and vasopressin integrate and synergize to regulate the frequency and extent to which [Ca2+]c waves propagate across hepatic lobules to control metabolism. Dysregulation of hepatic Ca2+ homeostasis has been implicated in the development of metabolic disease, but changes in hepatic GPCR-dependent Ca2+ signalling have been largely unexplored in this context. We show that short-term, 1-week, high fat diet (HFD) feeding of mice attenuates norepinephrine-stimulated Ca2+ signalling, reducing the number of cells responding and suppressing the frequency of [Ca2+]c oscillations in both isolated hepatocytes and intact liver. The 1-week HFD feeding paradigm did not change basal Ca2+ homeostasis; endoplasmic reticulum Ca2+ load, store-operated Ca2+ entry and plasma membrane Ca2+ pump activity were unchanged compared to low fat diet (LFD) fed controls. However, norepinephrine-induced IP3 production was significantly reduced after HFD feeding, demonstrating an effect of HFD on receptor-stimulated PLC activity. Thus, we have identified a lesion in the PLC signalling pathway induced by short-term HFD feeding, which interferes with hormonal Ca2+ signalling in isolated hepatocytes and the intact liver. These early events may drive adaptive changes in signalling, which lead to pathological consequences in fatty liver disease.

Key points summary

Non-alcoholic fatty liver disease (NAFLD) is a growing epidemic.

In healthy liver, the counteracting effects of catabolic and anabolic hormones regulate metabolism and energy storage as fat. Hormones and catecholamines promote catabolic metabolism via increases in cytosolic Ca2+ ([Ca2+]c).

We show that 1 week high fat diet (HFD) feeding of mice attenuated the Ca2+ signals induced by physiological concentrations of norepinephrine. Specifically, HFD suppressed the normal pattern of periodic [Ca2+]c oscillations in isolated hepatocytes and disrupted the propagation of intralobular [Ca2+]c waves in the intact perfused liver.

Short-term HFD inhibited norepinephrine-induced inositol 1,4,5-trisphosphate (IP3) generation, but did not change basal endoplasmic reticulum Ca2+ load or plasma membrane Ca2+ fluxes.

We propose that impaired Ca2+ signalling plays a key role in the earliest phases of the etiology of NAFLD, and is responsible for many of the ensuing metabolic and related dysfunctional outcomes at the cellular and whole tissue level.
Five decades of data yield no support for adaptive biasing of offspring sex ratio in wild baboons (Papio cynocephalus)
Authors: Zipple Matthew N , Archie Elizabeth A , Tung Jenny , Mututua Raphael S. , Warutere J. Kinyua , Siodi I. Long’ida , Altmann Jeanne , Alberts Susan C
Published: August 2022

Over the past 50 years, a wealth of testable, often conflicting, hypotheses have been generated about the evolution of offspring sex ratio manipulation by mothers. Several of these hypotheses have received support in studies of invertebrates and some vertebrate taxa. However, their success in explaining sex ratios in mammalian taxa, and especially in primates, has been mixed. Here, we assess the predictions of four different hypotheses about the evolution of biased offspring sex ratios in the well-studied baboons of the Amboseli basin in Kenya: the Trivers-Willard, female rank enhancement, local resource competition, and local resource enhancement hypotheses. Using the largest sample size ever analyzed in a primate population (n = 1372 offspring), we test the predictions of each hypothesis. Overall, we find no support for adaptive biasing of sex ratios. Offspring sex is not consistently related to maternal dominance rank or biased towards the dispersing sex, nor it is predicted by group size, population growth rates, or their interaction with maternal rank. Because our sample size confers power to detect even subtle biases in sex ratio, including modulation by environmental heterogeneity, these results suggest that adaptive biasing of offspring sex does not occur in this population.
Glisson’s capsule structure and function is altered in cirrhotic patients irrespective of etiology
Authors: Llewellyn Jessica , Fede Caterina , Loneker Abigail E. , Friday Chet S. , Hast Michael W. , Theise Neil D. , Furth Emma E. , Guido Maria , Stecco Carla , Wells Rebecca G.
Published: August 2022

Background and Aims

Glisson’s capsule is the interstitial connective tissue that surrounds the liver. As part of its normal physiology, it withstands significant daily changes in liver size. The pathophysiology of the capsule in disease is not well understood. The aim of this study was to characterize the changes in capsule matrix, cellular composition, and mechanical properties that occur in liver disease and to determine whether these correlate with disease severity or etiology.

Methods

10 control, 6 steatotic, 7 moderately fibrotic and 37 cirrhotic patient samples were collected from autopsies, intraoperative biopsies and liver explants. Matrix proteins and cell markers were assessed by staining and second harmonic generation imaging. Mechanical tensile testing was performed on a test frame.

Results

Capsule thickness was significantly increased in cirrhotic samples compared to normal controls irrespective of disease etiology (69.62 ± 9.99 and 171.269 ± 16.65 µm respectively), whereas steatosis and moderate fibrosis had no effect on thickness (62.15 ± 4.97 µm). Changes in cirrhosis included an increase in cell number (fibroblasts, vascular cells, infiltrating immune cells and biliary epithelial cells). Key matrix components (collagens 1 and 3, hyaluronan, versican and elastin) were all deposited in the lower capsule although only the relative amounts per area of hyaluronan and versican were increased. Organizational features including crimping and alignment of collagen fibers were also altered in cirrhosis. Unexpectedly, capsules from cirrhotic livers had decreased resistance to loading in comparison to controls.

Conclusions

The liver capsule, like the parenchyma, is an active site of disease, demonstrating changes in matrix and cell composition as well as mechanical properties.

Lay summary

We assessed the changes in composition and response to stretching of the liver outer sheath, the capsule, in human liver disease. We find an increase in key structural components and numbers of cells as well as a change in matrix organization of the capsule in the later stages of disease. This allows the diseased capsule to stretch more under any given force, suggesting it is less stiff than healthy tissue.

Graphical abstract

Highlights

The capsule is an active site of disease: thickness and cellularity increase markedly in cirrhosis

Extracellular matrix composition and organization change in cirrhosis

The cirrhotic capsule stretches more and is less stiff
Comparative membrane lipidomics of hepatocellular carcinoma cells reveals diacylglycerol and ceramide as key regulators of Wnt/β-catenin signaling and tumor growth
Authors: Azbazdar Yagmur , Demirci Yeliz , Heger Guillaume , Karabicici Mustafa , Ozhan Gunes
Published: August 2022

Hepatocellular carcinoma (HCC) is largely associated with aberrant activation of Wnt/β-catenin signaling. Nevertheless, how membrane lipid composition is altered in HCC cells with abnormal Wnt signaling remains elusive. Here, by exploiting comprehensive lipidome profiling, we unravel membrane lipid composition of six different HCC cell lines with mutations in components of Wnt/β-catenin signaling, leading to differences in their endogenous signaling activity. Among the differentially regulated lipids are diacylglycerol (DAG) and ceramide, which were downregulated at the membrane of HCC cells after Wnt3a stimulation. DAG and ceramide enhanced Wnt/β-catenin signaling in SNU475 and HepG2 cells. In contrast, depletion of DAG and ceramide suppressed Wnt/β-catenin signaling and significantly impeded the proliferation, tumor growth and in vivo migration capacity of SNU475 and HepG2 cells. This study, by pioneering plasma membrane lipidome profiling in HCC cells, exhibits the remarkable potential of lipids to correct dysregulated signaling pathways in cancer and stop abnormal tumor growth.
Lysosomal cystine export regulates mTORC1 signaling to guide kidney epithelial cell fate specialization
Authors: Berquez Marine , Chen Zhiyong , Festa Beatrice Paola , Krohn Patrick , Keller Svenja Aline , Parolo Silvia , Korzinkin Mikhail , Gaponova Anna , Laczko Endre , Domenici Enrico , Devuyst Olivier , Luciani Alessandro
Published: August 2022

Differentiation is critical for cell fate decisions, but the signals involved remain unclear. The kidney proximal tubule (PT) cells reabsorb disulphide-rich proteins through endocytosis, generating cystine via lysosomal proteolysis. Here we report that defective cystine mobilization from lysosomes through cystinosin (CTNS), which is mutated in cystinosis, diverts PT cells towards growth and proliferation, disrupting their functions. Mechanistically, cystine storage stimulates Ragulator-Rag GTPase-dependent recruitment of mechanistic target of rapamycin complex 1 (mTORC1) and its constitutive activation. Re-introduction of CTNS restores nutrient-dependent regulation of mTORC1 in knockout cells, whereas cell-permeant analogues of L-cystine, accumulating within lysosomes, render wild-type cells resistant to nutrient withdrawal. Therapeutic mTORC1 inhibition corrects lysosome and differentiation downstream of cystine storage, and phenotypes in a zebrafish model of cystinosis. Thus, cystine serves as a lysosomal signal that tailors mTORC1 and metabolism to direct epithelial cell fate decisions. These results identify mechanisms and therapeutic targets for dysregulated homeostasis in cystinosis.
Variation in density, immune gene suppression, and co-infection outcomes among strains of the aphid endosymbiont Regiella insecticola
Authors: Goldstein Elliott B. , de Anda Acosta Yazmin , Henry Lee M. , Parker Benjamin J.
Published: August 2022

Abstract

Many insects harbor heritable beneficial microbes that influence host phenotypes. Across systems, divergent symbiont strains have been shown to establish at different densities within hosts. This genetic variation is important evolutionarily because within-host density has been linked to the costs and benefits of the symbiosis for both partners. Studying the factors shaping within-host density is therefore important to our broader understanding of host-microbe coevolution. Here we focused on different strains of Regiella insecticola, a facultative symbiont of aphids. We first demonstrated that different strains of Regiella consistently establish in pea aphids at drastically different densities. We then found that variation in density is correlated with the expression levels of two key insect immune system genes (phenoloxidase and hemocytin), with immune gene suppression correlating with higher Regiella density. We then performed an experiment where we established co-infections of a higher- and lower-density Regiella strain, and we showed that the higher-density strain is better able to persist in co-infections than the lower-density strain. Together, our results point to a potential mechanism for strain-level variation in symbiont density in this system, and further suggest that symbiont fitness may be increased by establishing at higher density within hosts. Our work highlights the importance of within-host dynamics shaping symbiont evolution.
Characterization of factors that underlie transcriptional silencing inC. elegansoocytes
Authors: Belew Mezmur D. , Chien Emilie , Michael W. Matthew
Published: August 2022

Abstract/Summary

While it has been appreciated for decades that prophase-arrested oocytes are transcriptionally silenced on a global level, the molecular pathways that promote silencing have remained elusive. Previous work inC. eleganshas shown that both topoisomerase II (TOP-2) and condensin II collaborate with the H3K9me heterochromatin pathway to silence gene expression in the germline during L1 starvation, and that the PIE-1 protein silences the genome in the P-lineage of early embryos. Here, we show that all three of these silencing systems, TOP-2/condensin II, H3K9me, and PIE-1, are required for transcriptional repression in oocytes. We find that H3K9me3 marks increase dramatically on chromatin during silencing, and that silencing is under cell cycle control. We also find that PIE-1 localizes to the nucleolus just prior to silencing, and that nucleolar dissolution during silencing is dependent on TOP-2/condensin II. Our data identify both the molecular components and the trigger for genome silencing in oocytes and establish a link between PIE-1 nucleolar residency and its ability to repress transcription.
Genomic and phenotypic evolution of nematode-infecting microsporidia
Authors: Wadi Lina , El Jarkass Hala Tamim , Tran Tuan D. , Islah Nizar , Luallen Robert J. , Reinke Aaron W.
Published: August 2022

Microsporidia are a large phylum of intracellular parasites that can infect most types of animals. Species in theNematocidagenus can infect nematodes includingCaenorhabditis elegans, which has become an important model to study mechanisms of microsporidia infection. To understand the genomic properties and evolution of nematode-infecting microsporidia, we sequenced the genomes of nine species of microsporidia, including two genera,EnteropsectraandPancytospora,without any previously sequenced genomes. Core cellular processes, including metabolic pathways, are mostly conserved across genera of nematode-infecting microsporidia. Each species encodes unique proteins belonging to large gene families that are likely used to interact with host cells. Most strikingly, we observed one such family, NemLGF1, is present in bothNematocidaandPancytosporaspecies, suggesting horizontal gene transfer between species from different genera. To understand howNematocidaphenotypic traits evolved, we measured the host range, tissue specificity, spore size, and polar tube length of several species in the genus. Our phylogenetic analysis shows thatNematocidais composed of two groups of species with distinct traits and that species with longer polar tubes infect multiple tissues. Together, our work details both genomic and trait evolution between related microsporidia species and provides a useful resource for further understanding microsporidia evolution and infection mechanisms.

Author Summary

Microsporidia are microbial parasites that can infect many animals. Nematodes have become a useful system to study microsporidia as these animals are commonly infected by microsporidia and these infections can be easily studied in a laboratory environment. To better understand how microsporidia evolve and change their properties as they infect different hosts, we sequenced the genomes of nine microsporidia species which infect nematodes. We found that metabolic pathways were mostly conserved between different clades of these species. Surprisingly, we found a family of proteins predicted to facilitate host interactions that is present in two distinct genera, suggesting that these genes were transferred between microsporidia species. We also determined the hosts and tissues that these microsporidia can infect as well as morphological properties of the microsporidia. We show that these properties are quite variable in related microsporidia species. Our results provide insight into the evolution of microsporidia and also provide a resource for studying microsporidia infections in nematodes.
Promyelocytic Leukemia Protein regulates Angiogenesis and Epithelial-Mesenchymal Transition to limit metastasis in MDA-MB-231 breast cancer cells
Authors: Vogiatzoglou Amalia P , Spanou Syrago , Sachini Nikoleta , Drakos Elias , Nikolaou Christoforos , Makatounakis Takis , Kretsovali Androniki , Papamatheakis Joseph
Published: August 2022

Promyelocytic Leukemia Protein (PML) is the core protein of nuclear bodies (NBs) that regulate a large number of cellular processes, including, context dependent, tumor –suppressor and pro-oncogenic effects. PML knockdown (KD) in breast cancer lines MDA-MB-231, but not MCF7, cells showed higher cell proliferation, increased migration properties and prolonged stem cell –like survival in line with gene enrichment results from RNA sequencing analysis. MDA-MB-231 PML KD cells showed an increase of hypoxic and mesenchymal characteristics manifested by higher HIF1a and the EMT-TWIST2 protein levels respectively. Mechanistically, PML loss caused an increase of HIF1a and TWIST2 RNA levels. Interestingly, TWIST2 binds to PML. Moreover, PML directly opposed the action of HIF1a and TWIST2 on VEGFa and CD24 reporters, respectively. Tumor xenografts of MDA-MB-231 PML KD cells showed a higher micro vessel content, grew faster and had higher metastatic ability with a preference for lung. Thus, PML opposes the aggressive cancer phenotype by multiple mechanisms that antagonize the HIF-hypoxia-angiogenic and EMT axis.
Addressing the challenges of symbiont-mediated RNAi in aphids
Authors: Elston Katherine M. , Maeda Gerald P. , Perreau Julie , Barrick Jeffrey E.
Published: August 2022

Because aphids are global agricultural pests and models for bacterial endosymbiosis, there is a need for reliable methods to study and control their gene function. However, current methods available for aphid gene knockout and knockdown of gene expression are often unreliable and time consuming. Techniques like CRISPR-Cas genome editing can take several months to achieve a single gene knockout because they rely on aphids going through a cycle of sexual reproduction, and aphids often lack strong, consistent levels of knockdown when fed or injected with molecules that induce an RNA interference (RNAi) response. In the hopes of addressing these challenges, we attempted to adapt a new method called symbiont-mediated RNAi (smRNAi) for use in aphids. smRNAi involves engineering a bacterial symbiont of the insect to continuously supply dsRNA inside the insect body. This approach has been successful in thrips, kissing bugs, and honeybees. We engineered the laboratory E. coli strain HT115 and the native aphid symbiont S. symbiotica CWBI-2.3T to produce dsRNA inside the gut of the pea aphid (Acyrthosiphon pisum) targeting salivary effector protein (C002) or ecdysone receptor genes. For C002 assays, we also tested co-knockdown with an aphid nuclease (Nuc1) to reduce RNA degradation. However, we found that smRNAi was not a reliable method for aphid gene knockdown under our conditions. We were unable to consistently achieve the expected phenotypic changes with either target. However, we did see indications that elements of the RNAi pathway were modestly upregulated, and expression of some targeted genes appeared to be somewhat reduced in some trials. We conclude with a discussion of the possible avenues through which smRNAi, and aphid RNAi in general, could be improved in the future.
Clonally resolved single-cell multi-omics identifies routes of cellular differentiation in acute myeloid leukemia
Authors: Beneyto-Calabuig Sergi , Ludwig Anne Kathrin , Kniffka Jonas-Alexander , Szu-Tu Chelsea , Rohde Christian , Antes Magdalena , Waclawiczek Alexander , Gräßle Sarah , Pervan Philip , Janssen Maike , Landry Jonathan J. M. , Benes Vladimir , Jauch Anna , Brough Michaela , Bauer Marcus , Besenbeck Birgit , Felden Julia , Bäumer Sebastian , Hundemer Michael , Sauer Tim , Pabst Caroline , Wickenhauser Claudia , Angenendt Linus , Schliemann Christoph , Trumpp Andreas , Haas Simon , Scherer Michael , Raffel Simon , Müller-Tidow Carsten , Velten Lars
Published: August 2022

Inter-patient variability and the similarity of healthy and leukemic stem cells have impeded the characterization of leukemic stem cells (LSCs) in acute myeloid leukemia (AML), and their differentiation landscape. Here, we introduce CloneTracer, a novel method that adds clonal resolution to single-cell RNA-seq datasets. Applied to samples from 19 AML patients, CloneTracer revealed routes of leukemic differentiation. While residual healthy cells dominated the dormant stem cell compartment, active leukemic stem cells resembled their healthy counterpart and retained erythroid capacity. By contrast, downstream myeloid progenitors were highly aberrant and constituted the disease-defining compartment: Their gene expression and differentiation state determined both chemotherapy response and the leukemia’s ability to differentiate to transcriptomically normal monocytes. Finally, we demonstrated the potential of CloneTracer to identify surface markers mis-regulated specifically in leukemic cells by intra-patient comparisons. Taken together, CloneTracer revealed a differentiation landscape that mimics its healthy counterpart and determines biology and therapy response in AML.
Positive addiction recovery therapy: a pilot study
Authors: Ogilvie Lisa , Carson Jerome
Published: August 2022

Purpose

The purpose of this study is to evaluate a new programme of work designed to improve the recovery and well-being of people in early addiction recovery. The programme, known as positive addiction recovery therapy (PART), is attentive to the recovery process through the G-CHIME (growth, connectedness, hope, identity, meaning in life and empowerment) model of addiction recovery. It also uses the values in action character strengths and includes a set of relapse prevention techniques.

Design/methodology/approach

An experimental design using repeated measures has been adopted. Measures for recovery capital, well-being and level of flourishing were selected and pre- and post-data collected. Primary data analysis was conducted using the non-parametric Wilcoxon signed-rank test. Participants (n= 30) were required to be in early addiction recovery, classified as having been abstinent for between three and six months.

Findings

The results showed a statistically significant improvement in participant well-being. This was also true for recovery capital and flourishing. Whilst a meaningful increase was seen in all measures, exploratory analysis found females responded better to the PART programme.

Practical implications

This study emphasises the importance of adopting a holistic therapeutic approach, one that considers multifaceted components of recovery such as those outlined in the G-CHIME model.

Originality/value

This study evaluates a new programme of work designed to improve the recovery outcome and mental well-being of people who are in early addiction recovery.
Ground effect on the aerodynamics of a flapping wing in forward flight: an experimental study
Authors: Arasteh Mostafa , Azargoon Yegane , Djavareshkian M.H.
Published: August 2022

Purpose

Ground effect is one of the important factors in the enhancement of wing aerodynamic performance. This study aims to investigate the aerodynamic forces and performance of a flapping wing with the bending deflection angel under the ground effect.

Design/methodology/approach

In this study, the wing and flapping mechanism were designed and manufactured based on the seagull flight and then assembled. It is worth noting that this mechanism is capable of wing bending in the upstroke flight as big birds. Finally, the model was examined at bending deflection angles of 0° and 107° and different distances from the surface, flapping frequencies and velocities in forward flight in a wind tunnel.

Findings

The results revealed that the aerodynamic performance of flapping wings in forward flight improved due to the ground effect. The effect of the bending deflection mechanism on lift generation was escalated when the flapping wing was close to the surface, where the maximum power loading occurred.

Practical implications

Flapping wings have many different applications, such as maintenance, traffic control, pollution monitoring, meteorology and high-risk operations. Unlike fixed-wing micro aerial vehicles, flapping wings are capable of operating in very-low Reynolds-number flow regimes. On the other hand, ground effect poses positive impacts on the provision of aerodynamic forces in the take-off process.

Originality/value

Bending deflection in the flapping motion and ground effect are two influential factors in the enhancement of the aerodynamic performance of flapping wings. The combined effects of these two factors have not been studied yet, which is addressed in this study.
Is newer better? Evaluating the suitability of nighttime luminosity in proxying poverty in Africa
Authors: Hamman Nicolene , Phiri Andrew
Published: August 2022

Purpose

The purpose of the study is to evaluate whether nighttime luminosity sourced from the Defense Meteorological Satellite Program-Operational Linescan System satellite sensors is a suitable proxy for measuring poverty in Africa.

Design/methodology/approach

Our study performs wavelet coherence analysis to investigate the time-frequency synchronization between the nightlight data and “income-to-wealth” ratio for 39 African countries between 1992 and 2012.

Findings

All-in-all, the authors find that approximately a third of African countries produce positive synchronizations between nighttime data and “income-to-wealth” ratio and hence conclude that most African countries are not at liberty to use nighttime data to proxy conventional poverty statistics.

Originality/value

In differing from previous studies, the authors examine the suitability of nightlight intensity as a proxy of poverty for individual African countries using much more rigorous analysis.
The corporate governance-diversification link: exploring the heterogeneity of family firms
Authors: Galavotti Ilaria , D'Este Carlotta
Published: August 2022

Purpose

Building on behavioral agency theory, the authors explore the role played by corporate governance characteristics as drivers of the diversification strategies of family firms. Specifically, this study aims to investigate the effects of board size and board gender diversity on the likelihood that family firms will execute a diversifying acquisition vis-à-vis a related acquisition. Furthermore, the authors investigate the contingency effects played by foreign directorship and the firm’s listing status.

Design/methodology/approach

The hypotheses are tested on an original sample of 213 cross-border acquisitions executed by Italian family firms between 2008 and 2021.

Findings

The findings suggest that both large board sizes and greater gender diversity positively affect the diversification of family firms. While the presence of foreign directors magnifies the positive effect of board size, gender diversity discourages diversification in the case of listed firms.

Originality/value

The originality of this study is twofold. First, while prior literature has mostly focused on the family vs nonfamily dichotomy, this paper contributes to an emergent line of research investigating the heterogeneity among family firms’ corporate strategy decisions. Second, by exploring the corporate governance-diversification link in the context of family business, the authors answer to recent calls that diversification by family firms deserves further investigation in light of its highly controversial nature in terms of socioemotional wealth implications and potential mismatch among multiple objectives.