bluuebunny/crossref_metadata_2025_split huggingface dataset:
The SAM domain of mouse SAMHD1 is critical for its activation and regulation
Authors: Buzovetsky Olga , Tang Chenxiang , Knecht Kirsten , Antonucci Jenna M. , Wu Li , Ji Xiaoyun , Xiong Yong 
Published: October 2017

ABSTRACTHuman SAMHD1 (hSAMHD1) is a retroviral restriction factor that blocks HIV-1 infection by depleting the cellular nucleotides required for viral reverse transcription. SAMHD1 is allosterically activated by nucleotides that induce assembly of the active tetramer. Although the catalytic core of hSAMHD1 has been studied extensively, previous structures have not captured the regulatory SAM domain. In this study, we determined the first crystal structure of full-length SAMHD1 by capturing mouse SAMHD1 (mSAMHD1) structures in three different nucleotide bound states. Although mSAMHD1 and hSAMHD1 are highly similar in sequence and function, we found that mSAMHD1 possesses a more complex nucleotide-induced activation process, highlighting the regulatory role of the SAM domain. Our results provide new insights into the regulation of SAMHD1 activity, thereby will facilitate the improvement of HIV mouse models and the development of new therapies for certain cancers and autoimmune diseases.
Distribution of Purines and Pyrimidines over miRNAs of Human, Gorilla and Chimpanzee
Authors: Das Jayanta Kumar , Pal Choudhury Pabitra , Chaudhuri Adwitiya , Hassan Sk. Sarif , Basu Pallab 
Published: October 2017

AbstractMeaningful words in English need vowels to break up the sounds that consonants make. The Nature has encoded her messages in RNA molecules using only four alphabets A, U, C and G in which the nine member double-ring bases (adenine (A) and Guanine (G)) are purines, while the six member single-ring bases (cytosine (C) and uracil (U)) are pyrimidines. Four bases A, U, C and G of RNA sequences are divided into three kinds of classifications according to their chemical properties. One of the three classifications, thepurine-pyrimidineclass is important. In understanding the distribution (organization) of purines and pyrimidines over some of the non-coding regions of RNA, all miRNAs from three species of Family Hominidae (namely human, gorilla and chimpanzee) are considered. The distribution of purines and pyrimidines over miRNA shows deviation from randomness. Based on the quantitative metrics (fractal dimension, Hurst exponent, Hamming distance, distance pattern of purine-pyrimidine, purine-pyrimidine frequency distribution and Shannon entropy) five different clusters have been made. It is identified that there exists only one miRNA in humanhsa-miR-6124which is purely made of purine bases only.AMS Subject Classification:92B05 & 92B15
Small Molecule Inhibitors of the Human Histone Lysine Methyltransferase NSD2 / WHSC1 / MMSET Identified from a Quantitative High-Throughput Screen with Nucleosome Substrate
Authors: Coussens Nathan P. , Kales Stephen C. , Henderson Mark J. , Lee Olivia W. , Horiuchi Kurumi Y. , Wang Yuren , Chen Qing , Kuznetsova Ekaterina , Wu Jianghong , Cheff Dorian M. , Chih-Chien Cheng Ken , Shinn Paul , Brimacombe Kyle R. , Shen Min , Simeonov Anton , Ma Haiching , Jadhav Ajit , Hall Matthew D. 
Published: October 2017

AbstractThe activity of the histone lysine methyltransferase NSD2 is thought to play a driving role in oncogenesis. Both overexpression of NSD2 and point mutations that increase its catalytic activity are associated with a variety of human cancers. While NSD2 is an attractive therapeutic target, no potent, selective and cell-active inhibitors have been reported to date, possibly due to the challenging nature of developing high-throughput assays for NSD2. To establish a platform for the discovery and development of selective NSD2 inhibitors, multiple assays were optimized and implemented. Quantitative high-throughput screening was performed with full-length wild-type NSD2 and a nucleosome substrate against a diverse collection of known bioactives comprising 16,251 compounds. Actives from the primary screen were further interrogated with orthogonal and counter assays, as well as activity assays with the clinically relevant NSD2 mutants E1099K and T1150A. Five confirmed inhibitors were selected for follow-up, which included a radiolabeled validation assay, surface plasmon resonance studies, methyltransferase profiling, and histone methylation in cells. The identification of NSD2 inhibitors that bind the catalytic SET domain and demonstrate activity in cells validates the workflow, providing a template for identifying selective NSD2 inhibitors.
Needs and preferences of patients with head and neck cancer in integrated care
Authors: van Overveld L.F.J. , Takes R.P. , Turan A.S. , Braspenning J.C.C. , Smeele L.E. , Merkx M.A.W. , Hermens R.P.M.G. ,   the Dutch Head and Neck Audit Group
Published: October 2017

ObjectivesIncorporation of patients’ perspectives in daily practice is necessary to adapt care to users’ needs. However, information on patients’ needs and preferences for integrated care is lacking. The aim was to explore these needs and preferences, taking patients with head and neck cancer (HNC) as example, to adapt current integrated care to be more patient‐centred.DesignSemi‐structured interviews were held with current and former patients and chairmen of patient associations. Relevant needs and preferences were identified and categorised using the eight‐dimension Picker model of patient‐centred care.SettingIntegrated HNC in the Netherlands.ParticipantsPatients with HNC and chairmen of two Dutch HNC patient associations.Main outcome measuresPatients’ needs and preferences of integrated HNC care categorised according the Picker model.ResultsA total of 34 themes of needs and preferences were identified, by 14 patients with HNC or their delegates, using the Picker dimensions. Themes often emerged were as follows: personalisation of health care regarding patient values; clear insight into the healthcare process at organisational level; use of personalised communication, education and information that meets patients’ requirements; adequate involvement of allied health professionals for physical support; more attention to the impact of HNC and its treatment; adequate involvement of family and friends; adequate general practitioner involvement in the aftercare; and waiting time reduction.ConclusionsMonitoring the identified themes in integrated HNC care, fitting in the Picker model, will enable us to respond better to the needs and preferences of patients, and patient‐centred care in oncological care can be enhanced.
Developing control algorithms of a voluntary cough for an artificial bioengineered larynx using surface electromyography of chest muscles: A prospective cohort study
Authors: Banus M.S. , Birchall M.A. , Graveston J.A. 
Published: October 2017

ObjectiveThis prospective cohort study investigates the prediction of a voluntary cough using surface electromyography (EMG) of intercostal and diaphragm muscles, to develop control algorithms for an EMG‐controlled artificial larynx.SettingThe Ear Institute, London.Main outcome measuresElectromyography onset compared to voluntary cough exhalation onset and to 100 ms (to give the artificial larynx the time to close the bioengineered vocal cords) before voluntary cough exhalation onset, in twelve healthy participants.ResultsIn the 189 EMG of intercostal muscle‐detected voluntary coughs, 172 coughs (91% CI 70‐112) were detected before onset of cough exhalation and 128 coughs (67.6% CI 33.7‐101.7) 100 ms before onset of cough exhalation. In the 158 EMG of diaphragm muscle‐detected voluntary coughs, 149 coughs (94.3% CI 76.3‐112.3) were detected before onset of cough exhalation and 102 coughs (64.6% CI 26.6‐102.6) 100 ms before onset of cough exhalation. More coughs were detected before onset of cough exhalation when combining EMG activity of intercostal and diaphragm muscles and comparing this to intercostal muscle activity alone (183 coughs [96.8% CI 83.8‐109.8] vs 172 coughs, P = .0294). When comparing the mentioned combination to diaphragm muscle activity alone, the higher percentage of detected coughs before cough exhalation onset was not found to be significant (183 coughs vs 149 coughs, P = .295). In addition, more coughs were detected 100 ms before onset of cough exhalation with the mentioned combination of EMG activity and comparing this to intercostal muscles alone (149 coughs [78.8% CI 48.8‐108.8] vs 128 coughs, P = .0198) and to diaphragm muscles alone (149 coughs vs 102 coughs, P = .0038).ConclusionsMost voluntary coughs can be predicted based on combined EMG signals of intercostal and diaphragm muscles, and therefore, these two muscle groups will be useful in controlling the bioengineered vocal cords within the artificial larynx during a voluntary cough.
Internal anal sphincter nerves – a macroanatomical and microscopic description of the extrinsic autonomic nerve supply of the internal anal sphincter
Authors: Stelzner S. , Böttner M. , Kupsch J. , Kneist W. , Quirke P. , West N. P. , Witzigmann H. , Wedel T. 
Published: October 2017

AbstractAimThe internal anal sphincter (IAS) contributes substantially to anorectal functions. While its autonomic nerve supply has been studied at the microscopic level, little information is available concerning the macroscopic topography of extrinsic nerve fibres. This study was designed to identify neural connections between the pelvic plexus and the IAS, provide a detailed topographical description, and give histological proof of autonomic nerve tissue.MethodsMacroscopic dissection of pelvic autonomic nerves was performed under magnification in seven (five male, two female) hemipelvises obtained from body donors (67–92 years). Candidate structures were investigated by histological and immunohistochemical staining protocols to visualize nerve tissue.ResultsNerve fibres could be traced from the anteroinferior edge of the pelvic plexus to the anorectal junction running along the neurovascular bundle anterolaterally to the rectum and posterolaterally to the prostate/vagina. Nerve fibres penetrated the longitudinal rectal muscle layer just above the fusion with the levator ani muscle (conjoint longitudinal muscle) and entered the intersphincteric space to reach the IAS. Histological and immunohistochemical findings confirmed the presence of nerve tissue.ConclusionsAutonomic nerve fibres supplying the IAS emerge from the pelvic plexus and are distinct to nerves entering the rectum via the lateral pedicles. Thus, they should be classified as IAS nerves. The identification and precise topographical location described provides a basis for nerve‐sparing rectal resection procedures and helps to prevent postoperative functional anorectal disorders.
Histomorphometric approach to differentiate skin lesions of tuberculoid leprosy from sarcoidosis
Authors: Utino Fabiane Leonel , Damiani Gislaine Vieira , Garcia Marina , Soares Tânia Cristina Benetti , Stelini Rafael Fantelli , Velho Paulo Eduardo Neves Ferreira , de Souza Elemir Macedo , Cintra Maria Letícia 
Published: October 2017

BackgroundMore than 200 000 new cases of leprosy are detected worldwide annually. Physicians commonly have difficulty in differentiating tuberculoid form of leprosy (TL) from sarcoidosis’ cutaneous manifestation.MethodsSkin biopsies of 33 patients with TL and 24 with sarcoidosis were reviewed on hematoxylin and eosin‐ and Gomori‐stained sections, in order to find reliable criteria for distinguishing one disease from another.ResultsNine of the 24 features analyzed presented significant predictive value for diagnosis (P < .05). Predominance of tuberculoid granulomas in adnexal and neural distribution, and granulomas replacing the nerves localized within sweat gland glomeruli were predictive to TL diagnosis. For sarcoidosis, dermal fibrosis, back‐to‐back distribution of the granulomas, presence of atypical giant cells and plasma cells, greater number of conventional giant cells, and spared nerves beside the granuloma were predictive criteria. The median surface density of reticulin fibers was significantly higher in sarcoidosis (3.44) than in TL (2.99). Nonetheless, using logistic regression, this variable did not discriminate between the diseases (P = .096).ConclusionsIsolated histological features are not fully predictive to differentiate the 2 diseases. However, those with statistical value can assist this distinction in diagnostic practice. Although the results of the analysis of the reticulin fibers density did not tell apart TL from sarcoidosis, they corroborate the idea of fiber fragmentation within tuberculoid leprosy granulomas, reiterating the importance of morphometry in the histological examination.
The use of pneumatic impact lithotripsy and a retrieval pouch to create a closed system for removal of cystic calculi in standing male horses
Authors: De Bernardis N. P. , Seabaugh K. A. , Ismay J. , Mudge M. 
Published: October 2017

SummaryMultiple techniques exist for removal of cystic calculi in the male horse, some of which use a perineal urethrotomy (PU) to facilitate access to the urinary bladder for removal of small uroliths in the standing, sedated horse. These techniques have limited efficacy in the removal of uroliths that have a diameter larger than the PU site, typically 4–5 cm. Pneumatic lithotripsy as reported in this article provides a novel way to fragment these larger uroliths while containing the fragments and protecting the urethra and urinary bladder. Ten geldings and one stallion underwent a lithotripsy procedure to remove one (n = 10) or several (n = 1) uroliths ranging in diameter from 4 to 9 cm. A PU was performed and a laparoscopic retrieval bag was inserted into the urinary bladder through the PU site. The urolith was manipulated into the bag using blind transrectal manipulation or endoscopic guidance and the opening of the bag was exteriorised out of the PU site. A pneumatic lithotrite was used to fragment the stone. When the urolith was adequately fragmented, the fragments were removed by the use of sponge forceps and by flushing the fragments from the bag with obstetrical lube. This was continued until the bag could smoothly be withdrawn from the urinary bladder. All uroliths were successfully removed. The PU sites healed without complication and none of the horses had recurrence of presenting clinical signs. This article also discusses the difference between two types of laparoscopic retrieval bags. Pneumatic impact lithotripsy in combination with a retrieval pouch offers a safe alternative to other methods for removal of cystic calculi in the horse.
Radiological prevalence of equine odontoclastic tooth resorption and hypercementosis
Authors: Rehrl S. , Schröder W. , Müller C. , Staszyk C. , Lischer C. 
Published: October 2017

SummaryBackgroundEquine odontoclastic tooth resorption and hypercementosis (EOTRH) is a painful and progressive dental disease that mainly affects the incisors and canine teeth of aged horses. Diagnosis is based on radiographs to detect early stages of the disease.EOTRHis probably underdiagnosed and its prevalence in Germany unknown.ObjectiveThis study was performed to determine the radiological prevalence ofEOTRHin a large horse population in Berlin‐Brandenburg, Germany.Study designPrevalence study.MethodsThe study population (142 horses) consisted of all horses 10 years and older that were presented at the Equine Hospital for a routine dental examination. The horses were either presented as clinical cases (CCpopulation) or belonged to a riding school (RSpopulation). Digital radiographs of the incisor dentition were taken and evaluated for changes related toEOTRH, leading to an overall classification for each horse.ResultsThe mean age of the study population was 21 years and ranged from 10 to 37 years. Overall, 94% of all horses had at least minor and 62% had moderate to severe radiological changes of the incisor teeth associated toEOTRH. No horse older than 14 years was without radiological signs ofEOTRHand all horses over 28 years of age had at least moderate radiological changes of the incisor teeth.Main limitationsThe clinical cases group might have a bias towards horses with existing dental problems such asEOTRH, because they were presented explicitly for dental care to a clinic.ConclusionFocusing on radiological changes, this study shows thatEOTRHis a common condition of horses in Berlin‐Brandenburg. With older age, disease is more frequent and radiological changes become more severe. Since no horse older than 14 years was without radiological findings, it is likely that mild changes may be associated with the normal tooth ageing process.
New insights on the phylogeny of Tectaria (Tectariaceae), with special reference to Polydictyum as a distinct lineage
Authors: Dong Shi‐Yong , Chen Cheng‐Wei , Tan Shi‐Shi , Zhao Hui‐Guo , Zuo Zheng‐Yu , Chao Yi‐Shan , Chang Yi‐Han 
Published: October 2017

AbstractThe fern genus Tectaria (Tectariaceae) Cav. is morphologically diverse and difficult in terms of recognizing species and species groups. To infer the systematic positions of some species and identity‐unknown collections with special morphological characters, we undertook phylogenetic analyses based on sequences of five plastid regions (atpB, ndhF + ndhF‐trnL, rbcL, rps16‐matK + matK, and trnL‐F). Three analysis methods (maximum parsimony, maximum likelihood, and Bayesian inference) were used to reconstruct the phylogeny of Tectaria. The most surprising result is that T. menyanthidis (C. Presl) Copel., T. ternata (Baker) Copel., and T. variabilis Tardieu & Ching are revealed to represent a distinct lineage from Tectaria, which should be called Polydictyum C. Presl, and is supported as sister to Pteridrys C. Chr. & Ching. Other accessions of Tectaria are well resolved into four major clades, which is consistent with the results of previous studies. Of the four clades, Clade II (T. subtriphylla (Hook. & Arn.) Copel. group) is unpredictable, with morphologically very diverse species clustered there, and is supposed to be a minor evolutionary line within Tectaria in the Old World. In addition, the position of the climbing genus Arthropteris J. Sm. and the utility of molecular data in recognizing species of Tectaria are briefly discussed. As a conclusion, we formally reinstate the genus Polydictyum by providing diagnostic characters, key to species, nomenclature, and information of detailed distribution and habitat for the currently known three species.
Diagnostic utility of cortactin antibodies in myasthenia gravis
Authors: Illa Isabel , Cortés‐Vicente Elena , Martínez María Ángeles , Gallardo Eduard 
Published: October 2017

AbstractPatients with myasthenia gravis (MG) without antibodies to the acetylcholine receptor (AChR) or muscle‐specific tyrosine kinase (MuSK) have been classified as having double‐seronegative myasthenia gravis (dSNMG). We used the sera from six dSNMG patients with positive immunohistochemistry assays in a protein array to screen reactivity with 9000 human proteins. We identified cortactin, an intracellular protein that interacts with agrin/MuSK favoring AChR aggregation, as a new antigen in dSNMG. We then designed an in‐house enzyme‐linked immunosorbent assay as a screening assay and confirmed these results by western blot. We found that 19.7% of dSNMG patients had anti‐cortactin antibodies. In contrast, patients with AChR+ MG or other autoimmune disorders and healthy controls were positive at significantly lower rates. Five percent of healthy controls were positive. In a recent study, we screened sera from 250 patients (AChR+ MG, MuSK+ MG, dSNMG) and 29 healthy controls. Cortactin antibodies were identified in 23.7% of dSNMG and 9.5% AChR+ MG patients (P = 0.02). None of the MuSK+ MG patients, patients with other autoimmune disorders, or healthy controls had antibodies against cortactin. Patients with dSNMG cortactin+ MG were negative for anti‐striated muscle and anti‐LRP4 antibodies. Patients with dSNMG cortactin+ MG presented ocular or mild generalized MG without bulbar symptoms. We conclude that cortactin autoantibodies are biomarkers of MG that, when present, suggest that the disease will be mild.
Sedimentary architecture beneath lakes subjected to storms: Control by turbidity current bypass and turbidite armouring, interpreted from ground‐penetrating radar images
Authors: Arcone Steven A. 
Published: October 2017

AbstractTurbidites within Holocene lacustrine sediment cores occur worldwide and are valued deposits that record a history of earthquakes or storms. Without sedimentary architecture, however, interpretation of the cause, provenance and behaviour of their parent turbidity currents are speculative. Here, these interpretations are made from two‐dimensional ground‐penetrating radar images of ‘shore to shore’ architecture beneath three, previously cored lakes within the low seismicity New England (USA) region. Shallow depths, low water and sediment conductivities, and signal sensitivity to density contrasts uniquely provided up to 30 m of sediment signal penetration. Core comparisons and signal analysis reveal that most horizons represent multidecimetre‐thick clusters of Holocene turbidites, which are denser than their organic‐rich silt matrix. Some horizons also represent erosional unconformities and sediment bypass interfaces. The key, common, architectural consequences of turbidity current activity include limited foreset progradation, conformably pinched or unconformable layers of organic‐rich sediment onlapped against slopes beneath 5 to 6 m of water, and mounded stratified sediments beneath rises. These features indicate that turbidity currents repeatedly bypassed the same slope without deposition and regardless of dip, and then simultaneously armoured and bypassed inter‐turbidite sediment along rises and basins to provide basinward, generally age‐conformable accumulation. The mounding precludes significant basinward focusing. Variable horizon amplitude suggests metre‐scale changes in armouring density. Unconformities localized near breaks in dip beneath slopes suggest erosive hydraulic jumps. One lake shows evidence of historically maintained channels associated with specific deltas. Shelf strata indicating inland current generation, similar key architecture in other, uncored lakes, countable, lake‐wide horizons, and absent slumps, slides and faults are consistent with storm‐driven turbidity currents, and with previous, core‐based conclusions that severe, Holocene storms were episodic throughout this region. The results generalize marine bypass and armouring to lacustrine settings, and so probably occur worldwide in lakes subject only to storms, including lakes where ground‐penetrating radar may locate core sites.