bluuebunny/crossref_metadata_2025 huggingface dataset:
How intelligence interviewees mentally identify relevant information
Authors: Neequaye David A. , Lorson Alexandra
Published: August 2023

This research explored how intelligence interviewees mentally identify the relevant information at their disposal. We theorized that interviewees estimate the interviewer's objectives based on how they frame any attempt to solicit information. Then interviewees organize the information they possess into item designations that pragmatically correspond to the perceived interviewer-objective. The more an interviewer specifies what they want to know, the more the interviewee will mentally designate information items corresponding with that objective. To examine the theory, we conducted two identical experiments wherein participants assumed the role of an informant with one of two dispositions. They were to be cooperative or resistant when undergoing an interview. The interviewer posed specific or ambiguous questions. In Study 1 (
N
= 210), interviewees identified applicable information items based on their interviewer's questions. And interviewees answered their interviewer's questions in Study 2 (
N
= 199). We aimed to demonstrate that question type influences mental designations and disposition affects disclosures. Disposition had a stronger influence on interviewees' disclosure than when reasoning about what the interviewer wants to know. But contrary to our expectations, mental designation preferences indicated that interviewees generally assume interviewers want to know complete details, irrespective of question specificity. We suggest avenues for future research.
Molecular epidemiology of antimicrobial resistance in central africa: A systematic review
Authors: Dikoumba Annicet-Clotaire , Onanga Richard , Mangouka Laurette G. , Boundenga Larson , Ngoungou Edgard-Brice , Godreuil Sylvain
Published: August 2023

Background. In Central Africa, it is difficult to tackle antibiotic resistance, because of a lack of data and information on bacterial resistance, due to the low number of studies carried out in the field. To fill this gap, we carried out a systematic review of the various studies, and devised a molecular epidemiology of antimicrobial resistance from humans, animals and the environmental samples.

Method. A systematic search of all publications from 2005 to 2020 on bacterial resistance in Central Africa (Gabon, Cameroon, Democratic Republic of Congo, Central African Republic, Chad, Republic of Congo, Equatorial Guinea, São Tomé and Príncipe, Angola) was performed on Pubmed, Google scholar and African Journals Online (AJOL). All circulating resistance genes, prevalence and genetic carriers of these resistances were collected. The study area was limited to the nine countries of Central Africa.

Results. A total of 517 studies were identified through a literature search, and 60 studies carried out in eight countries were included. Among all articles included, 43 articles were from humans. Our study revealed not only the circulation of beta-lactamase and carbapenemase genes, but also several other types of resistance genes. To finish, we noticed that some studies reported mobile genetic elements such as integrons, transposons, and plasmids.

Conclusion. The scarcity of data poses difficulties in the implementation of effective strategies against antibiotic resistance, which requires a health policy in a ‘One Health’ approach.
Hepatobiliary organoids derived from leporids support the replication of hepatotropic lagoviruses
Authors: Kardia Egi , Fakhri Omid , Pavy Megan , Mason Hugh , Huang Nina , Smertina Elena , Jenckel Maria , Peng Nias Y. G. , Estes Mary K. , Strive Tanja , Frese Michael , Smith Ina , Hall Robyn N.
Published: August 2023

The genus Lagovirus of the family Caliciviridae contains some of the most virulent vertebrate viruses known. Lagoviruses infect leporids, such as rabbits, hares and cottontails. Highly pathogenic viruses such as Rabbit haemorrhagic disease virus 1 (RHDV1) cause a fulminant hepatitis that typically leads to disseminated intravascular coagulation within 24–72 h of infection, killing over 95 % of susceptible animals. Research into the pathophysiological mechanisms that are responsible for this extreme phenotype has been hampered by the lack of a reliable culture system. Here, we report on a new ex vivo model for the cultivation of lagoviruses in cells derived from the European rabbit (Oryctolagus cuniculus) and European brown hare (Lepus europaeus). We show that three different lagoviruses, RHDV1, RHDV2 and RHDVa-K5, replicate in monolayer cultures derived from rabbit hepatobiliary organoids, but not in monolayer cultures derived from cat (Felis catus) or mouse (Mus musculus) organoids. Virus multiplication was demonstrated by (i) an increase in viral RNA levels, (ii) the accumulation of dsRNA viral replication intermediates and (iii) the expression of viral structural and non-structural proteins. The establishment of an organoid culture system for lagoviruses will facilitate studies with considerable implications for the conservation of endangered leporid species in Europe and North America, and the biocontrol of overabundant rabbit populations in Australia and New Zealand.
Atrial Fibrillation Screening in High-Risk Patients Using a Single Lead ECG Device: A Tertiary Hospital Experience
Authors: Aklilu Tesfamariam Betemariam , Kebede Meskerem Aleka , Mekonnen Duffera , Asrat Yidnekachew Birhan , Petros Adane Sikamo , Mekonnen Desalew
Published: August 2023

Background

Atrial Fibrillation (AF) is a major public health problem and one of the commonest supraventricular arrhythmias. At least 20% of all strokes are directly attributable to AF. However, its burden is not clear in sub-Saharan Africa, possibly due in part to undervaluation and non-recognition. In recent decades several new devices have been developed for the betterment of the accuracy and rates of AF detection, which also offers flexibility and feasibility.

Objective

The objective of the study is to identify the prevalence of known and Unknown AF in a high-risk patient population using a validated single-lead ECG.

Methods and materials

An institution-based cross-sectional study was conducted in 410 adults (≥55 years) recruited from Tikur Anbessa hospital sub-specialty outpatient clinics from July to October 2021. ECG tracing was conducted using (AliveCor) SL ECG device. A standardized questionnaire was designed to collect socio-demographic and clinical information using ODK Collect v2021. 3.0. we used logistic regression to determine the potential associated factors.

Results

The overall prevalence of AF in our study was 4.8%. It was strongly associated with age, diagnosis of heart failure, Substance use and high monthly income according to World Bank (WB) category. All the newly diagnosed patients were not on anticoagulation for stroke prevention.

Conclusion and Recommendations

Single timepoint screening in high-risk patients identified previously unknown AF in 2.1 %, out of which the majority were eligible for anticoagulation therapy. Identification of AF through targeted screening with up incoming novel technologies could reduce the stroke burden associated with undiagnosed AF.
Antimicrobial resistance patterns of bacterial isolates from bloodstream infections at Jinja regional referral hospital: A cross-sectional study
Authors: Lwigale Fahad
Published: August 2023

Introduction

Bloodstream infections are a commonly encountered clinical syndrome of public health concern with variable epidemiology. The characteristic of resistance to multiple antibiotics by their etiologic agents has limited the options for empirical sepsis case management. This study determined the most frequent aetiologic agents responsible for bloodstream infections, their antimicrobial susceptibility patterns, and infection sources in Eastern-Central Uganda.

Materials and methods

This retrospective study involved analysis of all non-duplicate blood culture reports from 2019 to 2021. The frequency and percentage of significant pathogenic organisms and contaminants were calculated. Positivity distribution including infection sources was determined. World Health Organization Network (WHONET) 2022 desktop software was used for antimicrobial susceptibility data analysis.

Results

The 1364 participants had a diagnostic yield of 114(6.8%) and a 1.5% contamination rate. Over 37% and 13% of infections were hospital and community-acquired respectively. Most etiologic agents were Gram-positive bacteria dominated byStaphylococcus aureus39(34.2%). Gram-negatives mainly included unspecifiedColiforms12(10.5%), andE. coli10(8.8%). Polymicrobial growth existed in 4(0.3%) cases.S. aureuswas mainly resistant to Penicillin G (100%), Cefoxitin (60%), and Erythromycin (52.2%). BothEscherichia coliand unspecifiedcoliformsshowed high resistance to Ampicillin (87.5%) and third-generation Cephalosporins (100%). The least resistance was to Chloramphenicol and Carbapenems.

Conclusion

BSIs are mainly due to Gram-positive bacteria. Suspected sepsis cases byS. aureusin this region can be empirically managed using Gentamicin. Microbiology services should be routinely utilized to guide antimicrobial use, monitor blood culture contamination rates and resistance trends to strengthen regional antimicrobial stewardship.
Metabolomics-assisted mechanism analysis of γ-PGA synthesis regulated by PhoP inB. licheniformis
Authors: Zhang Qing , He Shisi , Zhu Wanying , Yang Fan , Chen Yaozhong , Cai Dongbo , Chen Shouwen
Published: August 2023

Poly γ-glutamic acid (γ-PGA) is a widely used biopolymer whose synthesis relies on external nitrogen sources. PhoP is a global transcription factor that has been reported to be involved in regulation of phosphorus and nitrogen metabolisms, whether PhoP regulates γ-PGA synthesis is worthy of further study. In this study, γ-PGA yield was decreased by 19.4% inphoPdeletion strain, while PhoP overexpression benefited γ-PGA synthesis inBacillus licheniformis, and the results of transcriptional level, electrophoretic mobility shift (EMSA) and GFP expression assays confirmed the direct positive regulation on γ-PGA synthetase genepgsBby PhoP. Furthermore, based on metabolomic and physiological analysis, we dissected three aspects that γ-PGA synthesis indirectly regulated by PhoP. (i) PhoP influences glutamate transport through positively regulating glutamate transporter GltT. (ii) PhoP influences nitrogen source utilization through negatively regulating nitrogen metabolic repressor TnrA and positively regulating GlnR. (iii) PhoP influences ammonia assimilation through GlnR and TnrA. Together, our study improved metabolic regulatory network of γ-PGA synthesis, and laid a foundation for PhoP regulation nitrogen metabolic network inBacillus.
RSV neutralizing antibodies in dried blood
Authors: Terstappen Jonne , Delemarre Eveline M. , Versnel Anouk , White Joleen T. , Derrien-Colemyn Alexandrine , Ruckwardt Tracy J , Bont Louis , Mazur Natalie I.
Published: August 2023

The key correlate of protection of respiratory syncytial virus (RSV) vaccines and monoclonal antibodies (mAb) is virus neutralization, measured using sera obtained through venipuncture. Dried blood obtained with a finger prick can simplify acquisition, processing, storage, and transport in trials, and thereby reduce costs. In this study we aim to validate a low-tech assay to measure RSV neutralization in dried capillary blood. Recovery of mAb from dried blood (volumetric absorptive microsampling) was used to validate the elution method using indirect ELISA. Functional antibodies measured by a neutralization assay were compared between matched serum and dried blood samples from a phase I trial with RSM01, a novel investigational anti-RSV Prefusion F mAb. Hep-2 cells were infected with a serial dilution of sample-virus mixture using RSV-A2-mKate to determine half-maximal inhibitory concentration. Stability of dried blood was evaluated over time and during temperature stress. Functional antibodies in dried blood were highly correlated with serum (R2= 0.98, p < 0.0001). The intra-assay, inter-assay, and inter-operator precision of the assay for dried blood was similar to serum. The function of mAb remained stable for 9 months at room temperature and frozen dried blood samples but lower concentrations showed instability after 6 months. Dried blood samples resisted 48 hours of temperature stress. We demonstrated the feasibility of measuring RSV neutralization using dried blood as an alternative to serum. Measuring antibody function using dried blood is a patient-centered solution that may replace serology testing in trials against RSV or other viruses, such as influenza and SARS-CoV-2.

Summary points

Neutralizing antibodies against RSV in serum and dried blood from clinical samples are highly correlated.

Neutralizing antibodies are stable in dried blood for 6 months and can withstand temperature variation.

Dried blood samples are a patient-centered and logistical solution for vaccine trials in remote areas and low- and lower-middle income countries.
Thigh muscle mass is associated with circulating valeric acid in healthy male volunteers
Authors: Hassler Eva M. , Reishofer Gernot , Köfeler Harald , Renner Wilfried , Hannes Deutschmann H , Mangge Harald , Herrmann Markus , Leber Stefan L. , Gunzer Felix , Almer Gunter
Published: August 2023

Short-chain fatty acids (SCFAs) are circulating metabolites generated by gut microbiota. Recently, a link between age-related muscle loss and gut microbiota has been described, and SCFAs could play a mediating role in this relationship. Acetic, propionic, and butyric acid are the abundant forms and are considered to have health benefits, less is known about valeric and caproic acid.

In a cross-sectional study including 155 healthy volunteers, we investigated the relationship between muscle area, as well as intramuscular adipose tissue measured by magnet resonance imaging and circulating SCFAs. SCFAs and additional parameters were measured from serum and sport activities recorded by means of a questionnaire.

We found a significant positive association between valeric acid (VA) levels and the thigh cross-sectional muscle area in males. This relationship was independent of age, BMI and weekly training times and was not observed in females. No associations between other SCFAs and the thigh muscle cross-sectional area were observed.

To our knowledge, this is the first human study demonstrating a significant relationship between thigh muscle mass and VA, supporting the thesis of the “gut–muscle axis” with VA as a possible interacting player, on the one hand, affected by sex differences, on the other.
Development of an electronic decision aid tool to facilitate mainstream genetic testing in ovarian cancer patients
Authors: Shannon Kristen M. , Patel Devanshi , Jonas Jessica , Blouch Erica L. , Hicks Stephanie , Wooters Mackenzie , Seidel Meredith , Grant Carly F. , Emmet Margaret , Chung Daniel C. , Sepucha Karen
Published: August 2023

Background

Multigene panel testing is an important component of cancer treatment plans and risk assessment, but there are many different panel options and choosing the most appropriate panel can be challenging for healthcare providers and patients. Electronic tools have been proposed to help patients make informed decisions about which gene panel to choose by considering their preferences and priorities.

Materials and Methods

An electronic decision aid tool was developed in line with the International Patient Decision Aids Standards (IPDAS) collaboration. The multidisciplinary project team collaborated with an external healthcare communications agency and the MGH Cancer Center patient family advisory committee (PFAC) to develop the decision aid. Surveys of genetic counselors and patients were used to scope the content, and alpha testing was used to refine the design and content.

Results

Surveys of genetic counselors (n=12) and patients (n=228) identified common themes in discussing panel size and strategies for helping patients decide between panels and in identifying confusing terms for patients and distribution of patients’ choices. The decision aid, organized into two major sections, provides educational text, graphics and videos to guide patients through the decision-making process. Alpha testing feedback from the PFAC (n=4), genetic counselors (n=3) and a group of lay people (n=8) identified areas to improve navigation, simplify wording and improve layout.

Conclusion

The decision aid developed in this study has the potential to facilitate informed decision-making by patients regarding cancer genetic testing. The distinctive feature of this decision aid is that it addresses the specific question of which multigene panel may be most suitable for the patient. Its acceptability and effectiveness will be evaluated in future studies.

Implications for Practice

The use of multigene panel testing in oncology has increased significantly, but selecting the most appropriate panel for each patient can be challenging for healthcare providers and patients. The complexity and heterogeneity of the data generated by these tests, coupled with the potential psychological, emotional, and financial impacts, make informed consent a critical component of the genetic testing process. With the expansion of germline genetic testing, the traditional model of pre-test informed consent by a genetic counselor may no longer be scalable. Electronic decision aids have shown promise in increasing patient knowledge and empowerment in the shared decision-making process. The development of a comprehensive electronic tool can facilitate patient education while maximizing patient autonomy, allowing for more personalized and informed decisions about which gene panel to choose.⍰
ThepFactor Outweighs the Specific Internalizing Factor in Predicting Recurrences of Adolescent Depression
Authors: Shu Yinuo , Ao Na , Wen Xue , Cui Zaixu , Qu Diyang , Chen Runsen
Published: August 2023

Background

The early prediction of adolescent depression recurrence poses a significant challenge in the field. This study aims to investigate and compare the abilities of two psychopathology factors, namely the general psychopathology factor (p) and the specific internalizing factor, in predicting depression recurrence over a 2-year course, as well as identifying remitted depression patients from healthy adolescents. Longitudinal changes of these two factors in different trajectory groups were also tracked to examine their sensitivity to sustained remission and relapse.

Methods

We included 255 baseline-remitted depression patients and a healthy control group (n=255) matched in age, sex, and race, sourced from the Adolescent Brain Cognitive Development Study. The Linear Mixed Model was employed to differentiate between healthy controls and remitted depression patients, predict depression recurrence, and track longitudinal changes over a subsequent 2-year course using thepfactor and the specific internalizing factor respectively.

Results

Thepfactor not only effectively discriminated between remitted depression patients and healthy controls, but also robustly predicted the depression recurrence over a subsequent 2-year course. The specific internalizing factor could only differentiate remitted depression patients from healthy controls. Additionally, a noteworthy longitudinal decline of thepfactor in the sustained-remission group was observed.

Conclusions

Psychopathology factors serve as the inherent and enduring measurement of long-term mental health aberrations. Longitudinal results indicate that the p factor is more sensitive to respond to sustained remission than the internalizing factor. The ability of the overallpfactor to anticipate depression relapse, unlike the specific internalizing factor, suggests clinical interventions should monitor and mitigate the coincident symptoms across all dimensions to preempt relapse of adolescent depression, rather than an exclusive focus on internalizing symptoms.
Near-Infrared Photothermal Ablation of Biofilms using Protein-Functionalized Gold Nanospheres with a Tunable Temperature Response
Authors: Amarasekara Dhanush L. , Kariyawasam Chathuri S. , Hejny Madison A. , Torgall Veeresh B. , Werfel Thomas A. , Fitzkee Nicholas C.
Published: August 2023

Temperature-responsive nanostructures with high antimicrobial efficacy are attractive for therapeutic applications against multi-drug-resistant bacteria. Here, we report temperature-responsive nanospheres (TRNs) that are engineered to undergo self-association and agglomeration above a tunable transition temperature (Tt). Temperature-responsive behavior of the nanoparticles is obtained by functionalizing citrate-capped, spherical gold nanoparticles (AuNPs) with elastin-like polypeptides (ELPs). Using protein design principles, we achieve a broad range of attainable Ttvalues and photothermal conversion efficiencies (η). Two approaches were used to adjust this range: First, by altering the position of the cysteine residue used to attach ELP to the AuNP, we attained a Ttrange from 34-42 °C. Then, functionalizing the AuNP with an additional small globular protein, we were able to extend this range to 34-50 °C. Under near-infrared (NIR) light exposure, all TRNs exhibited reversible agglomeration. Moreover, they showed enhanced photothermal conversion efficiency in their agglomerated state relative to the dispersed state. Despite their spherical shape, TRNs have a photothermal conversion efficiency approaching that of gold nanorods (η= 68±6%), yet unlike nanorods, the synthesis of TRNs requires no cytotoxic compounds. Finally, we tested TRNs for photothermal ablation of biofilms. Above Tt, NIR irradiation of TRNs resulted in a 10,000-fold improvement in killing efficiency compared to untreated controls (p < 0.0001). Below Tt, no enhanced anti-biofilm effect was observed. In conclusion, engineering the interactions between proteins and nanoparticles enables the tunable control of TRNs, resulting in a novel, anti-biofilm nanomaterial with low cytotoxicity.

TOC Image
Potent induction of humoral and cellular immunity after bivalent BA.4/5 mRNA vaccination in dialysis patients with and without history of SARS-CoV-2 infection
Authors: Bronder Saskia , Mihm Janine , Urschel Rebecca , Klemis Verena , Schmidt Tina , Marx Stefanie , Abu-Omar Amina , Hielscher Franziska , Guckelmus Candida , Widera Marek , Sester Urban , Sester Martina
Published: August 2023

Knowledge on immunogenicity of the bivalent Omicron BA.4/5 vaccine in dialysis patients and the effect of a previous infection is limited. Therefore, vaccine-induced humoral and cellular immunity was analyzed in dialysis patients and immunocompetent controls with and without prior infection.

In an observational study, 33 dialysis patients and 58 controls matched for age, sex and prior infection status were recruited. Specific IgG, neutralizing antibody activity and cellular immunity towards the spike-antigen from parental SARS-CoV-2 and Omicron subvariants BA.1, BA.2 and BA.4/5 were analyzed before and 13-18 days after vaccination.

The bivalent vaccine led to a significant induction of IgG, neutralizing titers, and specific CD4 and CD8 T-cell levels. Neutralizing activity towards the parental strain was highest, whereas specific T-cell levels towards parental spike and Omicron subvariants did not differ indicating substantial cross-reactivity. Dialysis patients with prior infection had significantly higher spike-specific CD4 T-cell levels with lower CTLA-4 expression compared to infection-naïve patients. When compared to controls, no differences were observed between individuals without prior infection. Among infected individuals, CD4 T-cell levels were higher in dialysis patients and neutralizing antibodies were higher in controls. Vaccination was overall well tolerated in both dialysis patients and controls with significantly less adverse events among dialysis patients.

In conclusion, our study did not provide any evidence for impaired immunogenicity of the bivalent Omicron BA.4/5 vaccine in dialysis patients. Unlike in controls, previous infection of patients was even associated with higher levels of spike-specific CD4 T cells, which may reflect prolonged encounter with antigen during infection.

Translational statement

Dialysis patients with uremic immunodeficiency are at increased risk for infectious complications after SARS-CoV-2 infection and have been shown to insufficiently respond towards the first doses of COVID-19 vaccines. Bivalent vaccines are now recommended, although knowledge on immunogenicity and on the effect of a previous infection is limited in this patient group. We show that the bivalent BA.4/5 vaccine was well tolerated and led to a pronounced induction of antibodies, neutralizing antibodies and T cells, which was overall similar in magnitude in non-infected patients and controls. Despite some differences between patients and controls with prior infection, our data do not provide any evidence towards impaired immunity in dialysis patients.
Deletion ofXistupstream sequences alters TAD interactions and leads to defects in Xist coating and expression
Authors: Majumdar S , Bammidi LS , Naik HC , Avinchal  , Baro R , Kalita A , Sundarraj N , Bariha GS , Notani D , Gayen S
Published: August 2023

The topological organization of the genome plays an important role in regulating gene expression. However, the connection between the two remains poorly understood. X-chromosome inactivation is a unique model system to explore the interlink between topologically associated domains (TADs) and gene expression. TADs are largely lost upon X-inactivation, and the inactive-X gets bipartitely reorganized into two large mega domains. However, the X-inactivation center (XIC) harbors two TADs – at the locus of long non-coding RNA Xist (Xist-TAD) and Tsix (Tsix-TAD). Xist is the master regulator of X-inactivation, which coat the inactive-X and facilitates heterochromatinization. Here, we deleted Xist upstream sequences (∼6 kb) near the Xist TAD’s boundary in extraembryonic endoderm stem cells (XEN), which undergo imprinted X-inactivation. This deletion led to the major rearrangement of TADs and affected the expression of genes located within Xist and Tsix TAD, specially the expression of Xist was upregulated, suggesting TADs are essential for proper transcriptional regulation. On the other hand, Xist-upstream deletion on the inactive-X resulted in dispersal of Xist coating and loss of enrichment of repressive chromatin marks on the inactive-X but no effect on X-linked gene silencing. However, we found that autosomal genes were dysregulated in Xist-upstream deleted cells, probably because of misregulation of genes located in Xist and Tsix-TAD, specially Xist. We conclude that Xist upstream sequences are necessary for proper organization of the TADs at the XIC, maintenance of Xist coating/expression and autosomal gene expression.
The Induced Fatigue on Attention Networks of Active and Inactive Individuals Effect of Exercise
Authors: Kayvani Maryam , Kavyani Akram , Soltani Sana
Published: August 2023

Background

The relationship between physical activity and cognitive functions is well established, with regular exercise improving cognitive functions. However, there is less clarity surrounding the effect of exercise-induced fatigue on attention network particularly in those with a history of continuous physical activity.

Aims

This research was aimed to determine whether exercise-induced fatigue can affect cognitive functions, especially those involved in attentional control (i.e., alerting, orientation, and executive functions) and to identify any differences in attentional control between active and inactive individuals after exercise-induced fatigue.

Methods

We compared the performance of 24 physically active and inactive participants in the Attentional Network Task, which allows for the assessment of the executive, orienting and alerting networks. Under two conditions regarding exercise-induced fatigue (pre-fatigue and post-fatigue), we used sub-maximum aerobic endurance training to induce fatigue to the exhaustion point.

Results

The results showed that fatiguing exercise improved alertness in both groups; however, the executive control network of the active group improved while the orienting and executive control networks of the inactive group performed worse.

Conclusions

Depending on the participants’ degree of physical activity and the particular task used to test each of these attention networks, exercise-induced exhaustion had a different impact on different attention networks.
Projection neurons are necessary for the maintenance of the mouse olfactory circuit
Authors: Sánchez-Guardado Luis , Razavi Peyman , Wang Bo , Callejas-Marín Antuca , Lois Carlos
Published: August 2023

The assembly and maintenance of neural circuits is crucial for proper brain function. Although the assembly of brain circuits has been extensively studied, much less is understood about the mechanisms controlling their maintenance as animals mature. In the olfactory system, the axons of olfactory sensory neurons (OSNs) expressing the same odor receptor converge into discrete synaptic structures of the olfactory bulb (OB) called glomeruli, forming a stereotypic odor map. The OB projection neurons, called mitral and tufted cells (M/Ts), have a single dendrite that branches into a single glomerulus, where they make synapses with OSNs. We used a genetic method to progressively eliminate the vast majority of M/T cells in early postnatal mice, and observed that the assembly of the OB bulb circuits proceeded normally. However, as the animals became adults the apical dendrite of remaining M/Ts grew multiple branches that innervated several glomeruli, and OSNs expressing single odor receptors projected their axons into multiple glomeruli, disrupting the olfactory sensory map. Moreover, ablating the M/Ts in adult animals also resulted in similar structural changes in the projections of remaining M/Ts and axons from OSNs. Interestingly, the ability of these mice to detect odors was relatively preserved despite only having 1-5% of projection neurons transmitting odorant information to the brain, and having highly disrupted circuits in the OB. These results indicate that a reduced number of projection neurons does not affect the normal assembly of the olfactory circuit, but induces structural instability of the olfactory circuitry of adult animals.
Empagliflozin reduces neointimal formation and vascular smooth muscle cell proliferation via the suppression of PDGF-related signaling
Authors: Chen Wei-Jan , Chang Gwo-Jyh , Hsu Yu-Juei , Chen Ying-Hwa
Published: August 2023

Objective

Emerging evidence has documented the beneficial effects of sodium glucose cotransporter 2 (SGLT2) inhibitors on reducing cardiovascular events. Beyond glucose regulation, the mechanisms behind their cardioprotective effects still remained unresolved. This study aims to investigate whether these benefits are mediated by their effects on vascular smooth muscle cell (VSMC) functions.

Approach and Results

Treatment of non-diabetic rats with empagliflozin (a SGLT2 inhibitor) attenuated balloon injury-induced neointimal formation in carotid arteries.In vitro, treatment of rat VSMCs with empagliflozin reduced platelet-derived growth factor (PDGF)-BB-induced proliferation and migration. Moreover, empagliflozin-treated VSMCs did not undergo apoptosis and cytosis. Notably, treating VSMCs with empagliflozinsuppressed the activation of PDGF-related signaling, such as that related to the phosphorylation of PDGF receptor b (PDGF-Rb), Akt, and STAT3. Furthermore, overactivation of PDGF-related signaling attenuated the inhibitory effects of empagliflozin on VSMC proliferation and migration. The relevantin vitrofindings were corroborated in the neointima of empagliflozin-treated rats. The fact that minimal SGLT2 was discovered in rat VSMCs and SGLT2 silencing did not alter the effect of empagliflozin supported the SGLT2-independent effect of empagliflozin on VSMC functions.

Conclusions

This study highlights the crucial role of PDGF-related signaling in mediating the beneficial effects of empagliflozin on VSMC functions and/or neointimal formation, which are independent of its effects on SGLT2 and glucose metabolism.
Robust collection and processing for label-free single voxel proteomics
Authors: Kitata Reta Birhanu , Velickovic Marija , Xu Zhangyang , Zhao Rui , Scholten David , Chu Rosalie K. , Orton Daniel J. , Chrisler William B. , Mathews Jeremy V. , Piehowski Paul D. , Liu Tao , Smith Richard D. , Liu Huiping , Wasserfall Clive H. , Tsai Chia-Feng , Shi Tujin
Published: August 2023

With advanced mass spectrometry (MS)-based proteomics, genome-scale proteome coverage can be achieved from bulk tissues. However, such bulk measurement lacks spatial resolution and obscures important tissue heterogeneity, which make it impossible for proteome mapping of tissue microenvironment. Here we report an integrated wet collection of single tissue voxel and Surfactant-assisted One-Pot voxel processing method termed wcSOP for robust label-free single voxel proteomics. wcSOP capitalizes on buffer droplet-assisted wet collection of single tissue voxel dissected by LCM into the PCR tube cap and MS-compatible surfactant-assisted one-pot voxel processing in the collection cap. This convenient method allows reproducible label-free quantification of ∼900 and ∼4,600 proteins for single voxel from fresh frozen human spleen tissue at 20 μm × 20 μm × 10 μm (close to single cells) and 200 μm × 200 μm × 10 μm (∼100 cells), respectively. 100s-1000s of protein signatures with differential expression levels were identified to be spatially resolved between spleen red and white pulp regions depending on the voxel size. Region-specific signaling pathways were enriched from single voxel proteomics data. Antibody-based CODEX imaging was used to validate label-free MS quantitation for single voxel analysis. The wcSOP-MS method paves the way for routine robust single voxel proteomics and spatial proteomics.
High-throughput generic single-entity sequencing using droplet microfluidics
Authors: Wang Guoping , Zhao Liuyang , Shi Yu , Qu Fuyang , Ding Yanqiang , Liu Weixin , Liu Changan , Luo Gang , Li Meiyi , Bai Xiaowu , Li Luoquan , Ho Yi-Ping , Yu Jun
Published: August 2023

Single-cell sequencing has revolutionized our understanding of cellular heterogeneity by providing a micro-level perspective over the past decades. Although heterogeneity is essential for various biological communities, the currently demonstrated platform predominantly focuses on eukaryotic cells without cell walls and their transcriptomics1,2, leaving significant gaps in the study of omics from other single biological entities such as bacteria and viruses. Due to the difficulty of isolating and acquiring their DNA3, contemporary methodologies for the characterization of generic biological entities remain conspicuously constrained, with low throughput4, compromised lysis efficiency5, and highly fragmented genomes6. Herein, we present the Generic Single Entity Sequencing platform (GSE-Seq), which boasts ample versatility, high throughput, and high coverage, and is enabled by an innovative workflow, addressing the critical challenges in single entities sequencing: (1) one-step manufacturing of massive barcodes, (2) degradable hydrogel-basedin situsample processing and whole genome amplification, (3) integrated in-drop library preparation, (4) compatible long-read sequencing. By GSE-Seq, we have achieved a significant milestone by enabling high-throughput, long-read single-entity profiling of dsDNA and ssDNA from single virus sequencing (SV-seq) and single bacteria sequencing (SB-seq) of the human gut and marine sediment for the first time. Notably, our analysis uncovered previously overlooked viral and bacterial dark matter and phage-host interactions. In summary, the presented conceptually new workflow offers a toolbox based on droplet microfluidics to tackle the persistent challenges in high-throughput profiling to generic applications, which hold immense promise for diverse biological entities, especially hard-to-lyse cells.
Machine learning approaches identify chemical features for stage-specific antimalarial compounds
Authors: van Heerden Ashleigh , Turon Gemma , Duran-Frigola Miquel , Pillay Nelisha , Birkholtz Lyn-Marié
Published: August 2023

Efficacy data from diverse chemical libraries, screened against the various stages of the malaria parasitePlasmodium falciparum, including asexual blood stage (ABS) parasites and transmissible gametocytes, serves as a valuable reservoir of information on the chemical space of compounds that are either active (or not) against the parasite. We postulated that this data can be mined to define chemical features associated with sole ABS activity and/or those that provide additional life cycle activity profiles like gametocytocidal activity. Additionally, this information could provide chemical features associated with inactive compounds, which could eliminate any future unnecessary screening of similar chemical analogues. Therefore, we aimed to use machine learning to identify the chemical space associated with stage-specific antimalarial activity. We collected data from various chemical libraries that were screened against the asexual (126 374 compounds) and sexual (gametocyte) stages of the parasite (93 941 compounds), calculated the compounds’ molecular fingerprints and trained machine learning models to recognize stage-specific active and inactiv compounds. We were able to build several models that predicts compound activity against ABS and dual-activity against ABS and gametocytes, with Support Vector Machines (SVM) showing superior abilities with high recall (90% and 66%) and low false positive predictions (15% and 1%). This allowed identification of chemical features enriched in active and inactive populations, an important outcome that could be mined for essential chemical features to streamline hit-to-lead optimization strategies of antimalarial candidates. The predictive capabilities of the models held true in diverse chemical spaces, indicating that the ML models are therefore robust and can serve as a prioritization tool to drive and guide phenotypic screening and medicinal chemistry programs.

For Table of Contents Graphic Only
Interrogation of single-neuron functional connectivity in the cortex and hippocampus via fast cross-layer all-optical physiology
Authors: Liu Chi , Hao Yuejun , Zhong Yi , Kong Lingjie , Lei Bo
Published: August 2023

The interrogation of functional neural circuits is crucial for uncovering how the brain works during diverse behaviors. Multi-plane neurophysiological measurement systems with high temporal resolution are indispensable, especially for dissecting inter-layer functional connectivity. Here, we develop a cross-layer all-optical physiology system (CLAOP) that enables the simultaneous recording and manipulation of single-neuron activities in multiple neuronal layers, with axial intervals as large as 530 μm, at high temporal resolutions. Based on spatiotemporal multiplexing, our system enables all-optical analysis with a high frame rate up to 396 Hz and minimal time delay in inter-layer imaging and photostimulation, in both the mouse cortex and hippocampus in vivo. Combined with behavioral experiments, CLAOP provides all-optical evidence linking behavioral responses to neuronal connectivity in the primary visual cortex (V1) of live mice. Furthermore, we demonstrate that CLAOP can perturb the activity response of inter-layer cortical neurons to sensory stimuli according to their functional signatures. Overall, CLAOP provides an all-optical approach for mapping inter-layer connectivity at the single-neuron level and for modifying neuronal responses in behaving animals.
Mechanisms of active diffusion of vesicular stomatitis virus inclusion bodies and cellular early endosomes in the cytoplasm of mammalian cells
Authors: Moran Steven J. , Oglietti Ryan , Smith Kathleen C. , Macosko Jed C. , Holzwarth George , Lyles Douglas S.
Published: August 2023

Viral and cellular particles too large to freely diffuse have two different types of mobility in the eukaryotic cell cytoplasm: directed motion mediated by motor proteins moving along cytoskeletal elements with the particle as its load, and motion in random directions mediated by motor proteins interconnecting cytoskeletal elements. The latter motion is referred to as “active diffusion.” Mechanisms of directed motion have been extensively studied compared to mechanisms of active diffusion, despite the observation that active diffusion is more common for many viral and cellular particles. Our previous research showed that active diffusion of vesicular stomatitis virus (VSV) ribonucleoproteins (RNPs) in the cytoplasm consists of hopping between traps and that actin filaments and myosin II motors are components of the hop-trap mechanism. This raises the question whether similar mechanisms mediate random motion of larger particles with different physical and biological properties. Live-cell fluorescence imaging and a variational Bayesian analysis used in pattern recognition and machine learning were used to determine the molecular mechanisms of random motion of VSV inclusion bodies and cellular early endosomes. VSV inclusion bodies are liquid-liquid phase separated compartments that are the major sites of viral RNA synthesis, and early endosomes are representative of cellular membrane-bound organelles. Like VSV RNPs, inclusion bodies and early endosomes moved from one trapped state to another, but the distance between states was inconsistent with hopping between traps, indicating that the apparent state-to-state movement is mediated by trap movement. Like VSV RNPs, treatment with the actin filament depolymerizing inhibitor latrunculin A increased VSV inclusion body mobility by increasing the size of the traps. In contrast neither treatment with latrunculin A nor depolymerization of microtubules by nocodazole treatment affected the size of traps that confine early endosome mobility, indicating that intermediate filaments are likely major trap components for these cellular organelles.
A critical period for prefrontal cortex PV interneuron myelination and maturation
Authors: Hijazi S. , Pascual-García M. , Nabawi Y. , Kushner S.A.
Published: August 2023

Abstract

Recent studies have highlighted axonal myelination as a common feature of parvalbumin-positive (PV) interneurons throughout the cerebral cortex. However, the precise function of PV interneuron myelination remains incompletely understood. In this study, we used the cuprizone model of demyelination to investigate how PV interneuron myelination might influence their neuronal physiology. Specifically, we examined whether impairing myelination from postnatal day 21 onwards, during a critical neurodevelopmental period of the prefrontal cortex (PFC), can affect PV interneuron maturation and function. Using whole-cell patch-clamp recordings to examine intrinsic properties of PV interneurons in the PFC, we found that juvenile demyelination induced robust alterations of PV interneuron firing patterns. Specifically, we observed that demyelination caused an impairment in the ability of PV interneurons to sustain high frequency firing associated with a substantial decrease in Kv3-specific currents. We also found a significant impairment in PV interneuron autaptic self-inhibitory transmission, a feature implicated in temporal control of PV interneuron firing during cortical network activity. Following a remyelination period of 5 weeks, PV interneuron properties were only partially recovered and mice showed clear social deficits, suggesting that transient juvenile demyelination leads to long-lasting behavioral impairments. In contrast, adult demyelination had no significant effects on PV interneuron firing properties. Together, our data uncovers a critical period for juvenile myelination as an important factor in PFC PV interneuron development and brain maturation.
Crystal structure of 2-{[5-(methylsulfanyl)-4-phenyl-4H-1,2,4-triazol-3-yl]methyl}benzo[d]thiazole
Authors: Azzam Rasha A. , Elgemeie Galal H. , Elboshi Heba A. , Jones Peter G.
Published: August 2023

In the structure of the title compound, C17H14N4O2, the triazole ring exhibits interplanar angles of 63.86 (2) and 76.96 (2)° with the phenyl and benzothiazole planes, respectively. The C—C—C angle at the methylene group is rather wide at 114.28 (4)°. The packing involves three borderline C—H...N contacts, two of which combine to form layers parallel to ac, and a pairing of the triazole rings across an inversion centre [interplanar distance of 3.1852 (2) Å].
Ecosystems of doing business and living standards: a configurational analysis based on Chinese cities
Authors: Li Jiaxin , Du Yunzhou , Sun Ning , Xie Zhimin
Published: August 2023

Purpose

This paper aims to explain the causal complexity between ecosystems of doing business and living standards based on the theoretical model of the ecosystem of doing business proposed by Li (2019) and Du et al. (2020). By integrating ecological theory, transaction cost theory and institutional logics theory, this study explored effective ecosystems of doing business that achieve high living standards and explained the interpretive mechanisms behind different ecosystems of doing business. Moreover, this study also analyzed whether there were any necessary elements that lead to high living standards and discussed how the interactions between these elements influence carrying capacity and transaction costs from government logic and market logic, thus affecting living standards.

Design/methodology/approach

In this study, fuzzy set qualitative comparative analysis (fsQCA) and necessary condition analysis (NCA) were combined to analyze the data from the 2020 China City Statistical Yearbook, covering the main socioeconomic statistical data of cities at all levels in 2019.

Findings

This study found that no individual factor of the ecosystems of doing business was necessary to achieve high living standards, but the high level of human capital, innovation capacity, financial access and market demand play a significant role in achieving high living standards. Furthermore, two effective types of ecosystems of doing business lead to high living standards, namely, market dominance (government’s “invisible hand” or “nudging hand”) and government–market logic mutualism/symbiosis (government’s “helping hand”).

Originality/value

First, this work found that individual elements were not a necessary condition for high living standards, not only in kind but also in degree, complementing fsQCA with NCA, which indicates that environmental elements can be substituted by others. Second, this study considered the complex effects and explained the mechanisms behind different ecosystems of doing business, drawing on ecological theory, transaction cost theory and institutional logics theory from a configurational perspective. This study deepened the theories’ applications in the field of living standards and further discussed the elements interactions. Third, this study introduced configurational perspective and QCA into living standards research and adopted a mixed method that combines fsQCA and NCA to analyze the causal complexity between ecosystems of doing business and people’s living standards.