bluuebunny/crossref_metadata_2025 huggingface dataset:
Objectively Measured Light Exposure During School and Summer in Children
Authors: Ostrin Lisa A. , Sajjadi Auzita , Benoit Julia S.
Published: March 2018

SIGNIFICANCE

Significant differences in light exposure were observed between school and summer in children, whereas activity and sleep were similar. Associations between parent and child behaviors suggest a potential mechanism for how myopia is transmitted from parents to children through patterns of environmental exposure, in addition to genetic factors.

PURPOSE

Objectively measured time outdoors, light exposure, activity, and sleep were examined in children during school and summer and assessed with eye growth. Associations between parent and child behaviors were evaluated.

METHODS

Children (aged 7.6 ± 1.8 years, n = 60) in Houston, TX, wore an actigraph device for three 2-week sessions (fall school, spring school, summer) to quantify time outdoors, light exposure, activity, and sleep. Cycloplegic autorefraction (WAM-5500; Grand-Seiko, Tokyo, Japan) and axial length (LenStar; Haag-Streit AG, Koeniz, Switzerland) were measured at baseline and 1 year. A subset of parents wore the device during their child's first 2-week session to compare behaviors (n = 33).

RESULTS

Children spent 94.4 ± 30.6 minutes per day outdoors in spring, 110.6 ± 45.7 minutes in summer, and 72.2 ± 31.0 minutes in fall, with significant differences between sessions (P < .0001). Daily activity and sleep duration were similar across sessions (P = .73 and .06, respectively). Axial growth rate decreased with light exposure, but did not reach significance after adjusting for baseline axial length, age, sex, activity, and parental myopia (P = .073). Parent and child time outdoors and sleep duration were significantly correlated (P = .0002 and 0.026, respectively).

CONCLUSIONS

Significant differences in light exposure were observed between school and summer, whereas activity and sleep were constant throughout the year. Children's behaviors were associated with their parent's behaviors, which may represent a modifiable component to potential environmental influences on eye growth. However, light exposure was not a significant environmental influence on axial growth in this study.
ACTH-Cell Pituitary Adenoma With Signet Ring Cells: A Rare Case Report and Review of The Literature
Authors: Trabzonlu Levent , Agirlar Trabzonlu Tugce , Gurbuz Yesim , Ceylan Savas
Published: March 2018

Here, we present a case of pituitary adenoma producing adrenocorticotropic hormone (ACTH) in a 19-year-old woman. The patient was admitted to neurosurgery clinic because of a headache and decreased visual acuity. Transsphenoidal resection was performed. Microscopic examination of the tumor revealed signet-ring-like cell areas intermixed with conventional pituitary adenoma cells. Both populations of tumor cells showed immunoreactivity for chromogranin, synaptophysin, and ACTH. To date, there have been 3 reports of pituitary adenoma with signet-ring-like changes. To our knowledge, this is the first case of ACTH-secreting pituitary adenoma with signet-ring-like cell changes. The clinical reflection of signet cells in pituitary adenoma is unclear. Accumulation of the similar cases and investigation of molecular background of them may lighten the importance of this morphologic variance.
A Quantitative Analysis of Weight Gain Following Mandibular Distraction Osteogenesis in Robin Sequence
Authors: Gary Cyril S. , Marczewski Sharon , Vitagliano Patricia M. , Sawh-Martinez Rajendra , Wu Robin , Steinbacher Derek M.
Published: March 2018

Mandibular distraction osteogenesis (MDO) is an effective treatment modality for children suffering from upper airway obstruction from Robin Sequence (RS). Mandibular distraction osteogenesis has been shown to have positive effects on oral feeding and for relieving respiratory obstruction, but its effects on postoperative weight gain are poorly understood. This study quantitatively analyzes weight gain following MDO. A retrospective chart review identified 22 RS children who underwent MDO. Patient weight data, feeding methods pre- and postoperatively, and polysomnography data pre- and postoperatively were collected. Each patient's weight plotted over time was then compared with his or her closest standardized growth curve, and linear regression analysis was utilized to quantify patient growth by calculating actual and expected average daily weight gain (g/d). Percentile changes were analyzed as well. Children gained significantly less weight than expected from birth to time of MDO and significantly more weight than expected from MDO to device removal, MDO to 6 months postoperatively, and MDO to 12 months postoperatively. The average growth percentile for the cohort was 37.3 at birth, declined to 22.7 by MDO, and increased to 28.5 and 33.5 at device removal and 6 months postoperatively, respectively. More than 70% of children were exclusively orally fed within 6 months of MDO. Children with isolated Robin Sequence had superior weight gain than children with syndromic Robin Sequence following surgery. In conclusion, MDO helps improve weight gain following surgery, particularly for infants with isolated Robin Sequence, and has positive effects on oral feeding and respiration.
Swallowing and Temporomandibular Disorders in Adults
Authors: Ciavarella Domenico , Tepedino Michele , Laurenziello Michele , Guida Laura , Troiano Giuseppe , Montaruli Graziano , Illuzzi Gaetano , Chimenti Claudio , Lo Muzio Lorenzo
Published: March 2018

Introduction:

Temporomandibular disease (TMD) etiology is multifactorial and is related to many perpetuating, predisposing, and initiating factors. The daytime parafunctions may have an important role in TMD pathogenesis. The most frequent parafunctions analyzed were the static parafunction (ie, clenching) and the dynamic parafunction (ie, grinding). In the present paper, the authors evaluated the swallowing (an oral function/parafunction) with the surface electromyography in patients with TMD.

Materials and Methods:

Twenty patients with TMD problems (nonhealthy patients, NHP) (mean age: 33 ± 1.994; 8 men and 12 women) and 20 healthy matched subjects (HP) (34.4 ± 2.782; 6 men and 14 women) were selected and examined. On each patient, an 8-channel surface electromyography was done during saliva swallowing.

Results:

Nonhealthy patients presented higher masseter and temporalis activation (P < 0.05) and an unbalancing of temporalis and submental muscles activation (P < 0.05) than the HP.

Discussion:

Nonhealthy patients presented a time of swallow higher than HP (P < 0.001). Nonhealthy patients presented a higher muscles activation and time of swallow than HP and a decrease of muscles balancing activation.
Traumatic Bony Ankylosis of Temporomandibular Joint as a Complication After Reduction Malarplasty
Authors: Subu Malavika , Paeng Jun-Young
Published: March 2018

Reduction malarplasty is one of the most commonly performed cosmetic and plastic surgery in Asian countries. Bony ankylosis of the temporomandibular joint (TMJ) occurs usually as a result of trauma, infection, failed surgeries, and autoimmune diseases. Reduction malarplasty has low incidence of TMJ-related complications. A 33-year-old female patient came with complaint of restricted mouth opening around 18 mm, which was developed immediately after the reduction malarplasty 2 years before. On computed tomography image, bony adhesion and the defect from the surgical drilling were found around right TMJ.

The TMJ interpositional gap arthroplasty with temporalis myofascial pedicled flap was done with simultaneous right coronoidectomy. Interincisal opening increased up to 47 mm intraoperatively.
High-Flow Extracranial–Intracranial Bypass for Giant Cavernous Carotid Aneurysm
Authors: Chen Junhui , Zhang Chunlei , Li Peipei , Chen Lei , Wang Yuhai
Published: March 2018

Giant intracranial aneurysms have always been remain the most difficult cerebrovascular lesions to treat, especially for giant cavernous carotid aneurysm (CCA). The treatment of giant CCA is a greatest challenge for neurosurgeons. Surgical clipping morbidity and mortality rates are relatively high, and endovascular embolization also have a high complication. The authors reported a special 74-year-old female patient who presented with blurred vision and double vision for 3 years, a giant CCA was found by digital subtraction angiography and computed tomography angiography. In the end, the CCA was treated using high-flow external carotid artery to middle cerebral artery bypass and clipping distal of the aneurysm. This technique and treatment was successful and without ischemia and neurologic sequelae. Also, their long-term follow-up demonstrated that brain tissue perfusion was better than before. Based on the literature reviewing, this technique might be an alternative strategy for intracranial giant unruptured aneurysms, especially for not suitable for direct clipping or with a high risk for endovascular embolization.
Algorithm for Airway Management in Patients With Pierre Robin Sequence
Authors: Hicks Katherine E. , Billings Kathleen R. , Purnell Chad A. , Carter John M. , Bhushan Bharat , Gosain Arun K. , Thompson Dana M. , Rastatter Jeffrey C.
Published: March 2018

Purpose:

Airway management in neonates with Pierre Robin sequence (PRS) can be challenging. The goal was to describe the algorithm developed by the authors over the past 8 years.

Methods:

A retrospective case series analyzing airway management in neonates with PRS admitted to the neonatal intensive care unit at a tertiary care pediatric hospital was performed. The utility of the proposed algorithm for airway management incorporating more consistent use of polysomnography (PSG), and airway assessment was assessed.

Results:

A total of 31 neonates with PRS (12 men, 19 women) with a mean gestational age of 38.2 weeks were analyzed. Thirteen (41.9%) patients had a named syndrome, chromosomal abnormality, or global delay. Twenty (64.5%) patients had pre-intervention PSG, and severe obstructive sleep apnea with an apnea-hypopnea index (AHI) ≥ 10 events/hour was identified in 19 (95.0%). Mandibular distraction osteogenesis was performed in 18 (58.1%) patients, and improved the AHI on post-operative PSGs. Direct assessment of the upper and lower airways was performed in 19 patients, and 13 (68.4%) were found to have secondary airway pathology. Presence of a concomitant syndrome was significantly associated with need for tracheostomy.

Conclusion:

The algorithm differs from previous ones in that it relies on rigorous pre- and post-intervention PSG (including with a nasopharyngeal airway), as well as that it allows flexibility between treatment options given the whole-patient clinical scenario and endoscopic findings. Results from these studies may be integrated to stratify patients into those who are most likely to benefit from conservative interventions or surgical procedures.
Osteosarcoma of the Ethmoid Sinus
Authors: Erdur Zülküf Burak , Gözen Emine Deniz , Inan Hakki Caner , Yener Haydar Murat , Çomunoğlu Nil , Yol Cansu , Papila Çiğdem , Cansiz Harun
Published: March 2018

Osteosarcoma (OS) is a malignant bone tumor and it is very rare in head and neck region. If it arises in this area, most common localizations of this tumor are mandible and maxilla and ethmoid sinus is very rare site for this malignancy. A 43-year-old female admitted to our clinic with the complaint of pain in the right half of the face and headache persisting for 2 months. According to the clinical symptoms and imaging studies, sinonasal ossifying fibroma was suspected. For this reason, patient was operated endoscopically and histopathological examination revealed that osteoid matrix producing atypical osteoblastic cells so these findings identified osteoblastic variant OS. This article is about a very rare case of OS of ethmoid sinus. The differential diagnosis, general characteristics, and classification of this tumor, radiological features, and surgical techniques are also presented.
Cranioplasty: An Institutional Experience
Authors: Alves Junior Aderaldo Costa , Hamamoto Filho Pedro Tadao , Gonçalves Marcelo Pacheco , Palhares Neto Aristides Augusto , Zanini Marco Antonio
Published: March 2018

Cranioplasty is a common procedure in neurosurgical practice, but associated with high complication rates. In the current study, the authors describe surgical characteristics and results of cranioplasty performed in a tertiary teaching hospital in Brazil. Data were obtained from electronic medical records of cranioplasties performed between January 2013 and November 2016. The sample comprised of 33 patients, and the mean follow-up time was 16 months. Patients presented most of the times a good preoperative status, with 84.8% of patients classified between 0 and 3 at modified Rankin scale and 78.7% with 4 or 5 points at Glasgow Outcome Scale. The most common initial diagnosis was vascular disease (48% of patients) followed by traumatic brain injury (36% of patients). The majority of cranioplasties used an autograft: the autologous bone flap removed during a previous surgery (craniectomy) and stored in the abdominal subcutaneous fat (67% of patients). In 3 patients, the polymethylmethacrylate prosthesis was custom-made prior to the operation using 3-dimensional printing, based on computed tomography images. Five patients (15% of patients) developed symptoms related to surgical site infection, manifesting at an average of 5 weeks following the procedure. Three of them presented scalp dehiscence before the infection symptoms. Cranioplasty should be performed early, as long as clinical conditions are good and the patient has overcome the acute phase of neurological injury.
Nano-Biphasic Calcium Phosphate Ceramic for the Repair of Bone Defects
Authors: Rezaei Majid , Farhadian Mohammad , Rashidi Ali Mohammad , Saeidipour Mahshid , Manshaei Maziar , Rezaee Masih
Published: March 2018

Calcium phosphate bioceramics has recently experienced increased interest in bone reconstruction. Mimicking of natural structure of bone, like the use of nanomaterials, is an attractive approach for generating scaffolds for bone regeneration. The aim of present study was to evaluate the effect of nanonization on the biphasic calcium phosphate (BCP) ceramic in the repair of bone cavities in the canine mandible. A commercial BCP was dry-milled in a high energy planetary ball mill with zirconia balls and container. Three holes (8 mm in diameter) were outlined to the depth of cortical bone of mandibular angle of 5 dogs bilaterally. The first hole (positive control group A, n = 10) was filled in with commercial BCP material. The second hole was loaded with the nanonized BCP (experimental group C, n = 10) and the third one was left untreated (negative control group B, n = 10). The defects were allowed to regenerate for 8 weeks. New bone formation was greater in groups A and C than in B. No difference was seen between group A and group C (P = 0.676). The residual bone material in group C (19.34 ± 8.03) was as much as one-half of that in group A (38.69 ± 7.90%) (P = 0.000). The negative control group B presented the highest amount of soft tissue within the bone defects. The least percentage of marrow space was found in the positive control group (13.23 ± 13.52). Our results depicted that the rate of resorption increased significantly after nanonization even though the nano-sized BCP failed to make a superior regeneration than the ordinary BCP.
The evolution of pediatric transfusion practice during combat operations 2001-2013
Authors: Cannon Jeremy W. , Neff Lucas P. , Pidcoke Heather F. , Aden James K. , Spinella Philip C. , Johnson Michael A. , Cap Andrew P. , Borgman Matthew A.
Published: March 2018

BACKGROUND

Hemostatic resuscitation principles have significantly changed adult trauma resuscitation over the past decade. Practice patterns in pediatric resuscitation likely have changed as well; however, this evolution has not been quantified. We evaluated pediatric resuscitation practices over time within a combat trauma system.

METHODS

The Department of Defense Trauma Registry was queried from 2001 to 2013 for pediatric patients (<18 years). Patients with burns, drowning, and missing injury severity score were excluded. Volumes of crystalloid, packed red blood cells (PRBC), whole blood, plasma, and platelets (PLT) given in the first 24 hours were calculated per kilogram body weight. Tranexamic acid use was also determined. Patients were divided into Early (2001–2005) and Late (2006–2013) cohorts, and subgroups of transfused (TX+) and massively transfused (MT+) patients were created. Intensive care unit and hospital length of stay and 24-hour and in-hospital mortality rates were compared.

RESULTS

A total of 4,358 patients met inclusion criteria. Comparing Early versus Late, injuries from explosions, isolated or predominant head injuries, and injury severity score all increased. The proportion of TX+ patients also increased significantly (13.6% vs 37.4%, p < 0.001) as did the number of MT+ patients (2.1% vs 15.5%, p < 0.001). Transfusion of high plasma:RBC and PLT:RBC ratios increased in both the TX+ and MT+ subgroups, although overall, PLT and whole blood use was low. After adjusting for differences between groups, the odds of death was no different Early versus Late but decreased significantly in the MT+ patients with time as a continuous variable.

CONCLUSION

Transfusion practice in pediatric combat casualty care shifted toward a more hemostatic approach over time. All-cause mortality was low and remained stable overall and even decreased in MT+ patients despite more injuries due to explosions, more head injuries, and greater injury severity. However, further study is required to determine the optimal resuscitation practices in critically injured children.

LEVEL OF EVIDENCE

Epidemiologic study, level IV.
Systemic hyperfibrinolysis after trauma: a pilot study of targeted proteomic analysis of superposed mechanisms in patient plasma
Authors: Banerjee Anirban , Silliman Christopher C. , Moore Ernest E. , Dzieciatkowska Monika , Kelher Marguerite , Sauaia Angela , Jones Kenneth , Chapman Michael P. , Gonzalez Eduardo , Moore Hunter B. , D’Alessandro Angelo , Peltz Erik , Huebner Benjamin E. , Einerson Peter , Chandler James , Ghasabayan Arsen , Hansen Kirk
Published: March 2018

BACKGROUND

Viscoelastic measurements of hemostasis indicate that 20% of seriously injured patients exhibit systemic hyperfibrinolysis, with increased early mortality. These patients have normal clot formation with rapid clot lysis. Targeted proteomics was applied to quantify plasma proteins from hyperfibrinolytic (HF) patients to elucidate potential pathophysiology.

METHODS

Blood samples were collected in the field or at emergency department arrival and thrombelastography (TEG) was used to characterize in vitro clot formation under native and tissue plasminogen activator (tPA)-stimulated conditions. Ten samples were taken from injured patients exhibiting normal lysis time at 30 min (Ly30), “eufibrinolytic” (EF), 10 from HF patients, defined as tPA-stimulated TEG Ly30 >50%, and 10 from healthy controls. Trauma patient samples were analyzed by targeted proteomics and ELISA assays for specific coagulation proteins.

RESULTS

HF patients exhibited increased plasminogen activation. Thirty-three proteins from the HF patients were significantly decreased compared with healthy controls and EF patients; 17 were coagulation proteins with anti-protease consumption (p < 0.005). The other 16 decreased proteins indicate activation of the alternate complement pathway, depletion of carrier proteins, and four glycoproteins. CXC7 was elevated in all injured patients versus healthy controls (p < 0.005), and 35 proteins were unchanged across all groups (p > 0.1 and fold change of concentrations of 0.75–1.3).

CONCLUSION

HF patients had significant decreases in specific proteins and support mechanisms known in trauma-induced hyperfibrinolysis and also unexpected decreases in coagulation factors, factors II, X, and XIII, without changes in clot formation (SP, R times, or angle). Decreased clot stability in HF patients was corroborated with tPA-stimulated TEGs.

LEVEL OF EVIDENCE

Prognostic, level III.
Programmed death 1/programmed cell death-ligand 1 pathway participates in gastric surgery-induced imbalance of T-helper 17/regulatory T cells in mice
Authors: Dong Linlin , Zheng Xiaoyu , Wang Kun , Wang Guonian , Zou Huichao
Published: March 2018

BACKGROUND

The T-helper 17 (Th17)/regulatory T (Treg) cell balance is essential for immune homeostasis. However, the effects of gastric surgery on this balance remain unclear. The aim of present study is to identify the influence of gastric surgery on Th17/Treg cell balance and the role of programmed death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway in this process.

METHODS

Mice were divided into control, sham, and surgery group randomly. Animals in surgery group accepted partial gastrectomy. Mice in sham group only received laparotomy without partial gastrectomy. Then, we detected the percentages of Treg and Th17 cells, the expression of fork-head/winged helix transcription factor (Foxp3) and retinoic acid-related orphan receptor γt (RORγt) in splenocytes, as well as plasma levels of transforming growth factor (TGF)-β1 and interleukin (IL)-17 on Days 1, 3, 5, 7 after surgery. We also analyzed the expression of PD-1 and PD-L1. The roles of PD-1/PD-L1 on the Th17/Treg balance were evaluated by the induction of Th17 or Treg cells in the presence or absence of PD-1 antibody and recombinant PD-L1 immunoglobulin (Ig) in vitro.

RESULTS

The percentage of Treg cells increased, accompanied with elevated expression of Foxp3 and TGF-β1 (p < 0.05), whereas the percentage of Th17 cells and the expression of RORγt and IL-17 decreased in mice that underwent partial gastrectomy (p < 0.05). The levels of PD-1 and PD-L1 were higher in surgery group than those in control and sham groups (p < 0.05). In vitro, the polarization of Th17 cells was enhanced, and the polarization of Treg cells was inhibited in anti–PD-1 treatment group compared with that in isotype group (p < 0.05).

CONCLUSION

Partial gastrectomy resulted in Th17/Treg imbalance, and increased the expression of PD-1 and PD-L1. blockade of PD-1/PD-L1 pathway alleviated gastric surgery-induced imbalance of Th17/Treg cells.
Adaptive and platform trials in remote damage control resuscitation
Authors: Tolles Juliana , Lewis Roger J.
Published: March 2018

The traditional approach to clinical trial design requires assuming precise values for multiple unknown parameters, resulting in a trial design that is unlikely to perform well if one or more of those assumptions turn out to be incorrect. During conduct of the trial, trial characteristics are often held fixed, even if incoming data suggest that one or more design assumptions were incorrect. This leads to an increased risk of a failed trial. In contrast, an adaptive clinical trial is designed to take advantage of partial, incoming data during the conduct of the trial, modifying key clinical trial characteristics according to prespecified rules, in order to avoid a failed or inconclusive trial, improve statistical efficacy, better treat patients within the trial, or achieve other scientific or ethical goals. The concept of an adaptive trial can be expanded to a platform trial, a clinical trial that is intended to evaluate multiple treatments or combinations of treatments, often for patients with any of a group of related diseases, and to continue beyond the evaluation of any particular treatment. Platform trial design strategies can be applied to the problem of finding the best treatment strategy for patients suffering from posttraumatic hemorrhagic shock. We present the rationale and considerations surrounding adaptive and platform trial design and apply these concepts to the problem of investigating strategies for remote damage control resuscitation.
Cerebrospinal Fluid Pressure Reduction Results in Dynamic Changes in Optic Nerve Angle on Magnetic Resonance Imaging
Authors: Hu Ranliang , Holbrook John , Newman Nancy J. , Biousse Valerie , Bruce Beau B. , Qiu Deqiang , Oshinski John , Saindane Amit M.
Published: March 2018

Background:

Optic nerve sheath tortuosity is a previously reported, but incompletely characterized, finding in idiopathic intracranial hypertension (IIH). We hypothesized that optic nerve angle (ONA), as a quantitative measure of tortuosity, would change dynamically with cerebrospinal fluid (CSF) pressure status of patients with IIH immediately before and after lumbar puncture (LP).

Methods:

Consecutive patients with suspected IIH referred for MRI and diagnostic LP were prospectively enrolled in this single institution, institutional review board–approved study. Each patient underwent a pre-LP MRI, diagnostic LP with opening pressure (OP) and closing pressure (CP), and then post-LP MRI all within 1 session. Sagittal and axial ONAs were measured on multiplanar T2 SPACE images by 2 neuroradiologists on pre- and post-LP MRI. Effects of measured pressure and CSF volume removal on changes in ONA were analyzed as was interrater reliability for ONA measurement.

Results:

Ten patients with IIH were included {all female, median age 29 (interquartile range [IQR] 25–32)}. All patients had elevated OP (median 37, IQR 34–41 cm H2O), and significantly reduced CP (median 18, IQR 16–19 cm H2O, P < 0.001) after CSF removal (IQR 13–16 mL). Within patients, mean ONAs (sagittal and axial) were significantly lower before (162 ± 9°, 163 ± 10°) than after (168 ± 7°, 169 ± 5°) LP (P = 0.001, 0.008, respectively). Interrater reliability was higher with sagittal ONA measurements (0.89) than axial (0.72).

Conclusions:

ONA changes with short-term CSF pressure reduction in patients with IIH, establishing optic nerve tortuosity as a dynamic process related to CSF status.
PI3Kδ hyper-activation promotes the development of B cells that exacerbateStreptococcus pneumoniaeinfection in an antibody-independent manner
Authors: Stark Anne-Katrien , Chandra Anita , Chakraborty Krishnendu , Alam Rafeah , Carbonaro Valentina , Clark Jonathan , Sriskantharajah Srividya , Bradley Glyn , Richter Alex G. , Banham-Hall Edward , Clatworthy Menna R. , Nejentsev Sergey , Nicole Hamblin J. , Hessel Edith M. , Condliffe Alison M. , Okkenhaug Klaus
Published: March 2018

Streptococcus pneumoniaeis a major cause of pneumonia and a leading cause of death world-wide. Antibody-mediated immune responses can offer protection against repeated exposure toS. pneumoniae, yet vaccines only offer partial protection. Patients with Activated PI3Kδ Syndrome (APDS) are highly susceptible toS. pneumoniae. We generated a conditional knockin mouse model of this disease and identified a CD19+B220−B cell subset that is induced by PI3Kδ signaling, is resident in the lungs, and which promotes increased susceptibility toS. pneumoniaeduring the early phase of infection via an antibody-independent mechanism. We show that an inhaled PI3Kδ inhibitor improves survival rates followingS. pneumoniaeinfection in wild-type mice and in mice with activated PI3Kδ. These results suggest that a subset of B cells in the lung can promote the severity ofS. pneumoniaeinfection, representing a novel therapeutic target.
Genome-wide features of introns are evolutionary decoupled among themselves and from genome size throughout Eukarya
Authors: Lozada-Chávez Irma , Stadler Peter F. , Prohaska Sonja J.
Published: March 2018

The impact of spliceosomal introns on genome and organismal evolution remains puzzling. Here, we investigated the correlative associations among genome-wide features of introns from protein-coding genes (e.g., size, density, genome-content, repeats), genome size and multicellular complexity on 461 eukaryotes. Thus, we formally distinguished simple from complex multicellular organisms (CMOs), and developed the program GenomeContent to systematically estimate genomic traits. We performed robust phylogenetic controlled analyses, by taking into account significant uncertainties in the tree of eukaryotes and variation in genome size estimates. We found that changes in the variation of some intron features (such as size and repeat composition) are only weakly, while other features measuring intron abundance (within and across genes) are not, scaling with changes in genome size at the broadest phylogenetic scale. Accordingly, the strength of these associations fluctuates at the lineage-specific level, and changes in the length and abundance of introns within a genome are found to be largely evolving independently throughout Eukarya. Thereby, our findings are in disagreement with previous estimations claiming a concerted evolution between genome size and introns across eukaryotes. We also observe that intron features vary homogeneously (with low repetitive composition) within fungi, plants and stramenophiles; but they vary dramatically (with higher repetitive composition) within holozoans, chlorophytes, alveolates and amoebozoans. We also found that CMOs and their closest ancestral relatives are characterized by high intron-richness, regardless their genome size. These patterns contrast the narrow distribution of exon features found across eukaryotes. Collectively, our findings unveil spliceosomal introns as a dynamically evolving non-coding DNA class and strongly argue against both, a particular intron feature as key determinant of eukaryotic gene architecture, as well as a major mechanism (adaptive or non-adaptive) behind the evolutionary dynamics of introns over a large phylogenetic scale. We hypothesize that intron-richness is a pre-condition to evolve complex multicellularity.
State-Unspecific Modes of Whole-Brain Functional Connectivity Predict Intelligence and Life Outcomes
Authors: Takagi Yu , Hirayama Jun-ichiro , Tanaka Saori C
Published: March 2018

Recent functional magnetic resonance imaging (fMRI) studies have increasingly revealed potential neural substrates of individual differences in diverse types of brain function and dysfunction. Although most previous studies have been inherently limited to state-specific characterizations of related brain networks and their functions, several recent studies have examined the potential state-unspecific nature of functional brain networks, such as their global similarities across different experimental conditions (i.e., states) including both task and rest. However, no previous studies have carried out direct, systematic characterizations of state-unspecific brain networks, or their functional implications. Here, we quantitatively identified several modes of state-unspecific individual variation in whole-brain functional connectivity patterns, called “Common Neural Modes (CNMs)”, from a large fMRI dataset including eight task/rest states, obtained from the Human Connectome Project. Furthermore, we tested how CNMs account for variability in individual behavioral measures. The results revealed that three CNMs were robustly extracted under various different preprocessing conditions. Each of these CNMs was significantly correlated with different aspects of behavioral measures of both fluid and crystalized intelligence. The three CNMs were also able to predict several life outcomes, such as income and life satisfaction, achieving the highest performance when combined with behavioral intelligence measures as inputs. Our findings highlight the importance of state-unspecific brain networks to characterize fundamental individual variation.
Selection signatures underlying dramatic male inflorescence transformation during modern hybrid maize breeding
Authors: Gage Joseph L. , White Michael R. , Edwards Jode W. , Kaeppler Shawn , de Leon Natalia
Published: March 2018

Inflorescence capacity plays a crucial role in reproductive fitness in plants, and in production of hybrid crops. Maize is a monoecious species bearing separate male and female flowers (tassel and ear, respectively). The switch from open-pollinated populations of maize to hybrid-based breeding schemes in the early 20thcentury was accompanied by a dramatic reduction in tassel size, and the trend has continued with modern breeding over the recent decades. The goal of this study was to identify selection signatures in genes that may underlie this dramatic transformation. Using a population of 942 diverse inbred maize accessions and a nested association mapping population comprised of three 200-line biparental populations, we measured 15 tassel morphological characteristics by manual and image-based methods. Genome-wide association studies identified 242 single nucleotide polymorphisms significantly associated with measured traits. We compared 41 unselected lines from the Iowa Stiff Stalk Synthetic (BSSS) population to 21 highly selected lines developed by modern commercial breeding programs and show that tassel size and weight were reduced significantly. We assayed genetic differences between the two groups using selection statistics XP-EHH, XP-CLR, and FST. All three selection statistics show evidence of selection at genomic regions associated with tassel morphology relative to genome-wide null distributions. These results support the tremendous effect, both phenotypic and genotypic, that selection has had on maize male inflorescence morphology.
Extensive horizontal exchange of transposable elements in theDrosophila pseudoobscuragroup
Authors: Hill Tom , Betancourt Andrea J.
Published: March 2018

While the horizontal transfer of a parasitic element can be a potentially catastrophic, it is increasingly recognized as a common occurrence. The horizontal exchange, or lack of exchange, of TE content between species results in different levels of divergence among a species group in the mobile component of their genomes. Here, we examine differences in the TE content of theDrosophila pseudoobscuraspecies group. We identify several putative horizontal transfer events, and examine the role that horizontal transfer plays in the spread of TE families to new species and the homogenization of TE content in these species. Despite rampant exchange of TE families between species, we find that both TE content differs hugely across the group, likely due to differing activity of each TE family and differing suppression of TEs due to divergence in Y chromosome size, and its resulting effects of TE regulation. Overall, we show that TE content is highly dynamic in this species group, and that it plays a large role in shaping the differences seen between species.

Data availability

All data used in this study (summarized in table S1) is freely available online through the NCBI short read archive (NCBI SRA: ERR127385, SRR330416, SRR330418, SRR1925723, SRR330426, SRR330420, SRR330423, SRR617430-74). All genomes used are either available throughflybase.orgorpopoolation.at.
Altered Bile Acid Profile in Mild Cognitive Impairment and Alzheimer’s Disease: Relationship to Neuroimaging and CSF Biomarkers
Authors: Nho Kwangsik , Kueider-Paisley Alexandra , MahmoudianDehkordi Siamak , Arnold Matthias , Risacher Shannon L. , Louie Gregory , Blach Colette , Baillie Rebecca , Han Xianlin , Kastenmüller Gabi , Jia Wei , Xie Guoxiang , Ahmad Shahzad , Hankemeier Thomas , van Duijn Cornelia M. , Trojanowski John Q. , Shaw Leslie M. , Weiner Michael W. , Doraiswamy P. Murali , Saykin Andrew J. , Kaddurah-Daouk Rima ,   for the Alzheimer’s Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics Consortium
Published: March 2018

Introduction

Bile acids (BAs) are the end products of cholesterol metabolism produced by human and gut microbiome co-metabolism. Recent evidence suggests gut microbiota influence pathological features of Alzheimer’s disease (AD) including neuroinflammation and amyloid-β deposition.

Method

Serum levels of 20 primary and secondary BA metabolites from the AD Neuroimaging Initiative (n=1562) were measured using targeted metabolomic profiling. We assessed the association of BAs with the “A/T/N” (Amyloid, Tau and Neurodegeneration) biomarkers for AD: CSF biomarkers, atrophy (MRI), and brain glucose metabolism ([18F]FDG-PET).

Results

Of 23 BA and relevant calculated ratios, three BA signatures were associated with CSF Aβ1-42 (“A”) and three with CSF p-tau181 (“T”) (correctedp<0.05). Furthermore, three, twelve, and fourteen BA signatures were associated with CSF t-tau, glucose metabolism, and atrophy (“N”), respectively (correctedp<0.05).

Conclusion

This is the first study to show serum-based BA metabolites are associated with “A/T/N” AD biomarkers, providing further support for a role of BA pathways in AD pathophysiology. Prospective clinical observations and validation in model systems are needed to assess causality and specific mechanisms underlying this association.
Epigenetic inheritance of telomere length in wild birds
Authors: Bauch Christina , Boonekamp Jelle J. , Korsten Peter , Mulder Ellis , Verhulst Simon
Published: March 2018

Telomere length (TL) predicts health and lifespan in humans and other organisms, making the identification of the causes of TL variation of interest. At conception, zygotes inherit genes that regulate TL during early development, but at the same time already express a phenotype, which is the TL of the parental gametes that formed the zygote. Whether the effect of gamete TL is transient or affects TL for life depends on the extent to which regulatory genes compensate for gamete TL variation during early development. A carry-over effect of parental TL, resulting in epigenetic inheritance, has been suggested to explain the observed relationship between parental age and offspring TL in humans and other species. However, reports of parental age effects are based on cross-sectional data, and age at reproduction has numerous confounds. Furthermore, parental age may affect offspring telomere dynamics between conception and sampling, which could also explain the paternal age effect. Using longitudinal telomere data of jackdaw parents and their chicks, we show that chicks hatched with shorter telomeres as individual fathers aged, whereas mother age had no effect. By cross-fostering eggs, we confirmed the paternal age effect to be independent of paternal care after conception. The epigenetic effect accounted for 34% of the variance in offspring TL that was explained by paternal telomere length; the remaining 66% we ascribe to a combination of environmental and additive genetic effects. Thus, our results strongly indicate epigenetic inheritance of TL, with potential consequences for offspring fitness prospects.

Significance statement

Telomeres are DNA-protein structures at chromosome ends and their length predicts remaining lifespan in humans and other organisms. Variation in telomere length is thought to be largely of genetic origin, but telomere inheritance may be unusual because a fertilised cell already has a telomere length (most traits are first expressed later in life). Telomeres shorten with age, and, using long-term individual-based data of jackdaw families, we show that as fathers aged, they produced chicks with shorter telomeres. This shows that paternal telomere length directly affects offspring telomere length, i.e. is inherited genetically but without the involvement of genes. This is known as an epigenetic effect and explained a large part (≥34%) of the telomere resemblance between fathers and their offspring.
Gene expression across tissues, sex, and life stages in the sea urchin Tripneustes gratilla [Toxopneustidae, Odontophora, Camarodonta]
Authors: Láruson Áki Jarl , Coppard Simon E. , Pespeni Melissa H. , Reed Floyd A.
Published: March 2018

The pan-tropical sea urchin Tripneustes gratilla is an ecologically and economically important shallow water algal grazer. The aquaculture of T. gratilla has spurred growing interest in the population biology of the species, and by extension the generation of more molecular resources. To this purpose, de novo transcriptomes of T. gratilla were generated for two adults, a male and a female, as well as for a cohort of approximately 1,000 plutei larvae. Gene expression profiles of three adult tissue samples were quantified and compared. These samples were of gonadal tissue, the neural ring, and pooled tube feet and pedicellariae. Levels of shared and different gene expression between sexes, as well as across functional categories of interest, including the immune system, toxins, genes involved in fertilization, and sensory genes are highlighted. Differences in expression of Sex determining Region Y-related High Mobility Group box groups and general isoform expression between the sexes is observed. Additionally an expansion of the tumor suppressor DMBT1 was observed in T. gratilla when compared to the annotated genome of the sea urchin Strongylocentrotus purpuratus. The draft transcriptome of T. gratilla is presented here in order to facilitate more genomic level analysis of de-novo sea urchin systems.
EXD2 and WRN exonucleases are required for interstrand crosslink repair in Drosophila
Authors: Chennuri Pratima , Cox Lynne S. , Saunders Robert D. C.
Published: March 2018

Interstrand crosslinks (ICLs) present a major threat to genome integrity, preventing both the correct transcription of active chromatin and complete replication of the genome. This is exploited in genotoxic chemotherapy where ICL induction is used to kill highly proliferative cancer cells. Repair of ICLs involves a complex interplay of numerous proteins, including those in the Fanconi anemia (FA) pathway, though alternative and parallel pathways have been postulated. Here, we investigate the role of the 3’-5’ exonuclease, EXD2, and the highly related WRN exonuclease (implicated in premature ageing human Werner syndrome), in repair of interstrand crosslinks in the fruit fly, Drosophila melanogaster. We find that flies mutant for EXD2 (DmEXD2) have elevated rates of genomic instability resulting from chromosome breakage and loss of the resulting acentric fragments, in contrast to WRN exonuclease (DmWRNexo) mutants where excess homologous recombination is the principal mechanism of genomic instability. Most notably, we demonstrate that proliferating larval neuroblasts mutant for either DmWRNexo or DmEXD2 are deficient in repair of DNA interstrand crosslinks caused by diepoxybutane or mitomycin C, strongly suggesting that each nuclease individually plays a role in repair of ICLs in flies. These findings have significant implications not only for understanding the complex process of ICL repair in humans, but also for enhancing cancer therapies that rely on ICL induction, with caveats for cancer therapy in Werner syndrome and Fanconi anemia patients.
Cyto-nuclear shuttling of afadin is required for rapid estradiol-mediated modifications of histone H3
Authors: Sellers Katherine J. , Watson Iain A. , Srivastava Deepak P.
Published: March 2018

Estrogens have been shown to rapidly regulate local signalling events at both synapses and within the nucleus. The result of these signalling events is to rapidly modulate synapse structure and function, as well as epigenetic mechanisms including histone modifications. Ultimately these mechanisms are thought to contribute to long-lasting changes in neural circuitry, and thus influences cognitive functions such as learning and memory. However, the mechanisms by which estrogen-mediated local synaptic and nuclear signalling events are coordinated are not well understood. In this study we have found that the scaffold protein afadin, (also known as AF-6), undergoes a bi-directional trafficking to both synaptic and nuclear compartment in response to acute 17β-estradiol (estradiol) treatment. Interestingly, nuclear accumulation of afadin was coincidental with an increase in the phosphorylation of histone H3 at serine 10 (H3S10p). This histone modification is associated with the remodelling of chromatin into an open euchromatin state, allowing for transcriptional activation and related learning and memory processes. Critically, the cyto-nuclear trafficking of afadin was required for estradiol-dependent H3S10p. We further determined that nuclear accumulation of afadin is sufficient to induce phosphorylation of the mitogentic kinases ERK1/2 (pERK1/2) within the nucleus. Moreover, nuclear pERK1/2 was required for estradiol-dependent H3S10p. Taken together, we propose a model whereby estradiol incudes the bi-directional trafficking of afadin to synaptic and nuclear sub-compartments. Within the nucleus, afadin is required for increased pERK1/2 which in turn is required for H3S10p. Therefore this represents a mechanism through which estrogens may be able to coordinate both synaptic and nucleosomal events within the same neuronal population.
Evaluation of Professıonal Ethics Prınciples by Candidate Teachers
Authors: Şahan Gülsün
Published: March 2018

The aim of this study is to evaluate the teaching ethics principles according to the opinions of the prospective teachers. From the teaching profession ethics principles of the students, the positive and negative aspects of professionalism, service, responsibility, justice, equality, ensuring a healthy and safe environment, morality, honesty, truth and trust, impartiality, professionalism and continuous improvement, specimens were asked to explain how they would behave when they would be teachers and the answers were evaluated. Qualitative research method was used in the research and students' opinions were taken with semi-structured interview forms. Bartin Faculty of Education was formed from a total of 54 students in the 4th grade with easily accessible sample from the sampling group for the study group. The opinions of students of 27 science teaching and 27 culture of religion and knowledge of ethics teaching were taken in written form and the content analysis of obtained data was examined. There are negative behaviors of the teacher candidates such as being inadequate in the field, being closed for development, not using the technology, being unprepared for the lesson, being unprepared in terms of lesson related materials while the positive examples are being planned, using new methods and techniques, teaching lesson with real examples, using time efficiently. They think that they will be teachers who are sufficient, self-developed, educating, updating, planned, regular, full-time teachers.
High School Students’ Critical Thinking Related to Their Metacognitive Self-Regulation and Physics Self-Efficacy Beliefs
Authors: Gurcay Deniz , Ferah Hatice Ozturk
Published: March 2018

The purpose of this study is to examine the relationships between ninth grade students’ metacognitive self-regulation skills and physics self-efficacy beliefs and their critical thinking. To this end, 162 students attending the ninth grade participated in the study. Critical thinking scale, metacognitive self-regulation scale and physics self-efficacy scale were used as data collection tools in the study. Data were analyzed by descriptive statistics, pearson product moment correlation analysis, and stepwise multiple regression analysis. According to descriptive analysis results the students’ critical thinking, metacognitive self-regulation and physics self-efficacy beliefs were high. Moreover, stepwise multiple regression analysis revealed that the students’ metacognitive self-regulation and physics self-efficacy belief scores were significant predictors of their critical thinking scores, explaining 55 % of the variance of critical thinking scores. In addition, it was also determined that the main variable that best explained critical thinking was metacognitive self-regulation, explaining 53 % of variance.