bluuebunny/crossref_metadata_2025 huggingface dataset:
RAD001 targeted HUVECs reverses 12‐lipoxygenase‐induced angiogenesis in oesophageal squamous cell carcinoma
Authors: Chen Xue , Chen Xuan , Sun Xiaozheng , Wang Cong , Wen Zhihua , Cheng Yufeng
Published: June 2021

12‐LOX plays an important role in the progression of various malignancies. However, the underlying mechanisms of the action of 12‐LOX and tumour treatment strategies remain not fully defined. In this study, we investigated the possible roles of 12‐LOX in ESCC and explored the new therapeutic target. Approximately 73% of ESCC tissues showed marked up‐regulation of 12‐LOX, which was associated with poor prognosis. 12‐LOX overexpression was positively correlated with the malignant progression of ESCC as demonstrated both in vitro and in vivo. Up‐regulation of 12‐LOX significantly increased the proliferation of ESCC cells and the xenograft volume. Moreover, 12‐LOX up‐regulation promoted tube formation of HUVECs and tumour angiogenesis in xenografts. Mechanism investigation indicated that 12‐LOX overexpression led to activation of the PI3K/AKT/mTOR pathway and the up‐regulation of VEGF in ESCC cells. Subsequent analysis indicated that the RAD001 could reverse the 12‐LOX‐induced promoting effect on ESCC. Specifically, the application of RAD001 inhibited the proliferation of ESCC cells and the tube‐forming ability of HUVECs. In the drug group, the xenografts exhibited significant volume reduction and angiogenesis inhibition. We demonstrated that RAD001 could inhibit HUVEC migration. These findings presented the evidence that RAD001 had distinct roles on HUVECs and could exert anti‐tumour effects by targeting not only the PI3K/AKT/mTOR pathway but the angiogenesis in ESCC.
Phylogenetic identification of symbiotic protists of five ChineseReticulitermesspecies indicates a cospeciation of gut microfauna with host termites
Authors: Song Yan‐Qiu , Zhang Dian , Chen Wen , Dang Xiao‐Xue , Yang Hong
Published: June 2021

Symbiotic protists play important roles in the wood digestion of lower termites. Previous studies showed that termites generally possess host‐specific flagellate communities. The genusReticulitermesis particularly interesting because its unique assemblage of gut flagellates bears evidence for transfaunation. The gut fauna ofReticulitermesspecies in Japan, Europe, and North America had been investigated, but data on species in China are scarce. For the first time, we analyzed the phylogeny of protists in the hindgut of fiveReticulitermesspecies in China. A total of 22 protist phylotypes were affiliated with the family Trichonymphidae, Teranymphidae, Trichomonadidae, and Holomastigotoididae (Phylum Parabasalia), and 45 protist phylotypes were affiliated with the family Pyrsonymphidae (Phylum Preaxostyla). The protist fauna of these fiveReticulitermesspecies is similar to those ofReticulitermesspecies in other geographical regions. The topology of Trichonymphidae subtree was similar to that ofReticulitermestree. All Preaxostyla clones were affiliated with the generaPyrsonymphaandDinenympha(Order Oxymonadida) as in the otherReticulitermesspecies. The results of this study not only add to the existing information on the flagellates present in otherReticulitermesspecies but also offer the opportunity to test the hypotheses for the coevolution of symbiotic protists with their host termites.
Sensory innervation of the human male prepuce: Meissner's corpuscles predominate
Authors: García‐Mesa Yolanda , García‐Piqueras Jorge , Cobo Ramón , Martín‐Cruces José , Suazo Iván , García‐Suárez Olivia , Feito Jorge , Vega José A.
Published: June 2021

Meissner's corpuscles are the most abundant sensory corpuscles in the glabrous skin of the male prepuce. They are type I, rapidly adapting, low‐threshold mechanoreceptors, and their function is linked to the expression of the mechanoprotein piezo‐type mechanosensitive ion channel component 2 (PIEZO2). Stimulation of genital Meissner's corpuscles gives rise to sexual sensations. It has been recently demonstrated that digital Meissner's corpuscles, Meissner‐like corpuscles, and genital end bulbs have an endoneurium‐like capsule surrounding their neuronal elements; that is, the axon and glial lamellar cells, and their axons, display PIEZO2 immunoreactivity. It is unknown whether this is also the case for preputial Meissner's corpuscles. Furthermore, the expression of certain proteins that have been found in Meissner's corpuscles at other anatomical locations, especially in the digits, has not been investigated in preputial Meissner's corpuscles. Here, we used immunohistochemistry to investigate the expression of axonal (neurofilament, neuron‐specific enolase), glial (S100 protein, glial fibrillary acidic protein, vimentin), endoneurial (CD34), and perineurial (glucose transporter 1) markers in the preputial and digital Meissner's corpuscles of male participants aged between 5 and 23 years. Furthermore, we investigated the occurrence of the mechanoprotein PIEZO2 in male preputial Meissner's corpuscles. Human male prepuce contains numerous Meissner's corpuscles, which may be grouped or isolated and are regularly distributed in the dermal papillae. Lamellar glial cells display strong expression of S100 protein and vimentin but lack expression of glial fibrillary acidic protein. In addition, they show axonal PIEZO2 expression and have an endoneurial capsule, but no perineurial. Our results indicate that human male preputial Meissner's corpuscles share the immunohistochemical profile of digital Meissner's corpuscles, which is considered to be necessary for mechanotransduction. These data strongly suggest that the structure and function of Meissner's corpuscles are independent of their anatomical location.
The relative locations of the supraorbital, infraorbital, and mental foramina: A cadaveric study
Authors: Hester Kathylin M. , Rahimi Omid B. , Fry Constance L. , Nation Haley L.
Published: June 2021

The purpose of this study is to investigate the applicability of the current surgical guideline stating that the main facial foramina that transmit cutaneous nerves to the face (supraorbital notch/foramen, infraorbital foramen, and mental foramen) are equidistant from the midline in European and Hispanic populations. Previous studies suggest this surgical guideline is not applicable for all ethnicities; however, to our knowledge, no data have been published regarding the accuracy of this guideline pertaining to the Hispanic population. An experimental study was performed on 67 cadavers donated to the Human Anatomy Program at UT Health San Antonio. The supraorbital, infraorbital, and mental foramina were dissected and midline structures including the crista galli, internasal suture, anterior nasal spine, and mandibular symphysis were identified. The distance from each foramen to midline was recorded using a digital caliper. For all cadavers/ethnicities studied, the supraorbital, infraorbital, and mental foramina were 25.32 mm, 29.57 mm, and 25.55 mm to the midline, respectively. Thus, the infraorbital foramen is located significantly more lateral compared to the supraorbital (p < 0.0001) and mental foramina (p < 0.0001). After dividing the sample based on ethnicity, this relationship was also true for the European sample and tended to be true for the Hispanic sample. Significant anatomical variations exist in the current surgical guideline stating that the supraorbital foramen, infraorbital foramen, and mental foramen are equidistant from the midline. Clinicians may need to adjust their methodology during surgical procedures of the face in order to optimize patient care.
“Better red than dead”: Socialism in British Public Schools, 1900–1918
Authors: Makarchev Nikita , Xiao Chelsea C.
Published: June 2021

This paper examines socialism in Edwardian public schools. It concentrates on understanding their students’ responses to, and conceptions of, socialism’s core tenets. For, existing scholarship has depicted these Edwardian institutions as almost uniformly conservative and proficient in inculcating students with pro‐social hierarchy, anti‐social innovation views. Any ideological tensions, then, stemmed from the interaction of popular, conservative‐compliant, dogmas within school contexts: social Darwinism, imperialism, athleticism, muscular Christianity and so on. This paper, however, draws on new Eton College archive sources to enhance and complicate this view. It argues socialism captivated the students’ attention and garnered a strong supportive minority that, at times, advocated complete collective ownership. Moreover, the school administration showed tolerance to even the most outspoken socialists, and its non‐hegemonic, semi‐decentralized nature gave rise to local, independent sites of support. Accordingly, this research is important to understanding Edwardian public school ideologies and socialization processes. In wider terms, too, it casts insight on Edwardian socialism’s penetration into secondary education and inter‐class acceptance.
Muscle‐strengthening activities and risk of cardiovascular disease, type 2 diabetes, cancer and mortality: A review of prospective cohort studies
Authors: Giovannucci Edward L. , Rezende Leandro F. M. , Lee Dong Hoon
Published: June 2021

The benefits of aerobic moderate‐to‐vigorous physical activity (MVPA) on major non‐communicable diseases (NCDs) are well established. However, much less is known whether muscle‐strengthening activities (i.e., resistance/weight/strength training) confer similar benefits. Herein, we conducted a narrative literature review and summarized the existing evidence from large prospective cohort studies on muscle strengthening activities and risk of major chronic diseases and mortality in adults generally free of major NCDs at baseline. Current epidemiologic evidence suggests that engagement in muscle‐strengthening activities over 1–2 sessions (or approximately 60–150 min) per week was associated with reduced risk of cardiovascular disease (seven studies; approximately 20%–25% reduction), type 2 diabetes (four studies; approximately 30% reduction), cancer mortality (four studies; approximately 15%–20% reduction) as well as all‐cause mortality (six studies; approximately 20%–25% reduction). For diabetes, the risk appears to lower further with even higher levels of muscle‐strengthening activities, but some studies for cardiovascular and all‐cause mortality suggest a reversal whereby higher levels (≥2.5 h/week) have less benefit, or are even harmful, relative to lower levels of activity. The likely mechanisms contributing to a benefit include improvement in body composition, lipid profile, insulin resistance and inflammation. The evidence supports engaging in 1–2 sessions (up to 2.5 h) per week, preferably performed complementary to the recommended levels of aerobic MVPA. Although data are limited, caution is suggested for training exceeding 2.5 h per week. Further studies are required to better understand the influence of frequency, duration and intensity of muscle‐strengthening activities on major NCDs and mortality in diverse populations.
Effect of dietary protease supplementation on growth performance, water quality, blood parameters and intestinal morphology of Nile tilapia (Oreochromisniloticus)
Authors: Saleh Elham S. E. , Tawfeek Samar S. , Abdel‐Fadeel Asmaa A. A. , Abdel‐Daim Asmaa S. A. , Abdel‐Razik Abdel‐Razik H. , Youssef Ibrahim M. I.
Published: June 2021

This study was conducted to evaluate the effect of using protease in diets of Nile tilapia on growth performance, water quality, blood parameters and intestinal morphology. The cost of these diets and their return on fish performance was calculated. A total of 360 fish were randomly allocated into four groups with triplicates (30 fish per replicate). Four diets were formulated; two controls (without protease supplementation) and two experimental diets (supplemented with protease). The first control diet contained the normal protein requirement (30% CP; control +ve), while the second control had a low protein content (29% CP; control −ve). The third diet was supplemented with protease at a dose of 500 g/ton, and its CP content was reduced to 29.0%, by reducing the fish meal content. The fourth diet contained the same CP level as the first control (30%) and supplemented with 250 g protease per ton feed. The experiment lasted for 14 weeks. The results showed that body weight and length, weight gain, specific growth rate, feed intake and feed conversion efficiency in the control −ve group (low CP) supplemented with protease were similar (p > 0.05) to that of the control +ve with normal CP content. However, these performance parameters were lower (p < 0.05) in fish fed low CP diet without protease supplementation. Providing protease to the control +ve diet improved all measured performance indices. The ammonia and nitrite concentrations of the water were reduced (p < 0.05) in control −ve and protease‐supplemented groups. The height and width of intestinal villi were increased (p < 0.05) in fish fed diets containing protease. The inclusion of protease reduced the diet cost and also the feed cost of fish weight gain. In conclusion, supplementation of protease can improve the productive performance of fish, spare dietary protein and produce economical diets. Moreover, it can help in improving the water quality of fish via lowering the ammonia and nitrite contents, or through increasing the degradation of dietary protein.
A horizontally acquired Legionella genomic island encoding a LuxR type regulator and effector proteins displays variation in gene content and regulation
Authors: Linsky Marika , Segal Gil
Published: June 2021

The intracellular pathogen Legionella pneumophila translocates >300 effector proteins into host cells, many of which are regulated at the transcriptional level. Here, we describe a novel L. pneumophila genomic island, which undergoes horizontal gene transfer within the Legionella genus. This island encodes two Icm/Dot effectors: LegK3 and a previously uncharacterized effector which we named CegK3, as well as a LuxR type regulator, which we named RegK3. Analysis of this island in different Legionella species revealed a conserved regulatory element located upstream to the effector‐encoding genes in the island. Further analyses, including gene expression analysis, mutagenesis of the RegK3 regulatory element, controlled expression studies, and gel‐mobility shift assays, all demonstrate that RegK3 directly activates the expression levels of legK3 and cegK3 effector‐encoding genes. Additionally, the expression of all the components of the island is silenced by the Fis repressors. Comparison of expression profiles of these three genes among different Legionella species revealed variability in the activation levels mediated by RegK3, which were positively correlated with the Fis‐mediated repression. Furthermore, LegK3 and CegK3 effectors moderately inhibit yeast growth, and importantly, they have a strong synergistic inhibitory effect on yeast growth, suggesting these two effectors are not only co‐regulated but also might function together.
Characterizing clinical features and location‐specific gene expression profiles associated with pain burden in children with functional dyspepsia
Authors: Mokha Jasmeet S. , Hyams Jeffrey S. , Glidden Nicole C. , Balarezo Fabiola , Young Erin
Published: June 2021

Background

In children with functional dyspepsia (FD), genes involved in pain modulation may be differentially expressed contributing to chronic pain.

Methods

Children with suspected FD (cases) and known eosinophilic esophagitis (controls) undergoing esophagogastroduodenoscopy completed the Rome IV Diagnostic, Pain Burden and Frequency Severity‐Duration questionnaires. Two antral and two duodenal biopsies were collected and relative fold differences in gene expression for 84 pain‐associated genes compared to pain‐free controls were calculated.

Results

Sixty‐six subjects with FD (postprandial distress syndrome = 34, epigastric pain syndrome = 7, both = 25; 65% female; mean age 13.7 years) and 13 pain‐free controls (8% female; mean age 12.7) were studied. There were no significant differences in antral and duodenal eosinophilic counts or distribution between the pain and pain‐free groups. Pain severity and burden did not differ significantly between FD subgroups and neither measure significantly correlated with eosinophil counts in the antrum or duodenum. Analysis of 47 antral and 39 duodenal biospecimens revealed 5 candidate genes significantly associated with pain burden: antral EDN1, PTGES3 and duodenal HTR1A, P2Y1, SCN3A (p < 0.01). Subsequent stringent statistical analysis comparing those with significant pain versus no pain revealed antral PTGES3 and duodenal SCN3A were the highest priority candidate genes (p < 0.001).

Conclusions

Pain burden in pediatric FD may be linked to antral EDN1, PTGES3 and duodenal HTR1A, P2Y1, SCN3A differential expression. These genes are known to be involved in pain conduction, modulation, and neurotransmission, suggesting potential therapeutic targets for managing pain in FD.
Validation of secondary peristalsis classification using FLIP panometry in 741 subjects undergoing manometry
Authors: Carlson Dustin A. , Baumann Alexandra J. , Prescott Jacqueline E. , Donnan Erica N. , Yadlapati Rena , Khan Abraham , Gyawali C Prakash , Kou Wenjun , Kahrilas Peter J. , Pandolfino John E.
Published: June 2021

Background and Aims

This study aimed to systematically evaluate a classification scheme of secondary peristalsis using functional luminal imaging probe (FLIP) panometry through comparison with primary peristalsis on high‐resolution manometry (HRM).

Methods

706 adult patients that completed FLIP and HRM for primary esophageal motility evaluation and 35 asymptomatic volunteers (“controls”) were included. Secondary peristalsis, that is, contractile responses (CRs), was classified on FLIP panometry by the presence and pattern of contractility as normal (NCR), borderline (BCR), impaired/disordered (IDCR), absent (ACR), or spastic‐reactive (SRCR). Primary peristalsis on HRM was assessed according to the Chicago Classification.

Results

All 35 of the controls had antegrade contractions on FLIP panometry with either NCR (89%) or BCR (11%). The average percentages of normal swallows on HRM varied across contractile response patterns from 84% in NCR, 68% in BCR, 39% in IDCR, to 11% in ACR, as did the percentage of failed swallows on HRM: 4% in NCR, 12% in BCR, 36% in IDCR, and 79% in ACR. SRCR on FLIP panometry was observed in 18/57 (32%) patients with type III achalasia, 4/15 (27%) with distal esophageal spasm, and 7/15 (47%) with hypercontractile esophagus on HRM.

Conclusions

The FLIP panometry contractile response patterns reflect a pathophysiologic transition from normal to abnormal esophageal peristaltic function with shared features with primary peristaltic function/dysfunction on HRM. Thus, these patterns of the contractile response to distension can facilitate the evaluation of esophageal motility using FLIP panometry.
Biliary and duodenal complications after « en bloc» liver‐small bowel transplantation in children. A single center cohort study
Authors: Hervieux Erik , Capito Carmen , Franchi‐Abella Stéphanie , Pariente Danièle , Lozach Cécile , Sauvat Frédérique , Lacaille Florence , Chardot Christophe
Published: June 2021

Background

The technique of « en bloc» liver and small bowel transplantation (L‐BT) spares a biliary anastomosis, but does not protect against biliary complications. We analyze biliary and duodenal complications (BDC) in our pediatric series.

Methods

Between 1994 and 2020, 54 L‐BT were performed in 53 children. The procurement technique included in situ vascular dissection and pancreatic reduction to the head until 2009 (group A). Thereafter, the whole pancreas was recovered (group B).

Results

Nine BDCs occurred in 8/53 (15%) patients (7 in group A and 1 in group B): leak of the donor's duodenal stump (2), stenosis of the extra‐pancreatic bile duct (5), and intra‐pancreatic bile duct stenosis (2). Median delay for diagnosis of stricture was 8 months (4–168). Interventional radiology was successful in one child only, the others required reoperations. Two patients died, of biliary cirrhosis or cholangitis, 15‐month and 12‐year post‐L‐BT. One was listed and liver re‐transplanted 13 years post‐L‐BT. At last follow‐up, two patients only had normal liver tests and ultrasound.

Conclusion

BDC after L‐BT can cause severe morbidities. Pancreatic reduction might increase this risk. Early surgical complications or chronic pancreatic rejection might be co‐factors. Early diagnosis and treatment are key to the long‐term prognosis.
The current state of pediatric transplant hepatology fellowships: A survey of recent graduates
Authors: Feldman Amy G. , Squires James E. , Hsu Evelyn K. , Lobritto Steven , Mohammad Saeed ,   the SPLIT Education Committee, the Pediatric Transplant Hepatology Fellowship Program Directors
Published: June 2021

Background

The number of programs offering a PTH fellowship has grown rapidly over the last 10 years. This study aimed to describe the clinical, didactic, procedural, and research experiences of recent PTH fellowship graduates. In addition, we sought to understand graduates’ post‐fellowship professional responsibilities and their perception about the utility of the PTH fellowship.

Methods

An anonymous survey was distributed from February to October 2020 through REDCap to all recent graduates (2015–2019) of an ACGME‐approved PTH fellowship program. The survey consisted of 49 questions focused on the PTH fellowship experience. Results were summarized using descriptive statistics.

Results

Thirty‐eight of 43 graduates (88%) responded to the survey representing 12 PTH fellowship programs. The didactic experience varied; 97% received pathology lectures, 81% radiology lectures, 54% organ allocation lectures, 54% procedural lectures, 57% immunology lectures, and 43% live donation lectures. During the PTH fellowship, the majority of fellows performed >10 liver biopsies (82%) and >5 variceal bandings (58%); however, 63%, 32%, 8%, and 8% never performed paracentesis, variceal sclerotherapy, variceal banding, and liver biopsies, respectively. The majority of fellows (95%) completed a research project during PTH fellowship. Currently, 84% of graduates are employed at a transplant academic institution. All graduates recommended the fellowship.

Conclusions

There is variability in the didactic, clinical, and procedural training among PTH fellowship programs. Although uniformly viewed as a beneficial fellowship year, there is an opportunity to collaborate to create a more standardized training experience.
Pediatric heart‐liver transplant outcomes in the United States: A 25‐year National Cohort Study
Authors: Choudhry Swati , Dreyer William J. , Hope Kyle D. , Wang Yunfei , Spinner Joseph A. , Tunuguntla Hari P. , Cabrera Antonio G. , Price Jack F. , Denfield Susan W.
Published: June 2021

Background

Pediatric HLT remains uncommon in the United States and criteria for HLT are unclear. The objectives of this study were to review the indications, and outcomes of pediatric HLT.

Methods

Data from the Scientific Registry of Transplant Recipients heart and liver databases were used to identify 9245 pediatric isolated heart transplants (PHT), 14 134 pediatric isolated liver transplant (PLT), and 20 pediatric HLT (16 patients underwent sHLT [same organ donor] and four patients with a history of PHT followed by PLT [different organ donors]; age ≤21 years) between 1992 and 2017. Outcomes included patient survival, and 1‐year rates of acute heart and liver rejection.

Results

The median age for pediatric HLT was 15.6 (IQR: 10.5, 17.9) years, and included 12 males (12/20 = 60%). In the HLT group, the most common indication for HT was CHD (12/20 = 60%), and the most common indication for liver transplant was cirrhosis (9/20 = 45%). The 1, 3, and 5 year actuarial survival rates in pediatric simultaneous HLT recipients (n = 16) were 93%, 93%, and 93%, respectively, and was similar to isolated PHT alone (88%, 81%, and 75.5%, respectively and isolated PLT alone (84%, 82%, and 80%), respectively. There was no heart or liver rejection reported in the HLT group versus 9.9% in heart and 10.6% in liver transplant‐only groups, respectively.

Conclusion

Pediatric HLT is an uncommon but acceptable option for recipients with combined end‐organ failure, with intermediate survival outcomes comparable to those of single‐organ recipients.
Lack of persisting antibody in a post‐transplant patient after vaccine‐strain varicella
Authors: Tamura Daisuke , Kurosaki Masanori , Shinjoh Masayoshi , Nishimura Hidekazu , Yamagishi Hirokazu , Yamagata Takanori
Published: June 2021

Background

LAVV have historically been avoided in children after solid organ transplantation. However, it has been reported that post‐transplant, children without severe immunosuppression can generate anti‐varicella antibody after immunization but the duration of the response is not clear. Furthermore, the origin of the varicella virus in immunosuppressed patients who develop varicella after vaccination is often unclear.

Clinical progress

A female child received LAVV 30 months after a living donor liver transplant at the age of 2 months. Varicella rash appeared on the trunk 16 days after vaccination and gradually spread over the body. The patient was treated with intravenous acyclovir followed by oral therapy and recovered fully. The virus detected in blisters was derived from the vaccine‐type strain. Paired sera before and after the onset of varicella showed an increase in antibody titer. However, 2 years after onset, the antibody titer decreased to undetectable again.

Conclusions

This was an informative case of varicella due to vaccine strain attenuated virus. Antibody levels were not maintained over many years. Although varicella was caused by the vaccine‐type strain, repeated vaccinations may be necessary for post‐transplant patients who develop varicella.
Improving Funding Operations of Equity‐based Crowdfunding Platforms
Authors: Aggarwal Rohit , Lee Michael J , Osting Braxton , Singh Harpreet
Published: June 2021

Equity‐based crowdfunding platforms enable investors to come together to invest in startups and help lay‐investors to follow the lead of investors with good startup evaluation skills. Crowdfunding platforms often gather users’ inputs to evaluate investors and startups, but such inputs are quite noisy and often rely on past performance. Many investors with good evaluation skills do not have substantial past investment experience but still can lead investment rounds. This helps provide investment opportunities to lay‐investors who otherwise do not get to join investors with proven records. Without identifying such investors with potential, platforms lose the opportunity to put together investors to fund worthy startups and lose business. We develop a Bayesian model to address this problem and improve funding operations of equity‐based crowdfunding platforms. Specifically, the model helps platforms to better assess investors’ evaluation skills, identify lead investors for lay‐investors to follow, and increase funding opportunities on the platforms. To test the effectiveness of the proposed model, we gathered data from 319 actual investors listed on one of the largest crowdfunding platforms in the United States, picked startups randomly for investors to evaluate, and had investors evaluate startups in two ways—our approach and the conventional approach. We also discuss an extension of this Bayesian model that penalizes investors in case investors perform well by randomness. Furthermore, we used a Bayesian framework to help platforms better predict startup valuations accounting for investors’ evaluation skills.
Capital controls and the volatility of the renminbi covered interest deviation
Authors: Lin Zhitao , Chen Jinzhao , Qian Xingwang
Published: June 2021

This paper examines how capital controls affect the volatility of the renminbi (RMB) covered interest deviation (CID). We find that capital controls amplify the volatility of RMB CID and the amplification effect becomes more prominent in more flexible RMB exchange regimes. Capital controls influence the volatility of interest rate differential (IRD) and forward premium (FP), two components of CID, differently, particularly during the U.S. Fed's QE era. In addition, using an error correction model, we show that, while capital controls magnify both the short‐ and long‐run volatility of the CID and the IRD, they do not affect FP volatility.
Identification of a Novel Plasmid-Mediated Carbapenemase-Encoding Gene,
bla
VMB-2
, in Vibrio diabolicus
Authors: Liu Ming , Zhang Wenhui , Peng Kai , Wang Zhiqiang , Li Ruichao
Published: June 2021

Here, we characterized a carbapenem-resistant
Vibrio diabolicus
strain of shrimp origin with various experiments and bioinformatics analysis. A novel metallo-β-lactamase (MBL) gene,
bla
VMB-2
, that confers resistance to β-lactams, including meropenem and cephalosporins, was identified on a plasmid-borne composite transposon, IS
Shfr9
-IS
CR1
-
bla
VMB-2
-
bla
CARB-12
-
aadA1-
IS
Shfr9
, which is capable of generating a
bla
VMB-2
-bearing circular intermediate. IS
Shfr9
was found to be disseminated in multidrug-resistant (MDR) pathogens, arousing the concern of further transmission of a
bla
VMB-2
-bearing circular intermediate to clinical
Enterobacterales
strains via such insertion sequences, which warrants further investigations.
Diversity of Sequence Types and Impact of Fitness Cost among Carbapenem-Resistant Acinetobacter baumannii Isolates from Tripoli, Libya
Authors: Abou Fayad Antoine G. , Haraoui Louis-Patrick , Sleiman Ahmad , Jaafar Mohamad , Zorgani Abdulaziz , Matar Ghassan M. , Higgins Paul G.
Published: June 2021

We investigated the molecular epidemiology of 21 carbapenem-resistant
Acinetobacter baumannii
isolates from Libya and assessed their relative fitness. Core genome multilocus sequence typing (MLST) revealed five interhospital transmission clusters.
The AcrAB-TolC Efflux Pump Impacts Persistence and Resistance Development in Stationary-Phase Escherichia coli following Delafloxacin Treatment
Authors: Byrd Brandon A. , Zenick Blesing , Rocha-Granados Maria C. , Englander Hanna E. , Hare Patricia J. , LaGree Travis J. , DeMarco Angela M. , Mok Wendy W. K.
Published: June 2021

Bacteria have a repertoire of strategies to overcome antibiotics in clinical use, complicating our ability to treat and cure infectious diseases. In addition to evolving resistance, bacteria within genetically clonal cultures can undergo transient phenotypic changes and tolerate high doses of antibiotics.
In VitroProfiling of Antitubercular Compounds by Rapid, Efficient, and Nondestructive Assays Using Autoluminescent Mycobacterium tuberculosis
Authors: Shetye Gauri S. , Choi Kyung Bae , Kim Chang-Yub , Franzblau Scott G. , Cho Sanghyun
Published: June 2021

Anti-infective drug discovery is greatly facilitated by the availability ofin vitroassays that are more proficient at predicting the preclinical success of screening hits. Tuberculosis (TB) drug discovery is hindered by the relatively slow growth rate ofMycobacteriumand the use of whole-cell-basedin vitroassays that are inherently time-consuming, and for these reasons, rapid, noninvasive bioluminescence-based assays have been widely used in anti-TB drug discovery and development. In this study,in vitroassays that employ autoluminescentMycobacterium tuberculosis.
Checkerboard Analysis To Evaluate Synergistic Combinations of Existing Antifungal Drugs and Propylene Glycol Monocaprylate in Isolates from Recalcitrant Tinea Corporis and Cruris Patients Harboring Squalene Epoxidase Gene Mutation
Authors: Sardana Kabir , Gupta Aastha , Sadhasivam Suresh , Gautam R. K. , Khurana Ananta , Saini Swamini , Gupta Swati , Ghosh Shamik
Published: June 2021

Recalcitrant dermatophytic infections of the glabrous skin (tinea corporis/cruris/faciei) pose a huge challenge to health care systems. Combinations of oral and topical drugs may potentially improve cure rates, but the same has never been objectively assessed for this condition in laboratory or clinical studies.
β-Lactam-Induced Cell Envelope Adaptations, Not Solely Enhanced Daptomycin Binding, Underlie Daptomycin-β-Lactam Synergy in Methicillin-Resistant Staphylococcus aureus
Authors: Lew Cassandra , Mishra Nagendra N. , Bayer Arnold S. , Rose Warren E.
Published: June 2021

Methicillin-resistant
Staphylococcus aureus
(MRSA) is a serious clinical threat due to innate virulence properties, high infection rates, and the ability to develop resistance to multiple antibiotics, including the lipopeptide daptomycin (DAP). The acquisition of DAP resistance (DAP-R) in MRSA has been linked with several characteristic alterations in the cell envelope.
Identification of
qnrE3
and
qnrE4
, New Transferable Quinolone Resistance
qnrE
Family Genes Originating from Enterobacter mori and Enterobacter asburiae, Respectively
Authors: Wang Chen , Yin Mengyun , Zhang Xuefei , Guo Qinglan , Wang Minggui
Published: June 2021

The
qnrE
family was designated in 2017. To date, two
qnrE
alleles have been discovered that are carried by plasmids.
Synergistic Action between PfHsp90 Inhibitor and PfRad51 Inhibitor Induces Elevated DNA Damage Sensitivity in the Malaria Parasite
Authors: Tabassum Wahida , Singh Priyanka , Suthram Niranjan , Bhattacharyya Sunanda , Bhattacharyya Mrinal Kanti
Published: June 2021

The DNA recombinase Rad51 from the human malaria parasite
Plasmodium falciparum
has emerged as a potential drug target due to its central role in the homologous recombination (HR)-mediated double-strand break (DSB) repair pathway. Inhibition of the ATPase and strand exchange activity of
P. falciparum
Rad51 (PfRad51) by a small-molecule inhibitor, B02 [3-(phenylmethyl)-2-[(1E)-2-(3-pyridinyl)ethenyl]-4(3H)-quinazolinone], renders the parasite more sensitive to genotoxic agents.
Efficacy of Antistaphylococcal Lysin LSVT-1701 in Combination with Daptomycin in Experimental Left-Sided Infective Endocarditis Due to Methicillin-Resistant Staphylococcus aureus
Authors: Huang David B. , Gaukel Eric , Kerzee Nancy , Borroto-Esoda Katyna , Lowry Simon , Xiong Yan Q. , Abdelhady Wessam , Bayer Arnold S.
Published: June 2021

We utilized the rabbit model of aortic valve infective endocarditis to examine the combined efficacy of the lysin LSVT-1701 plus daptomycin. The combination of LSVT-1701 plus daptomycin was highly effective at reducing methicillin-resistant
Staphylococcus aureus
(MRSA) counts in target tissue.
Antibiotic Cycling Reverts Extensive Drug Resistance in Burkholderia multivorans
Authors: Kavanaugh L. G. , Harrison S. K. , Flanagan J. N. , Steck T. R.
Published: June 2021

Antibiotic collateral sensitivity, in which acquired resistance to one drug leads to decreased resistance to a different drug, occurs in
Burkholderia multivorans
. Here, we observed that treatment of extensively drug-resistant variants from a cystic fibrosis (CF) sputum sample with either meropenem or sulfamethoxazole-trimethoprim, depending on past resistance phenotypes, resulted in increased sensitivity to five different classes of antibiotics. We further identified mutations, including putative resistance-nodulation-division efflux pump regulators and uncharacterized pumps, that may be involved in this phenotype in
B. multivorans
.
Efflux Pump Overexpression Profiling in Acinetobacter baumannii and Study of New 1-(1-Naphthylmethyl)-Piperazine Analogs as Potential Efflux Inhibitors
Authors: Choquet Morgane , Lohou Elodie , Pair Etienne , Sonnet Pascal , Mullié Catherine
Published: June 2021

Overexpression of efflux pumps extruding antibiotics currently used for the treatment of
Acinetobacter baumannii
infections has been described as an important mechanism causing antibiotic resistance. The first aim of this work was to phenotypically evaluate the overexpression of efflux pumps on a collection of 124 ciprofloxacin-resistant
A. baumannii
strains.
Sigmoid
E
max
Modeling To Define the Fixed Concentration of Enmetazobactam for MIC Testing in Combination with Cefepime
Authors: Knechtle Philipp , Shapiro Stuart , Morrissey Ian , De Piano Cyntia , Belley Adam
Published: June 2021

The use of carbapenem antibiotics to treat infections caused by
Enterobacterales
expressing increasingly aggressive extended-spectrum β-lactamases (ESBLs) has contributed to the emergence of carbapenem resistance. Enmetazobactam is a novel ESBL inhibitor being developed in combination with cefepime as a carbapenem-sparing option for infections caused by ESBL-producing
Enterobacterales
.
Polymyxin B Pharmacodynamics in the Hollow-Fiber Infection Model: What You See May Not Be What You Get
Authors: Maynard Michael , Drusano G. L. , Vicchiarelli Michael , Liu Weiguo , Myrick Jenny , Nole Jocelyn , Duncanson Brandon , Brown David , Louie Arnold
Published: June 2021

Dose range studies for polymyxin B (PMB) regimens of 0.75 to 12 mg/kg given every 12 h (q12h) were evaluated for bacterial killing and resistance prevention against an AmpC-overexpressing
Pseudomonas aeruginosa
and a
bla
KPC-3
-harboring
Klebsiella pneumoniae
in 10-day
in vitro
hollow-fiber models. An exposure-response was observed.
Hepatitis C Virus Protease Inhibitors Show Differential Efficacy and Interactions with Remdesivir for Treatment of SARS-CoV-2
In Vitro
Authors: Gammeltoft Karen A. , Zhou Yuyong , Duarte Hernandez Carlos R. , Galli Andrea , Offersgaard Anna , Costa Rui , Pham Long V. , Fahnøe Ulrik , Feng Shan , Scheel Troels K. H. , Ramirez Santseharay , Bukh Jens , Gottwein Judith M.
Published: June 2021

Antivirals targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could improve treatment of COVID-19. We evaluated the efficacy of clinically relevant hepatitis C virus (HCV) NS3 protease inhibitors (PIs) against SARS-CoV-2 and their interactions with remdesivir, the only direct-acting antiviral approved for COVID-19 treatment.
A Bioengineered Nisin Derivative To Control Streptococcus uberis Biofilms
Authors: Pérez-Ibarreche Mariana , Field Des , Ross R. Paul , Hill Colin
Published: June 2021

One of the four most prevalent species of bovine mastitis-causing pathogens is
S. uberis.
Its ability to form biofilms confers on the bacteria greater resistance to antibiotics, requiring higher doses to be more effective. In a bid to limit antibiotic resistance development, the need for alternative antimicrobials is paramount.
Deciphering the Regulation of the Mannitol Operon Paves the Way for Efficient Production of Mannitol in Lactococcus lactis
Authors: Xiao Hang , Bang-Berthelsen Claus Heiner , Jensen Peter Ruhdal , Solem Christian
Published: June 2021

Lactococcus lactis
is the most studied species of the lactic acid bacteria, and it is widely used in various food fermentations. To date, there have been several attempts to persuade
L. lactis
to produce mannitol, a sugar alcohol with important therapeutic and food applications.
Clinical Laboratory Biosafety Gaps: Lessons Learned from Past Outbreaks Reveal a Path to a Safer Future
Authors: Cornish Nancy E. , Anderson Nancy L. , Arambula Diego G. , Arduino Matthew J. , Bryan Andrew , Burton Nancy C. , Chen Bin , Dickson Beverly A. , Giri Judith G. , Griffith Natasha K. , Pentella Michael A. , Salerno Reynolds M. , Sandhu Paramjit , Snyder James W. , Tormey Christopher A. , Wagar Elizabeth A. , Weirich Elizabeth G. , Campbell Sheldon
Published: June 2021

Patient care and public health require timely, reliable laboratory testing. However, clinical laboratory professionals rarely know whether patient specimens contain infectious agents, making ensuring biosafety while performing testing procedures challenging.
Calprotectin (S100A8/A9) Is an Innate Immune Effector in Experimental Periodontitis
Authors: Johnstone Karen F. , Wei Yuping , Bittner-Eddy Peter D. , Vreeman Gerrit W. , Stone Ian A. , Clayton Jonathan B. , Reilly Cavan S. , Walbon Travis B. , Wright Elisa N. , Hoops Susan L. , Boyle William S. , Costalonga Massimo , Herzberg Mark C.
Published: June 2021

Upregulated in inflammation, calprotectin (complexed S100A8 and S100A9; S100A8/A9) functions as an innate immune effector molecule, promoting inflammation, and also as an antimicrobial protein. We hypothesized that antimicrobial S100A8/A9 would mitigate change to the local microbial community and promote resistance to experimental periodontitisin vivo.
Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) Contributes to Bordetella pertussis Inflammatory Pathology
Authors: Gallop Danisha , Scanlon Karen M. , Ardanuy Jeremy , Sigalov Alexander B. , Carbonetti Nicholas H. , Skerry Ciaran
Published: June 2021

Whooping cough (pertussis) is a severe pulmonary infectious disease caused by the bacteria
Bordetella pertussis
. Pertussis infects an estimated 24 million people annually, resulting in >150,000 deaths.
The Vibrio cholerae Type Six Secretion System Is Dispensable for Colonization but Affects Pathogenesis and the Structure of Zebrafish Intestinal Microbiome
Authors: Breen Paul , Winters Andrew D. , Theis Kevin R. , Withey Jeffrey H.
Published: June 2021

Zebrafish (
Danio rerio
) are an attractive model organism for a variety of scientific studies, including host-microbe interactions. The organism is particularly useful for the study of aquatic microbes that can colonize vertebrate hosts, including
Vibrio cholerae
, an intestinal pathogen.
V. cholerae
must colonize the intestine of an exposed host for pathogenicity to occur.
Immune Inhibitor A Metalloproteases Contribute to Virulence in
Bacillus
Endophthalmitis
Authors: Livingston Erin T. , Mursalin Md Huzzatul , Coburn Phillip S. , Astley Roger , Miller Frederick C. , Amayem Omar , Lereclus Didier , Callegan Michelle C.
Published: June 2021

Endophthalmitis is a devastating infection that can cause blindness. Over half of
Bacillus
endophthalmitis cases result in significant loss of useful vision.
Bacillus
produces many virulence factors that may contribute to retinal damage and robust inflammation.
The Murine Neonatal Fc Receptor Is Required for Transport of Immunization-Induced C. difficile-Specific IgG to the Gut and Protection against Disease but Does Not Affect Disease Susceptibility
Authors: Amadou Amani Souwelimatou , Lang Gillian A. , Ballard Jimmy D. , Lang Mark L.
Published: June 2021

The pathology associated with
Clostridioides difficile
disease is caused in large part by TcdB, an intracellular bacterial toxin that inactivates small GTPases. Despite
C. difficile
causing enteric disease, antitoxin IgG is a clear correlate of protection against infection-associated pathology.
Macrophage-Produced Peroxynitrite Induces Antibiotic Tolerance and Supersedes Intrinsic Mechanisms of Persister Formation
Authors: Beam Jenna E. , Wagner Nikki J. , Shook John C. , Bahnson Edward S. M. , Fowler Vance G. , Rowe Sarah E. , Conlon Brian P.
Published: June 2021

Staphylococcus aureus
is a leading human pathogen that frequently causes chronic and relapsing infections. Antibiotic-tolerant persister cells contribute to frequent antibiotic failure in patients.
Nontuberculous Mycobacteria, Macrophages, and Host Innate Immune Response
Authors: Shamaei Masoud , Mirsaeidi Mehdi
Published: June 2021

Although nontuberculous mycobacteria (NTM) are considered opportunistic infections, incidence and prevalence of NTM infection are increasing worldwide becoming a major public health threat. Innate immunity plays an essential role in mediating the initial host response against these intracellular bacteria. Specifically, macrophages phagocytose and eliminate NTM and act as antigen-presenting cells, which trigger downstream activation of cellular and humoral adaptive immune responses.
Identification and Enzymatic Analysis of an Archaeal ATP-Dependent Serine Kinase from the Hyperthermophilic Archaeon
Staphylothermus marinus
Authors: Mori Yasunobu , Kawamura Hiroki , Sato Takaaki , Fujita Takayuki , Nagata Ryuhei , Fujihashi Masahiro , Miki Kunio , Atomi Haruyuki
Published: June 2021

Homologs of the ADP-dependent Ser kinase from the archaeon
Thermococcus kodakarensis
(
Tk
-SerK) include representatives from all three domains of life. The results of this study show that even homologs from the archaeal order
Desulfurococcales
, which are the most structurally related to the ADP-dependent Ser kinases from the
Thermococcales
, are Ser kinases that utilize ATP, and in at least some cases inorganic polyphosphates, as the phosphate donor.
Glucose Decoration on Wall Teichoic Acid Is Required for Phage Adsorption and InlB-Mediated Virulence in Listeria ivanovii
Authors: Sumrall Eric T. , Schneider Stephan R. , Boulos Samy , Loessner Martin J. , Shen Yang
Published: June 2021

Listeria ivanovii
is a Gram-positive bacterial pathogen known to cause enteric infection in rodents and ruminants and occasionally in immunocompromised humans. Recent investigations revealed that in its better-known cousin
Listeria monocytogenes
, strains develop resistance to bacteriophage attack due to loss of glycosylated surface receptors, which subsequently results in disconnection of one of the bacterium's major virulence factors, InlB.
GraS Sensory Activity in Staphylococcus epidermidis Is Modulated by the “Guard Loop” of VraG and the ATPase Activity of VraF
Authors: Costa Stephen K. , Cho Junho , Cheung Ambrose L.
Published: June 2021

Staphylococcus epidermidis
has become an important opportunistic pathogen that is responsible for nosocomial and device-related infections that account for considerable morbidity worldwide. A thorough understanding of the mechanisms that enable
S. epidermidis
to colonize human skin successfully is essential for the development of alternative treatment strategies and prophylaxis.
Cautionary notes on the use of arabinose- and rhamnose-inducible expression vectors in
Pseudomonas aeruginosa
Authors: Williams McMackin Emily A. , Corley Jodi M. , Karash Sardar , Marden Jeremiah , Wolfgang Matthew C. , Yahr Timothy L.
Published: June 2021

The
Pseudomonas aeruginosa
virulence factor regulator (Vfr) is a cAMP-responsive transcription factor homologous to the
Escherichia coli
cyclic AMP receptor protein (CRP). Unlike CRP, which plays a central role in
E. coli
energy metabolism and catabolite repression, Vfr is primarily involved in the control of
P. aeruginosa
virulence factor expression. Expression of the Vfr regulon is controlled at the level of
vfr
transcription, Vfr translation, cAMP synthesis, and cAMP degradation. While investigating mechanisms that regulate Vfr translation, we placed
vfr
transcription under the control of the
rhaBp
rhamnose-inducible promoter system (designated P
Rha
) and found that P
Rha
promoter activity was highly dependent upon
vfr
. Vfr-dependence was also observed for the
araBp
arabinose-inducible promoter (designated P
BAD
). The observation of Vfr-dependence was not entirely unexpected. Both promoters are derived from
E. coli
where maximal promoter activity is dependent upon CRP. Like CRP, we found that Vfr directly binds to promoter probes derived from the P
Rha
and P
BAD
promoters in vitro. Because Vfr-cAMP activity is highly integrated into numerous global regulatory systems including c-di-GMP signaling, the Gac/Rsm system, MucA/AlgU/AlgZR signaling, and Hfq/sRNAs, potential exists for significant variability in P
Rha
and P
BAD
promoter activity in a variety of genetic backgrounds, and use of these promoter systems in
P. aeruginosa
should be employed with caution.

SIGNIFICANCE

Heterologous gene expression and complementation is a valuable and widely-utilized tool in bacterial genetics. The arabinose-inducible P

araBAD

(P
BAD
) and rhamnose-inducible P

rhaBAD

(P
Rha
) promoter systems are commonly used in
P. aeruginosa
genetics and prized for the tight control and dynamic expression ranges that can be achieved. In this study we demonstrate that the activity of both promoters is dependent upon the cAMP-dependent transcription factor Vfr. While this poses an obvious problem for use in a
vfr
mutant background, the issue is more pervasive considering that
vfr
transcription/synthesis and cAMP homeostasis are highly integrated into the cellular physiology of the organism and influenced by numerous global regulatory systems. Fortunately, the synthetic P
Tac
promoter is not subject to Vfr regulatory control.