Miracle-dz/UniFAR-FTUs huggingface dataset:
ZEB/miR‐200 feedback loop: At the crossroads of signal transduction in cancer

Embryonic differentiation programs of epithelial–mesenchymal and mesenchymal–epithelial transition (EMT and MET) represent a mechanistic basis for epithelial cell plasticity implicated in cancer. Transcription factors of the ZEB protein family (ZEB1 and ZEB2) and several microRNA species (predominantly miR‐200 family members) form a double negative feedback loop, which controls EMT and MET programs in both development and tumorigenesis. In this article, we review crosstalk between the ZEB/miR‐200 axis and several signal transduction pathways activated at different stages of tumor development. The close association of ZEB proteins with these pathways is indirect evidence for the involvement of a ZEB/miR‐200 loop in tumor initiation, progression and spread. Additionally, the configuration of signaling pathways involving ZEB/miR‐200 loop suggests that ZEB1 and ZEB2 may have different, possibly even opposing, roles in some forms of human cancer.
A multiplex PCR assay to distinguish among three sympatric marsupial taxa from Huon Peninsula, Papua New Guinea, using the mitochondrial control region

Matschie’s tree kangaroo (Dendrolagus matschiei) is an endangered arboreal macropodid marsupial that is difficult to locate in the wild. The Tree Kangaroo Conservation Program noninvasively collected D. matschiei faecal samples, but a high percentage of samples were misidentified and belonged to two terrestrial macropods, New Guinea pademelon (Thylogale browni) and small dorcopsis (Dorcopsulus vanheurni). We developed species‐specific primers that produced a unique sized mitochondrial DNA control region gene product for each taxon and achieved an 89% correct assignment rate. The species‐specific primers can increase the accuracy of D. matschiei density estimates and facilitate additional genetic analyses of wild D. matschiei.
Mechanism and utility of an RNA-cleaving DNA enzyme.

We previously reported the in vitro selection of a general-purpose RNA-cleaving DNA enzyme that exhibits a catalytic efficiency (kcat/KM) exceeding that of any other known nucleic acid enzyme [Santoro, S. W. and Joyce, G. F. (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 4262-4266]. This enzyme contains approximately 30 deoxynucleotides and can cleave almost any RNA substrate under simulated physiological conditions, recognizing the substrate through two Watson-Crick binding domains. The kinetics of cleavage under conditions of varying pH, choice of divalent metal cofactor, and divalent metal concentration are consistent with a chemical mechanism involving metal-assisted deprotonation of a 2'-hydroxyl of the substrate, leading to substrate cleavage. Kinetic measurements reveal that the enzyme strongly prefers cleavage of the substrate over ligation of the two cleavage products and that the enzyme's catalytic efficiency is limited by the rate of substrate binding. The enzyme displays a high level of substrate specificity, discriminating against RNAs that contain a single base mismatch within either of the two substrate-recognition domains. With appropriate design of the substrate-recognition domains, the enzyme exhibits a potent combination of high substrate sequence specificity and selectivity, high catalytic efficiency, and rapid catalytic turnover.
The effect of a novel transition state inhibitor of methylthioadenosine phosphorylase on pemetrexed activity

Pemetrexed is a new-generation antifolate inhibitor of thymidylate synthase (TS) and a weaker inhibitor of glycinamide ribonucleotide transformylase (GARFT) required for de novo purine synthesis. Methylthioadenosine phosphorylase (MTAP) salvages purines by releasing adenine from methylthioadenosine and is often deleted in mesothelioma. The current study addresses the effect of MTAP on pemetrexed activity using a highly potent transition state inhibitor of MTAP, MT-DADMe-Immucillin A (ImmA; Ki = 86 pmol/L) in the MTAP(+) NCI-H28 and MTAP(−) NCI-H2052 mesothelioma cell lines. Based on selective nucleoside protection, TS was found to be the primary pemetrexed target in both cell lines with GARFT inhibition requiring 20- to 30-fold higher pemetrexed concentrations. ImmA had no effect on pemetrexed activity but, when thymidine was added, the pemetrexed IC50 decreased by a factor of ∼3 in MTAP(+) H28 cells with no effect in MTAP(−) H2052 cells. Conversely, the transfection of MTAP into H2052 cells increased the pemetrexed IC50 by nearly 3-fold but only in the presence of thymidine; this was reversed by ImmA. An MTAP-specific short interfering RNA produced a 2-fold decrease in pemetrexed IC50 in MTAP(+) HeLa cells in the presence of thymidine. These data indicate that suppression of constitutive MTAP has no effect on pemetrexed activity when the primary target is TS. There is a modest salutary effect when the pemetrexed target is GARFT alone. [Mol Cancer Ther 2006;5(10):2549–55]
Dominant negative suppression of major histocompatibility complex genes occurs in trophoblasts.

BACKGROUND Polymorphic class I and II major histo-: compatibility complex (MHC) genes are not transcribed in trophoblasts although many immune system cells express these genes constitutively. To study the molecular biology of MHC suppression for the purposes of potential transgenic animal development, we examined the effect on MHC expression in B cells by fusing them with trophoblasts. METHODS Trophoblasts and B cells with separate selection markers were fused with polyethylene glycol. After growth in double selection media, the hybrids were analyzed for HLA-A, -B, -C, -DR, -DP, and -DQ expression by fluorescence-activated cell scanning and class I and II mRNA by Northern blotting. Class II promoter activity in trophoblasts was then analyzed by transfection of a lethal reporter construct and subsequently, the class II transactivator. RESULTS Class I and II surface antigens and their corresponding mRNA were completely suppressed in the hybrids. The lethal reporter construct demonstrated that class II suppression resulted from lack of activation of the class II promoter. This in turn was caused by lack of functional class II transactivator. CONCLUSIONS These data indicate that dominant negative trophoblast factors, either directly or indirectly, suppress expression of the MHC genes. If these factors can be cloned, the potential exists for developing transgenic animals that cannot express MHC or peptide antigen to T cell receptors through the MHC system.
Effect of vitrification on number of inner cell mass in mouse blastocysts in conventional straw, closed pulled straw, open pulled straw and cryoloop carriers.

OBJECTIVE To compare the effect of using open and closed carriers on count of inner cell mass in vitrified mouse blastocyst after warming. METHODS The experimental study was conducted at Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran, from April to September 2010. Forty female NMRI (Naval Medical Research Institute, USA) mice were injected with pregnant mare's serum gonadotropin and human chorionic gonadotropin in order to induce superovulation. Following the latter injection, two or three females were caged with the same-breed male mice. The presence of vaginal plug was examined the following morning. To collect blastocyst embryos, the pregnant females were sacrificed by cervical dislocation at 88-90 hours after the injection and dissected. Blastocysts were collected in phosphate-buffered saline and allocated to four groups: vitrification in conventional straw, closed pulled straw, open pulled straw and cryoloop. The vitrification solution was ethylene glycol, Ficol and sucrose (EFS) 20% and 40%. After storage for 1 month in liquid nitrogen, the blastocysts were thawed in 0.5 M sucrose then cultured in M16 medium. After 6 hours of culture, the number of expanded blastocysts was recorded and stained by double-dye technique. After staining, the number of total cell and inner cell mass was calculated. RESULTS The re-expansion rate of blastocysts in the cryoloop group (n = 90; 78.26%) was significantly higher (p < 0.05) than open pulled straw (n = 83; 69.16%), closed pulled straw (n = 68; 54.83%) and conventional straws (n = 63; 51.21%) groups. Significant differences (p < 0.05) in the number of inner cell mass in blastocysts vitrified in open pulled straws, closed straws and cryoloop with blastocysts cryopreserved in conventional straws. CONCLUSION The re-expansion rate and total cell number of mouse blastocysts vitrified using open system had a better result compared with the closed system. The value of cryoloop and open pulled straws as carriers in vitrification of blastocysts may also merit more investigation.
Karakterne osobine, etička pitanja i svakodnevni rad medicinskih sestara

Character traits of health personnel in modern medicine, marked by huge success in improvement of preventable death rates through approach based on scientific evidence, are gaining new importance. Evidence based medicine often requires of a medical professional to be emotionally detached from a patient to improve objectivity, which gives patients an impression of uncaring of their condition, and at a time a patient is the most vulnerable and the most sensitive. That is why the need to regress to more humane roots of medicine is larger than ever, and development of certain character traits of medical personnel is one of the proposed mechanisms to achieve that goal. A virtuous person taking care of a patient does that from the right reasons and in the right way, based on well defined character traits needed to respond to the requirements of patients, satisfying their need in technical, emotional and social sense. Here we review current understanding of the quality of medical care, virtues a nurse should possess, vices she should correct and mechanism that modern virtue ethics proposes to reconcile scientific and humanistic faces of medicine.
Health care resource utilization and costs associated with nonfatal major adverse cardiovascular events.

BACKGROUND Risk of recurrent cardiovascular events following an initial cardiovascular-related hospitalization remains high despite available interventions. Rates of cardiovascular events as well as associated health care resource utilization and costs are needed to assess the value of treatments. OBJECTIVE To quantify, in patients with previous hospitalization for acute coronary syndrome (ACS), rates of nonfatal major adverse cardiovascular events (MACE) and secondary coronary events (SCE), as well as health care utilization and costs associated with a first MACE. METHODS Administrative data from a large population of commercial managed care and managed Medicare enrollees in the United States were retrospectively analyzed. Patients with an ACS-related hospitalization from 2006 to 2011 were followed for 12 months to assess subsequent MACE and SCE rates. Patients were aged ≥ 18 years at initial ACS hospitalization (the index episode) and had ≥ 12 months of continuous health plan enrollment before and after the end of the index episode. Resource utilization and costs during a first MACE were assessed. Multivariable analyses were used to assess the associations between cardiovascular risk factors and the occurrence of a MACE, as well as the costs incurred during a first MACE. RESULTS Of 75,231 study patients identified, 3.3% had a MACE and 8.3% had an SCE during the 12-month follow-up. Median time to first MACE and SCE from end of the index episode was 4.6 and 3.7 months, respectively. Mean MACE-related cost incurred during the first MACE was $19,642. Logistic analyses showed that age and diabetes were associated with increased odds of a MACE, while index ACS episodes involving ST-elevation myocardial infarction were associated with reduced odds. Findings from generalized linear models indicated that statin use and age were associated with lower episode-related costs and that MACE occurrence within 3 months of ACS hospitalization was associated with increased episode-related costs. CONCLUSIONS MACEs and SCEs represent a common and costly burden in the year following ACS hospitalization. Our findings may inform future economic assessments of new therapies aimed at prevention of MACEs and SCEs.
Critically Evaluating the Role of Diagnostic Imaging in Osteomyelitis

Early diagnosis, essential for timely appropriate treatment and reduction of complications, can be difficult. This article aims to give an overview of the role that different imaging modalities have to play in the diagnosis of osteomyelitis. Osteomyelitis is a heterogeneous disease in its pathophysiology, clinical presentation, and management. It infers inflammation of bone and marrow, whereas osteitis is inflammation of the bone only. Thus, a soft-tissue infection that reaches the bone surface but has not infected the marrow is osteitis and not osteomyelitis. Chronic osteomyelitis is divided into active and inactive forms. Newly appearing periosteal reaction or bone destruction within the chronic involucrum are indicators of activation. Imaging modalities represent different underlying pathophysiological processes that may be represented in differing types and differing phases of osteomyelitis. Sequential selection of appropriate imaging modalities requires a thorough understanding of the disease processes and the process by which each modality visualizes this dynamic disease process.
HspB8 Chaperone Activity toward Poly(Q)-containing Proteins Depends on Its Association with Bag3, a Stimulator of Macroautophagy*

Mutations in HspB8, a member of the B group of heat shock proteins (Hsp), have been associated with human neuromuscular disorders. However, the exact function of HspB8 is not yet clear. We previously demonstrated that overexpression of HspB8 in cultured cells prevents the accumulation of aggregation-prone proteins such as the polyglutamine protein Htt43Q. Here we report that HspB8 forms a stable complex with Bag3 in cells and that the formation of this complex is essential for the activity of HspB8. Bag3 overexpression resulted in the accelerated degradation of Htt43Q, whereas Bag3 knockdown prevented HspB8-induced Htt43Q degradation. Additionally, depleting Bag3 caused a reduction in the endogenous levels of LC3-II, a key molecule involved in macroautophagy, whereas overexpressing Bag3 or HspB8 stimulated the formation LC3-II. These results suggested that the HspB8-Bag3 complex might stimulate the degradation of Htt43Q by macroautophagy. This was confirmed by the observation that treatments with macroautophagy inhibitors significantly decreased HspB8- and Bag3-induced degradation of Htt43Q. We conclude that the HspB8 activity is intrinsically dependent on Bag3, a protein that may facilitate the disposal of doomed proteins by stimulating macroautophagy.
Do high-performance work systems always help to retain employees or is there a dark side?

ABSTRACT This study considers both the positive and possible negative impact of high-performance work systms (HPWS) by investigating its relationship with job demands, job satisfaction and job search behavior. The parallel mediation effect of job satisfaction and physiological job demand on the link between HPWS and job search behavior is also examined. Data were collected in two phases from 22 branches of Iranian private banks (n = 269) employees in 2016. Results from a covariance-based structural equation modeling (CB-SEM) shows that HPWS positively relates to job satisfaction, physiological job demand and job search behavior. Job satisfaction negatively relates to job search behavior and mediates the link between HPWS and job search behavior. The results offer practical implications for managers and policy makers in the service industry to balance between job demands – resources in workplace and provide adequate resources for their employees to buffer specific negative effects of job demands.
One synchronous wave of B cell development in mouse fetal liver changes at day 16 of gestation from dependence to independence of a stromal cell environment

Precursor cells of the B lineage can be enriched from mouse fetal liver by FACS with the aid of the pre-B cell-specific mAb G-5-2. The cells are concomitantly enriched for cells expressing the pre-B cell-specific gene lambda 5, and for cells developing to LPS-reactive mature B cells. The enriched purified precursors are not influenced by rIL-2 through - 7, alone or in combination, to develop to mitogen-reactive, sIg+ cells. Marginal proliferation of the precursors is observed in response to IL- 3 plus -4, and IL-6 plus -7, and this does not change in the presence of stromal cells. Development to mitogen-reactive, sIg+ cells is dependent on interactions with embryonic stromal cells from fetal liver. Two mAbs raised against the stromal cells inhibit this development. Two phases of precursor cell development can be distinguished in fetal liver. Between days 13 and 15 of gestation, it is dependent on stromal cell interactions, thereafter, from days 16 to 19, it is independent. A sudden increase in the number of mitogen- reactive, sIg+ B lineage cells occurs within 24 h between days 16 and 17. All these results indicate that B cell development occurs in one wave with synchronous steps of changes from a mitogen-insensitive, sIg- , stromal cell dependent to a mitogen-reactive, sIg+, stromal cell- independent B lineage line.
Recent developments in plant zinc homeostasis and the path toward improved biofortification and phytoremediation programs

Zinc (Zn) is an essential micronutrient for all living organisms. Plants serve as a major entry point for this element into the food chain. Zn deficiency has become a widespread nutritional condition, which mirror the inadequate Zn reserves in significant proportion of the earth's arable land. A recent assessment by the World Health Organization revealed that one third of the world's population is at risk of Zn deficiency. To counter this alarming situation, substantial efforts have been made to increase Zn content and availability in staple crops and grains. Nevertheless, the absence of fundamental information has held back progress in this field. Developing a better understanding of how Zn homeostasis is regulated in plants, such as Zn transporters at loading bottlenecks, is of primary interest to biofortification and phytoremediation programs. Many reviews have been published on this subject, and here we briefly summarize the regulation of one limiting step in Zn distribution within plants — the loading of Zn into root xylem.
Dynamic self-configurable master-slave architecture for ad hoc wireless networks with a distributed MAC scheme

This paper proposes a distributed self-configurable architecture designed for wireless mobile ad hoc networks (MANET). In this kind of network, nodes move around varying constantly the topology of the network, so it is necessary to reconfigure the network as time goes by. The proposed self-configurable architecture permits the use of centralized or distributed MAC protocols in MANETs with only slight adaptations to these protocols.
‘LDL-C’ = LDL-C + Lp(a)-C: implications of achieved ultra-low LDL-C levels in the proprotein convertase subtilisin/kexin type 9 era of potent LDL-C lowering

Purpose of review The measurement that is termed ‘LDL-cholesterol’ (LDL-C) includes the cholesterol content of lipoprotein(a) [Lp(a)-C], which can contribute approximately 30–45% to measured LDL-C levels as a percentage of its mass. We review the implications of achieved very low LDL-C levels in patients treated with potent LDL-C-lowering agents in the context of varying Lp(a) levels. Recent findings Combination therapy with statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors can lower LDL-C to unprecedentedly low levels. Recent PCSK9 trials have shown that routine achievement of mean LDL-C less than 50 mg/dl is feasible, along with the modest reductions in Lp(a). Many patients will achieve LDL-C less than 25 mg/dl with concomitantly elevated Lp(a) levels that contribute substantially to the measured ‘LDL-C’. Therefore, it is possible that some of these patients may have little to no circulating LDL-C. Summary As the new era of ultralow LDL-C levels ensues, it is imperative to understand the contribution of Lp(a)-C to measured LDL-C and the consequences of achieving ultralow or potentially absent LDL-C in the setting of elevated Lp(a) levels and possibly free apo(a). We review this concept and suggest avenues of research, including analyses of existing datasets in current clinical trials and new research studies, to understand its pathophysiological and clinical significance.
Novel Hybrid-ARQ Chase Combining Algorithms for ZF-SIC V-BLAST

In the conventional zero-forcing successive interference cancellation (ZF-SIC) detection algorithm of vertical Bell-Labs layered space-time (V-BLAST) architecture, the detection algorithm does not attempt to eliminate the effect of the error propagation, which is significantly deleterious to hybrid automatic repeat request (H-ARQ) scheme using bit-level Chase combining. Based on two ordering approaches respectively, we propose two novel H-ARQ bit-level Chase combining algorithms in this paper, which employ a new log-likelihood ratio (LLR) calculation algorithm to minimize the effect of the error propagation. Through simulation results, it is shown that the new proposed algorithms outperform the conventional ones on system performance and these proposed approaches are also applicable in corresponding MMSE algorithms.
Questionable efficacy of extracorporeal shock wave therapy for Peyronie's disease: results of a prospective approach.

PURPOSE Extracorporeal shock wave therapy (ESWT) for Peyronie's disease is still a topic of debate. We evaluated the effects of ESWT in a large series of patients with Peyronie's disease via a prospective approach. MATERIALS AND METHODS In a prospective study 114 patients with Peyronie's disease were treated with ESWT. Baseline and followup examinations included ultrasound, and measurement of plaque size and curvature. Symptomatology was evaluated based on a standardized interview. A Minilith SL1 (Storz Medical AG, Kreuzlingen, Switzerland) lithotriptor was used with 4,000 shock waves at a maximum energy level of 0.17 mJ/mm2 applied per session. RESULTS A total of 96 patients were available for followup. Considering the total study group no significant changes in penile curvature, plaque size or sexual function were observed despite significant improvements in patients with a curvature of 31 to 60 degrees. Penile pain ceased in 76% of the affected patients. CONCLUSIONS According to our data ESWT does not appear to be significantly effective for decreasing penile curvature and plaque size or improving sexual function in the total population of patients with Peyronie's disease despite improvements in individuals. Penile pain seems to resolve earlier than during the natural course. Regarding the results of this study and previous reports with exact documentation of the clinical findings it can be concluded that ESWT cannot be recommended as a standard procedure for Peyronie's disease. To evaluate the exact efficacy of ESWT a controlled, single-blind, multicenter study with exact documentation of symptoms is urgently required.