bluuebunny/crossref_metadata_2025 huggingface dataset:
Anatomical Study of the Popliteal Artery Perforator–Based Propeller Flap and Its Clinical Application
Authors: Onishi Tadanobu , Shimizu Takamasa , Omokawa Shohei , Sananpanich Kanit , Kido Akira , Mahakkanukrauh Pasuk , Tanaka Yasuhito
Published: June 2018

There is lack of anatomical information regarding the cutaneous perforator of the popliteal artery and its connections with the descending branch of the inferior gluteal and profunda femoris arteries. The authors aimed to evaluate the anatomical basis of the popliteal artery perforator–based propeller flap from the posterior thigh region and to demonstrate their experience using this flap. Ten fresh cadaveric lower extremities were dissected following injection of a silicone compound into the femoral artery. The authors investigated the number, location, length, and diameter of cutaneous perforators of the popliteal artery. Based on the results, the authors treated three cases with a large soft-tissue defect around the knee using a popliteal artery perforator–based propeller flap. The authors found a mean of 1.9 cutaneous perforators arising from the popliteal artery, with a mean pedicle length of 6 cm and a mean arterial internal diameter of 0.9 mm, which were located at an average of 4 cm proximal to the bicondylar line. The most distal perforator consistently arose along the small saphenous vein and connected proximally with the concomitant artery of the posterior femoral cutaneous nerve, forming a connection with perforating arteries of the profunda femoris artery. A mean of 4.5 cutaneous perforators branched from the arterial connection sites. All clinical cases healed without any complications. The popliteal artery perforator–based propeller flap is reliable for reconstruction of soft-tissue defects around the knee. The flap should include the deep fascia and concomitant artery along with the posterior femoral cutaneous nerve for maintaining the blood supply.
New Strategies for Remnant Ear Treatment in Lobule-Type Microtia Reconstruction
Authors: Xu Zhicheng , Zhang Ruhong , Zhang Qun , Xu Feng , Li Datao , Li Yiyuan
Published: June 2018

Background:

Numerous modifications have been successfully applied in microtia reconstruction over the past several decades, and lobular transposition has become a routine technique in a two-stage operation. However, it is still a demanding challenge to manipulate the remnant ear with various quantities or positions in lobule-type microtia. The authors demonstrate the relevant details of treating remnant tissue in different conditions.

Methods:

A total of 390 lobule-type microtia patients underwent autogenous costal cartilage auricular reconstruction between 2010 and 2015. Because the quantity or position of the remnant ear varies from patient to patient, corresponding tactics need to be taken into consideration for appropriate treatment. Four possible scenarios of remnant ear shape have been described, and relevant strategies for each were introduced.

Results:

Favorable reconstructed auricles with aesthetic natural earlobes have been produced; the location of the reconstructed ear is symmetric to the contralateral ear. It provides a harmonized framework and periphery tissue for the integrity of the contour of the constructed auricle.

Conclusions:

Proper use of the remnant ear along with framework fabrication and skin flap dissection are critical factors for attaining a satisfactory contour of the auricle in microtia reconstruction. The authors’ technique made it possible to construct a cosmetically refined ear with harmonious integrity.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
Multicenter Study of Device-Associated Infection Rates, Bacterial Resistance, Length of Stay, and Mortality in Intensive Care Units of 2 Cities of Vietnam: International Nosocomial Infection Control Consortium Findings
Authors: Viet Hung Nguyen , Hang Phan Thi , Rosenthal Victor D. , Thi Anh Thu Le , Thi Thu Nguyet Le , Quy Chau Ngo , Anh Thu Truong , Anh Dinh Pham Phuong , Hanh Tran Thi My , Hang Tran Thi Thuy , Van Trang Dang Thi , Tien Nguyen Phuc , Hong Thoa Vo Thi , Minh Đao Quang
Published: June 2018

Objective

The aim of the study was to report the results of the International Nosocomial Infection Control Consortium (INICC) study conducted from May 2008 to March 2015.

Methods

A device-associated healthcare-acquired infection surveillance study in three adult intensive care units (ICUs) and 1 neonatal ICU from 4 hospitals in Vietnam using U.S. the Centers for Disease Control and Prevention’s National Healthcare Safety Network (CDC/NHSN) definitions and criteria as well as INICC methods.

Results

We followed 1592 adult ICU patients for 12,580 bed-days and 845 neonatal ICU patients for 4907 bed-days. Central line-associated bloodstream infection (CLABSI) per 1000 central line-days rate was 9.8 in medical/surgical UCIs and 1.5 in the medical ICU. Ventilator-associated pneumonia (VAP) rate per 1000 mechanical ventilator-days was 13.4 in medical/surgical ICUs and 23.7 in the medical ICU. Catheter-associated urinary tract infection (CAUTI) rate per 1000 urinary catheter-days was 0.0 in medical/surgical ICUs and 5.3 in the medical ICU. While most device-associated healthcare-acquired infection rates were similar to INICC international rates (4.9 [CLABSI]; 16.5 [VAP]; 5.3 [CAUTI]), they were higher than CDC/NHSN rates (0.8 [CLABSI], 1.1 [VAP], and 1.3 [CAUTI]) for medical/surgical ICUs, with the exception of CAUTI rate for medical/surgical ICU and CLABSI rate for the medical ICU. Because of limited resources of our Vietnamese ICUs, cultures could not be taken as required by the CDC/NHSN criteria, and therefore, there was underreporting of CLABSI and CAUTI, influencing their rates. Most device utilization ratios and bacterial resistance percentages were higher than INICC and CDC/NHSN rates.

Conclusions

Device-associated healthcare-acquired infection rates found in the ICUs of our study were higher than CDC/NHSN US rates, but similar to INICC international rates. It is necessary to build more capacity to conduct surveillance and prevention strategies.
Hematopoietically Active Adrenal Myelolipoma Mimicking Breast Cancer Metastasis
Authors: Manov John J. , Diaz-Bode Alexander , Kuker Russ
Published: June 2018

A 66-year old woman had a left breast mass. Biopsy showed invasive ductal carcinoma. A PET/CT scan demonstrated hypermetabolism in the left breast and atypical heterogeneously increased uptake throughout the skeleton as well as a minimally FDG-avid right adrenal myelolipoma. PET/CT 4 months later after 6 cycles of neoadjuvant chemotherapy demonstrated increased size and FDG avidity of this adrenal mass concerning for metastasis and uniformly increased skeletal FDG avidity. Biopsy demonstrated adrenal myelolipoma. The growth and increased FDG avidity of the adrenal myelolipoma were due to the action of colony-stimulating factors on the tumor's hematopoietic component.
Noncongenital Ventricular Septal Defects
Authors: DeClue Chris , Donatelli John M. , Rojas Carlos A.
Published: June 2018

The purpose of this article was to review the pathophysiology, imaging features, and imaging pitfalls of noncongenital ventricular septal defects (VSDs). Noncongenital VSDs can result from ischemic heart disease, trauma, infection, and iatrogenic causes. Ischemic VSDs typically involve the posterior descending or left anterior descending vascular territories and are commonly seen in the apical septum or basal-mid inferoseptum. VSDs can also occur in patients with infectious endocarditis or as a complication following cardiac surgery. Most of these involve the membranous portion of the interventricular septum. Traumatic VSDs are rare and commonly involve the mid to apical anteroseptum. Computed tomography and magnetic resonance imaging can accurately characterize the morphologic features of the defects and associated imaging findings.
The Arkansas Tessier Number 3 Cleft Experience: Soft Tissue and Skeletal Findings With Primary Surgical Management: Four-Step Approach
Authors: Golinko Michael S. , Pemberton John D. , Phillips James , Johnson Adam , Hartzell Larry D.
Published: June 2018

Tessier No 3 facial cleft (oro-nasal-ocular clefts) is the rarest and most challenging of all the Tessier clefts. Reports on Tessier No 3 clinical findings, surgical techniques, and outcomes are varied due to the scarcity of patients and the wide range of phenotypic findings. The authors present our experience of 2 children born with Tessier No 3 clefts who were both managed at the Arkansas Children's Hospital. Our purpose is to add knowledge on this rare craniofacial cleft by providing detailed soft tissue findings, skeletal findings, operative techniques, early postoperative outcome, and suggestions of a treatment protocol.

Both were born at 38 weeks gestation and had multiple associated anomalies including: syndactyly, limb anomalies, cardiac defects, and encephalocele in Patient 1 and hydrocephalus and dysphagia in Patient 2. While both patients had a bilateral cleft lip and palate, Patient 1 had a severe left-sided cleft and Patient 2 had a right-sided incomplete cleft. A multidisciplinary team of specialists in Plastic Surgery, Otolaryngology, and Oculoplastics were assembled to devise a top–down approach for repair. In brief, our surgical sequence for both infants was a dorsal nasal Reiger flap to level the ala, cheek advancement flap along with medial canthal repositioning, and more traditional bilateral cleft lip repair using a modified Millard technique. Postoperatively, Patient 1 experienced some early scarring, medial canthal rounding, lagophthalmos, and cicatricial retraction of the lower lid and patient 2 demonstrated under-correction of the displaced ala but had satisfactory medial canthal position.

Future evaluations will include serial photography and annual 3-dimensional computed tomography scans to evaluate the soft tissue and bony growth. After these initial procedures, both infants will be followed for routine cleft clinical and surgical care.
Benign Paroxysmal Positional Vertigo After Piezosurgical Removal of Osseointegrated Implants
Authors: Messina Antonello Maria , Marini Ettore
Published: June 2018

With the increasing popularity of dental implants, the explantation of fractured implants has become a major challenge for clinicians. Several tools can be used for the removal of osseointegrated implants; however, few of these have the characteristics of easy control, selective cutting, and rapid healing. We report a case of benign paroxysmal positional vertigo (BPPV) developed immediately after piezosurgical removal of osteointegrated implants.

The BPPV may be an unpleasant complication of piezosurgical removal of osseointegrated implants and may cause considerable stress if not identified correctly and managed properly.
Therapeutic Protocol for Orthosurgical Management of Class III Malocclusion in Patients With Cleidocranial Dysostosis
Authors: Barth Fernando André , Menuci Neto Angelo , Almeida-Pedrin Renata Rodrigues , Ladewig Victor de Miranda , Conti Ana Cláudia de Castro Ferreira
Published: June 2018

Cleidocranial dysostosis (CCD) is a congenital skeletal disorder with significant manifestations in facial and dental development. Patients are affected with CCD present maxillary deficiency, late dental eruption, and supernumerary teeth. Early and multidisciplinary approach is necessary to treat CCD patients, especially to manage dental eruption and Class III malocclusion with maxillary deficiency. Several orthodontic and surgical interventions are performed to enable traction and extraction of teeth. Yet the maxillary deficiency may be protracted followed by orthodontic dental compensation. On the other hand, it is important to note that CCD patients’ treatment is closely related to the severity of transversal and sagittal deformities, as well as the discrepancies in the lower third of the face. In this context, patients with facial impairment highly affected by CCD may need ortho-surgical decompensation to reach more aesthetic outcomes. The present study reports a case of a 14-year-old young patient affected by CCD. Clinically, the patient presented Class III malocclusion, maxillary deficiency, short lower facial third, posterior crossbite, and anterior open bite leading to facial disharmony. The patient underwent treatment in 2 stages: the interceptive approach aimed to transversally expand the maxilla and promote its protraction; and the corrective phase combined with the orthognathic surgery treated the patients’ main complains; the anterior open bite, unerupted teeth, and chin prominence. The treatment approach applied in the clinical report allowed the correction of the malocclusion and facial profile satisfying completely the patient's expectations.
The Effects of Vasoconstriction And Volume Expansion on Veno-Arterial ECMO Flow
Authors: Moller Per W. , Hana Anisa , Heinisch Paul Philipp , Liu Shengchen , Djafarzadeh Siamak , Haenggi Matthias , Bloch Andreas , Takala Jukka , Jakob Stephan M. , Berger David
Published: June 2018

Background:

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is gaining widespread use in the treatment of severe cardiorespiratory failure. Blood volume expansion is commonly used to increase ECMO flow (QECMO), with risk of positive fluid balance and worsening prognosis. We studied the effects of vasoconstriction on recruitment of blood volume as an alternative for increasing QECMO, based on the concepts of venous return.

Methods:

In a closed chest, centrally cannulated porcine preparation (n = 9) in ventricular fibrillation and VA-ECMO with vented left atrium, mean systemic filling pressure (MSFP), and venous return driving pressure (VRdP) were determined in Euvolemia, during Vasoconstriction (norepinephrine 0.05, 0.125, and 0.2 μg/kg/min) and after Volume Expansion (3 boluses of 10 mL/kg Ringer's lactate). Maximum achievable QECMO was examined.

Results:

Vasoconstriction and Volume Expansion both increased maximum achievable QECMO, delivery of oxygen (DO2), and MSFP, but right atrial pressure increased in parallel. VRdP did not change. The vascular elastance curve was shifted to the left by Vasoconstriction, with recruitment of stressed volume. It was shifted to the right by Volume Expansion with direct expansion of stressed volume. Volume Expansion decreased resistance to venous return and pump afterload.

Conclusions:

In a circulation completely dependent on ECMO support, maximum achievable flow directly depended on the vascular factors governing venous return—i.e., closing conditions, stressed vascular volume and the elastance and resistive properties of the vasculature. Both treatments increased maximum achievable ECMO flow at stable DO2, via increases in stressed volume by different mechanisms. Vascular resistance and pump afterload decreased with Volume Expansion.
The non-transcranial TMS-evoked potential is an inherent source of ambiguity in TMS-EEG studies
Authors: Conde Virginia , Tomasevic Leo , Akopian Irina , Stanek Konrad , Saturnino Guilherme B. , Thielscher Axel , Bergmann Til Ole , Siebner Hartwig Roman
Published: June 2018

Transcranial Magnetic Stimulation (TMS) excites populations of neurons in the stimulated cortex, and the resulting activation may spread to connected brain regions. The distributed cortical response can be recorded with electroencephalography (EEG). Since TMS also stimulates peripheral sensory and motor axons and generates a loud “click” sound, the TMS-evoked EEG potential (TEP) not only reflects neural activity induced by transcranial neuronal excitation but also neural activity reflecting somatosensory and auditory processing. In 17 healthy young individuals, we systematically assessed the contribution of multisensory peripheral stimulation to TEPs using a TMS-compatible EEG system. Real TMS was delivered with a figure-of-eight coil over the left para-median posterior parietal cortex or superior frontal gyrus with the coil being oriented perpendicularly or in parallel to the target gyrus. We also recorded the EEG responses evoked by sham stimulation over the posterior parietal and superior frontal cortex, mimicking the auditory and somatosensory sensations evoked by real TMS. We applied state-of-the-art procedures to attenuate somatosensory and auditory confounds during real TMS, including the placement of a foam layer underneath the coil and auditory noise masking. Despite these precautions, the temporal and spatial features of the cortical potentials evoked by real TMS at the prefrontal and parietal site closely resembled the cortical potentials evoked by realistic sham TMS, both for early and late TEP components. Our findings stress the need to include a peripheral multisensory control stimulation in the study design to enable a dissociation between truly transcranial and non-transcranial components of TEPs.
High genetic diversity and presence of genetic structure characterise the Corso-Sardinian endemicsRuta corsicaandRuta lamarmorae(Rutaceae)
Authors: Meloni Marilena , Dettori Caterina Angela , Reid Andrea , Bacchetta Gianluigi , Hugot Laetitia , Conti Elena
Published: June 2018

Corsica and Sardinia form one of the ten areas with highest biodiversity in the Mediterranean and are considered one of the priority regions for conservation in Europe. In order to preserve the high levels of endemism and biological diversity at different hierarchical levels, knowledge of the evolutionary history and current genetic structure of Corso-Sardinian endemics is instrumental. Microsatellite markers were newly developed and used to study the genetic structure and taxonomic status ofRuta corsicaandRuta lamarmorae, rare endemics of Corsica and Sardinia, respectively, and previously considered a single species. Our analyses identified high levels of genetic variation within each species (P=0.883,He=0.543 forR. corsica; P=0.972,He=0.627 forR. lamarmorae). Intrinsic traits of the species (hermaphroditism, proterandry and polyploidy) and island-dependent factors (i.e. age, origin and history of the islands) might explain the detected high levels of genetic variation. We discovered differentiation betweenR. corsicaandR. lamarmorae, and genetic structure within each species, which are consistent with the observation of low dispersal ability for both species. Our genetic results support the recent taxonomic classification ofR. corsicaandR. lamarmoraeas separate species and suggest that they diverge at only few loci. OneR. corsicapopulation (SA) strongly differed from all other studied populations and appeared to be the product of hybridization between the two species in STRUCTURE analyses. Our results provide important insights for the conservation of the two rare endemics. Further genetic analyses are recommended forR. lamarmoraeand for population SA (R. corsica).
Connectivity analyses of bioenergetic changes in schizophrenia: Identification of novel treatments
Authors: Sullivan Courtney R. , Mielnik Catharine A. , O’Donovan Sinead M. , Funk Adam J. , Bentea Eduard , DePasquale Erica A.K. , Wen Zhexing , Haroutunian Vahram , Katsel Pavel , Ramsey Amy J. , Meller Jarek , McCullumsmith Robert E.
Published: June 2018

We utilized a cell-level approach to examine glycolytic pathways in the DLPFC of subjects with schizophrenia (n=16) and control (n=16) subjects and found decreased mRNA expression of glycolytic enzymes in pyramidal neurons, but not astrocytes. To replicate these novel bioenergetic findings, we probed independent datasets for bioenergetic targets and found similar abnormalities. Next, we used a novel strategy to build a schizophrenia bioenergetic profile by a tailored application of the Library of Integrated Network-Based Cellular Signatures data portal (iLINCS) and investigated connected cellular pathways, kinases, and transcription factors using Enrichr. Finally, with the goal of identifying drugs capable of “reversing” the bioenergetic schizophrenia signature, we performed a connectivity analysis with iLINCS and identified peroxisome proliferator-activated receptor (PPAR) agonists as promising therapeutic targets. We administered a PPAR agonist to the GluN1 knockdown model of schizophrenia and found it improved long-term memory. Taken together, our findings suggest that tailored bioinformatics approaches, coupled with the LINCS library of transcriptional signatures of chemical and genetic perturbagens may be employed to identify novel treatment strategies for schizophrenia and related diseases.
Faces and voices in the brain: a modality-general person-identity representation in superior temporal sulcus
Authors: Tsantani Maria , Kriegeskorte Nikolaus , McGettigan Carolyn , Garrido Lúcia
Published: June 2018

Face-selective and voice-selective brain regions have been shown to represent face-identity and voice-identity, respectively. Here we investigated whether there are modality-general person-identity representations in the brain that can be driven by either a face or a voice, and that invariantly represent naturalistically varying face and voice tokens of the same identity. According to two distinct models, such representations could exist either in multimodal brain regions (Campanella and Belin, 2007) or in face-selective brain regions via direct coupling between face- and voice-selective regions (von Kriegstein et al., 2005). To test the predictions of these two models, we used fMRI to measure brain activity patterns elicited by the faces and voices of familiar people in multimodal, face-selective and voice-selective brain regions. We used representational similarity analysis (RSA) to compare the representational geometries of face- and voice-elicited person-identities, and to investigate the degree to which pattern discriminants for pairs of identities generalise from one modality to the other. We found no matching geometries for faces and voices in any brain regions. However, we showed crossmodal generalisation of the pattern discriminants in the multimodal right posterior superior temporal sulcus (rpSTS), suggesting a modality-general person-identity representation in this region. Importantly, the rpSTS showed invariant representations of face- and voice-identities, in that discriminants were trained and tested on independent face videos (different viewpoint, lighting, background) and voice recordings (different vocalizations). Our findings support the Multimodal Processing Model, which proposes that face and voice information is integrated in multimodal brain regions.

Significance statement

It is possible to identify a familiar person either by looking at their face or by listening to their voice. Using fMRI and representational similarity analysis (RSA) we show that the right posterior superior sulcus (rpSTS), a multimodal brain region that responds to both faces and voices, contains representations that can distinguish between familiar people independently of whether we are looking at their face or listening to their voice. Crucially, these representations generalised across different particular face videos and voice recordings. Our findings suggest that identity information from visual and auditory processing systems is combined and integrated in the multimodal rpSTS region.
Structural insights on TRPV5 gating by endogenous modulators
Authors: Hughes Taylor E.T. , Pumroy Ruth A. , Yazici Aysenur Torun , Kasimova Marina A. , Fluck Edwin C. , Huynh Kevin W. , Samanta Amrita , Mulugu Sudheer , Zhou Z. Hong , Carnevale Vincenzo , Rohacs Tibor , Moiseenkova-Bell Vera Y.
Published: June 2018

TRPV5 is a transient receptor potential channel involved in calcium reabsorption. Here we investigate the interaction of two endogenous modulators with TRPV5. Both phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and calmodulin (CaM) have been shown to directly bind to TRPV5 and activate or inactivate the channel, respectively. Using cryo-electron microscopy (cryo-EM), we determined TRPV5 structures in the presence of dioctanoyl PI(4,5)P2 and CaM. The PI(4,5)P2 structure revealed a novel binding site between the N-linker, S4-S5 linker and S6 helix of TRPV5. These interactions with PI(4,5)P2 induce conformational rearrangements in the lower gate, opening the channel. The CaM structure revealed two TRPV5 C-terminal peptides anchoring a single CaM molecule and that calcium inhibition is mediated through a cation-π interaction between Lys116 on the C-lobe of calcium-activated CaM and Trp583 at the intracellular gate of TRPV5. Overall, this investigation provides insight into the endogenous modulation of TRPV5, which has the potential to guide drug discovery.
In a temporally segmented experience hippocampal neurons represent temporally drifting context but not discrete segments
Authors: Bladon J. H. , Sheehan D. J. , De Freitas C. S. , Howard M. W.
Published: June 2018

There is widespread agreement that episodic memory is organized into a timeline of past experiences. Recent work suggests that the hippocampus may parse the flow of experience into discrete episodes separated by event boundaries. A complementary body of work suggests that context changes gradually as experience unfolds. We recorded from hippocampal neurons as male long evans rats performed 6 blocks of an object discrimination task in sets of 15 trials. Each block was separated by removal from the testing chamber for a delay to enable segmentation. The reward contingency reversed from one block to the next to incentivize segmentation. We expected animals to hold two distinct, recurring representations of context to match the two distinct rule contingencies. Instead, we found that overtrained rats began each block neither above nor below chance but by guessing randomly. While many units had clear firing fields selective to the conjunction of objects in places, a significant population also reflected a continuously drifting code both within block and across blocks. Despite clear boundaries between blocks, we saw no neural evidence for event segmentation in this experiment. Rather, the hippocampal ensemble drifted continuously across time. This continuous drift in the neural representation was consistent with the lack of segmentation observed in behavior.

Significance Statement

The neuroscience literature yet to reach consensus as to how hippocampal firing fields support the organizing of events across time in episodic memory. Initial reports of hippocampal activity focused on discrete episodes within which representations were stable, and across which representations remapped. However, it remains unclear whether this segmentation of representations is merely an artifact of cue responsivity. More recently, research has shown that a proportion of the population codes for temporal aspects of context by exhibiting varying degrees of drift in their firing fields. Drift is hypothesized to represent a continually evolving temporal context, however it is unclear whether this drift is continuous or is also a mere artifact of changing experiences. We recorded from the dorsal hippocampus of rats performing an object discrimination task that involved contexts that were segmented in time. Overtrained rats were unable to anticipate the identity of the upcoming context, but may have used context boundaries to their advantage. Event segmentation theory predicts that hippocampal ensembles would alternate between behaviorally-relevant segments. Contrary to these predictions, animals showed weak evidence of context segmentation, even across blocks with different reward contingencies. Hippocampal ensembles showed neither evidence of alternating between stable contexts nor sensitivity to context boundaries, but did show robust temporal drift.
Microtubule plus-tips act as signaling hubs for positioning the cleavage furrow during cytokinesis
Authors: Verma Vikash , Maresca Thomas J.
Published: June 2018

Cell division in animal cells culminates with the formation of a contractile ring that divides the cytosol through formation of a cleavage furrow. Microtubules (MTs) are essential for furrow positioning, but the molecular nature of MT-derived spatial signals is unresolved. In this study essential cytokinesis regulators (the centralspindlin complex, aurora B kinase (ABK), and polo kinase) were visualized in Drosophila melanogaster (Dm) cells and found localize to and track MT plus-ends during cytokinesis. The RhoA GEF Pebble (Dm ECT2) did not robustly tip-track but became enriched at MT plus-tips rapidly following cortical contact resulting in RhoA activation and enrichment of myosin-regulatory light chain. Abrogation of cytokinesis regulator tip-tracking by EB1 depletion or deletion of a novel EB1-interaction motif (hxxPTxh) in the centralspindlin component RacGAP50C resulted in higher incidences of cytokinesis failure. We propose that EB1-dependent, MT plus-tip-based signaling hubs recruit cortical Dm ECT2 upon contact to locally activate RhoA.
Dynamics and spatial genomics of the nascent transcriptome in single mESCs by intron seqFISH
Authors: Shah Sheel , Takei Yodai , Zhou Wen , Lubeck Eric , Yun Jina , Koulena Noushin , Liaw Eric J. , Amin Mina , Cai Long
Published: June 2018

Recent single cell experiments have revealed significant heterogeneities at the levels of transcription, DNA methylation and chromosome organization in individual cells. However, existing method of profiling mRNAs effectively averages transcriptional dynamics over many hours due to hours-long life time of most mRNAs. To capture the instantaneous activity of the transcriptome that reflects the rapid regulatory changes in cells, we imaged up to 10,421 nascent transcription active sites (TAS) in single mouse embryonic stem cells using seqFISH followed by multiple rounds of single molecule FISH and immunofluorescence. We observed that nascent transcription active sites appear to be distributed on the surface of individual chromosome territories and are dispersed throughout the nucleus. In addition, there are significant variability in the number of active transcription sites in single cells, representing globally more active to quiescent states. These states interconverted on the time scale of 2 hours as determined by a single cell pulse-chase experiment. Thus, transcriptome level seqFISH experiments provide an unprecedented spatial and dynamic view of chromosome organization and global nascent transcription activity in single cells.
Sampling native-like structures of RNA-protein complexes through Rosetta folding and docking
Authors: Kappel Kalli , Das Rhiju
Published: June 2018

RNA-protein complexes underlie numerous cellular processes including translation, splicing, and posttranscriptional regulation of gene expression. The structures of these complexes are crucial to their functions but often elude high-resolution structure determination. Computational methods are needed that can integrate low-resolution data for RNA-protein complexes while modeling de novo the large conformational changes of RNA components upon complex formation. To address this challenge, we describe a Rosetta method called RNP-denovo to simultaneously fold and dock RNA to a protein surface. On a benchmark set of structurally diverse RNA-protein complexes that are not solvable with prior strategies, this fold-and-dock method consistently sampled native-like structures with better than nucleotide resolution. We revisited three past blind modeling challenges in which previous methods gave poor results: human telomerase, an RNA methyltransferase with a ribosomal RNA domain, and the spliceosome. When coupled with the same sparse FRET, cross-linking, and functional data used in previous work, RNP-denovo gave models with significantly improved accuracy. These results open a route to computationally modeling global folds of RNA-protein complexes from low-resolution data.
mTOR-dependent phosphorylation controls TFEB nuclear export
Authors: Napolitano Gennaro , Esposito Alessandra , Choi Heejun , Benedetti Valerio , Matarese Maria , Di Malta Chiara , Monfregola Jlenia , Medina Diego Luis , Lippincott-Schwartz Jennifer , Ballabio Andrea
Published: June 2018

The transcriptional activation of catabolic processes during starvation is induced by the nuclear translocation and consequent activation of transcription factor EB (TFEB), a master modulator of autophagy and lysosomal biogenesis. However, how TFEB is inactivated upon nutrient re-feeding is currently unknown. Here we show that TFEB subcellular localization is dynamically controlled by its continuous shuttling between the cytosol and the nucleus, with the nuclear export representing a limiting step. TFEB nuclear export is mediated by CRM1 and is modulated by nutrient availability via mTOR-dependent hierarchical multisite phosphorylation of serines S142 and S138, which are localized in proximity of a nuclear export signal (NES). Our data reveal that modulation of TFEB nuclear export via phosphorylation plays a major role in the modulation of TFEB localization and activity.
Enhanced synaptic properties of the prefrontal cortex and hippocampus after learning a spatial working memory task in adult male mice
Authors: Stavroulaki Vasiliki , Ioakeimidis Vasileios , Konstantoudaki Xanthippi , Sidiropoulou Kyriaki
Published: June 2018

Working memory (WM) is the ability to hold on-line and manipulate information. The prefrontal cortex (PFC) is a key brain region involved in WM, while the hippocampus is also involved, particularly, in spatial WM. Although several studies have investigated the neuronal substrates of WM in trained animals, the effects and the mechanisms underlying learning WM tasks have not been explored. In our study, we investigated the effects of learning WM tasks in mice on the function of PFC and hippocampus, by training mice in the delayed alternation task for 9 days (adaptive group). This group was compared to naïve mice that stayed in their homecage (naïve) and mice trained in the alternation procedure only (non-adaptive). Following training, a cohort of mice (Experiment A) was tested in the left-right discrimination task and the reversal learning task, while another cohort (Experiment B) was tested in the attention set- shifting task (AST). The adaptive group performed significantly better in the reversal learning task (Experiment A) and AST (Experiment B), compared to non-adaptive and naïve groups. At the end of the behavioral experiments in Experiment A, field excitatory post-synaptic potential (fEPSP) recordings were performed in PFC and hippocampal brain slices. The adaptive group had enhanced the long-term potentiation (LTP) in the PFC, compared to the other groups. In the hippocampus, both the adaptive and the non-adaptive groups exhibited increased fEPSP compared to the naive group, but no differences in LTP. In Experiment B, the dendritic spine density was measured, which, in the PFC, was found increased in the adaptive group, compared to the non-adaptive and naive groups. In the hippocampus, there was an increase in mature dendritic spine density in the adaptive group, compared to the other two groups. Our results indicate a role for long-term potentiation and dendritic spine density in learning WM tasks.

Significance statement

Working memory (WM) allows for transient storage and manipulation of information and has a central role in cognition. While a great number of research studies have investigated the mechanisms underlying the ‘memory’ part of WM in well-trained animals, the mechanisms that underlie learning WM tasks are not known. Studies have indicated that learning a WM tasks alters and enhances neuronal firing during the delay period, suggesting that long-term plasticity mechanisms could be involved. Our results in this study suggest that learning a working memory task primarily increases long-term potentiation and dendritic spine density in the prefrontal cortex, providing evidence for a role of long-term plasticity processes in learning working memory tasks. Furthermore, learning working memory tasks enhances cognitive flexibility.
The chemokine receptor CXCR2 contributes to murine adipocyte development
Authors: Dyer Douglas P , Nebot Joan Boix , Kelly Christopher , Medina-Ruiz Laura , Schuette Fabian , Graham Gerard J
Published: June 2018

Chemokines are members of a large family of chemotactic cytokines that signal through their receptors to mediate leukocyte recruitment during inflammation and homeostasis. The chemokine receptor CXCR2 has largely been associated with neutrophil recruitment. However, there is emerging evidence of roles for chemokines and their receptors in processes other than leukocyte migration. We have previously demonstrated that CXCR2 KO mice have thinner skin compared to wild type mice. Herein we demonstrate that this is due to a thinner subcutaneous adipose layer, as a result of fewer and smaller individual adipocytes. We observe a similar phenotype in other fat depots and present data that suggests this may be due to reduced expression of adipogenesis related genes associated with adipocyte specific CXCR2 signalling. Interestingly, this phenotype is evident in female, but not male, CXCR2 KO mice. These findings expand our understanding of non-leukocyte related chemokine receptor functions and help to explain some previously observed adipose-related phenotypes in CXCR2 KO mice.
Pharmaceutical salts of emoxypine with dicarboxylic acids
Authors: Manin Alex N. , Voronin Alexander P. , Drozd Ksenia V. , Churakov Andrei V. , Perlovich German L.
Published: June 2018

New salt forms of the antioxidant drug emoxypine (EMX, 2-ethyl-6-methylpyridin-3-ol) with pharmaceutically acceptable maleic (Mlt), malonic (Mln) and adipic (Adp) acids were obtained {emoxypinium maleate, C8H12NO+·C4H3O4−, [EMX+Mlt], emoxypinium malonate, C8H12NO+·C3H3O4−, [EMX+Mln], and emoxypinium adipate, C8H12NO+·C6H9O4−, [EMX+Adp]} and their crystal structures determined. The molecular packing in the three EMX salts was studied by means of solid-state density functional theory (DFT), followed by QTAIMC (quantum theory of atoms in molecules and crystals) analysis. It was found that the major contribution to the packing energy comes from pyridine–carboxylate and hydroxy–carboxylate heterosynthons forming infinite one-dimensional ribbons, with [EMX+Adp] additionally stabilized by hydrogen-bondedC(9) chains of Adp−ions. The melting processes of the [EMX+Mlt] (1:1), [EMX+Mln] (1:1) and [EMX+Adp] (1:1) salts were studied and the fusion enthalpy was found to increase with the increase of the calculated lattice energy. The dissolution process of the EMX salts in buffer (pH 7.4) was also studied. It was found that the formation of binary crystals of EMX with dicarboxylic acids increases the EMX solubility by more than 30 times compared to its pure form.
Structural and optical profile of a multifunctionalized 2-pyridone derivative in a crystal engineering perspective
Authors: Joy Monu , Anabha E. R. , Gopi Subash , Mathew Bijo , Kumar S Ajeesh , Mathews Annie
Published: June 2018

The supramolecular structural features of organic molecules are very important with regard to their widespread properties in both solids and solutions. Herein, we describe the synthesis of a novel multifunctional 2-pyridone derivative, namely 6-(4-chlorophenyl)-5-formyl-4-methylsulfanyl-2-oxo-1,2-dihydropyridine-3-carbonitrile, C14H9ClN2O2S, denoted P1, and its structural features were established through X-ray crystallography. A Hirshfeld surface analysis followed by a two-dimensional fingerprint plot analysis was carried out. A frontier molecular orbital investigation and natural bond orbital (NBO) calculations explored the charge-transfer interactions associated with the molecular system. The optical properties of the 2-pyridone derivative were elucidated through UV–Vis absorption and emission spectroscopy, indicating a strong blue emissive nature with a colour purity of 82.5%, a short-lived lifetime and a large Stokes shift. Time-dependent density functional theory (TD-DFT) was used to gain some insight into the absorption behaviour and emissive characteristics of P1.
Crystal structure determination, Hirshfeld surface analysis and energy frameworks of 6-phenylsulfonyl-6H-thieno[3,2-c]carbazole
Authors: Mohamooda Sumaya U. , Sankar E. , Arasambattu MohanaKrishnan K. , Biruntha K. , Usha G.
Published: June 2018

In the title compound, C20H13NO2S2, the carbazole ring system forms a dihedral angle of 89.08 (1)° with the sulfonyl-substituted phenyl ring. Intramolecular C—H...O hydrogen bonds involving the sulfone O atoms and the carbazole moiety result in two S(6) rings. In the crystal, molecules are linked via pairs of C—H...O hydrogen bonds forming inversion dimers with an R
2
2(12) graph-set motif. Analysis of the Hirshfeld surfaces and two-dimensional fingerprint plots was used to explore the distribution of weak intermolecular interactions in the crystal structure.
4-(3,5-Dimethoxyphenyl)-6-(2-methoxyphenyl)pyrimidin-2-amine
Authors: Koh Dongsoo , Lee Ji Hye
Published: June 2018

In the title molecule, C19H19N3O3, the 2-methoxyphenyl and 3,5-dimethoxyphenyl rings are attached at the 4- and 6-positions, respectively, of the central 2-aminopyrimidine ring. The dihedral angles between the planes of the benzene rings and that of the 2-aminopyrimidine ring are 17.31 (9) and 44.39 (6)°, respectively. In the crystal, pairs of N—H...N hydrogen bonds form inversion dimers enclosing R
2
2(8) rings. Pairs of N—H...O hydrogen bonds link the dimers into chains along [010].
Improving the government performance management system in South Korea
Authors: Roh Jongho
Published: June 2018

Purpose

The purpose of this paper is to review the current performance management system of the South Korean Government and make recommendations for improvements to its institutional, operational, and value dimensions.

Design/methodology/approach

Based on a literature review, the government performance management system in South Korea is analyzed according to its institutional, operational, and value dimensions.

Findings

The Korean Government’s performance management system has developed distinct features such as strong political leadership, diversity in types of performance evaluation, the institutional involvement of civilian experts, and a mutually cooperative system among agencies tasked with efficient performance management. This paper concludes that the government performance management system requires further improvement in its institutional, operational, and value dimensions.

Originality/value

The paper provides scholars and policy makers concerned with government performance management, with diverse perspectives and suggested areas for improvement.
Examining the relationships between HR practices, organizational job embeddedness, job satisfaction, and quit intention
Authors: Dechawatanapaisal Decha
Published: June 2018

Purpose

The purpose of this paper is to extend job embeddedness research by investigating employees’ perception of human resource (HR) practices as the predictors of organizational job embeddedness, and its mediating role between HR practices and quit intention. It also assesses the moderating effect of job satisfaction on the job embeddedness-turnover relationship.

Design/methodology/approach

Data were collected through a questionnaire survey from 1,028 accountants in various disciplines from one of the largest corporations in Thailand, including its numerous subsidiaries and joint ventures. Hypotheses were tested and analyzed by means of a confirmatory factor analysis, multiple regressions, and a bootstrapping procedure.

Findings

The results reveal that all HR practices except training are positively related to organizational job embeddedness. Analysis also provides support for the mediating effects on quit intention of two HR practices, namely rewards and career development, through organizational job embeddedness. In addition, the interaction effect shows that the negative relationship between organizational job embeddedness and quit intention reduces when job satisfaction is high.

Research limitations/implications

The current research took place among accountants. Replicating the study in a variety of business sectors, professions, or cultures would be useful for the generalizability of the findings.

Practical implications

Several HR strategies and tactics can help improve employee loyalty. Particularly effective are attractive rewards that reflect work values, and a promising career roadmap. Organizations might need to consider work conditions that sustain job satisfaction for turnover prevention in the short-term, and continuously manage long-term retention through embeddedness.

Originality/value

This study extends current research by investigating the relationships of so far untested theorized antecedents that clarify how employees become embedded in the workplace in order to keep them from quitting.
The influence of production, IT, and logistics process innovations on ambidexterity performance
Authors: Ardito Lorenzo , Besson Ekaterina , Petruzzelli Antonio Messeni , Gregori Gian Luca
Published: June 2018

Purpose

The purpose of this paper is to elucidate the relationship between three types of process innovations (i.e. innovation in production, IT, and logistics processes) and ambidexterity performance. Specifically, the paper attempts to examine whether changes in business processes help companies to reconcile exploration and exploitation learning activities within the firm domain.

Design/methodology/approach

This research is based on data of 2,843 manufacturing firms, whose data are available from the Italian Innovation Survey (period 2010-2012). Hypotheses are developed and tested by using a Tobit regression approach.

Findings

Innovation in production and IT processes favors ambidexterity performance, whereas changes in logistics activities, despite being positive, are less relevant.

Originality/value

This is one of the first attempts to offer empirical evidence about the relationship between process innovations and ambidexterity performance (without engaging in domain separation), hence providing additional insights into the ambidexterity literature and the literature on process innovation.
Assessing export competitiveness of food manufacturers in SIDS
Authors: Wilson Shellyanne
Published: June 2018

Purpose

For Small Island Developing States (SIDS), achieving export manufacturing competitiveness is a major challenge. This paper aims to provide a framework that can be used to study the export competitiveness for food manufacturers.

Design/methodology/approach

The revealed comparative export advantage (RXA) and the constant market share (CMS) measures are used in a case study set in the Trinidad and Tobago’s food and beverage sector to study export manufacturing competitiveness.

Findings

When using the RXA and CMS measures to assess the current state of export manufacturing competitiveness in SIDS, specific product groupings should be used in the analysis to obtain a more accurate assessment of competitiveness than that provided when using aggregate commodity groups. Furthermore, the export market section of the conceptual framework provides a structured approach towards studying the distribution effect element of the CMS analysis.

Research limitations/implications

Trade data are heavily used, which is subject to a number of well-documented limitations. In addition, there is no mandatory registration for companies operating in the case country, which results in under-reporting of industrial activity, and so limits the use of the framework in studying the exporting companies and the export products. Finally, a single case study limits the generalizability of the findings.

Practical implications

In particular, policymakers responsible for designing interventions for increasing export manufacturing competitiveness can use the framework to consider specific strategies as they relate to the exporting companies, the export products and the export markets.

Originality/value

This paper brings together three basic elements that contribute to export manufacturing competitiveness in the form of the conceptual framework.