bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systolic and diastolic dysfunction is exacerbated by age and spinal cord injury in male and female mice with central nervous system serotonin deficiency
Authors: Qiu Qingchao , Komnenov Dragana , Hali Mirabela , Chung Charles S. , Mueller Patrick J. , Rossi Noreen F. , Kuhn Donald M. , Mateika Jason H. 
Published: February 2025

AbstractThe present study was designed to explore whether the depletion of serotonin (5‐HT) in the central nervous system (CNS5‐HT) leads to systolic and diastolic dysfunction and whether this dysfunction is exacerbated by sex, age and spinal cord injury. Echocardiographic assessment of systolic and diastolic function was completed in young and old male and female tryptophan hydroxylase 2 knockout (TPH2−/−) and wild‐type (TPH2+/+) mice with intact spinal cords, as well as in C2 spinal cord hemisected young TPH2−/− and TPH2+/+ mice. In addition, lumbar sympathetic nervous system activity was recorded in elderly male and female intact TPH2−/− and TPH2+/+ mice. Systolic and diastolic dysfunction was evident in young TPH2−/− mice, including a higher left ventricular mass (P < 0.001), left ventricular outflow parameters (e.g. peak velocity) and E/A (P < 0.001). Reductions in ejection fraction and fractional shortening were also evident (P < 0.001), although stroke volume and cardiac output were maintained. The assessed dysfunction was exacerbated by age and spinal cord injury, resulting in reductions in cardiac output (P ≤ 0.01). The dysfunction was accompanied by increases in sympathetic burst height (P = 0.038) and incidence (P = 0.001). Reductions in CNS5‐HT are coupled to systolic and diastolic dysfunction, which is exacerbated by age and spinal cord injury. This dysfunction is coupled to increases in sympathetic nervous system activity in elderly mice. Our findings are an initial step toward determining whether reductions in CNS5‐HT are a unifying mechanism that links central sleep apnoea, sympathoexcitation and heart failure in intact and spinal cord injured individuals.
imageKey points
Reductions in central nervous system serotonin (CNS5‐HT) may contribute to systolic and diastolic dysfunction. This dysfunction may be linked to increases in sympathetic nervous system activity and exacerbated by sex, age and spinal cord injury.
Echocardiographic assessment of systolic and diastolic function was completed in young and old male and female intact TPH2+/+ and TPH2−/− mice, as well as in C2 spinal cord hemisected young mice. Lumbar sympathetic nervous system activity was also recorded in elderly male and female intact TPH2+/+ and TPH2−/− mice.
Systolic and diastolic dysfunction was evident in young TPH2−/− mice. This dysfunction was exacerbated by age and spinal cord injury. The cardiac dysfunction was accompanied by increases in lumbar sympathetic nervous system activity.
Our findings are an initial step toward determining whether reductions in CNS5‐HT is a unifying mechanism that links central sleep apnoea, sympathoexcitation and heart failure in intact and spinal cord injured individuals.
The Eclipse
Authors: Vallelly Neil 
Published: February 2025

‘It is the only democracy in the Middle East’—this is a standard refrain about Israel. Some stand by it; others refute it. Many argue that Benjamin Netanyahu has been eroding democratic values in Israel over the last decade; others insist that so-called Israeli democracy is premised on the oppression and killing of Palestinians, which thus undermines the universalist principles of liberal democracy. While many disagree on Israel’s democratic credentials, what underpins these debates is an implicit understanding of democracy as an inherently pacifying political and social system, one that has ‘if not banished brutality and physical violence, then [it has] at least brought them under control’. Violence is not necessarily external to democracy, but something that democratic societies have learned to manage through a variety of political, social, and legal institutions.
A Randomized Crossover Trial on the Effects of Cadence on Calf Raise Test Outcomes: Cadence Does Matter
Authors: Hébert-Losier Kim , Fernandez Ma. Roxanne , Athens Josie , Kubo Masayoshi , O’Neill Seth 
Published: February 2025

The calf raise test (CRT) is commonly used to assess triceps surae muscle-tendon unit function. Often, a metronome set to 60 beats/min (30 repetitions/min) is used to set the cadence of calf raise repetitions, but studies report using cadences ranging from 30 to 120 beats/min. We investigated the effect of cadence on CRT outcomes, accounting for the potential confounders of sex, age, body mass index, and physical activity. Thirty-six healthy individuals (50% female) performed single-leg calf raise repetitions to volitional exhaustion in 3 randomized cadence conditions, 7 days apart: 30, 60, and 120 beats/min. Repetitions, total vertical displacement, total work, peak height, and peak power were recorded using the validated Calf Raise application. Cadence significantly affected all CRT outcomes (P ≤ .008), except repetitions (P = .200). Post hoc analysis revealed 60 beats/min resulted in significantly greater total vertical displacement and work than 30 and 120 beats/min. Peak height was greater at 60 and 120 than 30 beats/min, and peak power was greater at 120 beats/min. Males generated greater work and peak power (P ≤ .001), whereas individuals with greater body mass index completed less repetitions (P = .008), achieved lower total vertical displacements (P = .003), and generated greater peak power (P = .005). CRT cadence is important to consider when interpreting CRT outcomes and comparing data between studies.
Physical Activity Barriers and Facilitators for Older Women With Mild Cognitive Impairment and Alzheimer’s Disease
Authors: Tortosa-Martinez Juan , Martinez-Canales Celeste , Sanchis-Soler Gema , Beltran-Carrillo Vicente J. 
Published: February 2025

Objectives: The objective of this qualitative study was to analyze the barriers and facilitators for the practice of physical activity (PA) perceived by older women with Mild Cognitive Impairment and Alzheimer disease. Methods: Semistructured interviews were conducted with 22 female participants and 22 matching family members. Data were analyzed with a conventional content analysis. Results: The barriers for PA identified in this study need to be interpreted from an intersectional perspective, since these participants remained in a particular situation of vulnerability due to not only being Mild Cognitive Impairment/Alzheimer disease participants, but also women and older adults. The main barriers identified were health problems, feelings of insecurity and helplessness in their out-home activities, reliance on the social network, and lack of PA culture and exercise knowledge. The main facilitators were the perceived benefits of PA, social support, currently having more free time, and the doctor’s advice of doing PA. Conclusions: Based on the results, recommendations for promoting PA in this population include the following: (a) Promote a more constructive and positive conception of aging, gender roles, and cognitive impairment; (b) provide knowledge about the benefits of PA for this population; and (c) out-home PA with a social component could enhance the positive effects of PA, but exercise at home guided by a qualified professional could be an alternative for being active for those who suffer more from insecurity or dependence.
Necrosis drives susceptibility to
Mycobacterium tuberculosis
in Polg
D257A
mutator mice
Authors: Mabry C. J. , Weindel C. G. , Stranahan L. W. , VanPortfliet J. J. , Davis J. R. , Martinez E. L. , West A. P. , Patrick K. L. , Watson R. O. 
Published: February 2025

ABSTRACT

The genetic and molecular determinants that underlie the heterogeneity of
Mycobacterium tuberculosis
(Mtb) infection outcomes in humans are poorly understood. Multiple lines of evidence demonstrate that mitochondrial dysfunction can exacerbate mycobacterial disease severity, and mutations in some mitochondrial genes confer susceptibility to mycobacterial infection in humans. Here, we report that mutations in mitochondria DNA (mtDNA) polymerase gamma potentiate susceptibility to Mtb infection in mice. Polg
D257A
mutator mtDNA mice fail to mount a protective innate immune response at an early infection time point, evidenced by high bacterial burdens, reduced M1 macrophages, and excessive neutrophil infiltration in the lungs. Immunohistochemistry reveals signs of enhanced necrosis in the lungs of Mtb-infected Polg
D257A
mice, and Polg
D257A
mutator macrophages are hypersusceptible to extrinsic triggers of necroptosis
ex vivo
. By assigning a role for mtDNA mutations in driving necrosis during Mtb infection, this work further highlights the requirement for mitochondrial homeostasis in mounting balanced immune responses to Mtb.
Immunostimulatory effects of
Streptococcus sanguinis
extracellular membrane vesicles protect oral gingival epithelial cells from periodontal pathobiont damage
Authors: Helliwell Emily , Rauch Isabella , Nice Tim , Merritt Justin , Kreth Jens 
Published: February 2025

ABSTRACT

The commensal
Streptococcus sanguinis
is highly prevalent in the oral cavity and characterized for its ability to inhibit growth of oral pathogens. Like many other cell types, streptococci produce extracellular membrane vesicles (EMVs), which contain specific molecular cargo and facilitate interactions with host cells. We previously demonstrated that EMVs from
S. sanguinis
are internalized by gingival epithelial cells (GECs) without causing cell death. Our aim is to characterize the effects of vesicles on eukaryotic cells. Microscopy studies of gingival epithelial cells inoculated with EMVs from wild-type and specific deletion mutants show differential uptake, with decreased uptake of ΔSSA1099 EMVs and increased uptake of ΔSSA1882 EMVs relative to SK36 EMVs. However, EMVs from wild-type and deletion mutants showed similar patterns in cytokine and chemokine secretion. Transcriptomic analysis of gingival epithelial cells inoculated with SK36 EMVs showed a downregulation of genes implicated in apoptosis as well as interferon signaling, while showing an upregulation of genes involved in cytokine production. Gelatin zymography results show that SK36 EMVs have a contrasting result on production of MMP2/9; MMP2 production is decreased while MMP9 is increased by 48 hours post-inoculation (hpi). Dual-inoculation studies demonstrate that prior internalization of
S. sanguinis
EMVs protects gingival epithelial cells from exposure to pathobiont
Porphyromonas gingivalis
outer membrane vesicles (OMVs), preventing dissociation and cell death. Our overall findings suggest that
S. sanguinis
EMVs trigger an immune response on gingival epithelial cells; however, this response suggests inhibition of some immune signaling pathways. Our results highlight an important role in commensalism, in which a microbe induces an immune response but avoids damage to host cells, thus discouraging infection by pathobionts.
HSP90 interacts with VP37 to facilitate the cell-to-cell movement of broad bean wilt virus 2
Authors: Kim Myung-Hwi , Jang Seok-Yeong , Choi Ji-Soo , Kim Sora , Lee Yubin , Park Suejin , Kwon Sun-Jung , Seo Jang-Kyun 
Published: February 2025

ABSTRACT

The systemic spread of viruses in plants requires successful viral cell-to-cell movement through plasmodesmata (PD). Viral movement proteins (MPs) interact with cellular proteins to modify and utilize host transport routes. Broad bean wilt virus 2 (BBWV2) moves from cell to cell as a virion through the PD gated by VP37, the MP of BBWV2. However, the host proteins that function in the cell-to-cell movement of BBWV2 remain unclear. In this study, we identified cellular heat shock protein 90 (HSP90) as an interacting partner of VP37. The interaction between HSP90 and VP37 was assessed using the yeast two-hybrid assay, co-immunoprecipitation, and bimolecular fluorescence complementation. Tobacco rattle virus-based virus-induced gene silencing analysis revealed that
HSP90
silencing significantly inhibited the systemic spread of BBWV2 in
Nicotiana benthamiana
plants. Furthermore,
in planta
treatment with geldanamycin (GDA), an inhibitor of the chaperone function of HSP90, demonstrated the necessity of HSP90 in successful cell-to-cell movement and systemic infection of BBWV2. Interestingly, GDA treatment inhibited the HSP90-VP37 interaction at the PD, resulting in the inhibition of VP37-derived tubule formation through the PD. Our results suggest that the HSP90-VP37 interaction regulates VP37-derived tubule formation through the PD, thereby facilitating the cell-to-cell movement of BBWV2.

IMPORTANCE
This study highlights the regulatory role of heat shock protein 90 (HSP90) in facilitating the cell-to-cell movement of broad bean wilt virus 2 (BBWV2). HSP90 interacted with VP37, the movement protein of BBWV2, specifically at plasmodesmata (PD). This study demonstrated that the HSP90-VP37 interaction is crucial for viral cell-to-cell movement and the formation of VP37-derived tubules, which are essential structures for virus transport through the PD. The ATP-dependent chaperone activity of HSP90 is integral to this interaction, as demonstrated by the inhibition of virus movement upon treatment with geldanamycin, which disrupts the function of HSP90. These findings elucidate the molecular mechanisms underlying the cell-to-cell movement of plant viruses and highlight the role of HSP90 in viral infection. This study suggests that the chaperone activity of HSP90 may function in changing the conformational structure of VP37, thereby facilitating the assembly and function of virus-induced structures required for viral cell-to-cell movement.
Investigating the influence of
Diadematidae
scuticociliatosis on host microbiome composition
Authors: Vilanova-Cuevas Brayan , DeRito Christopher M. , Ritchie Isabella T. , Kellogg Christina A. , Evans James S. , Zimmerman Alizee , Williams Stacey M. , Brandt Marilyn , Sevier Moriah , Gittens Samuel , Budd Kayla A. , Warham Matthew , Sharp William C. , Delgado Gabriel A. , Hylkema Alwin , Kitson-Walters Kimani , Quod Jean-Pascal , Breitbart Mya , Hewson Ian 
Published: February 2025

ABSTRACT

Mass mortality of Diadematidae urchins, caused by the
Diadema antillarum
scuticociliatosis Philaster clade (DScPc)
,
affected the Caribbean in spring 2022 and subsequently spread to the eastern Mediterranean, Red Sea, and western Indian Ocean. A key question around Diadematidae scuticociliatosis (DSc), the disease caused by the scuticociliate, is whether the urchin microbiome varies between scuticociliatosis-affected and grossly normal urchins. Tissue samples from both grossly normal and abnormal
Diadema antillarum
were collected in the field during the initial assessment of the DSc causative agent and from an experimental challenge of DScPc culture on aquacultured
D. antillarum
. Specimens were analyzed using 16S rRNA gene amplicon sequencing. Additional abnormal urchin samples were collected from the most recent outbreak site in the western Indian Ocean (Réunion Island). At reference (i.e., unaffected by DSc) sites,
Kistimonas
spp.
, Propionigenium
spp., and
Endozoicomonas
spp. were highly represented in amplicon libraries. DSc-affected urchin amplicon libraries had lower taxonomic richness and a greater representation of taxa related to
Fangia hongkongensis
and
Psychrobium
spp. Amplicon libraries of urchins experimentally challenged with the DSc pathogen had some shifts in microbial composition, but
F. hongkongensis
was not a part of the core bacteria in DSc-challenged specimens. DSc-affected
Echinothrix diadema
from Réunion Island showed a similar high representation of
F. hongkongensis
as that seen on Caribbean
D. antillarum
. Our results suggest that DSc alters
Diadematidae
microbiomes and that
F. hongkongensis
may be a candidate bacterial biomarker for DSc in environmental samples. The mechanism driving microbiome variation in host–pathogen interactions remains to be explored.

IMPORTANCE

The mass mortality of Diadematidae urchins due to
Diadema antillarum
scuticociliatosis (DSc) has had significant ecological impacts, spreading from the Caribbean to the eastern Mediterranean, Red Sea, and western Indian Ocean. This study investigates whether the microbiome of urchins varies between those affected by DSc and those that are not. Using 16S rRNA gene amplicon sequencing, researchers found that DSc-affected urchins had lower taxonomic richness and a greater representation of
Fangia hongkongensis
and
Psychrobium
spp. The findings indicate that
F. hongkongensis
could serve as a bacterial biomarker for DSc in environmental samples, providing a potential tool for early detection and management of the disease. Understanding these microbiome changes is crucial for developing strategies to mitigate the spread and impact of DSc on marine ecosystems.
Lipid alterations in acute myocardial infarction are associated with gut microbiota
Authors: Zuo Jiebin , Wang Panpan , Xue Kewen , Tan Yuwen , Zhang Ting , Li Yang , He Feixiang , Wu Weikun , Yan Zhixiang , Cong Li , Li Gang 
Published: February 2025

ABSTRACT

Although lipid metabolism and gut microbiota dysregulation are known to participate in cardiovascular disease, few studies have examined these alterations and associations in acute myocardial infarction (AMI) patients. This study reveals altered and associated lipid metabolism and gut microbiome based on proteomic and lipidomic analyses of fecal and plasma samples from 30 patients with AMI and 33 healthy volunteers. Twenty-three differential plasma lipids, nine altered fecal lipids, and nine differential fecal bacterial species were identified in AMI patients relative to healthy volunteers, with nine plasma lipids, three fecal lipids, and two fecal bacteria as potential biomarkers. Correlation analysis revealed that the abundances of
Stenotrophomonas
and
Bilophila
were positively correlated with sphingosine and ceramide levels, respectively.
Alistipes indistinctus
and
Porphyromonas
were correlated with blood lipid indicators (total cholesterol, triglycerides, and low-density lipoprotein-C), and
A. indistinctus
,
Bilophila
, and
Stenotrophomonas
were associated with myocardial injury indicators (cTnI, CK, CK-MB, LDH, and BNP). This study identified potential lipid and gut microbe biomarkers and their associations in AMI patients.

IMPORTANCE
Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. While lipid metabolism and gut microbiota are known to play important roles in cardiovascular diseases, their interactions in the context of AMI are not fully understood. In this study, we explore the lipidomic and microbiome alterations in AMI patients, identifying key biomarkers associated with myocardial injury. By correlating specific lipid changes with bacterial species in fecal samples, we highlight the potential of lipid–microbe interactions in the pathogenesis of AMI. These findings provide novel insights into the complex mechanisms underlying AMI and suggest potential targets for early diagnosis and therapeutic interventions aimed at modulating lipid and microbial profiles to improve patient outcomes.
New insights into the testicular tropism of porcine reproductive and respiratory syndrome virus
Authors: Durazo-Martínez Kassandra , Osorio Fernando A. , Delhon Gustavo , Hernández Jesús , Vu Hiep L. X. 
Published: February 2025

ABSTRACT

Porcine reproductive and respiratory syndrome virus (PRRSV) has a restricted host specificity, primarily infecting porcine macrophages. Notably, an exception to such macrophage-restricted tropism has been observed in sexually active boars, where the virus infects and induces apoptosis in the germinal epithelium, resulting in viral dissemination in the ejaculate. Whether this phenomenon occurs in prepubertal animals remains unclear. In this study, we isolated spermatogonia stem cells (SSCs) from neonatal pigs and cultured them
in vitro
. These SSC cultures formed morula-like colonies, exhibited alkaline phosphatase activity—a characteristic of stem cells—and expressed protein gene product 9.5, a marker of SSCs. Notably, the SSC cultures supported PRRSV replication with kinetics similar to that observed in porcine alveolar macrophages. To assess the testicular tropism of PRRSV in prepuberal animals, 28-day-old male pigs were infected with a virulent PRRSV strain. Testicular tissues were sequentially analyzed using a combination of
in situ
hybridization for PRRSV RNA and immunohistochemistry for specific cellular markers. Unlike in sexually active boars, PRRSV did not infect the spermatogonia cells within the seminiferous tubules of prepubertal pigs. Instead, the virus primarily infected macrophages and myoid cells located in the interstitium and peritubular areas. It appeared that the anatomical separation of spermatogonia from the basal membrane of the seminiferous tubules in prepubertal pigs prevents these cells from being infected by PRRSV. Overall, our findings offer valuable insights into the age-dependent testicular tropism of PRRSV.

IMPORTANCE

Contaminated boar semen used in artificial insemination has significantly contributed to the global spread of porcine reproductive and respiratory syndrome virus (PRRSV), a virus that typically infects only cells within the monocyte and macrophage lineages. Our study reveals that spermatogonia stem cells (SSCs) from neonatal piglets are also susceptible to PRRSV, suggesting that non-macrophage cells can be infected by the virus. However, despite this susceptibility, PRRSV-infected cells were not found in the seminiferous tubules of prepubertal male pigs inoculated with a virulent PRRSV strain. This contrasts with sexually mature boars, where PRRSV-infected cells were prominently observed within the seminiferous tubules. The discrepancy is likely due to anatomical differences between the seminiferous tubules of sexually mature boars and prepubertal pigs. These findings provide new insights into PRRSV pathogenesis. Additionally, the
ex vivo
SSC culture provides a valuable model for identifying new viral receptors necessary for PRRSV infection and for investigating the virus’s impact on spermatogenesis.
Development of Australian mental health guidelines for community sport
Authors: Vella Stewart Anthony , Liddelow Caitlin , Rice Simon M , Keegan Richard , Hall Kate , Jones Mark A , Lubans David Revalds , McLeod Samantha , Okely Anthony David , Olive Lisa S , Purcell Rosemary , Reece Lindsey J , Rosenbaum Simon , Schweickle Matthew J , Singh Kelsey , Stewart Damien , Stimpson Leisl , Sutcliffe Jordan T , Teychenne Megan , Walton Courtney C , Swann Christian 
Published: February 2025

ObjectiveThe need for clear and actionable guidelines for the promotion and protection of mental health in organised community sport has previously been identified. This study aimed to provide guidelines to promote and protect mental health in organised community sport in Australia.MethodsGuideline development was informed by (1) systematic reviews of the evidence pertaining to existing mental health guidelines in sport and mental health interventions in community sport; (2) an expert Delphi consensus study and (3) key stakeholder input via focus groups. A Guideline Development Committee comprising experts and key stakeholder representatives articulated nine distinct guidelines.ResultsThese guidelines address the areas of: mental health literacy training; mental health support pathways and processes; responding to mental health emergencies; responding to major events that may impact mental health; having a mental health plan in place; reducing stigmatising attitudes; appointing a dedicated mental health champion; coach education and promoting well-being within the organisation.ConclusionsWe provide guidance for promoting and protecting mental health in community sport. Monitoring uptake and measuring the effectiveness of the guidelines are important areas of future work to advance positive mental health for everybody involved in community sport.