Analisis Resepsi Masyarakat Surakarta Terhadap Konflik Keraton Kasunanan Surakarta Hadiningrat Mengenai Pengukuhan K.G.P.H Panembahan Agung Tedjowulan Sebagai Maha Menteri Di Surat Kabar Solopos Edisi 26 – 31 Agustus 2013

Konflik dapat timbul dimana saja dalam masyarakat. Tidak memandang kelas social baik itu di masyarakat biasa, masyarakat menengah atas bahkan hingga di kalangan keluarga Keraton Kasunanan Surakarta. Sejak hari pertama terjadinya konflik pengukuhan K.G.P.H Panembahan Agung Tedjowulan sebagai Maha Menteri Solopos sebagai surat kabar yang 17 tahun dan masih eksis hingga sekarang selalu menjadikan berita tersebut topik utama. Penelitian ini dimaksudkan untuk mengetahui pemaknaan dari masyarakat Surakarta terhadap konflik di Keraton Kasunanan Surakarta mengenai Pengukuhan K.G.P.H Panembahan Agung Tedjowulan sebagai Maha Menteri dengan menggunakan metode analisis resepsi. Data didapatkan dengan cara dokumentasi dan wawancara mendalam dengan enam informan yang telah dikategorisasikan. Dari hasil wawancara dengan informan, dapat disimpulkan bahwa hampir seluruh informan berada di posisi oppositional yakni menolak dan tidak setuju dengan konflik yang terjadi di Keraton Surakarta. Para informan menolak makna dominan yang ditawarkan oleh media. Mereka memiliki pandangan yang berbeda mengenai konflik Keraton Surakarta atas konflik fisik, konflik kekerasan verbal dan konflik kepentingan yang ada di Solopos. Sedangkan beberapa informan berada pada posisi dominant dan negotiated mengenai beberapa hal mengenai konflik Keraton Surakarta

An Assessment of Funding and Other Capacity Needs for Health Equity Programming Within State-Level Chronic Disease Programs

Background: Chronic diseases are an important contributor to morbidity and mortality among racial/ethnic minority, low-income, and other under-resourced populations. Given that state health departments (and their chronic disease programs) play a significant role in providing population and preventive health services, their capacity to promote health equity is an important consideration in national efforts to address chronic diseases. The purpose of this study was to examine capacity needs of state chronic disease programs with respect to promoting health equity. Methods: In 2015, the National Association of Chronic Disease Directors (NACDD) conducted a survey of its members that work within a state chronic disease division (CDD) or the larger state health department. The survey was structured to provide information on major funding sources for chronic diseases, the extent to which key funders required a focus on health equity, dedicated staffing for health equity, and training and technical assistance needs of practitioners to support health equity integration in chronic disease programming. All data were analyzed using SPSS 19.0. Findings: A total of 147 chronic disease directors and practitioners responded to the survey from 43 states, the District of Columbia and three of the U.S. Affiliated Territories and Commonwealths. Forty-two percent (N=25) of the 59 directors of state, territorial and tribal chronic disease programs at the time of the study responded. Only 52% of respondents believed their CDD adequately addressed health inequities. Among the 70 respondents who did not know or did not believe their health departments adequately addressed health inequities, barriers identified include insufficient funding (62%), inadequate training (54%), and health inequities not being a priority (22%). Respondents also identified opportunities to strengthen funding requirements to address health disparities Conclusions: Overall, the data highlight some opportunities to enhance the capacity of state CDDs to promote health equity, such as through more direct funding requirements for health equity integration, staff training, increased funding, and specialized technical assistance. Because the response rate was less than 100%, we cannot generalize the findings to every state chronic disease program. However, the responses are relatable to their collective experience

Hypoxia-induced transcriptional stress is mediated by ROS-induced R-loops

Hypoxia is a common feature of solid tumors and is associated with poor patient prognosis, therapy resistance and metastasis. Radiobiological hypoxia (<0.1% O2) is one of the few physiologically relevant stresses that activates both the replication stress/DNA damage response and the unfolded protein response. Recently, we found that hypoxia also leads to the robust accumulation of R-loops, which led us to question here both the mechanism and consequence of hypoxia-induced R-loops. Interestingly, we found that the mechanism of R-loop accumulation in hypoxia is dependent on non-DNA damaging levels of reactive oxygen species. We show that hypoxia-induced R-loops play a critical role in the transcriptional stress response, evidenced by the repression of ribosomal RNA synthesis and the translocation of nucleolin from the nucleolus into the nucleoplasm. Upon depletion of R-loops, we observed a rescue of both rRNA transcription and nucleolin translocation in hypoxia. Mechanistically, R-loops accumulate on the rDNA in hypoxia and promote the deposition of heterochromatic H3K9me2 which leads to the inhibition of Pol I-mediated transcription of rRNA. These data highlight a novel mechanistic insight into the hypoxia-induced transcriptional stress response through the ROS–R-loop–H3K9me2 axis. Overall, this study highlights the contribution of transcriptional stress to hypoxia-mediated tumorigenesis

Association between monosodium glutamate intake and sleep-disordered breathing among Chinese adults with normal body weight

ObjectiveTo assess whether monosodium glutamate (MSG) intake is associated with sleep-disordered breathing (SDB).MethodsData from 1227 Chinese subjects who participated in the Jiangsu Nutrition Study were analyzed. All the participants were examined at two time points (baseline in 2002 and follow-up in 2007). The MSG intake was assessed quantitatively in 2002 and a sleep questionnaire was used to assess snoring and to construct an SDB probability score in 2007. Those within the fifth quintile of the score (highest) were defined as having a high probability of SDB.ResultsThe MSG intake was positively associated with snoring and a high probability of SDB in participants who had a normal body weight but in those who were overweight. A comparison of the extreme quartiles of MSG intake in subjects with a body mass index lower than 23 kg/m² showed an odds ratio of 2.02 (95% confidence interval 1.02-4.00) for snoring and an odds ratio of 3.11 (95% confidence interval 1.10-8.84) for a high probability of SDB. There was a joint effect between MSG and overweight in relation to SDB.ConclusionThe intake of MSG may increase the risk of SDB in Chinese adults with a normal body weight.Zumin Shi, Gary A. Wittert, Baojun Yuan, Yue Dai, Tiffany K. Gill, Gang Hu, Robert Adams, Hui Zuo, Anne W. Taylo

Hypoxia-induced SETX links replication stress with the unfolded protein response.

Tumour hypoxia is associated with poor patient prognosis and therapy resistance. A unique transcriptional response is initiated by hypoxia which includes the rapid activation of numerous transcription factors in a background of reduced global transcription. Here, we show that the biological response to hypoxia includes the accumulation of R-loops and the induction of the RNA/DNA helicase SETX. In the absence of hypoxia-induced SETX, R-loop levels increase, DNA damage accumulates, and DNA replication rates decrease. Therefore, suggesting that, SETX plays a role in protecting cells from DNA damage induced during transcription in hypoxia. Importantly, we propose that the mechanism of SETX induction in hypoxia is reliant on the PERK/ATF4 arm of the unfolded protein response. These data not only highlight the unique cellular response to hypoxia, which includes both a replication stress-dependent DNA damage response and an unfolded protein response but uncover a novel link between these two distinct pathways

The predictive value of G8 and the Cancer and aging research group chemotherapy toxicity tool in treatment-related toxicity in older Chinese patients with cancer

Introduction: Older patients experience a higher risk of treatment-related toxicity (TRT). The G8 screening tool was developed to separate cancer older patients fit to receive standard treatment from those who are frail and experiencing functional decline due to reduced organ function and multiple comorbidities. The Cancer and Aging Research Group chemotherapy toxicity tool (CARG-tt) questionnaire was developed to predict chemotherapy toxicity in geriatric patients. This prospective observational study evaluated the performance of G8 and CARG-tt in predicting severe TRT in older Chinese cancer patients. Methods: Chinese patients aged ≥65 with a diagnosis of solid malignancy and scheduled to receive anti-cancer treatment (chemotherapy or targeted therapy) were enrolled from March 2016 to July 2017 at the Department of Clinical Oncology at Queen Mary Hospital in Hong Kong. All patients completed the G8 and CARG-tt screening and pre-treatment assessments before starting treatment. Patients were monitored for any severe TRT, which was defined by grades 3–5 using the National Cancer Institute's Common Terminology Criteria for Adverse Events v4.03, treatment discontinuation, or unexpected hospitalization from starting to 30 days after treatment. Results: A total of 259 patients (male: 154, 59.5%; median age: 73.4, age range: 65–93) were enrolled in the study. Two hundred and ten (81.1%) patients received chemotherapy while the rest (n = 49, 18.9%) received targeted therapy. Overall, 146 patients (56.8%) experienced severe TRT. The mean G8 score was 12.4 (SD: 2.8). The G8 score had a significant association with unexpected admission (cutoff: 14, 41.3% vs. 26.5%, p = 0.03) but not significant in other types of TRTs. The mean CARG-tt score was 7.67 (SD: 3.7); it was not associated with severe TRTs. Conclusions: The G8 and CARG-tt demonstrated a weak prediction of severe TRT in older Chinese cancer patients. Future studies need to develop predictive tools for TRT in patients receiving novel antineoplastic therapies, with a focus on subgroup analysis for different populations

Expression of Telomerase and Telomere Length Are Unaffected by either Age or Limb Regeneration in Danio rerio

BACKGROUND:The zebrafish is an increasingly popular model for studying many aspects of biology. Recently, ztert, the zebrafish homolog of the mammalian telomerase gene has been cloned and sequenced. In contrast to humans, it has been shown that the zebrafish maintains telomerase activity for much of its adult life and has remarkable regenerative capacity. To date, there has been no longitudinal study to assess whether this retention of telomerase activity equates to the retention of chromosome telomere length through adulthood. METHODOLOGY/PRINCIPAL FINDINGS:We have systematically analyzed individual organs of zebrafish with regard to both telomere length and telomerase activity at various time points in its adult life. Heart, gills, kidney, spleen, liver, and intestine were evaluated at 3 months, 6 months, 9 months, and 2 years of age by Southern blot analysis. We found that telomeres do not appreciably shorten throughout the lifespan of the zebrafish in any organ. In addition, there was little difference in telomere lengths between organs. Even when cells were under the highest pressure to divide after fin-clipping experiments, telomere length was unaffected. All aged (2 year old) tissues examined also expressed active amounts of telomerase activity as assessed by TRAP assay. CONCLUSIONS/SIGNIFICANCE:In contrast to several other species including humans, the retention of lifelong telomerase and telomeres, as we have reported here, would be necessary in the zebrafish to maintain its tremendous regenerative capacity. The ongoing study of the zebrafish's ability to maintain telomerase activity may be helpful in unraveling the complexity involved in the maintenance (or lack thereof) of telomeres in other species such the mouse or human

Babesia duncani multi-omics identifies virulence factors and drug targets

Babesiosis is a malaria-like disease in humans and animals that is caused by Babesia species, which are tick-transmitted apicomplexan pathogens. Babesia duncani causes severe to lethal infection in humans, but despite the risk that this parasite poses as an emerging pathogen, little is known about its biology, metabolic requirements or pathogenesis. Unlike other apicomplexan parasites that infect red blood cells, B. duncani can be continuously cultured in vitro in human erythrocytes and can infect mice resulting in fulminant babesiosis and death. We report comprehensive, detailed molecular, genomic, transcriptomic and epigenetic analyses to gain insights into the biology of B. duncani. We completed the assembly, 3D structure and annotation of its nuclear genome, and analysed its transcriptomic and epigenetics profiles during its asexual life cycle stages in human erythrocytes. We used RNA-seq data to produce an atlas of parasite metabolism during its intraerythrocytic life cycle. Characterization of the B. duncani genome, epigenome and transcriptome identified classes of candidate virulence factors, antigens for diagnosis of active infection and several attractive drug targets. Furthermore, metabolic reconstitutions from genome annotation and in vitro efficacy studies identified antifolates, pyrimethamine and WR-99210 as potent inhibitors of B. duncani to establish a pipeline of small molecules that could be developed as effective therapies for the treatment of human babesiosis.We thank R. Gao for her contribution to the initial eforts to sequence the B. duncani genome. C.B.M.’s research was supported by grants from the National Institutes of Health (AI097218, GM110506, AI123321 and R43AI136118), the Steven and Alexandra Cohen Foundation (Lyme 62 2020), and the Global Lyme Alliance. S.L.’s research was supported by grants by the US National Science Foundation (IIS 1814359) and the National Institutes of Health (1R01AI169543-01). K.G.L.R.’s research was supported by the National Institutes of Allergy and Infectious Diseases (R01 AI136511, R01 AI142743-01 and R21 AI142506-01), the University of California, Riverside (NIFA-Hatch-225935) and the Health Institute Carlos III (PI20CIII/00037).S