bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting JAK2 reduces GVHD and xenograft rejection through regulation of T cell differentiation
Authors: Betts Brian C. , Bastian David , Iamsawat Supinya , Nguyen Hung , Heinrichs Jessica L. , Wu Yongxia , Daenthanasanmak Anusara , Veerapathran Anandharaman , O’Mahony Alison , Walton Kelly , Reff Jordan , Horna Pedro , Sagatys Elizabeth M. , Lee Marie C. , Singer Jack , Chang Ying-Jun , Liu Chen , Pidala Joseph , Anasetti Claudio , Yu Xue-Zhong
Published: January 2018

Significance

Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality among allogeneic stem-cell transplantation recipients. An effort to identify selective immune suppression whereby GVHD is reduced and the antitumor activity of the graft is preserved is key to improving the success of blood and marrow transplantation. Here we demonstrate that inhibition of Janus kinase 2 (JAK2) significantly decreases GVHD and maintains tumor killing by the donor T cells. Pharmacologic blockade of JAK1 and JAK2 in myelofibrosis patients is known to impair human T cell subsets broadly. Conversely, we show that JAK2 inhibition impairs alloreactive T cells yet promotes beneficial regulatory T cell and Th2 differentiation. This study emphasizes the relevance of JAK2 in GVHD pathogenesis and prevention.
Pyruvate cycle increases aminoglycoside efficacy and provides respiratory energy in bacteria
Authors: Su Yu-bin , Peng Bo , Li Hui , Cheng Zhi-xue , Zhang Tian-tuo , Zhu Jia-xin , Li Dan , Li Min-yi , Ye Jin-zhou , Du Chao-chao , Zhang Song , Zhao Xian-liang , Yang Man-jun , Peng Xuan-xian
Published: January 2018

Significance

Exogenous metabolites have been documented to potentiate antibiotics to kill multidrug-resistant pathogens, but the mechanisms are largely unknown. The work presented here shows that intermetabolites from the TCA cycle and the phosphoenolpyruvate (PEP)-pyruvate-AcCoA pathway have the potential to improve targeting of these resistant microorganisms. The enzymes that connect the PEP-pyruvate-AcCoA pathway to the TCA cycle are essential for this potentiation, indicating both pathway and cycle can be merged to be considered a pyruvate cycle (P cycle). The P cycle operates routinely as a general mechanism for energy production and regulating the TCA cycle in
Escherichia coli
and
Edwardsiella tarda
. The results reported here provide insights into metabolite-facilitated targeting by antibiotics as well as bacterial energy metabolism and homeostasis.
Heterogeneity within the frontoparietal control network and its relationship to the default and dorsal attention networks
Authors: Dixon Matthew L. , De La Vega Alejandro , Mills Caitlin , Andrews-Hanna Jessica , Spreng R. Nathan , Cole Michael W. , Christoff Kalina
Published: January 2018

Significance

The frontoparietal control network (FPCN) contributes to executive control, the ability to deliberately guide action based on goals. While the FPCN is often viewed as a unitary domain general system, it is possible that the FPCN contains a fine-grained internal organization, with separate zones involved in different types of executive control. Here, we use graph theory and meta-analytic functional profiling to demonstrate that the FPCN is composed of two separate subsystems: FPCN
A
is connected to the default network and is involved in the regulation of introspective processes, whereas FPCN
B
is connected to the dorsal attention network and is involved in the regulation of perceptual attention. These findings offer a distinct perspective on the systems-level circuitry underlying cognitive control.
RGMb protects against acute kidney injury by inhibiting tubular cell necroptosis via an MLKL-dependent mechanism
Authors: Liu Wenjing , Chen Binbin , Wang Yang , Meng Chenling , Huang Huihui , Huang Xiao-Ru , Qin Jinzhong , Mulay Shrikant R. , Anders Hans-Joachim , Qiu Andong , Yang Baoxue , Freeman Gordon J. , Lu Hua Jenny , Lin Herbert Y. , Zheng Zhi-Hua , Lan Hui-Yao , Huang Yu , Xia Yin
Published: January 2018

Significance

Necroptosis is critically involved in the development of acute kidney injury (AKI), but it has not been well demonstrated that necroptosis occurs in renal tubular epithelial cells in vivo during AKI. Now, we provide evidence that renal proximal tubular cells undergo necroptosis during ischemia/reperfusion injury or oxalate nephropathy. Repulsive guidance molecule-b protects against AKI by inhibiting mixed lineage kinase domain-like membrane association and necroptosis in proximal tubular cells.
Structures and mechanism of dipeptidyl peptidases 8 and 9, important players in cellular homeostasis and cancer
Authors: Ross Breyan , Krapp Stephan , Augustin Martin , Kierfersauer Reiner , Arciniega Marcelino , Geiss-Friedlander Ruth , Huber Robert
Published: January 2018

Dipeptidyl peptidases 8 and 9 are intracellular N-terminal dipeptidyl peptidases (preferentially postproline) associated with pathophysiological roles in immune response and cancer biology. While the DPP family member DPP4 is extensively characterized in molecular terms as a validated therapeutic target of type II diabetes, experimental 3D structures and ligand-/substrate-binding modes of DPP8 and DPP9 have not been reported. In this study we describe crystal and molecular structures of human DPP8 (2.5 Å) and DPP9 (3.0 Å) unliganded and complexed with a noncanonical substrate and a small molecule inhibitor, respectively. Similar to DPP4, DPP8 and DPP9 molecules consist of one β-propeller and α/β hydrolase domain, forming a functional homodimer. However, they differ extensively in the ligand binding site structure. In intriguing contrast to DPP4, where liganded and unliganded forms are closely similar, ligand binding to DPP8/9 induces an extensive rearrangement at the active site through a disorder-order transition of a 26-residue loop segment, which partially folds into an α-helix (R-helix), including R160/133, a key residue for substrate binding. As vestiges of this helix are also seen in one of the copies of the unliganded form, conformational selection may contributes to ligand binding. Molecular dynamics simulations support increased flexibility of the R-helix in the unliganded state. Consistently, enzyme kinetics assays reveal a cooperative allosteric mechanism. DPP8 and DPP9 are closely similar and display few opportunities for targeted ligand design. However, extensive differences from DPP4 provide multiple cues for specific inhibitor design and development of the DPP family members as therapeutic targets or antitargets.
Plasticity of
Mycobacterium tuberculosis
NADH dehydrogenases and their role in virulence
Authors: Vilchèze Catherine , Weinrick Brian , Leung Lawrence W. , Jacobs William R.
Published: January 2018

Significance

Tuberculosis drug development remains crucial for countering the spread of drug resistance worldwide. New susceptibilities in metabolic pathways must be identified to find novel drugs to eradicate tuberculosis. The electron transport chain (ETC) is the target of recently developed tuberculosis drugs. To assess whether the NADH dehydrogenases of the ETC would be potential drug candidates, we deleted the genes encoding the three
Mycobacterium tuberculosis
NADH dehydrogenases Nuo, Ndh, and NdhA. We found that although the NADH dehydrogenases were not essential for growth individually, deletion of both
nuo
and
ndh
had the most profound effect on
Mycobacterium tuberculosis
viability and virulence. We propose that screening compound libraries against both Ndh and Nuo will lead to promising drug candidates to fight tuberculosis.
Electron beam melting of Inconel 718: Effects of processing and post-processing
Authors: Nandwana Peeyush , Kirka Michael , Okello Alfred , Dehoff Ryan
Published: January 2018

This study reports the effect of process temperature on microstructure evolution of electron beam melted Inconel 718. Samples fabricated at 915°C had fine grain boundary δ (∼200 nm) along with coarse intragranular δ spanning through the length of the grains. On the other hand, samples fabricated at 990°C, only had grain boundary δ along with secondary carbides. During hot isostatic pressing, the distribution of carbides governs the grain growth vs. lack of it. The samples fabricated at 990°C having grain boundary carbides had no grain growth owing to the pinning effect of carbides. In contrast, the sample processed at 915°C had significant grain growth owing to dissolution of grain boundary δ phase and absence of grain boundary carbides.
Regulation of amyloid-β dynamics and pathology by the circadian clock
Authors: Kress Geraldine J. , Liao Fan , Dimitry Julie , Cedeno Michelle R. , FitzGerald Garret A. , Holtzman David M. , Musiek Erik S.
Published: January 2018

Nighttime restlessness and daytime drowsiness are common and early symptoms of Alzheimer’s Disease (AD). This symptomology implicates dysfunctional biological timing, yet the role of the circadian system in AD pathogenesis is unknown. To evaluate the role of the circadian clock in amyloid-β (Aβ) dynamics and pathology, we used a mouse model of β-amyloidosis and disrupted circadian clock function either globally or locally in the brain via targeted deletion of the core clock gene Bmal1. Our results demonstrate that loss of central circadian rhythms leads to disruption of daily hippocampal interstitial fluid Aβ oscillations and accelerates amyloid plaque accumulation, whereas loss of peripheral Bmal1 in the brain parenchyma increases expression of Apoe and promotes fibrillar plaque deposition. These results provide evidence that both central circadian rhythms and local clock function influence Aβ dynamics and plaque formation and demonstrate mechanisms by which poor circadian hygiene may directly influence AD pathogenesis.
Concatenated nicotinic acetylcholine receptors: A gift or a curse?
Authors: Ahring Philip Kiær , Liao Vivian Wan Yu , Balle Thomas
Published: January 2018

Nicotinic acetylcholine receptors (nAChRs) belong to the Cys-loop receptor family and are vital for normal mammalian brain function. Cys-loop receptors are pentameric ligand-gated ion channels formed from five identical or homologous subunits oriented around a central ion-conducting pore, which result in homomeric or heteromeric receptors, respectively. Within a given Cys-loop receptor family, many different heteromeric receptors can assemble from a common set of subunits, and understanding the properties of these heteromeric receptors is crucial for the continuing quest to generate novel treatments for human diseases. Yet this complexity also presents a hindrance for studying Cys-loop receptors in heterologous expression systems, where full control of the receptor stoichiometry and assembly is required. Therefore, subunit concatenation technology is commonly used to control receptor assembly. In theory, this methodology should facilitate full control of the stoichiometry. In reality, however, we find that commonly used constructs do not yield the expected receptor stoichiometries. With ternary or more complex receptors, concatenated subunits must assemble uniformly in only one orientation; otherwise, the resulting receptor pool will consist of receptors with mixed stoichiometries. We find that typically used constructs of α4β2 nAChR dimers, tetramers, and pentamers assemble readily in both the clockwise and the counterclockwise orientations. Consequently, we investigate the possibility of successfully directing the receptor assembly process using concatenation. We begin by investigating the three-dimensional structures of the α4β2 nAChR. Based on this, we hypothesize that the minimum linker length required to bridge the C terminus of one subunit to the N terminus of the next is shortest in the counterclockwise orientation. We then successfully express receptors with a uniform stoichiometry by systematically shortening linker lengths, proving the hypothesis correct. Our results will significantly aid future studies of heteromeric Cys-loop receptors and enable clarification of the current contradictions in the literature.
Quantitative Research on the Relationship between Yield of Winter Wheat and Agroclimatological Resources—the Case Study from Yanzhou District, Shandong Province, China
Authors: Yan Maoling , Liu Pingzeng , Zhang Chao , Zheng Yong , Wang Xizhi , Zhang Yan , Chen Weijie , Zhao Rui
Published: January 2018

Agroclimatological resources provide material and energy for agricultural production. This study is aimed to analyze the impact of selected climate factors change on wheat yield over the different growth period applied quantitatively method, by comparing two different time division modules of wheat growth cycle- monthly empirical-statistical multiple regression models ( From October to June of next year ) and growth stage empirical-statistical multiple regression models (Including sowing stage, seedling stage, tillering stage, overwintering period, regreening period, jointing stage, heading stage, maturity stage) analysis of relationship between agrometeorological data and growth stage records and winter wheat production in Yanzhou, Shandong Province of China. Correlation analysis(CA)was done for 35 years (from 1981 to 2015) between crop yield and corresponding weather parameters including daily mean temperature, sunshine duration, and average daily precipitation selected from 18 different meteorological factors. The results shows that the greatest impact on the winter wheat yield is the precipitation overwintering period in this area, each 1mm increase in daily mean rainfall was associated with 201.64 kg/hm2 lowered output. Moreover, the temperature and sunshine duration in heading period and maturity stage also exert significant influence on the output, every 1°C increase in daily mean temperature was associated with 199.85kg/hm2 adding output, every 1h increase in mean sunshine duration was associated with 130.68kg/hm2 reduced output. Comparing with the results of experiment which using months as step sizes and using farming as step sizes was in better agreement with the fluctuation in meteorological yield, offered a better explanation on the growth mechanism of wheat. Eventually the results indicated that 3 factors affects the yield during different growing periods of wheat in different extent and provided more specific reference to guide the agricultural production management in this area.
A Shortened Version of the Reasons for Living—Older Adults Scale for Clinical and Research Utility
Authors: Lutz Julie , Edelstein Barry , Katz Emma , Gallegos Jarred V
Published: January 2018

Background and Objectives

Older adults have elevated suicide rates, and identification of protective factors, such as reasons for living, is important in preventing suicide. The Reasons for Living—Older Adults scale (RFL-OA) is a 69-item measure of these protective factors in late life, which yields good psychometric properties. However, its length limits its utility in some clinical and research contexts where a shorter measure is ideal. The objective of this study was to create a shortened version of the RFL-OA.

Research Design and Methods

First, data collected previously during validation of the original RFL-OA (n = 199, age 65 and older, 65% female) were used to select 30 items, spanning all content areas, that were highly endorsed. Second, new data were collected (n = 219, age 60 and older, 52% female) with the 30-item RFL-OA and measures of depression, hopelessness, suicidal ideation, religiosity, health, and social desirability to examine the measure’s internal consistency and convergent and discriminant validity.

Results

Scores on the 30-item RFL-OA exhibited strong internal consistency. The short RFL-OA demonstrated good convergent validity via significant, moderate correlations with suicidal ideation, hopelessness, depression, and religiosity. It demonstrated adequate discriminant validity via only small correlations with disability, subjective health, and social desirability.

Discussion and Implications

The shorter RFL-OA has good psychometric properties among community-dwelling older adults. It may have greater utility, compared to the original 69-item measure, for clinicians and researchers with limited time but who want to assess protective factors against suicidal behavior in late life.
Collections of Orbits of Hyperplane Type in Homogeneous Spaces, Homogeneous Dynamics, and Hyperkähler Geometry
Authors: Amerik Ekaterina , Verbitsky Misha
Published: January 2018

Consider the space M = O(p, q)/O(p) × O(q) of positive p-dimensional subspaces in a pseudo-Euclidean space V of signature (p, q), where p > 0, q > 1 and $(p,q)\neq (1,2)$, with integral structure: $V = V_{\mathbb{Z}} \otimes \mathbb{Z}$. Let Γ be an arithmetic subgroup in $G = O(V_{\mathbb{Z}})$, and $R \subset V_{\mathbb{Z}}$ a Γ-invariant set of vectors with negative square. Denote by R⊥ the set of all positive p-planes W ⊂ V such that the orthogonal complement W⊥ contains some r ∈ R. We prove that either R⊥ is dense in M or Γ acts on R with finitely many orbits. This is used to prove that the squares of primitive classes giving the rational boundary of the Kähler cone (i.e., the classes of “negative” minimal rational curves) on a hyperkähler manifold X are bounded by a number which depends only on the deformation class of X. We also state and prove the density of orbits in a more general situation when M is the space of maximal compact subgroups in a simple real Lie group.
Negative Curves on Symmetric Blowups of the Projective Plane, Resurgences, and Waldschmidt Constants
Authors: Bauer Thomas , Di Rocco Sandra , Harbourne Brian , Huizenga Jack , Seceleanu Alexandra , Szemberg Tomasz
Published: January 2018

The Klein and Wiman configurations are highly symmetric configurations of lines in the projective plane arising from complex reflection groups. One noteworthy property of these configurations is that all the singularities of the configuration have multiplicity at least 3. In this paper we study the surface X obtained by blowing up $\mathbb{P}^{2}$ in the singular points of one of these line configurations. We study invariant curves on X in detail, with a particular emphasis on curves of negative self-intersection. We use the representation theory of the stabilizers of the singular points to discover several invariant curves of negative self-intersection on X, and use these curves to study Nagata-type questions for linear series on X.

The homogeneous ideal I of the collection of points in the configuration is an example of an ideal where the symbolic cube of the ideal is not contained in the square of the ideal; ideals with this property are seemingly quite rare. The resurgence and asymptotic resurgence are invariants which were introduced to measure such failures of containment. We use our knowledge of negative curves on X to compute the resurgence of I exactly. We also compute the asymptotic resurgence and Waldschmidt constant exactly in the case of the Wiman configuration of lines, and provide estimates on both for the Klein configuration.
Comparison of Anterior Cervical Discectomy and Fusion to Posterior Cervical Foraminotomy for Cervical Radiculopathy: Utilization, Costs, and Adverse Events 2003 to 2014
Authors: Witiw Christopher D , Smieliauskas Fabrice , O’Toole John E , Fehlings Michael G , Fessler Richard G
Published: January 2018

BACKGROUND

Surgery for cervical radiculopathy is often approached by either anterior cervical discectomy and fusion (ACDF) or posterior cervical foraminotomy (PCF). ACDF is more common; however, recent single center studies suggest comparable efficacy and significant cost savings with PCF in appropriately selected patients.

OBJECTIVE

To compare utilization, adverse events, and costs for each approach from a national perspective.

METHODS

Adults undergoing single level ACDF or PCF for cervical radiculopathy were included from a US commercial health insurance claims database spanning 2003 to 2014. Outcomes consisted of mortality, adverse events, length of stay, and total payments to the health provider. Propensity score matching balanced the groups on observed baseline covariates.

RESULTS

The PCF cohort comprised 4851 subjects and the ACDF cohort included 46 147. A greater proportion of PCF cases were discharged on the same day (70.6% vs 46.1%;P< .001). Mortality (0.1/1000,P= .012), vascular injury (0.2/1000,P= .001), postoperative dysphagia/dysphonia (14.5/1000,P< .001), cutaneous cerebrospinal fluid leak (0.2/1000,P= .002), and deep venous thrombosis (0.9/1000,P= .013) occurred more frequency in the ACDF cohort. Conversely, wound infections (14.6/1000,P< .001) and 30-d readmissions (9.8/1000,P< .001) were more frequent in the PCF cohort. Mean unadjusted total payments for the PCF cohort were $15 281 ± 12 225 and $26 849 ± 16 309 for ACDF. Matched difference was –$11 726 [95% confidence interval: –$12 221, –$11 232,P< .001] favoring PCF.

CONCLUSION

Within the inherent limitations of administrative data, our findings suggest an opportunity for value improvement in managing cervical radiculopathy and indicate a need for large-scale comparative study of clinical outcomes and costs.
The Effect of Cardiac Education on Knowledge and Self-care Behaviors Among Patients With Heart Failure
Authors: Tawalbeh Loai Issa
Published: January 2018

Background

No studies have been conducted in Jordan to examine the effect of cardiac education on knowledge and self-care behaviors among patients with heart failure in Jordan.

Purpose

The purpose of this study was to examine the effect of a cardiac educational program on knowledge and self-care behaviors among patients with heart failure.

Method

A quasi-experimental pretest/posttest design was used. A convenient sample of 127 patients with heart failure was recruited. The participants were randomly assigned to either experimental (n = 55) or control (n = 65) group. Knowledge and self-care were measured at 1 and 3 months after the program application.

Results

Results indicated that the change of knowledge mean score was statistically significant, P ≤ .001, between the pretest and both the first and second posttests for the experimental group compared with the control group. The change of maintenance self-care mean was statistically significant, P ≤ .001, between the pretest and both the first and second posttests for the experimental group compared with the control group. Moreover, the change in the management self-care mean was statistically significant, P ≤ .001, between the pretest and both the first and second posttests for the experimental group compared with the control group. Finally, the change of confidence self-care mean was statistically significant, P ≤ .001, between the pretest and both the first and second posttests for the experimental group compared with the control group.

Conclusion

Applying cardiac education program helps improve knowledge and self-care among patients with heart failure. Such educational programs should be adopted in clinical settings to enhance knowledge and self-care behaviors.
Optimizing Outcome Assessment in Multicenter TBI Trials: Perspectives From TRACK-TBI and the TBI Endpoints Development Initiative
Authors: Bodien Yelena G. , McCrea Michael , Dikmen Sureyya , Temkin Nancy , Boase Kim , Machamer Joan , Taylor Sabrina R. , Sherer Mark , Levin Harvey , Kramer Joel H. , Corrigan John D. , McAllister Thomas W. , Whyte John , Manley Geoffrey T. , Giacino Joseph T.
Published: January 2018

Traumatic brain injury (TBI) is a global public health problem that affects the long-term cognitive, physical, and psychological health of patients, while also having a major impact on family and caregivers. In stark contrast to the effective trials that have been conducted in other neurological diseases, nearly 30 studies of interventions employed during acute hospital care for TBI have failed to identify treatments that improve outcome. Many factors may confound the ability to detect true and meaningful treatment effects. One promising area for improving the precision of intervention studies is to optimize the validity of the outcome assessment battery by using well-designed tools and data collection strategies to reduce variability in the outcome data. The Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study, conducted at 18 sites across the United States, implemented a multidimensional outcome assessment battery with 22 measures aimed at characterizing TBI outcome up to 1 year postinjury. In parallel, through the TBI Endpoints Development (TED) Initiative, federal agencies and investigators have partnered to identify the most valid, reliable, and sensitive outcome assessments for TBI. Here, we present lessons learned from the TRACK-TBI and TED initiatives aimed at optimizing the validity of outcome assessment in TBI.
The Effect of Admission Functional Independence on Early Recovery in Pediatric Traumatic and Nontraumatic Brain Injury
Authors: Marino Cherylynn , Botticello Amanda , Coyne Julia H. , Dribbon Michael , DeLuca John
Published: January 2018

Objective:

To examine functional independence at admission as a predictor of outcomes during an initial inpatient hospitalization for a pediatric brain injury.

Participants:

A total of 531 pediatric inpatients with traumatic (n = 298) or nontraumatic (n = 233) brain injuries.

Design:

Retrospective analysis of data extracted from the Uniform Data System for Medical Rehabilitation.

Main Measure:

The Functional Independence Measure for Children, a measure of self-care, mobility, and cognitive independence.

Results:

Logistic regression analyses indicated that children with traumatic brain injury showed greater odds of making large functional gains in comparison with children with nontraumatic brain injury. For both groups, children entering rehabilitation with a moderate level of functional independence had the highest probability of making large gains. Children with a nontraumatic brain injury entering treatment with a high level of functioning made greater gains than those entering with low functioning. The opposite trend emerged for children with traumatic injuries.

Conclusions:

Level of functioning at admission may be a useful predictor of progress during an inpatient stay for youth with brain injuries. Children with nontraumatic brain injury entering treatment with low functioning are expected to make slower progress during hospitalization.
Anatomic Relationship Between the Hook of the Hamate and the Distal Transverse Carpal Ligament
Authors: Sytsma Terin T. , Ryan Holly S. , Lachman Nirusha , Kakar Sanjeev , Smith Jay
Published: January 2018

Objective

During ultrasound-guided carpal tunnel release, osseous landmarks may supplement direct visualization of the distal transverse carpal ligament (dTCL) to ensure a complete release. The purpose of this study was to determine the relationship between the apex of the hook of the hamate (aHH) and the dTCL within the transverse safe zone (TSZ) of the carpal tunnel.

Design

Twenty unembalmed cadaveric specimens were dissected to determine the aHH-dTCL distance and the aHH-SPA distance (the distance between the aHH and the superficial palmar arch) at the ulnar and radial limits of the TSZ (the distance between the hook of the hamate or ulnar artery to the median nerve).

Results

The aHH-dTCL distance averaged 11–12 mm across the TSZ (maximum, 18.2 mm), whereas the aHH-SPA distance was significantly greater on the radial side of the TSZ compared with the ulnar side (22.6 ± 3.6 mm vs. 14.0 ± 4.0 mm).

Conclusions

The dTCL lies approximately 11–12 mm distal to the aHH across the TSZ, with an upper limit of 18.2 mm. Along with direct sonographic visualization of the dTCL, the aHH can be used with other osseous landmarks to estimate the position of the dTCL during ultrasound-guided carpal tunnel release.
Novel PTCH1 Gene Mutation in Nevoid Basal Cell Carcinoma Syndrome
Authors: Sim Yookyeong Carolyn , Kim Gu-Hwan , Choi Sung-Weon , Ahn Kang-Min
Published: January 2018

The purpose of this study was to report clinical characteristics, surgical results, and new PTCH1 gene mutations in nevoid basal cell carcinoma syndrome (NBCCS). Five patients were referred to the Department of Oral and Maxillofacial Surgery from local dental clinics between 2006 and 2016 to treat multiple keratocystic odontogenic tumors (KOTs). The cystic lesions were enucleated and peripheral ostectomy was performed to obtain safety margin. Recurrence and/or de novo development of KOT were assessed. Gene analysis using peripheral blood was performed in all patients to identify the mutation of PTCH1 gene. Three patients showed familial history of first-degree relatives. Of the major criteria, all patients presented KOT but only 1 patient had basal cell carcinoma. Of the minor criteria, 4 of the 5 patients presented macrocephaly and hypertelorism. During follow-up periods, all patients showed recurrence and/or de novo development of KOT in the jaw bone. Mutation analysis of PTCH1 gene showed 3 frameshifts (c.817_818ins(T), c.1226_1227ins(A), and c.2748del(C)), 1 splicing (c.1504-2A>T), and 1 missense (c.385T>C) mutation. Mutations were found in exon 1, 6, 9, 17, and intron 10. Regular follow-up is necessary because recurrence rate of KOT was very high. To help early diagnosis, it is essential to routinely perform genetic testing to detect PTCH1 gene mutations among patients with NBCCS.
Treatment of Sagittal Fracture of the Zygomatic Arch Root Assisted by Surgical Navigation Technology
Authors: Dai Jin-Hong , Xu Dong-Dong , Yang Chang-Yuan , Li Zu-Bing , Li Zhi
Published: January 2018

Sagittal fracture at the temporal root of the zygomatic arch often occurs as a part of zygomaticomaxillary fractures. The authors described the application of computer-assisted navigation in the lag screw insertion for the fixation of sagittal fracture at the temporal root of zygomatic arch. Using the presurgical planning of the computer-assisted navigation system, the trajectory of lag screw insertion was designed, and the insertion depth was calculated. In the presurgical planning, the trajectory of screw insertion was placed with an anterior inclination of 10° to 15° (mean: 12.24°), and the screw insertion depth was 9.0 to 12.0 mm (mean: 10.65 mm). In the operation, the screw insertion in the fixation of the sagittal fracture was performed under the guidance of navigation system according to the presurgical planning. The postoperative CT scan showed exact reduction and fixation of the sagittal fracture in all cases. Computer-assisted navigation is a useful tool for the lag screw insertion in the precise fixation of sagittal fracture at the temporal root of the zygomatic arch in complex zygomaticomaxillary fractures.
The Impact of Velopharyngeal Surgery on the Polysomnographic Parameters After Cleft Palate Repair
Authors: Abdel-Aziz Mosaad , Hussien Ayman , Kamel Ahmed , Azooz Khaled , Fawaz Mohamed
Published: January 2018

Velopharyngeal surgical procedures may have adverse effect on the airway of the patients with velopharyngeal insufficiency (VPI). The aim of this study was to evaluate the polysomnographic parameters (PSG) in patients who underwent corrective surgery for treatment of VPI. The study included 39 patients who underwent 1 of 3 velopharyngeal surgical techniques; Furlow palatoplasty (12 patients), pharyngeal flap (18 patients), and sphincter pharyngoplasty (9 patients). The patients were subjected to PSG, and they were considered to have obstructive sleep apnea (OSA) with apnea-hypoapnea index (AHI) >1.

Comparison of PSG parameters of patients showed insignificant difference regarding the total sleep time, sleep efficiency, arousal index, desaturation index, and minimum oxygen saturation. Significant difference was detected regarding peak end-tidal CO2 and AHI. Pharyngeal flap was detected as the most surgical technique that worsened the PSG parameters with OSA in 78% of patients, followed by sphincter pharyngoplasty with OSA in 56% of patients. Furlow palatoplasty was detected as the least impacting technique on the airway in 25% of patients who demonstrated OSA. In conclusion, velopharyngeal surgery has a variable impact on the PSG; pharyngeal flap has the most worsening effect followed by sphincter pharyngoplasty, while Furlow palatoplasty has the least adverse effect.
Morphometric Measurements of Bony Nasolacrimal Canal in Children
Authors: Ela Araz Server , Cigdem Kalaycik Ertugay , Karagoz Yesim , Yigit Ozgur , Longur Ecem Sevim
Published: January 2018

Objective:

Morphology and dimensions of the bony nasolacrimal canal duct (BNLD) as a key factor in the development of primary acquired nasolacrimal duct obstruction. We aimed to obtain detailed morphometric analysis of BNLD in children without nasolacrimal duct pathology by using computed tomography and provide standard measurements by means of age which could be utilized in planning management or in invasive interventions.

Methods:

Picture Archiving Communication Systems database of our hospital's radiology department was searched for this retrospective study. Subjects were under 18 years of age who had undergone a paranasal, maxillofacial, or temporal bone high-resolution computed tomography scan in last 2 years with various indications. Those with fractures including facial bones and/or nasolacrimal canal or history of nasolacrimal duct pathology were excluded from the study. We measured the diameter, angle, and surface area of BNLD.

Results:

A total number of 136 subjects (86 boys, 50 girls) were included in the study. The average age was 7.3 ± 5.1 years. We documented statistically significantly positive correlation between all measured diameters and ages (P < 0.001), whereas there was a negative association between mean angle and age (P < 0.001). Mean angle is defined as the angle between BNLD and nasal floor. The surface area of BNLD was found to be significantly increasing depending on age (P < 0.001). However, we could not find any significant association between gender and measured parameters (P > 0.050).

Conclusion:

Our study demonstrated that development of BNLD continues during childhood, regardless of gender.
Simulation of Shoulder Dystocia for Skill Acquisition and Competency Assessment
Authors: Gurewitsch Allen Edith D.
Published: January 2018

Summary Statement

Mastery of shoulder dystocia management skills acquired via simulation training can reduce neonatal brachial plexus injury by 66% to 90%. However, the correlation between simulation drills and reduction in clinical injuries has been inconsistently replicated, and establishing a causal relationship between simulation training and reduction of adverse clinical events from shoulder dystocia is infeasible due to ethical limitations. Nevertheless, professional liability insurance carriers increasingly are mandating simulation-based rehearsal and competency assessment of their covered obstetric providers' shoulder dystocia management skills—a high-stakes demand that will require rapid scaling up of access to quality shoulder dystocia simulation. However, questions remain about differing simulation training schemes and instructional content used among clinically effective and ineffective educational interventions. This review of original research compares curricular content of shoulder dystocia simulation and reveals several critical gaps: (1) prescriptive instruction prioritizing maneuvers shown to decrease strain on the brachial plexus is inconsistently used. (2) Proscriptive instruction to avoid placing excessive and laterally directed traction on the head or to observe a brief hands-off period before attempting traction is infrequently explicit. (3) Neither relative effectiveness nor potential interaction between prescriptive and proscriptive elements of instruction has been examined directly. (4) Reliability of high-fidelity mannequins capable of objective measurement of clinician-applied traction force as compared with subjective assessment of provider competence is unknown. Further study is needed to address these gaps and inform efficient and effective implementation of clinically translatable shoulder dystocia simulation.
Capturing context-specific regulation in molecular interaction networks
Authors: Rush Stephen T , Repsilber Dirk
Published: January 2018

Motivation

Gene expression changes over time in response to perturbations. These changes are coordinated into functional modulesviaregulatory interactions. The genes within a functional module are expected to be differentially expressed in a manner coherent with their regulatory network. This perspective presents a promising approach to increase power to detect differential signals as well as for describing regulated modules from a mechanistic point of view.

Results

We present an effective procedure for identifying differentially activated subnetworks in molecular interaction networks. Differential gene expression coherent with the regulatory nature of the network is identified. Sequentially controlling error on genes and links results in more efficient inference. By focusing on local inference, our method is ignorant of the global topology, and as a result equally effective on exponential and scale-free networks. We apply our procedure both to systematically simulated data, comparing its performance to alternative methods, and to the transcription regulatory network in the context of particle-induced pulmonary inflammation, recapitulating and proposing additional candidates to some previously obtained results.

Contact

stephen.rush@oru.se,dirk.repsilber@oru.se
Linking signal detection theory and encoding models to reveal independent neural representations from neuroimaging data
Authors: Soto Fabian A. , Vucovich Lauren E. , Ashby F. G.
Published: January 2018

Many research questions in visual perception involve determining whether stimulus properties are represented and processed independently. In visual neuroscience, there is great interest in determining whether important object dimensions are represented independently in the brain. For example, theories of face recognition have proposed either completely or partially independent processing of identity and emotional expression. Unfortunately, most previous research has only vaguely defined what is meant by “independence,” which hinders its precise quantification and testing. This article develops a new quantitative framework that links signal detection theory from psychophysics and encoding models from computational neuroscience, focusing on a special form of independence defined in the psychophysics literature: perceptual separability. The new theory allowed us, for the first time, to precisely define separability of neural representations and to theoretically link behavioral and brain measures of separability. The framework formally specifies the relation between these different levels of perceptual and brain representation, providing the tools for a truly integrative research approach. In particular, the theory identifies exactly what valid inferences can be made about independent encoding of stimulus dimensions from the results of multivariate analyses of neuroimaging data and psychophysical studies. In addition, commonly used operational tests of independence are re-interpreted within this new theoretical framework, providing insights on their correct use and interpretation. Finally, we apply this new framework to the study of separability of brain representations of face identity and emotional expression (neutral/sad) in a human fMRI study with male and female participants.

Author Summary

A common question in vision research is whether certain stimulus properties, like face identity and expression, are represented and processed independently. We develop a theoretical framework that allowed us, for the first time, to link behavioral and brain measures of independence. Unlike previous approaches, our framework formally specifies the relation between these different levels of perceptual and brain representation, providing the tools for a truly integrative research approach in the study of independence. This allows to identify what kind of inferences can be made about brain representations from multivariate analyses of neuroimaging data or psychophysical studies. We apply this framework to the study of independent processing of face identity and expression.
IκBζ is constitutively expressed in human and murine airway epithelium
Authors: Sundaram Kruthika , Mitra Srabani , Lorscheid Sebastian , Steiner Haley , Sarkar Anasuya , Shilo Konstantin , Boyaka Prosper N. , Schulze-Osthoff Klaus , Wewers Mark D.
Published: January 2018

AIM

IκBζ is a transcriptional factor induced in immune cells upon Toll-like receptor (TLR) activation. Recent studies demonstrate unconventional, constitutive expression of IκBζ in epithelium of mouse skin and eyes, possibly reflecting continuous activation of TLRs by pathogen-associated molecular patterns (PAMPs). In this context, the lung epithelium which constitutes another important barrier also expresses IκBζ but may not be as actively exposed to pathogens as skin and eyes. Our aim was to determine if IκBζ expression in the lungs is constitutive or induced.

SIGNIFICANCE

IκBζ is linked to lung disorders due to its role in regulating protective cytokines and antimicrobial peptides in airway epithelium and can therefore be a potential biomarker and a key therapeutic target.

METHODS

We evaluated IκBζ expression in airway epithelia of healthy humans and three kinds of mice: normal, gnotobiotic and Nfkbiz−/− knockout, using immunostaining and immunoblotting.

RESULTS

Immunohistochemistry of ciliated airway epithelial cells in healthy humans and normal mice was positive for IκBζ. The pathogen free airway cells from gnotobiotic mice also stained positive, suggesting that lung epithelial IκBζ expression does not require induction by PAMPs. Although lung epithelia from Nfkbiz−/− knockout mice also stained positive, this knockout may not have eliminated exons 3-4 and 9-14, and so did not provide the specificity control for the IκBζ antiserum. Importantly, immunoblotting tissue homogenates from gnotobiotic mouse lungs and primary human airway epithelial cells demonstrated constitutive IκBζ expression at its correct 86 kDa size.

CONCLUSIONS

Our data demonstrates constitutive expression of IκBζ protein in airway epithelium, indicating a potential role for this molecule in lung homeostasis.
Mitochondrial membrane tension governs fission
Authors: Mahecic Dora , Carlini Lina , Kleele Tatjana , Colom Adai , Goujon Antoine , Matile Stefan , Roux Aurélien , Manley Suliana
Published: January 2018

During mitochondrial fission, key molecular and cellular factors assemble on the outer mitochondrial membrane, where they coordinate to generate constriction. Constriction sites can eventually divide, or reverse upon disassembly of the machinery. However, a role for membrane tension in mitochondrial fission, although speculated, has remained undefined. We captured the dynamics of constricting mitochondria in mammalian cells using live-cell structured illumination microscopy (SIM). By analyzing the diameters of tubules that emerge from mitochondria and implementing a fluorescence lifetime-based mitochondrial membrane tension sensor, we discovered that mitochondria are indeed under tension. Under perturbations that reduce mitochondrial tension, constrictions initiate at the same rate, but are less likely to divide. We propose a model based on our estimates of mitochondrial membrane tension and bending energy in living cells which accounts for the observed probability distribution for mitochondrial constrictions to divide.
In vivo optochemical control of cell contractility at single cell resolution by Ca2+ induced myosin activation
Authors: Kong Deqing , Lv Zhiyi , Häring Matthias , Wolf Fred , Grosshans Joerg
Published: January 2018

The spatial and temporal dynamics of cell contractility plays a key role in tissue morphogenesis, wound healing and cancer invasion. Here we report a simple, single cell resolution, optochemical method to induce minute-scale cell contractions in vivo during morphogenesis. We employed the photolabile Ca2+ chelator o-nitrophenyl EGTA to induce bursts of intracellular free Ca2+ by laser photolysis. Ca2+ bursts appear within seconds and are restricted to individual target cells. Cell contraction reliably followed within a minute, to about half of the cross-sectional area. Increased Ca2+ levels and contraction were reversible and the target cells further participated in tissue morphogenesis. Depending on Rho kinase (Rok) activity but not RhoGEF2, cell contractions are paralleled with non-muscle myosin-II accumulation in the apico-medial cortex, indicating that Ca2+ bursts trigger non-muscle myosin II activation. Our approach can be easily adapted to many experimental systems and species, as no specific genetic elements are required and a widely used reagent is employed.
Adaptation of olfactory receptor abundances for efficient coding
Authors: Tesileanu Tiberiu , Cocco Simona , Monasson Remi , Balasubramanian Vijay
Published: January 2018

Olfactory receptor usage is highly heterogeneous, with some receptor types being orders of magnitude more abundant than others. We propose an explanation for this striking fact: the receptor distribution is tuned to maximally represent information about the olfactory environment in a regime of efficient coding that is sensitive to the global context of correlated sensor responses. This model predicts that in mammals, where olfactory sensory neurons are replaced regularly, receptor abundances should continuously adapt to odor statistics. Experimentally, increased exposure to odorants leads variously, but reproducibly, to increased, decreased, or unchanged abundances of different activated receptors. We demonstrate that this diversity of effects is required for efficient coding when sensors are broadly correlated, and provide an algorithm for predicting which olfactory receptors should increase or decrease in abundance following specific environmental changes. Finally, we give simple dynamical rules for neural birth and death processes that might underlie this adaptation.
Sub-voxel light-sheet microscopy for high-resolution, high-throughput volumetric imaging of large biomedical specimens
Authors: Fei Peng , Nie Jun , Lee Juhyun , Ding Yichen , Li Shuoran , Zhang Hao , Hagiwara Masaya , Yu Tingting , Segura Tatiana , Ho Chih-Ming , Zhu Dan , Hsiai Tzung K.
Published: January 2018

A key challenge when imaging whole biomedical specimens is how to quickly obtain massive cellular information over a large field of view (FOV). Here, we report a sub-voxel light-sheet microscopy (SLSM) method enabling high-throughput volumetric imaging of mesoscale specimens at cellular-resolution. A non-axial, continuous scanning strategy is used to rapidly acquire a stack of large-FOV images with three-dimensional (3-D) nanoscale shifts encoded. Then by adopting a sub-voxel-resolving procedure, the SLSM method models these low-resolution, cross-correlated images in the spatial domain and iteratively recovers a 3-D image with improved resolution throughout the sample. This technique can surpass the optical limit of a conventional light-sheet microscope by more than three times, with high acquisition speeds of gigavoxels per minute. As demonstrated by quick reconstruction (minutes to hours) of various samples, e.g., 3-D cultured cells, an intact mouse heart, mouse brain, and live zebrafish embryo, the SLSM method presents a high-throughput way to circumvent the tradeoff between intoto mapping of large-scale tissue (>100 mm3) and isotropic imaging of single-cell (~1-μm resolution). It also eliminates the need of complicated mechanical stitching or precisely modulated illumination, using a simple light-sheet setup and fast graphics-processing-unit (GPU)-based computation to achieve high-throughput, high-resolution 3-D microscopy, which could be tailored for a wide range of biomedical applications in pathology, histology, neuroscience, etc.