bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Assessment Interview for Negative Symptoms (CAINS): A Systematic Review of Measurement Properties
Authors: Wehr Sophia , Weigel Lucia , Davis John , Galderisi Silvana , Mucci Armida , Leucht Stefan
Published: November 2023

Background and Hypothesis

Negative symptoms are very important for the overall loss of functioning observed in patients with schizophrenia. There is a need for valid tools to assess these symptoms.

Study Design

We used the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) systematic review guideline to evaluate the quality of the clinical assessment interview for negative symptoms (CAINS) as a clinician-rated outcome measurement (ClinROM).

Study Results

The search strategy resulted in the retrieval of 13 articles, 11 of which were included in this evaluation. In terms of risk of bias, most articles reported on measures of internal consistency and construct validity, which were overall of good quality. Structural validity, reliability, measurement error, and cross-cultural validity were reported with less than optimum quality. There was a risk of bias in ClinROM development. According to the updated criteria of good measurement properties, structural validity, internal consistency, and reliability showed good results. In contrast, hypothesis testing was somewhat poorer. Results for cross-cultural validity were indeterminate. According to the updated GRADE approach from the COSMIN group the scale received a moderate grade.

Conclusions

The COSMIN standard allows a judgment of the CAINS as an instrument with the potential to be recommended for use, but which requires further research to assess its quality, in particular in the domains of content validity, internal consistency, and cross-cultural validity.
Nicotinamide Riboside Modulates HIF-1 Signaling to Maintain and Enhance Odontoblastic Differentiation in Human Dental Pulp Stem Cells
Authors: Zhan Peimeng , Zhang Xinfang , Xie Zhuo , Chen Lingling , Huang Shuheng , Huang Qiting , Lin Zhengmei , Wang Runfu
Published: November 2023

Human dental pulp stem cells (hDPSCs) play a vital role in the regeneration of the pulp-dentin complex after pulp disease. While the regeneration efficiency relies on the odontoblastic differentiation capacity of hDPSCs, this is difficult to regulate within the pulp cavity. Although nicotinamide riboside (NR) has been found to promote tissue regeneration, its specific role in pulp-dentin complex regeneration is not fully understood. Here, we aimed to explore the role of NR in the odontoblastic differentiation of hDPSCs and its underlying molecular mechanism. It was found that NR enhanced the viability and retarded senescence in hDPSCs with higher NAD+/NADH levels. In contrast to the sustained action of NR, the multi-directional differentiation of hDPSCs was enhanced after NR pre-treatment. Moreover, in an ectopic pulp regeneration assay in nude mice, transplantation of hDPSCs pretreated with NR promoted the formation of a dentin-like structure surrounded by cells positively expressing DMP-1 and DSPP. RNA-Seq demonstrated inhibition of the HIF-1 signaling pathway in hDPSCs pretreated with NR. The number of HIF-1α-positive cells was significantly decreased in hDPSCs pretreated by NR in vivo. Similarly, NR significantly downregulated the expression of HIF-1α in vitro. The findings suggested that NR could potentially regulate hDPSC odontoblastic differentiation and promote the development of innovative strategies for dental pulp repair.
Entropy Meets Physiology: Should We Translate Aging as Disorder?
Authors: Tatullo Marco
Published: November 2023

Aging is characterized by an alteration of several physiological processes and biological pathways that leads to an increased susceptibility to age-related diseases and death. Normally, multipotential stem/progenitor cells may contribute to tissue homeostasis, and to minimize the age-depending DNA damage. Scientific research has demonstrated that aging induces several complex changes affecting even the mesenchymal stromal/stem cells (MSCs) ability to self-renew, differentiate, and immunomodulate the human tissues, causing further alterations in the local microenvironment. Cellular senescence can thus be considered as an overall response to several damages. Accordingly, aging seems to create the proper conditions to decrease the tissue’s metabolic performance, and the cell-to-cell communication, resulting in a progressive tissue destruction; on the other hand, the MSCs functions appear to be severely reduced. This concise review summarizes the main alterations affecting the MSCs during aging, and it also explains the role of inflammation as a key player in age-related syndromes. The hypothesis is to suggest a parallelism between the thermodynamic concept of “entropy” and biological aging, speculating that both can increase within irreversible systems and both lead toward an irreversible disorder; so, the question is: should we translate aging as disorder?
The effect of different implant programs on beef × dairy steer feedlot growth performance and carcass characteristics
Authors: Wesley K R , Word A B , Maxwell C L , Holland B P , Karr K J , Hutcheson J P , Walter L A J , Johnson B J
Published: November 2023

The objective of this study was to evaluate potency and timing of trenbolone acetate (TBA) administration on live performance and carcass characteristics of beef × dairy steers. A total of 6,895 beef × dairy steers [initial body weight (BW) = 157 ± 5.2 kg] were allotted into 30 pens, with pen as the experimental unit. Each pen was randomly assigned one of three implant treatments: 1) Revalor-IS (IS) at d 0, IS at d 80, and Revalor-XS (XS) at d 160 (IS/IS/XS); 2) Ralgro at d 0, IS at d 80, and XS at d 160 (Ral/IS/XS); or 3) Encore at d 0 and XS at d 160 (Enc/XS). Steers were blocked by arrival date, each pen was terminally sorted in three ways at 257 ± 22 days on feed and harvested at 329 ± 25 days on feed. For live and carcass outcomes, fixed effect of implant treatment and random effect of block was evaluated. Data are reported on a deads and removals out basis. Removals, morbidity, and mortality were similar (P ≥ 0.45). Steers administered TBA prior to d 160 were 5.8 kg heavier (P = 0.03) than Enc/XS steers at d 160. Final BW was not different (P = 0.78). Early administration of a TBA-containing implant resulted in an increased prevalence of bullers [2.40%, 5.18%, 6.86% (for Enc/XS, Ral/IS/XS, and IS/IS/XS) respectively; P < 0.01]. Dry matter intake (DMI) was 2.3% greater (P < 0.01) in steers administered Enc/XS compared to IS/IS/XS; however, DMI as a percentage of BW, average daily gain, and feed efficiency were not different (P ≥ 0.12). Dressing percentage, hot carcass weight, heavy carcass occurrence, Longissimus muscle area, and 12th rib fat thickness were similar among all steers (P ≥ 0.28). Marbling score tended to be greatest for Enc/XS and Ral/IS/XS (P = 0.09). Enc/XS graded a greater proportion of USDA Prime and fewer USDA Select carcasses than IS/IS/XS (P < 0.05). Enc/XS and Ral/IS/XS tended (P = 0.09) to have more USDA Yield Grade (YG) 1 carcasses. While delayed administration or decreased total potency of TBA-containing implants may decrease buller incidence and improve Quality Grade, few differences were observed in live or carcass outcomes.
New approaches build upon historical studies in dermal toxicology
Authors: Williams Faith M
Published: November 2023

These are my personal reflections on the history of approaches to understanding dermal toxicology brought together for the Paton Prize Award. This is not a comprehensive account of all publications from in vivo studies in humans to development of in vitro and in silico approaches but highlghts important progress. I will consider what is needed now to influence approaches to understanding dermal exposure with the current development and use of NAMs (new approach methodologies).
Perspectives Towards Collective Action for Pest and Disease Management in Vineyards in the Western United States
Authors: Lowder Sarah R. , Moyer Michelle M. , Cooper Monica L. , Pscheidt Jay , Mahaffee Walter F.
Published: November 2023

An individual grower's response to pests and diseases in their vineyard can have consequences for an entire growing region. Collective action strategies can help align grower responses to achieve better regional disease control. Ways in which we identify, approach, and address manager opinions regarding cooperative management efforts influence the success of collective action strategies. A Q-method survey was conducted to investigate the adoption obstacles of wine grape growers to regionally collective actions for managing pests and diseases. Qualitative information from the western United States ( n = 17 participants) was used to generate 36 statements describing opinions on collective management action and general disease management. A second set of grape producers ( n = 59) was asked to rank these statements relative to each other. Participants perceived that collective management action would be worth the extra associated time or costs. Four prominent archetypal perspectives arose from the Q-method analysis, explaining 66% of the variance in expressed opinions. Archetypes were termed “The Cooperators” (14 of 59), “The Quasi-Individualists” (9 of 59), “The Mid-Level Pragmatists” (8 of 59), and “The Bottom-Line Focused” (5 of 59). These groups were split across the demographic information collected; archetypes explained more variation between responses than demographic information. Overall, participants were likely to agree that cooperation was important, but they were more concerned about their individual vineyard economic and crop health concerns, thus suggesting that if outreach professionals want to increase the likelihood of grape growers participating in collective pest management actions, they should emphasize the individual benefits of participation.

[Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2024.
Weak SARS-CoV-2-specific responses of TIGIT-expressing CD8+ T cells in people living with HIV after a third dose of a SARS-CoV-2 inactivated vaccine
Authors: Jin Junyan , Wang Xiuwen , Li Yongzheng , Yang Xiaodong , Wang Hu , Han Xiaoxu , Sun Jin , Ma Zhenglai , Duan Junyi , Zhang Guanghui , Huang Tao , Zhang Tong , Wu Hao , Zhang Xin , Su Bin
Published: November 2023

Background:

T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), an inhibitory receptor expressed on T cells, plays a dysfunctional role in antiviral infection and antitumor activity. However, it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccines.

Methods:

Forty-five people living with HIV (PLWH) on antiretroviral therapy (ART) for more than two years and 31 healthy controls (HCs), all received a third dose of a SARS-CoV-2 inactivated vaccine, were enrolled in this study. The amounts, activation, proportion of cell subsets, and magnitude of the SARS-CoV-2-specific immune response of TIGIT+CD4+ and TIGIT+CD8+ T cells were investigated before the third dose but 6 months after the second vaccine dose (0W), 4 weeks (4W) and 12 weeks (12W) after the third dose.

Results:

Compared to that in HCs, the frequency of TIGIT+ CD8+ T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine, and the immune activation of TIGIT+CD8+ T cells also increased. A decrease in the ratio of both T naïve (TN) and central memory (TCM) cells among TIGIT+CD8+ T cells and an increase in the ratio of the effector memory (TEM) subpopulation were observed at 12W in PLWH. Interestingly, particularly at 12W, a higher proportion of TIGIT+CD8+ T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay. Compared with 0W, SARS-CoV-2-specific TIGIT+CD8+ T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs. Additionally, at all time points, the SARS-CoV-2-specific responses of TIGIT+CD8+ T cells in PLWH were significantly weaker than those of TIGIT–CD8+ T cells. However, in HCs, the difference in the SARS-CoV-2-specific responses induced between TIGIT+CD8+ T cells and TIGIT–CD8+ T cells was insignificant at 4W and 12W, except at 0W.

Conclusions:

TIGIT expression on CD8+ T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine, suggesting weakened resistance to SARS-CoV-2 infection, especially in PLWH. Furthermore, TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8+ T cells, thereby enhancing the effectiveness of vaccination.
Exposure to ultrafine particles and the incidence of asthma in children
Authors: da Silveira Fleck Alan , Vachon Julien , Buteau Stéphane , Laouan-Sidi Elhadji Anassour , Hatzopoulou Marianne , Weichenthal Scott , Smargiassi Audrey
Published: November 2023

Background:

Asthma is the most prevalent chronic respiratory disease in children. The role of ultrafine particles (UFPs) in the development of the disease remains unclear. We used a population-based birth cohort to evaluate the association between prenatal and childhood exposure to low levels of ambient UFPs and childhood-onset asthma.

Methods:

The cohort included all children born and residing in Montreal, Canada, between 2000 and 2015. Children were followed for asthma onset from birth until <13 years of age. Spatially resolved annual mean concentrations of ambient UFPs were estimated from a land use regression model. We assigned prenatal exposure according to the residential postal code at birth. We also considered current exposure during childhood accounting for time-varying residence location. We estimated hazard ratios (HRs) using Cox proportional hazards models adjusted for age, sex, neighborhood material and social deprivation, calendar year, and coexposure to ambient nitrogen dioxide (NO2) and fine particles (PM2.5).

Results:

The cohort included 352,966 children, with 30,825 children developing asthma during follow-up. Mean prenatal and childhood UFP exposure were 24,706 particles/cm3 (interquartile range [IQR] = 3,785 particles/cm3) and 24,525 particles/cm3 (IQR = 3,427 particles/cm3), respectively. Both prenatal and childhood UFP exposure were not associated with childhood asthma onset in single pollutant models (HR per IQR increase of 0.99 [95% CI = 0.98, 1.00]). Estimates of association remained similar when adjusting for coexposure to ambient NO2 and PM2.5.

Conclusion:

In this population-based birth cohort, childhood asthma onset was not associated with prenatal or childhood exposure to low concentrations of UFPs.
Baseline Quality of Life in Low-Flow Head and Neck Vascular Malformations in Children
Authors: Evans Sean S. , Goudy Steven L. , Siong Tey Ching , Swerdlin Rachel F. , Hawkins C. Matthew
Published: November 2023

Objective:

To determine baseline quality of life characteristics in patients with low-flow head and neck vascular malformations.

Study Design:

Retrospective review of prospectively collected data.

Setting:

Tertiary Pediatric Hospital.

Methods:

Patients with low-flow head and neck vascular malformations (age 0–18 years) evaluated through our vascular anomalies clinic from 2016 to 2019 were reviewed. Patients with completed PedsQL surveys using parent-proxy reports for children 2–7 years old and both patient and parent-proxy data for patients ≥8 years old were included.

Results:

In total 94 consecutive patients were included, with a mean age of 9.2 ± 4.7 years. Diagnoses included lymphatic malformations (n = 50), venous malformations (n = 41), and combined venolymphatic malformations (n = 3). Total parental quality of life scores were lower than their children’s (84.23 vs 87.45; P = .037), with lower emotional scores as age at presentation increased (d = −0.60; P < .01). Lower parental scores were also noted across multiple domains for submandibular/sublingual, oropharyngeal, hypopharyngeal, and orbital involvement. (g = −0.68 to −1.10; P < .05). Increasing subsite number involvement affected parents and children similarly (−0.30 vs −0.35; P ≤ .02). Higher physical function scores were noted in venous versus lymphatic malformations (d =−1.07; P = .01). The child-reported school function scores were lower in African-American versus Caucasian children (P = .04). Prior treatment was associated with lower parental scores (d = 0.59; P = .04).

Conclusion:

The parent and patient’s quality of life is reduced across multiple domains for low-flow head and neck vascular malformations based on age, lesion location and type, disease burden, race, and prior treatment.
COVID-19 Vaccine Policy Implementation and Differential Vaccine Uptake Trajectories in Chicago Communities
Authors: Kim Sage J. , McWhirter Noah , Duong Kelly , Khare Manorama M. , Giles Wayne H. , Basu Sanjib , Hershow Ronald C. , Stiehl Emily
Published: November 2023

Background:

Since the onset of the COVID-19 pandemic, multiple public health interventions have been implemented to respond to the rapidly evolving pandemic and community needs. This article describes the scope, timing, and impact of coordinated strategies for COVID-19 vaccine uptake in Chicago for the first year of vaccine distribution.

Methods:

Using a series of interviews with public health officials and leaders of community-based organizations (CBOs) who participated in the implementation of the citywide COVID-19 vaccine outreach initiatives, we constructed a timeline of vaccine outreach initiatives. The timeline was matched to the vaccine uptake rates to explore the impact of the vaccine outreach initiatives by community area. Finally, we discussed the nature of policy initiatives and the level of vaccine uptake in relation to community characteristics.

Results:

The Chicago Department of Public Health (CDPH) implemented myriad vaccine outreach strategies, including mass vaccination sites, improved access, and community-level vaccine campaigns. Protect Chicago+ was the primary vaccine outreach effort initiated by the CDPH, which identified 15 highly vulnerable community areas. More than 2.7 million (67%) Chicagoans completed the vaccine regimen by December 2021. Black (51.3%) Chicagoans were considerably less likely to be vaccinated than Asian (77.6%), White (69.8%), and Hispanic (63.6%) Chicago residents. In addition, there were significant spatial differences in the rate of COVID-19 vaccine completion: predominantly White and Hispanic communities, compared with Black communities, had higher rates of vaccine completion.

Conclusions:

The community outreach efforts to improve COVID-19 vaccine uptake in Chicago have shown the importance of community-engaged approaches in pandemic responses. Despite citywide efforts to build community infrastructure, Black communities had relatively lower levels of vaccine uptake than other communities. Broader social restructuring to mitigate disinvestment and residential segregation and to ameliorate medical mistrust will be needed to prepare for future pandemics and disasters.
Soil as a transdisciplinary research catalyst: from bioprospecting to biorespecting
Authors: Tarnowski Matthew J. , Varliero Gilda , Scown Jim , Phelps Emily , Gorochowski Thomas E.
Published: November 2023

The vast microbial biodiversity of soils is beginning to be observed and understood by applying modern DNA sequencing techniques. However, ensuring this potentially valuable information is used in a fair and equitable way remains a challenge. Here, we present a public engagement project that explores this topic through collaborative research of soil microbiomes at six urban locations using nanopore-based DNA sequencing. The project brought together researchers from the disciplines of synthetic biology, environmental humanities and microbial ecology, as well as school students aged 14–16 years old, to gain a broader understanding of views on the use of data from the environment. Discussions led to the transformation of ‘bioprospecting’, a metaphor with extractive connotations which is often used to frame environmental DNA sequencing studies, towards a more collaborative approach—‘biorespecting’. This shift in terminology acknowledges that genetic information contained in soil arises as a result of entire ecosystems, including the people involved in its creation. Therefore, any use of sequence information should be accountable to the ecosystems from which it arose. As knowledge can arise from ecosystems and communities, science and technology should acknowledge this link and reciprocate with care and benefit-sharing to help improve the wellbeing of future generations.
Towards a mathematical understanding of invasion resistance in multispecies communities
Authors: Gjini Erida , Madec Sten
Published: November 2023

Multispecies community composition and dynamics are key to health and disease across biological systems, a prominent example being microbial ecosystems. Explaining the forces that govern diversity and resilience in the microbial consortia making up our body’s defences remains a challenge. In this, theoretical models are crucial, to bridge the gap between species dynamics and underlying mechanisms and to develop analytic insight. Here we propose a replicator equation framework to model multispecies dynamics where an explicit notion of invasion resistance of a system emerges and can be studied explicitly. For illustration, we derive the conceptual link between such replicator equation and
N
microbial species’ growth and interaction traits, stemming from micro-scale environmental modification. Within this replicator framework, mean invasion fitness arises, evolves dynamically, and may undergo critical predictable shifts with global environmental changes. This mathematical approach clarifies the key role of this resident system trait for invader success, and highlights interaction principles among
N
species that optimize their collective resistance to invasion. We propose this model based on the replicator equation as a powerful new avenue to study, test and validate mechanisms of invasion resistance and colonization in multispecies microbial ecosystems and beyond.
Cessation of grazing causes biodiversity loss and homogenization of soil food webs
Authors: Schrama Maarten , Quist Casper W. , Arjen de Groot G. , Cieraad Ellen , Ashworth Deborah , Laros Ivo , Hansen Lars Hestbjerg , Leff Jonathan , Fierer Noah , Bardgett Richard D.
Published: November 2023

There is widespread concern that cessation of grazing in historically grazed ecosystems is causing biotic homogenization and biodiversity loss. We used 12 montane grassland sites along an 800 km north–south gradient across the UK, to test whether cessation of grazing affects local
α
- and
β
-diversity of below-ground food webs. We show cessation of grazing leads to strongly decreased
α
-diversity of most groups of soil microbes and fauna, particularly of relatively rare taxa. By contrast, the
β
-diversity varied between groups of soil organisms. While most soil microbial communities exhibited increased homogenization after cessation of grazing, we observed decreased homogenization for soil fauna after cessation of grazing. Overall, our results indicate that exclusion of domesticated herbivores from historically grazed montane grasslands has far-ranging negative consequences for diversity of below-ground food webs. This underscores the importance of grazers for maintaining the diversity of below-ground communities, which play a central role in ecosystem functioning.
The microstructure of intra- and interpersonal coordination
Authors: Nazzaro Giovanni , Emanuele Marco , Laroche Julien , Esposto Chiara , Fadiga Luciano , D'Ausilio Alessandro , Tomassini Alice
Published: November 2023

Movements are naturally composed of submovements, i.e. recurrent speed pulses (2–3 Hz), possibly reflecting intermittent feedback-based motor adjustments. In visuomotor (unimanual) synchronization tasks, partners alternate submovements over time, indicating mutual coregulation. However, it is unclear whether submovement coordination is organized differently between and within individuals. Indeed, different types of information may be variably exploited for intrapersonal and interpersonal coordination. Participants performed a series of bimanual tasks alone or in pairs, with or without visual feedback (solo task only). We analysed the relative timing of submovements between their own hands or between their own hands and those of their partner. Distinct coordinative structures emerged at the submovement level depending on the relevance of visual feedback. Specifically, the relative timing of submovements (between partners/effectors) shifts from alternation to simultaneity and a mixture of both when coordination is achieved using vision (interpersonal), proprioception/efference-copy only (intrapersonal, without vision) or all information sources (intrapersonal, with vision), respectively. These results suggest that submovement coordination represents a behavioural proxy for the adaptive weighting of different sources of information within action-perception loops. In sum, the microstructure of movement reveals common principles governing the dynamics of sensorimotor control to achieve both intra- and interpersonal coordination.
Early life adversity jointly regulates body-mass index and working memory development
Authors: Farkas Bence Csaba , Jacquet Pierre Olivier
Published: November 2023

Previous work has proposed that balancing energy expenditure towards body and brain development in an optimal fashion results in a negative relationship between somatic and neurocognitive growth during development. An important issue, largely overlooked so far, is the extent to which this energetic trade-off is influenced by early life environmental factors. In this study, we estimated the association between neurocognitive (measured by working memory ability) and somatic (measured by body-mass index) developmental trajectories, while taking into account multiple dimensions of early life adversity. Results of our initial growth curve model were consistent with this brain–body trade-off in both girls and boys. In a subsequent model, we showed that early life adversity had positive associations with somatic and negative associations with neurocognitive growth trajectories, although the direct negative coupling between them remained consistent. Finally, a multidimensional adversity model, separating the effects of deprivation, threat and unpredictability, revealed that the dimension of deprivation—reflecting lack of access to resources and cognitive stimulation—contributed the most to both somatic and neurocognitive growth patterns. These results suggest that the way individuals balance energy between these two biological constructs during development is partly linked to environmental influences through phenotypic plasticity.
Systematic analysis of plasmids of the Serratia marcescens complex using 142 closed genomes
Authors: Nagano Debora Satie , Taniguchi Itsuki , Ono Tomoyuki , Nakamura Keiji , Gotoh Yasuhiro , Hayashi Tetsuya
Published: November 2023

Plasmids play important roles in bacterial genome diversification. In the

Serratia marcescens

complex (SMC), a notable contribution of plasmids to genome diversification was also suggested by our recent analysis of >600 draft genomes. As accurate analyses of plasmids in draft genomes are difficult, in this study we analysed 142 closed genomes covering the entire complex, 67 of which were obtained in this study, and identified 132 plasmids (1.9–244.4 kb in length) in 77 strains. While the average numbers of plasmids in clinical and non-clinical strains showed no significant difference, strains belonging to clade 2 (one of the two hospital-adapted lineages) contained more plasmids than the others. Pangenome analysis revealed that of the 28 954 genes identified, 12.8 % were plasmid-specific, and 1.4 % were present in plasmids or chromosomes depending on the strain. In the latter group, while transposon-related genes were most prevalent (31.4 % of the function-predicted genes), genes related to antimicrobial resistance and heavy metal resistance accounted for a notable proportion (22.7 %). Mash distance-based clustering separated the 132 plasmids into 23 clusters and 50 singletons. Most clusters/singletons showed notably different GC contents compared to those of host chromosomes, suggesting their recent or relatively recent appearance in the SMC. Among the 23 clusters, 17 were found in only clinical or only non-clinical strains, suggesting the possible preference of their distribution on the environmental niches of host strains. Regarding the host strain phylogeny, 16 clusters were distributed in two or more clades, suggesting their interclade transmission. Moreover, for many plasmids, highly homologous plasmids were found in other species, indicating the broadness of their potential host ranges, beyond the genus, family, order, class or even phylum level. Importantly, highly homologous plasmids were most frequently found in

Klebsiella pneumoniae

and other species in the family

Enterobacteriaceae

, suggesting that this family, particularly

K. pneumoniae

, is the main source for plasmid exchanges with the SMC. These results highlight the power of closed genome-based analysis in the investigation of plasmids and provide important insights into the nature of plasmids distributed in the SMC.
SillyPutty: Improved clustering by optimizing the silhouette width
Authors: Bombina Polina , Tally Dwayne , Abrams Zachary B. , Coombes Kevin R.
Published: November 2023

Unsupervised clustering is an important task in biomedical science. We developed a new clustering method, called SillyPutty, for unsupervised clustering. As test data, we generated a series of datasets using the Umpire R package. Using these datasets, we compared SillyPutty to several existing algorithms using multiple metrics (Silhouette Width, Adjusted Rand Index, Entropy, Normalized Within-group Sum of Square errors, and Perfect Classification Count). Our findings revealed that SillyPutty is a valid standalone clustering method, comparable in accuracy to the best existing methods. We also found that the combination of hierarchical clustering followed by SillyPutty has the best overall performance in terms of both accuracy and speed.

Availability

The SillyPutty R package has been submitted to the Comprehensive R Archive Network (CRAN). Code to perform and analyze the simulations described here can be found in a Git project hosted athttps://gitlab.com/krcoombes/sillyputty.
The change of lymphocyte subsets and inflammatory cytokine in BK viruria
Authors: Jiang Yu Huan , Yuan Lei , Chen Qiang , He Hui Min , Liu Yang , Lai Lan Min
Published: November 2023

Background

Polyomavirus BK (BKV) infection as a serious complication after kidney transplantation. The process of infections in kidney transplant recipients is viruria, viremia, and BKVAN. The difference between BK negative and BK viruria in kidney recipients has not been defined.

Patients and Methods

We compared post-transplant lymphocyte subsets 、blood cytokines、urine cytokines levels of 19 renal transplant outpatients with (BK-positive) or without BK viruria (BK-negative, n=20), and 20 healthy controls (HCs). Group of BK-positive divide into low-(n=4) and high-level (n=15) According to BK viral load (VL).Immune cells including T cells, B cells, and natural killer (NK) cells、interleukin-2(IL-2),IL-5,IL-6, IL-1β, IL-10, IL-8, IL-17A,IL-4,IL-12P70, interferon-α(IFN-α), IFN-γ,and tumor necrosis factor-α (TNF-α)were determined by flow cytometry.

Results

BK-positive patients showed higher urine IL-1β (P=0.040), IL-10 (P=0.010), IFN-γ (P=0.002), and TNF-α (P=0.027) than BK-negative patients. Compared with HCs, BK-negative patients had lower urine IL-1β (P=0.04), IL-10 (P=0.01), TNF-α (P=0.027) and IFN-γ (P=0.004),suggesting that cytokine expression regulation BK-infection.

Conclusion

BK-positive renal transplant recipients, especially those with high VL, showed strong inflammatory cytokine responses with increases of urine IL-1β, IL-10, IFN-γ, and TNF-α. Our data suggest that monocyte- and Th-2-induced cytokines are involved in the pathogenesis of BKV-associated nephropathy.
Design and fabrication of flexible biodegradable microelectrode array for recording electrocorticography signals
Authors: Chatterjee Suman , Joshi Rathin K. , Bhaskara Sreenivas , Hari RS , Datta Shubham , Shabari Girishan KV , Pandya Hardik J.
Published: November 2023

Conventional flexible implantable microelectrode arrays, used for real-time brain activity monitoring, incur minimal tissue damage due to their flexibility; however, these require retrieval surgery, causing trauma to subjects. Implants, fabricated using biodegradable materials, dissolve gradually in body fluid, eliminating the necessity for retrieval surgery. This work reports designing and developing a 10-channel flexible biodegradable microelectrode array to acquire electrocorticography signals from rats’ brains. The array was fabricated using tungsten, a transient metal, and PLLA:PCL (80:20), a biodegradable composite polymer. The subdural implantation of the array on the somatosensory cortex of rats (n=3) facilitated electrical biopotentials acquisition using OpenBCI Cyton Boards. The baseline activities, the induced epileptic discharges after peripheral electrical stimulation, and the recovered baseline activities after antiepileptic drug administration were recorded from sedated rats. The chronic baselines and evoked activities were also acquired from awake rats. The gradual decline of chronic baselines was evident, suggesting a possible dissolution of electrodes. Furthermore, the time-frequency analyses demonstrate the differences between baselines and induced epileptic activities. The signals recorded from microelectrode arrays demonstrate their potential to monitor brain activities in a chronic study. Histology of the harvested vital organs from the euthanized rats confirmed minimal tissue damage due to implantation.
Insights into the early-life chemical exposome of Nigerian infants and potential correlations with the developing gut microbiome
Authors: Oesterle Ian , Ayeni Kolawole I. , Ezekiel Chibundu N. , Berry David , Rompel Annette , Warth Benedikt
Published: November 2023

Early-life exposure to natural and synthetic chemicals can impact acute and chronic health conditions. Here, a suspect screening workflow anchored on high-resolution mass spectrometry was applied to elucidate xenobiotics in breast milk and matching stool samples collected from Nigerian mother-infant pairs (n = 11) at three time points. Potential correlations between xenobiotic exposure and the developing gut microbiome, as determined by 16S rRNA gene amplicon sequencing, were subsequently explored. Overall, 12,192 and 16,461 features were acquired in the breast milk and stool samples, respectively. Following quality control and suspect screening, 562 and 864 features remained, respectively, with 149 of these features present in both matrices. Taking advantage of 242 authentic reference standards measured for confirmatory purposes of food bio-actives and toxicants, 34 features in breast milk and 68 features in stool were identified and semi-quantified. Moreover, 51 and 78 features were annotated with spectral library matching, as well as 416 and 652 byin silicofragmentation tools in breast milk and stool, respectively. The analytical workflow proved its versatility to simultaneously determine a diverse panel of chemical classes including mycotoxins, endocrine-disrupting chemicals (EDCs), antibiotics, plasticizers, perfluorinated alkylated substances (PFAS), and pesticides although it was originally optimized for polyphenols. Spearman rank correlation of the identified features revealed significant correlations between chemicals of the same classification such as polyphenols. One-way ANOVA and differential abundance analysis of the data obtained from stool samples revealed that molecules of plant-based origin were elevated when complementary foods were introduced to the infants’ diets. Annotated compounds in the stool, such as tricetin, positively correlated with the genusBlautia. Moreover, vulgaxanthin negatively correlated withEscherichia-Shigella. Despite the limited sample size, this exploratory study provides high-quality exposure data of matched biospecimens obtained from mother-infant pairs in sub-Saharan Africa and shows potential correlations between the chemical exposome and the gut microbiome.

Highlights

-

Suspect screening of exposure biomarkers in human breast milk and infant stool.

-

542 features in breast milk and 864 in stool were identified or annotated.

-

Consumption of complementary foods influenced the chemical exposure of infants.

-

Correlations between xenobiotics in both biological matrices evaluated.

-

Dietary exposure correlated to the stool microbiome composition.

Graphical abstract
In vivoscreening for toxicity-modulating drug interactions identifies antagonism that protects against ototoxicity in zebrafish
Authors: Bustad Ethan , Mudrock Emma , Nilles Elizabeth M. , McQuate Andrea , Bergado Monica , Gu Alden , Galitan Louie , Gleason Natalie , Ou Henry C. , Raible David W. , Hernandez Rafael E. , Ma Shuyi
Published: November 2023

Ototoxicity is a debilitating side effect of over 150 medications with diverse mechanisms of action, many of which could be taken concurrently to treat multiple conditions. Approaches for preclinical evaluation of drug interactions that might impact ototoxicity would facilitate design of safer multi-drug regimens and mitigate unsafe polypharmacy by flagging combinations that potentially cause adverse interactions for monitoring. They may also identify protective agents that antagonize ototoxic injury. To address this need, we have developed a novel workflow that we call Parallelized Evaluation of Protection and Injury for Toxicity Assessment (PEPITA), which empowers high-throughput, semi-automated quantification of ototoxicity and otoprotection in zebrafish larvae. By applying PEPITA to characterize ototoxic drug interaction outcomes, we have discovered antagonistic interactions between macrolide and aminoglycoside antibiotics that confer protection against aminoglycoside-induced damage to lateral line hair cells in zebrafish larvae. Co-administration of either azithromycin or erythromycin in zebrafish protected against damage from a broad panel of aminoglycosides, at least in part via inhibiting drug uptake into hair cells via a mechanism independent from hair cell mechanotransduction. Conversely, combining macrolides with aminoglycosides in bacterial inhibition assays does not show antagonism of antimicrobial efficacy. The proof-of-concept otoprotective antagonism suggests that combinatorial interventions can potentially be developed to protect against other forms of toxicity without hindering on-target drug efficacy.
Genomic architecture of nestmate recognition cues in the desert ant
Authors: Cohen Pnina , Inbar Shani , Privman Eyal
Published: November 2023

Nestmate recognition is the basis for cooperation within social insect colonies. Quantitative variation in cuticle hydrocarbons (CHCs) is used for nestmate recognition in ants and other social insects. We carried out a Genome Wide Association Study (GWAS) of CHCs in the desert antCataglyphis nigerby sampling 47 colonies, fully sequencing six workers from each colony, and measuring the relative amounts of their CHCs. Under the Gestalt colony odour model, social interactions between nestmates, in which CHCs are being transferred and mixed, are essential in creating a uniform colony CHC profile.

Therefore, we carried out a second GWAS between the colonies and their uniform Gestalt odour by averaging nestmate genotypes and comparing them to their averaged CHC amounts. Our results are in line with the Gestalt model. Together, the two analyses identified 99 candidate QTLs associated with 18 of the CHCs. Thirteen clusters of two to four QTLs located within 10cM from each other were identified, seven of which contained QTLs from both analyses. We conclude that nestmate recognition cues are a complex quantitative colony-level trait with a significant genetic component to their phenotypic variation and a highly polygenic architecture.
Physiological variability in mitochondrial rRNA predisposes to metabolic syndrome
Authors: Pecina Petr , Čunátová Kristýna , Kaplanová Vilma , Puertas-Frias Guillermo , Šilhavý Jan , Tauchmannová Kateřina , Vrbacký Marek , Čajka Tomáš , Gahura Ondřej , Pravenec Michal , Houštěk Josef , Mráček Tomáš , Pecinová Alena
Published: November 2023

Metabolic syndrome is a growing concern in developed societies, and due to its polygenic nature, the genetic component is only slowly being elucidated. Common mitochondrial DNA sequence variants have been associated with symptoms of metabolic syndrome and may be relevant players in the genetics of metabolic syndrome.

We investigate the effect of mitochondrial sequence variation on the metabolic phenotype in conplastic rat strains with identical nuclear but unique mitochondrial genomes, challenged by high-fat diet. We find that the variation in mitochondrial rRNA sequence represents a risk factor in insulin resistance development, which is caused by diacylglycerols accumulation induced by tissue-specific reduction of the oxidative capacity. These metabolic perturbations stem from the 12S rRNA sequence variation affecting mitochondrial ribosome assembly and translation. Our work demonstrates that physiological variation in mitochondrial rRNA might represent a relevant underlying factor in the progression of metabolic syndrome.

Competing interests

The authors declare that no competing interests exist.
Structure of scavenger receptor SCARF1 and its interaction with lipoproteins
Authors: Wang Yuanyuan , Xu Fan , Li Guangyi , Cheng Chen , Yu Bowen , Zhang Ze , Kong Dandan , Chen Fabao , Liu Yali , Fang Zhen , Cao Longxing , Yu Yang , Gu Yijun , He Yongning
Published: November 2023

SCARF1 (Scavenger receptor class F member 1, SREC-1 or SR-F1) is a type I transmembrane protein that recognizes multiple endogenous and exogenous ligands such as modified low-density lipoproteins (LDL) and is important for maintaining homeostasis and immunity. But the structural information and the mechanisms of ligand recognition of SCARF1 are largely unavailable. Here we solve the crystal structures of the N-terminal fragments of human SCARF1, which show that SCARF1 forms homodimers and its epidermal growth factor (EGF)-like domains adopt a long-curved conformation. Then we examine the interactions of SCARF1 with lipoproteins and are able to identify a region on SCARF1 for recognizing modified LDLs. The mutagenesis data show that the positively charged residues in the region are crucial for the interaction of SCARF1 with modified LDLs, which is confirmed by making chimeric molecules of SCARF1 and SCARF2. In addition, teichoic acids, a cell wall polymer expressed on the surface of gram-positive bacteria, are able to inhibit the interactions of modified LDLs with SCARF1, suggesting the ligand binding sites of SCARF1 might be shared for some of its scavenging targets. Overall, these results provide mechanistic insights into SCARF1 and its interactions with the ligands, which are important for understanding its physiological roles in homeostasis and the related diseases.
BrainCellR: A Precise Cell Type Nomenclature R Package for Comparative Analysis Across Brain Single-Cell Datasets
Authors: Chi Yuhao , Marini Simone , Wang Guang-Zhong
Published: November 2023

Single-cell studies in neuroscience require precise cell type classification and consistent nomenclature that allows for meaningful comparisons across diverse datasets. Current approaches often lack the ability to identify fine-grained cell types and establish standardized annotations at the cluster level, hindering comprehensive understanding of the brain’s cellular composition. To facilitate data integration across multiple models and datasets, we designed BrainCellR. This package provides researchers with a powerful and user-friendly tool for efficient cell type classification and nomination from single-cell transcriptomic data. BrainCellR goes beyond conventional classification approaches by incorporating a standardized nomenclature system for cell types at the cluster level. This feature enables consistent and comparable annotations across different studies, promoting data integration and providing deeper insights into the complex cellular landscape of the brain.

Contact

simone.marini@ufl.eduorguangzhong.wang@picb.ac.cn
A small-molecule TrkB ligand improves dendritic spine phenotypes and atypical behaviors in female Rett syndrome mice
Authors: Medeiros Destynie , Ayala-Baylon Karen , Egido-Betancourt Hailey , Miller Eric , Chapleau Christopher , Robinson Holly , Phillips Mary L. , Yang Tao , Longo Frank M. , Li Wei , Pozzo-Miller Lucas
Published: November 2023

Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in methyl-CpG-binding protein-2 (MECP2), encoding a transcriptional regulator of many genes, including brain-derived neurotrophic factor (Bdnf). BDNF mRNA and protein levels are lower in RTT autopsy brains and in multiple brain regions ofMecp2-deficient mice, and experimentally increasing BDNF levels improve atypical phenotypes inMecp2mutant mice. Due to the low blood-brain barrier permeability of BDNF itself, we tested the effects of a brain penetrant, small molecule ligand of its TrkB receptors. Appliedin vitro, LM22A-4 increased dendritic spine density in pyramidal neurons in cultured hippocampal slices from postnatal day (P) 7 maleMecp2knockout (KO) mice as much as recombinant BDNF, and both effects were prevented by the TrkB receptor inhibitors K-252a and ANA-12. Consistent with its partial agonist activity, LM22A-4 did not affect spine density in CA1 pyramidal neurons in slice cultures from male wildtype (WT) mice, where typical BDNF levels outcompete its binding to TrkB. To identify neurons of known genotypes in the ‘mosaic’ brain of femaleMecp2heterozygous (HET) mice, we treated 4–6-month-old female MeCP2-GFP WT and HET mice with peripheral injections of LM22A-4 for 4 weeks. Surprisingly, mutant neurons lacking MeCP2-GFP showed dendritic spine volumes comparable to that in WT controls, while MeCP2-GFP-expressing neurons showed larger spines, similar to the phenotype we described in symptomatic maleMecp2KO mice where all neurons lack MeCP2. Consistent with this non-cell-autonomous mechanism, a 4-week systemic treatment with LM22A-4 had an effect only in MeCP2-GFP-expressing neurons in femaleMecp2HET mice, bringing dendritic spine volumes down to WT control levels, and without affecting spines of MeCP2-GFP-lacking neurons. At the behavioral level, we found that femaleMecp2HET mice engaged in aggressive behaviors significantly more than WT controls, which were reduced to WT levels by a 4-week systemic treatment with LM22A-4. Altogether, these data revealed differences in dendritic spine size and altered behaviors inMecp2HET mice, in addition to provide support to the potential usefulness of BDNF-related therapeutic approaches such as the partial TrkB agonist LM22A-4.