bluuebunny/crossref_metadata_2025 huggingface dataset:
Employing Contemporary Integrative Interpersonal Theory to Understand Dysfunction in Those at Clinical High Risk for Psychosis
Authors: Williams Trevor F , Ellman Lauren M , Schiffman Jason , Mittal Vijay A
Published: February 2022

Poor social functioning is related to the development of psychosis; however, our current understanding of social functioning in those at-risk for psychosis is limited by (a) poor conceptual models of interpersonal behavior and (b) a reliance on comparisons to healthy controls (e.g., vs. clinical controls). In this study, we introduce Contemporary Integrated Interpersonal Theory (CIIT) and use its Interpersonal Circumplex (IPC) model to compare interpersonal behavior traits in those at clinical high-risk (CHR) for psychosis, clinical controls, and healthy controls. A community sample (N = 3460) was used to derive estimates of IPC dimensions (i.e., affiliation and dominance), which were then compared among a large subsample that completed diagnostic interviews (N = 337), which included a CHR group, as well as several control groups ranging on degree of psychosis vulnerability and internalizing disorders. CHR individuals were distinguished from healthy controls by low affiliation (d = –1.31), and from internalizing disorder groups by higher dominance (d = 0.64). Negative symptoms were consistently associated with low affiliation and low dominance, whereas positive symptoms were related primarily to coldness. These results connect social functioning in psychosis risk to a rich theoretical framework and suggest a potentially distinct interpersonal signature for CHR individuals. More broadly, this study suggests that CIIT and the IPC may have utility for informing diagnostics and treatment development in psychosis risk research.
The spatial distribution of public support for AI research
Authors: Chowdhury Farhat , Link Albert N , van Hasselt Martijn
Published: February 2022

A spatial distributional analysis of the population of Phase II research projects funded by the US SBIR program in FY 2020 shows differences across states in projects focused on artificial intelligence (AI). AI is a relatively new research field, and this paper contributes to a better understanding of government support for such research. We find that AI projects are concentrated in states with complementary AI research resources available from universities nationally ranked in terms of their own AI research. To achieve a more diverse spatial distribution of AI-related technology development, the availability of complementary AI research resources must be expanded. We suggest that the National Science Foundation’s National AI Research Institutes represents an important step in this direction.
Integrated DNA methylation, transcriptome and physiological analyses reveal new insights into superiority of poplars formed by interspecific grafting
Authors: Han Qingquan , Song Haifeng , Yang Congcong , Zhang Sheng , Korpelainen Helena , Li Chunyang
Published: February 2022

Plant grafting has a long history and it is extensively employed to improve plant performance. In our previous research, reciprocal grafts of Populus cathayana Rehder (C) and Populus deltoides Bart. Ex Marsh (D) were generated. The results showed that interspecific grafting combinations (scion/rootstock: C/D and D/C) grew better than intraspecific grafting combinations (C/C and D/D). To further understand differences in molecular mechanisms between interspecific and intraspecific grafting, we performed an integrated analysis, including bisulfite sequencing, RNA sequencing and measurements of physiological indicators, to investigate leaves of different grafting combinations. We found that the difference at the genome-wide methylation level was greater in D/C vs D/D than in C/D vs C/C, but no difference was detected at the transcription level in D/C vs D/D. Furthermore, the grafting superiority of D/C vs D/D was not as strong as that of C/D vs C/C. These results may be associated with the different methylation forms, mCHH (71.76%) and mCG (57.16%), that accounted for the highest percentages in C/D vs C/C and D/C vs D/D, respectively. In addition, the interspecific grafting superiority was found mainly related to the process of photosynthesis, phytohormone signal transduction, biosynthesis of secondary metabolites, cell wall and transcriptional regulation based on both physiological and molecular results. Overall, the results indicated that the physiological and molecular phenotypes of grafted plants are affected by the interaction between scion and rootstock. Thus, our study provides a theoretical basis for developing suitable scion–rootstock combinations for grafted plants.
Peripheral Perfusion Index as a Marker of Sepsis in Preterm Neonates
Authors: Singh Jasmine , Jain Suksham , Chawla Deepak , Randev Shivani , Khurana Supreet
Published: February 2022

Background

Neonatal sepsis is a major contributor to neonatal mortality in India. Blood culture, the gold standard for the diagnosis of sepsis takes 48–72 h while the serological markers have suboptimal diagnostic test characteristics. Perfusion index (PI) is a real time, non-invasive marker that can detect microcirculatory changes before other clinical manifestation of sepsis.

Objective

To determine the diagnostic accuracy of PI in detecting hospital-acquired sepsis before overt clinical manifestations.

Study design

A prospective observational study conducted in the Neonatal Intensive Care Unit (NICU) of a tertiary care hospital.

Participants

Preterm neonates admitted to NICU.

Methods

PI was continuously monitored in all enrolled neonates. Clinical sepsis was defined using the NeonatalKrankenhaus-Infektions-Surveillance-System (NeoKISS). The time of fall of PI below 0.88 and time of clinical sepsis as per NeoKISS were noted and the difference was calculated.

Results

Among 65 preterm neonates (gestational age: 31.5 ± 2.6 weeks, birth weight: 1350, IQR 1100–1700 g), a total of 86 events of suspected sepsis were noted, of which 69 were sepsis screen positive. Fifteen events were associated with culture positive sepsis. PI yielded a sensitivity of 89.47% (95% CI 78.48–96.04%), specificity of 56% (95% CI 34.93–75.60%), positive predictive value of 82.26% (95% CI 74.70–87.92%) and negative predictive value of 70% (95% CI 50.36–84.29%) in detection of hospital-acquired sepsis.

Conclusion

PI might serve as an early, non-invasive marker of hospital-acquired sepsis in preterm neonates.
Identification and Characterization of Fusarium nirenbergiae Associated with Saffron Corm Rot Disease
Authors: Mirghasempour S. Ali , Studholme David J. , Chen Weiliang , Cui Dongzhu , Mao Bizeng
Published: February 2022

Saffron (Crocus sativus L.) is the most expensive spice plant and is distributed widely around the world. However, its production is limited by corm rot, a disastrous disease, attributed to Fusarium oxysporum in many regions of the world. In 2020, extensive surveys were carried out in Zhejiang, Shanghai, Anhui, and Guizhou provinces as saffron growing areas of China. Fourteen single-spore isolates were obtained from rotted corms and identified as F. nirenbergiae according to morphological appearance and multilocus phylogenetic analysis with translation elongation factor 1-α (tef1), DNA-directed RNA polymerase II largest subunit (rpb2), and β-tubulin (tub2). Results of the pathogenicity assay supported the conclusion that F. nirenbergiae is the pathogen responsible for corm rot. In this study, we obtained the whole genome sequence of two highly virulent F. nirenbergiae strains via the Illumina HiSeq platform. Genome sequence assemblies of approximately 52.7 and 52.2 Mb were generated for isolates WY5 and SH1, respectively. To the best of our knowledge, this is the first report of F. nirenbergiae causing C. sativus corm rot in China and indeed worldwide. Results from this research contribute to our understanding of genetic diversity, genomic information, and host determination, which will enable researchers to design appropriate management measures for this hazardous disease.
Benzoxazines in the Root Exudates Responsible for Nonhost Disease Resistance of Maize to Phytophthora sojae
Authors: Liu Haixu , An Tai , Zhao Yifan , Du Xiuming , Bi Xiangqi , Zhang Zhuoqun , Chen Yufei , Wen Jingzhi
Published: February 2022

It has been reported that the root exudates of nonhost maize inhibit Phytophthora sojae because of the presence of benzoxazines in maize roots. To understand the concentrations of benzoxazines (Bxs) in maize root exudates and the molecular mechanism of P. sojae being inhibited, the transcriptomes of P. sojae responding to three different Bxs, 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one (DIMBOA), 6-methoxy-2-benzoxazolinone (MBOA), and benzoxazolinone (BOA), were analyzed by RNA sequencing method. We detected DIMBOA, MBOA, and BOA with a concentration range of 7 to 126 μg/ml in root exudates of three tested maize cultivars (A6565, Pengyu 1, and Xianyu 696). DIMBOA, MBOA, and BOA inhibited chemotaxis and invasiveness of P. sojae zoospores and mycelial growth. The inhibition was regulated mainly by endocytosis and the calcium signaling pathway, PI3K-Akt signaling pathway, and mTOR signaling pathway; meanwhile, the glutathione signaling pathway was activated to increase the antioxidant capacity and efflux of toxic substances. It was speculated that endocytosis plays an important role in the response of P. sojae to Bxs, and the specific functions of genes in this pathway must be further studied. This result provides new insights into the response mechanisms of P. sojae response to Bxs.
The Experience of Being a Full-Time Academic Nurse Educator During the COVID-19 Pandemic
Authors: Gazza Elizabeth A.
Published: February 2022

AIM

The aim of this study was to uncover the experience of being a full-time academic nurse educator (ANE) in a baccalaureate or higher degree nursing program during the COVID-19 pandemic.

BACKGROUND

In 2020, ANEs who were teaching in clinical and classroom settings, conducting in-person research, and engaging in service were suddenly required to work under new COVID-19-induced conditions.

METHOD

A hermeneutic phenomenological approach was used for the study. Personal interviews and a demographic questionnaire were utilized to collect data.

RESULTS

Fourteen ANEs participated. Five themes were uncovered through data analysis: riding a rollercoaster, figuring it out, giving and getting help, seeing silver linings, and feeling loss.

CONCLUSION

This study uncovered the experience of being an ANE during the pandemic. The findings inform strategies to enhance working conditions for current and future ANEs during the remainder of the pandemic and in post-COVID-19 nursing education.
Mindfulness
Authors: Parchment Joy
Published: February 2022

A must-have skill, being mindful is essential for all nurses, especially in the chaotic healthcare environment.
An introduction to motivational interviewing
Authors: Gary Annette , Kiper Valerie , Geist Rebecca
Published: February 2022

Nurses can use this tool for change in a variety of situations to help patients learn to live healthier lives.
Morganella morganii Infections in a Greek University Hospital
Authors: Maraki Sofia , Mantadakis Elpis , Spernovasilis Nikolaos , Mathioudaki Anna , Peristeris Giorgos , Alexakis Konstantinos , Kofteridis Diamantis , Samonis George
Published: February 2022

Background

Morganella morganii is an unusual opportunistic pathogen causing often health care–associated infections mostly in patients with underlying comorbidities. Except for bacteremia, few studies on other types of infections caused by this organism are available.

Methods

The characteristics and outcome of any type of M. morganii infection treated at the University Hospital of Heraklion, Crete, Greece, between January 2013 and December 2018 were retrospectively studied.

Results

A total of 90 patients (57.8% men; mean age ± SD, 67.8 ± 21.1 years) with M. morganii infections were identified. The patients were hospitalized in medical (52.2%), surgical (25.6%), and pediatric department (4.4%), and in the intensive care unit (10%). Only 7 (7.8%) were outpatients. The most frequent were urinary tract (34.5%), and skin and soft tissues infections (33.3%). Of all cases included, 58.9% were health care-associated, whereas in 66.7%, the infection was polymicrobial. Most patients (82.2%) had at least 1 underlying comorbidity. The clinical isolates of M. morganii exhibited high susceptibility rates to carbapenems (100%), amikacin (98.9%), cefepime (94.4%), piperacillin/tazobactam (93.3%), and third-generation cephalosporins and aztreonam (90% each). The empirical treatment given was appropriate for 90% of the 82 patients with available data. Οverall and M. morganii infection–related mortality rates were 10% and 7.8%, respectively.

Conclusions

Although M. morganii infections are infrequently encountered in healthy individuals, they should be considered in inpatients with underlying comorbidities. The urinary tract, and the skin and soft tissues are the most frequently affected sites, whereas polymicrobial infections are very common. Appropriate antimicrobial treatment is associated with favorable prognosis.
HIV-1 pretreatment drug resistance negatively impacts outcomes of first-line antiretroviral treatment
Authors: Hermans Lucas E. , Hofstra Laura M. , Schuurman Rob , Ter Heine Rob , Burger David M. , Talboom Stijn A.J. , De Jong Dorien , Tempelman Hugo A. , Venter Willem D.F. , Nijhuis Monique , Wensing Annemarie M.J.
Published: February 2022

Introduction:

Pretreatment drug resistance (PDR) prevalence in sub-Saharan Africa is rising, but evidence of its impact on efavirenz (EFV)-based antiretroviral treatment (ART) is inconclusive. We determined the impact of PDR on outcomes of EFV-based ART in a subanalysis of a randomized clinical trial comparing different ART monitoring strategies implemented at a rural treatment facility in Limpopo, South Africa.

Methods:

Participants initiating EFV-based first-line ART (2015–2017) were enrolled and received 96 weeks follow-up. Resistance to nucleos(t)ide reverse transcriptase inhibitors (NRTIs) and non-NRTI's (NNRTIs) was retrospectively assessed by population-based sequencing. Virological failure was defined as a viral load of at least 1000 copies/ml after at least 24 weeks of ART.

Results:

A total of 207 participants were included, 60.4% (125/207) of whom were female. Median age was 38.8 (interquartile range: 31.4–46.7) years. Median CD4+ cell count was 191 (interquartile range: 70–355) cells/μl. PDR was detected in 12.9% (25/194) of participants with available sequencing results; 19 had NNRTI-resistance, and six had NRTI- and NNRTI-resistance. 26.0% of participants (40/154) with sequencing results and virological follow-up developed virological failure. PDR was independently associated with failure (adjusted hazard ratio: 3.7 [95% confidence interval: 1.68.5], P = 0.002). At failure, 87.5% (7/8) of participants with PDR harboured dual-class resistant virus, versus 16.7% (4/24) of participants without PDR (P = 0.0007). Virological resuppression after failure on first-line ART occurred in 57.7% (15/26) of participants without PDR versus 14.3% (1/7) of participants with PDR (P = 0.09).

Conclusion:

PDR was detected in 13% of study participants. PDR significantly increased the risk of virological failure of EFV-based ART. Accumulation of resistance at failure and inability to achieve virological resuppression illustrates the profound impact of PDR on treatment outcomes.
Porphyromonas pasteri and Prevotella nanceiensis in the sputum microbiota are associated with increased decline in lung function in individuals with cystic fibrosis
Authors: Webb Karmel , Zain Nur Masirah M. , Stewart Iain , Fogarty Andrew , Nash Edward F. , Whitehouse Joanna L. , Smyth Alan R. , Lilley Andrew K. , Knox Alan , Williams Paul , Cámara Miguel , Bruce Kenneth , Barr Helen L.
Published: February 2022

Although anaerobic bacteria exist in abundance in cystic fibrosis (CF) airways, their role in disease progression is poorly understood. We hypothesized that the presence and relative abundance of the most prevalent, live, anaerobic bacteria in sputum of adults with CF were associated with adverse clinical outcomes. This is the first study to prospectively investigate viable anaerobic bacteria present in the sputum microbiota and their relationship with long-term outcomes in adults with CF. We performed 16S rRNA analysis using a viability quantitative PCR technique on sputum samples obtained from a prospective cohort of 70 adults with CF and collected clinical data over an 8 year follow-up period. We examined the associations of the ten most abundant obligate anaerobic bacteria present in the sputum with annual rate of FEV1 change. The presence of

Porphyromonas pasteri

and

Prevotella nanceiensis

were associated with a greater annual rate of FEV1 change; −52.3 ml yr−1 (95 % CI-87.7;−16.9), –67.9 ml yr−1 (95 % CI-115.6;−20.1), respectively. Similarly, the relative abundance of these live organisms were associated with a greater annual rate of FEV1 decline of −3.7 ml yr−1 (95 % CI: −6.1 to −1.3, P=0.003) and −5.3 ml yr−1 (95 % CI: −8.7 to −1.9, P=0.002) for each log2 increment of abundance, respectively. The presence and relative abundance of certain anaerobes in the sputum of adults with CF are associated with a greater rate of long-term lung function decline. The pathogenicity of anaerobic bacteria in the CF airways should be confirmed with further longitudinal prospective studies with a larger cohort of participants.
Understanding of and Trust in the Centers for Disease Control and Prevention’s Revised COVID-19 Isolation and Quarantine Guidance Among US Adults
Authors: Mishra Vishala , Dexter Joseph P.
Published: February 2022

On December 27, 2021 the Centers for Disease Control and Prevention (CDC) announced changes to their guidance for individuals who are exposed to or test positive for COVID-19. The revised recommendations have prompted widespread discussion of both the scientific rationale and communication strategy, including criticism from the American Medical Association.1,2 In this survey study, we assessed understanding of and trust in the CDC’s initial public statement about the new guidance among US adults.
Design and development of potent h-ACE2 derived peptide mimetics in SARS-CoV-2 Omicron variant therapeutics
Authors: Stanly Paul M. L. , Nadendla Swathi , Sobhia M Elizabeth
Published: February 2022

The pandemic of COVID-19 has become the global health challenge due to the emergence of new variants. The Receptor binding domain (RBD) of spike protein that makes direct interaction with ACE-2 has shown unique mutated residues in most of the variants of concern (VOC). Recently WHO declared the Omicron (B.1.1.529) as VOC considering it as a highly mutated variant which includes a total of 60 mutations out of which 15 mutations occurred in RBD region of SARS-CoV-2. Inhibition of Protein-protein (Omicron RBD-h-ACE2) interaction was already proved to inhibit the viral infection. In this study, by using molecular dynamic simulations efforts are made to explore the atomistic details of Omicron RBD-h-ACE2 interaction. Based on MD simulations, h-ACE2 motif is found to be interacting with omicron RBD domain. Interaction analysis had provided key residues interacting with Omicron-RBD that helped to extract h-ACE2 peptide. Here, rational design of the peptides that have resemblance with h-ACE2 is done and the peptide library is subjected for inhibition studies against Omicron-RBD. The current study helped to identify the significant peptides that can inhibit Omicron-RBD. Altogether the performed studies will provide an opportunity to develop potential therapeutic peptidomimetics effective against Omicron variant of SARS-CoV-2.
Decoding rRNA sequences for improved metagenomics of sylvatic mosquito species
Authors: Koh Cassandra , Frangeul Lionel , Blanc Hervé , Ngoagouni Carine , Boyer Sébastien , Dussart Philippe , Grau Nina , Girod Romain , Duchemin Jean-Bernard , Saleh Maria-Carla
Published: February 2022

As mosquito-borne virus epidemics are often preceded by undetected spillover events, surveillance and virus discovery studies in non-urban mosquitoes informs pre-emptive and responsive public health measures. RNA-seq metagenomics is a popular methodology but it is constrained by overabundant rRNA. The lack of reference sequences for most mosquito species is a major impediment against physical and computational removal of rRNA reads.

We describe a strategy to assemble novel rRNA sequences from mosquito specimens, producing an unprecedented dataset of 234 full-length 28S and 18S rRNA sequences of 33 medically important species from countries with known histories of mosquito-borne virus circulation (Cambodia, the Central African Republic, Madagascar, and French Guiana). We also evaluate the utility of rRNA sequences as molecular barcodes relative to the mitochondrial cytochrome c oxidase I (COI) gene. We show that rRNA sequences can be used for species identification when COI sequences are ambiguous or unavailable, revealing evolutionary relationships concordant with contemporary mosquito systematics.

This expansion of the rRNA reference library improves mosquito RNA-seq metagenomics by permitting the optimization of species-specific rRNA depletion protocols for a broader species range and streamlined species identification by rRNA barcoding. In addition, rRNA barcodes could serve as an additional tool for mosquito taxonomy and phylogeny.
Genomic and phenotypic analyses suggest moderate fitness differences among Zika virus lineages
Authors: Oliveira Glenn , Vogels Chantal B.F. , Zolfaghari Ashley , Saraf Sharada , Klitting Raphaelle , Weger-Lucarelli James , Ontiveros Carlos O. , Agarwal Rimjhim , Leon Karla P. , Tsetsarkin Konstantin A. , Harris Eva , Ebel Gregory D. , Wohl Shirlee , Grubaugh Nathan D. , Andersen Kristian G.
Published: February 2022

RNA viruses have short generation times and high mutation rates, allowing them to undergo rapid molecular evolution during epidemics. However, the extent of RNA virus phenotypic evolution within epidemics and the resulting effects on fitness and virulence remain mostly unknown. Here, we screened the 2015-2016 Zika epidemic in the Americas for lineage-specific fitness differences. We engineered a library of recombinant viruses representing twelve major Zika virus lineages and used them to measure replicative fitness within disease-relevant human primary cells and live mosquitoes. We found that two of these lineages conferred significant in vitro replicative fitness changes among human primary cells, but we did not find fitness changes in Aedes aegypti mosquitoes. Additionally, we found evidence for elevated levels of positive selection among five amino acid sites that define major Zika virus lineages. While our work suggests that Zika virus may have acquired several phenotypic changes during a short time scale, these changes were relatively moderate and do not appear to have enhanced virulence or transmission during the epidemic.
Mutability Patterns Across the Spike Glycoprotein Reveal the Diverging and Lineage-specific Evolutionary Space of SARS-CoV-2
Authors: Rojas Chávez Roberth A. , Fili Mohammad , Han Changze , Rahman Syed A. , Bicar Isaiah G. L. , Gregory Sullivan , Hu Guiping , Das Jishnu , Brown Grant D. , Haim Hillel
Published: February 2022

Mutations in the spike glycoprotein of SARS-CoV-2 allow the virus to probe the sequence space in search of higher-fitness states. New sublineages of SARS-CoV-2 variants-of-concern (VOCs) continuously emerge with such mutations. Interestingly, the sites of mutation in these sublineages vary between the VOCs. Whether such differences reflect the random nature of mutation appearance or distinct evolutionary spaces of spike in the VOCs is unclear. Here we show that each position of spike has a lineage-specific likelihood for mutations to appear and dominate descendent sublineages. This likelihood can be accurately estimated from the lineage-specific mutational profile of spike at a protein-wide level. The mutability environment of each position, including adjacent sites on the protein structure and neighboring sites on the network of comutability, accurately forecast changes in descendent sublineages. Mapping of imminent changes within the VOCs can contribute to the design of immunogens and therapeutics that address future forms of SARS-CoV-2.
Metabolic dyshomeostasis induced by SARS-CoV-2 structural proteins reveals immunological insights into viral olfactory interactions
Authors: Lachén-Montes Mercedes , Mendizuri Naroa , Ausín Karina , Echaide Miriam , Blanco Ester , Chocarro Luisa , de Toro María , Escors David , Fernández-Irigoyen Joaquín , Kochan Grazyna , Santamaría Enrique
Published: February 2022

One of the most common symptoms in COVID-19 is a sudden loss of smell. SARS-CoV-2 has been detected in the olfactory bulb (OB) from animal models and sporadically in COVID-19 patients. To decipher the specific role over the SARS-CoV-2 proteome at olfactory level, we characterized the in-depth molecular imbalance induced by the expression of GFP-tagged SARS-CoV-2 structural proteins (M, N, E, S) on mouse OB cells. Transcriptomic and proteomic trajectories uncovered a widespread metabolic remodeling commonly converging in extracellular matrix organization, lipid metabolism and signaling by receptor tyrosine kinases. The molecular singularities and specific interactome expression modules were also characterized for each viral structural factor. The intracellular molecular imbalance induced by each SARS-CoV-2 structural protein was accompanied by differential activation dynamics in survival and immunological routes in parallel with a differentiated secretion profile of chemokines in OB cells. Machine learning through a proteotranscriptomic data integration uncovered TGF-beta signaling as a confluent activation node by the SARS-CoV-2 structural proteome. Taken together, these data provide important avenues for understanding the multifunctional immunomodulatory properties of SARS-CoV-2 M, N, S and E proteins beyond their intrinsic role in virion formation, deciphering mechanistic clues to the olfactory inflammation observed in COVID-19 patients.
InvL, an invasin-like adhesin, is a type II secretion system substrate required for Acinetobacter baumannii uropathogenesis
Authors: Jackson-Litteken Clay D. , Di Venanzio Gisela , Le Nguyen-Hung , Scott Nichollas E. , Djahanschiri Bardya , Distel Jesus S. , Pardue Evan J. , Ebersberger Ingo , Feldman Mario F.
Published: February 2022

Acinetobacter baumannii is an opportunistic pathogen of growing concern, as isolates are commonly multidrug resistant. While A. baumannii is most frequently associated with pulmonary infections, a significant proportion of clinical isolates come from urinary sources, highlighting its uropathogenic potential. The type IIsecretion system (T2SS) of commonly used model Acinetobacter strains is important for virulence in various animal models, but the potential role of the T2SS in urinary tract infection (UTI) remains unknown. Herein, we used a catheter-associated UTI (CAUTI) model to demonstrate that a modern urinary isolate, UPAB1, requires the T2SS for full virulence. A proteomic screen to identify putative UPAB1 T2SS effectors revealed an uncharacterized lipoprotein with structural similarity to the intimin-invasin family, which serve as type Vsecretion system (T5SS) adhesins required for the pathogenesis of several bacteria. This protein, designated InvL, lacked the β-barrel domain associated with T5SSs, but was confirmed to require the T2SS for both surface localization and secretion. This makes InvL the first identified T2SS effector belonging to the intimin-invasin family. InvL was confirmed to be an adhesin, as the protein bound to extracellular matrix components and mediated adhesion to urinary tract cell lines in vitro. Additionally, the invL mutant was attenuated in the CAUTI model, indicating a role in Acinetobacter uropathogenesis. Finally, bioinformatic analyses revealed that InvL is present in nearly all clinical isolates belonging to international clone 2, a lineage of significant clinical importance. In all, we conclude that the T2SS substrate InvL is an adhesin required for A. baumannii uropathogenesis.

IMPORTANCE

While pathogenic Acinetobacter can cause various infections, we recently found that 20% of clinical isolates come from urinary sources. Despite the clinical relevance of Acinetobacter as a uropathogen, few virulence factors involved in urinary tract colonization have been defined. Herein, we identify a novel type II secretion system effector, InvL, which is required for full uropathogenesis by a modern urinary isolate. Though InvL has predicted structural similarity to the intimin-invasin family of autotransporter adhesins, InvL is predicted to be anchored to the membrane as a lipoprotein. Similar to other invasin homologs however, we demonstrate that InvL is a bona fide adhesin capable of binding extracellular matrix components and mediating adhesion to urinary tract cell lines. In all, this work establishes InvL as an adhesin important for Acinetobacter’s urinary tract virulence, and represents the first report of a type II secretion system effector belonging to the intimin-invasin family.
A quiescent resident progenitor pool is the central organizer of tendon healing
Authors: Grinstein Mor , Tsai Stephanie L , Montoro Daniel , Dingwall Heather L , Zou Ken , Sade-Feldman Moshe , Tanaka Miho J , Capellini Terence D , Rajagopal Jayaraj , Galloway Jenna L
Published: February 2022

A tendon’s ordered extracellular matrix (ECM) is integral for transmitting force and highly prone to injury. How tendon cells, or tenocytes, embedded within this dense ECM mobilize and contribute to healing is unknown. Here, we identify a specialized Axin2+ population in mouse and human tendons that remains latent in homeostasis yet initiates the healing response and serves as a major source of tendon progenitors. Axin2+ tenocytes readily expand in vitro and express stem cell markers. In vivo, Axin2+-descendants are major functional contributors to repair: Axin2+ tenocytes proliferate, acquire injury responsive states, and re-adopt a tenocyte fate post-injury. Specific loss of Wnt secretion in Axin2+ cells alters their progenitor identity, disrupts their activation upon injury, and severely compromises any healing response. Our work highlights an unusual paradigm, wherein quiescent Axin2+ tenocytes self-regulate their identity and mobilization upon injury and provide the key initiating signal to organize a tendon-wide healing response.
Complementing the EGFR dynamic interactome using live-cell proximity labeling
Authors: van Gelder Charlotte A.G.H. , van Bergen Wouter , van Breugel Pieter C. , Altelaar Maarten
Published: February 2022

The epidermal growth factor receptor (EGFR) is a member of the receptor tyrosine kinase family (RTK) of transmembrane receptors, known to regulate many key cellular processes, including growth, proliferation, and differentiation. Its expression, activation, trafficking, and degradation have been extensively studied, as dysregulation of EGFR activation has been linked to a vast number of cancers. Activation of EGFR by different ligands results in distinct cellular responses, and the relative distribution of EGFR in different endosome pools in a process called endosomal sorting, leading to lysosomal degradation, or cell surface recycling, respectively, is considered a fundamental process in EGFR stimulation outcome. The EGFR interactome is therefore an essential element in the study of RTK functional selectivity. Here, we aimed to complement the existing EGFR interactome with spatio-temporal information on EGFR, its interactors, and phosphorylation state. We identified and quantified EGFR stable and transient interactions at different time points after stimulation using an EGFR-APEX2 fusion construct expressed in HEK293T cells and were able to use bystander proteins to map EGFR subcellular location at each time point. Utilizing the fast and concise biotinylation of proximity proteins by APEX2, we were able to detect slight differences in early signaling kinetics between TGF-α and EGF, thereby increasing our knowledge on RTK signaling and differential trafficking.
Determining the targeting specificity of the selective peroxisomal targeting factor Pex9
Authors: Yifrach Eden , Rudowitz Markus , Cruz-Zaragoza Luis Daniel , Tirosh Asa , Gazi Zohar , Peleg Yoav , Kunze Markus , Eisenstein Miriam , Schliebs Wolfgang , Schuldiner Maya , Erdmann Ralf , Zalckvar Einat
Published: February 2022

Targeting proteins to their correct cellular location is a fundamental process that allows them to carry out their cellular functions. Peroxisomes utilize two paralog targeting factors, Pex5 and Pex9, for proteins with a Peroxisomal Targeting Signal 1 (PTS1). However, in spite of their similarity, Pex9 targets only a subset of Pex5 cargo proteins. Here, we studied the properties that facilitate the targeting specificity of Pex9, both by unbiased screens and by site-directed mutagenesis of the PTS1 motifs of either binders or non-binders. We find that the binding specificity of Pex9 is largely determined by the hydrophobic nature of the amino acid preceding the PTS1 tripeptide of its cargos. This is in line with structural modeling of the PTS1-binding cavity of the two factors, showing that while Pex5 has large negative electrostatic patches at the area surrounding the PTS1 binding cavity, Pex9 is mostly hydrophobic. Our work outlines the mechanism by which targeting specificity is achieved, enabling dynamic rewiring of the peroxisomal proteome in changing metabolic needs.
Fish oil Nano-emulsion Kills Macrophage: Ferroptosis and Autophagy Triggered by Catalase-catalysed Superoxide Eruption
Authors: Gao Guanzhen , Zhou Jingru , Wang Huiqin , Ke Lijing , Zhou Jianwu , Ding Yanan , Ding Wei , Zhang Suyun , Rao Pingfan
Published: February 2022

Fish oil is increasingly utilized in the form of nano-emulsion as nutrient and function fortifier. The nano-emulsion’s high polyunsaturated fatty acids content and electron donors at oil/water interface could be a potential site of redox reaction, if a previously unrecognised trigger was provided. Here we report that a vigorous superoxide production occurred in fish oil nano-emulsion in the presence of mammalian catalase in both acellular and cellular systems. Furthermore, the resulting superoxide increased cytosolic ROS and membrane lipid peroxidation of murine macrophage, and eventually caused fatal oxidative damage, which involves autophagy and ferroptosis but not apoptosis. The cell death was significantly inhibited by a catalase-specific inhibitor. The ferroptosis was independent of protease Caspase-3 activation or glutathione peroxidase suppression. Our findings discover a hidden risk factor of the widely acclaimed fish oil emulsion and suggest a novel mechanism of cellular damage by dietary lipids on mucosal layer of the alimentary tract.
Oncogenic c-Myc activity increases tolerance to proteotoxic and genotoxic stress through regulation of HSF1
Authors: Jones Joe , Kiso Koshiro , Bertoli Cosetta , de Bruin Robertus A. M.
Published: February 2022

Oncogenes, such as c-Myc, enhance growth and proliferative signaling to promote continuous cell cycle divisions, the hallmark of cancer. The inadvertent consequence of this is an increase in cellular stresses. However, whether and how oncogenes can directly contribute to cellular stress tolerance, and how much cancer cells rely on these mechanisms for survival, remains poorly understood. Here we show that c-Mycdependent proteotoxic stress contributes to the generation of genotoxic stress. We reveal an important role for the transcription factor Heat Shock Factor 1 (HSF1) in the tolerance to both these c-Myc-induced stresses. c-Myc upregulates HSF1 directly, by activating its expression, and indirectly, via c-Mycdependent proteotoxic stress activation. In addition to relieving c-Myc-induced proteotoxic and genotoxic stress, HSF1 also enables DNA damage response signalling through γH2AX. Consequently, acute depletion of HSF1 significantly increases c-Myc-driven genome instability and decreases cell viability. Our results establish that c-Myc-dependent regulation of HSF1 ensures that proteotoxic and genotoxic stress, resulting from c-Myc-induced enhanced growth and proliferation, are compatible with cell survival.
Impact of cell size on morphogen gradient precision
Authors: Adelmann Jan A. , Vetter Roman , Iber Dagmar
Published: February 2022

Tissue patterning during embryonic development is remarkably precise. We numerically determine the impact of the cell diameter, gradient length, and the morphogen source on the variability of morphogen gradients and show that the positional error increases with the gradient length relative to the size of the morphogen source, and with the square root of the cell diameter and the readout position. We provide theoretical explanations for these relationships, and show that they enable high patterning precision over developmental time for readouts that scale with expanding tissue domains, as observed in theDrosophilawing disc. Our analysis suggests that epithelial tissues generally achieve higher patterning precision with small cross-sectional cell areas. An extensive survey of measured apical cell areas shows that they are indeed small in developing tissues that are patterned by morphogen gradients. Enhanced precision may thus have led to the emergence of pseudostratification in epithelia, a phenomenon for which the evolutionary benefit had so far remained elusive.
A new fold in TANGO1 evolved from SH3 domains for the export of bulky cargos
Authors: Arnolds Oliver , Stoll Raphael
Published: February 2022

Bulky cargos like procollagens, apolipoproteins, and mucins exceed the size of conventional COPII vesicles. During evolution a process emerged in metazoans, predominantly governed by the TANGO1 protein family, that organizes cargo at the exit sites of the endoplasmic reticulum and facilitates export by the formation of tunnel-like connections between the ER and Golgi. Cargorecognition appears to be mediated by an SH3-like domain, however, just how the vastly different cargos are recognized remains elusive. Based on structural and dynamic data as well as interaction studies from NMR spectroscopy presented here, we show that the luminal cargo-recognition domain of TANGO1 adopts a new functional fold for which we suggest the term MOTH (MIA, Otoraplin, TALI/TANGO1 homology) domain. Also, differences in the structural properties within the domain family suggest fundamentally different mechanisms of cargo-recognition in vertebrates and invertebrates. Similarly, in vertebrates, it is proposed that cargo-specificity is mediated by structural differences within the vertebrate TANGO1 and TALI MOTH domains themselves.
Conformational transitions of the mitotic adaptor Spindly underlie its interaction with Dynein and Dynactin
Authors: d’Amico Ennio , Ud Din Ahmad Misbha , Cmentowski Verena , Girbig Mathias , Müller Franziska , Wohlgemuth Sabine , Brockmeyer Andreas , Maffini Stefano , Janning Petra , Vetter Ingrid R. , Carter Andrew P. , Perrakis Anastassis , Musacchio Andrea
Published: February 2022

Cytoplasmic Dynein 1, or Dynein, is a microtubule minus-end directed motor. Dynein motility requires Dynactin and a family of activating adaptors that stabilize the Dynein-Dynactin complex and promote regulated interactions with cargo in space and time. How activating adaptors limit Dynein activation to specialized subcellular locales is unclear. Here, we reveal that Spindly, a mitotic Dynein adaptor at the kinetochore corona, exists natively in a closed conformation that occludes binding of Dynein-Dynactin to its CC1 box and Spindly motif. A structure-based analysis identified various mutations promoting an open conformation of Spindly that binds Dynein-Dynactin. A region of Spindly downstream from the Spindly motif and not required for cargo binding faces the CC1 box and stabilizes the intramolecular closed conformation. This region is also required for robust kinetochore localization of Spindly, suggesting that kinetochores promote Spindly activation to recruit Dynein. This mechanism may be paradigmatic for Dynein activation by other adaptors at various cellular locales.
Functional crosstalk between the carrier translocase machinery and YME1 complex maintains mitochondrial proteostasis and integrity
Authors: Kumar Abhishek , D’Silva Patrick
Published: February 2022

The TIM22 pathway cargos are essential for sustaining mitochondrial proteostasis as an excess of these proteins leads to proteostatic stress and cell death. Yme1 is an inner membrane metalloprotease that regulates proteostasis with its chaperone-like and proteolytic activities. Although the mitochondrial translocase and protease machinery are critical for organelle health, the functional link between these complexes remains unexplored. The present study unravels a novel genetic connection between the TIM22 complex and YME1 machinery in maintaining mitochondrial proteostasis and quality control. Our genetic analyses indicate that impairment in the TIM22 complex rescues the respiratory growth defects of cells without Yme1. We further demonstrate that Yme1 is essential for the stability of the TIM22 complex and regulating the proteostasis of the TIM22 pathway substrates. Moreover, impairment in the TIM22 complex suppressed the mitochondrial structural and functional defects of Yme1 devoid cells. Notably, the functional dependence between the TIM22 and YME1 complexes remains functionally conserved from yeast to humans. Our findings suggest that excessive levels of the TIM22 pathway substrates could be one of the reasons for the respiratory growth defects of cells lacking Yme1 and compromising the TIM22 complex compensate for the imbalance in mitochondrial proteostasis caused by loss of Yme1.
Recruitment of transcriptional effectors by Cas9 creates cis regulatory elements and demonstrates distance-dependent transcriptional regulation
Authors: Boulos Jubran , Ehrlich Itai , Avidan Nili , Shkedi Omer , Haimovich-Caspi Lilac , Kaplan Noam , Kehat Izhak
Published: February 2022

It is essential to regulate the expression of genes, such as those encoding the proteins of the cardiac sarcomere. This regulation is often mediated by cis regulatory elements termed enhancers and repressors that recruit transcription factors to gene-distal sites. However, the relationship between transcription factors recruitment to gene-distant sites and the regulation of gene expression is not fully understood. Specifically, it is unclear if such recruitment to any genomic site is sufficient to form an enhancer or repressor at the site, and what is the relationship between the cis regulatory element’s position and its ability to control the transcription of distant genes. Using dead Cas9 to recruit either viral or endogenous transcription factor activation domains, we demonstrate that targeting ‘naïve’ genomic sites lacking open chromatin or active enhancer marks is sufficient to alter the chromatin signature of the target site, the distant gene promoter, and significantly induce the distant gene expression, even across chromatin insulating loci. The magnitude of induction is affected by the distance between the activation site and the cognate gene in a non-linear manner. Dead Cas9 mediated recruitment of repression domains behave similarly to activation in that targeting of non-regulatory regions could repress gene expression with a nonlinear distance dependence and across chromatin insulating loci. These findings expand the models of enhancer generation and function by showing that an arbitrary genomic site can become a regulatory element and interact epigenetically and transcriptionally with a distant promoter. They also provide new fundamental insights into the rules governing gene expression.
Application of theory of planned behavior in identifying factors affecting online health information seeking intention and behavior of women
Authors: Shamlou Zahra , Saberi Mohammad Karim , Amiri Mohammad Reza
Published: February 2022

Purpose

Today, the Internet has become an attractive source for obtaining health information. Since women play an important role in maintaining the health of the family and community and since they are active seekers of health information through the Internet, it is essential to examine their online health information seeking behavior. Therefore, the main purpose of this article is to identify the factors affecting the online health information seeking intention and behavior of women.

Design/methodology/approach

The theoretical framework of this quantitative study was based on the theory of planned behavior. A total of five hypothesized relationships were formulated to develop a conceptual model. The study approach was quantitative. Using simple random sampling, 400 women referred to specialized and sub-specialized clinics of Hamadan University of Medical Sciences, Iran participated in the study and responded to the survey. Descriptive and inferential data analysis was performed using SPSS 21 and Smart PLS 3 software.

Findings

The results showed that the intention to find health information online is a function of psychological variables. These variables include attitude, subjective norms and perceived behavioral control. Findings showed that attitude is the most important factor affecting online health information seeking intention. It was also found that online health information seeking intention has a positive and significant effect on women's information seeking behavior.

Originality/value

This study is the first attempt to use an important and universally accepted theory to identify the factors affecting the online health information seeking behavior of women referring to specialized and sub-specialized clinics and provides important practical concepts for health officials and managers to improve and develop online health information seeking behavior.
HRM practices, impersonal trust and service oriented OCB: an empirical evidence from Bangladesh
Authors: Sultana Sarmin , Johari Husna
Published: February 2022

Purpose

The preliminary purpose of the study is to explore the relationship between Human Resource Management (HRM) practices and service oriented organizational citizenship behavior (SO-OCB). The current study’s focus is on three HRM practices namely training, fair reward and promotion opportunity. Second, the study examines the mediating role of impersonal trust on the aforementioned relationship through the use of social exchange theory.

Design/methodology/approach

Data has been collected through purposive sampling technique from service employees of 39 private commercial banks of Bangladesh and was analyzed by using structural equation modeling-partial least square method.

Findings

Findings of the study comply with the theory of social exchange. All three HRM practices significantly predict SO-OCB. Additionally, impersonal trust positively mediates the relationship between HRM practices and SO-OCB.

Originality/value

As private commercial banks are growing rapidly in Bangladesh, this sector is facing enormous competition which makes frontline employees SO-OCB a competitive advantage. Due to the limited researches in the field of SO-OCB, this study provides a new avenue of knowledge for the researchers and practitioners on how to develop such behavior in a service setting. Further, no prior study tests the mediation of impersonal trust. Earlier, most of the studies focus on interpersonal trust. The current study contributes to the literature by offering a comprehensive framework that explains the mediation effect of impersonal trust on the association between HRM practices and SO-OCB.