bluuebunny/crossref_metadata_2025 huggingface dataset:
Reducing Overutilization of High-flow Nasal Cannula in Children with Bronchiolitis
Authors: Jo Diana , Gupta Nisha , Bastawrous David , Busch Hayley , Neptune Asha , Weis Amy , Port Courtney
Published: October 2023

Background:

Bronchiolitis is a leading cause of pediatric hospitalizations. A high-flow nasal cannula (HFNC) does not significantly improve clinical outcomes and is associated with increased costs and intensive care unit (ICU) utilization. Despite this, hospitals continue to overuse HFNC in children with bronchiolitis. We aimed to reduce HFNC initiation in children hospitalized with bronchiolitis by 20 percentage points within 6 months.

Methods:

This study included patients aged 1 month to 2 years diagnosed with bronchiolitis, excluding patients with prematurity less than 32 weeks or preexisting cardiopulmonary, genetic, congenital, or neuromuscular abnormalities. Measures included HFNC utilization, length of stay, length of oxygen supplementation (LOOS), ICU transfers, and emergency department (ED) revisits and readmissions. For our primary intervention, we implemented a HFNC initiation protocol incorporating a respiratory scoring system, a multidisciplinary care-team huddle, and an emphasis on supportive care. Staff education, electronic health record integration, and audit and feedback were used to support implementation. Statistical process control charts were used to track metrics.

Results:

We analyzed 325 hospitalizations (126 baseline and 199 postintervention). The proportion of children hospitalized with bronchiolitis who received HFNC decreased from a mean of 82% to 60% within 1 month of implementation. Length of stay decreased from a median of 54 to 42 hours, and length of oxygen supplementation decreased from 50 to 38 hours. There were no significant changes in ICU transfers, 7-day ED revisits, or readmissions.

Conclusions:

Implementing a HFNC initiation protocol can safely reduce the overutilization of HFNC in children hospitalized with bronchiolitis.
A Improving Birth-dose Hepatitis-B Vaccination in a Tertiary Level IV Neonatal Intensive Care Unit
Authors: Avulakunta Indirapriya , Balasundaram Palanikumar , Rechnitzer Alma , Morgan-Joseph Toshiba , Nafday Suhas
Published: October 2023

Background:

Perinatal hepatitis B is a global public health concern. To reduce perinatal hepatitis B and its complications, the Hepatitis B vaccine (HBV) is recommended by the New York State Department of Health and Advisory Committee on Immunization Practices within 24 hours of life for infants born with a birth weight ≥2000 g. Infants admitted to the neonatal intensive care unit (NICU) weighing over 2000 g missed their birth dose HBV frequently, which prompted the implementation of a quality improvement initiative to increase birth dose HBV immunization in a level IV NICU in New York.

Methods:

May 2019 to April 2021 baseline data showed the birth dose HBV rate of infants born ≥2000 g at 24% and 31% within 12 and 24 hours, respectively. The multidisciplinary QI team identified barriers using an Ishikawa cause-and-effect diagram. Our interventions included multidisciplinary collaboration, electronic medical record reminders, education, posters, and improved communication between staff and parents. We aimed to achieve a 25% improvement from the baseline.

Results:

After 19 months of QI interventions (four Plan-Do-Study-Act cycles), the rate of administering birth dose HBV within 12 hours of life increased from 24% to 56% and within 24 hours from 31% to 64%. Process measure compliance improved, exceeding the 25% target, and showed sustained improvement.

Conclusion:

This QI initiative improved the rate of eligible infants receiving HBV within the first 24 hours of life in the NICU. This work can serve as a model for other healthcare institutions to improve HBV immunization rates in NICUs.
Lateral Crural Turn-Up Flap for Increasing the Volume of Cartilaginous Nasal Sidewall in Closed-Approach Dorsal Preservation Rhinoplasty
Authors: Erdal Ayhan Işık , Genç İbrahim Giray , Şibar Serhat
Published: October 2023

Background

Dorsal preservation rhinoplasty can also be applied in crooked nose cases. This article describes a lower lateral cartilage-based flap (lateral crural turn-up flap) used to correct cartilaginous nasal sidewall asymmetries. It was aimed to introduce a flap to be used in crooked nose cases operated with dorsal preservation rhinoplasty and to show possible modifications of this flap.

Methods

Eight patients who had lateral crural turn-up flap due to crooked nose between July and December 2021 were included in this retrospective study. Standardized preoperative and postoperative 12-month front-view photographs were analyzed and scored for correction of midvault nasal sidewall asymmetries by 2 plastic surgeons. The Rhinoplasty Outcome Evaluation (ROE) scale was applied at 12 months.

Results

The mean score given by the surgeons for correction of midvault nasal sidewall asymmetries was 4.18. The mean ROE score was 89, and all patients were satisfied according to their ROE scores. There were no major complications.

Conclusions

Unilateral lateral crural turn-up flap seems to be effective in correcting cartilaginous nasal sidewall asymmetries in crooked nose cases operated with dorsal preservation rhinoplasty.
Customization of Soft Tissue Expanders
Authors: Gao Bowen , Lai Bohan , Wei Xian , Duan Ran , Wei Boxuan , Gu Jieyu , Xie Feng , Xiong Zhuyou
Published: October 2023

Background

Soft tissue expansion is a common technique for restoring large skin defects. Fixed-type expanders may be inappropriate for the following reasons: (1) the shapes and sizes of the defects vary in different patients; and (2) the bulged base of the fixed-type expander does not fit the curve of the human body, which may induce complications such as concave deformities or nerve palsy from continuous mechanical compression. The customized expander adjusts better to the shape and the topography of the expansion site compared with the fixed-type expander. It improves expansion efficiency and reduces complications caused by compression.

Methods

Between 2016 and 2022, customized soft tissue expansion was performed in 38 patients with skin lesions, including giant congenital melanocytic nevi and postburn scars. This series of patients included patients with a specific donor site shape that is unsuitable for fixed-type expanders. An expander was customized according to the shape of the donor site and then implanted in the subcutaneous pocket. After the expander reached a sufficient volume, the expander was removed, and the extra expanded skin flap was transferred to resurface the skin lesion. In the follow-up, the outcome and the complications were recorded.

Results

All the customized expanders fit not only the dimension but also the topography of the donor site. During expansion, 2 patients experienced leakage of the expander, and 3 patients suffered a skin rupture. In the remaining 33 patients, the expansion was successfully completed, and the expanded flaps restored the skin lesions as designed. The color and texture of the skin flaps remained satisfactory after long-term follow-up.

Conclusions

Unlike fixed-type expanders, our customized expanders make it possible for “accurate” expansion, irrespective of the dimension and topography of the donor area. Customization of the expander helps increase efficiency and reduce complications caused by undue compression.
Methylococcus mesophilus sp. nov., the first non-thermotolerant methanotroph of the genus Methylococcus, from a rice field
Authors: Awala Samuel Imisi , Kim Yongman , Gwak Joo-Han , Seo Chanmee , Lee Seungki , Kang Minseo , Rhee Sung-Keun
Published: October 2023

Strain 16-5T, a mesophilic methanotroph of the genus

Methylococcus

, was isolated from rice field soil sampled in Chungcheong Province, Republic of Korea. Strain 16-5T had both particulate and soluble methane monooxygenases and could only grow on methane and methanol as electron donors. Strain 16-5 T cells are Gram-negative, white to light tan in color, non-motile, non-flagellated, diplococcoid to cocci, and have the typical type I intracytoplasmic membrane system. Strain 16-5T grew at 18–38 °C (optimum, 27 °C) and at pH 5.0–8.0 (optimum, pH 6.5–7.0). C16 : 1 ω7c (38.8%), C16 : 1
 ω5c (18.8%), C16 : 1
 ω6c (16.8%) and C16 : 0 (16.9%) were the major fatty acids, and phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and an unidentified phospholipid were the major polar lipids. The main respiratory quinone was methylene-ubiquinone-8. Strain 16-5T displayed the highest 16S rRNA gene sequence similarities to other taxonomically recognized members of the genus

Methylococcus

, i.e.

Methylococcus capsulatus

TexasT (98.62%) and

Methylococcus geothermalis

IM1T (98.49 %), which were its closest relatives. It did, however, differ from all other taxonomically described

Methylococcus

species due to some phenotypic differences, most notably its inability to grow at temperatures above 38 °C, where other

Methylococcus

species thrive. Its 4.34 Mbp-sized genome has a DNA G+C content of 62.47 mol%, and multiple genome-based properties such as average nucleotide identity and digital DNA-DNA hybridization value distanced it from its closest relatives. Based on the data presented above, this strain represents the first non-thermotolerant species of the genus

Methylococcus

. The name Methylococcus mesophilus sp. nov. is proposed, and 16-5T (=JCM 35359T=KCTC 82050T) is the type strain.
Machine learning determines stemness associated with simple and basal-like canine mammary carcinomas
Authors: Xavier Pedro Luiz P. , Marção Maycon , Simões Renan L. S. , Job Maria Eduarda G. , de Francisco Strefezzi Ricardo , Fukumasu Heidge , Malta Tathiane M.
Published: October 2023

Simple and complex carcinomas are the most common type of malignant Canine Mammary Tumors (CMTs), with simple carcinomas exhibiting aggressive behavior and poorer prognostic. Stemness is an ability associated with cancer initiation and progression, malignancy, and therapeutic resistance, but is still few elucidated in different canine mammary cancer subtypes. Here, we first validated, using CMT samples, a previously published canine one-class logistic regression machine learning algorithm (OCLR) to predict stemness (mRNAsi) in canine cancer cells. Then, we observed that simple carcinomas exhibit higher stemness than other histological subtypes and confirmed that stemness is higher and associated with basal-like tumors and with NMF2 tumor-specific metagene signature. Furthermore, using correlation analysis, we suggested two promise stemness-associated targets in CMTs,POLA2andAPEX1, especially in simple canine mammary tumors. Thus, our work elucidates stemness as a potential mechanism behind the aggressiveness and development of simple canine mammary tumors, describing novel pieces of evidence of a promising strategy to target canine mammary carcinomas, especially the simple subtype.
MSIsensor-RNA: Microsatellite Instability Detection for Bulk and Single-cell Gene Expression Data
Authors: Jia Peng , Yang Xuanhao , Yang Xiaofei , Wang Tingjie , Xu Yu , Ye Kai
Published: October 2023

Microsatellite instability (MSI) is an indispensable biomarker in cancer immunotherapy. Currently, MSI scoring methods by high-throughput omics methods have gained popularity and demonstrated better performance than the gold standard method for MSI detection. However, the MSI detection method on expression data, especially single-cell expression data, is still lacking, limiting the scope of clinical application and prohibiting the investigation of MSI at a single-cell level. Herein, we developed MSIsensor-RNA, an accurate, robust, adaptable, and standalone software to detect MSI status based on expression values of MSI-associated genes. We demonstrated the favorable performance and promise of MSIsensor-RNA in both bulk and single-cell gene expression data in multiplatform technologies including RNA-seq, microarray, and single-cell RNA-seq. MSIsensor-RNA is a versatile, efficient, and robust method for MSI status detection from both bulk and single-cell gene expression data in clinical studies and applications. MSIsensor-RNA is available athttps://github.com/xjtu-omics/msisensor-rna.
Bayesian network models identify co-operative GPCR:G protein interactions that contribute to G protein coupling
Authors: Mukhaleva Elizaveta , Ma Ning , van der Velden Wijnand J. C. , Gogoshin Grigoriy , Branciamore Sergio , Bhattacharya Supriyo , Rodin Andrei S. , Vaidehi Nagarajan
Published: October 2023

Cooperative interactions in protein-protein interfaces demonstrate the interdependency or the linked network-like behavior of interface interactions and their effect on the coupling of proteins. Cooperative interactions also could cause ripple or allosteric effects at a distance in protein-protein interfaces. Although they are critically important in protein-protein interfaces it is challenging to determine which amino acid pair interactions are cooperative. In this work we have used Bayesian network modeling, an interpretable machine learning method, combined with molecular dynamics trajectories to identify the residue pairs that show high cooperativity and their allosteric effect in the interface of G protein-coupled receptor (GPCR) complexes with G proteins. Our results reveal a strong co-dependency in the formation of interface GPCR:G protein contacts. This observation indicates that cooperativity of GPCR:G protein interactions is necessary for the coupling and selectivity of G proteins and is thus critical for receptor function. We have identified subnetworks containing polar and hydrophobic interactions that are common among multiple GPCRs coupling to different G protein subtypes (Gs, Gi and Gq). These common subnetworks along with G protein-specific subnetworks together confer selectivity to the G protein coupling. This work underscores the potential of data-driven Bayesian network modeling in elucidating the intricate dependencies and selectivity determinants in GPCR:G protein complexes, offering valuable insights into the dynamic nature of these essential cellular signaling components.
“If I am alive, I am happy”: Defining quality of care from the perspectives of key maternal and newborn health stakeholders in Papua New Guinea
Authors: Faktor Lachlan M , Wilson Alyce N , Melepia Pele , Babona Delly , Wapi Pinip , Suruka Rose , Hezeri Priscah , Kabiu Duk Duk , Vallely Lisa M , Kennedy Elissa , Scoullar Michelle JL , Spotswood Naomi , Homer Caroline SE
Published: October 2023

Background

Quality maternal and newborn healthcare is essential to improve experiences and health outcomes for mothers and babies. In many low to middle income countries, such as Papua New Guinea, there are initiatives to increase antenatal care attendance and facility births. To develop and implement initiatives that are appropriate, relevant, and contextualised to a community, it is important to understand how quality of care is perceived and defined by different maternal and newborn healthcare stakeholders. The aim of this study was to understand how women, their partners, healthcare professionals, healthcare managers, and provincial health administrators in East New Britain, Papua New Guinea define quality of pregnancy, childbirth, and immediate postnatal care.

Methods

An exploratory qualitative study underpinned by a partnership-defined quality approach was undertaken. In total, 42 participants from five different healthcare facilities in East New Britain, Papua New Guinea, were interviewed. These included women, partners, healthcare professionals, healthcare managers, and provincial health administrators. Interviews were analysed using reflexive thematic analysis, assisted by NVivo computer software.

Results

Four themes were identified aligning with the journey a woman takes throughout the health system. These included (I) Ensuring Access: Arriving at the health centre, (II) Experiencing Positive Care: What the staff do, (III) Having the Bare Minimum: Resources available to the service, and (IV) Meeting Expectations: Outcomes of care.

Conclusion

Stakeholder groups had significant overlap in how quality of care was defined, however women and partners focussed more on elements relating to experience of care, while clinical stakeholders focussed on elements relating to provision of care. Participants believe that the current standard of care does not align with how they define quality of care.
Biocomposite Thermoplastic Polyurethanes Containing Evolved Bacterial Spores as Living Fillers to Facilitate Polymer Disintegration
Authors: Kim Han Sol , Noh Myung Hyun , White Evan M. , Kandefer Michael V. , Wright Austin F. , Datta Debika , Lim Hyun Gyu , Smiggs Ethan , Locklin Jason J. , Rahman Md Arifur , Feist Adam M. , Pokorski Jonathan K.
Published: October 2023

The field of engineered living materials (ELMs) seeks to pair living organisms with synthetic materials to generate biocomposite materials with augmented function since living systems can provide highly-programmable and complex behavior. ELMs have typically been fabricated using techniques in benign aqueous environments, limiting their application. In this work, biocomposite fabrication was demonstrated in which spores from polymer-degrading bacteria were incorporated into a thermoplastic polyurethane (TPU) using high-temperature melt processing. Bacteria were engineered using adaptive laboratory evolution to improve their heat tolerance to ensure nearly complete cell survivability during manufacturing at 135 °C. Furthermore, the overall tensile properties of spore-filled TPUs were substantially improved, resulting in a significant improvement in toughness. The biocomposites facilitated disintegration in compost in the absence of a microbe-rich environment. Finally, spores retained a programmed function, expressing green fluorescent protein. This research provides a scalable method to fabricate advanced biocomposite materials in industrially-compatible processes.
Single Cell Expression Analysis of Ductal Carcinoma in Situ Identifies Complex Genotypic-Phenotypic Relationships Altering Epithelial Composition
Authors: Qin Xiaodi , Strand Siri H. , Lee Marissa R. , Saraswathibhatla Aashrith , van IJzendoorn David G. P. , Zhu ChunFang , Vennam Sujay , Varma Sushama , Hall Allison , Factor Rachel E. , King Lorraine , Simpson Lunden , Luo Xiaoke , Colditz Graham A. , Jiang Shu , Chaudhuri Ovijit , Hwang E. Shelley , Marks Jeffrey R. , Owzar Kouros , West Robert B.
Published: October 2023

To identify mechanisms underlying the growth of ductal carcinoma in situ (DCIS) and properties that lead to progression to invasive cancer, we performed single-cell RNA-sequencing (scRNA-seq) on DCIS lesions and matched synchronous normal breast tissue. Using inferred copy number variations (CNV), we identified neoplastic epithelial cells from the clinical specimens which contained a mixture of DCIS and normal ducts. Phylogenetic analysis based on the CNVs demonstrated intratumoral clonal heterogeneity was associated with significant gene expression differences. We also classified epithelial cells into mammary cell states and found that individual genetic clones contained a mixture of cell states suggesting an ongoing pattern of differentiation after neoplastic transformation. Cell state proportions were significantly different based on estrogen receptor (ER) expression with ER-DCIS more closely resembling the distribution in the normal breast, particularly with respect to cells with basal characteristics. Using deconvolution from bulk RNA-seq in archival DCIS specimens, we show that specific alterations in cell state proportions are associated with progression to invasive cancer. Loss of an intact basement membrane (BM) is the functional definition of invasive breast cancer (IBC) and scRNA-seq data demonstrated that ongoing transcription of key BM genes occurs in specific subsets of epithelial cell states. Examining BM in archival microinvasive breast cancers and anin vitromodel of invasion, we found that passive loss of BM gene expression due to cell state proportion alterations is associated with loss of the structural integrity of the duct leading to an invasive phenotype. Our analyses provide detailed insight into DCIS biology.

SIGNIFICANCE

Single cell analysis reveals that preinvasive breast cancer is comprised of multiple genetic clones and there is substantial phenotypic diversity both within and between these clones. Ductal carcinoma in situ (DCIS) of the breast is a non-invasive condition commonly identified through mammographic screening. A primary diagnosis of DCIS carries little mortality risk on its own, but its presence is a risk factor for subsequent clonally related invasive breast cancer (IBC) (1–5).
Brefeldin A and M-COPA block the export of RTKs from the endoplasmic reticulum via simultaneous inactivation of ARF1, ARF4, and ARF5
Authors: Natsume Miyuki , Niwa Mariko , Ichikawa Sho , Okamoto Takuma , Tsutsui Hisazumi , Usukura Daiki , Murata Takatsugu , Abe Ryo , Shimonaka Motoyuki , Nishida Toshirou , Shiina Isamu , Obata Yuuki
Published: October 2023

Normal receptor tyrosine kinases (RTKs) need to reach the plasma membrane (PM) for ligand-induced activation, whereas its cancer-causing mutants can be activated before reaching the PM in organelles, such as the Golgi/trans-Golgi network (TGN). Inhibitors of protein export from the endoplasmic reticulum (ER), such as brefeldin A (BFA) and 2-methylcoprophilinamide (M-COPA), can suppress the activation of mutant RTKs in cancer cells, suggesting that RTK mutants cannot initiate signaling in the ER. BFA and M-COPA block the function of ADP-ribosylation factors (ARFs) that play a crucial role in ER–Golgi protein trafficking. However, which ARFs among AFR family proteins are inhibited by BFA or M-COPA, that is, which ARFs are involved in RTKs transport from the ER, remain unclear. In this study, we showed that M-COPA blocked the export of not only KIT but also PDGFRA/EGFR/MET RTKs from the ER. ER-retained RTKs could not fully transduce anti-apoptotic signals, thereby leading to cancer cell apoptosis. Moreover, single knockdown of ARF1, ARF3, ARF4, ARF5, or ARF6 could not block ER export of RTKs, indicating that BFA/M-COPA treatment cannot be mimicked by knockdown of only one ARF member. Interestingly, simultaneous transfection of ARF1, ARF4, and ARF5 siRNAs mirrored the effect of BFA/M-COPA treatment. Consistent with these results,in vitropulldown assays showed that BFA/M-COPA blocked the function of ARF1, ARF4, and ARF5. Taken together, these results suggest that BFA/M-COPA targets at least ARF1, ARF4, and ARF5; in other words, RTKs require the simultaneous activation of ARF1, ARF4, and ARF5 for their ER export.
Integration of 168,000 samples reveals global patterns of the human gut microbiome
Authors: Abdill Richard J. , Graham Samantha P. , Rubinetti Vincent , Albert Frank W. , Greene Casey S. , Davis Sean , Blekhman Ran
Published: October 2023

Understanding the factors that shape variation in the human microbiome is a major goal of research in biology. While other genomics fields have used large, pre-compiled compendia to extract systematic insights requiring otherwise impractical sample sizes, there has been no comparable resource for the 16S rRNA sequencing data commonly used to quantify microbiome composition. To help close this gap, we have assembled a set of 168,484 publicly available human gut microbiome samples, processed with a single pipeline and combined into the largest unified microbiome dataset to date. We use this resource, which is freely available at microbiomap.org, to shed light on global variation in the human gut microbiome. We find that Firmicutes, particularly Bacilli and Clostridia, are almost universally present in the human gut. At the same time, the relative abundance of the 65 most common microbial genera differ between at least two world regions. We also show that gut microbiomes in undersampled world regions, such as Central and Southern Asia, differ significantly from the more thoroughly characterized microbiomes of Europe and Northern America. Moreover, humans in these overlooked regions likely harbor hundreds of taxa that have not yet been discovered due to this undersampling, highlighting the need for diversity in microbiome studies. We anticipate that this new compendium can serve the community and enable advanced applied and methodological research.
Population genetic analyses of longitudinal vaginal microbiome reveal racioethnic evolutionary dynamics and prevailing positive selection ofLactobacillusadhesins
Authors: Wei Xin , Tsai Ming-Shian , Liang Liang , Jiang Liuyiqi , Hung Chia-Jui , Jelliffe-Pawlowski Laura , Rand Larry , Snyder Michael , Jiang Chao
Published: October 2023

The vaginal microbiome is important for reproductive health and should constantly evolve in response to dynamic host-microbe interactions. The composition of the vaginal microbiome is associated with ethnicity; however, the evolutionary landscape of the vaginal microbiome, especially in the multi-ethnic context, remains under-studied. In this study, we performed a longitudinal evolutionary vaginal microbiome analysis of 351 samples from 35 pregnant women with diverse ethnic backgrounds and validated the main findings in two cohorts totaling 462 samples from 90 multi-ethnic women. Microbiome alpha diversity and community states showed strong ethnic signatures.Lactobacillaceaespecies had a significantly higher nonsynonymous/synonymous mutation ratio (pN/pS) than non-Lactobacillaceaespecies in all ethnicities. In addition, non-Lactobacillaceaeanaerobic bacteria were enriched in Black and Latino women, with significantly elevated nucleotide diversity and lower pN/pS in Black women. Intriguingly, theLactobacillaceaespecies had a large repertoire of positively selected genes, including the human mucin-binding and bacterial cell wall anchor genes, which showed independent, recurrent signatures of positive selection across multiple strains, indicating that the host-microbiome interactions directly drive microbial evolution at the molecular interface. Finally, we propose that the evolutionary metrics reflect the environmental niches of adapting microbes. Our study revealed the extensive ethnic signatures in vaginal microbial diversity, composition, community state, and evolutionary dynamics at species and gene levels, highlighting the importance of studying the host-microbiome ecosystem from an evolutionary perspective.

Highlights

Extensive ethnic signatures in the vaginal microbial diversity, composition, community state, and evolutionary dynamics were demonstrated.

HealthyLactobacillaceaespecies showed lower nucleotide diversity but much more relaxed or even positive selection of genes than non-Lactobacillaceaespecies.

In Black women, non-Lactobacillaceaespecies displayed higher nucleotide diversity and more stringent negative selection.

Lactobacillusmucin-binding and cell wall anchor genes showed convergent signatures of positive selection across vaginal microbiomes.
Identification of residues potentially involved in optical shifts in the water-soluble chlorophyll-a binding protein through molecular dynamics simulations
Authors: Mai Martina , Zazubovich Valter , Mansbach R. A.
Published: October 2023

Reversible light- and thermally-induced spectral shifts are universally observed in a wide variety of pigment-protein complexes, at temperatures ranging from cryogenic to ambient. They can be observed either directly, in single-molecule spectroscopy experiments, or via non-photochemical spectral hole burning. These shifts are important to understand, for example, to gain a clearer picture of the primary processes of photosynthesis, or of general features of the protein energy landscapes. In this article, we have employed large-scale molecular dynamics simulations of a prototypical pigment-protein complex to better understand these shifts at a molecular scale. Although multiple mechanisms have been proposed over the years, no verification of these proposals via MD simulations has thus far been performed; our work represents the first step in this direction. The common requirement for all these mechanisms is the presence of doublewell (or multiple-well) features of the protein energy landscapes. In this work, from large-scale molecular dynamics simulations of the Water-Soluble Chlorophyll-binding Protein complex, we identified side chain rotations of certain amino acid residues as likely candidates for relevant multi-well landscape features. The protein free energy landscapes associated with side chain rotations feature energy barriers of around 1100- 1600 cm−1, in agreement with optical spectroscopy results, with the most promising residue type associated with experimental signatures being serine, which possesses a symmetric landscape and moment of inertia of a relevant magnitude.
Dynamic localization of the chromosomal passenger complex is controlled by the orphan kinesins KIN-A and KIN-B in the kinetoplastid parasiteTrypanosoma brucei
Authors: Ballmer Daniel , Akiyoshi Bungo
Published: October 2023

The chromosomal passenger complex (CPC) is an important regulator of cell division, which shows dynamic subcellular localization throughout mitosis, including kinetochores and the spindle midzone. In traditional model eukaryotes such as yeasts and humans, the CPC consists of the catalytic subunit Aurora B kinase, its activator INCENP, and the localization module proteins Borealin and Survivin. Intriguingly, Aurora B and INCENP as well as their localization pattern are conserved in kinetoplastids, an evolutionarily divergent group of eukaryotes that possess a unique set of kinetochore proteins and lack homologs of Borealin or Survivin. It is not understood how the kinetoplastid CPC assembles or how it is targeted to its subcellular destinations during the cell cycle. Here, we identify two orphan kinesins, KIN-A and KIN-B, as bona fide CPC proteins inTrypanosoma brucei, the causative agent of African sleeping sickness. By employing biochemical, structural, and cell biological approaches, we demonstrate that KIN-A and KIN-B serve as the scaffold for the assembly of the remaining CPC subunits. Kinetochore localization of the CPC depends on the KKT7 – KKT8 complex pathway, with the C-terminal unstructured tail of KIN-A serving as a key interaction partner for the KKT8 complex. Our data therefore show that, unlike other eukaryotes that take advantage of histone modifications for centromere recruitment, trypanosomes rely on kinetochore proteins to recruit the CPC onto kinetochores. Furthermore, the ATPase activity of KIN-A promotes chromosome alignment in prometaphase and CPC translocation to the central spindle upon anaphase onset. Thus, KIN-A constitutes a unique ‘two-in-one’ CPC localization module in complex with KIN-B, which directs the CPC to kinetochores (from S phase until metaphase) via its C-terminal tail, and to the central spindle (in anaphase) via its N-terminal kinesin motor domain. Our findings highlight the evolutionary diversity of CPC proteins and raise the possibility that kinesins may have served as the original transport vehicles for Aurora B kinases in early eukaryotes.
Structural identification of a selectivity filter in CFTR
Authors: Levring Jesper , Chen Jue
Published: October 2023

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel that regulates transepithelial salt and fluid homeostasis. CFTR dysfunction leads to reduced chloride secretion into the mucosal lining of epithelial tissues, thereby causing the inherited disease cystic fibrosis. Although several structures of CFTR are available, our understanding of the ion-conduction pathway is incomplete. In particular, the route that connects the cytosolic vestibule with the extracellular space has not been clearly defined, and the structure of the open pore remains elusive. Furthermore, although many residues have been implicated in altering the selectivity of CFTR, the structure of the “selectivity filter” has yet to be determined. In this study, we identify a chloride-binding site at the extracellular ends of transmembrane helices 1, 6, and 8, where a dehydrated chloride is coordinated by residues G103, R334, F337, T338, and Y914. Alterations to this site, consistent with its function as a selectivity filter, affect ion selectivity, conductance, and open channel block. The selectivity filter is accessible from the cytosol through a large inner vestibule and opens to the extracellular solvent through a narrow portal. The identification of a chloride-binding site at the intra- and extracellular bridging point leads us to propose a complete conductance path that permits dehydrated chloride ions to traverse the lipid bilayer.

Significance statement

Cystic fibrosis is a fatal disease caused by inherited defects in thecftrgene. Understanding the structure and function of the CFTR protein is crucial for cystic fibrosis research. As an ion channel evolved from a family of ATP-driven active transporters, CFTR is structurally distinct from any other ion channel. This study describes the structure of CFTR’s ‘selectivity filter’, which enables us to complete the molecular description of the CFTR pore. Moreover, it enriches our broader knowledge of ion channel physiology, with a particular focus on chloride permeation mechanisms.
Larixol is not an inhibitor of Gαicontaining G proteins and lacks effect on signaling mediated by human neutrophil expressed formyl peptide receptors
Authors: Björkman Lena , Forsman Huamei , Bergqvist Linda , Dahlgren Claes , Sundqvist Martina
Published: October 2023

Neutrophils express several G protein-coupled receptors (GPCRs) connected to intracellular Gαior Gαqcontaining G proteins for down-stream signaling. To dampen GPCR mediated inflammatory processes, several inhibitors targeting the receptors and/or their down-stream signals, have been developed. Potent and selective inhibitors for Gαqcontaining G proteins are available, but potent and specific inhibitors of Gαicontaining G proteins are lacking. Recently, Larixol, a compound extracted from the root ofEuphorbia formosana, was shown to abolish human neutrophil functions induced byN-formyl-methionyl-leucyl-phenylalanine (fMLF), an agonist recognized by formyl peptide receptor 1 (FPR1) which couple to Gαicontaining G proteins. The inhibitory effect was suggested to be due to interference with/inhibition of signals transmitted by βγ complexes of the Gαicontaining G proteins coupled to FPR1. In this study, we applied Larixol, obtained from two different commercial sources, to determine the receptor- and G protein-selectivity of this compound in human neutrophils. However, our data show that Larixol not only lacks inhibitory effect on neutrophil responses mediated through FPR1, but also on responses mediated through FPR2, a Gαicoupled GPCR closely related to FPR1. Furthermore, Larixol did not display any features as a selective inhibitor of neutrophil responses mediated through the Gαqcoupled GPCRs for platelet activating factor and ATP. Hence, our results imply that the inhibitory effects described for the root extract ofEuphorbia formosanaare not mediated by Larixol and that the search for a selective inhibitor of G protein dependent signals generated by Gαicoupled neutrophil GPCRs must continue.
State-transition Modeling of Blood Transcriptome Predicts Disease Evolution and Treatment Response in Chronic Myeloid Leukemia
Authors: Frankhouser David E. , Rockne Russell C. , Uechi Lisa , Zhao Dandan , Branciamore Sergio , O’Meally Denis , Irizarry Jihyun , Ghoda Lucy , Ali Haris , Trent Jeffery M. , Forman Stephen , Fu Yu-Hsuan , Kuo Ya-Huei , Zhang Bin , Marcucci Guido
Published: October 2023

Chronic myeloid leukemia (CML) is initiated and maintained by BCR::ABL which is clinically targeted using tyrosine kinase inhibitors (TKIs). TKIs can induce long-term remission but are also not curative. Thus, CML is an ideal system to test our hypothesis that transcriptome-based state-transition models accurately predict cancer evolution and treatment response. We collected time-sequential blood samples from tetracycline-off (Tet-Off) BCR::ABL-inducible transgenic mice and wild-type controls. From the transcriptome, we constructed a CML statespace and a three-well leukemogenic potential landscape. The potential’s stable critical points defined observable disease states. Early states were characterized by anti-CML genes opposing leukemia; late states were characterized by pro-CML genes. Genes with expression patterns shaped similarly to the potential landscape were identified as drivers of disease transition. Re-introduction of tetracycline to silence the BCR::ABL gene returned diseased mice transcriptomes to a near healthy state, without reaching it, suggesting parts of the transition are irreversible. TKI only reverted the transcriptome to an intermediate disease state, without approaching a state of health; disease relapse occurred soon after treatment. Using only the earliest time-point as initial conditions, our state-transition models accurately predicted both disease progression and treatment response, supporting this as a potentially valuable approach to time clinical intervention even before phenotypic changes become detectable.
Multiple lineages of transmissible neoplasia in the basket cockle (C. nuttallii) with repeated horizontal transfer of mitochondrial DNA
Authors: Yonemitsu Marisa A. , Sevigny Jordana K. , Vandepas Lauren E. , Dimond James L. , Giersch Rachael M. , Gurney-Smith Helen J. , Abbott Cathryn L. , Supernault Janine , Withler Ruth , Smith Peter D. , Weinandt Sydney A. , Garrett Fiona E. S. , Child Zachary J. , Sigo Robin Little Wing , Unsell Elizabeth , Crim Ryan N. , Metzger Michael J.
Published: October 2023

Transmissible cancers are clonal lineages of neoplastic cells able to infect multiple hosts, spreading through populations in the environment as an infectious disease. Transmissible cancers have been identified in Tasmanian devils, dogs, and bivalves. Several lineages of bivalve transmissible neoplasias (BTN) have been identified in multiple bivalve species. In 2019 in Puget Sound, Washington, USA, disseminated neoplasia was observed in basket cockles (Clinocardium nuttallii), a species that is important to the culture and diet of the Suquamish Tribe as well as other tribes with traditional access to the species. To test whether disseminated neoplasia in cockles is a previously unknown lineage of BTN, a nuclear locus was amplified from cockles from Agate Pass, Washington, and sequences revealed evidence of transmissible cancer in several individuals. We used a combination of cytology and quantitative PCR to screen collections of cockles from eleven locations in Puget Sound and along the Washington coastline to identify the extent of contagious cancer spread in this species. Two BTN lineages were identified in these cockles, with one of those lineages (CnuBTN1) being the most prevalent and geographically widespread. Within the CnuBTN1 lineage, multiple nuclear loci support the conclusion that all cancer samples form a single clonal lineage. However, the mitochondrial alleles in each cockle with CnuBTN1 are different from each other, suggesting mitochondrial genomes of this cancer have been replaced multiple times during its evolution, through horizontal transmission. The identification and analysis of these BTNs are critical for broodstock selection, management practices, and repopulation of declining cockle populations, which will enable continued cultural connection and dietary use of the cockles by Coast Salish Tribes.
A Hard Sphere Model for Single File Water Transport Across Biological Membranes
Authors: Manning Gerald S.
Published: October 2023

We use Gürsey’s statistical mechanics of a one-dimensional fluid to find a formula for thePf/Pdratio in the transport of hard spheres across a membrane through a narrow channel that can accommodate only single file movement.Pfis the membrane permeability for osmotic flow, andPdthe permeability for exchange across the membrane in the absence of osmotic flow. The deviation of the ratio from unity indicates the degree of cooperative transport relative to ordinary diffusion of independent isolated molecules. In contrast to an early idea thatPf/Pdmust be equal to the number of molecules in the channel, regardless of the physical nature of the interactions among the molecules, we find a functional dependence on the fractional occupancy of the length of the channel by the hard spheres. We also attempt a random walk calculation forPdindividually, which gives a result forPfas well when combined with the ratio.
Probing different conformational states of polar organizing protein Z with AlphaFold
Authors: Taneja Ishan , Lasker Keren
Published: October 2023

AlphaFold has been a remarkably powerful tool to predict the structures of proteins. Here, we demonstrate that AlphaFold is capable of sampling different conformational states of the oligomerization domain of polar organizing protein Z (PopZ). More broadly, our work suggests that conformational heterogeneity can be extracted from AlphaFold without directly modifying the input multiple sequence alignment.
Examining infantile facial features and their influence on caretaking behaviors in free-ranging Japanese macaques (Macaca fuscata)
Authors: Minami Toshiki , Furuichi Takeshi
Published: October 2023

Facial features of immature individuals play a pivotal role in eliciting caretaking behaviors in humans. It has been posited that non-human animals share particular infantile facial features with humans, which can elicit caregivers’ attention and caretaking behaviors. Nevertheless, the empirical examination of this hypothesis is extremely limited. In this study, we investigated infantile facial features in Japanese macaques (Macaca fuscata), their developmental processes, and their correlation with caretaking and infant behaviors, based on 470 facial photographs from one free-ranging group. We measured the size of facial parts and evaluated infantile facial features in Japanese macaques with non-contact procedures with the animals. The results indicated that, although some partial species differences were observed, the infantile facial features in Japanese macaques were broadly consistent with those previously observed in humans and great apes. Furthermore, half of the infant subjects displayed non-linear developmental trajectories of infantile faces similar to those suggested in humans. These changes were sex-based, with most females demonstrating a linear trajectory and most males a hump-shaped development in their facial proportions. However, unlike previous studies in humans, infantile faces were not significantly associated with maternal or non-maternal caretaking behaviors, nor were their developmental changes correlated with infant behavioral development. These findings indicate that while many aspects of infantile facial features are shared among particular primates, humans may have evolved a uniquely elevated preference for selecting such features among the primate lineage.
The prevalence of potential side effects of COVID-19 vaccines among vaccinated Iraqi people: a prospective cross-sectional study
Authors: Salman Hamzah Abdulrahman , Hussin Amer M. , Hassan Arshad Hamed , Al Sabbah Haleama , Al-Khafaji Khattab
Published: October 2023

Purpose

Several types of vaccines were manufactured by different companies to control and stop the spread of COVID-19. This study aimed to identify the postvaccination side effects of the three different vaccines (Pfizer, AstraZeneca and Sinopharm) among the Iraqi population in Baghdad, Iraq.

Design/methodology/approach

A prospective cross-sectional study was conducted in Baghdad, Iraq from May 2021 to March 2022. An online-based questionnaire was used to collect the data through social media, i.e. WhatsApp, Messenger and Google Classroom. A total of 737 vaccinated participants using a snowball sampling methodology were used in this study.

Findings

Among the study population, 328 (44.50%) were males and 409 (55.50%) were females. The highest age group that participated was 18–30 years (79.10%) followed by 31–40 years (12.10%), 41–50 years (4.20%), 51–60 years (2.40%) and 60 = years (2.20%). However, 58.8% of the participants received Pfizer-BioNTech, 23.7% received the AstraZeneca-Oxford vaccine and 17.5% received Sinopharm. Out of the total participants, 56.60% showed postvaccination side-effects such as fever, headache, fatigue and dizziness, while 33% showed no side-effects and 10.40% were not sure. Pfizer-BioNTech and AstraZeneca-Oxford vaccines were the most vaccines prevalent of side-effects.

Originality/value

The majority of the side reactions associated with the AstraZeneca and Pfizer vaccines were manageable and self-limiting, including fever, fatigue, headache, joint pain and dizziness, compared to the Sinopharm vaccines, which reported lower postside effects.
Smart HRM 4.0 practices for organizational performance: the role of dynamic capabilities
Authors: Pillai Rajasshrie , Srivastava Kailash B.L.
Published: October 2023

Purpose

The study explores the factors affecting the use of smart human resource management 4.0 (SHRM 4.0) practices and its effect on dynamic capabilities and, consequently, on organizational performance.

Design/methodology/approach

The authors used socio-technical and dynamic capabilities theory to propose the notable research model. The authors explored the factors driving the use of SHRM 4.0 practices and their contribution to organizational performance through the development of dynamic capabilities. The authors collected data from 383 senior HR managers using a structured questionnaire, and PLS-SEM was used to analyze the data.

Findings

The results show that socio-technical factors such as top management support, HR readiness, competitive pressure, technology readiness and perceived usefulness influence the use of SHRM 4.0 practices, whereas security and privacy concerns negatively influence them. Furthermore, the authors also found the use of SHRM 4.0 practices influencing the dynamic capacities (build (learning), integration and reconfiguration) and, subsequently, its impact on organizational performance.

Originality/value

Its novelty lies in developing a model using dynamic capabilities and socio-technical theory to explore how SHRM 4.0 practices influence organizational performance through dynamic capabilities. This study extends the literature on SHRM 4.0 practices, HR technology use, HR and dynamic capabilities by contributing to socio-technical theory and dynamic capabilities and expanding the scope of these theories in the area of HRM. It provides crucial insights into HR and top managers to benchmark SHRM 4.0 practices for improved organizational performance.
Preparing for Industry 5.0: a methodology for avoiding corporate amnesia
Authors: Leon Ramona Diana , Rodríguez-Rodríguez Raúl , Alfaro-Saiz Juan-José
Published: October 2023

Purpose

This research sought to identify the best strategy for avoiding corporate amnesia in the context of the Industry 5.0 and an aging society.

Design/methodology/approach

To achieve this goal, a multi-phase methodology based on analytic network process was proposed and tested in one of the biggest companies in the bakery industry.

Findings

The results highlight that online communities of practice and storytelling are the best way to avoid corporate amnesia. The most important factors are commitment, work satisfaction and organizational culture. Commitment and work satisfaction also enhance the use of online communities of practice, while work satisfaction and organizational culture foster the use of storytelling.

Originality/value

This article proposes a nexus between knowledge management and operations management. This research also presents a decision-making tool that can help managers determine the most appropriate strategy for avoiding corporate amnesia.