bluuebunny/crossref_metadata_2025 huggingface dataset:
Transient increase in atherosclerotic plaque macrophage content following Streptococcus pneumoniae pneumonia in ApoE-deficient mice
Authors: Bazaz Rohit , Marriott Helen M. , Wright Carl , Chamberlain Janet , West Laura E. , Gelsthorpe Catherine , Heath Paul R. , Maleki-Dizaji Afsaneh , Francis Sheila E. , Dockrell David H.
Published: March 2023

Introduction

Despite epidemiological associations between community acquired pneumonia (CAP) and myocardial infarction, mechanisms that modify cardiovascular disease during CAP are not well defined. In particular, largely due to a lack of relevant experimental models, the effect of pneumonia on atherosclerotic plaques is unclear. We describe the development of a murine model of the commonest cause of CAP, Streptococcus pneumoniae pneumonia, on a background of established atherosclerosis. We go on to use our model to investigate the effects of pneumococcal pneumonia on atherosclerosis.

Methods

C57BL/6J and ApoE-/- mice were fed a high fat diet to promote atherosclerotic plaque formation. Mice were then infected with a range of S. pneumoniae serotypes (1, 4 or 14) with the aim of establishing a model to study atherosclerotic plaque evolution after pneumonia and bacteremia. Laser capture microdissection of plaque macrophages enabled transcriptomic analysis.

Results

Intratracheal instillation of S. pneumoniae in mice fed a cholate containing diet resulted in low survival rates following infection, suggestive of increased susceptibility to severe infection. Optimization steps resulted in a final model of male ApoE-/- mice fed a Western diet then infected by intranasal instillation of serotype 4 (TIGR4) S. pneumoniae followed by antibiotic administration. This protocol resulted in high rates of bacteremia (88.9%) and survival (88.5%). Pneumonia resulted in increased aortic sinus plaque macrophage content 2 weeks post pneumonia but not at 8 weeks, and no difference in plaque burden or other plaque vulnerability markers were found at either time point. Microarray and qPCR analysis of plaque macrophages identified downregulation of two E3 ubiquitin ligases, Huwe1 and Itch, following pneumonia. Treatment with atorvastatin failed to alter plaque macrophage content or other plaque features.

Discussion

Without antibiotics, ApoE-/- mice fed a high fat diet were highly susceptible to mortality following S. pneumoniae infection. The major infection associated change in plaque morphology was an early increase in plaque macrophages. Our results also hint at a role for the ubiquitin proteasome system in the response to pneumococcal infection in the plaque microenvironment.
How attention and knowledge modulate memory: The differential impact of cognitive conflicts on subsequent memory—A review of a decade of research
Authors: Muhmenthaler Michèle C. , Dubravac Mirela , Meier Beat
Published: March 2023

In order to cope with cognitive conflicts, attention and knowledge are required. In some conditions, cognitive conflicts can boost subsequent memory and in other conditions, they can attenuate subsequent memory. The goal of the present study is to provide a narrative review of studies from the last decade in which Stroop or flanker conflicts, task switching, perceptual disfluency or semantic incongruence were manipulated at study. We propose an integrative framework considering attentional mechanisms and knowledge structures. Attentional mechanisms can refer to conflict resolution, which is required to explain the memory benefit for incongruent stimuli in Stroop and Flanker paradigms. Attentional mechanisms can also refer to attention allocation, which is required to explain the memory cost for targets and the memory benefit for task-irrelevant distractors in task-switching paradigms. Moreover, attention allocation policies can also account for the inconsistent results for perceptual disfluency manipulations. Prior knowledge is required to explain effects of semantic congruency and incongruency: Information that is expected, or congruent with prior knowledge, is better remembered, namely by pre-existing schemata. Moreover, information that is unexpected or incongruent with prior knowledge attracts attention and is better remembered. The impact of prior knowledge on memory performance thus results in a U-shape function. We integrate the findings according to this framework and suggest directions for future research.
Evaluation of large animal models for preclinical studies of heart failure with preserved ejection fraction using clinical score systems
Authors: Li Ke , Cardoso Cristiano , Moctezuma-Ramirez Angel , Elgalad Abdelmotagaly , Perin Emerson
Published: March 2023

Heart failure with preserved ejection fraction (HFpEF) is characterized by a complex, heterogeneous spectrum of pathologic features combined with average left ventricular volume and diastolic dysfunction. HFpEF is a significant public health problem associated with high morbidity and mortality rates. Currently, effective treatments for HFpEF represent the greatest unmet need in cardiovascular medicine. A lack of an efficient preclinical model has hampered the development of new devices and medications for HFpEF. Because large animal models have similar physiologic traits as humans and appropriate organ sizes, they are the best option for limiting practical constraints. HFpEF is a highly integrated, multiorgan, systemic disorder requiring a multipronged investigative approach. Here, we review the large animal models of HFpEF reported to date and describe the methods that have been used to create HFpEF, including surgery-induced pressure overloading, medicine-induced pressure overloading, and diet-induced metabolic syndrome. In addition, for the first time to our knowledge, we use two established clinical HFpEF algorithms (HFA-PEFF and H2FPEF scores) to evaluate the currently available large animal models. We also discuss new technologies, such as continuous remote pressure monitors and inflatable aortic cuffs, as well as how the models could be improved. Based on current progress and our own experience, we believe an efficient large animal model of HFpEF should simultaneously encompass multiple pathophysiologic factors, along with multiorgan dysfunction. This could be fully evaluated through available methods (imaging, blood work). Although many models have been studied, only a few studies completely meet clinical score standards. Therefore, it is critical to address the deficiencies of each model and incorporate novel techniques to establish a more reliable model, which will help facilitate the understanding of HFpEF mechanisms and the development of a treatment.
Basal mass balance and prevalence of ice tongues in the Western ross sea
Authors: Gomez-Fell Rodrigo , Marsh Oliver J. , Rack Wolfgang , Wild Christian T. , Purdie Heather
Published: March 2023

Ice tongues at the fringes of the Antarctic ice sheet lose mass primarily through both basal melting and calving. They are sensitive to ocean conditions which can weaken the ice both mechanically or through thinning. Ice tongues, which are laterally unconfined, are likely to be particularly sensitive to ocean-induced stresses. Here we examine ice tongues in the Western Ross Sea, by looking into the factors affecting their stability. We calculate the basal mass change of twelve Antarctic ice tongues using a flux gate approach, deriving thickness from ICESat-2 height measurements and ice surface velocities from Sentinel-1 feature-tracking over the same period (October 2018 to December 2021). The basal mass balance ranges between −0.14 ± 0.07 m yr−1 and −1.50 ± 1.2 m yr−1. The average basal mass change for all the ice tongues is −0.82 ± 0.68 m of ice yr−1. Low values of basal melt suggest a stable mass balance condition in this region, with low thermal ocean forcing, as other studies have shown. We found a heterogeneous basal melt pattern with no latitudinal gradient and no clear driver in basal melt indicating that local variables are important in the persistence of ice tongues in the absence of a strong oceanographic melting force. Moreover, thanks to the temporal resolution of the data we were able to resolve the seasonal variability of Drygalski and Aviator Ice Tongues, the two largest ice tongues studied.
Total quality management in the context of University 4.0: New game new rules
Authors: Ülker Nilüfer
Published: March 2023

There have been many changes in the field of higher education in accordance with the advancements brought by the new industrial era, which is defined as Industry 4.0. Introduction of Industry 4.0 has definitely influenced ongoing practices requiring alignment and adaptations in many spheres of higher education including but not limited to Total Quality Management (TQM). As a TQM system, ISO 21001 has been specifically designed and developed to serve to the needs of educational institutions, in this particular case universities. Considering the rate of advancements in the context of Industry 4.0 where previously defined rules and policies no longer apply, universities have an important role in revising and improving their current practices in TQM accordingly to maintain their quality in this competitive environment. To be successful in the new game with new rules, this paper will provide a framework for higher education institutions for successful implementation of TQM, particularly ISO 21001, in line with the essentials of University 4.0 through alignment of ISO 21001 principles with University 4.0 practices to contribute to quality and competitive advantage of universities under current circumstances.
Microvascular and macrovascular complications of type 2 diabetes mellitus: Exome wide association analyses
Authors: Mansour Afnan , Mousa Mira , Abdelmannan Dima , Tay Guan , Hassoun Ahmed , Alsafar Habiba
Published: March 2023

Background

Type 2 diabetes mellitus (T2DM) is a chronic, metabolic disorder in which concomitant insulin resistance and β-cell impairment lead to hyperglycemia, influenced by genetic and environmental factors. T2DM is associated with long-term complications that have contributed to the burden of morbidity and mortality worldwide. The objective of this manuscript is to conduct an Exome-Wide Association Study (EWAS) on T2DM Emirati individuals to improve our understanding on diabetes-related complications to improve early diagnostic methods and treatment strategies.

Methods

This cross-sectional study recruited 310 Emirati participants that were stratified according to their medically diagnosed diabetes-related complications: diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, and cardiovascular complications. The Illumina’s Infinium Exome-24 array was used and 39,840 SNPs remained for analysis after quality control.

Findings

The analysis revealed the associations of various genes with each complication category: 1) diabetic retinopathy was associated to SHANK3 gene in locus 22q13.33 (SNP rs9616915; p=5.18 x10-4), ZSCAN5A gene in locus 19q13.43 (SNP rs7252603; p=7.55 x10-4), and DCP1B gene in locus 12p13.33 (SNPs rs715146, rs1044950, rs113147414, rs34730825; p=7.62 x10-4); 2) diabetic neuropathy was associated to ADH4 gene in locus 4q23 (SNP rs4148883; p=1.23 x10-4), SLC11A1 gene in locus 2q35 (SNP rs17235409; p=1.85 x10-4), and MATN4 gene in locus 20q13.12 (SNP rs2072788; p=2.68 x10-4); 3) diabetic nephropathy was associated to PPP1R3A gene in locus 7q31.1 (SNP rs1799999; p=1.91 x10-4), ZNF136 gene in locus 19p13.2 (SNP rs140861589; p=2.80 x10-4), and HSPA12B gene in locus 20p13 (SNP rs6076550; p=2.86 x10-4); and 4) cardiovascular complications was associated to PCNT gene in locus 21q22.3 (SNPs rs7279204, rs6518289, rs2839227, rs2839223; p=2.18 x10-4,3.04 x10-4,4.51 x10-4,5.22 x10-4 respectively), SEPT14 gene in locus 7p11.2 (SNP rs146350220; p=2.77 x10-4), and WDR73 gene in locus 15q25.2 (SNP rs72750868; p=4.47 x10-4).

Interpretation

We have identified susceptibility loci associated with each category of T2DM-related complications in the Emirati population. Given that only 16% of the markers from the Illumina’s Infinium Exome chip passed quality control assessment, this demonstrates that multiple variants were, either, monomorphic in the Arab population or were not genotyped due to the use of a Euro-centric EWAS array that limits the possibility of including targeted ethnic-specific SNPs. Our results suggest the alarming possibility that lack of representation in reference panels could inhibit discovery of functionally important loci associated to T2DM complications. Further effort must be conducted to improve the representation of diverse populations in genotyping and sequencing studies.
Ecological aspects of volatile organic compounds emitted by exotic invasive plants
Authors: Clavijo McCormick Andrea , Effah Evans , Najar-Rodriguez Adriana
Published: March 2023

Exotic invasive plants are present in almost all terrestrial ecosystems. Their spread and ability to colonize new habitats are predicted to increase with human travel, global trade, and climate change. These plants alter the environments they invade in multiple ways, affecting surrounding species. Chemically, invasive plants can modify their environment by releasing secondary metabolites such as root exudates (liquid) or airborne (gaseous) volatile organic compounds (VOCs). The allelopathic effect of invasive species' root exudates is well studied and acknowledged as a trait contributing to invasiveness. However, less is known about the effects of invasive species' VOCs, which are likely to play important ecological roles. Therefore, we conducted a systematic review of the literature during the last decade (2012–2022) to explore what is known about the ecological aspects of VOCs emitted by invasive plants, focusing on the factors affecting their emission (genetic, biotic, and abiotic), and their role on plant-plant and plant-insect interactions. We found 29 studies matching our search criteria. These studies suggest that invasive species are more “chemically diverse” than their native counterparts and have different chemical behavior in native compared to invaded ranges. The studies further highlight that chemical traits are heritable and contribute to invasiveness. Multiple biotic and abiotic factors affecting invasive plants' VOC emission have been explored (e.g., herbivory, soil microorganisms, warming, and CO2). The studies indicate that invasive plants may experience less variation in their VOC emissions in response to environmental change than natives, with trade-offs between growth, reproduction and defense influencing VOC emissions. Regarding the impact on native species and their interactions, the allelopathic role of invasive plants' VOCs on native plants is well documented, consistently showing phytotoxic effects. There is also evidence of their involvement in neighbor detection. While volatile-mediated interactions between invasive plants and native insects remain poorly studied, the existing evidence shows that invasive plant VOCs have the potential to disrupt communication between native plants and insects. But insects also use multiple cues to make foraging/oviposition decisions, compensating for the disruptive effect of invasive plant VOCs. To conclude, we identify knowledge gaps and propose avenues for future research.
The devil is in the details: Problems in DNA barcoding practices indicated by systematic evaluation of insect barcodes
Authors: Cheng Zhentao , Li Qiang , Deng Jun , Liu Qian , Huang Xiaolei
Published: March 2023

In recent years, DNA barcoding has rapidly developed as a powerful tool in taxonomy, demonstrating its value in species identification and discovery of cryptic diversity. The number of barcoding sequences of various species continues to grow in the GenBank and BOLD databases; however, the accuracy of sequences and related raw information in public repositories is often questionable. In the present study, based on a dataset of 68,089 Hemiptera COI barcode sequences covering 3,064 species, 1,072 genera, and 48 families, we analyzed genetic differences within and between species and evaluated possible data errors in the insect barcodes. The results showed that errors in the barcode data are not rare, and most of them are due to human errors, such as specimen misidentification, sample confusion, and contamination. A significant portion of these errors can be attributed to inappropriate and imprecise practices in the DNA barcoding workflow. Herein, suggestions are provided to improve the practical operations and workflow of DNA barcoding to reduce human errors.
Post-fledging survival of Tengmalm’s owl offspring in boreal forests: Interactive effects of varying dynamics of main prey and habitat composition
Authors: Kouba Marek , Bartoš Luděk , Tulis Filip , Ševčík Michal , Sovadinová Simona , Bušina Tomáš , Janouš Martin , Kouba Petr , Bartošová Jitka , Hongisto Kari , Korpimäki Erkki
Published: March 2023

The knowledge about the mortality rate of offspring is crucial for estimating bird population dynamics and conserving species with declining populations. Parents of predatory birds provide food for their offspring during the post-fledging dependency period, which is frequently described as essential due to inexpert flying skills. Using radio telemetry, we studied fledglings’ probability of dying by starvation and predation in Tengmalms’ owls (Aegolius funereus). Nestlings (21 and 39) from 10 and 14 broods in 2019 and 2021, respectively, were equipped with leg-mounted tags and monitored throughout the post-fledging dependency period in west-central Finland. In total, 28 out of 60 fledglings did not survive the post-fledging dependency period (12 died due to starvation, and 16 were predated). The fledglings’ probability of dying by starvation and predation was 3.7 and 2.4 times higher, respectively, in the decreasing (2019) than during the increasing (2021) abundance of main foods (voles), showing that prey availability is essential for survival during the post-fledging dependency period. The probability of starvation increased with augmenting agricultural lands in the home range and increasing precipitation after fledging, which indicated that parent owls avoided hunting in open areas and during rainy nights. The predation rate during the post-fledging dependency period increased with augmenting cover of old-growth forests in the home range. This result suggested that coverage of old-growth forests is nowadays so small in the study area that they act as ecological traps for newly-fledged owlets. The reason is that the main avian enemies of Tengmalm’s owls’ (goshawks and Ural owls) also prefer old-growth forests for breeding and hunting.
An HLA map of the world: A comparison of HLA frequencies in 200 worldwide populations reveals diverse patterns for class I and class II
Authors: Arrieta-Bolaños Esteban , Hernández-Zaragoza Diana Iraíz , Barquera Rodrigo
Published: March 2023

HLA frequencies show widespread variation across human populations. Demographic factors as well as selection are thought to have shaped HLA variation across continents. In this study, a worldwide comparison of HLA class I and class II diversity was carried out. Multidimensional scaling techniques were applied to 50 HLA-A and HLA-B (class I) as well as 13 HLA-DRB1 (class II) first-field frequencies in 200 populations from all continents. Our results confirm a strong effect of geography on the distribution of HLA class I allele groups, with principal coordinates analysis closely resembling geographical location of populations, especially those of Africa-Eurasia. Conversely, class II frequencies stratify populations along a continuum of differentiation less clearly correlated to actual geographic location. Double clustering analysis revealed finer intra-continental sub-clusters (e.g., Northern and Western Europe vs. South East Europe, North Africa and Southwest Asia; South and East Africa vs. West Africa), and HLA allele group patterns characteristic of these clusters. Ancient (Austronesian expansion) and more recent (Romani people in Europe) migrations, as well as extreme differentiation (Taiwan indigenous peoples, Native Americans), and interregional gene flow (Sámi, Egyptians) are also reflected by the results. Barrier analysis comparing DST and geographic location identified genetic discontinuities caused by natural barriers or human behavior explaining inter and intra-continental HLA borders for class I and class II. Overall, a progressive reduction in HLA diversity from African to Oceanian and Native American populations is noted. This analysis of HLA frequencies in a unique set of worldwide populations confirms previous findings on the remarkable similarity of class I frequencies to geography, but also shows a more complex development for class II, with implications for both human evolutionary studies and biomedical research.
The dysregulation of leukemia inhibitory factor and its implications for endometriosis pathophysiology
Authors: Zutautas Katherine B. , Sisnett Danielle J. , Miller Jessica E. , Lingegowda Harshavardhan , Childs Timothy , Bougie Olga , Lessey Bruce A. , Tayade Chandrakant
Published: March 2023

Endometriosis is an estrogen dominant, chronic inflammatory disease characterized by the growth of endometrial-like tissue outside of the uterus. The most common symptoms experienced by patients include manifestations of chronic pelvic pain- such as pain with urination, menstruation, or defecation, and infertility. Alterations to Leukemia Inhibitory Factor (LIF), a cytokine produced by the luminal and glandular epithelium of the endometrium that is imperative for successful pregnancy, have been postulated to contribute to infertility. Conditions such as recurrent implantation failure, unexplained infertility, and infertility associated diseases such as adenomyosis and endometriosis, have demonstrated reduced LIF production in the endometrium of infertile patients compared to fertile counterparts. While this highlights the potential involvement of LIF in infertility, LIF is a multifaceted cytokine which plays additional roles in the maintenance of cell stemness and immunomodulation. Thus, we sought to explore the implications of LIF production within ectopic lesions on endometriosis pathophysiology. Through immunohistochemistry of an endometrioma tissue microarray and ELISA of tissue protein extract and peritoneal fluid samples, we identify LIF protein expression in the ectopic lesion microenvironment. Targeted RT qPCR for LIF and associated signaling transcripts, identify LIF to be significantly downregulated in the ectopic tissue compared to eutopic and control while its receptor, LIFR, is upregulated, highlighting a discordance in ectopic protein and mRNA LIF expression. In vitro treatment of endometriosis representative cell lines (12Z and hESC) with LIF increased production of immune-recruiting cytokines (MCP-1, MCP-3) and the angiogenic factor, VEGF, as well as stimulated tube formation in human umbilical vein endothelial cells (HUVECs). Finally, LIF treatment in a syngeneic mouse model of endometriosis induced both local and peripheral alterations to immune cell phenotypes, ultimately reducing immunoregulatory CD206+ small peritoneal macrophages and T regulatory cells. These findings suggest that LIF is present in the ectopic lesions of endometriosis patients and could be contributing to lesion vascularization and immunomodulation.
Pharmacological depletion of microglia alleviates neuronal and vascular damage in the diabetic CX3CR1-WT retina but not in CX3CR1-KO or hCX3CR1I249/M280-expressing retina
Authors: Church Kaira A. , Rodriguez Derek , Mendiola Andrew S. , Vanegas Difernando , Gutierrez Irene L. , Tamayo Ian , Amadu Abdul , Velazquez Priscila , Cardona Sandra M. , Gyoneva Stefka , Cotleur Anne C. , Ransohoff Richard M. , Kaur Tejbeer , Cardona Astrid E.
Published: March 2023

Diabetic retinopathy, a microvascular disease characterized by irreparable vascular damage, neurodegeneration and neuroinflammation, is a leading complication of diabetes mellitus. There is no cure for DR, and medical interventions marginally slow the progression of disease. Microglia-mediated inflammation in the diabetic retina is regulated via CX3CR1-FKN signaling, where FKN serves as a calming signal for microglial activation in several neuroinflammatory models. Polymorphic variants of CX3CR1, hCX3CR1I249/M280, found in 25% of the human population, result in a receptor with lower binding affinity for FKN. Furthermore, disrupted CX3CR1-FKN signaling in CX3CR1-KO and FKN-KO mice leads to exacerbated microglial activation, robust neuronal cell loss and substantial vascular damage in the diabetic retina. Thus, studies to characterize the effects of hCX3CR1I249/M280-expression in microglia-mediated inflammation in the diseased retina are relevant to identify mechanisms by which microglia contribute to disease progression. Our results show that hCX3CR1I249/M280 mice are significantly more susceptible to microgliosis and production of Cxcl10 and TNFα under acute inflammatory conditions. Inflammation is exacerbated under diabetic conditions and coincides with robust neuronal loss in comparison to CX3CR1-WT mice. Therefore, to further investigate the role of hCX3CR1I249/M280-expression in microglial responses, we pharmacologically depleted microglia using PLX-5622, a CSF-1R antagonist. PLX-5622 treatment led to a robust (~70%) reduction in Iba1+ microglia in all non-diabetic and diabetic mice. CSF-1R antagonism in diabetic CX3CR1-WT prevented TUJ1+ axonal loss, angiogenesis and fibrinogen deposition. In contrast, PLX-5622 microglia depletion in CX3CR1-KO and hCX3CR1I249/M280 mice did not alleviate TUJ1+ axonal loss or angiogenesis. Interestingly, PLX-5622 treatment reduced fibrinogen deposition in CX3CR1-KO mice but not in hCX3CR1I249/M280 mice, suggesting that hCX3CR1I249/M280 expressing microglia influences vascular pathology differently compared to CX3CR1-KO microglia. Currently CX3CR1-KO mice are the most commonly used strain to investigate CX3CR1-FKN signaling effects on microglia-mediated inflammation and the results in this study indicate that hCX3CR1I249/M280 receptor variants may serve as a complementary model to study dysregulated CX3CR1-FKN signaling. In summary, the protective effects of microglia depletion is CX3CR1-dependent as microglia depletion in CX3CR1-KO and hCX3CR1I249/M280 mice did not alleviate retinal degeneration nor microglial morphological activation as observed in CX3CR1-WT mice.
Macrophage-infectivity potentiator of Trypanosoma cruzi (TcMIP) is a new pro-type 1 immuno-stimulating protein for neonatal human cells and vaccines in mice
Authors: Radwanska Magdalena , de Lemos Esteves Frédéric , Linsen Loes , Coltel Nicolas , Cencig Sabrina , Widart Joelle , Massart Anne-Cécile , Colson Séverine , Di Paolo Alexandre , Percier Pauline , Ait Djebbara Sarra , Guillonneau François , Flamand Véronique , De Pauw Edwin , Frère Jean-Marie , Carlier Yves , Truyens Carine
Published: March 2023

This work identifies the protein “macrophage infectivity potentiator” of Trypanosoma cruzi trypomastigotes, as supporting a new property, namely a pro-type 1 immunostimulatory activity on neonatal cells. In its recombinant form (rTcMIP), this protein triggers the secretion of the chemokines CCL2 and CCL3 by human umbilical cord blood cells from healthy newborns, after 24h in vitro culture. Further stimulation for 72h results in secretion of IFN-γ, provided cultures are supplemented with IL-2 and IL-18. rTcMIP activity is totally abolished by protease treatment and is not associated with its peptidyl-prolyl cis-trans isomerase enzymatic activity. The ability of rTcMIP to act as adjuvant was studied in vivo in neonatal mouse immunization models, using acellular diphtheria-tetanus-pertussis-vaccine (DTPa) or ovalbumin, and compared to the classical alum adjuvant. As compared to the latter, rTcMIP increases the IgG antibody response towards several antigens meanwhile skewing antibody production towards the Th-1 dependent IgG2a isotype. The amplitude of the rTcMIP adjuvant effect varied depending on the antigen and the co-presence of alum. rTcMIP did by contrast not increase the IgE response to OVA combined with alum. The discovery of the rTcMIP immunostimulatory effect on neonatal cells opens new possibilities for potential use as pro-type 1 adjuvant for neonatal vaccines. This, in turn, may facilitate the development of more efficient vaccines that can be given at birth, reducing infection associated morbidity and mortality which are the highest in the first weeks after birth.
Responses of tidal dynamic and water exchange capacity to coastline change in the Bohai Sea, China
Authors: Wu Zhengcheng , Zhou Chunyan , Wang Peng , Fei Zihao
Published: March 2023

Bohai Sea (BHS) is a semi-enclosed shallow continental sea in China that has suffered from the deteriorative hydrodynamic environment due to large-scale reclamation. Single-factor simulations of tidal dynamic and material transport under the influence of the coastline changes from 1999 to 2019 in BHS were carried out. The model results showed that the amplitude of M2 tide increased slightly in Liaodong Bay and Bohai Bay, but decreased obviously in Laizhou Bay along with larger reclamation. The amplitude variation of the semi-diurnal constituents (M2, S2) was greater than the diurnal ones (K1, O1). The basin residence time in Liaodong Bay and Laizhou Bay increased by 5.44% and 49.44% from 1999 to 2019, respectively. Runoff of the Huanghe River can shorten the residence time of Laizhou bay while only having little effect on Bohai Bay and Liaodong Bay. The study of the Bohai Sea evolution can provide recommendations for subsequent marine ecological restoration efforts and serve as a reference for the study of other large semi-enclosed bays.
Advancing the robustness of risk regulation for offshore drilling operations in China
Authors: Yang Yuan
Published: March 2023

Robust regulation has become a pursuit in risk governance of offshore drilling operations over the recent decade. However, the idea of robust risk regulation has not been fully developed in China. This paper aims to explore what affects the robustness of risk regulation and how can a robust regulatory regime for offshore drilling operations be achieved in China. It begins with an identification of risks and values of the offshore petroleum industry, highlighting that robust regulation is the primary means to manage such risks in offshore drilling operations. It then discusses dimensions of regulatory robustness and assesses and compares regulatory regimes for this high-risk offshore petroleum industry in the United Kingdom, Norway, the United States and China. In specific, the Chinese paths to govern the risks of offshore operations are summarized. A key theoretical debate on regulating offshore drilling operations is which regulatory modes can better facilitate the robustness of risk regulation. The command-and-control regulation and self-regulation represent two primary regulatory modes of offshore risk regulation. The former is strongly dependent upon public enforcement while the latter emphasizes internal continuous improvement of the offshore petroleum industry. To develop robust offshore regulation in China, this paper suggests that a certain combination of the two modes is necessary to deliver optimal regulatory outcomes.
Peripheral and central capillary non-perfusion in diabetic retinopathy: An updated overview
Authors: Antropoli Alessio , Arrigo Alessandro , La Franca Lamberto , Bianco Lorenzo , Barlocci Eugenio , Fusi Emanuele , Bandello Francesco , Battaglia Parodi Maurizio
Published: March 2023

Capillary non-perfusion (CNP) is one of the key hallmarks of diabetic retinopathy (DR), which may develop both in the periphery and at the posterior pole. Our perspectives on CNP have extended with the introduction of optical coherence tomography angiography (OCTA) and ultra-widefield imaging, and the clinical consequences of peripheral and macular CNP have been well characterized. Fluorescein angiography (FA) continues to be the gold standard for detecting and measuring CNP, particularly when ultra-widefield imaging is available. OCTA, on the other hand, is a quicker, non-invasive approach that allows for a three-dimensional examination of CNP and may soon be regarded as an useful alternative to FA. In this review, we provide an updated scenario regarding the characteristics, clinical impact, and management of central and peripheral CNP in DR.
Differences in bacteria nanomotion profiles and neutrophil nanomotion during phagocytosis
Authors: Pleskova Svetlana Nikolaevna , Lazarenko Ekaterina Vladimirovna , Bezrukov Nikolay Alexandrovich , Bobyk Sergey Zenonovich , Boryakov Alexey Vladimirovich , Kriukov Ruslan Nikolaevich
Published: March 2023

The main goal of this work is to highlight the connection between nanomotion and the metabolic activity of living cells. We therefore monitored the nanomotion of four different clinical strains of bacteria (prokaryotes) and the bacterial phagocytosis by neutrophil granulocytes (eukaryotes). All clinical strains of bacteria, regardless of their biochemical profile, showed pronounced fluctuations. Importantly, the nature of their nanomotions was different for the different strains. Flagellated bacteria (Escherichia coli, Proteus mirabilis) showed more pronounced movements than the non-flagellated forms (Staphylococcus aureus, Klebsiella pneumoniae). The unprimed neutrophil did not cause any difference in cantilever oscillations with control. However, in the process of phagocytosis of S. aureus (metabolically active state), a significant activation of neutrophil granulocytes was observed and cell nanomotions were maintained at a high level for up to 30 min of observation. These preliminary results indicate that nanomotion seems to be specific to different bacterial species and could be used to monitor, in a label free manner, basic cellular processes.
Species identification, antibiotic resistance, and virulence in Enterobacter cloacae complex clinical isolates from South Korea
Authors: Ganbold Michidmaral , Seo Jungyu , Wi Yu Mi , Kwon Ki Tae , Ko Kwan Soo
Published: March 2023

This study aimed to identify the species of Enterobacter cloacae complex (ECC) isolates and compare the genotype, antibiotic resistance, and virulence among them. A total of 183 ECC isolates were collected from patients in eight hospitals in South Korea. Based on partial sequences of hsp60 and phylogenetic analysis, all ECC isolates were identified as nine species and six subspecies. Enterobacter hormaechei was the predominant species (47.0%), followed by Enterobacter kobei, Enterobacter asburiae, Enterobacter ludiwigii, and Enterobacter roggenkampii. Multilocus sequence typing analysis revealed that dissemination was not limited to a few clones, but E. hormaechei subsp. xiangfangensis, E. hormaechei subsp. steigerwaltii, and E. ludwigii formed large clonal complexes. Antibiotic resistance rates were different between the ECC species. In particular, E. asburiae, E. kobei, E. roggenkampii, and E. cloacae isolates were highly resistant to colistin, whereas most E. hormaechei and E. ludwigii isolates were susceptible to colistin. Virulence was evaluated through serum bactericidal assay and the Galleria mellonella larvae infection model. Consistency in the results between the serum resistance and the G. mellonella larvae infection assay was observed. Serum bactericidal assay showed that E. hormaechei, E. kobei, and E. ludwigii were significantly more virulent than E. asburiae and E. roggenkampii. In this study, we identified the predominant ECC species in South Korea and observed the differences in antibiotic resistance and virulence between the species. Our findings suggest that correct species identification, as well as continuous monitoring is crucial in clinical settings.
Chromosome-level analysis of the Colletotrichum graminicola genome reveals the unique characteristics of core and minichromosomes
Authors: Becerra Sioly , Baroncelli Riccardo , Boufleur Thaís R. , Sukno Serenella A. , Thon Michael R.
Published: March 2023

The fungal pathogen Colletotrichum graminicola causes the anthracnose of maize (Zea mays) and is responsible for significant yield losses worldwide. The genome of C. graminicola was sequenced in 2012 using Sanger sequencing, 454 pyrosequencing, and an optical map to obtain an assembly of 13 pseudochromosomes. We re-sequenced the genome using a combination of short-read (Illumina) and long-read (PacBio) technologies to obtain a chromosome-level assembly. The new version of the genome sequence has 13 chromosomes with a total length of 57.43 Mb. We detected 66 (23.62 Mb) structural rearrangements in the new assembly with respect to the previous version, consisting of 61 (21.98 Mb) translocations, 1 (1.41 Mb) inversion, and 4 (221 Kb) duplications. We annotated the genome and obtained 15,118 predicted genes and 3,614 new gene models compared to the previous version of the assembly. We show that 25.88% of the new assembly is composed of repetitive DNA elements (13.68% more than the previous assembly version), which are mostly found in gene-sparse regions. We describe genomic compartmentalization consisting of repeat-rich and gene-poor regions vs. repeat-poor and gene-rich regions. A total of 1,140 secreted proteins were found mainly in repeat-rich regions. We also found that ~75% of the three smallest chromosomes (minichromosomes, between 730 and 551 Kb) are strongly affected by repeat-induced point mutation (RIP) compared with 28% of the larger chromosomes. The gene content of the minichromosomes (MCs) comprises 121 genes, of which 83.6% are hypothetical proteins with no predicted function, while the mean percentage of Chr1–Chr10 is 36.5%. No predicted secreted proteins are present in the MCs. Interestingly, only 2% of the genes in Chr11 have homologs in other strains of C. graminicola, while Chr12 and 13 have 58 and 57%, respectively, raising the question as to whether Chrs12 and 13 are dispensable. The core chromosomes (Chr1–Chr10) are very different with respect to the MCs (Chr11–Chr13) in terms of the content and sequence features. We hypothesize that the higher density of repetitive elements and RIPs in the MCs may be linked to the adaptation and/or host co-evolution of this pathogenic fungus.
Cultureless enumeration of live bacteria in urinary tract infection by single-cell Raman spectroscopy
Authors: Wang Jingkai , Kong Kang , Guo Chen , Yin Guangyao , Meng Siyu , Lan Lu , Luo Liqiang , Song Yizhi
Published: March 2023

Urinary tract infections (UTIs) are the most common outpatient infections. Obtaining the concentration of live pathogens in the sample is crucial for the treatment. Still, the enumeration depends on urine culture and plate counting, which requires days of turn-around time (TAT). Single-cell Raman spectra combined with deuterium isotope probing (Raman-DIP) has been proven to identify the metabolic-active bacteria with high accuracy but is not able to reveal the number of live pathogens due to bacteria replication during the Raman-DIP process. In this study, we established a new approach of using sodium acetate to inhibit the replication of the pathogen and applying Raman-DIP to identify the active single cells. By combining microscopic image stitching and recognition, we could further improve the efficiency of the new method. Validation of the new method on nine artificial urine samples indicated that the exact number of live pathogens obtained with Raman-DIP is consistent with plate-counting while shortening the TAT from 18 h to within 3 h, and the potential of applying Raman-DIP for pathogen enumeration in clinics is promising.
Evolutionary dynamics of Usutu virus: Worldwide dispersal patterns and transmission dynamics in Europe
Authors: Siljic Marina , Sehovic Rastko , Jankovic Marko , Stamenkovic Gorana , Loncar Ana , Todorovic Marija , Stanojevic Maja , Cirkovic Valentina
Published: March 2023

Background

Usutu virus (USUV) is an emerging mosquito-borne Flavivirus, with birds as the main zoonotic reservoir. Humans are accidental hosts and mostly develop mild or even asymptomatic infections, although severe complications such as encephalitis can also arise. Detailed characterization of the pathogen's phylogenetics may offer valuable insights into the prediction and prevention of potential epidemics; however, lack of uniformity and the number of available USUV sequences worldwide hamper comprehensive investigation.

Aim

The study aimed to investigate USUV spatio-temporal dispersal inter- and intracontinentally and to estimate the dynamics of viral spread within Europe.

Methods

Phylogeographic and phylodynamic analyses were done using advanced phylogenetic methods implemented in Beast 1.10.4 and Beast 2.6.4 software packages.

Results

Herein, we report on a new USUV isolate from Culex pipiens collected in 2019 from Serbia. The results of this research revealed two newly described intercontinental migration events of USUV from Africa to Germany in the 1970s and from Africa to the Middle East (Israel) in the late 90s. Finally, phylodynamic analysis substantiated the ongoing active expansion of USUV in Europe.

Conclusion

The data would imply a high potential for further USUV expansion in Europe. Detailed phylogenetic characterization of the pathogen may offer valuable insights into prediction and prevention of potential epidemics; however, lack of uniformity and number of available USUV sequences worldwide hampers comprehensive investigation. This study draws attention to the need for upscaling USUV surveillance.
Bacterial expression systems based on Tymovirus-like particles for the presentation of vaccine antigens
Authors: Ogrina Anete , Balke Ina , Kalnciema Ieva , Skrastina Dace , Jansons Juris , Bachmann Martin F. , Zeltins Andris
Published: March 2023

Virus-like particles (VLPs) are virus-derived artificial nanostructures that resemble a native virus-stimulating immune system through highly repetitive surface structures. Improved safety profiles, flexibility in vaccine construction, and the ease of VLP production and purification have highlighted VLPs as attractive candidates for universal vaccine platform generation, although exploration of different types of expression systems for their development is needed. Here, we demonstrate the construction of several simple Escherichia coli expression systems for the generation of eggplant mosaic virus (EMV) VLP-derived vaccines. We used different principles of antigen incorporation, including direct fusion of EMV coat protein (CP) with major cat allergen Feld1, coexpression of antigen containing and unmodified (mosaic) EMV CPs, and two coexpression variants of EMV VLPs and antigen using synthetic zipper pair 18/17 (SYNZIP 18/17), and coiled-coil forming peptides E and K (Ecoil/Kcoil). Recombinant Fel d 1 chemically coupled to EMV VLPs was included as control experiments. All EMV-Feld1 variants were expressed in E. coli, formed Tymovirus-like VLPs, and were used for immunological evaluation in healthy mice. The immunogenicity of these newly developed vaccine candidates demonstrated high titers of Feld1-specific Ab production; however, a comparably high immune response against carrier EMV was also observed. Antibody avidity tests revealed very specific Ab production (more than 50% specificity) for four out of the five vaccine candidates. Native Feld1 recognition and subclass-specific antibody tests suggested that the EMV-SZ18/17-Feld1 complex and chemically coupled EMV-Feld1 vaccines may possess characteristics for further development.
Adaptive cueing strategy for gait modification: A case study using auditory cues
Authors: Wu Tina L. Y. , Murphy Anna , Chen Chao , Kulić Dana
Published: March 2023

People with Parkinson's (PwP) experience gait impairments that can be improved through cue training, where visual, auditory, or haptic cues are provided to guide the walker's cadence or step length. There are two types of cueing strategies: open and closed-loop. Closed-loop cueing may be more effective in addressing habituation and cue dependency, but has to date been rarely validated with PwP. In this study, we adapt a human-in-the-loop framework to conduct preliminary analysis with four PwP. The closed-loop framework learns an individualized model of the walker's responsiveness to cues and generates an optimized cue based on the model. In this feasibility study, we determine whether participants in early stages of Parkinson's can respond to the novel cueing framework, and compare the performance of the framework to two alternative cueing strategies (fixed/proportional approaches) in changing the participant's cadence to two target cadences (speed up/slow down). The preliminary results show that the selection of the target cadence has an impact on the participant's gait performance. With the appropriate target, the framework and the fixed approaches perform similarly in slowing the participants' cadence. However, the proposed framework demonstrates better efficiency, explainability, and robustness across participants. Participants also have the highest retention rate in the absence of cues with the proposed framework. Finally, there is no clear benefit of using the proportional approach.
Application of conditional generative adversarial network to multi-step car-following modeling
Authors: Ma Lijing , Qu Shiru
Published: March 2023

Car-following modeling is essential in the longitudinal control for connected and autonomous vehicles (CAVs). Considering the advantage of the generative adversarial network (GAN) in capturing realistic data distribution, this paper applies conditional GAN (CGAN) to car-following modeling. The generator is elaborately designed with a sequence-to-sequence structure to reflect the decision-making process of human driving behavior. The proposed model is trained and tested based on the empirical dataset, and it is compared with a supervised learning model and a mathematical model. Numerical simulations are conducted to verify the model's performance, especially in the condition of mixed traffic flow. The comparison result shows that the CGAN model outperforms others in trajectory reproduction, indicating it can effectively imitate human driving behavior. The simulation results suggest that the introduction of CGAN-based CAVs improves the stability and efficiency of the mixed traffic flow.
Inhibitory circuits in fear memory and fear-related disorders
Authors: Singh Sanjay , Topolnik Lisa
Published: March 2023

Fear learning and memory rely on dynamic interactions between the excitatory and inhibitory neuronal populations that make up the prefrontal cortical, amygdala, and hippocampal circuits. Whereas inhibition of excitatory principal cells (PCs) by GABAergic neurons restrains their excitation, inhibition of GABAergic neurons promotes the excitation of PCs through a process called disinhibition. Specifically, GABAergic interneurons that express parvalbumin (PV+) and somatostatin (SOM+) provide inhibition to different subcellular domains of PCs, whereas those that express the vasoactive intestinal polypeptide (VIP+) facilitate disinhibition of PCs by inhibiting PV+ and SOM+ interneurons. Importantly, although the main connectivity motifs and the underlying network functions of PV+, SOM+, and VIP+ interneurons are replicated across cortical and limbic areas, these inhibitory populations play region-specific roles in fear learning and memory. Here, we provide an overview of the fear processing in the amygdala, hippocampus, and prefrontal cortex based on the evidence obtained in human and animal studies. Moreover, focusing on recent findings obtained using genetically defined imaging and intervention strategies, we discuss the population-specific functions of PV+, SOM+, and VIP+ interneurons in fear circuits. Last, we review current insights that integrate the region-specific inhibitory and disinhibitory network patterns into fear memory acquisition and fear-related disorders.