bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of >3400 worldwide eggplant accessions reveals two independent domestication events and multiple migration‐diversification routes
Authors: Barchi Lorenzo , Aprea Giuseppe , Rabanus‐Wallace M. Timothy , Toppino Laura , Alonso David , Portis Ezio , Lanteri Sergio , Gaccione Luciana , Omondi Emmanuel , van Zonneveld Maarten , Schafleitner Roland , Ferrante Paola , Börner Andreas , Stein Nils , Díez Maria José , Lefebvre Veronique , Salinier Jérémy , Boyaci Hatice Filiz , Finkers Richard , Brouwer Matthijs , Bovy Arnaud G. , Rotino Giuseppe Leonardo , Prohens Jaime , Giuliano Giovanni
Published: September 2023

Eggplant (Solanum melongena) is an important Solanaceous crop, widely cultivated and consumed in Asia, the Mediterranean basin, and Southeast Europe. Its domestication centers and migration and diversification routes are still a matter of debate. We report the largest georeferenced and genotyped collection to this date for eggplant and its wild relatives, consisting of 3499 accessions from seven worldwide genebanks, originating from 105 countries in five continents. The combination of genotypic and passport data points to the existence of at least two main centers of domestication, in Southeast Asia and the Indian subcontinent, with limited genetic exchange between them. The wild and weedy eggplant ancestor S. insanum shows admixture with domesticated S. melongena, similar to what was described for other fruit‐bearing Solanaceous crops such as tomato and pepper and their wild ancestors. After domestication, migration and admixture of eggplant populations from different regions have been less conspicuous with respect to tomato and pepper, thus better preserving ‘local’ phenotypic characteristics. The data allowed the identification of misclassified and putatively duplicated accessions, facilitating genebank management. All the genetic, phenotypic, and passport data have been deposited in the Open Access G2P‐SOL database, and constitute an invaluable resource for understanding the domestication, migration and diversification of this cosmopolitan vegetable.
The Soybean Expression Atlas v2: A comprehensive database of over 5000 RNA‐seq samples
Authors: Almeida‐Silva Fabricio , Pedrosa‐Silva Francisnei , Venancio Thiago M.
Published: September 2023

Soybean is a crucial crop worldwide, used as a source of food, feed, and industrial products due to its high protein and oil content. Previously, the rapid accumulation of soybean RNA‐seq data in public databases and the computational challenges of processing raw RNA‐seq data motivated us to develop the Soybean Expression Atlas, a gene expression database of over a thousand RNA‐seq samples. Over the past few years, our database has allowed researchers to explore the expression profiles of important gene families, discover genes associated with agronomic traits, and understand the transcriptional dynamics of cellular processes. Here, we present the Soybean Expression Atlas v2, an updated version of our database with a fourfold increase in the number of samples, featuring transcript‐ and gene‐level transcript abundance matrices for 5481 publicly available RNA‐seq samples. New features in our database include the availability of transcript‐level abundance estimates and equivalence classes to explore differential transcript usage, abundance estimates in bias‐corrected counts to increase the accuracy of differential gene expression analyses, a new web interface with improved data visualization and user experience, and a reproducible and scalable pipeline available as an R package. The Soybean Expression Atlas v2 is available at https://soyatlas.venanciogroup.uenf.br/, and it will accelerate soybean research, empowering researchers with high‐quality and easily accessible gene expression data.
Experiences of baccalaureate nursing students in preceptorship during the COVID-19 pandemic: a systematic review protocol
Authors: Thomas Denise , Su Michelle , Walter Madelayne , Zakher Bernadette
Published: September 2023

Objective:

The objective of this review is to appraise and synthesize current evidence of the clinical experiences of baccalaureate nursing students in preceptorship during the COVID-19 pandemic.

Introduction:

Nursing education programs support quality clinical practice learning experiences, which are essential for preparing students for both the current and future workforce. The COVID-19 pandemic has drastically changed the health care system and, previous estimates of the global shortage of nurses have now almost doubled. Understanding nursing students’ clinical experiences during the pandemic can assist with identifying the needs of the future workforce. Nursing students complete the final practicum, also known as the last clinical, internship, or preceptorship, before they are eligible to apply for licensure. This review seeks to explore these pre-transitional, unprecedented preceptorship experiences during COVID-19 to better understand how to prepare pre-licensure nurses for the altered workforce.

Inclusion criteria:

This review will include qualitative studies that address the clinical experiences of undergraduate nursing students in preceptorship during the COVID-19 pandemic from 2020 until the present.

Methods:

The databases to be searched will include CINAHL, MEDLINE, ERIC, Google Scholar, and Embase. Reference lists of included studies will be reviewed to identify additional studies. Gray literature will be searched for via ProQuest Dissertations and Theses, Google, and GreyNet International. Unpublished studies will be searched for on websites, including those of national associations of nursing. Study selection, critical appraisal, data extraction, and data synthesis will be performed independently by 2 reviewers. The findings will be collated using meta-aggregation to produce comprehensive synthesized findings and a ConQual Summary of Findings.

Review registration:

PROSPERO CRD42022328303
Lower Extremity Injury Risk Curve Development for a Human Body Model in the Underbody Blast Environment
Authors: Hostetler Zachary S. , Gayzik F. Scott
Published: September 2023

Computational human body models (HBMs) provide the ability to explore numerous candidate injury metrics ranging from local strain based criteria to global combined criteria such as the Tibia Index. Despite these efforts, there have been relatively few studies that focus on determining predicted injury risk from HBMs based on observed postmortem human subjects (PMHS) injury data. Additionally, HBMs provide an opportunity to construct risk curves using measures that are difficult or impossible to obtain experimentally. The Global Human Body Models Consortium (GHBMC) M50-O v 6.0 lower extremity was simulated in 181 different loading conditions based on previous PMHS tests in the underbody blast (UBB) environment and 43 different biomechanical metrics were output. The Brier Metric Score were used to determine the most appropriate metric for injury risk curve development. Using survival analysis, three different injury risk curves (IRC) were developed: “any injury,” “calcaneus injury,” and “tibia injury.” For each injury risk curve, the top three metrics selected using the Brier Metric Score were tested for significant covariates including boot use and posture. The best performing metric for the “any injury,” “calcaneus injury” and “tibia injury” cases were calcaneus strain, calcaneus force, and lower tibia force, respectively. For the six different injury risk curves where covariates were considered, the presence of the boot was found to be a significant covariate reducing injury risk in five out of six cases. Posture was significant for only one curve. The injury risk curves developed from this study can serve as a baseline for model injury prediction, personal protective equipment (PPE) evaluation, and can aid in larger scale testing and experimental protocols.
Comparisons of Overall Performance Among Double-Jet Film Cooling Holes, Cylinder Holes, and Fan-Shaped Holes
Authors: Lei Jiang , Yao Jiaxu , He Jianhong , Yang Xi , Zhang Ke , Wright Lesley M.
Published: September 2023

In this paper, the film-cooling effectiveness (η) and heat transfer coefficient (h) of different film hole geometries are investigated, including double-jet film cooling (DJFC) holes, streamwise cylindrical holes, and fan-shaped holes, both experimentally and numerically. Results reveal that when the blowing ratio is less than 1.0, the DJFC holes have the highest η and the highest h, as well as the highest net heat flux reduction (NHFR). However, a higher blowing ratio (>1.0) leads to a quickly decreasing NHFR of DJFC holes. The asymmetric antikidney vortex and the high turbulent kinetic energy (TKE) are dominant in the performance of the DJFC holes. Owing to medium effectiveness and the lowest heat transfer coefficient, the fan-shaped holes possess the highest net heat flux reduction at M = 2.0 although the value is negative. The relatively weak kidney vortex and the low TKE can explain the phenomena. The cylindrical holes have the lowest η and the lowest NHFR due to the kidney vortex and relatively higher TKE.
Battery Thermal Management System on Trapezoidal Battery Pack With Liquid Cooling System Utilizing Phase Change Material
Authors: Masthan Vali P. S. N. , Murali G.
Published: September 2023

Electric vehicles (EVs) have grown in popularity in recent years due to their environmental friendliness and the potential scarcity of fossil fuels. Lithium-ion batteries (LIBs) are commonly utilized in EVs and hybrid electric vehicles (HEVs). They have a high specific charge, a high density of power, and a long life. A revolutionary design of a trapezoidal battery pack with a liquid cooling system based on composite phase change material (CPCM) is proposed in this research. The phase change material (PCM) is paraffin wax (PA), and the high thermal conductivity particles are graphite powder (GSP). CPCM is made in three different compositions and is filled in between cells with a 5 mm gap. Because PCM has a low thermal conductivity, it is filled with GSP, a high thermal conductive particle. The thermal conductivity is increased from 0.25 to 2.7 W/m K, which increases the heat transfer rate significantly. By adjusting different coolant flow velocities at varied discharge rates, the performance of the battery pack is examined. During the experiment, the discharge rates of 1 C, 2 C, and 3 C were used at a 28–30 °C ambient temperature. According to the findings, a trapezoidal battery pack based on CPCM exhibits a more efficient rate of heat transfer than a battery pack based on PCM. Moreover, BTMS with a liquid cooling system achieves consistent temperature distribution, with the maximum temperature remaining within the ideal range of below 45 °C under all test conditions.
A Computationally Efficient Method for the Thermo-Structural Analysis of a Turbocharger Turbine Wheel Under Engine Transient Operation
Authors: Balduzzi Francesco , Catalani Iacopo , Pini Nicola , Mosciaro Luigi , Mattiello Daniele , Rabbolini Silvio , Hoffer Pierre-Alain , Bianchini Alessandro , Ferrara Giovanni
Published: September 2023

The accurate evaluation of thermally-induced stresses is of particular importance for life-cycle analysis of modern turbochargers. Conjugated heat transfer (CHT), steady-state calculations represent the state-of-the-art, whose temperature distribution is usually imported into a structural solver as a thermal load for carrying out thermo-structural analyses. In the case of transient analyses, however, issues arise. Indeed, due to the different timescales of convective and conductive heat-transfer mechanisms, unsteady CHT simulations are burdened by high computational costs. Moreover, in the specific case of turbocharged engines, the timescales of engine load transients and turbocharger response may differ by a factor of up to 105. The present study proposes an approach for carrying out transient thermo-structural analyses of the solid domain only, characterized by a physical time in the order of 101 s, without the need for unsteady fluid flow calculations, which would imply the use of a solver time-step in the order of 10−5 s. In the proposed methodology, the effects of the fluid flow in the heat-transfer process are modeled by imposing adequate boundary conditions to wet surfaces of the solid domain with minimum computational effort. Indeed, by performing two steady-state CHT calculations and one steady-state computational fluid dynamics (CFD) calculation, time-dependent boundary conditions can be derived in terms of convective heat transfer coefficient and near-wall fluid temperature. The case study used for model development is a high-performance turbocharger turbine for automotive applications, responding to engine load transients of tenths of seconds. Initially, steady-state CFD and CHT models of the turbine stage are validated against experimental data. Then, transient analyses on the turbine wheel are carried out, and their results are imported as thermal loads into an unsteady structural solver, allowing for accurate transient thermo-structural analyses at sustainable computational cost.
Burst Speed Prediction of Impellers With Critical Strain Criteria
Authors: Sarıten Alper , Tabakçı Burak , Çopur Furkan , Kutmaral Alican , Akpınar İlkan Hasan
Published: September 2023

Accurate prediction of burst speed and critical location of a rotating disk is a great concern for turbomachinery designers and enables the reduction of test numbers required to show rotor integrity during turbo-engine certification. Existing burst methodologies mainly focused on axial disks with well-defined bore, web, and rim regions and mostly depended on correction factors that require previous test data of rotors with similar sizes and features. Furthermore, variation of radial and hoop stresses in a radial disk is less predictable than in axial disks due to the asymmetric nature of impellers, which results in uneven distribution of centrifugal and bending loads. This paper aims to explain the experimental and numerical effort dedicated to building an accurate burst methodology for impellers. Elastoplastic finite element analyses are performed by incorporating geometric and material nonlinearities. Analysis results allowed the prediction of failure locations and observation of redistribution of stresses due to material plasticity as rotor speed increases. An extensive test campaign is carried out to validate the numerical analysis. Critical strain criteria that correspond to the plastic strain of true ultimate tensile strength (UTS), are used to determine burst speeds before tests. Experimental results are compared with Robinson's average hoop stress criteria, Hallinan's criteria, and critical strain criteria to show the strong and weak sides of these methodologies for an impeller application. The numerical burst speeds and crack initiation locations associated with critical strain criteria are found to be in good agreement with the spin test results.
Comparisons and Conversions: A Methodological Note and Caution for Meta-Analysis in Sport and Exercise Psychology
Authors: Hill Andrew P.
Published: September 2023

Meta-analysis is a powerful tool in sport and exercise psychology. However, it has a number of pitfalls, and some lead to ill-advised comparisons and overestimation of effects. The impetus for this research note is provided by a recent systematic review of meta-analyses that examined the correlates of sport performance and has fallen foul of some of the pitfalls. Although the systematic review potentially has great value for researchers and practitioners alike, it treats effects from correlational and intervention studies as yielding equivalent information, double-counts multiple studies, and uses an effect size for correlational studies (Cohen’s d) that provides an extreme contrast of unclear practical relevance. These issues impact interpretability, bias, and usefulness of the findings. This methodological note explains each pitfall and illustrates use of an appropriate equivalent effect size for correlational studies (Mathur and VanderWeele’s d) to help researchers avoid similar issues in future work.
Valley-dimensionality locking of superconductivity in cubic phosphides
Authors: Ao Lingyi , Huang Junwei , Qin Feng , Li Zeya , Ideue Toshiya , Akhtari Keivan , Chen Peng , Bi Xiangyu , Qiu Caiyu , Huang Dajian , Chen Long , Belosludov Rodion V. , Gou Huiyang , Ren Wencai , Nojima Tsutomu , Iwasa Yoshihiro , Bahramy Mohammad Saeed , Yuan Hongtao
Published: September 2023

Two-dimensional superconductivity is primarily realized in atomically thin layers through extreme exfoliation, epitaxial growth, or interfacial gating. Apart from their technical challenges, these approaches lack sufficient control over the Fermiology of superconducting systems. Here, we offer a Fermiology-engineering approach, allowing us to desirably tune the coherence length of Cooper pairs and the dimensionality of superconducting states in arsenic phosphides As

x

P

1−
x

under hydrostatic pressure. We demonstrate how this turns these compounds into tunable two-dimensional superconductors with a dome-shaped phase diagram even in the bulk limit. This peculiar behavior is shown to result from an unconventional valley-dimensionality locking mechanism, driven by a delicate competition between three-dimensional hole-type and two-dimensional electron-type energy pockets spatially separated in momentum space. The resulting dimensionality crossover is further discussed to be systematically controllable by pressure and stoichiometry tuning. Our findings pave a unique way to realize and control superconducting phases with special pairing and dimensional orders.
Electromagnetically unclonable functions generated by non-Hermitian absorber-emitter
Authors: Yang Minye , Ye Zhilu , Pan Hongyi , Farhat Mohamed , Cetin Ahmet Enis , Chen Pai-Yen
Published: September 2023

Physically unclonable functions (PUFs) are a class of hardware-specific security primitives based on secret keys extracted from integrated circuits, which can protect important information against cyberattacks and reverse engineering. Here, we put forward an emerging type of PUF in the electromagnetic domain by virtue of the self-dual absorber-emitter singularity that uniquely exists in the non-Hermitian parity-time (
PT
)–symmetric structures. At this self-dual singular point, the reconfigurable emissive and absorptive properties with order-of-magnitude differences in scattered power can respond sensitively to admittance or phase perturbations caused by, for example, manufacturing imperfectness. Consequently, the entropy sourced from inevitable manufacturing variations can be amplified, yielding excellent PUF security metrics in terms of randomness and uniqueness. We show that this electromagnetic PUF can be robust against machine learning–assisted attacks based on the Fourier regression and generative adversarial network. Moreover, the proposed PUF concept is wavelength-scalable in radio frequency, terahertz, infrared, and optical systems, paving a promising avenue toward applications of cryptography and encryption.
Accelerated Miocene incision along the Yangtze River driven by headward drainage basin expansion
Authors: Rohrmann Alexander , Kirby Eric , Schwanghart Wolfgang
Published: September 2023

Along the southeastern margin of the Tibetan Plateau, the onset of rapid fluvial incision during the Miocene is commonly attributed to growth of high topography. Recent recognition of lacustrine strata preserved atop interfluves, however, suggest that headward expansion of river networks drove migration of the topographic divide. Here, we explore the impact of this process on fluvial incision along the Yangtze River. Landscape evolution simulations demonstrate that expansion of the Yangtze watershed since the Late Miocene could be responsible for 1 to 2 kilometers of fluvial incision. The distribution of modern knickpoints and river profiles is consistent with this hypothesis. We suggest that increased erosive power associated with capture and basin integration drove accelerated incision during the Late Miocene. Our results imply that eastern Tibet was elevated before middle Cenozoic time and that the tempo of fluvial incision may be out of phase with uplift of plateau topography.
Preexisting tumor-resident T cells with cytotoxic potential associate with response to neoadjuvant anti–PD-1 in head and neck cancer
Authors: Oliveira Giacomo , Egloff Ann Marie , Afeyan Alexander B. , Wolff Jacquelyn O. , Zeng Zexiang , Chernock Rebecca D. , Zhou Liye , Messier Cameron , Lizotte Patrick , Pfaff Kathleen L. , Stromhaug Kari , Penter Livius , Haddad Robert I. , Hanna Glenn J. , Schoenfeld Jonathan D. , Goguen Laura A. , Annino Donald J. , Jo Vickie , Oppelt Peter , Pipkorn Patrik , Jackson Ryan , Puram Sidharth V. , Paniello Randal C. , Rich Jason T. , Webb Jason , Zevallos Jose P. , Mansour Mena , Fu Jingxin , Dunn Gavin P. , Rodig Scott J. , Ley Jessica , Morris Luc G. T. , Dunn Lara , Paweletz Cloud P. , Kallogjeri Dorina , Piccirillo Jay F. , Adkins Douglas R. , Wu Catherine J. , Uppaluri Ravindra
Published: September 2023

About 50% of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) experience recurrences after definitive therapy. The presurgical administration of anti–programmed cell death protein 1 (PD-1) immunotherapy results in substantial pathologic tumor responses (pTR) within the tumor microenvironment (TME). However, the mechanisms underlying the dynamics of antitumor T cells upon neoadjuvant PD-1 blockade remain unresolved, and approaches to increase pathologic responses are lacking. In a phase 2 trial (NCT02296684), we observed that 45% of patients treated with two doses of neoadjuvant pembrolizumab experienced marked pTRs (≥50%). Single-cell analysis of 17,158 CD8
+
T cells from 14 tumor biopsies, including 6 matched pre-post neoadjuvant treatment, revealed that responding tumors had clonally expanded putative tumor-specific exhausted CD8
+
tumor-infiltrating lymphocytes (TILs) with a tissue-resident memory program, characterized by high cytotoxic potential (CTX
+
) and
ZNF683
expression, within the baseline TME. Pathologic responses after 5 weeks of PD-1 blockade were consistent with activation of preexisting CTX
+

ZNF683
+

CD8
+
TILs, paralleling loss of viable tumor and associated tumor antigens. Response was associated with high numbers of CD103
+
PD-1
+
CD8
+
T cells infiltrating pretreatment lesions, whereas revival of nonexhausted persisting clones and clonal replacement were modest. By contrast, nonresponder baseline TME exhibited a relative absence of
ZNF683
+
CTX
+
TILs and subsequent accumulation of highly exhausted clones. In HNSCC, revival of preexisting
ZNF683
+
CTX
+
TILs is a major mechanism of response in the immediate postneoadjuvant setting.
Innate receptors with high specificity for HLA class I–peptide complexes
Authors: Sim Malcolm J. W. , Brennan Paul , Wahl Katherine L. , Lu Jinghua , Rajagopalan Sumati , Sun Peter D. , Long Eric O.
Published: September 2023

Genetic studies associate killer cell immunoglobulin-like receptors (KIRs) and their HLA class I ligands with a variety of human diseases. The basis for these associations and the relative contribution of inhibitory and activating KIR to NK cell responses are unclear. Because KIR binding to HLA-I is peptide dependent, we performed systematic screens, which totaled more than 3500 specific interactions, to determine the specificity of five KIR for peptides presented by four HLA-C ligands. Inhibitory KIR2DL1 was largely peptide sequence agnostic and could bind ~60% of hundreds of HLA-peptide complexes tested. Inhibitory KIR2DL2, KIR2DL3, and activating KIR2DS1 and KIR2DS4 bound only 10% and down to 1% of HLA-peptide complexes tested, respectively. Activating KIR2DS1, previously described as weak, had high binding affinity for HLA-C, with high peptide sequence specificity. Our data revealed MHC-restricted peptide recognition by germline-encoded NK receptors and suggest that NK cell responses can be shaped by HLA-I–bound immunopeptidomes in the context of disease or infection.
A small-molecule membrane fluidizer re-sensitizes methicillin-resistant
Staphylococcus aureus
(MRSA) to β-lactam antibiotics
Authors: Podoll Jessica D. , Rosen Emma , Wang Wei , Gao Yuefeng , Zhang Jing , Wang Xiang
Published: September 2023

Novel antibacterial agents and strategies are urgently needed to fight against the ongoing global antibiotic resistance problem. While natural products remain the main source in antibiotic discovery, synthetic antibacterials provide an attractive alternative and may evade the ancient antibiotic resistance. Herein, we report a small molecule that re-sensitizes methicillin-resistant
Staphylococcus aureus
to β-lactam antibiotics with extremely low potential for resistance development. It belongs to a new class of broad-spectrum antibacterials, trypyricins, which share similar structural characteristics and mechanism of action to the cationic antimicrobial peptides. Mechanistic studies indicated that trypyricins fluidize and disrupt bacterial cytoplasmic membrane. These results suggested that trypyricins represent a promising new class of antibacterials and may be further developed as antibiotic adjuvants to fight against resistant bacteria in the clinic.
An improved PKPD modeling approach to characterize the pharmacodynamic interaction over time between ceftazidime/avibactam and colistin from
in vitro
time-kill experiments against multidrug-resistant
Klebsiella pneumoniae
isolates
Authors: Aubry Romain , Buyck Julien , Prouvensier Laure , Decousser Jean-Winoc , Nordmann Patrice , Wicha Sebastian G. , Marchand Sandrine , Grégoire Nicolas
Published: September 2023

In contrast to the checkerboard method, bactericidal experiments [time-kill curves (TKCs)] allow an assessment of pharmacodynamic (PD) interactions over time. However, TKCs in combination pose interpretation problems. The objective of this study was to characterize the PD interaction over time between ceftazidime/avibactam (CZA) and colistin (CST) using TKC against four multidrug-resistant
Klebsiella pneumoniae
susceptible to both antibiotics and expressing a widespread carbapenemase determinant KPC-3.
In vitro
TKCs were performed and analyzed using pharmacokinetic/pharmacodynamic (PKPD) modeling. The general pharmacodynamic interaction model was used to characterize PD interactions between drugs. The 95% confidence intervals (95%CIs) of the expected additivity and of the observed interaction were built using parametric bootstraps and compared to evaluate the
in vitro
PD interaction over time. Further simulations were conducted to investigate the effect of the combination at varying concentrations typically observed in patients. Regrowth was observed in TKCs at high concentrations of drugs alone [from 4 to 32× minimum inhibitory concentrations (MIC)], while the combination systematically prevented the regrowth at concentrations close to the MIC. Significant synergy or antagonism were observed under specific conditions but overall 95%CIs overlapped widely over time indicating an additive interaction between antibiotics. Moreover, simulations of typical PK profile at standard dosages indicated that the interaction should be additive in clinical conditions. The nature of the PD interaction varied with time and concentration in TKC. Against the four
K. pneumoniae
isolates, the bactericidal effect of CZA + CST combination was predicted to be additive and to prevent the emergence of resistance at clinical concentrations.
Three species of axenic mosquito larvae recruit a shared core of bacteria in a common garden experiment
Authors: Hyde Josephine , Brackney Doug E. , Steven Blaire
Published: September 2023

In this study, we describe the generation of two new species of axenic mosquito,Aedes albopictusandAedes triseriatus. Along withAedes aegypti, axenic larvae of these three species were exposed to an environmental water source to document the assembly of the microbiome in a common garden experiment. Additionally, the larvae were reared either individually or combinatorially with the other species to characterize the effects of co-rearing on the composition of the microbiome. We found that the microbiome of the larvae was composed of a relatively low-diversity collection of bacteria from the colonizing water. The abundance of bacteria in the water was a poor predictor of their abundance in the larvae, suggesting the larval microbiome is made up of a subset of relatively rare aquatic bacteria. We found 11 bacterial 16S rRNA gene amplicon sequence variants (ASVs) that were conserved among ≥90% of the mosquitoes sampled, including 2 found in 100% of the larvae, pointing to a conserved core of bacteria capable of colonizing all three species of mosquito. Yet, the abundance of these ASVs varied widely between larvae, suggesting individuals harbored largely unique microbiome structures, even if they overlapped in membership. Finally, larvae reared in a tripartite mix of the host-species consistently showed a convergence in the structure of their microbiome, indicating that multi-species interactions between hosts potentially lead to shifts in the composition of their respective microbiomes.

IMPORTANCE

This study is the first report of the axenic (free of external microbes) rearing of two species of mosquito,Aedes albopictusandAedes triseriatus. Our previous report of axenicAedes aegyptibrings the number of axenic species to three. We designed a method to perform a common garden experiment to characterize the bacteria the three species of axenic larvae assemble from their surroundings. Furthermore, species could be reared in isolation or in multi-species combinations to assess how host-species interactions influence the composition of the microbiome. We found all three species recruited a common core of bacteria from their rearing water, with a large contingent of rare and sporadically detected bacteria. Finally, we also show that co-rearing of mosquito larvae leads to a coalescence in the composition of their microbiome, indicating that host-species interactions potentially influence the composition of the microbiome.
Bifidobacterium longum
subsp.
infantis
as widespread bacteriocin gene clusters carrier stands out among the
Bifidobacterium
Authors: Yu Di , Pei Zhangming , Chen Yutao , Wang Hongchao , Xiao Yue , Zhang Hao , Chen Wei , Lu Wenwei
Published: September 2023

Bifidobacterium
is the dominant genus, particularly in the intestinal tract niche of healthy breast-fed infants, and many of these strains have been proven to elicit positive effects on infant development. In addition to its effective antimicrobial activity against detrimental microorganisms, it helps to improve the intestinal microbiota balance. The isolation and identification of bacteriocins from
Bifidobacterium
have been limited since the mid-1980s, leading to an underestimation of its ability for bacteriocin production. Here, we employed a silicon-based search strategy to mine 354 putative bacteriocin gene clusters (BGCs), most of which have never been reported, from the genomes of 759
Bifidobacterium
strains distributed across 9 species. Consistent with previous reports, most
Bifidobacterium
strains did not carry or carry only a single BGC; however,
Bifidobacterium longum
subsp.
infantis
, in contrast to other
Bifidobacterium
species, carried numerous BGCs, including lanthipeptides, lasso peptides, thiopeptides, and class IId bacteriocins. The antimicrobial activity of the crude bacteriocins and transcription analysis confirmed its potential for bacteriocin biosynthesis. Additionally, we investigated the association of bacteriocins with the phylogenetic positions of their homologs from other genera and niches. In conclusion, this study re-examines a few
Bifidobacterium
species traditionally regarded as a poor source of bacteriocins. These bacteriocin genes impart a competitive advantage to
Bifidobacterium
in colonizing the infant intestinal tract.

IMPORTANCE

Development of the human gut microbiota commences from birth, with bifidobacteria being among the first colonizers of the newborn intestinal tract and dominating it for a considerable period. To date, the genetic basis for the successful adaptation of bifidobacteria to this particular niche remains unclear since studies have mainly focused on glycoside hydrolase and adhesion-related genes. Bacteriocins are competitive factors that help producers maintain colonization advantages without destroying the niche balance; however, they have rarely been reported in
Bifidobacterium
. The advancement in sequencing methods and bacteriocin databases enables the use of a silicon-based search strategy for the comprehensive and rapid re-evaluation of the bacteriocin distribution of
Bifidobacterium
. Our study revealed that
B. infantis
carries abundant bacteriocin biosynthetic gene clusters for the first time, presenting new evidence regarding the competitive interactions of
Bifidobacterium
in the infant intestinal tract.
Transcription start site heterogeneity and its role in RNA fate determination distinguish HIV-1 from other retroviruses and are mediated by core promoter elements
Authors: Kharytonchyk Siarhei , Burnett Cleo , GC Keshav , Telesnitsky Alice
Published: September 2023

HIV-1 uses heterogeneous transcription start sites (TSSs) to generate two RNA 5´ isoforms that adopt radically different structures and perform distinct replication functions. Although these RNAs differ in length by only two bases, exclusively, the shorter RNA is encapsidated while the longer RNA is excluded from virions and provides intracellular functions. The current study examined TSS usage and packaging selectivity for a broad range of retroviruses and found that heterogeneous TSS usage was a conserved feature of all tested HIV-1 strains, but all other retroviruses examined displayed unique TSSs. Phylogenetic comparisons and chimeric viruses’ properties provided evidence that this mechanism of RNA fate determination was an innovation of the HIV-1 lineage, with determinants mapping to core promoter elements. Fine-tuning differences between HIV-1 and HIV-2, which uses a unique TSS, implicated purine residue positioning plus a specific TSS-adjacent dinucleotide in specifying multiplicity of TSS usage. Based on these findings, HIV-1 expression constructs were generated that differed from the parental strain by only two point mutations yet each expressed only one of HIV-1’s two RNAs. Replication defects of the variant with only the presumptive founder TSS were less severe than those for the virus with only the secondary start site.

IMPORTANCE

Retroviruses use RNA both to encode their proteins and to serve in place of DNA as their genomes. A recent surprising discovery was that the genomic RNAs and messenger RNAs of HIV-1 are not identical but instead differ subtly on one of their ends. These differences enable the functional separation of HIV-1 RNAs into genome and messenger roles. In this report, we examined a broad collection of HIV-1-related viruses and discovered that each produced only one end class of RNA, and thus must differ from HIV-1 in how they specify RNA fates. By comparing regulatory signals, we generated virus variants that pinpointed the determinants of HIV-1 RNA fates, as well as HIV-1 variants that produced only one or the other functional class of RNA. Competition and replication assays confirmed that HIV-1 has evolved to rely on the coordinated actions of both its RNA forms.
A genetic selection for
Mycobacterium smegmatis
mutants tolerant to killing by sodium citrate defines a combined role for cation homeostasis and osmotic stress in cell death
Authors: Williams John T. , Baker Jacob J. , Zheng Huiqing , Dechow Shelby J. , Fallon Jared , Murto Megan , Albrecht Veronica J. , Gilliland Haleigh N. , Olive Andrew J. , Abramovitch Robert B.
Published: September 2023

Mycobacteria can colonize environments where the availability of metal ions is limited. Biological or inorganic chelators play an important role in limiting metal availability, and we developed a model to examine
Mycobacterium smegmatis
survival in the presence of the chelator sodium citrate. We observed that instead of restricting
M. smegmatis
growth, concentrated sodium citrate killed
M. smegmatis
. RNAseq analysis during sodium citrate treatment revealed transcriptional signatures of metal starvation and hyperosmotic stress. Notably, metal starvation and hyperosmotic stress, individually, do not kill
M. smegmatis
under these conditions. A forward genetic transposon selection was conducted to examine why sodium citrate was lethal, and several sodium-citrate-tolerant mutants were isolated. Based on the identity of three tolerant mutants,
mgtE
,
treZ
, and
fadD6,
we propose a dual stress model of killing by sodium citrate, where sodium citrate chelate metals from the cell envelope and then osmotic stress in combination with a weakened cell envelope causes cell lysis. This sodium citrate tolerance screen identified mutants in several other genes with no known function, with most conserved in the pathogen
M. tuberculosis
. Therefore, this model will serve as a basis to define their functions, potentially in maintaining cell wall integrity, cation homeostasis, or osmotolerance.

IMPORTANCE

Bacteria require mechanisms to adapt to environments with differing metal availability. When
Mycobacterium smegmatis
is treated with high concentrations of the metal chelator sodium citrate, the bacteria are killed. To define the mechanisms underlying killing by sodium citrate, we conducted a genetic selection and observed tolerance to killing in mutants of the
mgtE
magnesium transporter. Further characterization studies support a model where killing by sodium citrate is driven by a weakened cell wall and osmotic stress, that in combination cause cell lysis.
Blocking ADP-ribosylation expands the anti-mycobacterial spectrum of rifamycins
Authors: Ganapathy Uday S. , Lan Tian , Dartois Véronique , Aldrich Courtney C. , Dick Thomas
Published: September 2023

The clinical utility of rifamycins against non-tuberculous mycobacterial (NTM) disease is limited by intrinsic drug resistance achieved by ADP-ribosyltransferase Arr. By blocking the site of ribosylation, we recently optimized a series of analogs with substantially improved potency against
Mycobacterium abscessus
. Here, we show that a representative member of this series is significantly more potent than rifabutin against major NTM pathogens expressing Arr, providing a powerful medicinal chemistry approach to expand the antimycobacterial spectrum of rifamycins.

IMPORTANCE

Lung disease caused by a range of different species of non-tuberculous mycobacteria (NTM) is difficult to cure. The rifamycins are very active against
Mycobacterium tuberculosis,
which causes tuberculosis (TB), but inactive against many NTM species. Previously, we showed that the natural resistance of the NTM
Mycobacterium abscessus
to rifamycins is due to enzymatic inactivation of the drug by the bacterium. We generated chemically modified versions of rifamycins that prevent inactivation by the bacterium and thus become highly active against
M. abscessus.
Here, we show that such a chemically modified rifamycin is also highly active against several additional NTM species that harbor the rifamycin inactivating enzyme found in
M. abscessus
, including
M. chelonae
,
M. fortuitum
, and
M. simiae
. This finding expands the potential therapeutic utility of our novel rifamycins to include several currently difficult-to-cure NTM lung disease pathogens beyond
M. abscessus.
Cytochrome bd as Antioxidant Redox Enzyme
Authors: Borisov V. B. , Nastasi M. R. , Forte E.
Published: September 2023

One of the main functions of enzyme complexes that constitute electron transport (respiratory) chains of organisms is to maintain cellular redox homeostasis by oxidizing reducing equivalents, NADH and quinol. Cytochrome bd is a unique terminal oxidase of the chains of many bacteria including pathogenic species. This redox enzyme couples the oxidation of ubiquinol or menaquinol by molecular oxygen to the generation of proton motive force, a universal energy currency. The latter is used by the organism to produce ATP, another cellular energy currency, via oxidative phosphorylation. Escherichia coli contains two bd-type oxidases, bd-I and bd-II, encoded by the cydAB and appCB operons, respectively. Surprisingly, both bd enzymes make a further contribution to molecular mechanisms of maintaining the appropriate redox balance in the bacterial cell by means of elimination of reactive oxygen species, such as hydrogen peroxide. This review summarizes recent data on the redox-modulated H2O2-scavenging activities of cytochromes bd-I and bd-II from E. coli. The possibility of such antioxidant properties in cytochromes bd from other bacteria is also discussed.
MicroProf
: Code-level Attribution of Unnecessary Data Transfer in Microservice Applications
Authors: Tariq Syed Salauddin Mohammad , Menard Lance , Su Pengfei , Roy Probir
Published: September 2023

The microservice architecture style has gained popularity due to its ability to fault isolation, ease of scaling applications, and developer’s agility. However, writing applications in the microservice design style has its challenges. Due to the loosely coupled nature, services communicate with others through standard communication APIs. This incurs significant overhead in the application due to communication protocol and data transformation. An inefficient service communication at the microservice application logic can further overwhelm the application. We perform a grey literature review showing that unnecessary data transfer is a real challenge in the industry. To the best of our knowledge, no effective tool is currently available to accurately identify the origins of unnecessary microservice communications that lead to significant performance overhead and provide guidance for optimization.

To bridge the knowledge gap, we propose
MicroProf
, a dynamic program analysis tool to detect unnecessary data transfer in Java-based microservice applications. At the implementation level,
MicroProf
proposes novel techniques such as remote object sampling and hardware debug registers to monitor remote object usage.
MicroProf
reports the unnecessary data transfer at the application source code level. Furthermore,
MicroProf
pinpoints the opportunities for communication API optimization.
MicroProf
is evaluated on four well-known applications involving two real-world applications and two benchmarks, identifying five inefficient remote invocations. Guided by
MicroProf
, API optimization achieves an 87.5% reduction in the number of fields within REST API responses. The empirical evaluation further reveals that the optimized services experience a speedup of up to 4.59×.
Assessing Urdu Language Processing Tools via Statistical and Outlier Detection Methods on Urdu Tweets
Authors: Zoya  , Latif Seemab , Latif Rabia , Majeed Hammad , Jamail Nor Shahida Mohd
Published: September 2023

Text pre-processing is a crucial step in Natural Language Processing (NLP) applications, particularly for handling informal and noisy content on social media. Word-level tokenization plays a vital role in text pre-processing by removing stop words, filtering irrelevant characters, and retaining relevant tokens. These tokens are essential for constructing meaningful n-grams within advanced NLP frameworks used for data modeling. However, tokenization in low-resource languages like Urdu presents challenges due to language complexity and limited resources. Conventional space-based methods and direct application of language-specific tools often result in erroneous tokens in Urdu Language Processing (ULP). This hinders language models from effectively learning language-specific and domain-specific tokens, leading to sub-optimal results for downstream tasks such as aspect mining, topic modeling, and Named Entity Recognition (NER). To address this issue for Urdu, we have proposed a data pre-processing technique that detects outliers using the Inter-Quartile-Range (IQR) method and proposed normalization algorithms for creating useful lexicons in conjunction with existing technologies. We have collected approximately 50 million Urdu tweets using the Twitter API and conducted the performance analysis of existing language-specific tokenizers (Urduhack and Space-based tokenizer). Dataset variants were created based on the language-specific tokenizers, and we performed statistical analysis tests and visualization techniques to compare tokenization results before and after applying the proposed outlier detection and normalization method. Our findings highlighted the noticeable improvement in token size distributions, handling of informal language tokens, and misspelled and lengthy tokens. The Urduhack tokenizer combined with the proposed outlier detection and normalization yielded tokens with the best-fitted distribution in ULP. Its effectiveness has been evaluated through the task of topic modeling using Non-negative Matrix Factorization (NMF) and Latent Dirichlet allocation (LDA). The results demonstrated new and distinct topics using unigram features while achieving highly coherent topics when utilizing bigram features. For the traditional space-based method, the results consistently demonstrated improved coherence and precision scores. However, the NMF topic modeling with bigram features outperformed LDA topic modeling with bigram features.
Explaining Cross-domain Recognition with Interpretable Deep Classifier
Authors: Zhang Yiheng , Yao Ting , Qiu Zhaofan , Mei Tao
Published: September 2023

The recent advances in deep learning predominantly construct models in their internal representations, and it is opaque to explain the rationale behind and decisions to human users. Such explainability is especially essential for domain adaptation, whose challenges require developing more adaptive models across different domains. In this article, we ask the question: How much does each sample in the source domain contribute to the network’s prediction on the samples from the target domain? To address this, we devise a novel Interpretable Deep Classifier (IDC) that learns the nearest source samples of a target sample as evidence upon which the classifier makes the decision. Technically, IDC maintains a differentiable memory bank for each category, and the memory slot derives a form of key–value pair. The key records the features of discriminative source samples, and the value stores the corresponding properties, e.g., representative scores of the features for describing the category. IDC computes the loss between the output of IDC and the labels of source samples to back-propagate to adjust the representative scores and update the memory banks. Extensive experiments on Office-Home and VisDA-2017 datasets demonstrate that our IDC leads to a more explainable model with almost no accuracy degradation and effectively calibrates classification for optimum reject options. More remarkably, when taking IDC as a prior interpreter, capitalizing on 0.1% source training data selected by IDC still yields superior results than that uses full training set on VisDA-2017 for unsupervised domain adaptation.