bluuebunny/crossref_metadata_2025_split huggingface dataset:
An evolutionarily conserved P‐subfamily pentatricopeptide repeat protein is required to splice the plastid ndhA transcript in the moss Physcomitrella patens and Arabidopsis thaliana
Authors: Ito Ayaka , Sugita Chieko , Ichinose Mizuho , Kato Yoshinobu , Yamamoto Hiroshi , Shikanai Toshiharu , Sugita Mamoru 
Published: March 2018

SummaryPentatricopeptide repeat (PPR) proteins are known to play important roles in post‐transcriptional regulation in plant organelles. However, the function of the majority of PPR proteins remains unknown. To examine their functions, Physcomitrella patens PpPPR_66 knockout (KO) mutants were generated and characterized. The KO mosses exhibited a wild‐type‐like growth phenotype but showed aberrant chlorophyll fluorescence due to defects in chloroplast NADH dehydrogenase‐like (NDH) activity. Immunoblot analysis suggested that disruption of PpPPR_66 led to a complete loss of the chloroplast NDH complex. To examine whether the loss of PpPPR_66 affects the expression of plastid ndh genes, the transcript levels of 11 plastid ndh genes were analyzed by reverse transcription PCR. This analysis indicated that splicing of the ndhA transcript was specifically impaired while mRNA accumulation levels as well as the processing patterns of other plastid ndh genes were not affected in the KO mutants. Complemented PpPPR_66 KO lines transformed with the PpPPR_66 full‐length cDNA rescued splicing of the ndhA transcript. Arabidopsis thaliana T‐DNA tagged lines of a PPR_66 homolog (At2 g35130) showed deficient splicing of the ndhA transcript. This indicates that the two proteins are functionally conserved between bryophytes and vascular plants. An in vitro RNA‐binding assay demonstrated that the recombinant PpPPR_66 bound preferentially to the region encompassing a part of exon 1 to a 5′ part of the ndhA group II intron. Taken together, these results indicate that PpPPR_66 acts as a specific factor to splice ndhA pre‐mRNA.
Mechanism of Darunavir (DRV)’s High Genetic Barrier to HIV-1 Resistance: A Key V32I Substitution in Protease Rarely Occurs, but Once It Occurs, It Predisposes HIV-1 To Develop DRV Resistance
Authors: Aoki Manabu , Das Debananda , Hayashi Hironori , Aoki-Ogata Hiromi , Takamatsu Yuki , Ghosh Arun K. , Mitsuya Hiroaki 
Published: March 2018

ABSTRACT

Darunavir (DRV) has bimodal activity against HIV-1 protease, enzymatic inhibition and protease dimerization inhibition, and has an extremely high genetic barrier against development of drug resistance. We previously generated a highly DRV-resistant HIV-1 variant (HIV
DRV
R
P51
). We also reported that four amino acid substitutions (V32I, L33F, I54M, and I84V) identified in the protease of HIV
DRV
R
P51
are largely responsible for its high-level resistance to DRV. Here, we attempted to elucidate the role of each of the four amino acid substitutions in the development of DRV resistance. We found that V32I is a key substitution, which rarely occurs, but once it occurs, it predisposes HIV-1 to develop high-level DRV resistance. When two infectious recombinant HIV-1 clones carrying I54M and I84V (rHIV
I54M
and rHIV
I84V
, respectively) were selected in the presence of DRV, V32I emerged, and the virus rapidly developed high-level DRV resistance. rHIV
V32I
also developed high-level DRV resistance. However, wild-type HIV
NL4-3
(rHIV
WT
) failed to acquire V32I and did not develop DRV resistance. Compared to rHIV
WT
, rHIV
V32I
was highly susceptible to DRV and had significantly reduced fitness, explaining why V32I did not emerge upon selection of rHIV
WT
with DRV. When the only substitution is at residue 32, structural analysis revealed much stronger van der Waals interactions between DRV and I-32 than between DRV and V-32. These results suggest that V32I is a critical amino acid substitution in multiple pathways toward HIV-1’s DRV resistance development and elucidate, at least in part, a mechanism of DRV’s high genetic barrier to development of drug resistance. The results also show that attention should be paid to the initiation or continuation of DRV-containing regimens in people with HIV-1 containing the V32I substitution.

IMPORTANCE
Darunavir (DRV) is the only protease inhibitor (PI) recommended as a first-line therapeutic and represents the most widely used PI for treating HIV-1-infected individuals. DRV possesses a high genetic barrier to development of HIV-1’s drug resistance. However, the mechanism(s) of the DRV’s high genetic barrier remains unclear. Here, we show that the preexistence of certain single amino acid substitutions such as V32I, I54M, A71V, and I84V in HIV-1 protease facilitates the development of high-level DRV resistance. Interestingly, all
in vitro
-selected highly DRV-resistant HIV-1 variants acquired V32I but never emerged in wild-type HIV (HIV
WT
), and V32I itself rendered HIV-1 more sensitive to DRV and reduced viral fitness compared to HIV
WT
, strongly suggesting that the emergence of V32I plays a critical role in the development of HIV-1’s resistance to DRV. Our results would be of benefit in the treatment of HIV-1-infected patients receiving DRV-containing regimens.
Carbapenem-Resistant
Klebsiella pneumoniae
Exhibiting Clinically Undetected Colistin Heteroresistance Leads to Treatment Failure in a Murine Model of Infection
Authors: Band Victor I. , Satola Sarah W. , Burd Eileen M. , Farley Monica M. , Jacob Jesse T. , Weiss David S. 
Published: March 2018

ABSTRACT

Antibiotic resistance is a growing crisis and a grave threat to human health. It is projected that antibiotic-resistant infections will lead to 10 million annual deaths worldwide by the year 2050. Among the most significant threats are carbapenem-resistant
Enterobacteriaceae
(CRE), including carbapenem-resistant
Klebsiella pneumoniae
(CRKP), which lead to mortality rates as high as 40 to 50%. Few treatment options are available to treat CRKP, and the polymyxin antibiotic colistin is often the “last-line” therapy. However, resistance to colistin is increasing. Here, we identify multidrug-resistant, carbapenemase-positive CRKP isolates that were classified as susceptible to colistin by clinical diagnostics yet harbored a minor subpopulation of phenotypically resistant cells. Within these isolates, the resistant subpopulation became predominant after growth in the presence of colistin but returned to baseline levels after subsequent culture in antibiotic-free media. This indicates that the resistance was phenotypic, rather than due to a genetic mutation, consistent with heteroresistance. Importantly, colistin therapy was unable to rescue mice infected with the heteroresistant strains. These findings demonstrate that colistin heteroresistance may cause
in vivo
treatment failure during
K. pneumoniae
infection, threatening the use of colistin as a last-line treatment for CRKP. Furthermore, these data sound the alarm for use of caution in interpreting colistin susceptibility test results, as isolates identified as susceptible may in fact resist antibiotic therapy and lead to unexplained treatment failures.

IMPORTANCE
This is the first report of colistin-heteroresistant
K. pneumoniae
in the United States. Two distinct isolates each led to colistin treatment failure in an
in vivo
model of infection. The data are worrisome, especially since the colistin heteroresistance was not detected by current diagnostic tests. As these isolates were carbapenem resistant, clinicians might turn to colistin as a last-line therapy for infections caused by such strains, not knowing that they in fact harbor a resistant subpopulation of cells, potentially leading to treatment failure. Our findings warn that colistin susceptibility testing results may be unreliable due to undetected heteroresistance and highlight the need for more accurate and sensitive diagnostics.
Collapse in the scrum
Authors: Donnelly David , Patrick David , Weir Robin A 
Published: March 2018

Clinical introductionA 17-year-old male patient was brought by ambulance to the ED following a witnessed collapse while playing rugby. He denied any significant trauma, chest pain or breathlessness, and was alert and uncomplaining on arrival, with normal observations and a normal physical exam. Witnesses described a loss of consciousness, with a period of respiratory arrest requiring rescue breaths at the scene. Paramedics reported frequent ventricular extrasystoles on their arrival.The patient had no medical history and was on no medication, although admitted to ‘fainting’ some 3 weeks previously, again while playing rugby. A paternal uncle had died suddenly at the age of 45.His initial ECG is shown in figure 1.Figure 1Initial ECG.QuestionWhat is the most likely diagnosis?Pulmonary embolism (PE)Hypertrophic obstructive cardiomyopathy (HOCM)Arrhythmogenic right ventricular cardiomyopathy (ARVC)Right ventricular outflow tract tachycardia (RVOT)
Current Advances in Molecular Imaging: Noninvasive in Vivo Bioluminescent and Fluorescent Optical Imaging in Cancer Research
Authors: Choy Garry , Choyke Peter , Libutti Steven K 
Published: March 2018

Recently, there has been tremendous interest in developing techniques such as MRI, micro-CT, micro-PET, and SPECT to image function and processes in small animals. These technologies offer deep tissue penetration and high spatial resolution, but compared with noninvasive small animal optical imaging, these techniques are very costly and time consuming to implement. Optical imaging is cost-effective, rapid, easy to use, and can be readily applied to studying disease processes and biology in vivo. In vivo optical imaging is the result of a coalescence of technologies from chemistry, physics, and biology. The development of highly sensitive light detection systems has allowed biologists to use imaging in studying physiological processes. Over the last few decades, biochemists have also worked to isolate and further develop optical reporters such as GFP, luciferase, and cyanine dyes. This article reviews the common types of fluorescent and bioluminescent optical imaging, the typical system platforms and configurations, and the applications in the investigation of cancer biology.
Collaborative Composition of Classical Arabic Poetry
Authors: Naaman Erez 
Published: March 2018

Abstract
Evidence of collaborative composition of poetry goes back to the earliest documented phases in the history of Arabic literature. Already during pre-Islamic times, poets like Imruʾ al-Qays used to challenge others to complete their impromptu verse and create poetry collaboratively with them. This practice—commonly called iǧāza or tamlīṭ and essentially different from the better known poetic dueling of the naqāʾiḍ (flytings)—has shown remarkable stability and adherence to its form and dynamics in the pre-modern Arabophone world. In this article, I will discuss evidence of collaborative poetry from pre-Islamic times to the early seventh/thirteenth century, in order to present a picture of the typical situations in which it was practiced, its functions, its composition process, and formal aspects. Although usually not producing poetic masterpieces, this practice has the merit of revealing much about the processes of composing classical Arabic poetry in general. In this respect, its study and critical assessment are highly important, given the fact that medieval Arabic literary criticism does not always reflect praxis or focus on the actual practicalities of composing poetry. This practice and the contextualized way in which it was preserved allow us to see vividly the inextricable link between poetic form and the conditions in which poetry was created. It likewise sheds light on the intricate ways in which poets resisted, influenced, and manipulated others by poetic means. Based on the obvious fact that collaborative composition is imbued with the spirit of play, I offer at the end of the article criticism of Johan Huizinga’s famous play concept and his (much less famous) views of early Arabic culture and poetry in light of the evidence I studied.
Procédés de décrédibilisation dans al-Fīl al-azraq, roman noir d’Aḥmad Murād
Authors: Ghosn Katia 
Published: March 2018

Abstract
Contemporary Egyptian author Aḥmad Murād writes works of fiction as well as crime novels. The detective genre emerged very late on the Arab literary scene in comparison to its birth in the 19th century in the West. Al-Fīl al-azraq (The blue elephant), that we are about to analyse, is based on a psychological story. It fits into the matrix of the black novel as it appeared in the United States in the interwar period and incorporates many of its strategies. In this article, we will try to uncover the processes of “decredibilization” established in the novel, in order to create “undecidability” as to the outcome of the investigation and to set up, from a hermeneutic point of view, some confusion of meaning. We will try subsequently to underline the distinctive features of the generic model of the novel, prominent among which, the open structure, the fantastic themes, the use of the vernacular and a certain social realism outlook.
Ossicular Chain Reconstruction in a Developing Country
Authors: Bedri Es-Hak , Redleaf Miriam 
Published: March 2018

Objectives: In Ethiopia, 2-stage operations with middle ear prostheses are economically unfavorable. We hypothesized that single-stage autologous ossiculoplasty results in acceptable tympanic membrane (TM) and hearing improvements in a setting of limited resources. Methods: One hundred eighty-eight patients (197 ears) who underwent 1-stage autologous ossiculoplasty for ossicular dysfunction are presented. All but 14 of these ears also had perforations of the TM. Conditions of the middle ear were granulation tissue, ossicular disruption only, tympanosclerosis, and cholesteatoma. Reconstructions of the ossicular chain were performed with autologous ossicles only. Results: The closure rate of TM perforations was 95%. Preoperative air bone gaps were 27 to 60 dB (mean [SD] = 44 [7] dB); postoperative air bone gaps were 0 to 50 dB (average [SD] = 23 [10] dB), for an average improvement of 21 dB across all reconstruction types ( P < .001). The largest favorable changes in air bone gaps were with incus and malleus columellas from the footplate to the TM (33 and 23 dB, respectively) ( P < .001). No patient had worsening of sensorineural hearing levels or extrusion of the reconstructed ossicles. Conclusion: Autologous ossiculoplasty performed well in this setting. Acceptable TM closure rates and improvement of air bone gaps were seen in 1-stage operations without the use of prostheses.
Does the Tempo of Music Impact Human Behavior Behind the Wheel?
Authors: Navarro Jordan , Osiurak François , Reynaud Emanuelle 
Published: March 2018

Objective: Assess the influence of background music tempo on driving performance. Background: Music with a fast tempo is known to increase the level of arousal, whereas the reverse is observed for slow music. The relationship between driving performance and level of arousal was expected to take the form of an inverted U-curve. Method: Three experiments were undertaken to manipulate the musical background during driving. In Experiment 1, the driver’s preferred music track played at its original and modified (plus or minus 30%) tempo were used together with the simple ticking of a metronome. In Experiment 2, music tracks of different tempos were played during driving. In Experiment 3, music tracks were categorized as arousing or relaxing based on the associated perceived level of arousal. Results: Listening to music tended to influence drivers’ performances in a car-following task by improving coherence and gain adjustments relative to the followed vehicle but simultaneously shortened the intervehicular time. Although the tempo of the music per se did not directly affect driving behavior, arousing music tracks improved drivers’ adjustments to the followed vehicle (Experiment 3). Conclusion: The tempo of the music listened to behind the wheel was not found to influence driving behaviors. However, arousing music improved drivers’ responsiveness to changes in the speed of the followed vehicle. However, this benefit was canceled out by a reduction in the drivers’ intervehicle safety margin. Application: Listening to arousing music while driving cannot be considered to improve road safety, at least in a car-following task without attentional impairments.
Twenty-three-year trend in firearm deaths in the Transkei subregion of South Africa (1993–2015)
Authors: Meel Banwari 
Published: March 2018

Background Firearm-related deaths are a serious public-health problem in South Africa, which has the second-highest rate of firearm-related deaths in the world. Objective The aim of this study was to examine the trend in firearm deaths in the Transkei subregion of South Africa. Method An autopsy record review study was conducted at the Forensic Pathology Laboratory at Mthatha over a period of 23 years (1993–2015). Results Over a 23-year period (1993–2015), 27,036 autopsies were performed at the Mthatha Forensic Pathology Laboratory on people who had died from unnatural causes. Of these, 3935 (14.2%) deaths were related to firearm injuries. The average gunshot death rate during the study period was 29/100,000 of the population annually. The majority (3236; 82%) were males, among whom the death rate was 24.4/100,000 of the population per year. The rate of gunshot deaths was 27/100,000 of the population in 1993, while in 2015 it was 12.8/100,000. About a third (1207; 31%) of victims were between 21 and 30 years of age. Conclusion The gunshot death rate is at an unacceptably high level in the Transkei subregion of South Africa, especially among young people.
Training Strategies for Effective Computerization
Authors: Singh S K 
Published: March 2018

Training has been a neglected area in the information systems function. When the technological perspective of the information systems function was dominant, the scope of training was restricted to upgrading/imparting technical skills for implementation of information systems. In recent years, the socio-technical perspective of information systems has gained wider acceptance and the role of training has come into sharper focus. Information systems-related training has multiple objectives and multiple constituencies. It has to be imparted in stages and must use appropriate tools for the particular objective-constituency configuration. This paper takes a total-system view of information systems-related training and proposes a comprehensive framework to enhance the effectiveness of computerization in organizations.
The Role of the Paratenon in Achilles Tendon Healing: A Study in Rats
Authors: Müller Sebastian A. , Evans Christopher H. , Heisterbach Patricia E. , Majewski Martin 
Published: March 2018

Background: The role of the paratenon in tendon healing is unknown. The present study compares healing in the presence or absence of the paratenon in an Achilles tendon defect model in rats. Hypothesis: Resection of the paratenon impairs tendon healing. Study Design: Controlled laboratory study. Methods: Sixty skeletally mature Sprague Dawley rats were randomly assigned to either a resected paratenon (RP) group or an intact paratenon (IP) group. In all animals, a 4-mm portion of the Achilles tendon was resected in the midsubstance. In the RP group, the paratenon was resected completely. In the IP group, the paratenon was opened longitudinally and closed again after the tendon defect had been created. One, 2, and 4 weeks after surgery, 7 animals per group were tested biomechanically and 3 animals per group examined histologically. Results: The recovery of mechanical strength was much more rapid in IP tendons. Tear resistance was significantly increased for IP tendons (41.3 ± 8.8 N and 47.3 ± 14.1 N, respectively) compared with RP tendons (19.3 ± 9.1 N and 33.2 ± 6.4 N, respectively) after 1 and 2 weeks. The cross-sectional area was larger in the IP group after 1 and 2 weeks (8.2 ± 2.3 mm2 and 11.3 ± 3.1 mm2 vs 5.0 ± 2.4 mm2 and 5.9 ± 2.0 mm2, respectively) compared with the RP group. Tendon stiffness was greater in the IP group after 1 week (10.4 ± 1.9 N/mm vs 4.5 ± 1.6 N/mm, respectively) compared with the RP group. In comparison, normal contralateral tendons had a maximal tear resistance of 56.6 ± 7.2 N, a cross-sectional area of 3.6 ± 0.7 mm2, and stiffness of 17.3 ± 3.8 N/mm. Hematoxylin and eosin staining revealed slightly delayed healing of RP tendons. Early collagen formation was seen in the IP group already after 1 week, whereas in the RP group, this only occurred after 2 weeks. After 4 weeks, the IP tendons showed more collagen crimp formation than the RP tendons. Conclusion: An intact paratenon promotes healing of the Achilles tendon. Clinical Relevance: Although incision or resection of the paratenon has been advocated when repairing injured or degenerative tendons, our data suggest that the integrity of the paratenon should be preserved.
Perfusion imaging and recurrent cerebrovascular events in intracranial atherosclerotic disease or carotid occlusion
Authors: Sacchetti Daniel C , Cutting Shawna M , McTaggart Ryan A , Chang Andrew D , Hemendinger Morgan , Mac Grory Brian , Siket Matthew S , Burton Tina , Thompson Bradford , Rostanski Sara K , Prabhakaran Shyam , Willey Joshua Z , Marshall Randolph S , Elkind Mitchell SV , Khatri Pooja , Furie Karen L , Jayaraman Mahesh V , Yaghi Shadi 
Published: March 2018

Background Large vessel disease stroke subtype carries the highest risk of early recurrent stroke. In this study we aim to look at the association between impaired perfusion and early stroke recurrence in patients with intracranial atherosclerotic disease or total cervical carotid occlusion. Methods This is a retrospective study from a comprehensive stroke center where we included consecutive patients 18 years or older with intracranial atherosclerotic disease or total cervical carotid occlusion admitted with a diagnosis of ischemic stroke within 24 h from symptom onset with National Institute Health Stroke Scale < 15, between 1 December 2016 and 30 June 2017. Patients with (1) evidence of ≥ 50% stenosis of a large intracranial artery or total carotid artery occlusion, (2) symptoms referable to the territory of the affected artery, and (3) perfusion imaging data using the RAPID processing software were included. The primary predictor was unfavorable perfusion imaging defined as Tmax > 6 s mismatch volume (penumbra volume–infarct volume) of 15 ml or more. The outcome was recurrent cerebrovascular events at 90 days defined as worsening or new neurological symptoms in the absence of a nonvascular cause attributable to the decline, or new infarct or infarct extension in the territory of the affected artery. We used Cox proportional hazards models to determine the association between impaired perfusion and recurrent cerebrovascular events. Results Sixty-two patients met our inclusion criteria; mean age 66.4 ± 13.1 years, 64.5% male (40/62) and 50.0% (31/62) with intracranial atherosclerotic disease. When compared to patients with favorable perfusion pattern, patients with unfavorable perfusion pattern were more likely to have recurrent cerebrovascular events (55.6% (10/18) versus 9.1% (4/44), p < 0.001). This association persisted after adjusting for potential confounders (adjusted hazard ratio 10.44, 95% confidence interval 2.30–47.42, p = 0.002). Conclusion Perfusion mismatch predicts recurrent cerebrovascular events in patients with ischemic stroke due to intracranial atherosclerotic disease or total cervical carotid occlusion. Studies are needed to determine the utility of revascularization strategies in this patient population.