sSgo1, a Major Splice Variant of Sgo1, Functions in Centriole Cohesion Where It Is Regulated by Plk1

SummaryShugoshin 1 (Sgo1) functions as a protector of centromeric cohesion of sister chromatids in higher eukaryotes. Here, we provide evidence for a previously unrecognized role for Sgo1 in centriole cohesion. Sgo1 depletion via RNA interference induces the formation of multiple centrosome-like structures in mitotic cells that result from the separation of paired centrioles. Sgo1+/− mitotic murine embryonic fibroblasts display split centrosomes. Localization study of two major endogenous splice variants of Sgo1 indicates that the smaller variant, sSgo1, is found at the centrosome in interphase and at spindle poles in mitosis. sSgo1 interacts with Plk1 and its spindle pole localization is Plk1 dependent. Centriole splitting induced by Sgo1 depletion or expression of a dominant negative mutant is suppressed by ectopic expression of sSgo1 or by Plk1 knockdown. Our studies strongly suggest that sSgo1 plays an essential role in protecting centriole cohesion, which is partly regulated by Plk1

Risk of Bias Tool in Systematic Reviews/Meta-Analyses of Acupuncture in Chinese Journals

BACKGROUND: Use of a risk of bias (ROB) tool has been encouraged and advocated to reviewers writing systematic reviews (SRs) and meta-analyses (MAs). Selective outcome reporting and other sources of bias are included in the Cochrane ROB tool. It is important to know how this specific tool for assessing ROB has been applied since its release. Our objectives were to evaluate whether and to what extent the new Cochrane ROB tool has been used in Chinese journal papers of acupuncture. METHODS: We searched CBM, TCM database, CJFD, CSJD, and the Wanfang Database from inception to March 2011. Two reviewers independently selected SRs that primarily focused on acupuncture and moxibustion, from which the data was extracted and analyzed. RESULTS: A total of 836 SRs were identified from the search, of which, 105 were included and four are awaiting assessment. Thirty-six of the 105 SRs were published before release of the Cochrane ROB tool (up to 2009). Most used the Cochrane Handbook 4.2 or Jadad's scale for risk or quality assessment. From 2009 to March 2011 69 SRs were identified. While "risk of bias" was reported for approximately two-thirds of SRs, only two SRs mentioned use of a "risk of bias tool" in their assessment. Only 5.8% (4/69) of reviews reported information on all six domains which are involved in the ROB tool. A risk of bias graph/summary figure was provided in 2.9% (2/69) of reviews. Most SRs gave information about sequence generation, allocation concealment, blindness, and incomplete outcome data, however, few reviews (5.8%; 4/69) described selective reporting or other potential sources of bias. CONCLUSIONS: The Cochrane "risk of bias" tool has not been used in all SRs/MAs of acupuncture published in Chinese Journals after 2008. When the ROB tool was used, reporting of relevant information was often incomplete

Overcoming Drug Resistance in Colon Cancer by Aptamer-Mediated Targeted Co-Delivery of Drug and siRNA Using Grapefruit-Derived Nanovectors

Background/Aims: Multidrug resistance (MDR) is the most common cause of chemotherapy failure. Upregulation of P-glycoprotein (P-gp) is one of the main mechanisms underlying MDR. Methods: In this study, we developed a targeted drug and small interfering (si)RNA co-delivery system based on specific aptamer-conjugated grapefruit-derived nanovectors (GNVs) that we tested in MDR LoVo colon cancer cells. The internalization of nanovectors in cancer cells was tested by fluorescence microscopy and flow cytometry. The anti-cancer activity in vitro was determined by colony formation and cell apoptosis assays. The biodistribution of nanovectors was analyzed by live imaging and the anti-cancer activity in vivo was observed. Results: GNVs loaded with aptamer increased doxorubicin (Dox) accumulation in MDR LoVo cells, an effect that was abolished by pretreatment with DNase. The LA1 aptamer effectively promoted nanovector internalization into cells at 4°C and increased the targeted delivery of Dox to tumors. Constructs harboring Dox, LA1, and P-gp siRNA more effectively inhibited proliferation and enhanced apoptosis in cultured MDR LoVo cells while exhibiting more potent anti-tumor activity in vivo than free Dox or GNVs loaded with Dox alone or in conjunction with LA1, an effect that was associated with downregulation of P-gp expression. Conclusion: This GNV-based system may be an effective strategy for overcoming MDR in clinical settings

Pengaruh sense of school belonging terhadap student's misbehavior

Penelitian ini bertujuan untuk mengetahu pengaruh sense of school belonging terhadap student’s misbehavior. Penelitian ini merupakan penelitian korelasional dengan menggunakan teknnik pengumpulan data berupa skala likert yaitu skala sense of school belonging dan skala student’s misbehavior masing masing terdiri dari 30 aitem yang sudah melalui uji coba. Skala sense of school belonging memiliki reabilitas sebesar 0,899 sedangkan skala student’s misbehavior memiliki reabilitas sebesar 0,924. Subjek penelitian berjumlah 144 siswa dari jumlah populasi sebesar 576 siswa. Pengambilan data menggunakan simple random sampling. Hasil penelitian menujukkan bahwa terdapat pengaruh sense of school belonging terhadap student’s misbehavior dengan nilai signifikansi 0,000 < 0,05. Dalam table model summary pada analisis regresi linier sederhana, sense of school belonging memberikan pengaruh sebesar 17,7% terhadap student’s misbehavior. Pada table correlation, terdapat nilai koerfisien korelasi sebesar -0,420 yang berarti semakin tinggi sense of school belonging maka semakin rendah student’s misbehavior yang dilakukan oleh siswa

A Novel Compound C12 Inhibits Inflammatory Cytokine Production and Protects from Inflammatory Injury In Vivo

Inflammation is a hallmark of many diseases. Although steroids and cyclooxygenase inhibitors are main anti-inflammatory therapeutical agents, they may cause serious side effects. Therefore, developing non-steroid anti-inflammatory agents is urgently needed. A novel hydrosoluble compound, C12 (2,6-bis(4-(3-(dimethylamino)-propoxy)benzylidene)cyclohexanone), has been designed and synthesized as an anti-inflammatory agent in our previous study. In the present study, we investigated whether C12 can affect inflammatory processes in vitro and in vivo. In mouse primary peritoneal macrophages, C12 potently inhibited the production of the proinflammatory gene expression including TNF-α, IL-1β, IL-6, iNOS, COX-2 and PGE synthase. The activity of C12 was partly dependent on inhibition of ERK/JNK (but p38) phosphorylation and NF-κB activation. In vivo, C12 suppressed proinflammatory cytokine production in plasma and liver, attenuated lung histopathology, and significantly reduced mortality in endotoxemic mice. In addition, the pre-treatment with C12 reduced the inflammatory pain in the acetic acid and formalin models and reduced the carrageenan-induced paw oedema and acetic acid-increased vascular permeability. Taken together, C12 has multiple anti-inflammatory effects. These findings, coupled with the low toxicity and hydrosolubility of C12, suggests that this agent may be useful in the treatment of inflammatory diseases

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat