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Burley K,Goulding CW
Protein engineering: Redirecting membrane machinery.
Nat Chem Biol. 2017 Aug 18;13(9):927-928
PMID: 28820876

Safarpour Y,Mousavi T,Jabbari B
Botulinum Toxin Treatment in Multiple Sclerosis-a Review.
Curr Treat Options Neurol. 2017 Aug 17;19(10):33
Purpose of review The purpose of this review is to provide updated information on the role of botulinum neurotoxin (BoNT) therapy in multiple sclerosis (MS). This review aims to answer which symptoms of multiple sclerosis may be amenable to BoNT therapy. Recent findings We searched the literature on the efficacy of BoNTs for treatment of MS symptoms up to April 1st 2017 via the Yale University Library's search engine including but not limited to Pub Med and Ovis SP. The level of efficacy was defined according to the assessment's criteria set forth by the Subcommittee on Guideline Development of the American Academy of Neurology. Significant efficacy was found for two indications based on the available blinded studies (class I and II) and has been suggested for several others through open-label clinical trials. Summary There is level A evidence (effective- two or more class I) that injection of BoNT-A into the bladder's detrusor muscle improves MS-related neurogenic detrusor overactivity (NDO) and MS-related overactive (OA) bladder. There is level B evidence (probably effective- two class II studies) for utility of intramuscular BoNT-A injections for spasticity of multiple sclerosis. Emerging data based on retrospective class IV studies demonstrates that intramuscular injection of BoNTs may help other symptoms of MS such as focal tonic spasms, focal myokymia, spastic dysphagia, and double vision in internuclear ophthalmoplegia. There is no data on MS-related trigeminal neuralgia and sialorrhea, two conditions which have been shown to respond to BoNT therapy in non-MS population.
PMID: 28819801

Foucard LC,Eaton JM,Dennin M,Levine AJ
Folding sticky elastica: dynamics and reversibility of folds in Langmuir monolayers.
Soft Matter. 2017 Aug 18;
Lipid monolayers at the air/water interface are often subject to large mechanical stresses when compressed laterally. For large enough compression they fold in the out-of-plane direction to relax stress. The repetitive folding and unfolding of lung surfactant monolayers during breathing plays a critical role in conserving monolayer material at the air/water interface lining the lung. Although the mechanisms behind the folding have been explored recently, relatively little information exists regarding the implications of folding dynamics on the long-term stability of the monolayer. We address this question by investigating the dynamical effect of folding rate in a lipid monolayer containing nano-particles, using a combination of analytic theory, simulation and experiment. We find that the presence of adsorbed particles are essential for monolayer rupture during unfolding. These particles act as linkers pinning the folds shut. The rate of folding affects reversibility as well. We construct a reversibility phase diagram spanned by the compression period and the size of the adsorbed particles showing the complex interaction of fold morphology, particle diffusion, and linker unbinding that results in reversible or irreversible folding.
PMID: 28819672

Jing JC,Chen JJ,Chou L,Wong BJF,Chen Z
Visualization and Detection of Ciliary Beating Pattern and Frequency in the Upper Airway using Phase Resolved Doppler Optical Coherence Tomography.
Sci Rep. 2017 Aug 17;7(1):8522
Ciliary motion plays a critical role in the overall respiratory health of the upper airway. These cilia beat at a native frequency and in a synchronized pattern to continuously transport foreign particulate trapped in a layer of mucous out of the upper airway. Disruption of ciliary motion can lead to severe respiratory diseases and compromised respiratory function. Currently, the study of cilia requires expensive high speed cameras and high powered microscopes which is unsuitable for in vivo imaging and diagnosis. Doppler based optical coherence tomography has the potential to visualize the microscopic motion of cilia during their beating cycle. We demonstrate the development of a high-speed Doppler optical coherence tomography system that not only can rapidly determine the cilia beat frequency, but also simultaneously visualize the temporal cilia beating pattern which plays critical roles in cilia function.
PMID: 28819309

Tejedor A,Longjas A,Zaliapin I,Ambroj S,Foufoula-Georgiou E
Network robustness assessed within a dual connectivity framework: joint dynamics of the Active and Idle Networks.
Sci Rep. 2017 Aug 17;7(1):8567
Network robustness against attacks has been widely studied in fields as diverse as the Internet, power grids and human societies. But current definition of robustness is only accounting for half of the story: the connectivity of the nodes unaffected by the attack. Here we propose a new framework to assess network robustness, wherein the connectivity of the affected nodes is also taken into consideration, acknowledging that it plays a crucial role in properly evaluating the overall network robustness in terms of its future recovery from the attack. Specifically, we propose a dual perspective approach wherein at any instant in the network evolution under attack, two distinct networks are defined: (i) the Active Network (AN) composed of the unaffected nodes and (ii) the Idle Network (IN) composed of the affected nodes. The proposed robustness metric considers both the efficiency of destroying the AN and that of building-up the IN. We show, via analysis of well-known prototype networks and real world data, that trade-offs between the efficiency of Active and Idle Network dynamics give rise to surprising robustness crossovers and re-rankings, which can have significant implications for decision making.
PMID: 28819206

Vorontsova I,Donaldson PJ,Kong Z,Wickremesinghe C,Lam L,Lim JC
The modulation of the phosphorylation status of NKCC1 in organ cultured bovine lenses: Implications for the regulation of fiber cell and overall lens volume.
Exp Eye Res. 2017 Aug 14;
In this study we have used an antibody that specifically detects the phosphorylation status of the Sodium/Potassium/2 Chloride Cotransporter (NKCC1) to study whether the activity of NKCC1 can be regulated in organ cultured bovine lenses. Western blotting was first used to confirm the expression of NKCC1, phosphorylated NKCC1 (NKCC1-P) and the regulatory kinases WNK/SPAK and phosphatases PP1/PP2A in bovine lenses at the protein level. Changes to NKCC1-P status were then assessed by organ culturing bovine lenses in either isotonic, hypertonic or hypotonic solutions in the presence or absence of the NKCC inhibitor, bumetanide, or phosphatase inhibitors okadaic acid and calyculin A. After 1 to 22 h of culturing, lenses were weighed, assessed for transparency and the cortical protein fractions analysed by western blot using antibodies to detect total NKCC1 and NKCC1-P. NKCC1, NKCC1-P, SPAK, PP1 and PP2A were all detected in the membrane fraction of bovine lenses. Under hypertonic conditions, NKCC1 is phosphorylated and activated to mediate a regulatory volume increase. Finally, NKCC1-P signal increased in the presence of phosphatase inhibitors indicating that PP1/PP2A can dephosphorylate NKCC1. These results show that the phosphorylation status and hence activity of NKCC1 is dynamically regulated and that in response to hypertonic stress, and that NKCC1 activity is increased to effect a regulatory volume increase that limits cell shrinkage. These findings support the view that the lens dynamically regulates ion fluxes to maintain steady state lens volume, and suggest that dysfunction of this regulation maybe an initiating factor in the localized fiber cell swelling that is a characteristic of diabetic lens cataract.
PMID: 28818393

Anosova I,Kowal EA,Sisco NJ,Sau S,Liao JY,Bala S,Rozners E,Egli M,Chaput JC,Van Horn WD
Structural Insights into Conformation Differences between DNA/TNA and RNA/TNA Chimeric Duplexes.
Chembiochem. 2016 Sep 15;17(18):1705-8
Threose nucleic acid (TNA) is an artificial genetic polymer capable of heredity and evolution, and is studied in the context of RNA chemical etiology. It has a four-carbon threose backbone in place of the five-carbon ribose of natural nucleic acids, yet forms stable antiparallel complementary Watson-Crick homoduplexes and heteroduplexes with DNA and RNA. TNA base-pairs more favorably with RNA than with DNA but the reason is unknown. Here, we employed NMR, ITC, UV, and CD to probe the structural and dynamic properties of heteroduplexes of RNA/TNA and DNA/TNA. The results indicate that TNA templates the structure of heteroduplexes, thereby forcing an A-like helical geometry. NMR measurement of kinetic and thermodynamic parameters for individual base pair opening events reveal unexpected asymmetric "breathing" fluctuations of the DNA/TNA helix. The results suggest that DNA is unable to fully adapt to the conformational constraints of the rigid TNA backbone and that nucleic acid breathing dynamics are determined from both backbone and base contributions.
PMID: 27347671

Oh H,Arem H,Matthews CE,Wentzensen N,Reding KW,Brinton LA,Anderson GL,Coburn SB,Cauley JA,Chen C,Goodman D,Pfeiffer RM,Falk RT,Xu X,Trabert B
Sitting, physical activity, and serum oestrogen metabolism in postmenopausal women: the Women's Health Initiative Observational Study.
Br J Cancer. 2017 Aug 17;
Prolonged sitting and lower levels of physical activity have been associated with increased levels of parent oestrogens (oestrone and oestradiol), the key hormones in female cancers, in postmenopausal women. However, it is unknown whether sitting and physical activity are associated with circulating oestrogen metabolite levels.
PMID: 28817836

Connor M,Wei RL,Yu S,Sehgal V,Klempner SJ,Daroui P
Radiation dermatitis caused by a bolus effect from an abdominal compression device.
Med Dosim. 2016;41(3):221-4
American Association of Physicists in Medicine (AAPM) Task Group 176 evaluated the dosimetric effects caused by couch tops and immobilization devices. The report analyzed the extensive physics-based literature on couch tops, stereotactic body radiation therapy (SBRT) frames, and body immobilization bags, while noting the scarcity of clinical reports of skin toxicity because of external devices. Here, we present a clinical case report of grade 1 abdominal skin toxicity owing to an abdominal compression device. We discuss the dosimetric implications of the utilized treatment plan as well as post hoc alternative plans and quantify differences in attenuation and skin dose/build-up between the device, a lower-density alternative device, and an open field. The description of the case includes a 66-year-old male with HER2 amplified poorly differentiated distal esophageal adenocarcinoma treated with neoadjuvant chemo-radiation and the use of an abdominal compression device. Radiation was delivered using volumetric modulated arc therapy (VMAT) with 2 arcs using abdominal compression and image guidance. The total dose was 50.4Gy delivered over 40 elapsed days. With 2 fractions remaining, the patient developed dermatitis in the area of the compression device. The original treatment plan did not include a contour of the device. Alternative post hoc treatment plans were generated, one to contour the device and a second with anterior avoidance. In conclusion, replanning with the device contoured revealed the bolus effect. The skin dose increased from 27 to 36Gy. planned target volume (PTV) coverage at 45Gy was reduced to 76.5% from 95.8%. The second VMAT treatment plan with an anterior avoidance sector and more oblique beam angles maintained PTV coverage and spared the anterior wall, however at the expense of substantially increased dose to lung. This case report provides an important reminder of the bolus effect from external devices such as abdominal compression. Special consideration must be given to contour and/or avoiding beam entrance to the device, and to the use of such devices in patients who may have heightened radiosensitivity, such as those who are human immunodeficiency virus (HIV)-positive.
PMID: 27264694

Schwed AC,Lee SL,Salcedo ES,Reeves ME,Inaba K,Sidwell RA,Amersi F,Are C,Arnell TD,Damewood RB,Dent DL,Donahue T,Gauvin J,Hartranft T,Jacobsen GR,Jarman BT,Melcher ML,Mellinger JD,Morris JB,Nehler M,Smith BR,Wolfe M,Kaji AH,de Virgilio C
Association of General Surgery Resident Remediation and Program Director Attitudes With Resident Attrition.
JAMA Surg. 2017 Aug 16;
Previous studies of resident attrition have variably included preliminary residents and likely overestimated categorical resident attrition. Whether program director attitudes affect attrition has been unclear.
PMID: 28813585

Valdebran M,Amber KT
Coverage of Intravenous Immunoglobulin for Autoimmune Blistering Diseases Among US Insurers.
JAMA Dermatol. 2017 Aug 16;
PMID: 28813559

Pillarisetti A,Allen T,Ruiz-Mercado I,Edwards R,Chowdhury Z,Garland C,Hill LD,Johnson M,Litton CD,Lam NL,Pennise D,Smith KR
Small, Smart, Fast, and Cheap: Microchip-Based Sensors to Estimate Air Pollution Exposures in Rural Households.
Sensors (Basel). 2017 Aug 16;17(8)
Over the last 20 years, the Kirk R. Smith research group at the University of California Berkeley-in collaboration with Electronically Monitored Ecosystems, Berkeley Air Monitoring Group, and other academic institutions-has developed a suite of relatively inexpensive, rugged, battery-operated, microchip-based devices to quantify parameters related to household air pollution. These devices include two generations of particle monitors; data-logging temperature sensors to assess time of use of household energy devices; a time-activity monitoring system using ultrasound; and a CO??-based tracer-decay system to assess ventilation rates. Development of each system involved numerous iterations of custom hardware, software, and data processing and visualization routines along with both lab and field validation. The devices have been used in hundreds of studies globally and have greatly enhanced our understanding of heterogeneous household air pollution (HAP) concentrations and exposures and factors influencing them.
PMID: 28812989

Sujatha-Bhaskar S,Alizadeh RF,Inaba CS,Koh CY,Jafari MD,Mills SD,Carmichael JC,Stamos MJ,Pigazzi A
Respiratory complications after colonic procedures in chronic obstructive pulmonary disease: does laparoscopy offer a benefit?
Surg Endosc. 2017 Aug 15;
Patients with severe chronic obstructive pulmonary disease (COPD) are at a higher risk for postoperative respiratory complications. Despite the benefits of a minimally invasive approach, laparoscopic pneumoperitoneum can substantially reduce functional residual capacity and raise alveolar dead space, potentially increasing the risk of respiratory failure which may be poorly tolerated by COPD patients. This raises controversy as to whether open techniques should be preferentially employed in this population.
PMID: 28812150

Dinday MT,Girskis KM,Lee S,Baraban SC,Hunt RF
PAFAH1B1 haploinsufficiency disrupts GABA neurons and synaptic E/I balance in the dentate gyrus.
Sci Rep. 2017 Aug 15;7(1):8269
Hemizygous mutations in the human gene encoding platelet-activating factor acetylhydrolase IB subunit alpha (Pafah1b1), also called Lissencephaly-1, can cause classical lissencephaly, a severe malformation of cortical development. Children with this disorder suffer from deficits in neuronal migration, severe intellectual disability, intractable epilepsy and early death. While many of these features can be reproduced in Pafah1b1(+/-) mice, the impact of Pafah1b1(+/-) on the function of individual subpopulations of neurons and ultimately brain circuits is largely unknown. Here, we show tangential migration of young GABAergic interneurons into the developing hippocampus is slowed in Pafah1b1(+/-) mice. Mutant mice had a decreased density of parvalbumin- and somatostatin-positive interneurons in dentate gyrus, but no change in density of calretinin interneurons. Whole-cell patch-clamp recordings revealed increased excitatory and decreased inhibitory synaptic inputs onto granule cells of Pafah1b1(+/-) mice. Mutant animals developed spontaneous electrographic seizures, as well as long-term deficits in contextual memory. Our findings provide evidence of a dramatic shift in excitability in the dentate gyrus of Pafah1b1(+/-) mice that may contribute to epilepsy or cognitive impairments associated with lissencephaly.
PMID: 28811646

Huang KM,Liang S,Yeung S,Oiyemhonlan E,Cleveland KH,Parsa C,Orlando R,Meyskens FL,Andresen B,Huang Y
Topically Applied Carvedilol Attenuates Solar Ultraviolet Radiation Induced Skin Carcinogenesis.
Cancer Prev Res (Phila). 2017 Aug 15;
In previous studies, the β-blocker carvedilol inhibited EGF-induced epidermal cell transformation and chemical carcinogen-induced mouse skin hyperplasia. As exposure to ultraviolet (UV) radiation leads to skin cancer, the present study examined whether carvedilol can prevent UV-induced carcinogenesis. Carvedilol absorbs UV like a sunscreen; thus, to separate pharmacological from sunscreen effects, 4-hydroxycarbazole (4-OHC), which absorbs UV to the same degree as carvedilol, served as control. JB6 P+ cells, an established epidermal model for studying tumor promotion, were used for evaluating the effect of carvedilol on UV-induced neoplastic transformation. Both carvedilol and 4-OHC (1 mM) blocked transformation induced by chronic UV (15 mJ/cm(2)) exposure for eight weeks. However, EGF-mediated transformation was only inhibited by carvedilol but not by 4-OHC. Carvedilol (1 and 5 mM), but not 4-OHC, attenuated UV-induced AP-1 and NF-kB luciferase reporter activity, suggesting a potential anti-inflammatory activity. In a single dose UV (200 mJ/cm(2)) induced skin inflammation mouse model, carvedilol (10 mM), applied topically after UV exposure, reduced skin hyperplasia and the levels of cyclobutane pyrimidine dimers, IL-1β, IL-6, and COX-2 in skin. In SKH-1 mice exposed to gradually increasing levels of UV (50-150 mJ/cm(2)) three times a week for 25 weeks, topical administration of carvedilol (10 mM) after UV exposure increased tumor latency compared with control (week 18 vs. 15), decreased incidence and multiplicity of squamous cell carcinomas, while 4-OHC had no effect.  These data suggest that carvedilol has a novel chemopreventive activity and topical carvedilol following UV exposure may be repurposed for preventing skin inflammation and cancer.
PMID: 28811301

Bloss CS,Stoler J,Brouwer KC,Bietz M,Cheung C
Public Response to a Proposed Field Trial of Genetically Engineered Mosquitoes in the United States.
JAMA. 2017 Aug 15;318(7):662-664
PMID: 28810013

Marchese A,Arciola CR,Barbieri R,Silva AS,Nabavi SF,Tsetegho Sokeng AJ,Izadi M,Jafari NJ,Suntar I,Daglia M,Nabavi SM
Update on Monoterpenes as Antimicrobial Agents: A Particular Focus on p-Cymene.
Materials (Basel). 2017 Aug 15;10(8)
p-Cymene [1-methyl-4-(1-methylethyl)-benzene] is a monoterpene found in over 100 plant species used for medicine and food purposes. It shows a range of biological activity including antioxidant, anti-inflammatory, antinociceptive, anxiolytic, anticancer and antimicrobial effects. This last property has been widely investigated due to the urgent need for new substances with antimicrobial properties, to be used to treat communicable diseases whose diffusion in developed countries has been facilitated by globalization and the evolution of antimicrobial resistance. This review summarizes available scientific data, as reported by the most recent studies describing the antimicrobial activity of p-cymene either alone, or as the main component of plant extracts, as well as addressing the mechanisms of action of cymenes as antimicrobial agents. While p-cymene is one of the major constituents of extracts and essential oils used in traditional medicines as antimicrobial agents, but considering the limited data on its in vivo efficacy and safety, further studies are required to reach a definitive recommendation on the use and beneficial effects of p-cymene in human healthcare and in biomedical applications as a promising candidate to functionalize biomaterials and nanomaterials.
PMID: 28809799

Alachkar A,Wang L,Yoshimura R,Hamzeh AR,Wang Z,Sanathara N,Lee SM,Xu X,Abbott GW,Civelli O
Prenatal one-carbon metabolism dysregulation programs schizophrenia-like deficits.
Mol Psychiatry. 2017 Aug 15;
The methionine-folate cycle-dependent one-carbon metabolism is implicated in the pathophysiology of schizophrenia. Since schizophrenia is a developmental disorder, we examined the effects that perturbation of the one-carbon metabolism during gestation has on mice progeny. Pregnant mice were administered methionine equivalent to double their daily intake during the last week of gestation. Their progeny (MET mice) exhibited schizophrenia-like social deficits, cognitive impairments and elevated stereotypy, decreased neurogenesis and synaptic plasticity, and abnormally reduced local excitatory synaptic connections in CA1 neurons. Neural transcript expression of only one gene, encoding the Npas4 transcription factor, was >twofold altered (downregulated) in MET mice; strikingly, similar Npas4 downregulation occurred in the prefrontal cortex of human patients with schizophrenia. Finally, therapeutic actions of typical (haloperidol) and atypical (clozapine) antipsychotics in MET mice mimicked effects in human schizophrenia patients. Our data support the validity of MET mice as a model for schizophrenia, and uncover methionine metabolism as a potential preventive and/or therapeutic target.Molecular Psychiatry advance online publication, 15 August 2017; doi:10.1038/mp.2017.164.
PMID: 28809400

Jiang B,Bender MT,Hasjim B,Hsu FPK,Tamargo RJ,Huang J,Colby GP,Coon AL,Lin LM
Aneurysm treatment practice patterns for newly appointed dual-trained cerebrovascular/endovascular neurosurgeons: Comparison of open surgical to neuroendovascular procedures in the first 2 years of academic practice.
Surg Neurol Int. 2017;8:154
The practice patterns of a hybrid open cerebrovascular/neuroendovascular (CVNV) neurosurgeon in early academic practice is unknown.
PMID: 28808603

Ryu KA,McGonnigal B,Moore T,Kargupta T,Mancini RJ,Esser-Kahn AP
Light Guided In-vivo Activation of Innate Immune Cells with Photocaged TLR 2/6 Agonist.
Sci Rep. 2017 Aug 14;7(1):8074
The complexity of the immune system creates challenges in exploring its importance and robustness. To date, there have been few techniques developed to manipulate individual components of the immune system in an in vivo environment. Here we show a light-based dendritic cell (DC) activation allowing spatial and temporal control of immune activation in vivo. Additionally, we show time dependent changes in RNA profiles of the draining lymph node, suggesting a change in cell profile following DC migration and indicating that the cells migrating have been activated towards antigen presentation.
PMID: 28808328

Hong C,Song D,Lee DK,Lin L,Pan HC,Lee D,Deng P,Liu Z,Hadaya D,Lee HL,Mohammad A,Zhang X,Lee M,Wang CY,Ho D
Reducing posttreatment relapse in cleft lip palatal expansion using an injectable estrogen-nanodiamond hydrogel.
Proc Natl Acad Sci U S A. 2017 Aug 14;
Patients with cleft lip and/or palate (CLP), who undergo numerous medical interventions from infancy, can suffer from lifelong debilitation caused by underdeveloped maxillae. Conventional treatment approaches use maxillary expansion techniques to develop normal speech, achieve functional occlusion for nutrition intake, and improve esthetics. However, as patients with CLP congenitally lack bone in the cleft site with diminished capacity for bone formation in the expanded palate, more than 80% of the patient population experiences significant postexpansion relapse. While such relapse has been a long-standing battle in craniofacial care of patients, currently there are no available strategies to address this pervasive problem. Estrogen, 17β-estradiol (E2), is a powerful therapeutic agent that plays a critical role in bone homeostasis. However, E2's clinical application is less appreciated due to several limitations, including its pleiotropic effects and short half-life. Here, we developed a treatment strategy using an injectable system with photo-cross-linkable hydrogel (G) and nanodiamond (ND) technology to facilitate the targeted and sustained delivery of E2 to promote bone formation. In a preclinical expansion/relapse model, this functionalized E2/ND/G complex substantially reduced postexpansion relapse by nearly threefold through enhancements in sutural remodeling compared with unmodified E2 administration. The E2/ND/G group demonstrated greater bone volume by twofold and higher osteoblast number by threefold, compared with the control group. The E2/ND/G platform maximized the beneficial effects of E2 through its extended release with superior efficacy and safety at the local level. This broadly applicable E2 delivery platform shows promise as an adjuvant therapy in craniofacial care of patients.
PMID: 28808036

Karabadzhak AG,Petti LM,Barrera FN,Edwards APB,Moya-Rodríguez A,Polikanov YS,Freites JA,Tobias DJ,Engelman DM,DiMaio D
Two transmembrane dimers of the bovine papillomavirus E5 oncoprotein clamp the PDGF β receptor in an active dimeric conformation.
Proc Natl Acad Sci U S A. 2017 Aug 14;
The dimeric 44-residue E5 protein of bovine papillomavirus is the smallest known naturally occurring oncoprotein. This transmembrane protein binds to the transmembrane domain (TMD) of the platelet-derived growth factor β receptor (PDGFβR), causing dimerization and activation of the receptor. Here, we use Rosetta membrane modeling and all-atom molecular dynamics simulations in a membrane environment to develop a chemically detailed model of the E5 protein/PDGFβR complex. In this model, an active dimer of the PDGFβR TMD is sandwiched between two dimers of the E5 protein. Biochemical experiments showed that the major PDGFβR TMD complex in mouse cells contains two E5 dimers and that binding the PDGFβR TMD to the E5 protein is necessary and sufficient to recruit both E5 dimers into the complex. These results demonstrate how E5 binding induces receptor dimerization and define a molecular mechanism of receptor activation based on specific interactions between TMDs.
PMID: 28808001

Scott H,Kim JK,Yu C,Huang L,Qiao F,Taylor DJ
Spatial organization and molecular interactions of the Schizosaccharomyces pombe Ccq1-Tpz1-Poz1 shelterin complex.
J Mol Biol. 2017 Aug 11;
The shelterin complex is a macromolecular assembly of proteins that binds to and protects telomeric DNA, which composes the ends of all linear chromosomes. Shelterin proteins prevent chromosome ends from fusing together and from eliciting erroneous induction of DNA damage response pathways. Additionally, shelterin proteins play key roles in regulating the recruitment and activation of telomerase, an enzyme that extends telomeric DNA. In fission yeast, Schizosaccharomyces pombe, interactions between the shelterin proteins Ccq1, Tpz1, and Poz1, are important for regulating telomerase-mediated telomere synthesis, and thus, telomere length homeostasis. Here, we used electron microscopy combined with genetic labeling to define the three-dimensional arrangement of the S. pombe Ccq1-Tpz1-Poz1 (CTP) complex. Cross-linking mass spectrometry was used to identify individual residues that are in proximity to the protein-protein interfaces of the assembled CTP complex. Together, our data provide a first glimpse into the architectural design of the CTP complex and reveals unique interactions that are important in maintaining the S. pombe telomere in a non-extendible state.
PMID: 28807855

Licking N,Murchison C,Cholerton B,Zabetian CP,Hu SC,Montine TJ,Peterson-Hiller AL,Chung KA,Edwards K,Leverenz JB,Quinn JF
Homocysteine and cognitive function in Parkinson's disease.
Parkinsonism Relat Disord. 2017 Aug 09;
Increased plasma homocysteine (HC) is a risk factor for dementia in the general population. Levodopa therapy causes increased plasma HC, but it remains unclear whether elevated plasma HC is associated with cognitive impairment in Parkinson's disease (PD).
PMID: 28807493

Oliver KE,Brady WE,Birrer M,Gershenson DM,Fleming G,Copeland LJ,Tewari K,Argenta PA,Mannel RS,Secord AA,Stephan JM,Mutch DG,Stehman FB,Muggia FM,Rose PG,Armstrong DK,Bookman MA,Burger RA,Farley JH
An evaluation of progression free survival and overall survival of ovarian cancer patients with clear cell carcinoma versus serous carcinoma treated with platinum therapy: An NRG Oncology/Gynecologic Oncology Group experience.
Gynecol Oncol. 2017 Aug 11;
We examined disparities in prognosis between patients with ovarian clear cell carcinoma (OCCC) and serous epithelial ovarian cancer (SOC).
PMID: 28807367


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