bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevation filters bat, rodent and shrew communities differently by morphological traits
Authors: Monadjem Ara , Farooq Harith , Kane Adam
Published: December 2023

Aim

Mountains are geographic features that provide sharp elevational gradients which can accommodate a diversity of terrestrial flora and fauna. In the face of climate change, many of these species are being pushed higher to escape ever‐increasing temperatures. Despite this, we have little understanding of how species distribute themselves across mountains. African mountains in particular are less studied than mountains elsewhere and the small mammal groups that inhabit them are also poorly studied when compared to other groups. In this study, we examined the responses of three functionally distinct small mammal taxonomic groups to changes in elevation across Africa.

Location

Africa.

Methods

We calculated four functional diversity metrics for 166, 97 and 153 communities of rodents, bats and shrews comprising 225, 183 and 109 species, respectively. We employed RLQ and fourth‐corner analyses to identify any associations between the functional traits of the small mammals and elevation and other climatic variables.

Results

We show that the species richness of the three taxa responded differently to increases in elevation, with only rodents showing a mid‐elevational hump. The composition of rodent and bat communities differed significantly in upland versus lowland sites, but bat communities showed far more overlap across the elevational gradient. Functional diversity metrics responded differently for each taxon highlighting the importance of using different taxonomic groups when studying elevational patterns of functional diversity.

Main Conclusions

Our study shows that functional divergence increases with elevation in all three taxa, indicating a pervasive and broadly applicable strong environmental filtering at higher elevations. Our findings suggest that species at higher elevations may be at higher risk due to specialization. These species are losing habitat due to ongoing climate change that will force them up the elevational gradient. At the same time, the human population in Africa is predicted to triple in size by the year 2100, which will also likely contribute to further habitat loss and fragmentation. As small mammals often play essential roles in ecosystems, from seed dispersal to soil aeration and predation, understanding the susceptibility of the specialization of species at higher elevations is crucial for the effective conservation and management of mountain ecosystems, especially in light of climatic change and human expansion.
Efficacy of adipose‐derived mesenchymal stem cell therapy in the treatment of chronic micro‐ and macrovascular complications of diabetes
Authors: Mikłosz Agnieszka , Chabowski Adrian
Published: December 2023

Diabetes mellitus is a highly prevalent disease characterized by hyperglycaemia that damages the vascular system, leading to micro‐ (retinopathy, neuropathy, nephropathy) and macrovascular diseases (cardiovascular disease). There are also secondary complications of diabetes (cardiomyopathy, erectile dysfunction or diabetic foot ulcers). Stem cell‐based therapies have become a promising tool targeting diabetes symptoms and its chronic complications. Among all stem cells, adipose‐derived mesenchymal stem cells (ADMSCs) are of great importance because of their abundance, non‐invasive isolation and no ethical limitations. Characteristics that make ADMSCs good candidates for cell‐based therapy are their wide immunomodulatory properties and paracrine activities through the secretion of an array of growth factors, chemokines, cytokines, angiogenic factors and anti‐apoptotic molecules. Besides, after transplantation, ADMSCs show great ex vivo expansion capacity and differentiation to other cell types, including insulin‐producing cells, cardiomyocytes, chondrocytes, hepatocyte‐like cells, neurons, endothelial cells, photoreceptor‐like cells, or astrocytes. Preclinical studies have shown that ADMSC‐based therapy effectively improved visual acuity, ameliorated polyneuropathy and foot ulceration, arrested the development and progression of diabetic kidney disease, or alleviated the diabetes‐induced cardiomyocyte hypertrophy. However, despite the positive results obtained in animal models, there are still several challenges that need to be overcome before the results of preclinical studies can be translated into clinical applications. To date, there are several clinical trials or ongoing trials using ADMSCs in the treatment of diabetic complications, most of them in the treatment of diabetic foot ulcers. This narrative review summarizes the most recent outcomes on the usage of ADMSCs in the treatment of long‐term complications of diabetes in both animal models and clinical trials.
Combining fibril‐induced alpha‐synuclein aggregation and 6‐hydroxydopamine in a mouse model of Parkinson's disease and the effect of cerebral dopamine neurotrophic factor on the induced neurodegeneration
Authors: Singh Aastha , Panhelainen Anne , Reunanen Saku , Luk Kelvin C. , Voutilainen Merja H.
Published: December 2023

The existent pre‐clinical models of Parkinson's disease do not simultaneously recapitulate severe degeneration of dopamine neurons and the occurrence of alpha‐synuclein (aSyn) aggregation in one study system. In this study, we injected aSyn pre‐formed fibrils (PFF) and 6‐hydroxydopamine (6‐OHDA) unilaterally into the striatum of C57BL/6 wild‐type male mice at an interval of 2 weeks to induce aggregation of aSyn protein and trigger the loss of dopamine neurons simultaneously in one model and studied the behavioural effects of the combination in these mice. 6‐OHDA was tested at three different doses, and 2 μg of 6‐OHDA combined with PFF‐induced aSyn aggregation was found to produce the most optimal disease phenotype. At 14 weeks timepoint, mice injected with a combination of PFF and 6‐OHDA sustained significant damage to the nigrostriatal pathway and exhibited aSyn‐positive aggregation. Our data suggest that the neurons that formed large aSyn aggregates were particularly vulnerable to 6‐OHDA‐induced degeneration. We also demonstrate the manifestation of a relatively aggressive pathology in 2‐ to 4‐month‐old mice, as compared to younger 7‐ to 9‐week‐old ones. Furthermore, cerebral dopamine neurotrophic factor (CDNF) administered intrastriatally rescued dopamine neurons and motor behaviour of the animals to some extent from 6‐OHDA toxicity. However, no such effect could be seen in the novel 6‐OHDA + PFFs combination model. For the first time, we demonstrate the combined effect of PFF and 6‐OHDA simultaneously in one model. We further discuss the scope for further optimizing this combination model to develop it as a promising pre‐clinical platform for drug screening and development.
Engaging fathers who commit family violence: Issues and challenges for family courts
Authors: Nonomura Robert , Zamfir Dan , Scott Katreena , Jaffe Peter , Bukhari Shaz , Heslop Lisa
Published: December 2023

Intervention with fathers who commit family violence is an essential but often overlooked part of effective family court proceedings. This article provides an overview of how evidence‐informed engagement with fathers around family violence can complement family court efforts to achieve safe and healthy outcomes for children. The focus on fathers is not based on bias against fathers, men, or masculinity, but rather it is consistent with the fact that fathers comprise a substantial proportion of those who use family violence. These men need more effective engagement and interventions. Fathers in these circumstances need to be engaged in services that can assess, monitor, and manage ongoing family violence and risk as well as develop skills to form more positive, healthy relationships with their children and children's mothers. Courts, in turn, need to consider evidence of accountability and change. Application and continued development of the strategies recommended herein would enhance the safety of mothers who experience violence, their children, and the well‐being of fathers who have used family violence. Collaboration with community partners serving families must become cornerstones in promoting the safety for and with all family members.
Phasing out palm and soy oil biodiesel in the EU: What is the benefit?
Authors: Heimann Tobias , Argueyrolles Robin , Reinhardt Manuel , Schuenemann Franziska , Söder Mareike , Delzeit Ruth
Published: December 2023

The Renewable Energy Directive (RED II) by the European Union (EU) provides an updated framework for the use of renewable energy in the EU transport sector until 2030, and bans the use of biofuels with a high risk of causing indirect land‐use change in high carbon stock areas (high ILUC‐risk criteria). The only biofuel feedstock affected by this criterion is palm oil. We employ the computable general equilibrium (CGE) model DART‐BIO for a scenario‐based policy analysis and evaluate a phase‐out of palm oil‐based biodiesel, and an additional phase‐out of soy oil‐based biodiesel in the EU. Our results show that the palm phase‐out has only a relatively small impact on global palm fruit production and total crop land use in tropical and subtropical regions, while the soy phase‐out leads to a comparable stronger decrease in global soy production, and a reduction in total cropland use in soy‐producing regions. Both policies lead to increased oilseed production in the EU. Therefore, farmer in Malaysia and Indonesia face a significantly reduced income. While European farmers profit the most, EU firms and households are confronted with higher expenditures. Finally, this study indicates that unilateral demand‐side regulations for a single good in a single sector is not sufficient for effective environmental protection. Enhanced binding sustainability criteria and certification schemes for the use of all vegetable oils in every sector and industry as well as improved protection schemes for sensible forest areas are necessary.
Effect of alkali and alkaline earth metal ion as glass modifiers on the spectroscopic characteristics of Er3+‐ion doped lead silicate glasses
Authors: Zheng Ruoyu , Wang Xin , Sun Yan , Wen Lei , Hu Lili , Arkadievich Khazanov Efim , Olegovich Andrey , Chen Shubin
Published: December 2023

The spectroscopic characteristics of Er‐doped lead silicate glasses were investigated with respect to the effects of glass modifiers (Li+, Na+, K+, Mg2+, Ca2+, Sr2+, and Ba2+) with various optical basicities. Using the absorption spectra of the glasses, the Judd–Ofelt parameters of the glasses were calculated and examined, with an emphasis on the glass emission intensity ratio at 1572 nm. The spectra of the samples at low temperatures were examined, and the Stark splitting of Er3+ was investigated. The McCumber method was used to determine the emission cross sections of glasses. The SPM glass exhibited high values of full width at half maximum (51.24 nm) and the emission cross section at 1572 nm (1.908 × 10−21 cm2), with potential applications for guiding component design of 1.5‐μm fiber lasers and amplifiers.
Free riding, democracy, and sacrifice in the workplace: Evidence from a real‐effort experiment
Authors: Kamei Kenju , Tabero Katy
Published: December 2023

Teams are increasingly popular decision‐making and work units in firms. This paper uses a novel real‐effort experiment to show that (a) some teams in the workplace reduce their members' private benefits to achieve a group optimum in a social dilemma and (b) such endogenous choices by themselves enhance their work productivity (per‐work‐time production)—a phenomenon called the “dividend of democracy.” In the experiment, worker subjects are randomly assigned to a team of three, and they then jointly solve a collaborative real‐effort task under a revenue‐sharing rule in their group with two other teams, while each individual worker can privately and independently shirk by playing a Tetris game. Strikingly, teams exhibit significantly higher productivity (per‐work‐time production) when they can decide whether to reduce the return from shirking by voting than when the policy implementation is randomly decided from above, irrespective of the policy implementation outcome. This means that democratic culture directly affects behavior. On the other hand, the workers under democracy also increase their shirking, presumably due to enhanced fatigue owing to the stronger productivity. Despite this, democracy does not decrease overall production thanks to the enhanced work productivity.
Eimeria falciformis extracellular vesicles differentially express host cell lncRNAs
Authors: Olajide Joshua S. , Qu Zigang , Yang Shunli , Yang Bin , Xu Xiao , Wang Jing , Cai Jianping
Published: December 2023

Long noncoding RNAs (lncRNAs) are regulatory transcripts during protozoan infections in the host intestinal epithelial cells (IECs). Apicomplexan Eimeria falciformis sporozoite extracellular vesicles (EVs) contain virulence factors that modulate host IECs pro‐inflammatory genes and immune responses. In this study, E. falciformis sporozoites were made to interact with inactivated host cells, and the parasite EVs were separated from total secretome by ultracentrifugation and purified on density gradient medium. Dose‐dependent bio‐activity of E. falciformis EVs was investigated by RNA sequencing, functional annotation and quantitative PCR. It was found that E. falciformis EVs induced mRNA, circRNA, and lncRNA expressions in mouse IECs. Of 38, 217 lncRNAs assembled, 157 and 152 were upwardly and downwardly expressed respectively. Differentially expressed lncRNAs were associated with cytokines, pyroptosis, and immune signaling pathways including FoxO, NF‐κB, MAPK, and TGF‐β. In essence, E. falciformis EVs altered host cell RNA expressions during the interaction with host IECs. Also, differentially expressed lncRNAs are potential diagnostic transcripts during Eimeria infections.
Antagonistic actions of Paucibacter aquatileB51 and its lasso peptide paucinodin toward cyanobacterial bloom‐forming Microcystis aeruginosaPCC7806
Authors: Cha Yeji , Kim Wonjae , Park Yerim , Kim Minkyung , Son Yongjun , Park Woojun
Published: December 2023

Superior antagonistic activity against axenic Microcystis aeruginosa PCC7806 was observed with Paucibacter sp. B51 isolated from cyanobacterial bloom samples among 43 tested freshwater bacterial species. Complete genome sequencing, analyzing average nucleotide identity and digital DNA–DNA hybridization, designated the B51 strain as Paucibacter aquatile. Electron and fluorescence microscopic image analyses revealed the presence of the B51 strain in the vicinity of M. aeruginosa cells, which might provoke direct inhibition of the photosynthetic activity of the PCC7806 cells, leading to perturbation of cellular metabolisms and consequent cell death. Our speculation was supported by the findings that growth failure of the PCC7806 cells led to low pH conditions with fewer chlorophylls and down‐regulation of photosystem genes (e.g., psbD and psaB) during their 48‐h co‐culture condition. Interestingly, the concentrated ethyl acetate extracts obtained from B51‐grown supernatant exhibited a growth‐inhibitory effect on PCC7806. The physical separation of both strains by a filter system led to no inhibitory activity of the B51 cells, suggesting that contact‐mediated anti‐cyanobacterial compounds might also be responsible for hampering the growth of the PCC7806 cells. Bioinformatic tools identified 12 gene clusters that possibly produce secondary metabolites, including a class II lasso peptide in the B51 genome. Further chemical analysis demonstrated anti‐cyanobacterial activity from fractionated samples having a rubrivinodin‐like lasso peptide, named paucinodin. Taken together, both contact‐mediated inhibition of photosynthesis and the lasso peptide secretion of the B51 strain are responsible for the anti‐cyanobacterial activity of P. aquatile B51.
A roadmap to realist interviews in health professions education research: Recommendations based on a critical analysis
Authors: Rees Charlotte E. , Davis Corinne , Nguyen Van N. B. , Proctor Dominic , Mattick Karen L.
Published: December 2023

Context

Realist evaluation is increasingly employed in health professions education research (HPER) because it can unpack the extent to which complex educational interventions work (or not), for whom under what circumstances and how. While realist evaluation is not wedded to particular methods, realist interviews are commonly the primary, if not only, data collection method in realist evaluations. While qualitative interviewing from an interpretivist standpoint has been well‐articulated in the HPER literature, realist interviewing differs substantially. The former elicits participants' views and experiences of a topic of inquiry, whereas realist interviewing focuses on building, testing and/or refining programme theory. Therefore, this article aims to help readers better understand, conduct, report and critique realist interviews as part of realist evaluations.

Methods

In this paper, we describe what realist approaches are, what realist interviewing is and why realist interviewing matters. We outline five stages to realist interviewing (developing initial programme theory, realist sampling/samples, the interview itself, realist analysis and reporting realist interviews), drawing on two illustrative cases from our own realist evaluations employing interviewing to bring theory to life. We provide a critical analysis of 12 realist evaluations employing interviewing in the HPER literature. Alongside reporting standards, and our own realist interviewing experiences, this critical analysis of published articles serves to foreground our recommendations for realist interviewing.

Conclusions

We encourage HPE researchers to consider realist interviews as part of realist evaluations of complex interventions. Our critical analysis reveals that realist interviews can provide unique insights into HPE, but authors now need to report their sampling approach, type of interviewing and interview questions more explicitly. Studies should also more explicitly draw on existing realist interviewing literature and follow reporting guidelines for realist evaluations. We hope this paper provides a useful roadmap to conducting, reporting and critically appraising realist interviews in HPER.
Value‐at‐Risk under Measurement Error
Authors: Doukali Mohamed , Song Xiaojun , Taamouti Abderrahim
Published: December 2023

We propose a method for estimating Value‐at‐Risk that corrects for the effect of measurement errors in stock prices. We show that the presence of measurement errors might pose serious problems for estimating risk measures. In particular, when stock prices are contaminated, existing estimators of Value‐at‐Risk are inconsistent and might lead to an underestimation of risk, which can result in extreme leverage ratios within the held portfolios. Using a Fourier transform and a deconvolution kernel estimator of the probability distribution function of actual latent prices, we derive a robust estimator of Value‐at‐Risk in the presence of measurement errors. Monte Carlo simulations and real data analysis illustrate satisfactory performance of the proposed method.
Imaging‐based diagnosis and classification of radioactive iodine‐induced sialadenitis
Authors: Li Xiao , Zheng Dan‐Ni , Ling Xiao‐Tong , Yang Jing , Xie Xiao‐Yan , Liu Deng‐Gao , Yu Guang‐Yan
Published: December 2023

Objectives

To establish an inflammation grading system for radioactive iodine‐induced sialadenitis (RAIS) based on spiral computed tomography (CT), ultrasonography and sialography.

Methods

In all, 120 RAIS patients (18 males and 102 females) were retrospectively included. Spiral CT, ultrasonography and sialography appearances were analysed and categorized as follows: grade I, approximately normal or mild sialadenitis; grade II, moderate sialadenitis; and grade III, severe sialadenitis. Adenitis severity was analysed relative to sex, age, RAI treatment sessions and cumulative doses.

Results

Spiral CT showed heterogeneous (78.9%) and atrophic changes (36.8%) in the parotid glands (PGs) and duct ectasia (24.8%) in the submandibular glands (SMGs). Ultrasonography showed heterogeneous echogenicity (54.3%) and diminished gland size (30.2%) in PGs and duct ectasia in SMGs (34.7%). Sialography showed duct obliteration in 25.3% PGs and 3.2% SMGs. Statistical analysis showed good consistency among the three imaging grading results. The incidence and severity of PG lesions were significantly higher than that of SMGs (p < 0.001). As for PGs, adenitis severity was associated with both treatment sessions and cumulative doses; but in SMGs, disease severity was only related to treatment sessions.

Conclusions

A grading system for severity of RAIS was established based on spiral CT, ultrasonography and sialography appearances.
Cutaneous adenovirus infection in an immunocompromised child
Authors: Soenjoyo Karina Ruth , Lee Elis Yuexian , Koh Mark Jean Aan
Published: December 2023

Adenoviruses are common viral pathogens in childhood; however, cutaneous manifestations are not well‐documented. We present a rare case of cutaneous adenovirus infection in a 23‐month‐old boy with a background of CD40 ligand deficiency, post bone marrow transplant. The clinical morphology of the skin lesions in our patient, described as skin‐colored papules with central crusting, has not been previously described and contributes to the growing literature of cutaneous adenovirus cases.
Effect of ultraviolet light on field emission performance and lifetime of lateral field emitter devices
Authors: Bhattacharya Ranajoy , Turchetti Marco , Yeung Matthew , Donald Keathley P. , Berggren Karl K. , Browning Jim
Published: December 2023

Lateral field emission devices have been characterized before and after ultraviolet (UV) light exposure. Two types of planar device structures, diode and bowtie, were studied. These nanoscale devices have 9–15 nm tip-to-tip (bowtie) or tip-to-collector (diode) dimensions with the tips fabricated from Au/Ti. Typical currents of 2–5 nA per tip at 6 V were measured. It was observed that after UV exposure, the collected current was reduced by >28% for the case of a bowtie device; whereas the current was reduced by >39% for the case of a diode device. This reduction can be attributed to water vapor desorption on the dielectric surface between the structures, which in turn reduces surface leakage. The Fowler–Nordheim plot showed a straighter line after UV exposure. After the I-V test, the UV-exposed devices were placed on lifetime tests in a vacuum of <10−8 Torr and were biased at 5 V DC. After 2600 h, an abrupt current decrease was observed: ∼25% for the case of the bowtie and ∼28% for the case of the diode device. Scanning electron microscope images of the bowtie and diode devices showed damage to the tips.
I

n vitro
pharmacokinetics/pharmacodynamics of the β-lactamase inhibitor, durlobactam, in combination with sulbactam against
Acinetobacter baumannii-calcoaceticus
complex
Authors: O'Donnell John , Tanudra Angela , Chen April , Miller Alita A. , McLeod Sarah M. , Tommasi Rubén
Published: December 2023

Infections caused by
Acinetobacter baumannii
are increasingly multidrug resistant and associated with high rates of morbidity and mortality. Sulbactam is a β-lactamase inhibitor with intrinsic antibacterial activity against
A. baumannii
. Durlobactam is a non-β-lactam β-lactamase inhibitor with an extended spectrum of activity compared to other inhibitors of its class.
In vitro
pharmacodynamic infection models were undertaken to establish the pharmacokinetic/pharmacodynamic (PK/PD) index and magnitudes associated with sulbactam and durlobactam efficacy and to simulate epithelial lining fluid (ELF) exposures at clinical doses to understand sulbactam-durlobactam activity with and without co-administration of a carbapenem. Hollow fiber infection models (HFIMs) and one-compartment systems were used to identify the PK/PD indices and exposure magnitudes associated of 1-log
10
and 2-log
10
colony-forming unit (CFU)/mL reductions. Sulbactam and durlobactam demonstrated PK/PD drivers of % time above the minimum inhibition concentration (%T > MIC) and area under the plasma concentration-time curve from time 0 to 24 h (AUC
0–24
)/MIC, respectively. Against a sulbactam-susceptible strain, sulbactam %T > MIC of 71.5 and 82.0 were associated with 1-log
10
and 2-log
10
CFU/mL reductions, respectively, in the HFIM. Against a non-susceptible strain, durlobactam restored the activity of sulbactam with an AUC
0–24
/MICs of 34.0 and 46.8 using a polysulfone cartridge to achieve a 1-log
10
and 2-log
10
CFU/mL reduction. These magnitudes were reduced to 13.8 and 24.2, respectively, using a polyvinylidene fluoride cartridge with a membrane pore size of 0.1 μm. In the one-compartment model, durlobactam AUC
0–24
/MIC to achieve 1-log
10
and 2-log
10
CFU/mL reduction were 7.6 and 33.4, respectively. Simulations of clinical ELF exposures in the HFIM showed cidal activity at MICs ≤4 µg/mL. Penicillin binding protein 3 mutant strains with MICs of 8 μg/mL may benefit from the addition of a carbapenem at clinical exposures.
Nitrous oxide reduction by two partial denitrifying bacteria requires denitrification intermediates that cannot be respired
Authors: LaSarre Breah , Morlen Ryan , Neumann Gina C. , Harwood Caroline S. , McKinlay James B.
Published: December 2023

Denitrification is a form of anaerobic respiration wherein nitrate (NO
3
−
) is sequentially reduced via nitrite (NO
2
−
), nitric oxide, and nitrous oxide (N
2
O) to dinitrogen gas (N
2
) by four reductase enzymes. Partial denitrifying bacteria possess only one or some of these four reductases and use them as independent respiratory modules. However, it is unclear if partial denitrifiers sense and respond to denitrification intermediates outside of their reductase repertoire. Here, we tested the denitrifying capabilities of two purple nonsulfur bacteria,
Rhodopseudomonas palustris
CGA0092 and
Rhodobacter capsulatus
SB1003. Each had denitrifying capabilities that matched their genome annotation; CGA0092 reduced NO
2
−
to N
2
, and SB1003 reduced N
2
O to N
2
. For each bacterium, N
2
O reduction could be used both for electron balance during growth on electron-rich organic compounds in light and for energy transformation via respiration in darkness. However, N
2
O reduction required supplementation with a denitrification intermediate, including those for which there was no associated denitrification enzyme. For CGA0092, NO
3
−
served as a stable, non-catalyzable molecule that was sufficient to activate N
2
O reduction. Using a β-galactosidase reporter, we found that NO
3
−
acted, at least in part, by stimulating N
2
O reductase gene expression. In SB1003, NO
2
−
but not NO
3
−
activated N
2
O reduction, but NO
2
−
was slowly removed, likely by a promiscuous enzyme activity. Our findings reveal that partial denitrifiers can still be subject to regulation by denitrification intermediates that they cannot use.

IMPORTANCE

Denitrification is a form of microbial respiration wherein nitrate is converted via several nitrogen oxide intermediates into harmless dinitrogen gas. Partial denitrifying bacteria, which individually have some but not all denitrifying enzymes, can achieve complete denitrification as a community by cross-feeding nitrogen oxide intermediates. However, the last intermediate, nitrous oxide (N2O), is a potent greenhouse gas that often escapes, motivating efforts to understand and improve the efficiency of denitrification. Here, we found that at least some partial denitrifying N2O reducers can sense and respond to nitrogen oxide intermediates that they cannot otherwise use. The regulatory effects of nitrogen oxides on partial denitrifiers are thus an important consideration in understanding and applying denitrifying bacterial communities to combat greenhouse gas emissions.
Identification of a non-exported Plasmepsin V substrate that functions in the parasitophorous vacuole of malaria parasites
Authors: Fréville Aline , Ressurreição Margarida , van Ooij Christiaan
Published: December 2023

Malaria parasites alter multiple properties of the host erythrocyte by exporting proteins into the host cell. Many exported proteins contain a five-amino acid motif called the
Plasmodium
export element (PEXEL) that is cleaved by the parasite protease Plasmepsin V (PM V). The presence of a PEXEL is considered a signature of protein export and has been used to identify a large number of exported proteins. The export of proteins becomes essential midway through the intraerythrocytic cycle—preventing protein export blocks parasite development 18–24 h after invasion. However, a genetic investigation revealed that the absence of the PEXEL protein PFA0210c (PF3D7_0104200) causes parasite development to arrest immediately after invasion. We now show that this protein is cleaved by PM V but not exported into the host erythrocyte and instead functions in the parasitophorous vacuole; hence, the protein was renamed PV6. We additionally show that the lysine residue that becomes the N-terminus of PV6 after processing by PM V prevents export. This is the first example of a native
Plasmodium falciparum
PM V substrate that remains in the parasitophorous vacuole. We also provide evidence suggesting that the parasite may produce at least one additional essential, non-exported PM V substrate. Therefore, the presence of a PEXEL and, hence, processing of a protein by PM V do not always target a protein for export, and PM V likely has a broader function in parasite growth beyond processing exported proteins. Furthermore, we utilized this finding to investigate possible requirements for protein export further.

IMPORTANCE

In the manuscript, the authors investigate the role of the protease Plasmepsin V in the parasite–host interaction. Whereas processing by Plasmepsin V was previously thought to target a protein for export into the host cell, the authors now show that there are proteins cleaved by this protease that are not exported but instead function at the host–parasite interface. This changes the view of this protease, which turns out to have a much broader role than anticipated. The result shows that the protease may have a function much more similar to that of related organisms. The authors also investigate the requirements for protein export by analyzing exported and non-exported proteins and find commonalities between the proteins of each set that further our understanding of the requirements for protein export.
Genome sequencing and
de novo
assembly of
Trichoderma longibrachiatum
isolate collected from Florida agricultural soils
Authors: Suazo Tejada Andrea Karina , Yu Pei-Ling , Smith Katherine E. , Huguet-Tapia Jose C. , Carrillo Joseph , Brawner Jeremy T. , Vallad Gary E.
Published: December 2023

We report a draft genome assembly of
Trichoderma longibrachiatum
isolate GEV 3550, obtained from Florida, United States of America.
Spatio-temporal coherence of circadian clocks and temporal control of differentiation in
Anabaena
filaments
Authors: Arbel-Goren Rinat , Dassa Bareket , Zhitnitsky Anna , Valladares Ana , Herrero Antonia , Flores Enrique , Stavans Joel
Published: December 2023

Circadian clock arrays in multicellular filaments of the heterocyst-forming cyanobacterium
Anabaena
sp. strain PCC 7120 display remarkable spatio-temporal coherence under nitrogen-replete conditions. To shed light on the interplay between circadian clocks and the formation of developmental patterns, we followed the expression of a clock-controlled gene under nitrogen deprivation, at the level of individual cells. Our experiments showed that differentiation into heterocysts took place preferentially within a limited interval of the circadian clock cycle, that gene expression in different vegetative intervals along a developed filament was discoordinated, and that the circadian clock was active in individual heterocysts. Furthermore,
Anabaena
mutants lacking the
kaiABC
genes encoding the circadian clock core components produced heterocysts but failed in diazotrophy. Therefore, genes related to some aspect of nitrogen fixation, rather than early or mid-heterocyst differentiation genes, are likely affected by the absence of the clock. A bioinformatics analysis supports the notion that RpaA may play a role as master regulator of clock outputs in
Anabaena
, the temporal control of differentiation by the circadian clock and the involvement of the clock in proper diazotrophic growth. Together, these results suggest that under nitrogen-deficient conditions, the clock coherent unit in
Anabaena
is reduced from a full filament under nitrogen-rich conditions to the vegetative cell interval between heterocysts.

IMPORTANCE

Circadian clocks, from unicellular organisms to animals, temporally align biological processes to day and night cycles. We study the dynamics of a circadian clock-controlled gene at the individual cell level in the multicellular filamentous cyanobacterium
Anabaena
, under nitrogen-stress conditions. Under these conditions, some cells along filaments differentiate to carry out atmospheric nitrogen fixation and lose their capability for oxygenic photosynthesis. We found that clock synchronization is limited to organismic units of contiguous photosynthetic cells, contrary to nitrogen-replete conditions in which clocks are synchronized over a whole filament. We provided evidence that the circadian clock regulates the process of differentiation, allowing it to occur preferentially within a limited time window during the circadian clock period. Lastly, we present evidence that the signal from the core clock to clock-regulated genes is conveyed in
Anabaena
as in unicellular cyanobacteria.
POOE: predicting oomycete effectors based on a pre-trained large protein language model
Authors: Zhao Miao , Lei Chenping , Zhou Kewei , Huang Yan , Fu Chen , Yang Shiping , Zhang Ziding
Published: December 2023

Oomycetes are fungus-like eukaryotic microorganisms which can cause catastrophic diseases in many plants. Successful infection of oomycetes depends highly on their effector proteins that are secreted into plant cells to subvert plant immunity. Thus, systematic identification of effectors from the oomycete proteomes remains an initial but crucial step in understanding plant–pathogen relationships. However, the number of experimentally identified oomycete effectors is still limited. Currently, only a few bioinformatics predictors exist to detect potential effectors, and their prediction performance needs to be improved. Here, we used the sequence embeddings from a pre-trained large protein language model (ProtTrans) as input and developed a support vector machine-based method called POOE for predicting oomycete effectors. POOE could achieve a highly accurate performance with an area under the precision-recall curve of 0.804 (area under the receiver operating characteristic curve = 0.893, accuracy = 0.874, precision = 0.777, recall = 0.684, and specificity = 0.936) in the fivefold cross-validation, considerably outperforming various combinations of popular machine learning algorithms and other commonly used sequence encoding schemes. A similar prediction performance was also observed in the independent test. Compared with the existing oomycete effector prediction methods, POOE provided very competitive and promising performance, suggesting that ProtTrans effectively captures rich protein semantic information and dramatically improves the prediction task. We anticipate that POOE can accelerate the identification of oomycete effectors and provide new hints to systematically understand the functional roles of effectors in plant–pathogen interactions. The web server of POOE is freely accessible at
http://zzdlab.com/pooe/index.php
. The corresponding source codes and data sets are also available at
https://github.com/zzdlabzm/POOE
.

IMPORTANCE

In this work, we use the sequence representations from a pre-trained large protein language model (ProtTrans) as input and develop a Support Vector Machine-based method called POOE for predicting oomycete effectors. POOE could achieve a highly accurate performance in the independent test set, considerably outperforming existing oomycete effector prediction methods. We expect that this new bioinformatics tool will accelerate the identification of oomycete effectors and further guide the experimental efforts to interrogate the functional roles of effectors in plant-pathogen interaction.
Ultrasensitive one-pot detection of monkeypox virus with RPA and CRISPR in a sucrose-aided multiphase aqueous system
Authors: Wang Yue , Tang Yixin , Chen Yukang , Yu Guangxi , Zhang Xue , Yang Lihong , Zhao Chenjie , Wang Pei , Gao Song
Published: December 2023

The monkeypox virus, which was declared as a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO), continues to cause infection cases worldwide. Given the risk of virus evolution, it is essential to identify monkeypox virus infection in a timely manner and isolate patients to prevent outbreaks so that the vulnerable population is protected and the emergence of dangerous monkeypox variants is restrained. In this study, a novel one-pot recombinase polymerase amplification-Clustered Regularly Interspaced Short Palindromic Repeats (RPA-CRISPR) assay for monkeypox based on a sucrose-aided multiphase aqueous system has been established with an ultra-high sensitivity of a single copy, which is 10 times higher than the existing RPA-CRISPR one-pot method. The entire reaction was completed within 60 min at 37°C. The detection method exhibited good specificity, effectively distinguishing monkeypox from other orthopoxviruses. The detection results could be observed by the naked eye under ultraviolet or blue light, making it highly suitable for home or limited healthcare settings. The assay has solved the incompatibility between the Cas12a cleavage reaction and the RPA reaction and shows good specificity, accuracy, and the rapidness and convenience important for point-of-care testing. It provides an effective tool for the early diagnosis of monkeypox and sets a technical example of using a multiphase aqueous system to establish one-pot RPA-CRISPR detection.

IMPORTANCE

The monkeypox virus was declared as a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) and continues to cause infection cases worldwide. Given the risk of virus evolution, it is essential to identify monkeypox virus infection in a timely manner to prevent outbreaks. This study establishes a novel one-pot recombinase polymerase amplification-Clustered Regularly Interspaced Short Palindromic Repeats (RPA-CRISPR) assay for monkeypox virus with an ultra-high sensitivity. The assay shows good specificity, accuracy, and the rapidness and convenience important for point-of-care testing. It provides an effective tool for the early diagnosis of monkeypox, which is useful for the prevention of an epidemic.
Mobile class A β-lactamase gene
bla
GMA-1
Authors: Yano Hirokazu , Suzuki Masato , Nonaka Lisa
Published: December 2023

The first reported
bla
GMA-1
gene encoding gammaproteobacterial mobile class A β-lactamase (GMA-1) was identified in a recently defined mobile DNA element, a strand-biased circularizing integrative element (SE). Increased genomic data revealed the presence of
bla
GMA-1
in marine bacteria, including pathogenic species such as
Vibrio parahaemolyticus
and
Photobacterium damselae
. Herein, we address the substrate range of GMA-1 and how frequently
bla
GMA-1
was acquired by the chromosomes or plasmids via SEs using sequences in a publicly available database. An
Escherichia coli
strain carrying
bla
GMA-1
exhibited resistance to amoxicillin, piperacillin, and carbenicillin, but it remained susceptible to cephalosporins, monobactam, and carbapenems, indicating that GMA-1 belongs to functional group 2c, narrow-spectrum β-lactamases.
bla
GMA-1
-flanking sequence analysis for sequences in the RefSeq/GenBank database revealed a total of eight distinct SE-mediated
bla
GMA-1
acquisition events and six SE-independent
bla
GMA-1
acquisition events, including
bla
GMA-1
alone translocation, without involving a specific insertion sequence, or integron. Thus, this study shows that GMA-1 is specialized for penicillin degradation and is mainly disseminated by SEs; however, SE is not the only genetic mechanism transmitting
bla
GMA-1
.

IMPORTANCE

Despite increasing reports, class A β-lactamases of environmental bacteria remain very poorly characterized, with limited understanding of their transmission patterns. To address this knowledge gap, we focused on a recently designated GMA family β-lactamase gene,
bla
GMA-1
, found in marine bacterial genera such as
Vibrio
. This study shows that gammaproteobacterial mobile class A β-lactamase is specialized for penicillin degradation, and
bla
GMA-1
is frequently linked to strand-biased circularizing integrative elements (SEs) in sequences in the RefSeq/GenBank database. Evidence for the implication of SEs in β-lactamase environmental transmission provides insights for future surveillance studies of antimicrobial resistance genes in human clinical settings.
Fast and sensitive differential diagnosis of pseudorabies virus-infected versus pseudorabies virus-vaccinated swine using CRISPR-Cas12a
Authors: Wang Hao , Li Hongzhao , Tang Bo , Ye Chen , Han Meiqing , Teng Lin , Yue Min , Li Yan
Published: December 2023

Pseudorabies virus (PRV) is the causative pathogen of Aujeszky’s disease. It causes high mortality and miscarriage rates in the infected swine, leading to tremendous economic losses in the global swine industry. PRV has also been demonstrated to trigger viral encephalitis in humans. The eradication policy and large-scale vaccination have been adopted globally as the most effective strategy against PRV. A simple, fast, and sensitive diagnostic method is highly demanded to differentiate between vaccinated and infected swine. Herein, we designed a detection system combining multienzyme isothermal rapid amplification (MIRA) and CRISPR-Cas12a (termed MIRA-Cas12a), characterized by high sensitivity and specificity, low cost, less equipment, and convenient visualization. By targeting the gB, gE, and TK genes of PRV, the MIRA-Cas12a assay is able to distinguish the infected, uninfected, and vaccinated swine by the naked eyes in 40 min (from DNA extraction to result readout) and with comparable sensitivity to conventional quantitative PCR. A 37°C heater and a source of blue light are all the equipment required to detect PRV. Thus, the MIRA-Cas12a detection will facilitate PRV surveillance and minimize the financial losses to the swine industry.

IMPORTANCE

Pseudorabies virus (PRV) causes high mortality and miscarriage rates in the infected swine, and the eradication policy coupled with large-scale vaccination of live attenuated vaccines has been adopted globally against PRV. Differential diagnosis of the vaccinated and infected swine is highly demanded. Our multienzyme isothermal rapid amplification (MIRA)-Cas12a detection method described in this study can diagnose PRV with a superior sensitivity comparable to the quantitative PCR (qPCR) and a competitive detection speed (only half the time as qPCR needs). The portable feature and the simple procedure of MIRA-Cas12a make it easier to deploy for clinical diagnosis, even in resource-limited settings. The MIRA-Cas12a method would provide immediate and accurate diagnostic information for policymakers to respond promptly.
Diversity of
Salmonella enterica
phages isolated from chicken farms in Kenya
Authors: Gunathilake K. M. Damitha , Makumi Angela , Loignon Stéphanie , Tremblay Denise , Labrie Simon , Svitek Nicholas , Moineau Sylvain
Published: December 2023

In this study, we describe the characterization of 67
Salmonella enterica
phages isolated from Kenya. Specifically, the phages were isolated from chicken feces as well as from swabs and water samples obtained from chicken farms and slaughterhouses in Nairobi and Kiambu counties. Genome sequencing and analysis revealed that 59 phage isolates were distinct and could be grouped into 17 clusters belonging to four major types of phages (MT1–4). Further taxonomic analysis showed that each MT represents one phage genus. Of the 17 selected representative genomes (one per cluster), seven phages belong to the MT1 group and to the genus
Jerseyvirus
. The MT2 cluster contained eight representative phages that were similar to Escherichia phage T5 and belong to the
Tequintavirus
genus. The unique MT3 cluster with one phage representative belongs to the
Zindervirus
genus, while the sole MT4 phage isolate is a member of the
Dhillonvirus
genus. All representative phages are siphophages, except MT3 phage which is a podophage. All genomes do not contain genes associated with lysogeny and therefore, they are considered exclusively lytic. No known virulence genes or antibiotic resistance genes were detected in any of the genomes. Phage DNA termini analyses showed that MT2 phages have a direct terminal repeat-based packaging mechanism while MT1 has a headful packaging mechanism. Host range studies showed that phages belonging to MT1 and MT3 appear to only infect
Salmonella
strains, while MT2 and MT4 phages were also capable of infecting
Escherichia
and
Shigella
strains.

IMPORTANCE

Non-typhoidal
Salmonella enterica
infections are one of the leading causes of diarrhoeal diseases that spread to humans from animal sources such as poultry. Hence, keeping poultry farms free of
Salmonella
is essential for consumer safety and for a better yield of animal products. However, the emergence of antibiotic resistance due to over usage has sped up the search for alternative biocontrol methods such as the use of bacteriophages. Isolation and characterization of novel bacteriophages are key to adapt phage-based biocontrol applications. Here, we isolated and characterized
Salmonella
phages from samples collected at chicken farms and slaughterhouses in Kenya. The genomic characterization of these phage isolates revealed that they belong to four ICTV (International Committee on Taxonomy of Viruses) phage genera. All these phages are lytic and possibly suitable for biocontrol applications because no lysogenic genes or virulence factors were found in their genomes. Hence, we recommend further studies on these phages for their applications in
Salmonella
biocontrol.
Holocene gigascale rock avalanches in Vaigat strait, West Greenland—Implications for geohazard
Authors: Svennevig Kristian , Owen Matthew J. , Citterio Michele , Nielsen Tove , Rosing Salik , Harff Jan , Endler Rudolf , Morlighem Mathieu , Rignot Eric
Published: December 2023

Rock avalanche–triggered displacement waves (also termed tsunamis) have recently occurred in Greenland and Alaska, and they illustrate the presence of such hazards in polar regions. To improve understanding of the magnitude of this hazard for these areas, we investigated gigascale subaerial rock avalanches impacting a partially confined water body within the Vaigat strait (western Greenland). We present a new combined subaerial to subaqueous digital elevation model, alongside a new compilation of seismic data, which revealed nine deglacial to Holocene rock avalanche complexes that are between one and two orders of magnitude larger than nearby historical rock avalanches. The three largest complexes have deposit thicknesses up to 300 m, runout distances reaching 19 km, and best-estimate volumes from 1.7 to 8.4 km3. Based on the morphology and the volume–angle of reach relations, it is likely that each complex represents a single or few events, thus making them among the largest displacement wave–generating subaerial to submarine rock avalanches on Earth. We estimated displacement wave magnitude up to 280 m on the opposite shore. The ages of the deposits are poorly constrained but the main rock avalanche activity is referable to early Holocene times. With significant climatic changes predicted in the Arctic, we recommend that hazard assessments account for events not only from the historical record but also those from the recent geological past.