bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for convergent evolution of a neocortex‐like structure in a late Permian therapsid
Authors: Laaß Michael , Kaestner Anders
Published: June 2017

The special sensory, motor, and cognitive capabilities of mammals mainly depend upon the neocortex, which is the six‐layered cover of the mammalian forebrain. The origin of the neocortex is still controversial and the current view is that larger brains with neocortex first evolved in late Triassic Mammaliaformes. Here, we report the earliest evidence of a structure analogous to the mammalian neocortex in a forerunner of mammals, the fossorial anomodontKawingasaurus fossilisfrom the late Permian of Tanzania. The endocranial cavity ofKawingasaurusis almost completely ossified, which allowed a less hypothetical virtual reconstruction of the brain endocast to be generated. A parietal foramen is absent. A small pit between the cerebral hemispheres is interpreted as a pineal body. The inflated cerebral hemispheres are demarcated from each other by a median sulcus and by a possible rhinal fissure from the rest of the endocast. The encephalization quotient estimated by using the method of Eisenberg is 0.52, which is 2–3 times larger than in other nonmammalian synapsids. Another remarkable feature are the extremely ramified infraorbital canals in the snout. The shape of the brain endocast, the extremely ramified maxillary canals as well as the small frontally placed eyes suggest that special sensory adaptations to the subterranean habitat such as a well developed sense of touch and binocular vision may have driven the parallel evolution of an equivalent of the mammalian neocortex and a mammal‐like lemnothalamic visual system inKawingasaurus. The gross anatomy of the brain endocast ofKawingasaurussupports the Outgroup Hypothesis, according to which the neocortex evolved from the dorsal pallium of an amphibian‐like ancestor, which receives sensory projections from the lemnothalamic pathway. The enlarged brain as well as the absence of a parietal foramen may be an indication for a higher metabolic rate ofKawingasauruscompared to other nonmammalian synapsids.
Aromatic amino acids and their relevance in the specificity of the PH domain
Authors: Morales Ja , Sobol M. , Rodriguez‐Zapata L.C. , Hozak P. , Castano E.
Published: June 2017

Phosphoinositides are phosphatidylinositol derived, well known to be second messengers in various cell signaling pathways as well as in processes such as cell differentiation, cellular stress response, gene transcription, and chromatin remodeling. The pleckstrin homology domain of phospholipase C‐delta 1 is responsible for recognizing and binding to PI(4,5)P2 and for this reason has been widely used to study this phosphoinositide as a biosensor when it is conjugated to a fluorescent tag. In this work, we modified the primary structure of pleckstrin homology domain by site‐specific mutagenesis to change the specificity for phosphoinositides. We obtained 3 mutants: K30A, W36F, and W36Y with different specificity to phosphoinositides. Mutant domain K30A recognized PI(4,5)P2, PI(3,4,5)P3, phosphatidic acid (PA), and weakly PI(3,5)P2. Mutant domain W36F recognized all the phosphoinositides studied and the PA. Finally, mutant domain W36Y seemed to interact with PA and all the other phosphoinositides studied, except PI(3)P. The changes in recognition argue against a simple charge and nonpolar region model for these interactions and more in favor of a specific docking region with a specific recognition site. We conducted in silico modeling that explains the mechanisms behind the observed changes and showed that aromatic amino acids appear to play more important role, than previously thought, in the specificity of phospholipids' binding domains.
Projected precipitation changes within the Great Lakes and Western Lake Erie Basin: a multi‐model analysis of intensity and seasonality
Authors: Basile Samantha J. , Rauscher Sara A. , Steiner Allison L.
Published: June 2017

The Great Lakes region encompasses the largest freshwater lake network in the world and supports a diverse network of agriculture, transportation, and tourism. Recently, Lake Erie has experienced increased hypoxia events, which have been attributed to agricultural practices and changes in run‐off. Here we examine the projected changes in extreme precipitation events to address concerns regarding regional agriculture, surface run‐off, and subsequent water quality. Precipitation projections within the overall Great Lakes Basin and the Western Lake Erie Basin subregion are examined using climate model simulations of varying spatial resolutions to understand historical precipitation and projected future precipitation. We develop three model ensembles for the historical period (1980–1999) and the mid‐century (2041–2060) that cover a range of spatial resolutions and future emissions scenarios, including: (1) 12 global model members from the fifth Climate Model Intercomparison Project (CMIP5) using Representative Concentration Pathway (RCP) 8.5, (2) ten regional climate model (RCM) members from the North American Regional Climate Change Assessment Program driven by CMIP3 global models using the A2 emissions scenario, and (3) two high resolution RCM simulations (RCM4) driven by CMIP5 global models using the RCP 8.5 scenario. For the historical period, all model ensembles overestimate winter and spring precipitation, and many of the models simulate a summer drying that is not observed. At mid‐century, most of the models predict a 10–20% increase in precipitation depending on the time of year. Daily probability distribution functions from three model ensembles reveal spring seasonal increases in high precipitation event probabilities when compared to the historical period, suggesting an increase in the frequency of high intensity precipitation at mid‐century. Overall, the presence of lakes or higher spatial resolution does not ensure improved representation of historical processes, and more complex interactions between large‐scale dynamics, local feedbacks, and physical parameterizations drive the model spread.
Effect of applying cinnamaldehyde incorporated in wax on green mould decay in citrus fruits
Authors: Duan Xiaofang , OuYang Qiuli , Tao Nengguo
Published: June 2017

BACKGROUND

Green mould caused by Penicillium digitatum is the most damaging postharvest diseases of citrus fruit. Cinnamaldehyde (CA) is a food additive that has potential use in controlling postharvest disease of fruits and vegetables. In this study, the effectiveness of wax with CA (WCA) in controlling Ponkan (Citrus reticulata Blanco) green mould was investigated.

RESULTS

The mycelial growth of P. digitatum was inhibited by CA in a dose‐dependent manner. The minimum inhibitory concentration and minimum fungicidal concentration (MFC) were both 0.50 mL L−1. In vivo tests demonstrated that WCA (1 × and 10 × MFC) applied to Ponkan fruits inoculated with P. digitatum could significantly decrease the incidence of green mould for up to 5 days. The WCA treatment increased the activities of catalase, superoxide dismutase, peroxidase, phenylalanine ammonia lyase, polyphenol oxidase, as well as the total phenols and flavonoids contents. Meanwhile, the treatment remarkably decreased the weight loss rate of fruits and maintained fruit quality. These results indicated that WCA treatment might induce defence responses against green mould in citrus fruit.

CONCLUSION

Our findings suggest that WCA might be a promising approach in controlling green mould of citrus fruits. © 2017 Society of Chemical Industry
The impact of a head and neck microvascular fellowship program on otolaryngology resident training
Authors: Zender Chad A. , Clancy Kate , Melki Sami , Li Shawn , Fowler Nicole
Published: June 2017

Objective

To assess the impact of a microvascular head and neck (H&N) fellowship on senior residents' surgical experience.

Study Design

Retrospective review of Accreditation Council for Graduate Medical Education‐generated operative case log reports, retrospective chart review, and electronic survey.

Methods

A retrospective review of one institution's residents' H&N operative case logs and free flap operative reports was performed to determine changes in key indicator cases (KICs) after the addition of a H&N fellowship. An electronic survey was distributed to senior residents at all U.S. otolaryngology residency programs to determine residents' perceptions of a H&N fellow's impact on their surgical experience. An electronic survey was distributed to senior medical students applying to surgical residencies to explore the perceived impact that a fellowship has on the desirability of a residency program.

Results

The average number of each postgraduate year (PGY)5's H&N KIC before and after the addition of the fellowship were: parotidectomy, 19 versus 17.8; neck dissection, 33.2 versus 40.6; oral cavity resection, 15.3 versus 12.6; thyroid/parathyroid, 45.5 versus 45.6; and flaps/grafts, 56.7 versus 42. PGY5 participation as first assistant in free flaps dropped from 78% to 17%; however, residents still participated in some aspect of 45% of the cases. Seventy percent of senior residents reported a positive perception of the H&N fellow on their H&N operative experience. Eighty‐nine percent of senior medical student respondents reported a nonnegative perception of a fellowship in their applied field.

Conclusion

The addition of a H&N fellowship did not decrease senior residents' H&N KIC, and most senior residents at programs with fellowships report that the fellow has a positive impact on their H&N operative experience.

Level of Evidence

4. Laryngoscope, 128:52–56, 2018
Coregulation of the cyclic lipopeptides orfamide and sessilin in the biocontrol strain Pseudomonas sp. CMR12a
Authors: Olorunleke Feyisara E. , Kieu Nam P. , De Waele Evelien , Timmerman Marc , Ongena Marc , Höfte Monica
Published: June 2017

Cyclic lipopeptides (CLPs) are synthesized by nonribosomal peptide synthetases (NRPS), which are often flanked by LuxR‐type transcriptional regulators. Pseudomonas sp. CMR12a, an effective biocontrol strain, produces two different classes of CLPs namely sessilins and orfamides. The orfamide biosynthesis gene cluster is flanked up‐ and downstream by LuxR‐type regulatory genes designated ofaR1 and ofaR2, respectively, whereas the sessilin biosynthesis gene cluster has one LuxR‐type regulatory gene which is situated upstream of the cluster and is designated sesR. Our study investigated the role of these three regulators in the biosynthesis of orfamides and sessilins. Phylogenetic analyses positioned OfaR1 and OfaR2 with LuxR regulatory proteins of similar orfamide‐producing Pseudomonas strains and the SesR with that of the tolaasin producer, Pseudomonas tolaasii. LC‐ESI‐MS analyses revealed that sessilins and orfamides are coproduced and that production starts in the late exponential phase. However, sessilins are secreted earlier and in large amounts, while orfamides are predominantly retained in the cell. Deletion mutants in ofaR1 and ofaR2 lost the capacity to produce both orfamides and sessilins, whereas the sesR mutant showed no clear phenotype. Additionally, RT‐PCR analysis showed that in the sessilin cluster, a mutation in either ofaR1 or ofaR2 led to weaker transcripts of the biosynthesis genes, sesABC, and putative transporter genes, macA1B1. In the orfamide cluster, mainly the biosynthesis genes ofaBC were affected, while the first biosynthesis gene ofaA and putative macA2B2 transport genes were still transcribed. A mutation in either ofaR1, ofaR2, or sesR genes did not abolish the transcription of any of the other two.
Diagnostic Value of Combined Acute Levodopa Challenge and Olfactory Testing to Predict Parkinson's Disease
Authors: Terroba Chambi Cinthia , Rossi Malco , Bril Andrea , Vernetti Patricio Millar , Cerquetti Daniel , Cammarota Angel , Merello Marcelo
Published: June 2017

Background

The diagnosis of Parkinson's disease (PD) can be challenging early in the disease course, when motor features are subtle. The objective of this study was to explore the diagnostic value of combining acute levodopa challenge and olfactory testing to predict PD.

Methods

Data from 210 patients with a recent onset of parkinsonism who had at least 2 years of follow‐up and underwent acute levodopa challenge for the clinical prediction of long‐term dopaminergic response and had olfactory testing with Sniffin’ Sticks Test were evaluated. Single and combined diagnostic measures were analyzed.

Results

After 2 years of follow‐up, a PD diagnosis was confirmed in 157 patients who fulfilled United Kingdom Parkinson's Disease Society Brain Bank criteria and was ruled out in 53. Sensitivity and specificity of acute levodopa challenge to predict PD diagnosis were 0.71 and 0.94, respectively. Sensitivity and specificity of olfactory tests were calculated according to the total olfactory score for hyposmia (0.61 and 0.77 respectively), the hyposmia identification subscore (0.63 and 0.74, respectively), and the anosmia score (0.40 and 0.85, respectively). The best combination identified was response to acute levodopa challenge together with hyposmia according to the total olfactory score (sensitivity, 0.90; specificity, 0.74; positive predictive value, 0.91; negative predictive value, 0.72; accuracy, 0.86).

Conclusion

The combination of response to acute levodopa challenge with hyposmia according to the total olfactory score improved sensitivity for the early diagnosis of PD.
Ultrasound‐guided hydrodissection decreases gliding resistance of the median nerve within the carpal tunnel
Authors: Evers Stefanie , Thoreson Andrew R. , Smith Jay , Zhao Chunfeng , Geske Jennifer R. , Amadio Peter C.
Published: June 2017

Introduction: The aim of this study was to assess alterations in median nerve (MN) biomechanics within the carpal tunnel resulting from ultrasound‐guided hydrodissection in a cadaveric model. Methods: Twelve fresh frozen human cadaver hands were used. MN gliding resistance was measured at baseline and posthydrodissection, by pulling the nerve proximally and then returning it to the origin. Six specimens were treated with hydrodissection, and 6 were used as controls. Results: In the hydrodissection group there was a significant reduction in mean peak gliding resistance of 92.9 ± 34.8 mN between baseline and immediately posthydrodissection (21.4% ± 10.5%; P = 0.001). No significant reduction between baseline and the second cycle occurred in the control group: 9.6 ± 29.8 mN (0.4% ± 5.3%; P = 0.467). Discussion: Hydrodissection can decrease the gliding resistance of the MN within the carpal tunnel, at least in wrists unaffected by carpal tunnel syndrome. A clinical trial of hydrodissection seems justified. Muscle Nerve 57: 25–32, 2018
Modification of polyoxymethylene for increased thermal resistance
Authors: Merijs Meri Remo , Zicans Jānis , Ābele Agnese , Ivanova Tatjana , Kalniņš Mārtiņš , Kundziņš Kārlis
Published: June 2017

Ternary nanocomposites, composed of polyoxymethylene (POM), ethylene octene copolymer and zinc oxide (ZnO), are prepared by melt compounding. The effects of two types of ethylene‐octene copolymers, differing with α‐octene content (38% for EOC38 and 17% for EOC17), as well as nanostructured ZnO on thermal behavior of POM are investigated. The content of EOC in the POM based composites is varied between 10 and 50 wt%, while the content of ZnO is 2 wt%. Thermal behavior of POM based systems are studied by using differential scanning calorimetry and thermogravimetric analysis coupled with Fourier transform infrared spectroscopy. Results of thermogravimetric analysis show that, by rising either the elastomer or ZnO content, thermal stability of the investigated POM composites can be increased. The modifying effect of EOC17 in respect of thermal resistance is somewhat greater than that of EOC38. Simultaneous addition of EOC and ZnO to POM is synergistic with respect to thermal stability of the composite material. POLYM. ENG. SCI., 57:772–778, 2017. © 2017 Society of Plastics Engineers
Divergent regeneration‐competent cells adopt a common mechanism for callus initiation in angiosperms
Authors: Hu Bo , Zhang Guifang , Liu Wu , Shi Jianmin , Wang Hua , Qi Meifang , Li Jiqin , Qin Peng , Ruan Ying , Huang Hai , Zhang Yijing , Xu Lin
Published: June 2017

In tissue culture, the formation of callus from detached explants is a key step in plant regeneration; however, the regenerative abilities in different species are variable. While nearly all parts of organs of the dicot Arabidopsis thaliana are ready for callus formation, mature regions of organs in monocot rice (Oryza sativa) and other cereals are extremely unresponsive to tissue culture. Whether there is a common molecular mechanism beyond these different regenerative phenomena is unclear. Here we show that the Arabidopsis and rice use different regeneration‐competent cells to initiate callus, whereas the cells all adopt WUSCHEL‐RELATED HOMEOBOX 11 (WOX11) and WOX5 during cell fate transition. Different from Arabidopsis which maintains regeneration‐competent cells in mature organs, rice exhausts those cells during organ maturation, resulting in regenerative inability in mature organs. Our study not only explains this old perplexity in agricultural biotechnology, but also provides common molecular markers for tissue culture of different angiosperm species.
Influence of corn variety, drying temperature, and moisture content at harvest on the saccharides released during an in vitro pepsin‐pancreatin digestion
Authors: Odjo Sylvanus , Huart François , Béra François , Jacquet Nicolas , Richel Aurore , Blecker Christophe , Malumba Paul
Published: June 2017

High‐performance anion‐exchange chromatography coupled with pulsed amperometric detection (HPAEC‐PAD) was used to quantify and to determine the nature of saccharides released after the digestion of two corn grains submitted to different drying and harvesting protocols. Five saccharides were quantified: glucose, maltose, isomaltose, maltotriose, and glucosyl‐maltotriose. After a subsequent hydrolysis with amyloglucosidase of the released saccharides, the amount of total glucose recovered increased with the increase in drying temperature and the moisture content of grain at harvest. These results suggest that structural changes induced within corn starch granules during drying affect their hydrolysis by amylases. These changes may lead to different pathways of sugar absorption in the small intestine of monogastrics. Thus, corn grains with a similar composition may lead to different levels of metabolizable energy upon gastro‐intestinal digestion.
Situational Awareness: Detecting Critical Dependencies and Devices in a Network
Authors: Laštovička Martin , Čeleda Pavel
Published: June 2017

Large-scale networks consisting of thousands of connected devices are like a living organism, constantly changing and evolving. It is very difficult for a human administrator to orient in such environment and to react to emerging security threats. With such motivation, this PhD proposal aims to find new methods for automatic identification of devices, the services they provide, their dependencies and importance. The main focus of the proposal is to find novel approaches to building cyber situational awareness in an unknown network for the purpose of computer security incident response. Our research is at the initial phase and will contribute to a PhD thesis in four years.
An Optimized Resilient Advance Bandwidth Scheduling for Media Delivery Services
Authors: Barshan Maryam , Moens Hendrik , Volckaert Bruno , De Turck Filip
Published: June 2017

In IP-based media delivery services, we often deal with predictable network load and traffic, making it beneficial to use advance reservations even when network failure occurs. In such a network, to offer reliable reservations, fault-tolerance related features should be incorporated in the advance reservation system. In this paper, we propose an optimized protection mechanism in which backup paths are selected in advance to protect the transfers when any failure happens in the network. Using a shared backup path protection, the proposed approach minimizes the backup capacity of the requests while guaranteeing 100% single link failure recovery. We have evaluated the quality and complexity of our proposed solution and the impact of different percentages of backup demands and timeslot sizes have been investigated in depth. The presented approach has been compared to our previously-designed algorithm as a baseline. Our simulation results reveal a noticeable improvement in request acceptance rate, up to 9.2%. Moreover, with fine-grained timeslot sizes and under limited network capacity, the time complexity of the proposed solution is up to 14% lower.
Impact of Residency Training Level on the Surgical Quality Following General Surgery Procedures
Authors: Loiero Dominik , Slankamenac Maja , Clavien Pierre‐Alain , Slankamenac Ksenija
Published: June 2017

Objective

To investigate the safety of surgical performance by residents of different training level performing common general surgical procedures.

Methods

Data were consecutively collected from all patients undergoing general surgical procedures such as laparoscopic cholecystectomy, laparoscopic appendectomy, inguinal, femoral and umbilical hernia repair from 2005 to 2011 at the Department of Surgery of the University Hospital of Zurich, Switzerland. The operating surgeons were grouped into junior residents, senior residents and consultants. The comprehensive complication index (CCI) representing the overall number and severity of all postoperative complications served as primary safety endpoint. A multivariable linear regression analysis was used to analyze differences between groups. Additionally, we focused on the impact of senior residents assisting junior residents on postoperative outcome comparing to consultants.

Results

During the observed time, 2715 patients underwent a general surgical procedure. In 1114 times, a senior resident operated and in 669 procedures junior residents performed the surgery. The overall postoperative morbidity quantified by the CCI was for consultants 5.0 (SD 10.7), for senior residents 3.5 (8.2) and for junior residents 3.6 (8.3). After adjusting for possible confounders, no difference between groups concerning the postoperative complications was detected. There is also no difference in postoperative complications detectable if junior residents were assisted by consultants then if assisted by senior residents.

Discussion

Patient safety is ensured in general surgery when performed by surgical junior residents. Senior residents are able to adopt the role of the teaching surgeon in charge without compromising patients’ safety.
In Vitro Apoptosis Induction in a Human Prostate Cancer Cell Line by Thermotolerant Glycolipid from Bacillus licheniformis SV1
Authors: Gupta Sonam , Varshney Ritu , Jha Rajan Kumar , Pruthi Parul A. , Roy Partha , Pruthi Vikas
Published: June 2017

A highly potent glycolipid was isolated from a crude oil‐contaminated soil bacterium Bacillus licheniformis SV1 (NCBI GenBank Acc. No. KX130852) when grown on a modified mineral salt medium supplemented with 2% oleic acid. The maximum reduction in surface tension of cell‐free broth from 71 ± 0.812 to 25.919 ± 0.984 mN/m with 89 ± 0.346% emulsification activity was recorded after 120 h of growth. Glycolipid was purified using chromatographic techniques and the presence of aliphatic chain (C–H stretch) and OH‐band was revealed by NMR, GC–MS and FTIR analysis. Stability of glycolipid up to 250 °C and its complete decomposition at 507 °C was recorded by thermogravimetric analysis (TGA). MTT assay (IC50 = 0.473 ± 0.048 mg/ml) along with 4′,6‐diamidino‐2‐phenylindole (DAPI) and acridine orange and ethidium bromide (AO/EtBr) staining validated that glycolipid induces cell apoptosis in human prostate cancer cell line (PC‐3). Furthermore, potent anti‐cancerous compounds such as 9‐octadecanoic acid (22.55%), linoleic acid methyl ester (2.2%) and palmitic acid (1.18%) were also detected in the GC–MS spectra of the purified glycolipid.
Revisión del tema de sinergias corporativas: origen, resultados y beneficiarios
Authors: Rivas Luz Maria , Londoño Correa Diana
Published: June 2017

La materialización de sinergias es un reto para la administración de empresas multinegocios. En este texto se  presenta el estado del conocimiento sobre las sinergias en el subcampo de la estrategia corporativa. Para ello se estudian artículos publicados entre 2003 y 2015 en revistas académicas, reconocidas por el Institute for Scientific Información  ISI Web of Science y por Scimago. Esta revisión de tema diferencia las investigaciones que abordan las sinergias como resultado en la etapa de adquisición y se centra en la de integración, donde la práctica administrativa toma mayor relevancia. Por lo tanto, se propone estudiarlas sinergias a partir de criterios de clasificación identificados en la literatura: origen, resultados y beneficiarios. De esta forma, reconocer la diversidad de sinergias abre un camino para enfrentar el reto de la administración multinegocios.
Hematopoietic stem cell transplantation for sickle cell disease
Authors: Kassim Adetola A. , Sharma Deva
Published: June 2017

Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative therapy for sickle cell disease (SCD); however, its use is limited by lack of suitable human leukocyte antigen (HLA)-matched donors and decreased application in older patients with significant morbidity. Myeloablative, HLA-identical sibling transplantation in children with SCD offers excellent long-term survival, with overall and event-free survival rates of 95% and 92%, respectively. However, the risk of graft-versus-host-disease, infections, infertility, and other long-term transplant complications, further limits its widespread use. Recent approaches using reduced intensity conditioning (RIC) are associated with lower toxicity, allowing extension of this modality to children and adults with significant morbidity; however, these approaches are also associated with increased risk of graft failure. The optimal RIC regimen that strikes the optimal balance between maximizing the rate of stable engraftment while minimizing transplant-related morbidity and mortality is unknown. Alternative donor transplants, most prominently, partial HLA-mismatched related transplants (haploidentical), are being investigated with promising initial results. This review will discuss long-term results of HLA- matched sibling HSCT for SCD, and recent updates on HLA-matched unrelated donor and unrelated umbilical cord blood HSCT for SCD.
Hematopoietic cell transplantation in Fanconi anemia and dyskeratosis congenita
Authors: Ayas Mouhab
Published: June 2017

Bone marrow failure syndrome is an epithet of bone marrow failure (all or single-cell lineage) that is attributable to an underlying genetic aberration usually with a constellation of somatic abnormalities. Multiple inheritance patterns have been described in these disorders; many are transmitted in an autosomal recessive pattern, which may consequently lead to a higher prevalence of such illnesses in homogeneous societies such as Saudi Arabia, where consanguineous marriages are not uncommon. At King Faisal Specialist Hospital and Research Center, the most common entity referred for allogeneic hematopoietic cell transplantation (HCT) is Fanconi anemia, followed by pure red aplasia, and, less commonly, dyskeratosis congenita, congenital neutropenia, and others. Of all the congenital bone marrow failure syndromes, two of them- Fanconi anemia and dyskeratosis congenita-represent a real challenge in terms of conditioning for HCT and require special attention. This minireview is a snapshot of the recent international and local experience of HCT in these two entities.
No Difference Between Noxious and Innocuous Thermal Stimulation on Motor Recovery of Upper Extremity in Patients With Acute Stroke: A Randomized Controlled Trial With 6‐Month Follow‐up
Authors: Lin Roxane , Hsu Miao‐Ju , Lin Ruey‐Tay , Huang Mao‐Hsiung , Koh Chia‐Lin , Hsieh Ching‐Lin , Lin Jau‐Hong
Published: June 2017

Background

Thermal stimulation (TS) has been developed and incorporated into stroke rehabilitation. However, whether noxious and innocuous TS induce the same effects on motor function recovery after stroke is still unknown. A comparative study of different temperature combination regimens is needed.

Objective

To compare the short‐ and long‐term effectiveness between noxious and innocuous TS on motor recovery of upper extremity in patients with acute stroke.

Design

Randomized, controlled trial with concealed allocation, intention‐to‐treat analysis and blinded outcome assessors.

Setting

A university hospital rehabilitation department in Taiwan.

Participants

A total of 79 patients with acute ischemic stroke were recruited. The majority had moderate to severe motor impairment of the upper extremity (UE).

Intervention

In addition to traditional rehabilitation, the experimental group (n = 39) underwent noxious TS (heat pain 46‐47°C/cold pain 7‐8°C), and the control group (n = 40) received innocuous TS (heat 40‐41°C/cold 20‐21°C). TS intervention was applied for 30 minutes once per day and for a total of 20‐24 times during hospital stay. A custom‐made TS instrument, comprising 2 thermal stimulators and their respective thermal pads constructed in a closed‐loop system, was used.

Outcomes

The Fugl‐Meyer upper extremity score (the primary outcome), Action Research Arm Test, Motricity Index, Barthel Index, and modified Ashworth scale (the secondary outcomes) were administered by a blinded assessor at baseline, post–12th TS, post‐intervention, 1‐month, and 6‐month follow‐ups.

Results

No significant differences between groups were found on the primary outcome at postintervention and follow‐up assessments. At 1‐month follow‐up, the innocuous group showed a small effect (partial η2 = 0.02) that was greater than that of the noxious group, but that effect was eliminated at 6 months. Both groups presented significant within‐group improvements over time (both P < .001).

Conclusions

Combining noxious TS with traditional rehabilitation did not yield better short‐term or long‐term results than combining innocuous TS with traditional rehabilitation on UE functional recovery for individuals with acute stroke.

Level of Evidence

II
Presentación de reporte de caso: adenocarcinoma de célula clara de uretra
Authors: González Nataly , Ramirez Yuly , Szelezsán Jose , Rojas Daniel
Published: June 2017

El adenocarcinoma de célula clara de uretra es un tumor agresivo, poco frecuente, que afecta predominantemente a mujeres adultas. Se presenta el caso de una paciente de 64 años con hematuria de larga data, en quien se diagnostica este tipo de tumor se realiza tratamiento quirúrgico y actualmente presenta evolución satisfactoria.
Lab Tests Probe Carbon Planets’ Inner Dynamics
Authors: Cook Terri
Published: June 2017

Thermal convection in deep interiors could be more vigorous in carbide planets than in comparably sized silicate planets, according to new high-pressure measurements of silicon carbide.
Paleomagnetic Data Hint at Link from Earth’s Core to Continents
Authors: den Hond Bas
Published: June 2017

Earth’s magnetic field waxes and wanes as supercontinents form and break up, suggests a new study postulating a direct connection between our planet’s crust and its core.
Targeted two-photon chemical apoptotic ablation of defined cell types in vivo
Authors: Hill Robert A. , Damisah Eyiyemisi C. , Chen Fuyi , Kwan Alex C. , Grutzendler Jaime
Published: June 2017

A major bottleneck limiting understanding of mechanisms and consequences of cell death in complex organisms is the inability to induce and visualize this process with spatial and temporal precision in living animals. Here we report a technique termed two-photon chemical apoptotic targeted ablation (2Phatal) that uses focal illumination with a femtosecond-pulsed laser to bleach a nucleic acid-binding dye causing dose-dependent apoptosis of individual cells without collateral damage. Using 2Phatal, we achieve precise ablation of distinct populations of neurons, glia and pericytes in the mouse brain and in zebrafish. When combined with organelle-targeted fluorescent proteins and biosensors, we uncover previously unrecognized cell-type differences in patterns of apoptosis and associated dynamics of ribosomal disassembly, calcium overload and mitochondrial fission. 2Phatal provides a powerful and rapidly adoptable platform to investigate in vivo functional consequences and neural plasticity following cell death as well as apoptosis, cell clearance and tissue remodelling in diverse organs and species.
Observing electron localization in a dissociating H2+ molecule in real time
Authors: Xu H. , Li Zhichao , He Feng , Wang X. , Atia-Tul-Noor A. , Kielpinski D. , Sang R. T. , Litvinyuk I. V.
Published: June 2017

Dissociation of diatomic molecules with odd number of electrons always causes the unpaired electron to localize on one of the two resulting atomic fragments. In the simplest diatomic molecule H2+ dissociation yields a hydrogen atom and a proton with the sole electron ending up on one of the two nuclei. That is equivalent to breaking of a chemical bond—the most fundamental chemical process. Here we observe such electron localization in real time by performing a pump–probe experiment. We demonstrate that in H2+ electron localization is complete in just 15 fs when the molecule’s internuclear distance reaches 8 atomic units. The measurement is supported by a theoretical simulation based on numerical solution of the time-dependent Schrödinger equation. This observation advances our understanding of detailed dynamics of molecular dissociation.
Francisella requires dynamic type VI secretion system and ClpB to deliver effectors for phagosomal escape
Authors: Brodmann Maj , Dreier Roland F. , Broz Petr , Basler Marek
Published: June 2017

Francisella tularensis is an intracellular pathogen that causes the fatal zoonotic disease tularaemia. Critical for its pathogenesis is the ability of the phagocytosed bacteria to escape into the cell cytosol. For this, the bacteria use a non-canonical type VI secretion system (T6SS) encoded on the Francisella pathogenicity island (FPI). Here we show that in F. novicida T6SS assembly initiates at the bacterial poles both in vitro and within infected macrophages. T6SS dynamics and function depends on the general purpose ClpB unfoldase, which specifically colocalizes with contracted sheaths and is required for their disassembly. T6SS assembly depends on iglF, iglG, iglI and iglJ, whereas pdpC, pdpD, pdpE and anmK are dispensable. Importantly, strains lacking pdpC and pdpD are unable to escape from phagosome, activate AIM2 inflammasome or cause disease in mice. This suggests that PdpC and PdpD are T6SS effectors involved in phagosome rupture.
Lkb1 maintains Treg cell lineage identity
Authors: Wu Di , Luo Yuechen , Guo Wei , Niu Qing , Xue Ting , Yang Fei , Sun Xiaolei , Chen Song , Liu Yuanyuan , Liu Jingru , Sun Zhina , Zhao Chunxiao , Huang Huifang , Liao Fang , Han Zhongchao , Zhou Dongming , Yang Yongguang , Xu Guogang , Cheng Tao , Feng Xiaoming
Published: June 2017

Regulatory T (Treg) cells are a distinct T-cell lineage characterized by sustained Foxp3 expression and potent suppressor function, but the upstream dominant factors that preserve Treg lineage-specific features are mostly unknown. Here, we show that Lkb1 maintains Treg cell lineage identity by stabilizing Foxp3 expression and enforcing suppressor function. Upon T-cell receptor (TCR) stimulation Lkb1 protein expression is upregulated in Treg cells but not in conventional T cells. Mice with Treg cell-specific deletion of Lkb1 develop a fatal early-onset autoimmune disease, with no Foxp3 expression in most Treg cells. Lkb1 stabilizes Foxp3 expression by preventing STAT4-mediated methylation of the conserved noncoding sequence 2 (CNS2) in the Foxp3 locus. Independent of maintaining Foxp3 expression, Lkb1 programs the expression of a wide spectrum of immunosuppressive genes, through mechanisms involving the augmentation of TGF-β signalling. These findings identify a critical function of Lkb1 in maintaining Treg cell lineage identity.
Adaptive self-assembly and induced-fit transformations of anion-binding metal-organic macrocycles
Authors: Zhang Ting , Zhou Li-Peng , Guo Xiao-Qing , Cai Li-Xuan , Sun Qing-Fu
Published: June 2017

Container-molecules are attractive to chemists due to their unique structural characteristics comparable to enzymes and receptors in nature. We report here a family of artificial self-assembled macrocyclic containers that feature induced-fit transformations in response to different anionic guests. Five metal-organic macrocycles with empirical formula of MnL2n (M=Metal; L=Ligand; n=3, 4, 5, 6, 7) are selectively obtained starting from one simple benzimidazole-based ligand and square-planar palladium(II) ions, either by direct anion-adaptive self-assembly or induced-fit transformations. Hydrogen-bonding interactions between the inner surface of the macrocycles and the anionic guests dictate the shape and size of the product. A comprehensive induced-fit transformation map across all the MnL2n species is drawn, with a representative reconstitution process from Pd7L14 to Pd3L6 traced in detail, revealing a gradual ring-shrinking mechanism. We envisage that these macrocyclic molecules with adjustable well-defined hydrogen-bonding pockets will find wide applications in molecular sensing or catalysis.
Probing ultrafast ππ*/nπ* internal conversion in organic chromophores via K-edge resonant absorption
Authors: Wolf T. J. A. , Myhre R. H. , Cryan J. P. , Coriani S. , Squibb R. J. , Battistoni A. , Berrah N. , Bostedt C. , Bucksbaum P. , Coslovich G. , Feifel R. , Gaffney K. J. , Grilj J. , Martinez T. J. , Miyabe S. , Moeller S. P. , Mucke M. , Natan A. , Obaid R. , Osipov T. , Plekan O. , Wang S. , Koch H. , Gühr M.
Published: June 2017

Many photoinduced processes including photosynthesis and human vision happen in organic molecules and involve coupled femtosecond dynamics of nuclei and electrons. Organic molecules with heteroatoms often possess an important excited-state relaxation channel from an optically allowed ππ* to a dark nπ* state. The ππ*/nπ* internal conversion is difficult to investigate, as most spectroscopic methods are not exclusively sensitive to changes in the excited-state electronic structure. Here, we report achieving the required sensitivity by exploiting the element and site specificity of near-edge soft X-ray absorption spectroscopy. As a hole forms in the n orbital during ππ*/nπ* internal conversion, the absorption spectrum at the heteroatom K-edge exhibits an additional resonance. We demonstrate the concept using the nucleobase thymine at the oxygen K-edge, and unambiguously show that ππ*/nπ* internal conversion takes place within (60 ± 30) fs. High-level-coupled cluster calculations confirm the method’s impressive electronic structure sensitivity for excited-state investigations.
Predicting conformational ensembles and genome-wide transcription factor binding sites from DNA sequences
Authors: Andrabi Munazah , Hutchins Andrew Paul , Miranda-Saavedra Diego , Kono Hidetoshi , Nussinov Ruth , Mizuguchi Kenji , Ahmad Shandar
Published: June 2017

DNA shape is emerging as an important determinant of transcription factor binding beyond just the DNA sequence. The only tool for large scale DNA shape estimates,DNAshapewas derived from Monte-Carlo simulations and predicts four broad and static DNA shape features,Propeller twist,Helical twist,Minor groove widthandRoll. The contributions of other shape features e.g.Shift,SlideandOpeningcannot be evaluated usingDNAshape. Here, we report a novel methodDynaSeq, which predicts molecular dynamics-derived ensembles of a more exhaustive set of DNA shape features. We compared theDNAshapeandDynaSeqpredictions for the common features and applied both to predict the genome-wide binding sites of 1312 TFs available from protein interaction quantification (PIQ) data. The results indicate a good agreement between the two methods for the common shape features and point to advantages in usingDynaSeq. Predictive models employing ensembles from individual conformational parameters revealed thatbase-pair opening -known to be important instrand separation -was the best predictor of transcription factor-binding sites (TFBS) followed by features employed byDNAshape. Of note, TFBS could be predicted not only from the features at the target motif sites, but also from those as far as 200 nucleotides away from the motif.
SLC4A11 depletion impairs NRF2 mediated antioxidant signaling and increases reactive oxygen species in human corneal endothelial cells during oxidative stress
Authors: Guha Sanjukta , Chaurasia Sunita , Ramachandran Charanya , Roy Sanhita
Published: June 2017

Corneal endothelial dystrophy is a progressive disease with gradual loss of vision and characterized by degeneration and dysfunction of corneal endothelial cells. Mutations in SLC4A11, a Na+ dependent OH− transporter, cause congenital hereditary endothelial dystrophy (CHED) and Fuchs’ endothelial corneal dystrophy (FECD), the two most common forms of endothelial degeneration. Along with genetic factors, oxidative stress plays a role in pathogenesis of several corneal diseases. In this study we looked into the role of SLC4A11 in antioxidant stress response in human corneal endothelial cells (HCEnC). We found increased expression of SLC4A11 in presence of oxidative stress. Depletion of SLC4A11 using targeted siRNA, caused an increase in reactive oxygen species, cytochrome c, lowered mitochondrial membrane potential, and reduced cell viability during oxidative stress. Moreover, SLC4A11 was found to be necessary for NRF2 mediated antioxidant gene expression in HCEnC. On the other hand, over expression of SLC4A11 reduces reactive oxygen species levels and increases cell viability. Lastly, CHED tissue specimens show evidence of oxidative stress and reduced expression of NRF2. In conclusion, our data suggests a possible role of SLC4A11 in regulating oxidative stress, and might be responsible for both the etiology and treatment of corneal endothelial dystrophy.
Tracing the epidemic history of HIV-1 CRF01_AE clusters using near-complete genome sequences
Authors: Li Xingguang , Liu Haizhou , Liu Lu , Feng Yi , Kalish Marcia L. , Ho Simon Y. W. , Shao Yiming
Published: June 2017

Human immunodeficiency virus (HIV) has a number of circulating recombinant forms that are the product of recombination between different HIV subtypes. The first circulating recombinant form of HIV-1 to be identified was CRF01_AE, which originated in Central Africa and is now most prevalent in Southeast and East Asia. In this study, we investigated the timescale, evolutionary history, and population genetics of the HIV-1 CRF01_AE strains primarily responsible for the epidemic in Asia. A further aim of our study was to define and standardize the nomenclature and provide well-characterized reference sequences for the phylogenetic transmission clusters of CRF01_AE. We analysed a data set of 334 near-complete genome sequences from various risk groups, sampled between 1990 and 2011 from nine countries. Phylogenetic analyses of these sequences were performed using maximum likelihood and Bayesian methods. Our study confirms that the diversity of HIV-1 CRF01_AE originated in Central Africa in the mid-1970s, was introduced into Thailand between 1979 and 1982, and began expanding there shortly afterwards (1982–1984). Subsequently, multiple clusters significantly contributed to China’s HIV epidemic. A Bayesian skyline plot revealed the rapid expansion of CRF01_AE in China around 1999–2000. We identified at least eight different clusters of HIV-1 CRF01_AE formed by rapid expansion into different risk groups and geographic regions in China since the late 1980s.
Influence of Fermi arc states and double Weyl node on tunneling in a Dirac semimetal
Authors: Siu Zhuo Bin , Yesilyurt Can , Jalil Mansoor B. A. , Tan Seng Ghee
Published: June 2017

Most theoretical studies of tunneling in Dirac and the closely related Weyl semimetals have modeled these materials as single Weyl nodes described by the three-dimensional Dirac equation $${\boldsymbol{H}}{\boldsymbol{=}}{{\boldsymbol{v}}}_{{\boldsymbol{f}}}\overrightarrow{{\boldsymbol{p}}}\cdot \overrightarrow{{\boldsymbol{\sigma }}}$$
H
=

v

f

p
→

⋅

σ
→

. The influence of scattering between the different valleys centered around different Weyl nodes, and the Fermi arc states which connect these nodes are hence not evident from these studies. In this work we study the tunneling in a thin film system of the Dirac semimetal Na3Bi consisting of a central segment with a gate potential, sandwiched between identical semi-infinite source and drain segments. The model Hamiltonian we use for Na3Bi gives, for each spin, two Weyl nodes separated in k-space symmetrically about k
z
 = 0. The presence of a top and bottom surface in the thin film geometry results in the appearance of Fermi arc states and energy subbands. We show that (for each spin) the presence of two Weyl nodes and the Fermi arc states results in enhanced transmission oscillations, and finite transmission even when the energy falls within the bulk band gap in the central segment respectively. These features are not captured in single Weyl node models.
Human age and skin physiology shape diversity and abundance of Archaea on skin
Authors: Moissl-Eichinger Christine , Probst Alexander J. , Birarda Giovanni , Auerbach Anna , Koskinen Kaisa , Wolf Peter , Holman Hoi-Ying N.
Published: June 2017

The human skin microbiome acts as an important barrier protecting our body from pathogens and other environmental influences. Recent investigations have provided evidence that Archaea are a constant but highly variable component of the human skin microbiome, yet factors that determine their abundance changes are unknown. Here, we tested the hypothesis that the abundance of archaea on human skin is influenced by human age and skin physiology by quantitative PCR of 51 different skin samples taken from human subjects of various age. Our results reveal that archaea are more abundant in human subjects either older than 60 years or younger than 12 years as compared to middle-aged human subjects. These results, together with results obtained from spectroscopy analysis, allowed us gain first insights into a potential link of lower sebum levels and lipid content and thus reduced skin moisture with an increase in archaeal signatures. Amplicon sequencing of selected samples revealed the prevalence of specific eury- and mainly thaumarchaeal taxa, represented by a core archaeome of the human skin.
Targeting Coronaviral Replication and Cellular JAK2 Mediated Dominant NF-κB Activation for Comprehensive and Ultimate Inhibition of Coronaviral Activity
Authors: Yang Cheng-Wei , Lee Yue-Zhi , Hsu Hsing-Yu , Shih Chuan , Chao Yu-Sheng , Chang Hwan-You , Lee Shiow-Ju
Published: June 2017

Tylophorine-based compounds exert broad spectral, potent inhibition of coronaviruses. NF-κB activation is a common pro-inflammatory response of host cells to viral infection. The aims of this study were to (i) find an effective combination treatment for coronaviral infections through targeting of the virus per se and cellular NF-κB activity; and (ii) to study the underling mechanisms. We found that tylophorine-based compounds target the TGEV viral RNA and effectively inhibit TGEV replication. NF-κB inhibition also leads to anti-TGEV replication. NF-κB activation induced by TGEV infection was found to be associated with two convergent pathways, IKK-2_IκBα/p65 and JAK2 mediated p65 phosphorylation, in swine testicular cells. JAK2 inhibition either by CYT387 (a JAK family inhibitor) or by silencing JAK2-expression revealed a dominant JAK2 mediated p65 phosphorylation pathway for NF-κB activation and resulted in NF-κB inhibition, which overrode the IκBα regulation via the IKK-2. Finally, tylophorine-based compounds work cooperatively with CYT387 to impart comprehensive anti-TGEV activities. The combination treatment, wherein a tylophorine compound targets TGEV and a JAK2 inhibitor blocks the alternative dominant NF-κB activation mediated by JAK2, is more effective and comprehensive than either one alone and constitutes a feasible approach for the treatment of SARS-CoV or MERS-CoV.