tbuckley/cabot-search huggingface dataset:
Quantitative principles of cis-translational control by general mRNA sequence features in eukaryotes
Authors: Jingyi Jessica Li, Guo-Liang Chew, Mark Douglas Biggin
Journal: Genome biology (2019)

General translational cis-elements are present in the mRNAs of all genes and affect the recruitment, assembly, and progress of preinitiation complexes and the ribosome under many physiological states. These elements include mRNA folding, upstream open reading frames, specific nucleotides flanking the initiating AUG codon, protein coding sequence length, and codon usage. The quantitative contributions of these sequence features and how and why they coordinate to control translation rates are not well understood. Here, we show that these sequence features specify 42–81% of the variance in translation rates in Saccharomyces cerevisiae, Schizosaccharomyces pombe, Arabidopsis thaliana, Mus musculus, and Homo sapiens. We establish that control by RNA secondary structure is chiefly mediated by highly folded 25–60 nucleotide segments within mRNA 5′ regions, that changes in tri-nucleotide frequencies between highly and poorly translated 5′ regions are correlated between all species, and that control by distinct biochemical processes is extensively correlated as is regulation by a single process acting in different parts of the same mRNA. Our work shows that general features control a much larger fraction of the variance in translation rates than previously realized. We provide a more detailed and accurate understanding of the aspects of RNA structure that directs translation in diverse eukaryotes. In addition, we note that the strongly correlated regulation between and within cis-control features will cause more even densities of translational complexes along each mRNA and therefore more efficient use of the translation machinery by the cell.
THU0236 Undifferentiated connective tissue disease: outcome of 40 patients
Authors: M Romero, MA Aguirre, A Cisnal, P Font, MJ Cuadrado, FG Martinez, J Gonzalez, A Escudero, V Perez, C Castro, MC Muñoz-Villanueva, E Collantes
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> There are a substantial number of patients with symptoms strongly suggestive of a connective tissue disease (CTD) that does not adequately fulfil enough classification criteria to be labelled as such. The outcome of these patients is difficult to predict. They are classified as undifferentiated connective tissue disease (UCTD). <h3>Objectives</h3> To prospectively analyse the outcome of a cohort of patients with UCTD. <h3>Methods</h3> Patients with 2 clinical criteria plus 1 serological criteria or 2 serological plus 1 clinical criteria for the classification of any CTD were included. A protocol including clinical and serological parameters was completed at entry in the study and, thereafter, annually. The end point of the study was for the patient to have met enough classification criteria to be labelled as a defined CTD. <h3>Results</h3> Forty patients with UCTD (37 women and 3 men, mean age 43 ± 15 years and mean follow-up 3.43 ± 2.5 years) were included. During the follow-up, 13 patients fulfilled criteria for a defined CTD (32.5%): 6 fulfilled criteria for rheumatoid arthritis, 4 for systemic lupus erythematosus, 2 for systemic sclerosis and 1 for Sjogren`s syndrome. Sixteen patients still remained unclassified (40%) and 11 patients (27.5%) were completely asymptomatic. There was no association between clinical or serological parameters and outcome. <h3>Conclusion</h3> After a mean follow-up of 3.5 years, one third of the UCTD patients evolved into a defined CTD. We found no clinical or serological factors to predict outcome.
Interim Data from a Phase 1 Study Evaluating Pyrrolobenzodiazepine-Based Antibody Drug Conjugate ADCT-402 (Loncastuximab Tesirine) Targeting CD19 for Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia
Authors: Nitin Jain, Rebecca B. Klisovic, Wendy Stock, David Ungar, Amer M. Zeidan, Ehab Atallah, James McCloskey, Leonard Heffner, Benjamin Tomlinson, Hagop M. Kantarjian, Shui He, Joseph Boni, Matthew J. Wieduwilt
Journal: Blood (2017)
Five C/EPB gene family members are deregulated by IGH@ in B-cell precursor acute lymphoblastic leukemia.
Authors: Lisa J. Russell, Takashi Akasaka, Theo Balasas, Aneela Majid, Stephanie Struski, Isabelle Radford-Weiss, Jonathan C. Strefford, Reiner Siebert, Martin Js Dyer, Christine J. Harrison
Journal: Cancer Research (2006)

5685  Chromosomal translocations lead to oncogene activation in a significant number of haematological malignancies. Those involving the immunoglobulin heavy chain locus, IGH@, at chromosome band 14q32 are frequently observed in B cell malignant proliferation. A small number have been described in B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). However, their biological and clinical significance is currently unknown. Detailed fluorescence in situ hybridisation (FISH) and molecular studies were carried out on a series of BCP-ALL patients with chromosomal abnormalities involving 14q32. Novel and recurrent translocations affecting different chromosomes were highlighted. Refined FISH mapping identified putative IGH@ partner genes at, or flanking, the translocation breakpoints. Four translocations: two previously reported, t(14;19)(q32;q13), t(8;14)(q11;q32), and two novel, t(14;14)(q11;q32)/inv(14)(q11q32) and t(14;20)(q32;q13), were identified. Molecular analyses showed that four different members of the CAATT enhancer binding protein (CEBP) gene family were involved: CEBPA (19q13, n=9), CEBPD (8q11, n=8), CEBPE (14q11, n=3) and CEBPB (20q13, n=2). One patient with a t(14;19)(q32;q13) was observed to involve the fifth family member CEBPG (19q13, n=1). Breakpoints were located within the 3′ untranslated region (UTR) of CEBPA and either 3′ UTR or 5′ of CEBPE, whereas breakpoints in 8q11 were ∼30kb centromeric of CEBPD. Where material was available, over-expression of target genes was shown by quantitative real-time PCR. Overall, this study has demonstrated for the first time the involvement of five members of the same gene family in a single subtype of haematological disease. It has indicated that transcriptional upregulation of CEBP gene family members, by juxtaposition to IGH@, is important in BCP-ALL: a mechanism in complete contrast to that involving CEPBA in acute myeloid leukaemia.
Patient compliance as a risk factor for the outcome of implant treatment
Authors: Simone Cortellini, Charlotte Favril, Mathieu De Nutte, Wim Teughels, Marc Quirynen
Journal: Periodontology 2000 (2019)

Abstract Peri‐implantitis can be explained using a multicausality model. Many factors are involved in the etiology of peri‐implantitis, but patient compliance also plays a key role. Oral hygiene, attending recall visits, smoking behavior, and therapy comprehension are relevant factors that contribute to peri‐implant health. The clinician should create the most optimal conditions for patients to facilitate adequate oral self‐care and to help patients improve their oral hygiene skills. Implementation of a supportive periodontal therapy program is mandatory to control inflammation and plaque accumulation, as well as to keep the incidence of peri‐implant diseases low. Patient compliance, including plaque control and dental follow‐up, must be optimal. Consequently, precautions must be taken with patients treated with dental implants.
Exposure–Response Associations of Household Air Pollution and Buccal Cell Telomere Length in Women Using Biomass Stoves
Authors: Sabrina Li, Ming Yang, Ellison Carter, James J. Schauer, Xudong Yang, Majid Ezzati, Mark S. Goldberg, Jill Baumgartner
Journal: Environmental Health Perspectives (2019)

Background: Telomere shortening is associated with early mortality and chronic disease. Recent studies indicate that environmental exposures, including urban and traffic-related air pollution, may shorten telomeres. Associations between exposure to household air pollution from solid fuel stoves and telomere length have not been evaluated. Methods: Among 137 rural Chinese women using biomass stoves (mean=55y of age), we measured 48-h personal exposures to fine particulate matter [PM ≤ 2.5μm in aerodynamic diameter (PM2.5)] and black carbon and collected oral DNA on up to three occasions over a period of 2.5 y. Relative telomere length (RTL) was quantified using a modified real-time polymerase chain reaction protocol. Mixed effects regression models were used to investigate the exposure–response associations between household air pollution and RTL, adjusting for key sociodemographic, behavioral, and environmental covariates. Results: Women's daily exposures to air pollution ranged from 13–1,136 μg/m3 for PM2.5 (mean=154) and 0.1–34 μg/m3 for black carbon (mean=3.6). Natural cubic spline models indicated a mostly linear association between increased exposure to air pollution and shorter RTL, except at very high concentrations where there were few observations. We thus modeled the linear associations with all observations, excluding the highest 3% and 5% of exposures. In covariate-adjusted models, an interquartile range (IQR) increase in exposure to black carbon (3.1 μg/m3) was associated with shorter RTL [all observations: −0.27 (95% CI: −0.48, −0.06); excluding highest 5% exposures: −1.10 (95% CI: −1.63, −0.57)]. Further adjustment for outdoor temperature brought the estimates closer to zero [all observations: −0.15 (95% CI: −0.36, 0.06); excluding highest 5% exposures: −0.68 (95% CI: −1.26, −0.10)]. Models with PM2.5 as the exposure metric followed a similar pattern. Conclusion: Telomere shortening, which is a biomarker of biological aging and chronic disease, may be associated with exposure to air pollution in settings where household biomass stoves are commonly used. https://doi.org/10.1289/EHP4041
Sleep-related epileptic behaviors and non-REM-related parasomnias: Insights from stereo-EEG
Authors: Steve A. Gibbs, Paola Proserpio, Michele Terzaghi, Andrea Pigorini, Simone Sarasso, Giorgio Lo Russo, Laura Tassi, Lino Nobili
Journal: Sleep Medicine Reviews (2015)

During the last decade, many clinical and pathophysiological aspects of sleep-related epileptic and non-epileptic paroxysmal behaviors have been clarified. Advances have been achieved in part through the use of intracerebral recording methods such as stereo-electroencephalography (S-EEG), which has allowed a unique "in vivo" neurophysiological insight into focal epilepsy. Using S-EEG, the local features of physiological and pathological EEG activity in different cortical and subcortical structures have been better defined during the entire sleep-wake spectrum. For example, S-EEG has contributed to clarify the semiology of sleep-related seizures as well as highlight the specific epileptogenic networks involved during ictal activity. Moreover, intracerebral EEG recordings derived from patients with epilepsy have been valuable to study sleep physiology and specific sleep disorders. The occasional co-occurrence of NREM-related parasomnias in epileptic patients undergoing S-EEG investigation has permitted the recordings of such events, highlighting the presence of local electrophysiological dissociated states and clarifying the underlying pathophysiological substrate of such NREM sleep disorders. Based on these recent advances, the authors review and summarize the current and relevant S-EEG literature on sleep-related hypermotor epilepsies and NREM-related parasomnias. Finally, novel data and future research hypothesis will be discussed.
Coronary Plaque Features on CTA Can Identify Patients at Increased Risk of Cardiovascular Events
Authors: Daniele Andreini, Marco Magnoni, Edoardo Conte, Serge Masson, Saima Mushtaq, Sergio Berti, Mauro Canestrari, Giancarlo Casolo, Domenico Gabrielli, Roberto Latini, Paolo Marraccini, Tiziano Moccetti, Maria Grazia Modena, Gianluca Pontone, Marco Gorini, Aldo P. Maggioni, Attilio Maseri
Journal: JACC. Cardiovascular imaging (2019)
Motility Patterns Following Esophageal Pharmacologic Provocation With Amyl Nitrite or Cholecystokinin During High-Resolution Manometry Distinguish Idiopathic vs Opioid-Induced Type 3 Achalasia
Authors: Arash Babaei, Sadaf Shad, Benson T. Massey
Journal: Clinical Gastroenterology and Hepatology (2019)
Blocking of DLL4/Notch signaling deregulates tumor angiogenesis
Authors: Minhong Yan, John Ridgway, Gu Zhang, Yan Wu, Wei-Ching Liang, Scott Stawicki, Joe Kowalski, Yvan Chanthery, Ryan Watts, Christopher Callahan, Ian Kasman, Greg Plowman
Journal: Cancer Research (2007)

1621  Haploinsufficiency of Dll4, a vascular specific Notch ligand, underscores its essential role in embryonic vascular development and arteriogenesis. Mechanistically, it remains to be defined how the Dll4-mediated Notch pathway contributes to the complex vascular processes. We took advantage of a Dll4-selective antibody and found that neutralizing Dll4 rendered endothelial cells hyperproliferative, and caused defective cell fate specification /differentiation both in vitro and in vivo. Preferential expression of Dll4 in tumor vasculature as opposed to normal tissue vessels suggests its possible role in tumor angiogenesis, yet it is still speculative whether Dll4 is directly involved in tumor angiogenesis. In our study, blocking of Dll4 showed significant anti-tumor efficacy in tumor models. Remarkably, anti-Dll4 and anti-VEGF exhibited paradoxically distinct effects on tumor vasculature. Our data also supports the notion that Dll4-mediated Notch signaling is largely restricted to the vascular compartment. Therefore, targeting Dll4 may represent a broadly efficacious and well-tolerated approach for the treatment of solid tumors.
연구논문 : PDGF-BB를 처리한 hTERT 간성상세포주의 유전자 발현 양상과 Wnt 신호 활성 양상 분석
Authors: 신혜원, Soo Young Park, Kyoungbun Lee, 신은, Nam Suk Woo, 이정용, Jang， Ja-June
Journal: Clinical and Molecular Hepatology (2009)

목적: 간 성상세포의 증식은 간 섬유화 과정에서 중요한 역할을 한다. Platelet-derived growth factor (PDGF)는 매우 강력한 간성상세포 증식 촉진 물질이다. 사람의 간성상세포의 활성에 관여하는 유전자 발현 양상과 Wnt신호 활성화 과정을 이해하기 위하여 PDGF-BB로 증식이 유도된 인체 간성상세포에서 올리고뉴클레오티드 마이크로어레이를 이용한 유전자 분석을 시행하였다. 대상과 방법: 본 연구에서는 Telomerase 역전사 효소가 첨가된 불사멸화된 사람의 간성상세포주 (hTERT HSC)가 사용되었다. PDGF-BB의 세포증식 촉진효과는 WST-1 실험을 통해 확인하였다. PDGF-BB를 처리한 hTERT HSC의 전체적인 유전자 발현 정도를 보기 위해 1만 9천개의 사람 유전자가 포함된 칩을 사용하여 올리고뉴클레오티드 마이크로어레이를 수행하였다. 마이크로어레이 데이터는 실시간의 정량적 중합효소연쇄반응으로 검증하였다. Wnt 신호 활성화는 웨스턴블롯으로 확인하였다. 결과: PDGF-BB는 hTERT HSC의 증식을 강력하게 유도하였다. 마이크로어레이 데이터에서 PDGF-BB를 처리한 hTERT HSC의 경우 243개 유전자의 발현이 증가하였고 265개 유전자의 발현이 감소하였다. 무보정의 수직적인 군 분류 결과 PDGF-BB 처리군과 대조군은 유의하게 분리되었다. 마이크로어레이 데이터에서 대조군 대비 차이가 가장 큰 유전자들 중 glypican3(GPC3), BH3 interacting domain death agonist(BID) mRNA 실시간 PCR에서의 발현 양상은 마이크로어레이 데이터와 통계적으로 상응하였다. Wnt 신호 전달계 중 frizzled10 (FZD10), calcium/calmodulin-dependent protein kinase II alpha (CAMK2A)는 시간의 경과에 따라 증가하였고 FZD10 단백질 발현 증가는 웨스턴블롯에서도 확인되었다. 결론: PDGF-BB로 활성화된 인체 간성상세포의 전반적인 유전자 발현 및 Wnt 신호 전달계의 활성 양상은 간성상세포 활성 조절 유전자들을 찾는데 기여할 것으로 기대된다. 이런 결과들은 활성화된 간성상세포에 의한 초기 간섬유화의 기전을 이해하는 데에 중요한 단서를 제공해 줄 것이다.
The Role of Equity in US States’ Breastfeeding Policies
Authors: Sarah Gonzalez-Nahm, Elyse R. Grossman, Sara E. Benjamin-Neelon
Journal: JAMA Pediatrics (2019)

This Viewpoint reviews state-level policies on breastfeeding, with particular attention to finding out if any policies include means to maintain or increase equity across racial/ethnic or socioeconomic groups.
A functional Epo-EpoR axis modulates the growth and survival of prostate cancer cells
Authors: Jee-Yeong Jeong, Gerta Hoxhaj, Arthur Sytkowski, Laurie Feldman
Journal: Cancer Research (2008)

5094  A growing number of reports have identified erythropoietin receptors (EpoR) on a variety of cancer-derived cell lines and primary cancer cells, including those of prostate cancer (CaP). However, the functional status of the EpoR on cancer cells remains a matter of some dispute. The publication of several large clinical trials suggesting a direct effect of erythropoietin (Epo) on the growth and survival of primary tumors adds further importance to the question of whether the EpoR on cancer cells are functional. We have reported previously that human prostate cancer (CaP) cell lines and primary prostate cancer cells express functional EpoR and that exogenous Epo stimulates increased cell proliferation and STAT5 phosphorylation (Feldman et al 2006, The Prostate 66:135). Moreover, we have demonstrated that Epo stimulates the growth of CaP cell colonies in soft agar culture in a dose-dependent manner. Soft agar colony formation is considered to be an in vitro model for predicted in vivo tumorigenicity of cancer cells, suggesting that Epo may stimulate the growth of prostate tumors in vivo. We now demonstrate 1) that chronic Epo-treatment of prostate cancer cells results in cells with increased resistance to docetaxel and 2) that each of the transformed and tumorigenic prostate cancer cell lines that we have examined expresses high levels of the Epo gene and produces biologically active Epo endogenously. The co-expression of functional receptor and biologically-active ligand in the cells has led us to hypothesize that an autocrine-paracrine mechanism, driven by endogenous Epo, may play a significant role in the growth and progression of prostate cancer. To test our hypothesis we have knocked-down the EpoR on CaP cells (=EpoRKD) by stable transfection with shRNAs and have isolated several clonal populations of EpoRKD cells. The cells that lack EpoR expression grow significantly more slowly than their EpoR-bearing counterparts in monolayer culture and produce fewer, smaller colonies in soft agar. Further, the EpoRKD cells neither respond to exogenous Epo mitogenically nor exhibit Epo-induced signaling. Taken together, our data support the coordinated regulation of a functional Epo-EpoR axis in CaP cells that is integral to the growth and progression of prostate cancer. The identification of a functional Epo - EpoR axis on CaP cells introduces the EpoR as a novel therapeutic target in CaP and may suggest the potential need for re-evaluation of the use of rhEpo as an adjuvant to chemotherapy in at least some CaP patients.
Parallel Evolution of Complex Centipede Venoms Revealed by Comparative Proteotranscriptomic Analyses
Authors: Ronald A Jenner, Bjoern M von Reumont, Lahcen I Campbell, Eivind A B Undheim
Journal: Molecular Biology and Evolution (2019)

Centipedes are among the most ancient groups of venomous predatory arthropods. Extant species belong to five orders, but our understanding of the composition and evolution of centipede venoms is based almost exclusively on one order, Scolopendromorpha. To gain a broader and less biased understanding we performed a comparative proteotranscriptomic analysis of centipede venoms from all five orders, including the first venom profiles for the orders Lithobiomorpha, Craterostigmomorpha, and Geophilomorpha. Our results reveal an astonishing structural diversity of venom components, with 93 phylogenetically distinct protein and peptide families. Proteomically-annotated gene trees of these putative toxin families show that centipede venom composition is highly dynamic across macroevolutionary timescales, with numerous gene duplications as well as functional recruitments and losses of toxin gene families. Strikingly, not a single family is found in the venoms of representatives of all five orders, with 67 families being unique for single orders. Ancestral state reconstructions reveal that centipede venom originated as a simple cocktail comprising just four toxin families, with very little compositional evolution happening during the approximately 50 My before the living orders had diverged. Venom complexity then increased in parallel within the orders, with scolopendromorphs evolving particularly complex venoms. Our results show that even venoms composed of toxins evolving under the strong constraint of negative selection can have striking evolutionary plasticity on the compositional level. We show that the functional recruitments and losses of toxin families that shape centipede venom arsenals are not concentrated early in their evolutionary history, but happen frequently throughout.
Training dogs to differentiate <i>Pseudomonas aeruginosa</i> from other cystic fibrosis bacterial pathogens: not to be sniffed at?
Authors: Jane C. Davies, Eric Alton, Ameze Simbo, Ronan Murphy, Ishani Seth, Kate Williams, Mark Somerville, Libby Jolly, Steve Morant, Claire Guest
Journal: European Respiratory Journal (2019)

<b>Detection dogs can be trained to distinguish the major cystic fibrosis pathogen, <i>P. aeruginosa</i>, from a range of organisms. High sensitivity/specificity support the harnessing of this skill to detection in clinical airway samples.</b>http://bit.ly/31GHl0Y
Mitochondria in the signaling pathways that control longevity and health span
Authors: Mansour Akbari, Thomas B.L. Kirkwood, Vilhelm A. Bohr
Journal: Ageing Research Reviews (2019)

Genetic and pharmacological intervention studies have identified evolutionarily conserved and functionally interconnected networks of cellular energy homeostasis, nutrient-sensing, and genome damage response signaling pathways, as prominent regulators of longevity and health span in various species. Mitochondria are the primary sites of ATP production and are key players in several other important cellular processes. Mitochondrial dysfunction diminishes tissue and organ functional performance and is a commonly considered feature of the aging process. Here we review the evidence that through reciprocal and multilevel functional interactions, mitochondria are implicated in the lifespan modulation function of these pathways, which altogether constitute a highly dynamic and complex system that controls the aging process. An important characteristic of these pathways is their extensive crosstalk and apparent malleability to modification by non-invasive pharmacological, dietary, and lifestyle interventions, with promising effects on lifespan and health span in animal models and potentially also in humans.
Practice advised patient who shared its CQC rating on Facebook to go elsewhere
Authors: Abi Rimmer
Journal: BMJ (2019)

A general practice in Warrington, Cheshire, has been criticised for writing to a patient advising her to register elsewhere after she posted about its Care Quality Commission inspection result on Facebook.

The patient had used Facebook to share a news story by the Warrington Guardian reporting that the practice had received a “requires improvement” rating from the CQC after an inspection in May.1

The Culcheth Medical Centre’s practice manager, Shelley Moores, sent the letter, which was published online by the Warrington Guardian , to the unnamed patient earlier this month.2 The letter advised the patient that she may wish to register with another practice because of the breakdown in …
Evaluation of <i>POLE</i> and <i>POLD1</i> Mutations as Biomarkers for Immunotherapy Outcomes Across Multiple Cancer Types
Authors: Feng Wang, Qi Zhao, Ying-Nan Wang, Ying Jin, Ming-Ming He, Ze-Xian Liu, Rui-Hua Xu
Journal: JAMA Oncology (2019)

Discussion | Our findings extend prior research in other settings [1][2][3] to support visible, innovative actions by oncology meeting organizers, including women's networking centers and facilitation of childcare services, as steps to ensure full participation of all those who might contribute or benefit at conferences. 4he primary limitations of this study are that the data were self-reported and respondents (55% response rate) might not be representative of the full population.We did not measure training institution or socioeconomic status (which may vary even in this high-earning population, creating unique challenges for some).The sample contained too few single parents to analyze separately.Confounding or reverse causation is possible.However, the findings suggest the possibility that facilitating attendance at national meetings might engage physicians in ways that may improve well-being and professional satisfaction.