bluuebunny/crossref_metadata_2025 huggingface dataset:
Grading Pancreatic Neuroendocrine Tumors Via Endoscopic Ultrasound-guided Fine Needle Aspiration
Authors: Javed Ammar A. , Pulvirenti Alessandra , Razi Samrah , Zheng Jian , Michelakos Theodoros , Sekigami Yurie , Thompson Elizabeth , Klimstra David S. , Deshpande Vikram , Singhi Aatur D. , Weiss Matthew J. , Wolfgang Christopher L. , Cameron John L. , Wei Alice C. , Zureikat Amer H. , Ferrone Cristina R. , He Jin ,   Pancreatic Neuroendocrine Disease Alliance (PANDA)
Published: January 2022

Objectives:

To identify factors associated with concordance between World Health Organization (WHO) grade on cytological analysis (c-grade) and histopathological analysis (h-grade) of surgical specimen in patients with PanNETs and examine trends in utilization and accuracy of EUS-FNA in preoperatively predicting grade.

Background:

WHO grading system is prognostic in pancreatic neuroendo-crine tumors (PanNETs). The concordance between c-grade and h-grade is reported to be between 50% and 92%.

Methods:

A multicenter retrospective study was performed on patients undergoing resection for PanNETs at four high-volume centers between 2010 and 2019. Patients with functional or syndrome-associated tumors, and those receiving neoadjuvant therapy were excluded. Factors associated with concordance between c-grade and h-grade and trends of utilization of EUS-FNA were assessed.

Results:

Of 869 patients included, 517 (59.5%) underwent EUS-FNA; 452 (87.4%) were diagnostic of PanNETs and WHO-grade was reported for 270 (59.7%) patients. The concordance between c-grade and h-grade was 80.4% with moderate concordance (Kc = 0.52, 95% CI: 0.41–0.63). Significantly higher rates of concordance were observed in patients with smaller tumors (<2 vs. ≥2cm, 81.1% vs. 60.4%, P = 0.005). Highest concordance (98.1%) was observed in patients with small tumors undergoing assessment between 2015-2019 with a near-perfect concordance (Kc = 0.88, 95% CI: 0.61–1.00). An increase in the utilization of EUS-FNA (56.1% to 64.1%) was observed over the last 2 decades (P = 0.017) and WHO-grade was more frequently reported (44.2% vs. 77.6%, P < 0.001). However, concordance between c-grade and h-grade did not change significantly (P = 0.118).

Conclusion:

Recently, a trend towards increasing utilization and improved diagnostic accuracy of EUS-FNA has been observed in PanNETs. Concordance between c-grade and h-grade is associated with tumor size with near-perfect agreement when assessing PanNETs <2cm in size.
Rib fixation in non–ventilator-dependent chest wall injuries: A prospective randomized trial
Authors: Marasco Silvana Francesca , Balogh Zsolt J. , Wullschleger Martin E. , Hsu Jeremy , Patel Bhavik , Fitzgerald Mark , Martin Kate , Summerhayes Robyn , Bailey Michael
Published: January 2022

BACKGROUND

The aim of this study was to assess pain and quality of life (QoL) outcomes in patients with multiple painful displaced fractured ribs with and without operative fixation. Rib fractures are common and can lead to significant pain and disability. There is minimal level 1 evidence for rib fixation in non–ventilator-dependent patients with chest wall injuries. We hypothesized that surgical stabilization of rib fractures would reduce pain and improve QoL during 6 months.

METHODS

A prospective multicenter randomized controlled trial comparing rib fixation to nonoperative management of nonventilated patients with at least three consecutive rib fractures was conducted. Inclusion criteria were rib fracture displacement and/or ongoing pain. Pain (McGill Pain Questionnaire) and QoL (Short Form 12) at 3 and 6 months postinjury were assessed. Surgeons enrolled patients in whom they felt there was clinical equipoise. Patients who were deemed to need surgical fixation or who were deemed to be too well to be randomized to rib fixation were not enrolled.

RESULTS

A total of 124 patients were enrolled at four sites between 2017 and 2020. Sixty-one patients were randomized to operative management and 63 to nonoperative management. No differences were seen in the primary endpoint of Pain Rating Index at 3 months or in the QoL measures. Return-to-work rates improved between 3 and 6 months, favoring the operative group.

CONCLUSION

In this study, no improvements in pain or QoL at 3 and 6 months in patients undergoing rib fixation for nonflail, non–ventilator-dependent rib fractures have been demonstrated.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level II.
SARS-CoV-2–specific Humoral and Cellular Immunities in Kidney Transplant Recipients and Dialyzed Patients Recovered From Severe and Nonsevere COVID-19
Authors: Bertrand Dominique , Hamzaoui Mouad , Drouot Laurent , Lamulle Julie , Hanoy Mélanie , Edet Stéphane , Laurent Charlotte , Lebourg Ludivine , Etienne Isabelle , Lemoine Mathilde , Le Roy Frank , Nezam Dorian , Mauger Eleusis , Boyer Olivier , Guerrot Dominique , Candon Sophie
Published: January 2022

Background.

Kidney transplantation and dialysis are two major risk factors for severe forms of coronavirus disease 2019 (COVID-19). The dynamics of the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in this population remain largely unknown.

Methods.

We report here the analysis of anti–SARS-CoV-2 antibody– and T cell–mediated immune responses in 26 kidney transplant recipients (KTRs) and 11 dialyzed patients (DPs) who recovered from COVID-19.

Results.

After a mean time of 83 ± 26 d post–symptom onset for KTRs and 97 ± 31 d for DPs, 20 KTRs (76.9%) and 10 DPs (90.9%) displayed anti-S1 immunoglobulin G SARS-CoV-2 antibodies (P = 0.34), at similar titers in both groups. SARS-CoV-2–specific interferon-γ–producing T cells were evidenced in 26 KTRs (100%) and 10 DPs (90.9%). Total numbers of SARS-CoV-2–reactive T cells were high and not statistically different between the 2 groups. No correlation between the severity of the disease and the number of reactive T cells was found in KTRs. In 5 KTRs, also evaluated 10 mo after COVID-19, weak or absent antibody response was observed, whereas specific memory T-cell response was detected in all cases.

Conclusion.

T-cell response persisted up to 3 mo post–symptom onset, even in KTRs in whom full immunosuppressive regimen was reinstated at recovery, and seems to be present up to 10 mo after infection. Our findings have implications in the understanding of the natural course of the disease in transplant patients and DPs.
Acute on Chronic Liver Failure: Factors Associated With Transplantation
Authors: Goussous Naeem , Xie Wen , Zhang Talan , Malik Saad , Alvarez-Casas Josue , Gray Stephen H. , Barth Rolf N. , Thuluvath Paul J. , LaMattina John C.
Published: January 2022

Background.

Acute on chronic liver failure (ACLF) carries a poor prognosis unless liver transplantation is offered. We present risk factors associated with proceeding with liver transplantation in patients with ACLF.

Methods.

A retrospective review of all patients with ACLF who presented to a single transplant center between January 2016 and December 2017 was performed. We compared patients who were transplanted with patients who were not.

Results.

During the study period, 144 patients with ACLF were identified, 86 patients (59.7%) were transplanted, and 58 were not. The transplanted patients had a lower number of failed organs (4 versus 5, P < 0.001) and lower incidence of ACLF grade 3 (76.7% versus 94.8%, P = 0.014) compared with nontransplanted patients. Liver transplantation offered a 1-y survival of 86% as compared to 12% in the nontransplanted group. Hospital charges were significantly higher among transplanted patients as compared with the nontransplanted patients ($227 886 versus $88 900, P < 0.001). Elevated serum lactate was a risk factor in not offering liver transplantation in ACLF patients.

Conclusions.

In appropriately selected patients with ACLF, liver transplantation is feasible and can provide above 86% 1-y patient survival even in grade 3 ACLF.
How and why grasshopper community maturation rates are slowing on a North American tall grass prairie
Authors: Kaspari Michael , Joern Anthony , Welti Ellen A. R.
Published: January 2022

Invertebrate growth rates have been changing in the Anthropocene. We examine rates of seasonal maturation in a grasshopper community that has been declining annually greater than 2% a year over 34 years. As this grassland has experienced a 1°C increase in temperature, higher plant biomass and lower nutrient densities, the community is maturing more slowly. Community maturation had a nutritional component: declining in years/watersheds with lower plant nitrogen. The effects of fire frequency were consistent with effects of plant nitrogen. Principal components analysis also suggests associated changes in species composition—declines in the densities of grass feeders were associated with declines in community maturation rates. We conclude that slowed maturation rates—a trend counteracted by frequent burning—likely contribute to long-term decline of this dominant herbivore.
Identification of eight novel variants acrossPAX3, SOX10, EDNRBandMITFgenes in Waardenburg syndrome with next-generation sequencing
Authors: Lee Chen-Yu , Lo Ming-Yu , Chen You-Mei , Lin Pei-Hsuan , Hsu Chuan-Jen , Chen Pei-Lung , Wu Chen-Chi , Hsu Jacob Shu-jui
Published: January 2022

Waardenburg syndrome (WS) is a hereditary, genetically heterogeneous disorder characterized by variable presentations of sensorineural hearing impairment and pigmentation anomalies. This study aimed to investigate the clinical features of WS in detail and determine the genetic causes of patients with clinically suspected WS. A total of 24 patients from 21 Han Taiwanese families were enrolled and underwent comprehensive physical and audiological examination. We applied targeted next-generation sequencing (NGS) to investigate the potential causative variants in these patients and further validated the candidate variants through Sanger sequencing. We identified 18 causative variants of WS in our cohort. Of these variants, eight were novel and discovered inPAX3, SOX10, EDNRB, MITFgenes, including missense, nonsense, deletion, and splice site variants. Several patients presented skeletal deformities, hypotonia, megacolon, and neurological disorders that were rarely seen in WS. This study revealed highly phenotypic variability in Taiwanese WS patients and demonstrated that targeted NGS allowed us to clarify the genetic diagnosis and extend the genetic variant spectrum of WS.
Reticulospinal drive increases maximal motoneuron output in humans
Authors: Škarabot Jakob , Folland Jonathan P , Holobar Aleš , Baker Stuart N , Del Vecchio Alessandro
Published: January 2022

Maximal rate of force development in adult humans is determined by the maximal motoneuron output, however the origin of the underlying synaptic inputs remains unclear. Here, we tested a hypothesis that the maximal motoneuron output will increase in response to a startling cue, a stimulus that purportedly activates the pontomedullary reticular formation neurons that make mono- and disynaptic connections to motoneurons via fast-conducting axons. Twenty-two men were required to produce isometric knee extensor forces “as fast and as hard” as possible from rest to 75% of maximal voluntary force, in response to visual (VC), visual-auditory (VAC), or visual-startling cue (VSC). Motoneuron activity was estimated via decomposition of high-density surface electromyogram recordings over the vastus lateralis and medialis muscles. Reaction time was significantly shorter in response to VSC compared to VAC and VC (i.e., the StartReact effect). The VSC further elicited faster neuromechanical responses including a greater number of discharges per motor unit per second and greater maximal rate of force development, with no differences between VAC and VC. We provide evidence, for the first time, that the synaptic input to motoneurons increases in response to a startling cue, suggesting a contribution of subcortical pathways to maximal motoneuron output in humans, likely originating from the pontomedullary reticular formation.
BOLD cofluctuation ‘events’ are predicted from static functional connectivity
Authors: Ladwig Zach , Seitzman Benjamin A. , Dworetsky Ally , Yu Yuhua , Adeyemo Babatunde , Smith Derek M. , Petersen Steven E. , Gratton Caterina
Published: January 2022

Recent work identified single time points (“events”) of high regional cofluctuation in functional Magnetic Resonance Imaging (fMRI) which contain more large-scale brain network information than other, low cofluctuation time points. This suggested that events might be a discrete, temporally sparse signal which drives functional connectivity (FC) over the timeseries. However, a different, not yet explored possibility is that network information differences between time points are driven by sampling variability on a constant, static, noisy signal. Using a combination of real and simulated data, we examined the relationship between cofluctuation and network structure and asked if this relationship was unique, or if it could arise from sampling variability alone. First, we show that events are not discrete – there is a gradually increasing relationship between network structure and cofluctuation; ∼50% of samples show very strong network structure. Second, using simulations we show that this relationship is predicted from sampling variability on static FC. Finally, we show that randomly selected points can capture network structure about as well as events, largely because of their temporal spacing. Together, these results suggest that, while events exhibit particularly strong representations of static FC, there is little evidence that events are unique timepoints that drive FC structure. Instead, a parsimonious explanation for the data is that events arise from a single static, but noisy, FC structure.

HIGHLIGHTS

Past results suggested high cofluctuation BOLD “events” drive fMRI functional connectivity, FC

Here, events were examined in both real fMRI data and a stationary null model to test this model

In real data, >50% of BOLD timepoints show high modularity and similarity to time- averaged FC

Stationary null models identified events with similar behavior to real data

Events may not be a transient driver of static FC, but rather an expected outcome of it.
Data-driven modelling captures dynamics of the circadian clock of Neurospora crassa
Authors: Singh Amit , Li Congxin , Diernfellner Axel C. R. , Höfer Thomas , Brunner Michael
Published: January 2022

Eukaryotic circadian clocks are based on self-sustaining, cell-autonomous oscillatory feedback loops that can synchronize with the environment via recurrent stimuli (zeitgebers) such as light. The components of biological clocks and their network interactions are becoming increasingly known, calling for a quantitative understanding of their role for clock function. However, the development of data-driven mathematical clock models has remained limited by the lack of sufficiently accurate data. Here we present a comprehensive model of the circadian clock of Neurospora crassa that describe free-running oscillations in constant darkness and entrainment in light-dark cycles. To parameterize the model, we measured high-resolution time courses of luciferase reporters of morning and evening specific clock genes in WT and a mutant strain. Fitting the model to such comprehensive data allowed estimating parameters governing circadian phase, period length and amplitude, and the response of genes to light cues. Our model suggests that functional maturation of the core clock protein Frequency (FRQ) causes a delay in negative feedback that is critical for generating circadian rhythms.
A murine Wac model exhibits phenotypes relevant to DeSanto-Shinawi Syndrome
Authors: Stafford April M , Pacheco-Vergara Maria , Uhl Katie L , Jager Tara E , Li Xiaopeng , Jeong Juhee , Vogt Daniel
Published: January 2022

Several monogenic syndromes are associated with neurodevelopmental changes that result in cognitive impairments, including autism, attention deficit hyperactivity disorder (ADHD) and seizures. Limited studies and resources are available to make meaningful headway into the underlying mechanisms that result in these symptoms. One such example, DeSanto-Shinawi Syndrome (DESSH), is a rare disorder caused by mutations in the WAC gene. Those diagnosed with DESSH experience craniofacial alterations as well as cognitive symptoms that include autism, ADHD and seizures. However, no thorough studies from a mammalian model exist to understand how these changes occur. To overcome this, we generated constitutive murine Wac mutants and assessed phenotypes that are relevant to humans diagnosed with DESSH. Wac mutants have craniofacial, anatomical, behavioral and seizure susceptibility that are relevant to DESSH; this new model is suited to study some of the core symptoms of DESSH and the biology of Wac.
Wolbachia promotes its own uptake by host cells
Authors: Nevalainen Lindsay , Newton Irene L.G.
Published: January 2022

Wolbachia pipientis is an incredibly widespread bacterial symbiont of insects, present in an estimated 25-52% of species worldwide. Wolbachia is faithfully maternally transmitted both in a laboratory setting and in the wild. In an established infection, Wolbachia is primarily intracellular, residing within host-derived vacuoles that are associated with the endoplasmic reticulum. However, Wolbachia also frequently transfer between host species, requiring an extracellular stage to their life cycle. Indeed, Wolbachia has been moved between insect species for the precise goal of controlling populations. The use of Wolbachia in this application requires we better understand how it initiates and establishes new infections. Here we designed a novel method for live-tracking Wolbachia during infection using a combination of stains and microscopy. We show that live Wolbachia are taken up by host cells at a much faster rate than dead Wolbachia cells, indicating that Wolbachia play a role in their own uptake and that Wolbachia colonization is not just a passive process. We also show that the host actin cytoskeleton must be intact for this to occur, and that drugs that disrupt the actin cytoskeleton effectively abrogate Wolbachia uptake. The development of this live infection assay will assist in future efforts to characterize Wolbachia factors used during host infection.
Transient RNA structures cause aberrant influenza virus replication and innate immune activation
Authors: French Hollie , Pitré Emmanuelle , Oade Michael S. , Elshina Elizaveta , Bisht Karishma , King Alannah , Bauer David L.V. , te Velthuis Aartjan J.W.
Published: January 2022

During infection, the influenza A virus RNA polymerase produces both full-length and aberrant RNA molecules, such as defective viral genomes (DVG) and mini viral RNAs (mvRNA). Subsequent innate immune activation involves the binding of host pathogen receptor retinoic acid-inducible gene I (RIG-I) to viral RNAs. However, not all influenza A virus RNAs are strong RIG-I agonists. Here we show that potent innate immune activation by mvRNAs is determined by transient RNA structures, called template loops (t-loop) that stall the viral RNA polymerase. The effect of t-loops depends on the formation of an RNA duplex near the template entry and exit channels of the RNA polymerase, and their effect is enhanced by mutation of the template exit path from the RNA polymerase active site. Overall, these findings provide a mechanism that links aberrant viral replication to the activation of the innate immune response.
Preparing for the unknown: How working memory provides a link between perception and anticipated action
Authors: Rösner Marlene , Sabo Melinda , Klatt Laura-Isabelle , Wascher Edmund , Schneider Daniel
Published: January 2022

What mechanisms underlie the transfer of a working memory representation into a higher-level code for guiding future actions? Electrophysiological correlates of attentional selection and motor preparation processes within working memory were investigated in two retrospective cuing tasks. In the first experiment, participants stored the orientation and location of a grating. Subsequent feature cues (selective vs. neutral) indicated which feature would be the target for later report. The oscillatory response in the mu and beta frequency range with an estimated source in the sensorimotor cortex contralateral to the responding hand was used as correlate of motor preparation. Mu/beta suppression was stronger following the selective feature cues compared to the neutral cue, demonstrating that purely feature-based selection is sufficient to form a prospective motor plan. In the second experiment, another retrospective cue was included to study whether knowledge of the task at hand is necessary to initiate motor preparation. Following the feature cue, participants were cued to either compare the stored feature(s) to a probe stimulus (recognition task) or to adjust the memory probe to match the target feature (continuous report task). An analogous suppression of mu oscillations was observed following a selective feature cue, even ahead of task specification. Further, a subsequent selective task cue again elicited a mu/beta suppression, which was stronger after a continuous report task cue. This indicates that working memory is able to flexibly store different types of information in higher-level mental codes to provide optimal prerequisites for all required action possibilities.

Highlights

•

Selectively cueing features results in an overall performance benefit

•

Feature-based attention is sufficient to form a prospective motor plan

•

Prospective motor preparation can be initiated ahead of task specification

•

Retro-active task specification leads to forming of higher-level action codes

•

Different tasks requirements result in different prospective action plans
Selecting an effective amplitude threshold for neural spike detection
Authors: Zhang Zheng , Constandinou Timothy G.
Published: January 2022

This paper assesses and challenges whether commonly used methods for defining amplitude thresholds for spike detection are optimal. This is achieved through empirical testing of single amplitude thresholds across multiple recordings of varying SNR levels. Our results suggest that the most widely used noise-statistics-driven threshold can suffer from parameter deviation in different noise levels. The spike-noise-driven threshold can be an ideal approach to set the threshold for spike detection, which suffers less from the parameter deviation and is robust to sub-optimal settings.
TooT-SC: Predicting Eleven Substrate Classes of Transmembrane Transport Proteins
Authors: Alballa Munira , Butler Gregory
Published: January 2022

Background

Transporters form a significant proportion of the proteome and play an important role in mediating the movement of compounds across membranes. Transport proteins are difficult to characterize experimentally, so there is a need for computational tools that predict the substrates transported in order to annotate the large number of genomes being sequenced. Recently we developed a dataset of eleven substrate classes from Swiss-Prot using the ChEBI ontology as the basis for the definition of the classes.

Results

We extend our earlier work TranCEP, which predicted seven substrate classes, to the new dataset with eleven substrate classes. Like TranCEP, TooT-SC combines pairwise amino acid composition (PAAC) of the protein, with evolutionary information captured in a multiple sequence alignment (MSA) using TM-Coffee, and restriction to important positions of the alignment using TCS. Our experimental results show that TooT-SC significantly outperforms the state-of-the-art predictors, including our earlier work, with an overall MCC of 0.82 and the MCC for the eleven classes ranging from 0.66 to 1.00.

Conclusion

TooT-SC is a useful tool with high performance covering a broad range of substrate classes. The results quantify the contribution made by each type of information used during the prediction process. We believe the methodology is applicable more generally for protein sequence analysis.
T cell transcription factor expression evolves as adaptive immunity matures in granulomas fromMycobacterium tuberculosis-infected cynomolgus macaques
Authors: Grant Nicole L. , Maiello Pauline , Klein Edwin , Lin Philana Ling , Borish H. Jacob , Tomko Jaime , Frye L. James , White Alexander G. , Kirschner Denise E. , Mattila Joshua T. , Flynn JoAnne L.
Published: January 2022

Mycobacterium tuberculosis(Mtb), the causative agent of tuberculosis (TB), is a global health concern, yearly resulting in 10 million new cases of active TB. Immunologic investigation of lung granulomas is essential for understanding host control of bacterial replication. We identified and compared the pathological, cellular, and functional differences in granulomas at 4, 12, and 20 weeks post-infection in Chinese cynomolgus macaques. Original granulomas differed in transcription factor expression within adaptive lymphocytes with those at 12 weeks showing higher frequencies of CD8+T-bet+T cells, while increases in CD4+T-bet+T cells were observed at 20 weeks post-infection. The appearance of T-bet+adaptive T cells at 12 and 20 weeks was coincident with a reduction in bacterial burden, suggesting their critical role inMtbcontrol. This study highlights the evolution of T cell responses within lung granulomas, suggesting that vaccines promoting the development and migration of T-bet+T cells would enhance mycobacterial control.
Deconstructing the role of iron and heme in the structure of healthy human gut microbial communities
Authors: Celis Arianna I. , Relman David A. , Huang Kerwyn Casey
Published: January 2022

The response of the human gut microbiome to disruptions is often difficult to discern without model systems that remove the complexity of the host environment. Fluctuations in iron availability provide a case in point: the responses of pathogenic bacteria to iron in vitro are much better understood than those of the indigenous human gut commensal microbiota. In a clinical study of iron supplementation in healthy humans, we identified gradual, participant-specific microbiota shifts correlated with bacterial iron internalization. To identify direct effects due to taxon-specific iron sensitivity, we used stool samples from these participants as inocula to derive in vitro communities. Iron supplementation of these communities caused small shifts in structure, similar to in vivo, whereas iron deprivation dramatically inhibited growth with irreversible and cumulative reduction in diversity and replacement of some dominant species. Sensitivity of individual species to iron deprivation during growth in axenic culture generally predicted iron dependency in a community context. Finally, exogenous heme acted as a source of inorganic iron to prevent depletion of some community members. Our results highlight the complementarity of in vivo and in vitro studies in deconstructing how environmental factors affect gut microbiome structure.
S-Acylation Regulates the Membrane Association and Activity of Calpain-5
Authors: Gal Jozsef , Bondada Vimala , Mashburn Charles B. , Rodgers David W. , Croall Dorothy E. , Geddes James W.
Published: January 2022

Calpain-5 (CAPN5) is a member of the calpain family of calcium-activated neutral thiol proteases. CAPN5 is partly membrane associated, despite its lack of a transmembrane domain. Unlike classical calpains, CAPN5 contains a C-terminal C2 domain. C2 domains often have affinity to lipids, mediating membrane association. We recently reported that the C2 domain of CAPN5 was essential for its membrane association and the activation of its autolytic activity. However, despite the removal of the C2 domain by autolysis, the N-terminal fragment of CAPN5 remained membrane associated. S-acylation, also referred to as S-palmitoylation, is a reversible post-translational lipid modification of cysteine residues that promotes membrane association of soluble proteins. In the present study several S-acylated cysteine residues were identified in CAPN5 with the acyl-PEG exchange method. Data reported here demonstrate that CAPN5 is S-acylated on up to three cysteine residues including Cys-4 and Cys-512, and likely Cys-507. The D589N mutation in a potential calcium binding loop within the C2 domain interfered with the S-acylation of CAPN5, likely preventing initial membrane association. Mutating specific cysteine residues of CAPN5 interfered with both its membrane association and the activation of CAPN5 autolysis. Taken together, our results suggest that the S-acylation of CAPN5 is critical for its membrane localization which appears to favor its enzymatic activity.
Structural diversity of the SARS-CoV-2 Omicron spike
Authors: Gobeil Sophie M-C. , Henderson Rory , Stalls Victoria , Janowska Katarzyna , Huang Xiao , May Aaron , Speakman Micah , Beaudoin Esther , Manne Kartik , Li Dapeng , Parks Rob , Barr Maggie , Deyton Margaret , Martin Mitchell , Mansouri Katayoun , Edwards Robert J. , Sempowski Gregory D. , Saunders Kevin O. , Wiehe Kevin , Williams Wilton , Korber Bette , Haynes Barton F. , Acharya Priyamvada
Published: January 2022

Aided by extensive spike protein mutation, the SARS-CoV-2 Omicron variant overtook the previously dominant Delta variant. Spike conformation plays an essential role in SARS-CoV-2 evolution via changes in receptor binding domain (RBD) and neutralizing antibody epitope presentation affecting virus transmissibility and immune evasion. Here, we determine cryo-EM structures of the Omicron and Delta spikes to understand the conformational impacts of mutations in each. The Omicron spike structure revealed an unusually tightly packed RBD organization with long range impacts that were not observed in the Delta spike. Binding and crystallography revealed increased flexibility at the functionally critical fusion peptide site in the Omicron spike. These results reveal a highly evolved Omicron spike architecture with possible impacts on its high levels of immune evasion and transmissibility.
An LTR retrotransposon in the promoter of a PsMYB10.2 gene associated with the regulation of fruit flesh color in Japanese plum
Authors: Fiol Arnau , García Sergio , Dujak Christian , Pacheco Igor , Infante Rodrigo , Aranzana Maria José
Published: January 2022

Japanese plums exhibit wide diversity of fruit coloration. The red to black hues are caused by the accumulation of anthocyanins, while their absence results in yellow, orange or green fruits. In Prunus, MYB10 genes are determinants for anthocyanin accumulation. In peach, QTLs for red plant organ traits map in an LG3 region with three MYB10 copies (PpMYB10.1, PpMYB10.2 and PpMYB10.3). In Japanese plum the gene copy number in this region differs with respect to peach, with at least three copies of PsMYB10.1. Polymorphisms in one of these copies correlate with fruit skin color. The objective of this study was to determine a possible role of LG3-PsMYB10 genes in the natural variability of the flesh color trait and to develop a molecular marker for marker-assisted selection (MAS). We explored LG3-PsMYB10 variability, including the analysis of long-range sequences obtained in previous studies through CRISPR-Cas9 enrichment sequencing. We found that the PsMYB10.2 gene was only expressed in red flesh fruits. Its role in promoting anthocyanin biosynthesis was validated by transient overexpression in Japanese plum fruits. The analysis of long-range sequences identified an LTR retrotransposon in the promoter of the expressed PsMYB10.2 gene that explained the trait in 93.1% of the 145 individuals analyzed. We hypothesize that the LTR retrotransposon may promote the PsMYB10.2 expression and activate the anthocyanin biosynthesis pathway. We provide a molecular marker for the red flesh trait which, together with that for skin color, will serve for the early selection of fruit color in breeding programs.
The Third Transmembrane Domain of Synaptophysin Regulates Initial Fusion Pore Dynamics during Ca2+-Triggered Exocytosis in Chromaffin cells
Authors: Hsiao Yu-Tien , Jackson Meyer B.
Published: January 2022

Synaptophysin (syp) is a major secretory vesicle protein comprising four transmembrane domains (TMDs) and a large cytoplasmic C-terminus. The C-terminus of syp has been shown to regulate exocytosis, vesicle cycling, and synaptic plasticity, but the roles of its TMDs remain unclear. SNARE TMDs line initial fusion pores, and structural work along with sequence analysis suggest that TMD III of syp may play a similar role. To test this hypothesis, we expressed TMD III tryptophan mutants in chromaffin cells from mice lacking both syp and its homolog synaptogyrin, and used amperometry to evaluate fusion pores. In contrast to SNARE TMDs, tryptophan substitutions in syp TMD III had no effect on the flux through initial fusion pores. However, these mutants increased the fraction of kiss-and-run events and decreased the initial fusion pore lifetime. Thus, syp TMD III does not line the initial fusion pore, but interacts with it to influence its stability and choice of release mode.
A timer gene network is spatially regulated by the terminal system in theDrosophilaembryo
Authors: Clark Erik , Battistara Margherita , Benton Matthew A.
Published: January 2022

In insect embryos, anteroposterior patterning is coordinated by the sequential expression of the “timer” genescaudal,Dichaeteandodd-paired, whose expression dynamics correlate with the mode of segmentation. InDrosophila, the timer genes are expressed broadly across much of the blastoderm, which segments simultaneously, but their expression is delayed in a small “tail” region, just anterior to the hindgut, which segments during germband extension. Specification of the tail and the hindgut depends on the terminal gap genetailless, but beyond this the regulation of the timer genes is poorly understood. We used a combination of multiplexed imaging, mutant analysis, and gene network modelling to resolve the regulation of the timer genes, identifying 11 new regulatory interactions and clarifying the mechanism of posterior terminal patterning. We propose that a dynamic Tailless expression gradient modulates the intrinsic dynamics of a timer gene cross-regulatory module, delineating the tail region and delaying its developmental maturation.
SepN is essential for assembly and gating of septal junctions in Nostoc sp. PCC 7120
Authors: Kieninger Ann-Katrin , Tokarz Piotr , Weiss Gregor L. , Pilhofer Martin , Maldener Iris
Published: January 2022

The multicellular life style of filamentous cyanobacteria like Nostoc sp. PCC7120 relies on a cell-cell communication system involving so called septal junctions. These are multiprotein complexes, which traverse the septal peptidoglycan through nanopores, connecting the neighboring cells and enabling molecule transfer along the filament. The intercellular communication is crucial when different cell types in the filament, vegetative cells and heterocysts, have to exchange metabolites and signaling molecules. Septal junctions of cyanobacteria can even control the molecule exchange by gating. The multiprotein complex consists of three modules: the septum spanning tube, the plug residing within the cytoplasmic membrane at both ends of the tube and a membrane associated cap module, covering the plug/tube modules on the cytoplasmic side of each neighboring cell. Until now, FraD was the only identified protein component of the septal junction protein complexes and localizes to the plug module. Here, we identified SepN as a new component via co-immunoprecipitation using FraD as bait and further demonstrated its essential role in septal junction assembly. Despite normal septal nanopore formation, a mutant in sepN exhibited a highly reduced rate of intercellular communication and was unable to gate the exchange of molecules. Cryo-electron tomography of cryo-focused ion beam thinned sepN-mutant filaments revealed septal junctions lacking the plug module and lateral cap openings. The combination of missing plug but present cap allowed to deduce the importance of the plug module in ensuring the correct cap architecture and, more importantly, in sealing the diffusion area in the closed septal junction state.
Macrophages facilitate peripheral nerve regeneration by organizing regeneration tracks through Plexin-B2
Authors: Li Yuhuan , Kang Sangjo , Halawani Dalia , Wang Yiqun , Junqueira Alves Chrystian , Ramakrishnan Aarthi , Estill Molly , Shen Li , Li Fengtao , He Xijing , Friedel Roland H. , Zou Hongyan
Published: January 2022

The regeneration of peripheral nerves is guided by regeneration tracks formed through an interplay of many cell types, but the underlying signaling pathways remain unclear. Here, we demonstrate that macrophages are mobilized ahead of Schwann cells in the nerve bridge after transection injury to participate in building regeneration tracks. This requires the function of guidance receptor Plexin-B2, which is robustly up-regulated in infiltrating macrophages in injured nerves. Conditional deletion of Plexin-B2 in myeloid lineage resulted in not only macrophage misalignment but also matrix disarray and Schwann cell disorganization, leading to misguided axons and delayed functional recovery. Plexin-B2 is not required for macrophage recruitment or activation but enables macrophages to steer clear of colliding axons, in particular the growth cones at the tip of regenerating axons, leading to parallel alignment postcollision. Together, our studies unveil a novel reparative function of macrophages and the importance of Plexin-B2-mediated collision-dependent contact avoidance between macrophages and regenerating axons in forming regeneration tracks during peripheral nerve regeneration.
Effective coordination numbers from EXAFS: general approaches for lanthanide and actinide dioxides
Authors: Romanchuk Anna , Trigub Alexander , Plakhova Tatiana , Kuzenkova Anastasiia , Svetogorov Roman , Kvashnina Kristina , Kalmykov Stepan
Published: January 2022

Extended X-ray absorption fine structure (EXAFS) is a comprehensive and usable method for characterizing the structures of various materials, including radioactive and nuclear materials. Unceasing discussions about the interpretation of EXAFS results for actinide nanoparticles (NPs) or colloids were still present during the last decade. In this study, new experimental data for PuO2 and CeO2 NPs with different average sizes were compared with published data on AnO2 NPs that highlight the best fit and interpretation of the structural data. In terms of the structure, PuO2, CeO2, ThO2, and UO2 NPs exhibit similar behaviors. Only ThO2 NPs have a more disordered and even partly amorphous structure, which results in EXAFS characteristics. The proposed new core-shell model for NPs with calculated effective coordination number perfectly fits the results of the variations in a metal–metal shell with a decrease in NP size.
Vibration and position tracking control for a flexible Timoshenko robot arm with disturbance rejection mechanism
Authors: Yang Yan , Shi Jun , Liu Zhijie , Liu Shuangyin
Published: January 2022

Purpose

This paper aims to study the boundary disturbance rejection control design for a flexible Timoshenko robot arm to diminish external disturbances and achieve desired angle tracking, with system vibration and elastic deformation considered.

Design/methodology/approach

This study introduces disturbance observer and disturbance rejection mechanism into the boundary control design for flexible Timoshenko robot arm systems. The uniform bounded stability of controlled systems is proved via Lyapunov analysis without any simplification of the infinite-dimensional system dynamics.

Findings

The proposed boundary disturbance rejection control scheme can effectively suppress vibrations and shear deformations, achieve the required angular positioning and reject external disturbances. Numerical simulations developed by the finite difference method are adapted to demonstrate the validity of the designed controller.

Originality/value

The originality of this study is to design boundary disturbance rejection control to suppress vibrations and shear deformations for the flexible Timoshenko robot arm, thereby improving the performance and control accuracy of the system.
Architectural approaches to housing customization: introducing the Inhabitant-Driven Customization approach and the MyChanges tool
Authors: Eloy Sara , Vermaas Pieter E.
Published: January 2022

Purpose

Customization is a paradox in architecture, providing necessary modernization for buildings but potentially damaging their architectural integrity. In this paper, the authors introduce the Inhabitant-Driven Customization approach for avoiding this paradox; this approach lets inhabitants design the customization from options created by architects that safeguard architectural rules. As a first implementation of the Inhabitant-Driven Customization approach, the MyChanges tool is presented. The authors assess whether the approach avoids the customization paradox by a qualitative stakeholder evaluation of the MyChanges tool and by a comparison of the Inhabitant-Driven Customization approach with existing approaches to housing customization.

Design/methodology/approach

MyChanges is a shape grammar-based design tool developed to enable inhabitants of the Álvaro Siza Vieira Malagueira housing complex to customize their houses in accordance with the architectural language of the complex. In this study, the authors qualitatively evaluated MyChanges with architects and other professional stakeholders. MyChanges is used in this paper to assess if the Inhabitant-Driven Customization approach avoids the paradox of customization. The initial reception of MyChanges produced diverging outcomes, suggesting that Inhabitant-Driven Customization is also unable to avoid the customization paradox. For analyzing this possibility further, this paper describes the main existing approaches to housing customization, including the Inhabitant-Driven Customization approach, formulates nine conditions for these approaches, and provides a qualitative comparative assessment of the approaches.

Findings

The customization paradox is demonstrated in the outcomes of the interviews with professional stakeholders on the MyChanges customization tool for the Malagueira housing complex. An argument is given that makes plausible that the Inhabitant-Driven Customization approach avoids the customization paradox by creating a co-design process in which inhabitants and architects alternately shape customization.

Originality/value

The originality of this paper lies in the introduction and discussion of the paradox of customization in housing. The paper identifies the conditions advanced in architecture for assessing housing customization approaches. Additionally, the authors propose a new customization approach and a design tool that to a large extent fulfills those conditions and avoids the customization paradox.
Uncovering the antecedents of trust in social commerce: an application of the non-linear artificial neural network approach
Authors: Alnoor Alhamzah , Al-Abrrow Hadi , Al Halbusi Hussam , Khaw Khai Wah , Chew XinYing , Al-Maatoq Marwa , Alharbi Raed Khamis
Published: January 2022

Purpose

The internet creates ample opportunities to start a mobile social commerce business. The literature confirms the issue of customer trust for social commerce businesses is a challenge that must be addressed. Hence, this study aims to examine the antecedents of trust in mobile social commerce by applying linear and non-linear relationships based on partial least squares structural equation modeling and artificial neural network model.

Design/methodology/approach

This study applied a non-linear artificial neural network approach to provide a further understanding of the determinants of trust in mobile social commerce based on a non-linear and non-compensatory model. Besides, a questionnaire was distributed to 340 social commerce customers in Malaysia.

Findings

The conceptual framework for investigating trust in mobile social commerce has various advantages and contributions to predicting consumer behavior. The results of the study showed there is a positive and significant relationship between social support, presence and unified theory of acceptance and use of technology2 (UTAUT2). In addition, UTAUT2 has fully mediated the relationship between social support, presence and trust in social commerce. Finally, the results concluded the relationship between UTAUT2 and trust in social commerce would be stronger when the diffusion of innovation and innovation resistance is high and low, respectively.

Research limitations/implications

The current study provides a novel perspective on how customers can trust social m-commerce to provide real solutions to managers of encouraging e-marketing among consumers.

Practical implications

This paper shows how businesses can develop trust in social m-commerce in Malaysian markets. The findings of this study probably could be extended to other businesses in Asia or other countries. Because trust in social e-commerce has a dynamic role in consumer behavior and intention to purchase.

Originality/value

This study provided a new perspective on mobile social commerce and paid more attention to an investigation of such emerging commerce. The originality of this study is embodied by investigating an integrated model that included different theories that presented new directions of trust in mobile social commerce through social and behavioral determinants.
“A home away from hem”: exploring and assessing hotel staycation as the new normal in the Covid-19 era
Authors: Yan Qi , Shen Huawen , Hu Yunhong
Published: January 2022

Purpose

Enlightened by the theoretical framework of adapted protection motivation, this study aims to explore and assess the viability and resilience of hospitality consumption in the ongoing Covid-19 era as embodied in the activity of staycation, which is gaining popularity as a rare escape from the hemming in of the pandemic.

Design/methodology/approach

This study collects data from staycation guests in Hong Kong, which at the time was under semi-lockdown imposing compulsory quarantine for inbound visitors. The data was analyzed through structural equation modeling (SEM).

Findings

It is revealed by the study results that staycation experiences in Hong Kong are underpinned by a full mediating effect between place attachment and experience quality is performed by sense of presence, together with consolidation of experience quality and psychological detachment as tenable mediators in the research model. Aside from the utilitarian and hedonic values, hospitality and tourism consumption have been engrained with profound socio-cultural implications congenial to the collective identities, recollection and contemplation of a civilized society, with the Covid-19 era and the foreseeable future expected to be no exception.

Practical implications

The results of this study can serve as reference regarding better planning and development of the staycation product as effective responses against the grave repercussions of the Covid-19 pandemic by hotel and hospitality practitioners and destination marketers and managers at large. In particular, the pandemic has inadvertently availed the opportunity for the destinationalization of the hotel and hospitality sector, with rich implications for industrial consolidations and coordination with destination authorities.

Originality/value

The holistic structural research model derived and empirically examined entails major antecedents and consequences of the experience quality of staycation guests in locked-down Hong Kong, with the incorporation of the variables of place attachment and extended conceptualization of sense of presence accounting for the efficacy factors of the staycation takers in terms of locality and recollection appraisals, respectively. This study enriches theoretical articulations on staycation as the new normal of hospitality consumption in the lingering pandemic era.