bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Approaches and Therapeutic Options for Mycobacterium tuberculosis in a Dormant State
Authors: Caño-Muñiz Santiago , Anthony Richard , Niemann Stefan , Alffenaar Jan-Willem C. 
Published: November 2017

SUMMARY

We are far away from the days when tuberculosis (TB) accounted for 1 in 4 deaths during the 19th century. However,
Mycobacterium tuberculosis
complex (MTBC) strains are still the leading cause of morbidity and mortality by a single infectious disease, with 9.6 million cases and 1.5 million deaths reported. One-third of the world's population is estimated by the WHO to be infected with latent TB. During the last decade, several studies have aimed to define the characteristics of dormant bacteria in these latent infections. General features of the shift to a dormant state encompass several phenotypic changes that reduce metabolic activity. This low metabolic state is thought to increase the resistance of MTBC strains to host/environmental stresses, including antibiotic action. Once the stress ceases (e.g., interruption of treatment), dormant cells can reactivate and cause symptomatic disease again. Therefore, a proper understanding of dormancy could guide the rational development of new treatment regimens that target dormant cells, reducing later relapse. Here, we briefly summarize the latest data on the genetics involved in the regulation of dormancy and discuss new approaches to TB treatment.
Recombinant Endolysins as Potential Therapeutics against Antibiotic-Resistant Staphylococcus aureus: Current Status of Research and Novel Delivery Strategies
Authors: Haddad Kashani Hamed , Schmelcher Mathias , Sabzalipoor Hamed , Seyed Hosseini Elahe , Moniri Rezvan 
Published: November 2017

SUMMARY

Staphylococcus aureus
is one of the most common pathogens of humans and animals, where it frequently colonizes skin and mucosal membranes. It is of major clinical importance as a nosocomial pathogen and causative agent of a wide array of diseases. Multidrug-resistant strains have become increasingly prevalent and represent a leading cause of morbidity and mortality. For this reason, novel strategies to combat multidrug-resistant pathogens are urgently needed. Bacteriophage-derived enzymes, so-called endolysins, and other peptidoglycan hydrolases with the ability to disrupt cell walls represent possible alternatives to conventional antibiotics. These lytic enzymes confer a high degree of host specificity and could potentially replace or be utilized in combination with antibiotics, with the aim to specifically treat infections caused by Gram-positive drug-resistant bacterial pathogens such as methicillin-resistant
S. aureus
. LysK is one of the best-characterized endolysins with activity against multiple staphylococcal species. Various approaches to further enhance the antibacterial efficacy and applicability of endolysins have been demonstrated. These approaches include the construction of recombinant endolysin derivatives and the development of novel delivery strategies for various applications, such as the production of endolysins in lactic acid bacteria and their conjugation to nanoparticles. These novel strategies are a major focus of this review.
Pathogenesis, Humoral Immune Responses, and Transmission between Cohoused Animals in a Ferret Model of Human Respiratory Syncytial Virus Infection
Authors: Chan Kok Fei , Carolan Louise A. , Druce Julian , Chappell Keith , Watterson Daniel , Young Paul , Korenkov Daniil , Subbarao Kanta , Barr Ian G. , Laurie Karen L. , Reading Patrick C. 
Published: November 2017

ABSTRACT
Small-animal models have been used to obtain many insights regarding the pathogenesis and immune responses induced following infection with human respiratory syncytial virus (hRSV). Among those described to date, infections in cotton rats, mice, guinea pigs, chinchillas, and Syrian hamsters with hRSV strains Long and/or A2 have been well characterized, although clinical isolates have also been examined. Ferrets are also susceptible to hRSV infection, but the pathogenesis and immune responses elicited following infection have not been well characterized. Here, we describe the infection of adult ferrets with hRSV Long or A2 via the intranasal route and characterized virus replication, as well as cytokine induction, in the upper and lower airways. Virus replication and cytokine induction during the acute phase of infection (days 0 to 15 postinfection) were similar between the two strains, and both elicited high levels of F glycoprotein-specific binding and neutralizing antibodies following virus clearance (days 16 to 22 postinfection). Importantly, we demonstrate transmission from experimentally infected donor ferrets to cohoused naive recipients and have characterized virus replication and cytokine induction in the upper airways of infected contact animals. Together, these studies provide a direct comparison of the pathogenesis of hRSV Long and A2 in ferrets and highlight the potential of this animal model to study serological responses and examine interventions that limit transmission of hRSV.

IMPORTANCE
Ferrets have been widely used to study pathogenesis, immunity, and transmission following human influenza virus infections; however, far less is known regarding the utility of the ferret model to study hRSV infections. Following intranasal infection of adult ferrets with the well-characterized Long or A2 strain of hRSV, we report virus replication and cytokine induction in the upper and lower airways, as well as the development of virus-specific humoral responses. Importantly, we demonstrate transmission of hRSV from experimentally infected donor ferrets to cohoused naive recipients. Together, these findings significantly enhance our understanding of the utility of the ferret as a small-animal model to investigate aspects of hRSV pathogenesis and immunity.
The Absence of DHHC3 Affects Primary and Latent Herpes Simplex Virus 1 Infection
Authors: Wang Shaohui , Mott Kevin R. , Cilluffo Marianne , Kilpatrick Casey L. , Murakami Shoko , Ljubimov Alexander V. , Kousoulas Konstantin G. , Awasthi Sita , Luscher Bernhard , Ghiasi Homayon 
Published: November 2017

ABSTRACT

UL20, an essential herpes simplex virus 1 (HSV-1) protein, is involved in cytoplasmic envelopment of virions and virus egress. We reported recently that UL20 can bind to a host protein encoded by the zinc finger DHHC-type containing 3 (
ZDHHC3
) gene (also known as Golgi-specific DHHC zinc finger protein [GODZ]). Here, we show for the first time that HSV-1 replication is compromised in murine embryonic fibroblasts (MEFs) isolated from GODZ
−/−
mice. The absence of GODZ resulted in blocking palmitoylation of UL20 and altered localization and expression of UL20 and glycoprotein K (gK); the expression of gB and gC; and the localization and expression of tegument and capsid proteins within HSV-1-infected MEFs. Electron microscopy revealed that the absence of GODZ limited the maturation of virions at multiple steps and affected the localization of virus and endoplasmic reticulum morphology. Virus replication in the eyes of ocularly HSV-1-infected GODZ
−/−
mice was significantly lower than in HSV-1-infected wild-type (WT) mice. The levels of UL20, gK, and gB transcripts in the corneas of HSV-1-infected GODZ
−/−
mice on day 5 postinfection were markedly lower than in WT mice, whereas only UL20 transcripts were reduced in trigeminal ganglia (TG). In addition, HSV-1-infected GODZ
−/−
mice showed notably lower levels of corneal scarring, and HSV-1 latency reactivation was also reduced. Thus, normal HSV-1 infectivity and viral pathogenesis are critically dependent on GODZ-mediated palmitoylation of viral UL20.

IMPORTANCE
HSV-1 infection is widespread. Ocular infection can cause corneal blindness; however, approximately 70 to 90% of American adults exposed to the virus show no clinical symptoms. In this study, we show for the first time that the absence of a zinc finger protein called GODZ affects primary and latent infection, as well as reactivation, in ocularly infected mice. The reduced virus infectivity is due to the absence of the GODZ interaction with HSV-1 UL20. These results strongly suggest that binding of UL20 to GODZ promotes virus infectivity
in vitro
and viral pathogenesis
in vivo
.
Inflammasome Antagonism by Human Parainfluenza Virus Type 3 C Protein
Authors: Shil Niraj K. , Pokharel Swechha M. , Banerjee Amiya K. , Hoffman Michael , Bose Santanu 
Published: November 2017

ABSTRACT

Human parainfluenza virus type 3 (HPIV3) is a negative-sense single-stranded RNA virus belonging to the
Paramyxoviridae
family. HPIV3 is a lung-tropic virus causing airway diseases, including pneumonia, croup, and bronchiolitis, during infancy and childhood. The activation of the inflammasome by pathogens results in the production of proinflammatory cytokines such as interleukin-1β (IL-1β) during infection. Thus, the inflammasome-mediated proinflammatory response plays a critical role in regulating the immune response and virus clearance. The inflammasome is a multimeric protein complex triggering caspase-1 activation. Activated caspase-1 cleaves pro-IL-1β into its mature (and active) secretory form. Our study revealed inflammasome activation in macrophages following HPIV3 infection. Specifically, the activation of the NLRP3/ASC inflammasome resulted in the production of mature IL-1β from HPIV3-infected cells. Furthermore, Toll-like receptor 2 (TLR2) activation (first signal) and potassium efflux (second signal) constituted two cellular events mediating inflammasome activation following HPIV3 infection. During our studies, we surprisingly identified the HPIV3 C protein as an antagonist of inflammasome activation. The HPIV3 C protein is an accessory protein encoded by the open reading frame of the viral phosphoprotein (P) gene. The HPIV3 C protein interacted with the NLRP3 protein and blocked inflammasome activation by promoting the proteasomal degradation of the NLRP3 protein. Thus, our studies report NLRP3/ASC inflammasome activation by HPIV3 via TLR2 signaling and potassium efflux. Furthermore, we have identified HPIV3 C as a viral component involved in antagonizing inflammasome activation.

IMPORTANCE
Human parainfluenza virus type 3 (HPIV3) is a paramyxovirus that causes respiratory tract diseases during infancy and childhood. Currently, there is no effective vaccine or antiviral therapy for HPIV3. Therefore, in order to develop anti-HPIV3 agents (therapeutics and vaccines), it is important to study the HPIV3-host interaction during the immune response. Inflammasomes play an important role in the immune response. Inflammasome activation by HPIV3 has not been previously reported. Our studies demonstrated inflammasome activation by HPIV3 in macrophages. Specifically, HPIV3 activated the NLRP3/ASC inflammasome by TLR2 activation and potassium efflux. C proteins of paramyxoviruses are accessory proteins encoded by the viral phosphoprotein gene. The role of the C protein in inflammasome regulation was unknown. Surprisingly, our studies revealed that the HPIV3 C protein antagonizes inflammasome activation. In addition, we highlighted for the first time a mechanism utilized by paramyxovirus accessory proteins to block inflammasome activation. The HPIV3 C protein interacted with the NLRP3 protein to trigger the proteasomal degradation of the NLRP3 protein.
Recipient-Biased Competition for an Intracellularly Generated Cross-Fed Nutrient Is Required for Coexistence of Microbial Mutualists
Authors: McCully Alexandra L. , LaSarre Breah , McKinlay James B. 
Published: November 2017

ABSTRACT

Many mutualistic microbial relationships are based on nutrient cross-feeding. Traditionally, cross-feeding is viewed as being unidirectional, from the producer to the recipient. This is likely true when a producer’s waste, such as a fermentation product, has value only for a recipient. However, in some cases the cross-fed nutrient holds value for both the producer and the recipient. In such cases, there is potential for nutrient reacquisition by producer cells in a population, leading to competition against recipients. Here, we investigated the consequences of interpartner competition for cross-fed nutrients on mutualism dynamics by using an anaerobic coculture pairing fermentative
Escherichia coli
and phototrophic
Rhodopseudomonas palustris
. In this coculture,
E. coli
excretes waste organic acids that provide a carbon source for
R. palustris
. In return,
R. palustris
cross-feeds
E. coli
ammonium (NH
4
+
), a compound that both species value. To explore the potential for interpartner competition, we first used a kinetic model to simulate cocultures with varied affinities for NH
4
+
in each species. The model predicted that interpartner competition for NH
4
+
could profoundly impact population dynamics. We then experimentally tested the predictions by culturing mutants lacking NH
4
+
transporters in both NH
4
+
competition assays and mutualistic cocultures. Both theoretical and experimental results indicated that the recipient must have a competitive advantage in acquiring cross-fed NH
4
+
to sustain the mutualism. This recipient-biased competitive advantage is predicted to be crucial, particularly when the communally valuable nutrient is generated intracellularly. Thus, the very metabolites that form the basis for mutualistic cross-feeding can also be subject to competition between mutualistic partners.

IMPORTANCE
Mutualistic relationships, particularly those based on nutrient cross-feeding, promote stability of diverse ecosystems and drive global biogeochemical cycles. Cross-fed nutrients within these systems can be either waste products valued by only one partner or nutrients valued by both partners. Here, we explored how interpartner competition for a communally valuable cross-fed nutrient impacts mutualism dynamics. We discovered that mutualism stability necessitates that the recipient have a competitive advantage against the producer in obtaining the cross-fed nutrient, provided that the nutrient is generated intracellularly. We propose that the requirement for recipient-biased competition is a general rule for mutualistic coexistence based on the transfer of intracellularly generated, communally valuable resources.
Use of humour in medical education: a survey of students and teachers at a medical school in China
Authors: Liu Yan-Ping , Sun Lei , Wu Xiao-Fen , Yang Yi , Zhang Cun-Tai , Zhou Hong-Lian , Quan Xiao-Qing 
Published: November 2017

ObjectiveHumour is a powerful resource in medical education. The purpose of this study is to investigate what students and teachers think about the use of humour. What challenges do teachers face in using humour and how they address them are also the subject of the present study.DesignSeparate cross-sectional questionnaire surveys.SettingTongji Medical College and Tongji Hospital in China.Participants327 students at Tongji Medical College and 165 physician teachers at Tongji Hospital in China.Main outcome measuresThe primary study outcome was assessed by proportion.Results87% of student and teacher respondents agreed with using humour in the didactic setting. They felt humour fostered a positive didactic atmosphere. Interesting clinical case was the most frequently used humour type by teachers and considered the most effective by students. Lack of humorous materials related to the lecture subject was the main challenge to humour use cited by teachers. Collecting humorous materials in teacher’s daily work and life, observing teachers with a reputation for successfully using humour, and efficiently using the internet-enhanced humour use ability.ConclusionThe present study confirms that most medical students and physician teachers support the use of humour in medical didactics, with particular strategies aiding its use and positive impact.
Surgical academic reach: the higher degree effect quantified
Authors: Brown Chris , Abdelrahman Tarig , Thomas Charlotte , Pollitt John , Lewis Wyn G 
Published: November 2017

AbstractIntroductionProof of professional specific academic attainment is embedded within the Joint Committee on Surgical Training 2013 general surgery curriculum, mandating that all higher general surgical trainees (HST) obtain three peer-reviewed publications to qualify for Certification of Completion of Training. Yet, Modernising Medical Careers (MMC) has been associated with a trend away from the gold standard postgraduate credentials of higher degrees by research. This study aimed to evaluate the academic achievements of a post-MMC UK Deanery HST cohort to determine what additional benefits higher degree study might confer.MethodThe Scopus bibliographic database (Elsevier, RELX Group) was used to characterise the academic profiles of 101 consecutive HSTs and supplemented with Intercollegiate Surgical Programme Curriculum data. Primary outcome measures were numbers of publications, citations and Hirsch indices (HI).ResultsThirty-seven HSTs (36.6%) had been awarded higher degrees (29 Doctor of Medicine, 8 Doctor of Philosophy). Academic profiles of HSTs with higher degrees were stronger than those of HSTs without, specifically: median (range) publication numbers 16 (2–57) vs 2 (0–11, P&lt;0.001), citations 93 (0–1600) vs 6 (0–132, P&lt;0.001), first author publications 6 (0–33) vs 3 (0–106, P&lt;0.001), communications to learnt societies 30 (5–79) vs 8 (2–35, P&lt;0.001) and HI 6 (1–26) vs 1 (0–6, P&lt;0.001).ConclusionProof of academic reach by higher degree was associated with important enhanced professional credentials, strengthening HIs sixfold. Trainers and trainees alike should be aware of the relative magnitude of such benefits when planning educational programmes.
0∘ to 90∘ arbitrary controllable optical activity with an array of L-shaped silver holes inside a silica cube
Authors: Wang Wenbo , Hu Xiaobin , Wei Xin 
Published: November 2017

We realize high efficiency 0–90[Formula: see text] arbitrary polarization rotation by using a single layer of L-shaped silver hole array inside a silica cube. The simulation results show that the 0–90[Formula: see text] arbitrary polarization rotation can be manipulated easily by adjusting the arm length of L-shaped holes, and the degree of linear polarization (DoLP) of the transmission spectra can achieve high over all range of 0–90[Formula: see text]. Our design has been optimized for 1550 nm wavelength. This arbitrary polarization rotation plasmonic metamaterial may provide more possibilities for applications in photonics.
LSR Antibody Therapy Inhibits Ovarian Epithelial Tumor Growth by Inhibiting Lipid Uptake
Authors: Hiramatsu Kosuke , Serada Satoshi , Enomoto Takayuki , Takahashi Yusuke , Nakagawa Satoshi , Nojima Satoshi , Morimoto Akiko , Matsuzaki Shinya , Yokoyama Takuhei , Takahashi Tsuyoshi , Fujimoto Minoru , Takemori Hiroshi , Ueda Yutaka , Yoshino Kiyoshi , Morii Eiichi , Kimura Tadashi , Naka Tetsuji 
Published: November 2017

Abstract
Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, but it still lacks effective treatment options. In this study, we utilized proteomic technology to identify lipolysis-stimulated lipoprotein receptor (LSR) as a new tumor antigen of EOC. Immunohistochemical analysis of EOC tissues in conjunction with survival analysis of EOC patients showed that high expression of LSR is associated with poor prognosis. High LSR expression also occurred in tumor metastases including to the lymph node and omentum. To evaluate the possible benefits of blocking this antigen in EOC, we raised a new monoclonal antibody (mAb) to human LSR (hLSR). In mouse xenograft models of hLSR+ EOC (cell lines or patient-derived tumors), we found that administration of anti-hLSR mAb inhibited tumor growth in a manner independent of both antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Mechanistic investigations showed that hLSR expression increased incorporation of very-low-density lipoprotein (VLDL) into EOC cells and that anti-hLSR mAb inhibited lipid uptake in vitro and in vivo. Moreover, VLDL promoted cell proliferation in hLSR-positive EOC cells in vitro, and this effect was inhibited by anti-hLSR mAb. While the anti-hLSR mAb studied cross reacted with the mouse antigen, we observed no adverse effects on normal organs and lipid metabolism in murine hosts. Our findings suggest that hLSR plays a key functional role in EOC development and that this antigen can be therapeutically targeted by specific mAb to improve EOC treatment.
Significance: These findings offer preclinical evidence of the therapeutic efficacy of a novel targeted antibody therapy against deadly epithelial ovarian cancers. Cancer Res; 78(2); 516–27. ©2017 AACR.
Thulium Vaporesection of the Prostate and Thulium Vapoenucleation of the Prostate: A Retrospective Bicentric Matched-Paired Comparison with 24-Month Follow-Up
Authors: Becker Benedikt , Buttice Salvatore , Magno Carlo , Gross Andreas J. , Netsch Christopher 
Published: November 2017

<b><i>Introduction:</i></b> To evaluate the intermediate-term outcomes of thulium vapoenucleation of the prostate (ThuVEP) and thulium vaporesection of the prostate (ThuVaRP) in patients with benign prostate obstruction (BPO). <b><i>Materials and Methods:</i></b> A bicentric retrospective matched-paired comparison of patients treated by ThuVEP (<i>n</i> = 80) or ThuVaRP (<i>n</i> = 80) was performed. The patients were preoperatively assessed with International Prostate Symptom Score (IPSS), quality of life (QoL), post-void residual urine (PVR), maximum urinary flow rate (Qmax), prostatespecific antigen (PSA) and re-evaluated at 12- and 24-month follow-up. <b><i>Results:</i></b> Median prostate volume was 65 mL and not different between the groups. The immediate re-operation rate was significantly different between ThuVEP and ThuVaRP (5 vs. 0%, <i>p</i> ≤ 0.0434). IPSS, QoL, Qmax and PVR had improved significantly compared to preoperative assessment in both groups at 12- and 24-month follow-up (<i>p</i> ≤ 0.001). Median Qmax (18.2 vs. 21.0 mL/s) and PVR (29.4 vs. 0 mL) were significantly different between ThuVEP and ThuVaRP at 24-month follow-up (<i>p</i> ≤ 0.001), while IPSS and QoL showed no differences between the groups. However, the PSA reduction was significantly higher after ThuVEP compared to ThuVaRP (78.93 vs. 23.39%, <i>p</i> ≤ 0.006) at 24-month follow-up. <b><i>Conclusions:</i></b> ThuVEP and ThuVaRP are safe and efficacious procedures for patients with BPO. Although the peri-operative re-intervention rates were lower after ThuVaRP, the low PSA reduction rate after ThuVaRP at 24-month follow-up favours the ThuVEP procedure.
Collective behaviour of wild Asian elephants in risky situations: how do social groups cross roads?
Authors: Mizuno Kaori , Sharma Nachiketha , Idani Gen’ichi , Sukumar Raman 
Published: November 2017

Among group-living animals, some members may derive benefit by following the decisions of other members. Free-ranging wild Asian elephants in Mudumalai National Park, southern India, must often cross roads and can be disturbed by vehicles. We assessed if measures of road and traffic characteristics serve as indicators of risk, and compared behaviours of different age classes during road-crossing events. More individuals displayed excitable behaviour on wider roads. A larger number of adults entered the road first, which is considered the most dangerous position, compared with immature elephants. Immature individuals tended to move ahead of others on the road, suggesting that it is more important for immature individuals to follow adults at the beginning of a crossing than to follow along for the entire crossing. These findings may suggest that less experienced group members derive benefit by following the decisions of experienced ones under risky situations.