bluuebunny/crossref_metadata_2025 huggingface dataset:
New insight into Ca2+‐permeable channel in plant immunity
Authors: Wang Wei , Cheng Hang‐Yuan , Zhou Jian‐Min
Published: January 2024

Calcium ions (Ca2+) are crucial intracellular second messengers in eukaryotic cells. Upon pathogen perception, plants generate a transient and rapid increase in cytoplasmic Ca2+ levels, which is subsequently decoded by Ca2+ sensors and effectors to activate downstream immune responses. The elevation of cytosolic Ca2+ is commonly attributed to Ca2+ influx mediated by plasma membrane‐localized Ca2+–permeable channels. However, the contribution of Ca2+ release triggered by intracellular Ca2+‐permeable channels in shaping Ca2+ signaling associated with plant immunity remains poorly understood. This review discusses recent advances in understanding the mechanism underlying the shaping of Ca2+ signatures upon the activation of immune receptors, with particular emphasis on the identification of intracellular immune receptors as non‐canonical Ca2+‐permeable channels. We also discuss the involvement of Ca2+ release from the endoplasmic reticulum in generating Ca2+ signaling during plant immunity.
Time‐varying associations between parental closeness, self‐esteem, and sexual behavior across adolescence and emerging adulthood
Authors: Jiang Linghua , Wang Xiafei , Cui Shuangyue , Vasilenko Sara A.
Published: January 2024

This study applied the time‐varying effect model (TVEM) to data from the National Longitudinal Study of Adolescent to Adult Health to explore how self‐esteem mediated age‐varying associations of closeness to mother and father and their child's sexual behavior through adolescence and emerging adulthood. Paternal closeness is associated with lesser odds of sexual behaviors for both female and male adolescents until age 20, whereas maternal closeness only predicts for female adolescents between ages 13 and 15. Self‐esteem mediated the association between mother closeness and multiple partners in male adolescents between ages 14.5 and 16.5. Fathers have an impact on adolescent sexual behavior across adolescence and emerging adulthood, while mothers' roles are more important for female adolescents in early adolescence.
An endophytic Trichoderma‐based wettable powder formulation for biocontrol of apple stem cankers
Authors: Ranjbar Zahra , Salehi Mina , Safaie Naser
Published: January 2024

Fungal stem cankers are common and destructive diseases in apple orchards. Cytospora cincta and Neoscytalidium dimidiatum are the apple canker causal agents in Iran. Formulated biocontrol agents of plant diseases are considered alternatives to synthetic pesticides in sustainable agriculture. The results showed that Trichoderma zelobreve T20 strongly inhibited the in vitro growth of C. cincta and N. dimidiatum. Wettable powder formulation (WPF) based on T. zelobreve T20 was developed to control apple canker caused by C. cincta and N. dimidiatum. The dual culture test showed that T20 inhibited C. cincta and N. dimidiatum growth by 55.19% and 44.07% respectively. T20 culture filtrate reduced the mycelial growth of C. cincta (72.22%) but showed no activity against N. dimidiatum. T20‐based WPF inhibited C. cincta (94.62%) and N. dimidiatum (14.71%) growth on detached branches of 2‐year‐old apple trees (golden delicious cultivar). Also, T20‐based WPF inhibited apple tree canker caused by C. cincta and N. dimidiatum by 82.8% and 60% respectively. The performance of T20‐based WPF on apple trees was significantly better than detached branches. The spore count of T20‐based WPF was about 71.54% of the original count after 4 months, marking its suitable shelf life. T20‐based WPF could be considered a promising control measure against apple canker pathogens.
Habitat loss and small‐scale fishery: A controversial issue
Authors: Silvestrini Chiara , Colletti Alberto , Di Franco Antonio , Colloca Francesco , Milisenda Giacomo , Zampardi Serena , Mangano Maria Cristina , Aglieri Giorgio , Ranù Marco , Liguori Gianluca , Danovaro Roberto , Foglini Federica , Grande Valentina , Fraschetti Simonetta
Published: January 2024

Fishery is one of the most impacting human activities and is responsible for habitat loss in marine systems. While the effects of large‐scale fisheries have been largely investigated, impacts of small‐scale fisheries (SSF) on seafloor integrity are more often assumed than quantitatively investigated. We carried out a literature review at global scale, resulting in 19 studies with quantitative data on sessile benthic bycatch and only one documenting habitat loss driven by SSF. We also conducted a fine‐scale assessment within a Mediterranean partially protected area (PPA). Results showed that 513 m2 of the Posidonia oceanica meadow are removed annually by local SSF within the PPA, considering bycatch, fishing effort, and shoot density. Knowledge on fishing effort and fine‐scale mapping is critical to assess habitat loss, suggesting the need for specific recommendations for eco‐sustainable local fisheries.
Global mesozooplankton communities show lower connectivity in deep oceanic layers
Authors: Canals Oriol , Corell Jon , Villarino Ernesto , Chust Guillem , Aylagas Eva , Mendibil Iñaki , Michell Craig T. , González‐Gordillo Juan Ignacio , Irigoien Xabier , Rodríguez‐Ezpeleta Naiara
Published: January 2024

Mesozooplankton is a key component of the ocean, regulating global processes such as the carbon pump, and ensuring energy transfer from lower to higher trophic levels. Yet, knowledge on mesozooplankton diversity, distribution and connectivity at global scale is still fragmented. To fill this gap, we applied DNA metabarcoding to mesozooplankton samples collected during the Malaspina‐2010 circumnavigation expedition across the Atlantic, Indian and Pacific oceans from the surface to bathypelagic depths. We highlight the still scarce knowledge on global mesozooplankton diversity and identify the Indian Ocean and the deep sea as the oceanic regions with the highest proportion of hidden diversity. We report no consistent alpha‐diversity patterns for mesozooplankton at a global scale, neither across vertical nor horizontal gradients. However, beta‐diversity analysis suggests horizontal and vertical structuring of mesozooplankton communities mostly attributed to turnover and reveals an increase in mesozooplankton beta‐diversity with depth, indicating reduced connectivity at deeper layers. Additionally, we identify a water mass type‐mediated structuring of mesozooplankton bathypelagic communities instead of an oceanic basin‐mediated as observed at upper layers. This suggests limited dispersal at deep ocean layers, most likely due to weaker currents and lower mixing of water mass types, thus reinforcing the importance of oceanic currents and barriers to dispersal in shaping global plankton communities.
The ABI4‐RGL2 module serves as a double agent to mediate the antagonistic crosstalk between ABA and GA signals
Authors: Xian Baoshan , Rehmani Muhammad Saad , Fan Yueni , Luo Xiaofeng , Zhang Ranran , Xu Jiahui , Wei Shaowei , Wang Lei , He Juan , Fu Aigen , Shu Kai
Published: January 2024

Abscisic acid (ABA) and gibberellins (GA) antagonistically mediate several biological processes, including seed germination, but the molecular mechanisms underlying ABA/GA antagonism need further investigation, particularly any role mediated by a transcription factors module.

Here, we report that the DELLA protein RGL2, a repressor of GA signaling, specifically interacts with ABI4, an ABA signaling enhancer, to act as a transcription factor complex to mediate ABA/GA antagonism.

The rgl2, abi3, abi4 and abi5 mutants rescue the non‐germination phenotype of the ga1‐t. Further, we demonstrate that RGL2 specifically interacts with ABI4 to form a heterodimer. RGL2 and ABI4 stabilize one another, and GA increases the ABI4‐RGL2 module turnover, whereas ABA decreases it. At the transcriptional level, ABI4 enhances the RGL2 expression by directly binding to its promoter via the CCAC cis‐element, and RGL2 significantly upregulates the transcriptional activation ability of ABI4 toward its target genes, including ABI5 and RGL2. Abscisic acid promotes whereas GA inhibits the ability of ABI4‐RGL2 module to activate transcription, and ultimately ABA and GA antagonize each other. Genetic analysis demonstrated that both ABI4 and RGL2 are essential for the activity of this transcription factor module.

These results suggest that the ABI4‐RGL2 module mediates ABA/GA antagonism by functioning as a double agent.
Hurricanes: an unexpected mechanism linking disturbance and seed production in trees
Authors: Pearse Ian S. , Wion Andreas P.
Published: January 2024

This article is a Commentary on Cannon et al. (2024), 242: 289–301.
Temporomandibular joint disorders and associated factors in a Turkish pediatric population
Authors: Torul Damla , Yılmaz Muhammed Furkan , Örnek Akdoğan Emine , Omezli Mehmet Melih
Published: January 2024

Objective

To explore the presence and severity of temporomandibular disorders (TMD) signs and symptoms in a Turkish pediatric population, as well as their relationship to parafunctional behaviors, bruxism, malocclusion, anxiety, and sociodemographic traits.

Methods

A cross‐sectional study was conducted with patients between the ages of 5–15. Demographic variables, TMD signs and symptoms, parafunctional habits, bruxism, and malocclusion were evaluated by clinical examination. Fonseca Anamnestic Index (FAI) was used to determine the presence and severity of TMD. State‐Trait Anxiety Scale for Children (STAI‐C) was used to evaluate the anxiety. Student t, Mann–Whitney U, chi‐square tests, and logistic regression were used for statistical analysis.

Results

One hundred sixty‐two participants (85 girls, 77 boys) with a mean age of 10.03 ± 1.88 years were included. The frequency of the participants who reported signs/symptoms of TMD was 19.7% according to FAI scores. Logistic regression analysis with the associated factors showed a significant relationship between the presence of the signs/symptoms of TMD and parafunctional habits (OR 4.24, 95% CI 1.64–10.93), and the presence of signs/symptoms of anxiety (OR 1.09, 95% CI 1.02–1.16).

Conclusions

Children and adolescents who exhibit parafunctional behaviors and anxiety had a higher likelihood of having TMD signs/symptoms of varying degrees of severity.
Perioperative methadone for posterior spinal fusion in adolescents: Results from a double‐blind randomized‐controlled trial
Authors: Fons Roger A. , Hainsworth Keri R. , Michlig Johanna , Jablonski Megan , Czarnecki Michelle L. , Weisman Steven J.
Published: January 2024

Background

Posterior spinal fusion is the most common surgical procedure performed for correction of adolescent idiopathic scoliosis in the United States. Intraoperative methadone has been shown to improve pain control in adult patients undergoing complex spine surgery, and current pediatric studies show encouraging results; however, prospective randomized‐controlled trials are lacking in the pediatric literature.

Aims

We conducted a single‐center double‐blind randomized‐controlled trial to compare intraoperative use of methadone to morphine in pediatric patients undergoing posterior spinal fusion.

Methods

A total of 47 adolescents undergoing posterior spinal fusion were randomized (stratified by sex) to either a methadone (n = 25) or morphine (n = 22) group. The primary outcome was postoperative opioid consumption. Secondary outcomes included postoperative pain severity, opioid‐related side effects, and ratio of patient‐controlled analgesia injections: attempts as a behavioral index of uncontrolled pain.

Results

Patients in the methadone group consumed less total opioid postoperatively (median [interquartile range], 0.3 mg/kg [0.1, 0.5]) than patients in the morphine group (0.3 mg/kg [0.2, 0.6]), median difference [95% confidence interval] −0.07 [−0.2 to 0.02]; (p = .026). Despite the lower amount of opioid used postoperatively, pain scores for the methadone group (3.5 [3.0, 4.3]) were not significantly different from those in the morphine group (4.0 [3.2, 5.0]; p = .250). Groups did not differ on opioid‐related side effects.

Conclusions

A two‐dose intraoperative methadone regimen resulted in decreased opioid consumption compared to morphine. Although the clinical significance of these results may be limited, the analgesic equipoise without increased opioid‐related side effects and potential for a lower incidence of chronic pain may tip the balance in favor of routine methadone use for adolescents undergoing posterior spinal fusion.
A precise balance of TETRASPANIN1/TORNADO2 activity is required for vascular proliferation and ground tissue patterning in Arabidopsis
Authors: Konstantinova Nataliia , Mor Eliana , Verhelst Eline , Nolf Jonah , Vereecken Kenzo , Wang Feng , Van Damme Daniel , De Rybel Bert , Glanc Matouš
Published: January 2024

The molecular mechanisms guiding oriented cell divisions in the root vascular tissues of Arabidopsis thaliana are still poorly characterised. By overlapping bulk and single‐cell transcriptomic datasets, we unveiled TETRASPANIN1 (TET1) as a putative regulator in this process. TET1 is expressed in root vascular cells, and loss‐of‐function mutants contain fewer vascular cell files. We further generated and characterised a CRISPR deletion mutant and showed, unlike previously described mutants, that the full knock out is additionally missing endodermal cells in a stochastic way. Finally, we show that HA‐tagged versions of TET1 are functional in contrast to fluorescent TET1 translational fusions. Immunostaining using HA‐TET1 lines complementing the mutant phenotype suggested a dual plasma membrane and intracellular localisation in the root vasculature and a polar membrane localisation in the young cortex, endodermal and initial cells. Taken together, we show that TET1 is involved in both vascular proliferation and ground tissue patterning. Our initial results pave the way for future work to decipher its precise mode of action.
On the expectations of equivariant matrix‐valued functions of Wishart and inverse Wishart matrices
Authors: Hillier Grant , Kan Raymond M.
Published: January 2024

Many matrix‐valued functions of an Wishart matrix , , say, are homogeneous of degree in , and are equivariant under the conjugate action of the orthogonal group , that is, , . It is easy to see that the expectation of such a function is itself homogeneous of degree in , the covariance matrix, and are also equivariant under the action of on . The space of such homogeneous, equivariant, matrix‐valued functions is spanned by elements of the type , where and, for each , varies over the partitions of , and denotes the power‐sum symmetric function indexed by . In the analogous case where is replaced by , these elements are replaced by . In this paper, we derive recurrence relations and analytical expressions for the expectations of such functions. Our results provide highly efficient methods for the computation of all such moments.
Trans health training objectives: A scoping review
Authors: Ahmad Tehmina , Robinson Lilian , Uleryk Elizabeth , Yu Catherine
Published: January 2024

Background

Transgender individuals are discriminated against in health care environments and consistently experience poorer health outcomes than their cisgender counterparts. Enhancing physician training in transgender‐specific health is critical to closing the transgender health gap.

Methods

We conducted a scoping review to identify transgender health training objectives in Internal Medicine and Internal Medicine Subspecialty residency programmes in Canada and the United States. A systematic search was conducted from 1946 to 15 February 2022. Studies were eligible for inclusion if they were written in English, included transgender training objectives, and were aimed at resident physicians in Internal Medicine or Internal Medicine Subspecialty training programmes in Canada or the United States.

Findings

We found 4048 papers, of which 11 were included for analysis. Transgender health training objectives were synthesised into five themes, including (1) terminology, physiology, and gender presentation, (2) gender‐affirming care and communication, (3) hormonal and surgical management, (4) routine health management and maintenance, and (5) equity, diversity, and inclusion in clinical care. The majority of objectives pertained to equity, diversity, and inclusion in clinical care, namely, respectful communication and non‐judgemental care of transgender patients.

Discussion

Our findings provide a comprehensive overview of published transgender health objectives in Canada and the United States and highlight existing gaps in postgraduate medical education for Internal Medicine and Subspecialty programmes.

Conclusions

We argue a need for standardisation of transgender‐related residency training and suggest that postgraduate Internal Medicine programmes can utilise this review as a framework to begin enhancing transgender health education for their residents.
ASME’S Unique Approach to Climate Change
Authors: Winters Jeffrey
Published: January 2024

ASME Executive Director and CEO Thomas Costabile talks to the editor in chief of Mechanical Engineering about ASME’s approach to tackling climate change and the role engineers will play in developing and deploying the necessary technologies.
An Experimental Study on the Accuracy of Cumulative Damage Models in Gear Tooth Bending Fatigue
Authors: Anichowski Gabriel , Damm Riley , Kahraman Ahmet , Hong Isaac
Published: January 2024

Tooth bending fatigue failure is a primary design concern for gear designers in power transmission applications. Fracture of a gear tooth in operation results in overload conditions to adjacent teeth, which cascades into potential failure. Total loss of power transmission usually occurs within seconds of the primary failure. While standard constant stress amplitude fatigue evaluations are common to experimentally determine probabilistic stress–life (PSN) relationships, they do not directly measure the fatigue lives under complex, non-constant amplitude loading scenarios applied to gears in most applications. Various cumulative damage models exist to estimate fatigue life under duty cycle loading, but their accuracy is both material and stress state dependent. Most models are validated under only uniaxial stress states and for limited materials. There is a void of experimental data that would enable the evaluation of the accuracy of cumulative damage models for gear tooth bending fatigue in typical cases of carburized gear steels. This research study conducts a standard fatigue evaluation along with two sets of dual stress amplitude single tooth bending fatigue tests to empirically determine the effects of multi-stage loading. Various cumulative damage fatigue models are then employed to estimate the fatigue lives of the dual stress amplitude specimens, and the accuracy of each model is assessed.
Atomic layer etching of indium tin oxide
Authors: Kauppinen Christoffer
Published: January 2024

This work presents the atomic layer etching (ALE) process for sputtered indium tin oxide (ITO) thin films using thermal surface modification with BCl3 and modified surface removal by low ion energy Ar plasma. In this approach, an elevated temperature is required for high synergy ALE due to the low volatility of indium chlorides, and 150°C is proved to be suitable. An etch per cycle (EPC) of 1.1 Å and ALE synergy of 82% was achieved. Both surface modification and modified surface removal steps exhibited self-limited EPC. The ALE process was developed in a conventional reactive ion etching tool and retains the thin film absolute uniformity on the wafer. ITO was photolithographically patterned on whole wafers using photoresist as an etch mask for the ALE, and clear smoothing of the unmasked areas is observed, which is a characteristic of an ideal ALE process. This confirms that the developed ALE process can be utilized to pattern ITO using conventional photolithography. The demonstrated ITO ALE can be used to fabricate, for example, thin channel or recessed channel transistors, with self-smoothened channels for reduced surface scattering.
Characterization of the vocal behavior of the miniature and transparent fish model, Danionella cerebrum
Authors: Vasconcelos Raquel O. , Bolgan Marta , Matos André B. , Van-Dunem Sheila P. , Penim Jorge , Amorim M. Clara P.
Published: January 2024

Danionella cerebrum has recently been proposed as a promising model to investigate the structure and function of the adult vertebrate brain, including the development of vocal–auditory neural pathways. This genetically tractable and transparent cypriniform is highly vocal, but limited information is available on its acoustic behavior and underlying biological function. Our main goal was to characterize the acoustic repertoire and diel variation in sound production of D. cerebrum, as well as to investigate the relationship between vocal behavior and reproduction. Sound recordings demonstrated high vocal activity, with sounds varying from short sequences of pulses known as “bursts” (comprising up to 15 pulses) to notably longer sounds, termed “long bursts”, which extended up to 349 pulses with over 2.7 s. Vocal activity peaked at midday and it was very low at night with only a few bursts. While the number of pulses was higher during the daytime, the interpulse interval was longer at night. In addition, calling time was positively associated with the number of viable eggs, suggesting that acoustic communication is important for reproduction. These preliminary findings reveal the potential of using D. cerebrum to investigate vocal plasticity and the implications for sexual selection and reproduction in a novel vertebrate model for neuroscience.
Pannexin-3 stabilizes the transcription factor Bcl6 in a channel-independent manner to protect against vascular oxidative stress
Authors: Wolpe Abigail G. , Luse Melissa A. , Baryiames Christopher , Schug Wyatt J. , Wolpe Jacob B. , Johnstone Scott R. , Dunaway Luke S. , Juśkiewicz Zuzanna J. , Loeb Skylar A. , Askew Page Henry R. , Chen Yen-Lin , Sabapathy Vikram , Pavelec Caitlin M. , Wakefield Brent , Cifuentes-Pagano Eugenia , Artamonov Mykhaylo V. , Somlyo Avril V. , Straub Adam C. , Sharma Rahul , Beier Frank , Barrett Eugene J. , Leitinger Norbert , Pagano Patrick J. , Sonkusare Swapnil K. , Redemann Stefanie , Columbus Linda , Penuela Silvia , Isakson Brant E.
Published: January 2024

Targeted degradation regulates the activity of the transcriptional repressor Bcl6 and its ability to suppress oxidative stress and inflammation. Here, we report that abundance of endothelial Bcl6 is determined by its interaction with Golgi-localized pannexin 3 (Panx3) and that Bcl6 transcriptional activity protects against vascular oxidative stress. Consistent with data from obese, hypertensive humans, mice with an endothelial cell–specific deficiency inPanx3had spontaneous systemic hypertension without obvious changes in channel function, as assessed by Ca2+handling, ATP amounts, or Golgi luminal pH. Panx3 bound to Bcl6, and its absence reduced Bcl6 protein abundance, suggesting that the interaction with Panx3 stabilized Bcl6 by preventing its degradation.Panx3deficiency was associated with increased expression of the gene encoding the H2O2-producing enzyme Nox4, which is normally repressed by Bcl6, resulting in H2O2-induced oxidative damage in the vasculature. Catalase rescued impaired vasodilation in mice lacking endothelial Panx3. Administration of a newly developed peptide to inhibit the Panx3-Bcl6 interaction recapitulated the increase inNox4expression and in blood pressure seen in mice with endothelialPanx3deficiency. Panx3-Bcl6-Nox4 dysregulation occurred in obesity-related hypertension, but not when hypertension was induced in the absence of obesity. Our findings provide insight into a channel-independent role of Panx3 wherein its interaction with Bcl6 determines vascular oxidative state, particularly under the adverse conditions of obesity.
Transposition mechanism of IS
Apl1
—the determinant of colistin resistance dissemination
Authors: Li Wei , He Zhien , Di Wei , Xu Weifeng , Li Yujie , Sun Baolin
Published: January 2024

Multidrug-resistant
Enterobacteriaceae
, a prominent family of gram-negative pathogenic bacteria, causes a wide range of severe diseases. Strains carrying the mobile colistin resistance (
mcr-1
) gene show resistance to polymyxin, the last line of defense against multidrug-resistant gram-negative bacteria. However, the transmission of
mcr-1
is not well understood. In this study, genomes of
mcr-1
-positive strains were obtained from the NCBI database, revealing their widespread distribution in China. We also showed that IS
Apl1
, a crucial factor in
mcr-1
transmission, is capable of self-transposition. Moreover, the self-cyclization of IS
Apl1
is mediated by its own encoded transposase. The electrophoretic mobility shift assay experiment validated that the transposase can bind to the inverted repeats (IRs) on both ends, facilitating the cyclization of IS
Apl1
. Through knockout or shortening of IRs at both ends of IS
Apl1
, we demonstrated that the cyclization of IS
Apl1
is dependent on the sequences of the IRs at both ends. Simultaneously, altering the ATCG content of the bases at both ends of IS
Apl1
can impact the excision rate by modifying the binding ability between IRs and ISAPL1. Finally, we showed that heat-unstable nucleoid protein (HU) can inhibit IS
Apl1
transposition by binding to the IRs and preventing ISAPL1 binding and expression. In conclusion, the regulation of IS
Apl1
-self-circling is predominantly controlled by the inverted repeat (IR) sequence and the HU protein. This molecular mechanism deepens our comprehension of
mcr-1
dissemination.
sRNA molecules participate in hyperosmotic stress response regulation in
Sphingomonas melonis
TY
Authors: Wang Xiaoyu , Wang Lvjing , Wang Yihan , Fu Xueni , Wang Xuejun , Wu Hao , Wang Haixia , Lu Zhenmei
Published: January 2024

Drought and salinity are ubiquitous environmental factors that pose hyperosmotic threats to microorganisms and impair their efficiency in performing environmental functions. However, bacteria have developed various responses and regulatory systems to cope with these abiotic challenges. Posttranscriptional regulation plays vital roles in regulating gene expression and cellular homeostasis, as hyperosmotic stress conditions can lead to the induction of specific small RNA molecules (sRNAs) that participate in stress response regulation. Here, we report a candidate functional sRNA landscape of
Sphingomonas melonis
TY under hyperosmotic stress, and 18 sRNAs were found with a clear response to hyperosmotic stress. These findings will help in the comprehensive analysis of sRNA regulation in
Sphingomonas
species. Weighted correlation network analysis revealed a 263 nucleotide sRNA, SNC251, which was transcribed from its own promoter and showed the most significant correlation with hyperosmotic response factors. Deletion of
snc251
affected biofilm formation and multiple cellular processes, including ribosome-related pathways, aromatic compound degradation, and the nicotine degradation capacity of
S. melonis
TY, while overexpression of SNC251 facilitated biofilm formation by TY under hyperosmotic stress. Two genes involved in the TonB system were further verified to be activated by SNC251, which also indicated that SNC251 is a
trans
-acting sRNA. Briefly, this research reports a landscape of sRNAs participating in the hyperosmotic stress response in
S. melonis
and reveals a novel sRNA, SNC251, which contributes to the
S. melonis
TY biofilm formation and thus enhances its hyperosmotic stress response ability.

IMPORTANCE

Sphingomonas
species play a vital role in plant defense and pollutant degradation and survive extensively under drought or salinity. Previous studies have focused on the transcriptional and translational responses of
Sphingomonas
under hyperosmotic stress, but the posttranscriptional regulation of small RNA molecules (sRNAs) is also crucial for quickly modulating cellular processes to adapt dynamically to osmotic environments. In addition, the current knowledge of sRNAs in
Sphingomonas
is extremely scarce. This research revealed a novel sRNA landscape of
Sphingomonas melonis
and will greatly enhance our understanding of sRNAs’ acting mechanisms in the hyperosmotic stress response.
Listeria monocytogenes
utilizes glutathione and limited inorganic sulfur compounds as sources of essential cysteine
Authors: Berude John C. , Kennouche Paul , Reniere Michelle L. , Portnoy Daniel A.
Published: January 2024

Listeria monocytogenes
(
Lm
) is a Gram-positive facultative intracellular pathogen that leads a biphasic lifecycle, transitioning its metabolism and selectively inducing virulence genes when it encounters mammalian hosts. Virulence gene expression is controlled by the master virulence regulator PrfA, which is allosterically activated by the host- and bacterially derived glutathione (GSH). The amino acid cysteine is the rate-limiting substrate for GSH synthesis in bacteria and is essential for bacterial growth. Unlike many bacteria,
Lm
is auxotrophic for cysteine and must import exogenous cysteine for growth and virulence. GSH is enriched in the host cytoplasm, and previous work suggests that
Lm
utilizes exogenous GSH for PrfA activation. Despite these observations, the import mechanism(s) for GSH remains elusive. Analysis of known GSH importers predicted a homologous importer in
Lm
comprised of the Ctp ABC transporter and the OppDF ATPases of the Opp oligopeptide importer. Here, we demonstrated that the Ctp complex is a high-affinity GSH/GSSG importer that is required for
Lm
growth at physiologically relevant concentrations. Furthermore, we demonstrated that OppDF is required for GSH/GSSG import in an Opp-independent manner. These data support a model where Ctp and OppDF form a unique complex for GSH/GSSG import that supports growth and pathogenesis. In addition, we show that
Lm
utilizes the inorganic sulfur sources thiosulfate and H
2
S for growth in a CysK-dependent manner in the absence of other cysteine sources. These findings suggest a pathoadaptive role for partial cysteine auxotrophy in
Lm
, where locally high GSH/GSSG or inorganic sulfur concentrations may signal arrival to distinct host niches.
Fitness benefits of a synonymous substitution in an ancient EF-Tu gene depend on the genetic background
Authors: McGrath Kaitlyn M. , Russell Steven J. , Fer Evrim , Garmendia Eva , Hosgel Ali , Baltrus David A. , Kaçar Betül
Published: January 2024

Synonymous mutations are changes to DNA sequence, which occur within translated genes but which do not affect the protein sequence. Although often referred to as silent mutations, evidence suggests that synonymous mutations can affect gene expression, mRNA stability, and even translation efficiency. A collection of both experimental and bioinformatic data has shown that synonymous mutations can impact cell phenotype, yet less is known about the molecular mechanisms and potential of beneficial or adaptive effects of such changes within evolved populations. Here, we report a beneficial synonymous mutation acquired via experimental evolution in an essential gene variant encoding the translation elongation factor protein EF-Tu. We demonstrate that this particular synonymous mutation increases EF-Tu mRNA and protein levels as well as global polysome abundance on RNA transcripts. Although presence of the synonymous mutation is clearly causative of such changes, we also demonstrate that fitness benefits are highly contingent on other potentiating mutations present within the genetic background in which the mutation arose. Our results underscore the importance of beneficial synonymous mutations, especially those that affect levels of proteins that are key for cellular processes.

IMPORTANCE

This study explores the degree to which synonymous mutations in essential genes can influence adaptation in bacteria. An experimental system whereby an
Escherichia coli
strain harboring an engineered translation protein elongation factor-Tu (EF-Tu) was subjected to laboratory evolution. We find that a synonymous mutation acquired on the gene encoding for EF-Tu is conditionally beneficial for bacterial fitness. Our findings provide insight into the importance of the genetic background when a synonymous substitution is favored by natural selection and how such changes have the potential to impact evolution when critical cellular processes are involved.
Porcine deltacoronavirus nsp5 antagonizes type I interferon signaling by cleaving IFIT3
Authors: Huang Haixin , Lei Xiaoxiao , Zhao Chenchen , Qin Yan , Li Yuying , Zhang Xinyu , Li Chengkai , Lan Tian , Zhao Baopeng , Sun Wenchao , Lu Huijun , Jin Ningyi
Published: January 2024

Porcine deltacoronavirus (PDCoV) is a potential emerging zoonotic pathogen, and studies on the prevalence and pathogenesis of PDCoV are ongoing. The main protease (nsp5) of PDCoV provides an excellent target for antivirals due to its essential and conserved function in the viral replication cycle. Previous studies have revealed that nsp5 of PDCoV antagonizes type I interferon (IFN) production by targeting the interferon-stimulated genes. Here, we provide the first demonstration that nsp5 of PDCoV antagonizes IFN signaling by cleaving IFIT3, which affects the IFN response after PDCoV infection. Our findings reveal that PDCoV nsp5 is an important interferon antagonist and enhance the understanding of immune evasion by deltacoronaviruses.
HIV-1 RNAs whose transcription initiates from the third deoxyguanosine of GGG tract in the 5′ long terminal repeat serve as a dominant genome for efficient provirus DNA formation
Authors: Yoshida Takeshi , Kasuya Yuho , Yamamoto Hiroyuki , Kawai Gota , Hanaki Ken-ichi , Matano Tetsuro , Masuda Takao
Published: January 2024

Since the promoter for transcribing HIV-1 RNA is unique, all viral elements including genomic RNA and viral proteins have to be generated by the unique transcripts through ingenious mechanisms including RNA splicing and frameshifting during protein translation. Previous studies suggested a new mechanism for diversification of HIV-1 RNA functions by heterogeneous transcriptional initiation site usage; HIV-1 RNAs whose transcription initiates from a certain nucleotide were predominant in virus particles. In this study, we established two methods to analyze heterogenous transcriptional initiation site usage by HIV-1 during viral infection and showed that RNAs beginning with one guanosine (G1-form RNAs), whose transcription initiates from the third deoxyguanosine of the GGG tract in 5′ LTR, were primarily selected as viral genome in infectious particles and thus are used as a template to generate provirus for continuous replication. This study provides insights into the mechanism for diversification of unspliced RNA functions and requisites of lentivirus infectivity.
Human cytomegalovirus modulates mTORC1 to redirect mRNA translation within quiescently infected monocytes
Authors: Miller Michael J. , Akter Dilruba , Mahmud Jamil , Chan Gary C.
Published: January 2024

Human cytomegalovirus (HCMV) infection is a significant cause of morbidity and mortality among the immunonaïve and immunocompromised. Peripheral blood monocytes are a major cell type responsible for disseminating the virus from the initial site of infection. In order for monocytes to mediate viral spread within the host, HCMV must subvert the naturally short lifespan of these cells. In this study, we performed polysomal profiling analysis, which demonstrated HCMV to globally redirect mRNA translation toward the synthesis of cellular prosurvival factors within infected monocytes. Specifically, HCMV entry into monocytes induced the translation of cellular SIRT1 to generate an antiapoptotic state. Defining the precise mechanisms through which HCMV stimulates survival will provide insight into novel anti-HCMV drugs able to target infected monocytes.
Mycobacterial FtsEX-RipC interaction is required for normal growth and cell morphology in rifampicin and low ionic strength conditions
Authors: Samuels Veneshley , Mulelu Andani E. , Ndlovu Hlumani , Marakalala Mohlopheni J.
Published: January 2024

Tuberculosis, a lung disease caused by
Mycobacterium tuberculosis
(
Mtb
), remains a major global health problem ranking as the second leading cause of death from a single infectious agent. One of the major factors contributing toward
Mtb’s
success as a pathogen is its unique cell wall and its ability to counteract various arms of the host’s immune response. A recent genome-scale study profiled a list of candidate genes that are predicted to be essential for
Mtb
survival of host-mediated responses. One candidate was FtsEX, a protein complex composed of an ATP-binding domain, FtsE, and a transmembrane domain, FtsX. FtsEX functions through interaction with a periplasmic hydrolase, RipC. Homologs of FtsEX exist in other bacteria and have been linked with playing a key role in regulating peptidoglycan hydrolysis during cell elongation and division. Here, we report on
Mycobacterium smegmatis,
FtsE, FtsX, and RipC and their protective roles in stressful conditions. We demonstrate that the individual genes of FtsEX complex and RipC are not essential for survival in normal growth conditions but conditionally essential in low-salt media and antibiotic-treated media. Growth defects in these conditions were characterized by short and bulgy cells as well as elongated filamentous cells. Our results suggest that FtsE, FtsX, and RipC are required for both normal cell elongation and division and ultimately for survival in stressful conditions.

IMPORTANCE

Mycobacterial cell growth and division are coordinated with regulated peptidoglycan hydrolysis. Understanding cell wall gene complexes that govern normal cell division and elongation will aid in the development of tools to disarm the ability of mycobacteria to survive immune-like and antibiotic stresses. We combined genetic analyses and scanning electron microscopy to analyze morphological changes of mycobacterial FtsEX and RipC mutants in stressful conditions. We demonstrate that FtsE, FtsX, FtsEX, and RipC are conditionally required for the survival of
Mycobacterium smegmatis
during rifampicin treatment and in low-salt conditions. Growth defects in these conditions were characterized by short and bulgy cells as well as elongated filamentous cells. We also show that the FtsEX-RipC interaction is essential for the survival of
M. smegmatis
in rifampicin. Our results suggest that FtsE, FtsX, and RipC are required for normal cell wall regulation and ultimately for survival in stressful conditions.
Development and evaluation of three automated media pooling and molecular diagnostic systems for the detection of SARS-CoV-2
Authors: Matsumura Yasufumi , Noguchi Taro , Shinohara Koh , Yamamoto Masaki , Nagao Miki
Published: January 2024

Pooled testing combined with molecular diagnostics for the detection of SARS-CoV-2 is a promising method that can increase testing capacities and save costs. However, pooled testing is also associated with the risks of decreased test sensitivity and specificity. To perform reliable pooled testing, we developed and validated three automated media pooling and molecular diagnostic systems. These pooling systems (geneLEAD-PS, Panther-PS, and Biomek-PS) comprised existing automated molecular detection platforms, corresponding automated media pooling devices, and laboratory information management systems. Analytical sensitivity analysis and mock sample evaluation were performed, and the obtained data were used to determine the sizes of the pool for the validation study. In the validation study, a total of 2,448, 3,228, and 6,420 upper respiratory samples were used for geneLEAD-PS, Panther-PS, and Biomek-PS, respectively, and the diagnostic performances were compared with the reference RT‒PCR assay. A pool size of 6 for geneLEAD-PS and a pool size of 4 for Panther-PS and Biomek-PS were selected for the validation studies. All three systems showed high positive percent agreement values of ≥90.5% and negative percent agreement values of ≥99.8% for any specimen type. Pooled testing resulted in a 65%–71% reduction in cost per sample. The testing capacities of geneLEAD-PS, Panther-PS, and Biomek-PS were 144 samples in 3 hours, 384 samples in 5.5 hours, and 376 samples in 4 hours, respectively. The developed pooling systems showed robust diagnostic performances and will increase the testing capacities of molecular diagnostic tests while saving costs and may contribute to infection control of COVID-19.

IMPORTANCE

During the COVID-19 pandemic, there have been surges in demand for accurate molecular diagnostic testing and laboratory supply shortages. Pooled testing combined with highly sensitive molecular testing, which entails mixing multiple samples as a single sample, is a promising approach to increase testing capacities while reducing the use of consumables. However, pooled testing is associated with risks that compromise diagnostic performance, such as false negatives due to dilution of positive samples or false positives due to cross-contamination. To perform reliable pooled testing, three different pooling systems (an automated pooling device, an automated molecular detection platform, and a laboratory information management system) were developed to accurately interpret pooled testing results. These three systems were validated using multiple clinical samples and showed high concordance with individual testing. The developed pooling systems will contribute to increasing reliable molecular testing capacities while using fewer consumables and saving costs.
Astronomical influence on Miocene continental environments in Tibet, east-central Asia
Authors: Yao Xu , Dai Shuang , Wang Zhixiang , Li Mingsong , Hinnov Linda
Published: January 2024

Studies of Cenozoic lacustrine cyclostratigraphy in northeastern Tibet have been successful in reconstructing the history of precipitation and aridification at astronomical (Milankovitch) time scales. However, the phase relationships between Milankovitch forcing mechanisms and hydrologic changes are ambiguous because of challenges in interpreting climate proxies and dating continental successions. We present an analysis of Miocene red and green mudstone rhythmites in two basins (Jiuxi and Guide, NE Tibet) using a climate proxy based on lithologic color. Time-series analysis of the color proxy indicated a dominance of 405 k.y. cycles, from which we constructed an orbital eccentricity metronome astrochronology from 18 Ma to 10 Ma. Periods of lake expansion and contraction are characterized by the green and red mudstones, respectively, and correspond to orbital eccentricity minima and maxima, respectively. We interpreted the antiphase relationship between orbital eccentricity and hydrologic evolution using a net precipitation model, with low precipitation/evaporation ratio being due to excessively high evaporation during times of high orbital eccentricity, and vice versa. High orbital eccentricity scenarios with strong seasonality and insolation extremes are analogous to anthropogenic global warming, and our results provide insights into a future of Central Asian intensified aridification, following the “dry-gets-drier” global warming projections and regionally high aridity sensitivity.
Pharmacological class effects of anticancer drugs: opportunities for decreasing healthcare spending
Authors: Goldstein Daniel A , Saltz Leonard B , Pond Gregory R , Tannock Ian F
Published: January 2024

In the field of general medicine, class effects, or therapeutic interchangeability, have been declared for several families of drugs including statins, calcium channel blockers and ACE inhibitors. The existence of such class effects enables healthcare payers to negotiate for substantially lower drug prices, thereby reducing financial toxicity, both at an individual and societal levels. Until now, the existence of class effects in oncology has been considered rare. Here, we review evidence from clinical trials that supports the existence of class effects for several types of anticancer drugs. These class effects in oncology should be exploited to reduce healthcare costs.
Association between workplace social capital and systolic blood pressure among 23 173 workers at 367 small-sized and medium-sized enterprises in Japan: a cross-sectional study
Authors: Inoue Yosuke , Yazawa Aki , Muto Shigetaka , Odagiri Yuko , Miyake Haruka , Tobayama Mutsuko , Mizoue Tetsuya
Published: January 2024

Objectives

Social capital (SC) has been shown to be inversely associated with elevated blood pressure. While SC in the workplace may also be associated with blood pressure, it has not been extensively studied. We aimed to investigate the association between workplace SC and systolic blood pressure (SBP).

Design

A cross-sectional study.

Setting

367 small-sized and medium-sized companies in Japan.

Participants

A total of 23 173 participants (15 991 males and 7182 females) aged ≥18 years.

Exposure of interest

SC was assessed using individual responses to eight 4-point Likert questions used in the Brief Job Stress Questionnaire. Workplace SC was assessed as the mean of individual-level responses to the SC questions from those working in the same company.

Outcome measure

Systolic blood pressure (SBP)

Results

A multilevel linear regression model revealed that higher workplace-level SC was linked with lower SBP (coef.=−0.53 per 1SD increment in workplace SC, 95% CI=−1.02 to −0.05) among females in the age-adjusted model, which remained statistically significant after adjusting for other covariates. After adjusting for individual-level SC, this association was attenuated and became non-significant (coef.=−0.41, 95% CI=−0.87 to 0.05), while individual-level SC was inversely associated with SBP (coef.=−0.43, 95% CI=−0.73 to −0.13). Among males, we did not find any evidence of significant inverse associations either in relation to workplace SC (coef.=−0.12, 95% CI=−0.46 to 0.21) or individual-level SC (coef.=0.19, 95% CI=−0.01 to 0.39).

Conclusions

Our study findings suggested that workplace-level SC can affect SBP differently by sex.
Potential applications and implications of large language models in primary care
Authors: Andrew Albert
Published: January 2024

The recent release of highly advanced generative artificial intelligence (AI) chatbots, including ChatGPT and Bard, which are powered by large language models (LLMs), has attracted growing mainstream interest over its diverse applications in clinical practice, including in health and healthcare. The potential applications of LLM-based programmes in the medical field range from assisting medical practitioners in improving their clinical decision-making and streamlining administrative paperwork to empowering patients to take charge of their own health. However, despite the broad range of benefits, the use of such AI tools also comes with several limitations and ethical concerns that warrant further consideration, encompassing issues related to privacy, data bias, and the accuracy and reliability of information generated by AI. The focus of prior research has primarily centred on the broad applications of LLMs in medicine. To the author’s knowledge, this is, the first article that consolidates current and pertinent literature on LLMs to examine its potential in primary care. The objectives of this paper are not only to summarise the potential benefits, risks and challenges of using LLMs in primary care, but also to offer insights into considerations that primary care clinicians should take into account when deciding to adopt and integrate such technologies into their clinical practice.