bluuebunny/crossref_metadata_2025 huggingface dataset:
Ceftazidime, Carbapenems, or Piperacillin-tazobactam as Single Definitive Therapy for Pseudomonas aeruginosa Bloodstream Infection: A Multisite Retrospective Study
Authors: Babich Tanya , Naucler Pontus , Valik John Karlsson , Giske Christian G , Benito Natividad , Cardona Ruben , Rivera Alba , Pulcini Celine , Abdel Fattah Manal , Haquin Justine , Macgowan Alasdair , Grier Sally , Gibbs Julie , Chazan Bibiana , Yanovskay Anna , Ben Ami Ronen , Landes Michal , Nesher Lior , Zaidman-Shimshovitz Adi , McCarthy Kate , Paterson David L , Tacconelli Evelina , Buhl Michael , Mauer Susanna , Rodriguez-Bano Jesus , Morales Isabel , Oliver Antonio , Ruiz De Gopegui Enrique , Cano Angela , Machuca Isabel , Gozalo-Marguello Monica , Martinez Martinez Luis , Gonzalez-Barbera Eva M , Alfaro Iris Gomez , Salavert Miguel , Beovic Bojana , Saje Andreja , Mueller-Premru Manica , Pagani Leonardo , Vitrat Virginie , Kofteridis Diamantis , Zacharioudaki Maria , Maraki Sofia , Weissman Yulia , Paul Mical , Dickstein Yaakov , Leibovici Leonard , Yahav Dafna
Published: July 2019

Background

The optimal antibiotic regimen for Pseudomonas aeruginosa bacteremia is controversial. Although β-lactam monotherapy is common, data to guide the choice between antibiotics are scarce. We aimed to compare ceftazidime, carbapenems, and piperacillin-tazobactam as definitive monotherapy.

Methods

A multinational retrospective study (9 countries, 25 centers) including 767 hospitalized patients with P. aeruginosa bacteremia treated with β-lactam monotherapy during 2009–2015. The primary outcome was 30-day all-cause mortality. Univariate and multivariate, including propensity-adjusted, analyses were conducted introducing monotherapy type as an independent variable.

Results

Thirty-day mortality was 37/213 (17.4%), 42/210 (20%), and 55/344 (16%) in the ceftazidime, carbapenem, and piperacillin-tazobactam groups, respectively. Type of monotherapy was not significantly associated with mortality in either univariate, multivariate, or propensity-adjusted analyses (odds ratio [OR], 1.14; 95% confidence interval [CI], 0.52–2.46, for ceftazidime; OR, 1.3; 95% CI, 0.67–2.51, for piperacillin-tazobactam, with carbapenems as reference in propensity adjusted multivariate analysis; 542 patients). No significant difference between antibiotics was demonstrated for clinical failure, microbiological failure, or adverse events. Isolation of P. aeruginosa with new resistance to antipseudomonal drugs was significantly more frequent with carbapenems (36/206 [17.5%]) versus ceftazidime (25/201 [12.4%]) and piperacillin-tazobactam (28/332 [8.4%] (P = .007).

Conclusions

No significant difference in mortality, clinical, and microbiological outcomes or adverse events was demonstrated between ceftazidime, carbapenems, and piperacillin-tazobactam as definitive treatment of P. aeruginosa bacteremia. Higher rates of resistant P. aeruginosa after patients were treated with carbapenems, along with the general preference for carbapenem-sparing regimens, suggests using ceftazidime or piperacillin-tazobactam for treating susceptible infection.
Is a New Cold War Inevitable? Chinese Perspectives on US–China Strategic Competition
Authors: Zhao Minghao
Published: July 2019

In recent years, Chinese scholars and policy elites have discussed the ever intensifying strategic competition between the United States and China and its multifaceted implications for Chinese foreign policy. Some even worry about the possibility of a new Cold War between the United States and China. This article aims to offer an analysis of Chinese perspectives on US–China strategic competition. In the view of most Chinese observers, US–China strategic competition is inevitable because China is closing the national power gap between itself and the United States, while the latter resolutely upholds its global primacy. Other factors, including ideological disagreements, may fuel the major power competition that has extended to most aspects of US–China relations. Chinese observers believe that economic and technological rivalry between the United States and China has heightened and that the Western Pacific is the focal point of US–China strategic competition. Meanwhile, certain Chinese scholars attach greater importance to US–China competition over international prestige and leadership. However, Chinese analysts are not overly pessimistic about the prospects for US–China relations and have raised policy recommendations geared to managing US–China strategic competition and restoring a new equilibrium between the two major powers.
Development of molecular markers associated with resistance to Meloidogyne incognita by performing quantitative trait locus analysis and genome-wide association study in sweetpotato
Authors: Sasai Rumi , Tabuchi Hiroaki , Shirasawa Kenta , Kishimoto Kazuki , Sato Shusei , Okada Yoshihiro , Kuramoto Akihide , Kobayashi Akira , Isobe Sachiko , Tahara Makoto , Monden Yuki
Published: July 2019

The southern root-knot nematode, Meloidogyne incognita, is a pest that decreases yield and the quality of sweetpotato [Ipomoea batatas (L.) Lam.]. There is a demand to produce resistant cultivars and develop DNA markers to select this trait. However, sweetpotato is hexaploid, highly heterozygous, and has an enormous genome (∼3 Gb), which makes genetic linkage analysis difficult. In this study, a high-density linkage map was constructed based on retrotransposon insertion polymorphism, simple sequence repeat, and single nucleotide polymorphism markers. The markers were developed using F1 progeny between J-Red, which exhibits resistance to multiple races of M. incognita, and Choshu, which is susceptible to multiple races of such pest. Quantitative trait locus (QTL) analysis and a genome-wide association study detected highly effective QTLs for resistance against three races, namely, SP1, SP4, and SP6-1, in the Ib01-6 J-Red linkage group. A polymerase chain reaction marker that can identify genotypes based on single nucleotide polymorphisms located in this QTL region can discriminate resistance from susceptibility in the F1 progeny at a rate of 70%. Thus, this marker could be helpful in selecting sweetpotato cultivars that are resistant to multiple races of M. incognita.
Nephromyces represents a diverse and novel lineage of the Apicomplexa that has retained apicoplasts
Authors: Muñoz-Gómez Sergio A , Durnin Keira , Eme Laura , Paight Christopher , Lane Christopher E , Saffo Mary B , Slamovits Claudio H
Published: July 2019

A most interesting exception within the parasitic Apicomplexa is Nephromyces, an extracellular, probably mutualistic, endosymbiont found living inside molgulid ascidian tunicates (i.e., sea squirts). Even though Nephromyces is now known to be an apicomplexan, many other questions about its nature remain unanswered. To gain further insights into the biology and evolutionary history of this unusual apicomplexan, we aimed to (1) find the precise phylogenetic position of Nephromyces within the Apicomplexa, (2) search for the apicoplast genome of Nephromyces, and (3) infer the major metabolic pathways in the apicoplast of Nephromyces. To do this, we sequenced a metagenome and a metatranscriptome from the molgulid renal sac, the specialized habitat where Nephromyces thrives. Our phylogenetic analyses of conserved nucleus-encoded genes robustly suggest that Nephromyces is a novel lineage sister to the Hematozoa, which comprises both the Haemosporidia (e.g., Plasmodium) and the Piroplasmida (e.g., Babesia and Theileria). Furthermore, a survey of the renal sac metagenome revealed 13 small contigs that closely resemble the genomes of the non-photosynthetic reduced plastids, or apicoplasts, of other apicomplexans. We show that these apicoplast genomes correspond to a diverse set of most closely related but genetically divergent Nephromyces lineages that co-inhabit a single tunicate host. In addition, the apicoplast of Nephromyces appears to have retained all biosynthetic pathways inferred to have been ancestral to parasitic apicomplexans. Our results shed light on the evolutionary history of the only probably mutualistic apicomplexan known, Nephromyces, and provide context for a better understanding of its life style and intricate symbiosis.
Effects of Clostridium butyricum and Enterococcus faecalis on growth performance, intestinal structure, and inflammation in lipopolysaccharide-challenged weaned piglets
Authors: Wang Kangli , Chen Guangyong , Cao Guangtian , Xu Yinglei , Wang Yongxia , Yang Caimei
Published: July 2019

This study was conducted to investigate the effects of Clostridium butyricum and Enterococcus faecalis on growth performance, immune function, inflammation-related pathways, and microflora community in weaned piglets challenged with lipopolysaccharide (LPS). One hundred and eighty 28-d-old weaned piglets were randomly divided into 3 treatments groups: piglets fed with a basal diet (Con), piglets fed with a basal diet containing 6 × 109 CFU C. butyricum·kg−1 (CB), and piglets fed with a basal diet containing 2 × 1010 CFU E. faecali·kg−1 (EF). At the end of trial, 1 pig was randomly selected from for each pen (6 pigs per treatment group) and these 18 piglets were orally challenged with LPS 25 μg·kg−1 body weight. The result showed that piglets fed C. butyricum and E. faecalis had greater final BW compared with the control piglets (P < 0.05). The C. butyricum and E. faecalis fed piglets had lower levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), IL-1β, tumor inflammatory factor-α (TNF-α), and had greater level of serum interferon-γ (IFN-γ) than control piglets at 1.5 and 3 h after injection with LPS (P < 0.05). Furthermore, piglets in the C. butyricum or E. faecalis treatment groups had a greater ratio of jejunal villus height to crypt depth (V/C) compared with control piglets after challenge with LPS for 3 h (P < 0.05). Compared with the control treatment, the CB and EF treatments significantly decreased the expression of inflammation-related pathway factors (TLR4, MyD88, and NF-κB) after challenge with LPS for 3 h (P < 0.05). High-throughput sequencing revealed that C. butyricum and E. faecalis modulated bacterial diversity in the colon. The species richness and alpha diversity (Shannon) of bacterial samples in CB or EF piglets challenged with LPS were higher than those in LPS-challenged control piglets. Furthermore, the relative abundance of Bacteroidales-Rikenellanceae in the CB group was higher than that in the control group (P < 0.05), whereas EF piglets had a higher relative abundance of Lactobacillus amylovorus and Lactobacillus gasseri (P < 0.05). In conclusion, dietary supplementation with C. butyricum or E. faecalis promoted growth performance, improved immunity, relieved intestinal villus damage and inflammation, and optimized the intestinal flora in LPS-challenged weaned piglets.
Eroded GDA coil surgically managed with Roux-en-Y reconstruction
Authors: Iannamorelli Michael , Bowling Adam , Semaan Elie
Published: July 2019

Here, we describe the case of a 56-year-old African American male who initially presented to the emergency department with 2 days of abdominal cramping, epigastric pain, loss of consciousness, melena and hematochezia. He underwent coil embolization of his gastroduodenal artery by the interventional radiology team after it was felt he was a high risk for rebleed. The patient then returned to the hospital with 3 weeks of epigastric pain, lightheadedness and melanotic stool. An upper endoscopy revealed a metallic coil embedded into the duodenal bulb. This coil was believed to be from prior embolization to the gastroduodenal artery. The patient then underwent a laparoscopic distal gastrectomy and partial duodenectomy with antecolic antegastric Roux-en-Y reconstruction bypassing the area where erosion occurred.
Correlations between supermassive black holes, hot atmospheres, and the total masses of early-type galaxies
Authors: Lakhchaura K , Truong N , Werner N
Published: July 2019

We present a study of relations between the masses of the central supermassive black holes (SMBHs) and the atmospheric gas temperatures and luminosities measured within a range of radii between Re and 5Re, for a sample of 47 early-type galaxies observed by the Chandra X-ray Observatory. We report the discovery of a tight correlation between the atmospheric temperatures of the brightest cluster/group galaxies (BCGs) and their central SMBH masses. Furthermore, our hydrostatic analysis reveals an approximately linear correlation between the total masses of BCGs (Mtot) and their central SMBH masses (MBH). State-of-the-art cosmological simulations show that the SMBH mass could be determined by the binding energy of the halo through radiative feedback during the rapid black hole growth by accretion, while for the most massive galaxies mergers are the chief channel of growth. In the scenario of a simultaneous growth of central SMBHs and their host galaxies through mergers, the observed linear correlation could be a natural consequence of the central limit theorem.
Staufen1 and UPF1 exert opposite actions on the replacement of the nuclear cap-binding complex by eIF4E at the 5′ end of mRNAs
Authors: Jeong Kwon , Ryu Incheol , Park Joori , Hwang Hyun Jung , Ha Hongseok , Park Yeonkyoung , Oh Sang Taek , Kim Yoon Ki
Published: July 2019

Newly synthesized mRNAs are exported from the nucleus to cytoplasm with a 5′-cap structure bound by the nuclear cap-binding complex (CBC). During or after export, the CBC should be properly replaced by cytoplasmic cap-binding protein eIF4E for efficient protein synthesis. Nonetheless, little is known about how the replacement takes place. Here, we show that double-stranded RNA-binding protein staufen1 (STAU1) promotes efficient replacement by facilitating an association between the CBC–importin α complex and importin β. Our transcriptome-wide analyses and artificial tethering experiments also reveal that the replacement occurs more efficiently when an mRNA associates with STAU1. This event is inhibited by a key nonsense-mediated mRNA decay factor, UPF1, which directly interacts with STAU1. Furthermore, we find that cellular apoptosis that is induced by ionizing radiation is accompanied by inhibition of the replacement via increased association between STAU1 and hyperphosphorylated UPF1. Altogether, our data highlight the functional importance of STAU1 and UPF1 in the course of the replacement of the CBC by eIF4E, adding a previously unappreciated layer of post-transcriptional gene regulation.
Impact of Extent of Resection on Incidence of Postoperative Complications in Patients With Glioblastoma
Authors: Laurent Dimitri , Freedman Rachel , Cope Logan , Sacks Patricia , Abbatematteo Joe , Kubilis Paul , Bova Frank , Rahman Maryam
Published: July 2019

BACKGROUND

Extent of resection (EOR) is well established as correlating with overall survival in patients with glioblastoma (GBM). The impact of EOR on reported quality metrics such as patient safety indicators (PSIs) and hospital-acquired conditions (HACs) is unknown.

OBJECTIVE

To perform a retrospective study to evaluate possible associations between EOR and the incidence of PSIs and HACs.

METHODS

We queried all patients diagnosed with GBM who underwent surgical resection at our institution between January 2011 and May 2017. Pre- and postoperative magnetic resonance images were analyzed for EOR. Each chart was reviewed to determine the incidence of PSIs and HACs.

RESULTS

A total of 284 patients met the inclusion criteria. EOR ranged from 39.00 to 100%, with a median of 99.84% and a mean of 95.7%. There were 16 PSI, and 13 HAC, events. There were no significant differences in the rates of PSIs or HACs when compared between patients stratified by gross total resection (EOR ≥ 95%) and subtotal resection (EOR < 95%). The odds of encountering a PSI or HAC were 2.5 times more likely in the subtotal resection group compared to the gross total resection group (P = .58). After adjusting for confounders, the odds of encountering a PSI or HAC in the subtotal resection group were 3.9 times greater than for the gross total resection group (P < .05).

CONCLUSION

Gross total resection of GBM is associated with a decreased incidence of PSIs and HACs, as compared to subtotal resection.
Knowledge and Practices of Physicians and Nurses Related to Urine Cultures in Catheterized Patients: An Assessment of Adherence to IDSA Guidelines
Authors: Advani Sonali D , Gao Catherine A , Datta Rupak , Sann Lawrence , Smith Cindy , Leapman Michael S , Hittelman Adam B , Sabetta James , Dembry Louise-Marie , Martinello Richard A , Juthani-Mehta Manisha
Published: July 2019

Background

A positive urine culture often drives initiation of antimicrobials even in the absence of symptoms. Our objectives were to evaluate the knowledge and practice patterns related to ordering urine cultures in patients with indwelling urinary catheters.

Methods

We performed chart reviews of catheter-associated urinary tract infections (CAUTIs) at our academic health care system between October 1, 2015, and September 30, 2017, to assess practice patterns related to the assessment of potential CAUTIs. Following this, we surveyed physicians and nurses about indications for ordering urine cultures in catheterized patients between January 11, 2018, and April 17, 2018. The accuracy of these indications was assessed based on Infectious Diseases Society of America CAUTI and asymptomatic bacteriuria guidelines.

Results

On chart review, we identified 184 CAUTIs in 2 years. In 159 episodes (86%), urine cultures were ordered inappropriately. In 114 episodes (62%), CAUTI criteria were met by “pan-culturing” rather than symptom-directed testing. Twenty cases (11%) experienced partial or delayed management of other infections, drug adverse events, and Clostridioides difficile infections (CDIs). On our survey, we received 405 responses, for a response rate of 45.3%. Mean scores varied by occupation and level of training. Nurses were more likely than physicians to consider change in appearance (61% vs 23%; P < .05) and odor (74% vs 42%; P < .05) of urine as indications to order urine cultures.

Conclusions

Our data reveal specific knowledge gaps among physicians and nurses related to ordering urine cultures in catheterized patients. The practice of pan-culturing and inappropriate urine culture orders may contribute to overdiagnosis of surveillance CAUTIs, delay in diagnosis of alternative infections, and excess CDIs.
Centralized Communication of Blood Culture Results Leveraging Antimicrobial Stewardship and Rapid Diagnostics
Authors: Shemanski Shelby , Bennett Nicholas , Essmyer Cynthia , Kennedy Kevin , Buchanan Donna M , Warnes Andrew , Boyd Sarah
Published: July 2019

Objective

This study aimed to determine if integrating antimicrobial stewardship program (ASP) personnel with rapid diagnostic testing resulted in improved outcomes for patients with positive blood cultures.

Method

Beginning in 2016, Saint Luke’s Health System (SLHS) implemented a new process where all positive blood cultures were communicated to ASP personnel or SLHS pharmacy staff. Pharmacists then became responsible for interpreting results, assessing patient specific information, and subsequently relaying culture and treatment information to providers. This was a multisite, pre-post, quasi-experimental study (Pre: August to December 2014; Post: August to December 2016). Patients 18 years of age and older with a positive blood culture during admission were included (2014, n = 218; 2016, n = 286). Coprimary outcomes of time to optimal and appropriate therapy were determined from time of culture positivity via gram stain. Secondary outcomes focused on clinical, process, and fiscal endpoints. A pre-post intervention physician survey was conducted to assess the impact on antimicrobial decision making and perceived effect on patient outcomes.

Results

There was no difference in time to appropriate therapy groups (P = .079). Time to optimal therapy was 9.2 hours shorter in 2016 (P = .004). Provider surveys indicated the process improved communication among clinicians and facilitated a shared decision-making process with a perceived improvement in patient care.

Conclusions

An ASP-led blood culture communication process for patients with positive blood cultures was shown to improve time to optimal therapy, support physicians in their decision making on critical lab data, and improve the care for hospitalized patients.
Brucellosis Presenting as Cholecystitis: A Case Report and Literature Review
Authors: Speiser Lisa , Hsieh Lanny , Huang Susan S , Bittencourt Cassiana , Forthal Donald
Published: July 2019

Brucellosis is a zoonotic disease endemic to much of the world. It most often presents with nonspecific symptoms and is a well known cause of undulant fever. Focal forms occur less frequently, with osteoarticular complications being the most common. In this study, we describe a rare case of brucellosis presenting as cholecystitis.
The balancing role of evaluation mechanisms in organizational governance—The case of publicly funded research institutions
Authors: Luo Junwen , Ordóñez-Matamoros Gonzalo , Kuhlmann Stefan
Published: July 2019

Evaluation taking place within publicly funded research institutions (PRIs) has been practiced as a useful instrument to justify PRIs’ public funding and to provide evidence for their internal decision-making. The role of evaluation in organizational governance is well-acknowledged as being important in PRIs’ management practices. However, it has not attracted much attention from research evaluation scholars. In this article, we propose that evaluation mechanisms perform a balancing role in organizational governance of PRIs with respect to three main aspects: strategy, funding, and operation, where governance tensions often occur between different stakeholders. This research attempts to contribute to a better understanding of why and how evaluation helps to deal with such governance tensions by looking at three case studies, namely the Max Planck Society (MPG), the Helmholtz Association (HGF), both in Germany, and the Chinese Academy of Sciences (CAS). We illustrate the circumstances and conditions in which evaluation mechanisms, where evaluation procedures and culture are institutionalized and stakeholders’ interactions are facilitated, help indeed to mitigate the governance tensions.
Bibliometric analysis of literature in AIDS-related stigma and discrimination
Authors: Sweileh Waleed M
Published: July 2019

Stigma and discrimination are major barriers in the global fight against human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). The aim of this study was to create an analytical inventory of worldwide research output in AIDS-related stigma and discrimination. SciVerse Scopus was used for the study period from 1980 to 2017 to retrieve literature in AIDS-related stigma and discrimination. Results were presented as bibliometric tables and maps. In total, 2,509 documents were retrieved. Approximately 40% (n = 990) of the retrieved documents were published in the last 5 years (2013–2017). Retrieved documents received an average of 19.8 citations per article and had an average of 3.2 authors per article. The Hirsh index of the retrieved documents was 94. Most frequently encountered topics were mental health, adherence, adolescents, women, disclosure, and Africa. The USA contributed to 1,226 (48.9%) documents while the African region contributed to 531 (21.2%) documents. Research collaboration among most active countries was relatively low. Authors and institutions from the USA dominated this field. AIDS Care was the most active journal in publishing documents in this field with 307 (13.4%) documents while documents published in Social Medicine journal received the highest citations. Research in AIDS-related stigma and discrimination had witnessed a noticeable increase in the past decade, but the overall number of publications is considered insignificant relative to the size of the problem and the global number of infected people. There was a relative underpresentation of literature from African region despite the fact that more than two-thirds of HIV-infected people in the world are living in Africa.
Identification, characterization, and application of a highly sensitive lactam biosensor fromPseudomonas putida
Authors: Thompson Mitchell G. , Pearson Allison N. , Barajas Jesus F. , Cruz-Morales Pablo , Sedaghatian Nima , Costello Zak , Garber Megan E. , Incha Matthew R. , Valencia Luis E. , Baidoo Edward E. K. , Martin Hector Garcia , Mukhopadhyay Aindrila , Keasling Jay D.
Published: July 2019

Caprolactam is an important polymer precursor to nylon traditionally derived from petroleum and produced on a scale of 5 million tons per year. Current biological pathways for the production of caprolactam are inefficient with titers not exceeding 2 mg/L, necessitating novel pathways for its production. As development of novel metabolic routes often require thousands of designs and result in low product titers, a highly sensitive biosensor for the final product has the potential to rapidly speed up development times. Here we report a highly sensitive biosensor for valerolactam and caprolactam fromPseudomonas putidaKT2440 which is >1000x more sensitive to exogenous ligand than previously reported sensors. Manipulating the expression of the sensoroplR(PP_3516) substantially altered the sensing parameters, with various vectors showing Kdvalues ranging from 700 nM (79.1 μg/L) to 1.2 mM (135.6 mg/L). Our most sensitive construct was able to detectin vivoproduction of caprolactam above background at ~6 μg/L. The high sensitivity and range of OplR is a powerful tool towards the development of novel routes to the biological synthesis of caprolactam.
Female × male and male × male interactions have limited influence on competitive fertilization inDrosophila melanogaster
Authors: Lüpold Stefan , Reil Jonathan Bradley , Manier Mollie K. , Zeender Valérian , Belote John M. , Pitnick Scott
Published: July 2019

How males and females contribute to joint reproductive success has been a long-standing question in sexual selection. Under postcopulatory sexual selection (PSS), paternity success is predicted to derive from complex interactions among females engaging in cryptic female choice and males engaging in sperm competition. Such interactions have been identified as potential sources of genetic variation in sexually selected traits but are also expected to inhibit trait diversification. To date, studies of interactions between females and competing males have focused almost exclusively on genotypes and not phenotypic variation in sexually selected traits. Here, we characterize within- and between-sex interactions inDrosophila melanogasterusing isogenic lines with heritable variation in both male and female traits known to influence competitive fertilization. We found surprisingly few genotypic interaction effects on various stages of PSS such as female remating interval, copulation duration, sperm transfer, or sperm storage. Only the timing of female sperm ejection depended on female × male genotypic interactions. By contrast, several reproductive events, including sperm transfer, female sperm ejection and sperm storage, were explained by two- and three-way interactions among sex-specific phenotypes. We also documented complex interactions between the lengths of competing males’ sperm and the female seminal receptacle, which are known to have experienced rapid female-male co-diversification. Our results highlight the non-independence of sperm competition and cryptic female choice and demonstrate that complex interactions between the sexes do not limit the ability of multivariate systems to respond to directional sexual selection.

Significance statement

For species with internal fertilization and female promiscuity, postcopulatory sexual selection (PSS) is believed to depend, in part, on complex interactions between rival males and between the sexes. Although little investigated, clarifying such interactions is critical as they may limit the efficacy of PSS in the diversification of reproductive traits (e.g., ejaculate biochemistry and sperm, genitalia and female reproductive tract morphology). Here, we resolve how sex-specific traits and their interactions contribute to key reproductive events and outcomes related to competitive fertilization success, including traits known to have experienced rapid diversification. Our results provide novel insights into the operation and complexity of PSS and demonstrate that the processes of sperm competition and cryptic female choice are not independent selective forces.
Cell types of the human retina and its organoids at single-cell resolution: developmental convergence, transcriptomic identity, and disease map
Authors: Cowan Cameron S. , Renner Magdalena , Gross-Scherf Brigitte , Goldblum David , Munz Martin , Krol Jacek , Szikra Tamas , Papasaikas Panagiotis , Cuttat Rachel , Waldt Annick , Diggelmann Roland , Patino-Alvarez Claudia P. , Gerber-Hollbach Nadine , Schuierer Sven , Hou Yanyan , Srdanovic Aldin , Balogh Marton , Panero Riccardo , Hasler Pascal W. , Kusnyerik Akos , Szabo Arnold , Stadler Michael B. , Orgül Selim , Hierlemann Andreas , Scholl Hendrik P. N. , Roma Guglielmo , Nigsch Florian , Roska Botond
Published: July 2019

How closely human organoids recapitulate cell-type diversity and cell-type maturation of their target organs is not well understood. We developed human retinal organoids with multiple nuclear and synaptic layers. We sequenced the RNA of 158,844 single cells from these organoids at six developmental time points and from the periphery, fovea, pigment epithelium and choroid of light-responsive adult human retinas, and performed histochemistry. Cell types in organoids matured in vitro to a stable ‘developed’ state at a rate similar to human retina development in vivo and the transcriptomes of organoid cell types converged towards the transcriptomes of adult peripheral retinal cell types. The expression of disease-associated genes was significantly cell-type specific in adult retina and cell-type specificity was retained in organoids. We implicate unexpected cell types in diseases such as macular degeneration. This resource identifies cellular targets for studying disease mechanisms in organoids and for targeted repair in adult human retinas.
Description ofKlebsiella spallanzaniisp. nov. and ofKlebsiella pasteuriisp. nov
Authors: Merla Cristina , Rodrigues Carla , Passet Virginie , Corbella Marta , Thorpe Harry A. , Kallonen Teemu V.S. , Zong Zhiyong , Marone Piero , Bandi Claudio , Sassera Davide , Corander Jukka , Feil Edward J. , Brisse Sylvain
Published: July 2019

Klebsiella oxytocacauses opportunistic human infections and post-antibiotic haemorrhagic diarrhoea. ThisEnterobacteriaceaespecies is genetically heterogeneous and is currently subdivided into seven phylogroups (Ko1 to Ko4, Ko6 to Ko8). Here we investigated the taxonomic status of phylogroups Ko3 and Ko4. Genomic sequence-based phylogenetic analyses demonstrate that Ko3 and Ko4 formed well-defined sequence clusters related to, but distinct from,Klebsiella michiganensis(Ko1),Klebsiella oxytoca(Ko2),K. huaxiensis(Ko8) andK. grimontii(Ko6). The average nucleotide identity of Ko3 and Ko4 were 90.7% withK. huaxiensisand 95.5% withK. grimontii, respectively. In addition, three strains ofK. huaxiensis, a species so far described based on a single strain from a urinary tract infection patient in China, were isolated from cattle and human faeces. Biochemical and MALDI-ToF mass spectrometry analysis allowed differentiating Ko3, Ko4 and Ko8 from the otherK. oxytocaspecies. Based on these results, we propose the namesKlebsiella spallanzaniifor the Ko3 phylogroup, with SPARK_775_C1T(CIP 111695T, DSM 109531T) as type strain, andKlebsiella pasteuriifor Ko4, with SPARK_836_C1T(CIP 111696T, DSM 109530T) as type strain. Strains ofK. spallanzaniiwere isolated from human urine, cow faeces and farm surfaces, while strains ofK. pasteuriiwere found in faecal carriage from humans, cows and turtles.

Accession numbers

The nucleotide sequences generated in this study were deposited in ENA and are available through the INSDC databases under accession numbersMN091365(SB6411T= SPARK775C1T), MN091366 (SB6412T= SPARK836C1T) and MN104661 to MN104677 (16S rRNA), MN076606 to MN076643 (gyrAandrpoB), and MN030558 to MN030567 (blaOXY). Complete genomic sequences were submitted to European Nucleotide Archive under the BioProject number PRJEB15325.

Abbreviations

ANI, average nucleotide identity; HCCA, a-cyano-4-hydroxycinnamic acid; isDDH,in silicoDNA-DNA hybridization; SCAI, Simmons citrate agar with inositol; MALDI57 ToF MS: Matrix-assisted laser desorption/ionization time of flight mass spectrometry
Comparison of CPU and GPU Bayesian Estimates of Fibre Orientations from Diffusion MRI
Authors: Kim Danny H.C. , Williams Lynne J. , Hernandez-Fernandez Moises , Bjornson Bruce H.
Published: July 2019

Background

The correct estimation of fibre orientations is a crucial step for reconstructing human brain tracts. Bayesian Estimation of Diffusion Parameters Obtained using Sampling Techniques (bedpostx) is able to estimate several fibre orientations and their diffusion parameters per voxel using Markov Chain Monte Carlo (MCMC) in a whole brain diffusion MRI data, and it is capable of running on GPUs, achieving speed-up of over 100 times compared to CPUs. However, few studies have looked at whether the results from the CPU and GPU algorithms differ. In this study, we compared CPU and GPU bedpostx outputs by running multiple trials of both algorithms on the same whole brain diffusion data and compared each distribution of output using Kolmogorov-Smirnov tests.

Results

We show that distributions of fibre fraction parameters and principal diffusion direction angles from bedpostx and bedpostx_gpu display few statistically significant differences in shape and are localized sparsely throughout the whole brain. Average output differences are small in magnitude compared to underlying uncertainty.

Conclusions

Despite small amount of differences in output between CPU and GPU bedpostx algorithms, results are comparable given the difference in operation order and library usage between CPU and GPU bedpostx.
Target Capture Sequencing UnravelsRubusEvolution
Authors: Carter Katherine A. , Liston Aaron , Bassil Nahla V. , Alice Lawrence A. , Bushakra Jill M. , Sutherland Brittany L. , Mockler Todd C. , Bryant Douglas W. , Hummer Kim E.
Published: July 2019

Background

Rubus(Rosaceae) comprises more than 500 species with additional commercially cultivated raspberries and blackberries. The most recent (> 100 years old) global taxonomic treatment of the genus defined 12 subgenera; two subgenera were subsequently described and some species were rearranged. Intra- and interspecific ploidy levels and hybridization make phylogenetic estimation ofRubuschallenging. Our objectives were to: estimate the phylogeny of 94 geographically diverse species and 3 cultivars using chloroplast DNA sequences and target capture of approximately 1,000 low copy nuclear genes; estimate divergence times between majorRubusclades; and examine the historical biogeography of species diversification.

Results

Target capture sequencing identified eight major groups withinRubus. SubgenusOrobatusand Subg.Anoplobatuswere monophyletic, while other recognized subgenera were para- or polyphyletic. Multiple hybridization events likely occurred across the phylogeny at subgeneric levels,e.g., Subg.Rubus(blackberries) × Subg.Idaeobatus(raspberries) and Subg.Idaeobatus× Subg.Cylactis(Arctic berries) hybrids. The raspberry heritage within known cultivated blackberry hybrids was confirmed. The most recent common ancestor of the genus was most likely distributed in North America. Multiple distribution events occurred during the Miocene (about 20 Ma) from North America into Asia and Europe across the Bering land bridge and southward crossing the Panamanian Isthmus.Rubusspecies diversified greatly in Asia during the Miocene.

Conclusions

Rubustaxonomy does not reflect phylogenetic relationships and subgeneric revision is warranted. Target capture sequencing confirmed that most subgenera are para- or polyphyletic. The most recent common ancestor migrated from North America towards Asia, Europe, and Central and South America early in the Miocene then diversified. Ancestors of the genusRubusmay have migrated to Oceania by long distance bird dispersal. This phylogeny presents a roadmap for furtherRubustaxonomic and phylogenetic research.
Recovirus NS1-2 has viroporin activity that induces aberrant cellular calcium signaling to facilitate virus replication
Authors: Strtak Alicia C. , Perry Jacob L. , Sharp Mark N. , Chang-Graham Alexandra L. , Farkas Tibor , Hyser Joseph M.
Published: July 2019

Enteric viruses in theCaliciviridaefamily cause acute gastroenteritis in humans and animals, but the cellular processes needed for virus replication and disease remain unknown. A common strategy among enteric viruses, including rotaviruses and enteroviruses, is to encode a viral ion channel (i.e., viroporin) that is targeted to the endoplasmic reticulum (ER) and disrupts host calcium (Ca2+) homeostasis. Previous reports have demonstrated genetic and functional similarities between the nonstructural proteins of caliciviruses and enteroviruses, including the calicivirus NS1-2 protein and the 2B viroporin of enteroviruses. However, it is unknown whether caliciviruses alter Ca2+homeostasis for virus replication or whether the NS1-2 protein has viroporin activity like its enterovirus counterpart. To address these questions, we used Tulane virus (TV), a rhesus enteric calicivirus, to examine Ca2+signaling during infection and determine whether NS1-2 has viroporin activity that disrupts Ca2+homeostasis. We found that TV disrupts increases Ca2+signaling during infection and increased cytoplasmic Ca2+levels is important for efficient replication. Further, TV NS1-2 localizes to the endoplasmic reticulum (ER), the predominant intracellular Ca2+store and the NS2 region has characteristics of a viroporin domain (VPD). NS1-2 had viroporin activity in a classic bacterial functional assay and caused aberrant Ca2+signaling when expressed in mammalian cells, but truncation of the VPD abrogated these functions. Together, our data provide new mechanistic insights into the function of the NS2 region of NS1-2 and show that like many other enteric viruses, enteric caliciviruses also exploit host Ca2+signaling to facilitate their replication.

Importance

Tulane virus is one of many enteric caliciviruses that cause acute gastroenteritis and diarrheal disease. Globally, enteric caliciviruses affect both humans and animals and result in >65 billion dollars per year in treatment and healthcare-associated costs, thus imposing an enormous economic burden. Recent progress has resulted in several cultivation systems (B cell, enteroid and zebrafish larvae) to study human noroviruses, but mechanistic insights into the viral factors and host pathways important for enteric calicivirus replication and infection are largely still lacking. Here we used Tulane virus, a calicivirus that is biologically similar to human noroviruses and can be cultivated in conventional cell culture, to identify and functionally validate NS1-2 as an enteric calicivirus viroporin. Viroporin-mediated calcium signaling may be a broadly utilized pathway for enteric virus replication, and its existence within caliciviruses provides a novel approach to developing antivirals and comprehensive therapeutics for enteric calicivirus diarrheal disease outbreaks.
Single-cell transcriptome profiling reveals dermal and epithelium cell fate decisions during embryonic hair follicle development
Authors: Ge Wei , Tan Shao-Jing , Wang Shan-He , Li Lan , Sun Xiao-Feng , Shen Wei , Wang Xin
Published: July 2019

Characterization of the morphological structure during hair follicle development has been well documented, while the current understanding of the molecular mechanisms involved in follicle development remain limited. Here, using unbiased single-cell RNA sequencing, we analyzed 15,086 single cell transcriptome profiles from E13.5 and E16.5 fetal mice, and newborn mouse (postnatal day 0, P0) dorsal skin cells. Based on t-distributed Stochastic Neighbor Embedding (tSNE) clustering, we identified 14 cell clusters from skin cells and delineated their cell identity gene expression profiles. Pseudotime ordering analysis successfully constructed epithelium/dermal cell lineage differentiation trajectory and revealed sequential activation of key regulons involved during cell fate decisions. Along with this, intercellular communication between different cell populations were inferred based on a priori knowledge of ligand-receptor pairs. Together, our findings here provide a molecular landscape during hair follicle epithelium/dermal cell lineage fate decisions, and more importantly, recapitulate sequential activation of core regulatory transcriptional factors for different cell populations during hair follicle morphogenesis.
Cell-to-cell diversification in ERBB-RAS-MAPK signal transduction that produces cell-type specific growth factor responses
Authors: Miyagi Hiraku , Hiroshima Michio , Sako Yasushi
Published: July 2019

Growth factors regulate cell fates, including their proliferation, differentiation, survival, and death, according to the cell type. Even when the response to a specific growth factor is deterministic for collective cell behavior, significant levels of fluctuation are often observed between single cells. Statistical analyses of single-cell responses provide insights into the mechanism of cell fate decisions but very little is known about the distributions of the internal states of cells responding to growth factors. Using multi-color immunofluorescent staining, we have here detected the phosphorylation of seven elements in the early response of the ERBB–RAS–MAPK system to two growth factors. Among these seven elements, five were analyzed simultaneously in distinct combinations in the same single cells. Although principle component analysis suggested cell-type and input specific phosphorylation patterns, cell-to-cell fluctuation was large. Mutual information analysis suggested that cells use multitrack (bush-like) signal transduction pathways under conditions in which clear cell fate changes have been reported. The clustering of single-cell response patterns indicated that the fate change in a cell population correlates with the large entropy of the response, suggesting a bet-hedging strategy is used in decision making. A comparison of true and randomized datasets further indicated that this large variation is not produced by simple reaction noise, but is defined by the properties of the signal-processing network.

Author Summary

How extracellular signals, such as growth factors (GFs), induce fate changes in biological cells is still not fully understood. Some GFs induce cell proliferation and others induce differentiation by stimulating a common reaction network. Although the response to each GF is reproducible for a cell population, not all single cells respond similarly. The question that arises is whether a certain GF conducts all the responding cells in the same direction during a fate change, or if it initially stimulates a variety of behaviors among single cells, from which the cells that move in the appropriate direction are later selected. Our current statistical analysis of single-cell responses suggests that the latter process, which is called a bet-hedging mechanism is plausible. The complex pathways of signal transmission seem to be responsible for this bet-hedging.
Single-Cell RNA-Seq Reveals Novel Mitochondria-related Musculoskeletal Cell Populations during Adult Axolotl Limb Regeneration Process
Authors: Qin Tian , Fan Chun-mei , Wang Ting-zhang , Yang Long , Shen Wei-liang , Sun Heng , Lin Jun-xin , Cucchiarini Magali , Clement Nicholas D. , Mason Christopher E. , Bunpetch Varitsara , Nakamura Norimasa , Bhonde Rameah , Clement Nicholas D. , Yin Zi , Chen Xiao
Published: July 2019

While the capacity to regenerate tissues or limbs is limited in mammals including humans, unlike us, axolotls are able to regrow entire limbs and major organs. The wound blastema have been extensively studied in limb regeneration. However, due to the inadequate characterization and coordination of cell subpopulations involved in the regeneration process, it hinders the discovery of the key clue for human limb regeneration. In this study, we applied unbiased large-scale single-cell RNA sequencing to classify cells throughout the adult axolotl limb regeneration process. We computationally identified 7 clusters in regenerating limbs, including the novel regeneration-specific mitochondria-related cluster supporting regeneration through energy providing and the COL2+ cluster contributing to regeneration through cell-cell interactions signals. We also discovered the dedifferentiation and re-differentiation of the COL1+/COL2+ cellular subpopulation and uncovered a COL2-mitochondria sub-cluster supporting the musculoskeletal system regeneration. On the basis of these findings, we reconstructed the dynamic single-cell transcriptome atlas of adult axolotl limb regenerative process, and identified the novel regenerative mitochondria-related musculoskeletal populations, which yielded deeper insights into the crucial interactions between cell clusters within the regenerative microenvironment.
Environmental innovation practices and operational performance
Authors: Gomez-Conde Jacobo , Lunkes Rogerio Joao , Rosa Fabricia Silva
Published: July 2019

Purpose

The purpose of this paper is to analyze the effect of management accounting and control systems (MACS) on environmental innovation practices and operational performance. Specifically, this study relies on Simons’ levers of control (LOC) framework to investigate how managers implement environmental innovation practices. This paper hypothesizes that a forward-looking use of MACS (i.e. interactive use) triggers the implementation of environmental innovation practices, resulting in higher operational performance. Furthermore, the authors argue that the monitoring role of MACS (i.e. diagnostic use) combined with environmental training improves the effect of environmental innovation practices on operational performance.

Design/methodology/approach

Hypotheses are examined through a questionnaire survey. The analyses are based on responses in an empirical study from 89 Brazilian hotels.

Findings

Empirical findings from a hierarchical moderated regression analysis support the hypothesized links.

Originality/value

This study contributes to the environmental management and management control literature by providing novel evidence on the roles MACS play in the field of sustainable development. Based on the LOC framework, the authors shed light on the understanding of how managers introduce and monitor environmental innovation practices, as well as also outlining the key effects of environmental training in enabling the novel abilities of managers and employees to better understand environmental data and identify novel potential environmentally friendly solutions in the case of deviations. This paper also adds to Wijethilakeet al.(2017), providing new empirical evidence on how firms design, implement and use MACS that capture institutional pressures for sustainability from multiple stakeholders.