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Affective instability

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https://www.readbyqxmd.com/read/28806726/replication-fork-slowing-and-stalling-are-distinct-checkpoint-independent-consequences-of-replicating-damaged-dna
#1
Divya Ramalingam Iyer, Nicholas Rhind
In response to DNA damage during S phase, cells slow DNA replication. This slowing is orchestrated by the intra-S checkpoint and involves inhibition of origin firing and reduction of replication fork speed. Slowing of replication allows for tolerance of DNA damage and suppresses genomic instability. Although the mechanisms of origin inhibition by the intra-S checkpoint are understood, major questions remain about how the checkpoint regulates replication forks: Does the checkpoint regulate the rate of fork progression? Does the checkpoint affect all forks, or only those encountering damage? Does the checkpoint facilitate the replication of polymerase-blocking lesions? To address these questions, we have analyzed the checkpoint in the fission yeast Schizosaccharomyces pombe using a single-molecule DNA combing assay, which allows us to unambiguously separate the contribution of origin and fork regulation towards replication slowing, and allows us to investigate the behavior of individual forks...
August 14, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28805467/protective-microencapsulation-of-%C3%AE-lapachone-using-porous-glass-membrane-technique-based-on-experimental-optimization
#2
Ki Hyun Kim, Tuan-Ho Le, Hee Kyung Oh, Bora Heo, Jeonghyun Moon, Sangmun Shin, Seong Hoon Jeong
Even though β-lapachone is a novel drug with pharmacological activity, it has limitations including instability under light conditions. The main purpose of the study was to enhance the stability of β-lapachone using the microencapsulation method. The Shirasu porous glass membrane was used to achieve uniform-sized microcapsules. The prepared microcapsules were evaluated to investigate how process parameters affect the encapsulation efficiency, photostability, and particle size distribution. The experimental design was conducted to obtain optimal formulations...
August 14, 2017: Journal of Microencapsulation
https://www.readbyqxmd.com/read/28802421/symptomatic-medial-humeral-epicondylar-fracture-non-union-rare-presentation-of-a-relatively-common-injury
#3
Vidisha S Kulkarni, Nitish Arora, Harshit Gehlot, Sagar Saxena, Sunil G Kulkarni, Supreet Bajwa
BACKGROUND: Symptomatic non-union of medial humeral epicondylar fractures is a limited entity. Some studies recommend surgical excision of the fragment, but the results are controversial. The purpose of this study is to evaluate the outcome of open reduction and internal fixation of a medial epicondyle non-union fragment. MATERIALS AND METHODS: A retrospective study was conducted in all the patients, who were operated in our hospital between the year 2010 and 2015 for symptomatic medial humeral epicondyle non-union...
August 2017: Injury
https://www.readbyqxmd.com/read/28800335/an-overview-of-human-immunodeficiency-virus-type-1-associated-common-neurological-complications-does-aging-pose-a-challenge
#4
Anantha Ram Nookala, Joy Mitra, Nitish S Chaudhari, Muralidhar L Hegde, Anil Kumar
With increasing survival of patients infected with human immunodeficiency virus type 1 (HIV-1), the manifestation of heterogeneous neurological complications is also increasing alarmingly in these patients. Currently, more than 30% of about 40 million HIV-1 infected people worldwide develop central nervous system (CNS)-associated dysfunction, including dementia, sensory, and motor neuropathy. Furthermore, the highly effective antiretroviral therapy has been shown to increase the prevalence of mild cognitive functions while reducing other HIV-1-associated neurological complications...
August 9, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28800016/fish-analysis-of-top2a-and-her-2-aberrations-in-female-breast-carcinoma-on-archived-material-egyptian-nci-experience
#5
Omnia M Badawy, Iman Loay
BACKGROUND: HER-2 and TOP2A genes are considered of great importance in breast cancer. Their copy number variability has been proposed to be a marker for the degree of chromosomal instability. Owing to the close proximity of TOP2A gene to HER-2 gene chromosome 17, TOP2A status is believed to affect therapeutic plan. The percentage of TOP2A aberrations is greatly variable among different studies. AIM OF WORK: Is to investigate the relation between TOP2A and HER-2 gene amplification using fluorescence in situ hybridization technique...
August 9, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28799049/-diagnostics-and-treatment-concepts-for-anteroinferior-shoulder-instability-current-trends
#6
F Martetschläger, M Tauber, P Habermeyer
Shoulder instability arises when static or dynamic stabilizers deviate from the natural equilibrium. The most common form of shoulder instability is in an anteroinferior direction, affects young athletes in contact sports and can lead to permanent impairment of shoulder function and early degeneration of the joint. Conservative as well as operative therapy options have been controversially discussed for years. This article describes the current state of diagnostics, current trends in therapy decisions and relevant therapy options for anterior shoulder instability...
August 10, 2017: Der Orthopäde
https://www.readbyqxmd.com/read/28797555/to-log-roll-or-not-to-log-roll-that-is-the-question-a-review-of-the-use-of-the-log-roll-for-patients-with-pelvic-fractures
#7
REVIEW
Inês Filipa da Cunha Rodrigues
Pelvic fractures are one of the most serious injuries in polytrauma - massive haemorrhage is a major complication and the leading cause of death. The assessment and early management of these injuries in the Emergency Department (ED) focuses on the recognition of haemodynamic instability and should follow Advanced Trauma Life Support (ATLS) guidelines. The log-roll technique, although an accepted practice in trauma care, has been reported to be inadvisable when a pelvic fracture is suspected. This paper, which includes a case study, briefly explains the pathophysiology and initial management of pelvic fractures...
May 10, 2017: International Journal of Orthopaedic and Trauma Nursing
https://www.readbyqxmd.com/read/28796254/sunitinib-induces-genomic-instability-of-renal-carcinoma-cells-through-affecting-the-interaction-of-lc3-ii-and-parp-1
#8
Siyuan Yan, Ling Liu, Fengxia Ren, Quan Gao, Shanshan Xu, Bolin Hou, Yange Wang, Xuejun Jiang, Yongsheng Che
Deficiency of autophagy has been linked to increase in nuclear instability, but the role of autophagy in regulating the formation and elimination of micronuclei, a diagnostic marker for genomic instability, is limited in mammalian cells. Utilizing immunostaining and subcellular fractionation, we found that either LC3-II or the phosphorylated Ulk1 localized in nuclei, and immunoprecipitation results showed that both LC3 and Unc-51-like kinase 1 (Ulk1) interacted with γ-H2AX, a marker for the DNA double-strand breaks (DSB)...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28794908/unusual-de-novo-partial-trisomy-17p12p11-2-due-to-unbalanced-insertion-into-5p13-1-in-a-severely-affected-boy
#9
Luis Alberto Mendez-Rosado, Araceli Lantigua, Juan Galarza, Ahmed B Hamid Al-Rikabi, Monika Ziegler, Thomas Liehr
Gain of copy numbers can be due to different chromosomal rearrangements such as direct or indirect duplications, translocations, small supernumerary marker chromosomes, or insertions. In a 3-year-old boy with dysmorphic features and developmental delay, chromosome analyses revealed a derivative chromosome 5. Microdissection and reverse fluorescence in situ hybridization identified the in 5p13.1 inserted part as 17p12-p11.2 material. Thus the patient suffered from a rare combination of genomic disorder, that is, Charcot-Marie-Tooth disease type 1A and Potocki-Lupski syndrome...
September 2017: Journal of Pediatric Genetics
https://www.readbyqxmd.com/read/28793334/spheroid-growth-in-ovarian-cancer-alters-transcriptome-responses-for-stress-pathways-and-epigenetic-responses
#10
Trillitye Paullin, Chase Powell, Christopher Menzie, Robert Hill, Feng Cheng, Christopher J Martyniuk, Sandy D Westerheide
Ovarian cancer is the most lethal gynecological cancer, with over 200,000 women diagnosed each year and over half of those cases leading to death. These poor statistics are related to a lack of early symptoms and inadequate screening techniques. This results in the cancer going undetected until later stages when the tumor has metastasized through a process that requires the epithelial to mesenchymal transition (EMT). In lieu of traditional monolayer cell culture, EMT and cancer progression in general is best characterized through the use of 3D spheroid models...
2017: PloS One
https://www.readbyqxmd.com/read/28790064/atm-deficiency-generating-genomic-instability-sensitizes-pancreatic-ductal-adenocarcinoma-cells-to-therapy-induced-dna-damage
#11
Lukas Perkhofer, Anna Schmitt, Maria Carolina Romero Carrasco, Michaela Ihle, Stephanie Hampp, Dietrich Alexander Ruess, Elisabeth Hessmann, Ronan Russell, André Lechel, Ninel Azoitei, Qiong Lin, Stefan Liebau, Meike Hohwieler, Hanibal Bohnenberger, Marina Lesina, Hana Algül, Laura Gieldon, Evelin Schröck, Jochen Gaedcke, Martin Wagner, Lisa Wiesmüller, Bence Sipos, Thomas Seufferlein, Hans Christian Reinhardt, Pierre-Olivier Frappart, Alexander Kleger
Pancreatic adenocarcinomas (PDAC) harbour recurrent functional mutations of the master DNA damage response kinase ATM which has been shown to accelerate tumorigenesis and epithelial-mesenchymal transition. To study how ATM deficiency affects genome integrity in this setting, we evaluated the molecular and functional effects of conditional Atm deletion in a mouse model of PDAC. ATM deficiency was associated with increased mitotic defects, recurrent genomic rearrangements and deregulated DNA integrity checkpoints, reminiscent of human PDAC...
August 8, 2017: Cancer Research
https://www.readbyqxmd.com/read/28789949/reduced-hippocampal-il-10-expression-altered-monoaminergic-activity-and-anxiety-and-depressive-like-behavior-in-female-mice-subjected-to-chronic-social-instability-stress
#12
Ainitze Labaka, Eneritz Gómez-Lázaro, Oscar Vegas, Joana Pérez-Tejada, Amaia Arregi, Larraitz Garmendia
Evidence indicates that release of pro-inflammatory cytokines induced by social stress contributes to affective disorders. Additionally, there are known sex differences in both the stress response and the stressors that can elicit this response. In this regard, the chronic social instability (CSI) rodent model of stress appears to be the best fit for the social nature of females. This study analyzed the effects of CSI on female mouse behavior, hippocampal cytokine expression, tryptophan metabolism and monoaminergic activity...
August 5, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28783137/acetylation-and-methylation-related-epigenetic-proteins-in-the-context-of-their-targets
#13
REVIEW
Nasir Javaid, Sangdun Choi
The nucleosome surface is covered with multiple modifications that are perpetuated by eight different classes of enzymes. These enzymes modify specific target sites both on DNA and histone proteins, and these modifications have been well identified and termed "epigenetics". These modifications play critical roles, either by affecting non-histone protein recruitment to chromatin or by disturbing chromatin contacts. Their presence dictates the condensed packaging of DNA and can coordinate the orderly recruitment of various enzyme complexes for DNA manipulation...
August 7, 2017: Genes
https://www.readbyqxmd.com/read/28780707/evidence-for-association-between-hepatitis-c-virus-and-parkinson-s-disease
#14
REVIEW
Abdelrahman Ibrahim Abushouk, Mostafa Wanees Ahmed El-Husseny, Mayar Magdy, Ammar Ismail, Attia Attia, Hussien Ahmed, Ravikishore Pallanti, Ahmed Negida
Parkinson's disease (PD) is a globally prevalent neurodegenerative disorder, characterized by progressive neuronal loss in the substantia nigra and formation of Lewy bodies. These pathological characteristics are clinically translated into motor symptoms, such as bradykinesia, rigidity, resting tremors, and postural instability. Emerging data from epidemiological studies suggest a possible association between PD and hepatitis C virus (HCV) infection, which affects up to 71 million individuals worldwide. Preclinical studies have shown that HCV can penetrate and replicate within the brain macrophages and microglial cells, increasing their production of pro-inflammatory cytokines that can directly cause neuronal toxicity...
August 5, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28780180/neuropathology-of-parkinson-disease
#15
Dennis W Dickson
INTRODUCTION: Parkinson's disease (PD) is characterized by bradykinesia, rigidity, postural instability and tremor. Several pathologic processes can produce this syndrome, but neurodegeneration accompanied by neuronal inclusions composed of α-synuclein (Lewy bodies) is considered the typical pathologic correlate of PD. METHODS: The neuropathologic features of PD are reviewed based upon personal experience and review of the literature. Molecular pathology of PD is summarized from cell biological and animal studies...
August 1, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28777931/biallelic-mutations-in-mrps34-lead-to-instability-of-the-small-mitoribosomal-subunit-and-leigh-syndrome
#16
Nicole J Lake, Bryn D Webb, David A Stroud, Tara R Richman, Benedetta Ruzzenente, Alison G Compton, Hayley S Mountford, Juliette Pulman, Coralie Zangarelli, Marlene Rio, Nathalie Bodaert, Zahra Assouline, Mingma D Sherpa, Eric E Schadt, Sander M Houten, James Byrnes, Elizabeth M McCormick, Zarazuela Zolkipli-Cunningham, Katrina Haude, Zhancheng Zhang, Kyle Retterer, Renkui Bai, Sarah E Calvo, Vamsi K Mootha, John Christodoulou, Agnes Rötig, Aleksandra Filipovska, Ingrid Cristian, Marni J Falk, Metodi D Metodiev, David R Thorburn
The synthesis of all 13 mitochondrial DNA (mtDNA)-encoded protein subunits of the human oxidative phosphorylation (OXPHOS) system is carried out by mitochondrial ribosomes (mitoribosomes). Defects in the stability of mitoribosomal proteins or mitoribosome assembly impair mitochondrial protein translation, causing combined OXPHOS enzyme deficiency and clinical disease. Here we report four autosomal-recessive pathogenic mutations in the gene encoding the small mitoribosomal subunit protein, MRPS34, in six subjects from four unrelated families with Leigh syndrome and combined OXPHOS defects...
August 3, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28777219/anterior-glenohumeral-instability
#17
Adam Pickett, Steven Svoboda
Anterior shoulder dislocations, subluxations, and recurrent instability of the shoulder joint are common problems usually affecting a young active population. However, it can be a problem for patients up to the late decades in life and can lead to major shoulder arthropathy if left untreated or improperly treated. This article discusses the natural history, pathologic morphologic changes of the shoulder joint associated with anterior instability along with normal anatomic variants. We will also discuss current treatment recommendations and possible causes of the patient with recurrent instability despite prior stabilization procedures...
September 2017: Sports Medicine and Arthroscopy Review
https://www.readbyqxmd.com/read/28777216/posterior-shoulder-instability
#18
Alaina Brelin, Jonathan F Dickens
Posterior shoulder instability is a relatively uncommon condition, occurring in ∼10% of those with shoulder instability. Because of the rarity of the condition and the lack of knowledge in treatment, it is often misdiagnosed or patients experience a delay in diagnosis. Posterior instability typically affects athletes participating in contact or overhead sports and is usually the result of repetitive microtrauma or blunt force with the shoulder in the provocative position of flexion, adduction, and internal rotation, leading to recurrent subluxation events...
September 2017: Sports Medicine and Arthroscopy Review
https://www.readbyqxmd.com/read/28773935/a-numerical-investigation-of-the-thermal-stresses-of-a-planar-solid-oxide-fuel-cell
#19
Paulina Pianko-Oprych, Tomasz Zinko, Zdzisław Jaworski
A typical operating temperature of a solid oxide fuel cell (SOFC) is quite high above 750 °C and affects the thermomechanical behavior of the cell. Thermal stresses may cause microstructural instability and sub-critical cracking. Therefore, a joint analysis by the computational fluid dynamics (CFD) and computational structural mechanics based on the finite element method (FEM) was carried out to analyze thermal stresses in a planar SOFC and to predict potential failure locations in the cell. A full numerical model was based on the coupling of thermo-fluid model with the thermo-mechanical model...
September 30, 2016: Materials
https://www.readbyqxmd.com/read/28771906/cdk1-interacting-protein-cip1-is-regulated-by-the-s%C3%A2-phase-checkpoint-in-response-to-genotoxic-stress
#20
Ze Zhang, Ping Ren, Ajay A Vashisht, James A Wohlschlegel, David G Quintana, Fanli Zeng
In eukaryotic cells, a surveillance mechanism, the S phase checkpoint, detects and responds to insults that challenge chromosomal replication, arresting cell cycle progression and triggering appropriate events to prevent genomic instability. In the budding yeast Saccharomyces cerevisiae, Mec1/ATM/ATR, and its downstream kinase, Rad53/Chk2, mediate the response to genotoxic stress. In this study, we place Cip1, a recently identified Cdk1 inhibitor (CKI), under the regulation of Mec1 and Rad53 in response to genotoxic stress...
August 3, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
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