bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid in situ diversification rates in Rhamnaceae explain the parallel evolution of high diversity in temperate biomes from global to local scales
Authors: Tian Qin , Stull Gregory W. , Kellermann Jürgen , Medan Diego , Nge Francis J. , Liu Shui‐Yin , Kates Heather R. , Soltis Douglas E. , Soltis Pamela S. , Guralnick Robert P. , Folk Ryan A. , Onstein Renske E. , Yi Ting‐Shuang 
Published: January 2024

Summary
The macroevolutionary processes that have shaped biodiversity across the temperate realm remain poorly understood and may have resulted from evolutionary dynamics related to diversification rates, dispersal rates, and colonization times, closely coupled with Cenozoic climate change.
We integrated phylogenomic, environmental ordination, and macroevolutionary analyses for the cosmopolitan angiosperm family Rhamnaceae to disentangle the evolutionary processes that have contributed to high species diversity within and across temperate biomes.
Our results show independent colonization of environmentally similar but geographically separated temperate regions mainly during the Oligocene, consistent with the global expansion of temperate biomes. High global, regional, and local temperate diversity was the result of high in situ diversification rates, rather than high immigration rates or accumulation time, except for Southern China, which was colonized much earlier than the other regions. The relatively common lineage dispersals out of temperate hotspots highlight strong source‐sink dynamics across the cosmopolitan distribution of Rhamnaceae.
The proliferation of temperate environments since the Oligocene may have provided the ecological opportunity for rapid in situ diversification of Rhamnaceae across the temperate realm. Our study illustrates the importance of high in situ diversification rates for the establishment of modern temperate biomes and biodiversity hotspots across spatial scales.
The halothane era in pediatric anesthesia: The convergence of a cardiac depressant anesthetic with the immature myocardium of infancy
Authors: Friesen Robert H. 
Published: January 2024

AbstractIntroduced in the late 1950s, halothane became the anesthetic of choice for inhalational induction of children for over 40 years. Halothane enjoyed a generally favorable safety record during its time, but its cardiac contractility depressant effect—well tolerated by most age groups—was profoundly heightened in neonates and infants, leading to increased incidences of hypotension and cardiac arrest. The neonatal myocardium is immature and is characterized by poor ventricular compliance, poor contractility due to fewer contractile elements, immature sympathetic innervation with decreased norepinephrine stores, and immature mechanisms for storage and exchange of calcium in the sarcoplasmic reticulum. In vitro studies of myocardial contractility of mammalian fetal and adult myocardium demonstrated that the fetal heart was twice as sensitive to halothane as the adult. Clinical studies demonstrated that most neonates and infants less than 6 months of age experienced hypotension during halothane induction of anesthesia and significantly (p < .01) greater decreases in blood pressure than older children at equipotent concentrations of halothane. Intraoperative cardiac arrest during the halothane era occurred over twice as frequently in neonates aged less than 1 month than in infants aged 1–12 months and nearly 10 times more frequently than children 1–5 years of age. Halothane was associated with 66% of intraoperative drug‐related cardiac arrests in children. The halothane era began to close in the late 1990s with the introduction of sevoflurane, which had a more favorable hemodynamic profile. Shortly thereafter, halothane was completely displaced from pediatric anesthesia practice in North America.
External jasmonic acid isoleucine mediates amplification of plant elicitor peptide receptor (PEPR) and jasmonate‐based immune signalling
Authors: Mittal Deepika , Gautam Janesh Kumar , Varma Mahendra , Laie Amrutha , Mishra Shruti , Behera Smrutisanjita , Vadassery Jyothilakshmi 
Published: January 2024

AbstractJasmonic acid‐isoleucine (JA‐Ile) is a plant defence hormone whose cellular levels are elevated upon herbivory and regulate defence signalling. Despite their pivotal role, our understanding of the rapid cellular perception of bioactive JA‐Ile is limited. This study identifies cell type‐specific JA‐Ile‐induced Ca2+ signal and its role in self‐amplification and plant elicitor peptide receptor (PEPR)‐mediated signalling. Using the Ca2+ reporter, R‐GECO1 in Arabidopsis, we have characterized a monophasic and sustained JA‐Ile‐dependent Ca2+ signature in leaf epidermal cells. The rapid Ca2+ signal is independent of positive feedback by the JA‐Ile receptor, COI1 and the transporter, JAT1. Microarray analysis identified up‐regulation of receptors, PEPR1 and PEPR2 upon JA‐Ile treatment. The pepr1 pepr2 double mutant in R‐GECO1 background exhibits impaired external JA‐Ile induced Ca2+cyt elevation and impacts the canonical JA‐Ile responsive genes. JA responsive transcription factor, MYC2 binds to the G‐Box motif of PEPR1 and PEPR2 promoter and activates their expression upon JA‐Ile treatment and in myc2 mutant, this is reduced. External JA‐Ile amplifies AtPep‐PEPR pathway by increasing the AtPep precursor, PROPEP expression. Our work shows a previously unknown non‐canonical PEPR‐JA‐Ile‐Ca2+‐MYC2 signalling module through which plants sense JA‐Ile rapidly to amplify both AtPep‐PEPR and jasmonate signalling in undamaged cells.
Predictive model for CAR‐T cell therapy success in patients with relapsed/refractory B‐cell acute lymphoblastic leukaemia
Authors: Pu Lianfang , Wang Huiping , Wu Fan , An Furun , Xiao Hao , Wang Yangyang , Liang Xue , Zhai Zhimin 
Published: January 2024

AbstractChimeric antigen receptor T‐cell (CAR‐T) therapy has demonstrated remarkable efficacy in treating relapsed/refractory acute B‐cell lymphoblastic leukaemia (R/R B‐ALL). However, a subset of patients does not benefit from CAR‐T therapy. Our study aims to identify predictive indicators and establish a model to evaluate the feasibility of CAR‐T therapy. Fifty‐five R/R B‐ALL patients and 22 healthy donors were enrolled. Peripheral blood lymphocyte subsets were analysed using flow cytometry. Sensitivity, specificity, accuracy, positive and negative predictive values and receiver operating characteristic (ROC) areas under the curve (AUC) were determined to evaluate the predictive values of the indicators. We identified B lymphocyte, regulatory T cell (Treg) and peripheral blood minimal residual leukaemia cells (B‐MRD) as indicators for predicting the success of CAR‐T cell preparation with AUC 0.936, 0.857 and 0.914. Furthermore, a model based on CD3+ T count, CD4+ T/CD8+ T ratio, Treg and extramedullary diseases (EMD) was used to predict the response to CAR‐T therapy with AUC of 0.938. Notably, a model based on CD4+ T/CD8+ T ratio, B, Treg and EMD were used in predicting the success of CAR‐T therapy with AUC 0.966 [0.908–1.000], with specificity (92.59%) and sensitivity (91.67%). In the validated group, the predictive model predicted the success of CAR‐T therapy with specificity (90.91%) and sensitivity (100%). We have identified several predictive indicators for CAR‐T cell therapy success and a model has demonstrated robust predictive capacity for the success of CAR‐T therapy. These results show great potential for guiding informed clinical decisions in the field of CAR‐T cell therapy.
Downscaling platelet cryopreservation: Are platelets frozen in tubes comparable to standard cryopreserved platelets?
Authors: Waters Lauren , Marks Denese C. , Johnson Lacey 
Published: January 2024

AbstractBackgroundPlatelet cryopreservation extends the shelf‐life to at least 2 years. However, platelets are altered during the freeze/thaw process. Downscaling platelet cryopreservation by freezing in tubes would enable rapid screening of novel strategies to improve the quality of cryopreserved platelets (CPPs). The aim of this study was to characterize the effect of freezing conditions on the in vitro phenotype and function of platelets frozen in a low volume compared to standard CPPs.MethodsPlatelets were prepared for cryopreservation using 5%–6% DMSO and processed using standard protocols or aliquoted into 2 mL tubes. Platelets were hyperconcentrated to 25 mL (standard CPPs) or 200 μL (tubes) before freezing at −80°C (n = 8). Six insulators/controlled rate freezing containers were used to vary the freezing rate of platelets in tubes. Platelets were thawed, resuspended in plasma, and then assessed by flow cytometry and thromboelastography.ResultsThe use of different insulators for tubes changed the freezing rate of platelets compared to platelets frozen using the standard protocol (p < .001). However, this had no impact on the recovery of the platelets (p = .87) or the proportion of platelets expressing GPIbα (p = .46) or GPVI (p = .07), which remained similar between groups. A lower proportion of platelets frozen in tubes externalized phosphatidylserine compared to standard CPPs (p < .001). The clot‐forming ability (thromboelastography) of platelets was similar between groups (p > .05).ConclusionFreezing platelets in tubes modified the freezing rate and altered some platelet characteristics. However, the functional characteristics remained comparable, demonstrating the feasibility of downscaling platelet cryopreservation for high‐throughput exploratory investigations.
Wastewater contaminants in a fractured bedrock aquifer and their potential use as enteric virus indicators
Authors: Race Amy S. , Spoelstra John , Parker Beth L. 
Published: January 2024

ABSTRACT

Domestic wastewater is a source of persistent organic pollutants and pathogens to the aquatic environment, including groundwater aquifers. Wastewater contaminants include a variety of personal care products, pharmaceuticals, endocrine disrupters, bacteria, and viruses. Groundwater from 22 wells completed in a semi-confined to confined, fractured Silurian dolostone aquifer in southern Wellington County, Ontario, Canada, was analyzed for 14 organic wastewater contaminants (4 artificial sweeteners, 10 pharmaceuticals) as well as
E. coli
, total coliforms, and 6 human enteric viruses. Enteric viruses were detected in 8.6% of 116 samples, and at least one organic wastewater contaminant was detected in 82% of the wells (in order of decreasing detection frequency: acesulfame, ibuprofen, sulfamethoxazole, triclosan, carbamazepine, and saccharin). Virus indicator metrics [positive and negative predictive values (PPV, NPV), sensitivity, specificity] were calculated at the sample and well level for the organic wastewater compounds,
E. coli
, and total coliforms. Fecal bacteria were not good predictors of virus presence (PPV = 0%–8%). Of the potential chemical indicators, triclosan performed the best at the sample level (PPV = 50%, NPV = 100%), and ibuprofen performed the best at the well level (PPV = 60%, NPV = 67%); however, no samples had triclosan or ibuprofen concentrations above their practical quantification limits. Therefore, none of the compounds performed sufficiently well to be considered reliable for assessing the potential threat of enteric viruses in wastewater-impacted groundwater in this bedrock aquifer. Future studies need to evaluate the indicator potential of persistent organic wastewater contaminants in different types of aquifers, especially in fractured rock where heterogeneity is strong.

IMPORTANCE

Assessing the potential risk that human enteric viruses pose in groundwater aquifers used for potable water supply is complicated by several factors, including: (i) labor-intensive methods for the isolation and quantification of viruses in groundwater, (ii) the temporal variability of these viruses in domestic wastewater, and (iii) their potentially rapid transport in the subsurface, especially in fractured rock aquifers. Therefore, aquifer risk assessment would benefit from the identification of suitable proxy indicators of enteric viruses that are easier to analyze and less variable in wastewater sources. Traditional fecal indicators (e.g.,
E. coli
and coliforms) are generally poor indicators of enteric viruses in groundwater. While many studies have examined the use of pharmaceutical and personal care products as tracers of domestic wastewater and fecal pollution in the environment, there is a paucity of data on the potential use of these chemical tracers as enteric virus indicators, especially in groundwater.
Decarboxylase activity of the non-starter lactic acid bacterium
Loigolactobacillus rennini
gives crack defects in Gouda cheese through the production of γ-aminobutyric acid
Authors: Decadt Hannes , Vermote Louise , Díaz-Muñoz Cristian , Weckx Stefan , De Vuyst Luc 
Published: January 2024

ABSTRACT

Ten Gouda cheese wheels with an age of 31 weeks from six different batch productions were affected by a crack defect and displayed an unpleasant off-flavor. To unravel the causes of these defects, the concentrations of free amino acids, other organic acids, volatile organic compounds, and biogenic amines were quantified in zones around the cracks and in zones without cracks, and compared with those of similar Gouda cheeses without crack defect. The Gouda cheeses with cracks had a significantly different metabolome. The production of the non-proteinogenic amino acid γ-aminobutyric acid (GABA) could be unraveled as the key mechanism leading to crack formation, although the production of the biogenic amines cadaverine and putrescine contributed as well. High-throughput amplicon sequencing of the full-length 16S rRNA gene based on whole-community DNA revealed the presence of
Loigolactobacillus rennini
and
Tetragenococcus halophilus
as most abundant non-starter lactic acid bacteria in the zones with cracks. Shotgun metagenomic sequencing allowed to obtain a metagenome-assembled genome of both
Loil. rennini
and
T. halophilus
. However, only
Loil. rennini
contained genes necessary for the production of GABA, cadaverine, and putrescine. Metagenetics further revealed the brine and the rennet used during cheese manufacturing as the most plausible inoculation sources of both
Loil. rennini
and
T. halophilus
.

IMPORTANCE
Crack defects in Gouda cheeses are still poorly understood, although they can lead to major economic losses in cheese companies. In this study, the bacterial cause of a crack defect in Gouda cheeses was identified, and the pathways involved in the crack formation were unraveled. Moreover, possible contamination sources were identified. The brine bath might be a major source of bacteria with the potential to deteriorate cheese quality, which suggests that cheese producers should regularly investigate the quality and microbial composition of their brines. This study illustrated how a multiphasic approach can understand and mitigate problems in a cheese company.
Exogenous methionine contributes to reversing the resistance of
Streptococcus suis
to macrolides
Authors: Dong Chun-Liu , Wu Tong , Dong Yue , Qu Qian-Wei , Chen Xue-Ying , Li Yan-Hua 
Published: January 2024

ABSTRACT

Streptococcus suis
(
S. suis
) has been increasingly recognized as a porcine zoonotic pathogen that threatens the health of both pigs and humans. Multidrug-resistant
Streptococcus suis
is becoming increasingly prevalent, and novel strategies to treat bacterial infections caused by these organisms are desperately needed. In the present study, an untargeted metabolomics analysis showed that the significant decrease in methionine content and the methionine biosynthetic pathway were significantly affected by the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis in drug-resistant
S. suis
. The addition of L-methionine restored the bactericidal activity of macrolides, doxycycline, and ciprofloxacin on
S. suis in vivo
and
in vitro
. Further studies showed that the exogenous addition of methionine affects methionine metabolism by reducing S-adenosylmethionine synthetase activity and the contents of S-adenosylmethionine, S-adenosyl homocysteine, and S-ribose homocysteine. Methionine can decrease the total methylation level and methylesterase activity in multidrug resistant
S. suis
. The drug transport proteins and efflux pump genes were significantly downregulated in
S. suis
by exogenous L-methionine. Moreover, the exogenous addition of methionine can reduce the survival of
S. suis
by affecting oxidative stress and metal starvation in bacteria. Thus, L-methionine may influence the development of resistance in
S. suis
through methyl metabolism and metal starvation. This study provides a new perspective on the mitigation of drug resistance in
S. suis
.

IMPORTANCE

Bacterial antibiotic resistance has become a severe threat to human and animal health. Increasing the efficacy of existing antibiotics is a promising strategy against antibiotic resistance. Here, we report that L-methionine enhances the efficacy of macrolides, doxycycline, and ciprofloxacin antibiotics in killing
Streptococcus suis
, including multidrug-resistant pathogens. We investigated the mechanism of action of exogenous methionine supplementation in restoring macrolides in
Streptococcus suis
and the role of the methionine cycle pathway on methylation levels, efflux pump genes, oxidative stress, and metal starvation in
Streptococcus suis
. It provides a theoretical basis for the rational use of macrolides in clinical practice and also identifies a possible target for restoring drug resistance in
Streptococcus suis
.
Longitudinal gut microbiota composition of South African and Nigerian infants in relation to tetanus vaccine responses
Authors: Iwase Saori C. , Osawe Sophia , Happel Anna-Ursula , Gray Clive M. , Holmes Susan P. , Blackburn Jonathan M. , Abimiku Alash'le , Jaspan Heather B. 
Published: January 2024

ABSTRACT

Infants who are exposed to HIV but uninfected (iHEU) have higher risk of infectious morbidity than infants who are HIV-unexposed and uninfected (iHUU), possibly due to altered immunity. As infant gut microbiota may influence immune development, we evaluated the effects of HIV exposure on infant gut microbiota and its association with tetanus toxoid vaccine responses. We evaluated the gut microbiota of 82 South African (61 iHEU and 21 iHUU) and 196 Nigerian (141 iHEU and 55 iHUU) infants at <1 and 15 weeks of life by 16S rRNA gene sequencing. Anti-tetanus antibodies were measured by enzyme-linked immunosorbent assay at matched time points. Gut microbiota in the 278 included infants and its succession were more strongly influenced by geographical location and age than by HIV exposure. Microbiota of Nigerian infants, who were exclusively breastfed, drastically changed over 15 weeks, becoming dominated by
Bifidobacterium longum
subspecies
infantis
. This change was not observed among South African infants, even when limiting the analysis to exclusively breastfed infants. The Least Absolute Shrinkage and Selection Operator regression suggested that HIV exposure and gut microbiota were independently associated with tetanus titers at week 15, and that high passively transferred antibody levels, as seen in the Nigerian cohort, may mitigate these effects. In conclusion, in two African cohorts, HIV exposure minimally altered the infant gut microbiota compared to age and setting, but both specific gut microbes and HIV exposure independently predicted humoral tetanus vaccine responses.

IMPORTANCE
Gut microbiota plays an essential role in immune system development. Since infants HIV-exposed and uninfected (iHEU) are more vulnerable to infectious diseases than unexposed infants, we explored the impact of HIV exposure on gut microbiota and its association with vaccine responses. This study was conducted in two African countries with rapidly increasing numbers of iHEU. Infant HIV exposure did not substantially affect gut microbial succession, but geographic location had a strong effect. However, both the relative abundance of specific gut microbes and HIV exposure were independently associated with tetanus titers, which were also influenced by baseline tetanus titers (maternal transfer). Our findings provide insight into the effect of HIV exposure, passive maternal antibody, and gut microbiota on infant humoral vaccine responses.
Oral microbiome associated with differential ratios of
Porphyromonas gingivalis
and
Streptococcus cristatus
Authors: Wang Qingguo , Wang Bing-Yan , Pratap Siddharth , Xie Hua 
Published: January 2024

ABSTRACT

Periodontitis has recently been defined as a dysbiotic disease caused by an imbalanced oral microbiota. The transition from commensal microbial communities to periodontitis-associated ones requires colonization by specific pathogens, including
Porphyromonas gingivalis
. We previously reported an antagonistic relationship between
Streptococcus cristatus
and
P. gingivalis
. To determine the role of
S. cristatus
in altering the interactions of
P. gingivalis
with other oral bacteria in a complex context, we collected dental plaque samples from patients with periodontitis and assigned them to two groups based on the ratios of
S. cristatus
and
P. gingivalis
. We then characterized the microbial profiles of the dental plaque samples using shotgun metagenomic sequencing and compared the oral microbial composition and functional capabilities of the group with high
S. cristatus-P. gingivalis
ratios with the low ratio group. Taxonomic annotation revealed significant differences in the microbial composition at both the genus and species levels between the low and high
S. cristatus-P. gingivalis
ratio groups. Notably, a higher microbial diversity was observed in the samples with low
S. cristatus-P. gingivalis
ratios. Furthermore, the antibiotic resistance gene profiles of the two groups were also distinct, with a significantly increased abundance of the genes in the dental plaque samples with low
S. cristatus-P. gingivalis
ratios. It, therefore, indicates that the
S. cristatus-P. gingivalis
ratios influenced the virulence potential of the oral microbiome. Our work shows that enhancing the
S. cristatus-P. gingivalis
ratio in oral microbial communities can be an attractive approach for revising the dysbiotic oral microbiome.

IMPORTANCE

Periodontitis, one of the most common chronic diseases, is linked to several systemic diseases, such as cardiovascular disease and diabetes. Although
Porphyromonas gingivalis
is a keystone pathogen that causes periodontitis, its levels, interactions with accessory bacteria and pathobionts in the oral microbiome, and its association with the pathogenic potential of the microbial communities are still not well understood. In this study, we revealed the role of
Streptococcus cristatus
and the ratios of
S. cristatus
and
P. gingivalis
in modulating the oral microbiome to facilitate a deeper understanding of periodontitis and its progression. The study has important clinical implications as it laid a foundation for developing novel non-antibiotic therapies against
P. gingivalis
and improving the efficiency of periodontal treatments.