bluuebunny/crossref_metadata_2025 huggingface dataset:
Diet-specific responses of skull traits to aridity gradients in bovids and cervids
Authors: Quibod Ma. Niña Regina M , Gélin Uriel , van Langevelde Frank , Tomlinson Kyle W
Published: July 2023

Feeding efficiency of mammalian herbivores is associated with skull traits known to differ between feeding guilds. As climate is known to affect the architecture and functional traits of plants, skull morphology may change as plant traits change along climate gradients. We tested whether skull traits of more than 70% of the extant bovid and cervid species are related to aridity, and whether these relationships differ across feeding guilds (browser, grazer, mixed feeder). We used muzzle width to represent food ingestion and masseteric fossa length to represent oral processing. For the models without phylogeny, both muzzle width and masseteric fossa length increased towards wetter climates for grazers, but not for mixed feeders or browsers. These patterns suggest that grazer diets may change more dramatically across aridity gradients than the other two groups, possibly linked to changes in both the architecture and toughness of grasses. In models accounting for phylogeny, no changes in either trait across aridity gradient were found, which appeared to be due to subfamily differentiation along the aridity gradient. Our results suggest that deeper insights into the evolution of herbivore skulls may be achieved by using quantified diet data to directly test plant trait effects on skull morphology.
Thoracolumbar Vertebral Endplate Defect Morphology
Authors: Faul James , Umoh Joseph , Holdsworth David W. , Battié Michele C.
Published: July 2023

Study Design:

A descriptive, cross-sectional cadaver study

Objective:

This study aimed to provide a thorough depiction of vertebral endplate defects classified based on their morphological features and reported with respect to size, location, and prevalence in human cadaveric spines of older adults.

Summary of Background Data:

Back pain has been associated with vertebral endplate defects; however, findings have been inconsistent. This is partially due to miscommunication surrounding the classification of endplate defects observed using clinical imaging, and limited knowledge of the types of defects present on the endplate and their prevalence. Comprehensive study of vertebral endplates is needed to clarify types of structural defects, their character and prevalence.

Methods:

Using micro-CT, three-dimensional reconstructed images were created of 409 endplates from 19 cadaveric spines (9 men and 10 women, aged 62-91; T6-S1). Endplate defects were categorized based on their morphology, size and location in order to investigate distribution patterns.

Results:

Seven types of endplate defects were identified: Schmorl’s nodes, corner fracture or limbus vertebra, other fractures, erosion, jagged surface, calcification, and depressions. Defects were identified on 63.6% of endplates. Multiple defects were present on 19.1% of endplates. Fracture and erosion were the most common defect types. Defects were more common on the endplate cranial to the intervertebral disc and in male specimens (P=0.01). Defects were larger in the lumbar spine and the ‘total area of endplate defect’ was larger on the cranial than caudal endplate in the thoracic spine (P<0.05).

Conclusion:

This is the first study of which we are aware that provides a thorough depiction of the morphology and distribution of endplate defects across the entire lower thoracic and lumbar spine (T6-S1) using micro-CT. Results support the presence of several distinct endplate defect phenotypes with different prevalence rates and provide a reference when considering endplate defects in the elderly.

Level of evidence:

N/A
Acyl-CoA synthase ACSL4: an essential target in ferroptosis and fatty acid metabolism
Authors: Ding Kaiyue , Liu Chongbin , Li Li , Yang Ming , Jiang Na , Luo Shilu , Sun Lin
Published: July 2023

Long-chain acyl-coenzyme A (CoA) synthase 4 (ACSL4) is an enzyme that esterifies CoA into specific polyunsaturated fatty acids, such as arachidonic acid and adrenic acid. Based on accumulated evidence, the ACSL4-catalyzed biosynthesis of arachidonoyl-CoA contributes to the execution of ferroptosis by triggering phospholipid peroxidation. Ferroptosis is a type of programmed cell death caused by iron-dependent peroxidation of lipids; ACSL4 and glutathione peroxidase 4 positively and negatively regulate ferroptosis, respectively. In addition, ACSL4 is an essential regulator of fatty acid (FA) metabolism. ACSL4 remodels the phospholipid composition of cell membranes, regulates steroidogenesis, and balances eicosanoid biosynthesis. In addition, ACSL4-mediated metabolic reprogramming and antitumor immunity have attracted much attention in cancer biology. Because it facilitates the cross-talk between ferroptosis and FA metabolism, ACSL4 is also a research hotspot in metabolic diseases and ischemia/reperfusion injuries. In this review, we focus on the structure, biological function, and unique role of ASCL4 in various human diseases. Finally, we propose that ACSL4 might be a potential therapeutic target.
Immunodynamics of Macrophages in Renal Fibrosis
Authors: Chung Jeff Yat-Fai , Zhang Ying-Ying , Ji Zoey Ze-Yuan , Tang Tian , Chen Jiao-Yi , Chi-Wai Tang Sydney , Tang Patrick Ming-Kuen
Published: July 2023

Macrophages are crucial mediators in the development of inflammatory diseases, including kidney diseases. Unresolved renal inflammation can progressively develop into chronic kidney disease (CKD), resulting in structural and functional impairment of the injured kidney due to renal fibrosis and leading to irreversible end-stage renal disease (ESRD). Increasing evidence suggests that phenotypic changes in macrophages are essential for CKD development and progression. Interestingly, advanced bioinformatics and single-cell RNA-sequencing analyses have revealed the crucial mechanism of macrophage-myofibroblast transition, which may be a novel therapeutic target for renal fibrosis. Therefore, a better understanding of the immunodynamics of macrophages in diseased kidneys may help identify effective therapeutic strategies for unmet clinical needs. This review summarizes the regulatory roles and underlying mechanisms of macrophages in renal fibrosis and their therapeutic implications in kidney diseases, including ESRD.
The Age-Related Growth of Mastoid Air Cells in Infancy: A Retrospective Cross-Sectional Study
Authors: Chen Chenyu , Huang Xiying , Chen Zhen , Liu Yang , Chen Zhifeng , Zeng Chaojun , Chen Yuqing , Nian Shengqing , Weng Simin , Xu Yuanteng , Lin Chang
Published: July 2023

Objectives

To investigate the normal growth and development of mastoid pneumatization volume from 5 to 12 months for pediatric otosurgeons.

Study Design

Retrospective chart review.

Setting

A tertiary referral center.

Patients

This study evaluated age-dependent changes in mastoid air cell volume in 94 (188 ears) patients aged 5 to 12 months without a history of middle ear disease.

Main Outcome Measures

Volume reconstruction was based on high-resolution computed tomography images using a three-dimensional reconstruction that is considered normal by radiologists. One-way analysis of variance and linear regression were used to determine the relationship between the volume and age in male and female subjects.

Results

Forty-eight scans were from male and 46 from female patients. In the age group from 5 to 12 months, the mastoid pneumatization was independent of age (p > 0.05). There were no significant volume differences found between the age groups. Neither male/female nor right/left significant differences were observed in relation to the algebraic data of the mastoid air cells volume (p > 0.05).

Conclusions

Based on this analytic study, we are the first to use three-dimensional volume quantification based on high-resolution computed tomography in such large samples of early infancy. Because of its potential role as a susceptibility factor for otitis media and other otologic problems, it is important to describe the growth and development of mastoid pneumatization. More extensive clinical studies are needed to give a comprehensive insight into the air cell volume across age groups in different populations.
The Relationship Between Regional Growth in Neonatal Intensive Care Capacity and Perinatal Risk
Authors: Davis Rebekah , Stuchlik Patrick M. , Goodman David C.
Published: July 2023

Background:

The supply of US neonatal intensive care unit (NICU) beds and neonatologists is known to vary markedly across regions, but there have been no investigation of patterns of recent growth (1991–2017) in NICUs in relation to newborn need.

Objective:

The objective of this study was to test the hypothesis that greater growth in NICU capacity occurred in neonatal intensive care regions with higher perinatal risk.

Research Design:

A longitudinal ecological analysis with neonatal intensive care regions (n=246) as the units of analysis. Associations were tested using linear regression.

Subjects:

All US live births ≥400 g in 1991 (n=4,103,528) and 2017 (n=3,849,644).

Measures:

Primary measures of risk were the proportions of low–birth weight and very low–birth weight newborns and mothers who were Black or had low educational attainment.

Results:

Over 26 years, the numbers of NICU beds and neonatologists per live birth increased 42% and 200%, respectively, with marked variation in growth across regions (interquartile range: 0.3–4.1, beds; neonatologists, 0.4–1.0 per 1000 live births). A weak association of capacity with perinatal risk in 1991 was absent in 2017. There was no meaningful (ie, clinical or policy relevant) association between regional changes in capacity and regions with higher perinatal risk or lower capacity in 1991; higher increases in perinatal risk were not associated with higher capacity growth.

Conclusion:

The lack of association between newborn medical needs and the supply of NICU resources raises questions about the current effectiveness of newborn care at a population level.
Sexual Health and Quality of Life in Cancer Survivors With Pelvic Radiation Injuries
Authors: Hauken May Aasebø , Velure Grete Kalleklev , Müller Bernd , Sekse Ragnhild Johanne Tveit
Published: July 2023

Background

Little knowledge exists on how late radiation tissue injuries (LRTIs) affect sexual health and health-related quality of life (HRQOL) in pelvic cancer survivors.

Objective

To explore sexual health and HRQOL in cancer survivors with pelvic LRTI.

Method

A descriptive cross-sectional study was conducted, including 83 pelvic cancer survivors with LRTI. Data on sexual health, LTRIs, and HRQOL were collected by validated questionnaires, whereas medical variables were collected from medical records.

Results

Participants’ sexual health was severely impaired. Bowel and urinary LRTIs correlated with most of the symptoms of impaired sexual health (Pearson r = −0.241 to −0.376, P < .05–.01). Men and women reported different sexual challenges related to functional and symptomatic variables but not on the gender-neutral aspects of sexual health. Younger survivors, gynecological cancer survivors, or those who received external and internal radiation or additional chemotherapy reported significantly (P < .05–.001) higher levels of sexual impairment. Participants’ HRQOL was impaired. Several dimensions of sexual health correlated significantly (P < .05–.001) with the functional dimensions of reduced HRQOL.

Conclusion

Cancer survivors with pelvic LRTIs experience severely impaired sexual health across genders, with negative consequences for their HRQOL.

Implications for Practice

Healthcare professionals should include sexual health as an important part of individual patients’ health and HRQOL throughout their treatment trajectory and follow-up, by screening sexual health, implementing measures and interventions to promote sexual health, and supporting survivors’ coping and health-promoting strategies.
Increased Dispersion of Ventricular Repolarization as an Arrhythmic Risk Marker in Drug-free Patients With Major Depressive Disorder: A Preliminary Comparative Study
Authors: Balcioglu Yasin H. , Gokcay Hasan , Kirlioglu Balcioglu Simge S. , Solmaz Mustafa
Published: July 2023

Objective:

Drug-free patients with major depressive disorder (MDD) are understudied in terms of increased risk for arrhythmias. In this study, we compared changes in corrected QT interval (QTc), QTc dispersion (QTcd), Tpeak-Tend(Tp-e), Tp-e/QT ratio, corrected JT interval (JTc), and JTc dispersion (JTcd), which are considered to be among the risk factors for the emergence of ventricular arrhythmias in patients with MDD.

Methods:

The study involved 50 patients with MDD who had been free of psychotropic medications for at least 1 month and 52 age-matched and sex-matched healthy controls. Illness-related characteristics, including duration of illness and Beck Depression Inventory scores, were recorded. Electrocardiography recordings made under a standardized procedure were performed for all participants, and arrhythmia risk markers were calculated from the electrocardiograms.

Results:

The patient group had significantly higher QTcd, JTc, and JTcd values compared with the controls. Among electrocardiogram markers, only Tp-e/QTc was significantly and inversely correlated with the duration of illness, while none of the markers was associated with Beck Depression Inventory scores.

Conclusions:

Alterations in electrocardiogram-derived markers of ventricular arrhythmia, which can be obtained easily and inexpensively, can be evaluated for the prediction and prevention of severe cardiac conditions in patients with MDD and considered in selecting the safest antidepressant options available.
Incidence and severity of SARS-CoV-2 infection in children and young people with HIV in Europe
Authors:   The European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC) study group∗
Published: July 2023

We assessed incidence of SARS-CoV-2 infection and disease severity among children and young people with HIV from cohorts across nine European countries. Of 1717 included, with median duration of follow-up 20.1 months, 134 (8%) had documented SARS-CoV-2 infection, a rate of 49 [95% confidence interval (CI) 42–58] per 1000 person-years. All symptomatic cases had mild coronavirus disease 2019 (COVID-19), three were hospitalized, and no deaths were reported, which may be reassuring for clinicians and families.
Correction of Cleft Lip Nose Deformity With Circular Shape Alar Graft and Block Costal Cartilage
Authors: Zhang Xulong , Song Zhen , Xu Yihao , You Jianjun , Wang Huan , Zheng Ruobing , Tian Le , Guo Junsheng , Fan Fei
Published: July 2023

Background

Secondary deformities of the cleft lip and nose are mainly caused by the long period of craniofacial development and the secondary scarring. Correction of the secondary cleft lip-nose deformity is a complex process that requires both the correction of the soft tissue and skeletal support. The purpose of this study was to present our experience in correcting the secondary unilateral cleft lip-nose deformities with autologous costal cartilage.

Methods

A retrospective analysis of patients who underwent correction of unilateral cleft nasal deformity with simultaneous rhinoplasty by a senior surgeon from January 2015 to January 2022 was conducted. Preoperative and postoperative measurements of the columellar-labial angle and the inclination of nasal base were conducted to evaluate the surgical outcomes.

Results

A total of 54 patients were included in this study according to the inclusion criteria. The mean follow-up period was 4 years (range, 1–7 years). The mean values of the columellar-labial angle were 91.1 ± 9.2 degrees preoperatively and 101.0 ± 5.9 degrees postoperatively. The mean values of the inclination of nasal base were 4.5 ± 1.2 degrees preoperatively and 0.9 ± 0.4 degrees postoperatively. There was a considerable increase in the columellar-labial angle after the surgery (9.9 ± 6.0 degrees; P < 0.01). The inclination of nasal base decreased significantly (3.6 ± 1.1 degrees; P < 0.01).

Conclusions

Our approach on correction the secondary clef lip nose through repositioning the muscles by Z-plasty and application of the block cartilage graft and circular shape alar graft has achieved long-term satisfactory results.
Should the Eigenfactor Replace the Impact Factor?
Authors: Skorochod Ron , Grinblat Golda , Uri Ophir , Wolf Yoram
Published: July 2023

Background

Despite the global acceptance of the impact factor (IF) by researchers and academic institutions as one, criticism has been voiced regarding its effectiveness in evaluating the unbiased impact of a journal. To overcome the limitations and drawbacks of the IF that were presented by the scientific community, they introduced several other citation-based bibliometric indices.

Methods

All plastic and reconstructive surgery journals were analyzed, and bibliometric indices were extracted from the relevant source. Pearson correlation coefficients were used to determine correlations between the various indices.

Results

All correlations in between the various bibliometric indices were found to be positively and statistically significant, ranging from moderately highly associated for the IF and Eigenfactor (r= 0.632) to very strongly associated (r= 0.962) for the IF and the Article Influence Score.

Conclusion

In the field of plastic and reconstructive surgery, the Eigenfactor and its derivative, the Article Influence Score, could potentially serve as better indices than the IF in demonstrating the overall picture. This information is based on the inclusion of a greater number of journals in the calculation and subtraction of self-citations, without compromising their correlation with other indices.

The use of Eigenfactor and other additional bibliometrics cooperatively with the IF could provide the most extensive evaluation of a journal's scientific impact.
Improving the Care of Our Patients
Authors: Linkugel Andrew D. , Mackinnon Susan E. , Snyder-Warwick Alison K.
Published: July 2023

Background

James Barrett Brown was one of the founders of Plastic and Reconstructive Surgery as a specialty in the United States. Susan Mackinnon started the James Barrett Brown Resident Research Day in 1997 in his honor to serve as an annual opportunity for trainees to present their research to the Division and a visiting contemporary leader in plastic surgery. We sought to determine the proportion of Resident Research Day projects that have progressed to publication.

Methods

Available internal records from 1998 to 2019 were used to identify presenters and projects. Academic productivity of presenters was estimated with the h-index from the Scopus database.

Results

One hundred forty-five students, residents, and fellows presented 276 projects at Resident Research Day from 1998 to 2019. These presentations were associated with 144 unique peer-reviewed publications, representing 52% of the presented projects. They were published an average of 1.8 years after presentation, and the presenter was the first or last author on 67% of them. The current average h-index of trainees who published at least 1 project (8.3) is significantly higher than the h-index of those who did not (5.0, P < 0.001).

Conclusions

The James Barrett Brown Resident Research Day not only honors the legacy of Brown but also enhances scholarly activity of trainees. The opportunity to present and publish research teaches project planning, implementation, and data analysis, followed by manuscript preparation and the publication process. This important skill set can provide the foundation for the academic careers of future leaders in plastic surgery.
Serum Interleukin 6 Level is Associated With Overall Survival and Treatment Response in Gastric and Gastroesophageal Junction Cancer
Authors: Karalis John D. , Ju Michelle R. , Yoon Lynn Y. , Castro-Dubon Esther C. , Reznik Scott I. , Hammer Suntrea T.G. , Porembka Matthew R. , Wang Sam C.
Published: July 2023

Objective:

Identify novel prognostic and predictive biomarkers for gastric and gastroesophageal junction adenocarcinoma (G+GEJ).

Background:

There are few biomarkers to guide treatment for G+GEJ. The systemic inflammatory response of G+GEJ patients is associated with survival. In this study, we evaluated the relationship of circulating serum cytokine levels with overall survival (OS) and pathologic tumor regression grade (TRG) in G+GEJ patients.

Methods:

We queried the UT Southwestern gastric cancer biobank to identify consecutive patients diagnosed with G+GEJ from 2016-2022; these patients had pre-treatment serum collected at diagnosis. For patients who received neoadjuvant therapy, an additional serum sample was collected immediately prior to surgical resection. An unbiased screen of 17 cytokines were measured in a discovery cohort. A multivariable Cox proportional hazards model was used to assess the association of cytokine concentration with OS. Findings were validated in additional patients. In patients who received neoadjuvant therapy, we assessed whether the change in IL-6 after therapy was associated with TRG.

Results:

67 patients were included in the discovery cohort and IL-6 was the only pre-treatment cytokine associated with OS; this was validated in 134 other patients (HR: 1.012 per 1 pg/mL increase, 95%CI: 1.006-1.019, P=0.0002). Patients in the top tercile of IL-6 level had worse median OS (10.6 mo) compared to patients in the intermediate (17.4 mo) and bottom tercile (35.8 mo, P<0.0001). Among patients who underwent neoadjuvant therapy (n=50), an unchanged or decrease in IL-6 level from pre-treatment to post-treatment had a sensitivity and specificity of 80% for predicting complete or near-complete pathologic tumor regression (TRG 0-1).

Conclusion:

Pre-treatment serum level of IL-6 is a promising prognostic biomarker for G+GEJ patients. Comparing pre- and post-neoadjuvant IL-6 levels may predict pathologic response to neoadjuvant therapy.
Bacteriophages as an alternative for biofilm eradication in Klebsiella Pneumonia Strains.
Authors: Chipurupalli Alikya , Rathore Rohit , Karumidze Natia
Published: July 2023

Background -Biofilms are a cause for a variety of infectious diseases given its abundant existence throughout nature. With the help of biofilm, the pathogenic bacteria are protected from unfavorable environments and conditions like extreme pH and temperature, high salinity, UV radiation. Most importantly is that it increases the resistance to antibiotics by 1000 times. Antimicrobial resistance has serious consequences not only in health care but also in food processing, drinking water distribution system, the paper industry, and others.
 
Materials and Methods – In our study were used three K. pneumoniae (kp41, kp42, kp47), and two P. aeruginosa strains (PA315, PA88). Klebsiella pneumoniae and P. aeruginosa specific bacteriophages (vB-kB-41, vB-Kp-42, vB-kp-47, vB-Psa-315, and vB-Psa-88) were used to test the formation of biofilm by using the Microtiter plate method (TCP) and Tube method (TM).
 
Results – All the tested bacteria showed to form biofilms in tubes, while on 96 well plates we could observe obvious biofilm with P.aeruginosa N88. With both methods, we had biofilm reduction that was treated with appropriate bacteriophages and incubated for 24 hours.
 
Conclusion- Emerging antimicrobial resistance needs to be addressed before we run out of our potential antibiotics. Usage of biofilms can be one of the alternatives to effectively and specifically treat these serious gram-negative infections. A more standardized approach should be established for identification of such specific bacteriophage strains which curb the bacterial growth efficiently.
The proteolysis of ZP proteins is essential to control cell membrane structure and integrity of developing tubes
Authors: Drees Leonard , Riedel Dietmar , Schuh Reinhard , Behr Matthias
Published: July 2023

Membrane expansion integrates multiple forces to mediate precise tube growth and network formation. Defects lead to deformations, as found in diseases such as polycystic kidney diseases, aortic aneurysms, stenosis, and tortuosity. We identified a mechanism of sensing and responding to the membrane expansion of tracheal tubes. We show inDrosophilathat Zona Pellucida domain proteins Piopio and Dumpy cooperate to integrate mechanical stress at cell membranes and luminal matrix. When tension appears at the apical membrane due to tracheal tube length expansion, Piopio undergoes ectodomain shedding by the Matriptase homolog Notopleural, which releases Piopio-mediated linkages between membranes and extracellular matrix. Failure of this process leads to deformations of the apical membrane and comprises tubular network function. We also show conserved ectodomain shedding by the human matriptase during TGF-β signaling, both of which are required in the lung, providing novel approaches for in-depth analysis of pulmonary diseases caused by cell and tube shape changes.
Functional profiling of the sequence stockpile: a review and assessment of in silico prediction tools
Authors: Ramakrishnan Prabakaran , Bromberg Yana
Published: July 2023

In silico functional annotation of proteins is crucial to narrowing the sequencing-accelerated gap in our understanding of protein activities. Numerous function annotation methods exist, and their ranks have been growing, particularly so with the recent deep learning-based developments. However, it is unclear if these tools are truly predictive. As we are not aware of any methods that can identify new terms in functional ontologies, we ask if they can, at least, identify molecular functions of new protein sequences that are non-homologous to or far-removed from known protein families. Here, we explore the potential and limitations of the existing methods in predicting molecular functions of thousands of such orphan proteins. Lacking the ground truth functional annotations, we transformed the assessment of function prediction into evaluation of functional similarity of orphan siblings, i.e. pairs of proteins that likely share function, but that are unlike any of the currently functionally annotated sequences. Notably, our approach transcends the limitations of functional annotation vocabularies and provides a platform to compare different methods without the need for mapping terms across ontologies. We find that most existing methods are limited to identifying functional similarity of homologous sequences and are thus descriptive, rather than predictive of function. Curiously, despite their seemingly unlimited by-homology scope, novel deep learning methods also remain far from capturing functional signal encoded in protein sequence. We believe that our work will inspire the development of a new generation of methods that push our knowledge boundaries and promote exploration and discovery in the molecular function domain.
Exploring the parity paradox: Differential effects on neuroplasticity and neuroinflammation by APOEe4 genotype at middle-age
Authors: Lee Bonnie H , Cevizci Mel , Lieblich Stephanie E , Ibrahim Muna , Wen Yanhua , Eid Rand S , Lamers Yvonne , Duarte-Guterman Paula , Galea Liisa A.M.
Published: July 2023

Female sex and Apolipoprotein E (APOE) ε4 genotype are top non-modifiable risk factors for Alzheimer’s disease (AD). Although female-unique experiences like parity (pregnancy and motherhood) have positive effects on neuroplasticity at middle age, previous pregnancy may also contribute to AD risk. To explore these seemingly paradoxical long-term effects of parity, we investigated the impact of parity with APOEε4 genotype by examining behavioural and neural biomarkers of brain health in middle-aged female rats. Our findings show that primiparous (parous one time) hAPOEε4 rats display increased use of a non-spatial cognitive strategy and exhibit decreased number and recruitment of new-born neurons in the ventral dentate gyrus of the hippocampus in response to spatial working memory retrieval. Furthermore, primiparity and hAPOEε4 genotype synergistically modulate neuroinflammatory markers in the ventral hippocampus. Collectively, these findings demonstrate that previous parity in hAPOEε4 rats confers an added risk to present with reduced activity and engagement of the hippocampus as well as elevated pro-inflammatory signaling, and underscores the importance of considering female-specific factors and genotype in health research.

Highlights

hAPOEε4 rats made more errors and used a non-spatial cognitive strategy

Primiparous hAPOEε4 rats increased use of a non-spatial cognitive strategy

Parity increased neurogenesis in wildtype rats, but decreased it in hAPOEε4 rats

Primiparous hAPOEε4 rats had less active new neurons in response to memory retrieval

Parity and hAPOEε4 affect the neuroimmune milieu in a region-specific manner
Recombination map tailored to Native Hawaiians improves robustness of genomic scans for positive selection
Authors: Dinh Bryan L. , Tang Echo , Taparra Kekoa , Nakatsuka Nathan , Chen Fei , Chiang Charleston W. K.
Published: July 2023

Recombination events establish the patterns of haplotypic structure in a population and estimates of recombination rates are used in several downstream population and statistical genetic analyses. Using suboptimal maps from distantly related populations may reduce the efficacy of genomic analyses, particularly for underrepresented populations such as the Native Hawaiians. To overcome this challenge, we constructed recombination maps using genome-wide array data from two study samples of Native Hawaiians: one reflecting the current admixed state of Native Hawaiians (NH map), and one based on individuals of enriched Polynesian ancestries (PNS map) with the potential to be used for less admixed Polynesian populations such as the Samoans. We found the recombination landscape to be less correlated with those from other continental populations (e.g. Spearman’s rho = 0.79 between PNS and CEU (Utah residents with Northern and Western European ancestry) compared to 0.92 between YRI (Yoruba in Ibadan, Nigeria) and CEU at 50 kb resolution), likely driven by the unique demographic history of the Native Hawaiians. PNS also shared the fewest recombination hotspots with other populations (e.g. 8% of hotspots shared between PNS and CEU compared to 27% of hotspots shared between YRI and CEU). We found that downstream analyses in the Native Hawaiian population, such as local ancestry inference, imputation, and IBD segment and relatedness detections, would achieve similar efficacy when using the NH map compared to an omnibus map. However, for genome scans of adaptive loci using integrated haplotype scores, we found several loci with apparent genome-wide significant signals (|Z-score| > 4) in Native Hawaiians that would not have been significant when analyzed using NH-specific maps. Population-specific recombination maps may therefore improve the robustness of haplotype-based statistics and help us better characterize the evolutionary history that may underlie Native Hawaiian-specific health conditions that persist today.
ScreenDMT reveals linoleic acid diols replicably associate with BMI and stimulate adipocyte calcium fluxes
Authors: Dreyfuss Jonathan M. , Djordjilovic Vera , Pan Hui , Bussberg Valerie , MacDonald Allison M. , Narain Niven R. , Kiebish Michael A. , Blüher Matthias , Tseng Yu-Hua , Lynes Matthew D.
Published: July 2023

Activating brown adipose tissue (BAT) improves systemic metabolism, making it a promising target for metabolic syndrome. BAT is activated by 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME), which we previously identified to be inversely associated with BMI and which directly improves metabolism in multiple tissues. Here we profile plasma lipidomics from a cohort of 83 people and test which lipids’ association with BMI replicates in a concordant direction using our novel tool ScreenDMT, whose power and validity we demonstrate via mathematical proofs and simulations. We find that the linoleic acid diols 12,13-diHOME and 9,10-diHOME both replicably inversely associate with BMI and mechanistically activate calcium fluxes in mouse brown and white adipocytes in vitro, which implicates this pathway and 9,10-diHOME as candidate therapeutic targets. ScreenDMT can be applied to test directional mediation, directional replication, and qualitative interactions, such as identifying biomarkers whose association is shared (replication) or opposite (qualitative interaction) across diverse populations.
A microfluidic strategy to capture antigen-specific high affinity B cells
Authors: Alhassan Ahmed M. , Shirure Venktesh S. , Luo Jean , Nguyen Bryan B. , Rollins Zachary A. , Shergill Bhupinder S. , Zhu Xiangdong , Baumgarth Nicole , George Steven C.
Published: July 2023

Assessing B cell affinity to pathogen-specific antigens prior to or following exposure could facilitate the assessment of immune status. Current standard tools to assess antigen-specific B cell responses focus on equilibrium binding of the secreted antibody in serum. These methods are costly, time-consuming, and assess antibody affinity under zero-force. Recent findings indicate that force may influence BCR-antigen binding interactions and thus immune status. Here, we designed a simple laminar flow microfluidic chamber in which the antigen (hemagglutinin of influenza A) is bound to the chamber surface to assess antigen-specific BCR binding affinity of five hemagglutinin-specific hybridomas under 65- to 650-pN force range. Our results demonstrate that both increasing shear force and bound lifetime can be used to enrich antigen-specific high affinity B cells. The affinity of the membrane-bound BCR in the flow chamber correlates well with the affinity of the matched antibodies measured in solution. These findings demonstrate that a microfluidic strategy can rapidly assess BCR-antigen binding properties and identify antigen-specific high affinity B cells. This strategy has the potential to both assess functional immune status from peripheral B cells and be a cost-effective way of identifying individual B cells as antibody sources for a range of clinical applications.
Extrasynaptic localization is essential for α5GABAAreceptor modulation of dopamine system function
Authors: McCoy Alexandra M. , Prevot Thomas D. , Mian Md Yeunus , Sharmin Dishary , Ahmad Adeeba N. , Cook James M. , Sibille Etienne L. , Lodge Daniel J.
Published: July 2023

Dopamine system dysfunction, observed in animal models with psychosis-like symptomatology, can be restored by targeting Gamma-Aminobutyric Acid type A receptors (GABAAR) containing the α5, but not α1, subunit in the ventral hippocampus (vHipp). The reason for this discrepancy in efficacy remains elusive; however, one key difference is that α1GABAARs are primarily located in the synapse, whereas α5GABAARs are mostly extrasynaptic. To test whether receptor location is responsible for this difference in efficacy, we injected a small interfering ribonucleic acid (siRNA) into the vHipp to knock down radixin, a scaffolding protein that holds α5GABAARs in the extrasynaptic space. We then administered GL-II-73, a positive allosteric modulator of α5GABAARs (α5-PAM) known to reverse shock-induced deficits in dopamine system function, to determine if shifting α5GABAARs from the extrasynaptic space to the synapse would prevent the effects of α5-PAM on dopamine system function. As expected, knockdown of radixin significantly decreased radixin-associated α5GABAARs and increased the proportion of synaptic α5GABAARs, without changing the overall expression of α5GABAARs. Importantly, GL-II-73 was no longer able to modulate dopamine neuron activity in radixin-knockdown rats, indicating that the extrasynaptic localization of α5GABAARs is critical for hippocampal modulation of the dopamine system. These results may have important implications for clinical use of GL-II-73, as periods of high hippocampal activity appear to favor synaptic α5GABAARs, thus efficacy may be diminished in conditions where aberrant hippocampal activity is present.

Significance Statement

Dopamine activity is known to be altered in both psychosis patients and in animal models, with promising new antipsychotics restoring normal dopamine system function. One such drug is GL-II-73, a positive allosteric modulator of α5GABAARs (α5-PAM). Interestingly, previous research has shown that a positive allosteric modulator of α1GABAARs (α1-PAM) does not share this ability, even when directly given to the ventral hippocampus, a region known to modulate dopamine activity. One potential explanation for this difference we examined in this study is that α1GABAARs are primarily located in the synapse, whereas α5GABAARs are mostly extrasynaptic. Determining the mechanism of this differential efficacy could lead to the refinement of antipsychotic treatment and improve patient outcomes overall.
Low-dose inhalation exposure to trichloroethylene induces dopaminergic neurodegeneration in rodents
Authors: Adamson Ashley B. , Ilieva Neda M. , Stone William J. , De Miranda Briana R.
Published: July 2023

Trichloroethylene (TCE) is one of the most pervasive environmental contaminants in the world and is associated with Parkinson disease (PD) risk. Experimental models in rodents show that TCE is selectively toxic to dopaminergic neurons at high doses of ingestion, however, TCE is a highly volatile toxicant, and the primary pathway of human exposure is inhalation. As TCE is a highly lipophilic, volatile organic contaminant (VOC), inhalation exposure results in rapid diffusion throughout the brain, avoiding first-pass hepatic metabolism that necessitated high doses to recapitulate exposure conditions observed in human populations. We hypothesized that inhalation of TCE would induce significantly more potent neurodegeneration than ingestion and better recapitulate environmental conditions of vapor intrusion or off gassing from liquid TCE. To this end, we developed a novel, whole-body passive exposure inhalation chamber in which we exposed 10-month-old male and female Lewis rats to 50 ppm TCE (time weighted average, TWA) or filtered room air (control) over 8 weeks. In addition, we exposed 12-month-old male and female C57Bl/6 mice to 100 ppm TCE (TWA) or control over 12 weeks. Both rats and mice exposed to chronic TCE inhalation showed significant degeneration of nigrostriatal dopaminergic neurons as well as motor and gait impairments. TCE exposure also induced accumulation of pSer129-αSyn in dopaminergic neurons as well as microglial activation within the substantia nigra of rats. Collectively, these data indicate that TCE inhalation causes highly potent dopaminergic neurodegeneration and recapitulates some of the observed neuropathology associated with PD, providing a future platform for insight into the mechanisms and environmental conditions that influence PD risk from TCE exposure.
Relationship Between the P300 and Sequence Knowledge in a Changing Environment
Authors: Chou Ko-Ping , Hsu Tzu-Yu
Published: July 2023

The P300 amplitude has been linked to the processing of uncertain events. Studies have assumed that knowledge extracted from sequences of events corresponds to event probability. The relationship between the P300 and event uncertainty has been studied using the model-based analysis, in which the subjective expectancy of event probability is modeled and examined by using a quantity called “surprise.” However, other types of sequence knowledge exist, such as event transition probabilities, which comprises both event repetitions and event alterations. Whether the state of the environment affects the encoded sequence knowledge is not fully understood, and the type of sequence knowledge, event probability or event transition probability, that is encoded in the brain in a changing environment remains unknown. We determined whether fluctuations in the P300 are better explained by surprise based on a model of event probability or by surprise based on a model of event transition probability. Participants completed a two-choice response task in which a binary sequence was generated from a hidden Markov model. Reaction times indicated that behavior changed depending on the event transitions. The model-based analysis revealed that trial-by-trial P300 was better explained by surprise based on a model of event transition probability. Our results suggest that humans use the sequence knowledge of event transitions in a changing environment.
Snapshots of ribosome dynamics near atomic-resolution in situ: full insight into the eukaryotic elongation cycle
Authors: Cheng Jing , Wu Chunling , Li Junxi , Yang Qi , Zhao Mingjie , Zhang Xinzheng
Published: July 2023

Many protein complexes are highly dynamic in cells, characterizing their conformational changes in cells is crucial for unraveling their functions. In this report, using cryo-electron microscopy, 451,700 ribosome particles fromSaccharomyces cerevisiaecell lamellae were obtained to solve the 60S region to 2.9 Å resolution by in situ single particle analysis. Over 20 distinct conformations were identified by 3D classification with resolutions typically higher than 4 Å. These conformations were used to reconstruct a complete elongation cycle of eukaryotic translation with elongation factors. We found that compact eEF2 anchors to the partially rotated ribosome after subunit rolling, and hypothesize that it stabilizes the local conformation for peptidyl transfer. Moreover, an open eEF3 binding to a fully rotated ribosome was observed, whose conformational change was coupled with head swiveling and body back-rotation of the 40S subunit.
Bark traits affect epiphytic bryophyte community assembly in a temperate forest
Authors: Tatsumi Shinichi , Ohgue Takayuki , Azuma Wakana A. , Nishizawa Keita
Published: July 2023

Bark traits of trees often serve as a key factor determining the community structure of epiphytes. However, the extent to which barks modulate the relative importance of abiotic and biotic assembly processes of epiphytes is poorly understood. Here, using a community phylogenetic approach, we aimed to infer the assembly processes of epiphytic mosses and liverworts on tree species with varying bark traits in a temperate forest of central Japan. We observed a total of 56 moss and 35 liverwort species on 150 trees. Moss communities showed decreasing species richness and a tendency toward phylogenetic overdispersion, that is, higher phylogenetic diversity than expected by chance, in relation to increasing bark roughness, acidity, and wetness. Along the same bark gradients, liverwort communities became phylogenetically clustered. Species richness of both mosses and liverworts increased with the nitrogen content of barks. The results indicate non-random assembly processes such as interspecific competition on resource-rich barks and abiotic filtering associated with environmental harshness and microhabitat variety determined by barks. Our findings imply that bark traits modulate community assembly processes through which epiphyte diversity is maintained.
Is using Dual Energy Virtual Enhancing over Non-Contrast CT beneficial in terms of Diagnostic Accuracy of finding Adrenal Adenoma? : A Meta-analysis
Authors: Desai Dev , Duisenbayev Arman , Maniyar Pankti , Malafi Maria Eleni , Andharia Dev , Shah Abhijay B.
Published: July 2023

Background

The study compared the diagnostic accuracy of Dual Energy Virtual Non-Contrast CT (DEvNCT) to Non-Contrast CT (NCT) for adrenal adenomas. Adrenal nodules on CT scans require precise characterization to differentiate between benign and malignant lesions. CT imaging uses features like low attenuation and contrast enhancement to identify adenomas. However, distinguishing adenomas from non-adenoma lesions can be challenging due to overlapping attenuation levels.

DEvNCT, a post-processing technique enabled by dual-energy CT, optimizes adrenal lesion evaluation. The study aimed to compare the diagnostic accuracy of DEvNCT and NCT for adrenal adenomas.

Methodology

A systematic review and meta-analysis searched relevant literature in PubMed, Google Scholar, and Cochrane Library databases. The analysis included nine randomized controlled trials (RCTs) with 407 patients: three RCTs for NCT vs. Biopsy and six RCTs for DEvNCT vs. NCT. Study quality was assessed using appropriate tools.

Result

Results revealed DEvNCT had 72% sensitivity, 94% specificity, and 0.878 positive predictive value for adrenal adenoma diagnosis. NCT had 80% sensitivity, 68.1% specificity, and 0.831 positive predictive values. The difference in specificity between DEvNCT and NCT was significant, indicating DEvNCT’s superior ability to identify adenomas accurately.

Conclusion

The study concluded that DEvNCT exhibited comparable sensitivity but higher specificity than NCT in diagnosing adrenal adenomas. DEvNCT could potentially reduce follow-up imaging, lower costs, and minimize radiation exposure. However, biopsy remains the gold standard for confirming adrenal adenoma diagnosis.

Overall, DEvNCT shows promise for improving diagnostic accuracy compared to NCT in diagnosing adrenal adenomas. Further research and clinical validation are needed to confirm these findings.
Molecular mechanism of acid stress response ofA. acidoterrestrisDSM 3922Tunder sublethal pH environment
Authors: Liu Xiaoxue , Wu Youzhi , Jiao Lingxia , Ran Junjian , Sun Linjun , Ye Fuzhou , Liang Xinhong , Zhao Ruixiang
Published: July 2023

Acid-responsive proteome expression profiles ofAlicyclobacillus acidoterrestris(A. acidoterrestris) were analysed using label-free quantitative mass spectrometry to investigate its acid resistance mechanism at sublethal pH. Totally, 325 differential expression proteins were identified during acid stress at pH2.5 condition for 15 min, of which the expressions of 83 proteins were up-regulated and the other 242 proteins expressions were down-regulated. Differentially expressed proteins were mainly involved in organic nitrogen compounds metabolism, small molecule metabolism, organic acid metabolism and signal transduction. Overall, they were mapped into 97 metabolic pathways. Combination of KEGG pathway analysis and protein functional analysis suggested that the pH homeostasis system, changes in metabolic pathways, cell membrane permeability and DNA repair are the main acid resistance mechanisms ofA. acidoterrestrisat sublethal pH conditions. It is speculated thatA. acidoterrestrismay sense and transmit pH signals from the external environment through the nhaB protein which holds histidine-dependent acid resistance system, initiating a series of acid tolerance reactions. Our study demonstrated global physiological response ofA. acidoterrestristo sublethal pH, which provided a better understanding of acid adaption mechanism ofA. acidoterrestris.