Miracle-dz/UniFAR-FTUs huggingface dataset:
Abstract 1650: CYC065, a novel CDK2/5/9 inhibitor: detailed mechanistic studies, determinants of sensitivity and synergistic combinations

Background: CYC065 is a novel, second generation aminopurine inhibitor highly selective for CDK2, CDK5 and CDK9 over other CDKs and non-CDK enzymes. CYC065 has completed IND-directed drug development and is ready for FIH studies. The unique target profile of CYC065 can be exploited in cyclin E-overexpressing tumors, including a trastuzumab-resistant Her2+ breast cancer model (Scaltriti et al, PNAS 2011; 9:3761). The aim of this study was to gather key dosing information for this compound in advance of FIH studies, and provide understanding of the compound mechanism of action in additional key target indications. CDK9 is a key regulator of mixed lineage leukemia (MLL)-driven leukemogenesis and Mcl-1-dependent survival and therefore represents a potential therapeutic target for AML and MLL leukaemia. Methods: A panel of acute leukemia cell lines with different MLL status (WT, MLL translocations and MLL PTD) was used in this study. Resazurin and flow cytometry-based annexin V assays were used to determine cell viability and apoptosis induction. PI staining was used to examine cell cycle distribution. Protein levels were quantified by Western blotting and quantitative imaging. Combinations were studied using the Chou and Talalay method. The in vivo activity of CYC065 was studied in murine xenograft models. Results: CYC065 rapidly decreased phosphorylation of Ser2 -RNAP II and expression of proteins involved in cell cycle control, survival and leukemogenesis (such as Mcl-1, Cyclin E, PNUTS, Hoxa9 and Meis 1), leading to robust and early induction of apoptosis (within 4 h). Time- and dose-dependent studies indicated that 6 h pulse treatment at 0.5-1 μM CYC065 was sufficient to cause ≥ 90% cell death in sensitive cell lines. Cell lines with MLL rearrangements were highly sensitive to CYC065, whilst sensitivity of AML cell lines with WT MLL correlated with the level of Bcl-2 family proteins. Cell lines with reduced sensitivity to CYC065 could be effectively targeted by exposure to longer, 10 h pulse treatments with CYC065, or in combination with short pulses of Bcl-2 inhibitors. In vivo, CYC065 achieved >90% TGI at well tolerated dose levels in HL60 (WT MLL) and EOL-1 (MLL PTD) xenograft models. Conclusion: CYC065 has therapeutic potential for AML and MLL leukemia. MLL status and the levels of Bcl-2 family proteins might be useful patient stratification markers for predicting sensitivity/resistance. Citation Format: Chiara Saladino, Sheelagh Frame, Susan Davis, David Blake, Daniella Zheleva. CYC065, a novel CDK2/5/9 inhibitor: detailed mechanistic studies, determinants of sensitivity and synergistic combinations. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1650. doi:10.1158/1538-7445.AM2015-1650
Protective effect of a prostaglandin oligomer on liver mitochondria in situ: time‐shared measurements of fluorescence and reflectance in the cold‐preserved rat liver

Abstract. The protective effect of a new oligomeric derivative of prostaglandin B2, known as OC‐5186, was evaluated using time‐sharing spectrofluorometry in the cold‐preserved rat liver. Experiments were divided into three groups: in group A, a 5000 ng dose of OC‐5186 was administered via the peripheral vein, 1000 ng via the portal vein, and 200 ng/ml in University of Wisconsin (UW) solution; in group B, the OC‐5186 dosage was ten times greater than that in group A; in group C (control group), liver procurement and storage were performed without OC‐5186. At 0,12, and 24 h after cold preservation at 4d̀C, the liver was perfused for 30min at 12d̀C with oxygenized Krebs‐Henseleit solution, after which the perfusate was switched to deoxygenized Krebs‐Henseleit solution. Time sharing spectrofluorometry was used to follow NADH fluorescence at 450 nm with a 360‐nm excitation wavelength, as well as the reflectance of cytochrome aa3j with 605 minus 620 nm from oxidation to reduction. Rate constants of NADH fluorescence and cytochrome aa3 reflectance were used as indices of integrity of the mitochondrial respiratory chain. In group C, the rate constant of NADH fluorescence decreased significantly (P≤ 0.05) from the control value of 8.31±0.21times1O‐3 (sec‐1) to 4.97±0.15times10‐3 and 5.58±0.16times10‐3 (mean±SEM) at 12 and 24 h after cold preservation, respectively. By contrast, in groups A and B, the rate constant of NADH fluorescence was maintained at significantly (P≤0.05) higher levels of 6.57±0.54times10‐3 and 7.29±0.48times10‐3, and 6.94±0.44times10‐3 and 6.86±0.44times10‐3 at 12 and 24 h, respectively. The rate constant of cytochrome aa3 reflectance between the OC‐5186 groups and the control group was not significant. It is concluded that OC‐5186 has a protective effect on the mitochondrial respiratory chain against cold‐preservation and/or reperfusion injury.
Plasma levels of endothelin‐1 in patients with the hepatorenal syndrome after successful liver transplantation

Abstract The hepatorenal syndrome (HRS) is characterized by renal vasoconstriction leading to deterioration of renal function in patients with liver disease. A possible role of endothelin‐1 (ET‐1) in the pathogenesis of HRS has been suggested, but a correlation between ET‐1 plasma levels and the development of HRS as well as the recovery from HRS following OLT has not been shown yet. We performed longitudinal measurements of ET‐1 plasma levels in four groups of patients, 5 patients with HRS before and after orthotopic liver transplantation (OLT), 10 patients without HRS undergoing OLT, 20 patients with chronic renal failure but without liver disease, and 12 healthy controls. Before OLT, plasma levels of ET‐1 were higher in patients with HRS (19.5 ± 8.6 ng/1, P < 0.001; n= 5) compared to patients without HRS (4.9 ± 1.1 ng/1; n= 10), normals (1.2 ± 0.18 ng/l; n= 12), and patients with chronic renal failure (2.4 ± 0.4 ng/l; n= 20). Patients with HRS compared to patients without HRS had higher levels for creatinine (2.42 ± 0.6 vs. 0.89 ± 0.05 mg/dl, P < 0.05), creatinine clearance (107 ± 9 ml/min vs. 44.6 ± 5.5 ml/ min, P < 0.001), and bilirubin (11.4 ± 3.8 vs. 3.7 ± 1 mg/dl, P < 0.05) before OLT. Within one week after OLT, there was a rapid decrease in ET‐1 levels in patients with HRS while creatinine and bilirubin levels decreased slower. Regression analysis revealed a weak correlation between serum creatinine and ET‐1 (r= 0.192, P= 0.04) and a significant correlation between serum bilirubin and ET‐1 (r= 0.395, P < 0.001). The means of the ET‐1 levels decreases rapidly with improvement of liver function after OLT. Levels of ET‐1 correlate with excretory liver function assessed by bilirubin. The fall in ET‐1 levels preceding improvement of renal function further strengthens the concept of ET‐1 being a causative factor in HRS.
Duplicate Gene Expression and Allozyme Divergence Diagnostic for Catostomus tahoensis and the Endangered Chasmistes cujus in Pyramid Lake, Nevada

The allotetraploid catostomid fish, Catostomus tahoensis and the endangered Chasmistes cujus, from Pyramid Lake, Nevada, were examined electrophoretically for duplicate gene expression and allozyme variation. Both species resemble other advanced catostomids in the retention of relatively few ancestrally duplicated genes: 34% and 36%, respectively. The two species were diagnostically different for 20 genetic characters: number of genes for fructose-bisphosphate aldolase (Fba-A'), tissue expression of an NADP-dependent malate dehydrogenase, and allelic composition at 18 loci. No genetic evidence of hybridization was detected in a sample of 28 C. cujus suspected, on the basis of morphology, to be of hybrid origin.
Effects of the microclimate in natural nests on development of embryonic painted turtles, Chrysemys picta

Temperature and moisture influence the development of embryonic reptiles in the laboratory but the importance of these variables to embryos developing in nature is a topic of debate. We measured temperature and water potential in 12 nests of painted turtles, Chrysemys picta, and subsequently assessed the influence of these factors on survival by embryos, net change in mass of eggs, length of incubation, and live mass and body size of hatchlings. Average temperature in nests varied between 23.4 and 26.2 °C, and average water potential ranged from − 0.06 MPa to − 2.11 MPa. Hatching success varied from 33 to 100%, and was correlated more highly with the water potential in nests than with temperature
Mastitis incidence and bacterial causative agents isolated from lactating she-camel (Camelus dromedaries).

This study was carried out to determine the incidence of mastitis in lactating she-camel in North Kordofan State, Sudan. Furthermore, the causative bacterial agents were identified. Sixty lactating she-camels were examined clinically for mastitis. Thereafter milk samples (n= 216 samples) were collected from each quarter of the udders of the she-camels. The samples were subjected to white side test (WST), somatic cell count test (SCC) and bacteriological examination. The results of the clinical examination revealed that the incidence of mastitis was 25% (n=15 she-camels) while upon the WST and SCC were15% (n= 9 she-camels) and 13.33% (n= 8 she-camels), respectively. However, the incidence of mastitis (41.66%) was significantly high (p<0.001) when the milk samples were bacteriological examined (n=25 she-camel). The bacterial examination revealed that the predominant cause is Staphylococcus spp. (80.30%) followed by Bacillus spp. (9.09%), Pasteurella spp. (6.06%), Corynebacteria spp. (3.03%), and Streptococcus spp. (1.52). It is concluded that the mastitis prevails in lactating she-camels in North Kordofan State and the most predominant cause of mastitis are Staphylococcus species. Mastitis emerges as a serious hazard and problem that affect a resource essential for many nomadic tribes that lives in the desert and semi desert areas. A national program to diagnose and compact this disease should be launched.
Presumed Chronological, Developmental and Clinical Classification of Human Dentitions

Diphyodont, including man, have traditionally two dentitions the deciduous and permanent. The significances of the presence of two dentitions may lie behind the fact that once the teeth have been developed, they are unable to grow, by the common sense of the word. Since the individual organs and tissues grow by time and the jaws also do, therefore, other generation of dentition is needed to match the new situation, that is, the permanent dentition. However, this typing of dentition into two sets is oversimplified and nonindcative for the condition in which the teeth are variably represented. It also, does not exhibit the different and definite cases by which the teeth are expressed. Taking these drawbacks into consideration, a presumed classification has been presented indicating the developmental, clinical and chronological situations of the different sets of dentitions. The presumed classification may be valuable not only for pedagogic purposes but also for the developmental and clinical studies. (Journal of American Science 2010;6(11):1085-1090). (ISSN: 1545-1003). (http://www.americanscience.org).
Expression of Survivin and P53 in Salivary Adenoid Cystic Carcinoma

Objective:To evaluate the clinical significance of Survivin and P53expression in salivary adenoid cystic carcinoma(SACC)and its relationship.Methods:Immunohistochemical staining(SP)was used to quantify Survivin and P53expression in specimens from 36patients with SACC and normal parotid gland tissues nearby from 10patients as control.SPSS13. 0statistical software was used.Results:The expression rates of Survivin and P53in the36cases of SACC were 66.67%and 69.44%respectively.The positive rate of Survivin and P53strongly associated clinicopathologic stage.P53associated with lymphatic metastasis and pathology category.Survivin and P53were not expressed at adjacent normal parotid gland tissues.Conclusion:Survivin and P53may participate in the onset and development of SACC.Quantification of Survivin and P53in SACC may provide a valuable marker for prognosis of patients with SACC.
Some aspects of behavior of the protoplasmic streaming in plant cells

It is generally known that the protoplasmic streaming is active in adult cells but is not conspicuous when the cell is young. Though the reason for this is not clear, it must be due either to the difference in the physico-chemical nature of the protoplasm in different developmental stages or to the difference in physical factors such as the size of the cell, the development of vacuoles, etc. In the present report, special reference has been made to the behavior of the protoplasmic motion when the cell is bound off into smaller fragments. The internodial and leaf cells of Chara Braunii and those of some unidentified species of Chara were also used as materials. The unusually large size of the cell which we used permitted us to perform the operation of binding off the cell, an operation which is impossible with ordinary adult plant cells. The rate of flow being sensitive to the change in temperature, in all the following experiments the cell was observed in a small water bath kept at 27'C and placed on the microscopic stage. I) The rate of flow in relation to the length and width of the cell The length of the internodial cells in nature varies from a few millimeters to 100 mm or so, the diameter being 0.2-0.4 mm, while the leaf cells are usually several millimeters long and 0.1-0.2 mm wide. The protoplasm in all the normal internodial cells having the diameter of about 0.3 mm flows nearly with the same velocity, namely 75μ per second, irrespective of the length of the cell. This situation can be demonstrated more clearly by a method applied by Linsbauer (199), in which the cell is bound with a hair or silk thread. As a result of such an operation the cell is divided, without serious injury into two or more fragments. Such a procedure seems not to affect the activities of the cell. Each fragment thus divided not only survives for long time, but can even grow, under suitable conditions. In this manner, we can make cell fragments of any size we want, even smaller in size than those produced naturally.
The Respiratory Microenvironment within the Burrows of Gopher Tortoises (Gopherus polyphemus)

contrast, burrows in clayey soils, while exhibiting only moderate hypoxia (18.19%), had concentrations of CO2 high enough (2.35%, maximum 6.77%) to be of physiological consequence. Three sources contribute to the hypercarbia in the burrows: CO2 in the surrounding soil; the metabolism of the tortoise; and the metabolism of commensals, particularly those that decompose the feces. Burrows in clayey soils are shorter (3.2 m) than those in sandy soils (4.1 m). We propose that this is due to the significant relationship between the degree of hypercarbia and burrow length that is characteristic of the former, but not of the latter.
A Tale of Success: Preventing Establishment of the Gypsy Moth in Kentucky

American Entomologist • Fall 2008 Since its introduction from France in 1869, the gypsy moth, Lymantria dispar L. , has become one of the most destructive forest pests in eastern North America (USDA Forest Service 1981, Drooz 1985, USDA 1995). Lacking natural co-evolved population regulators, North American gypsy moths are prone to population eruptions that lead to extensive defoliation in highly susceptible, oak-dominated forests. Immediately following its escape from a captive population in Medford, MA (Liebhold et al. 1989), sporadic defoliation was evident, and within a few years, this species became problematic in eastern Massachusetts. Over the next 130 years, populations radiated from the point of introduction to become established in many northeast, mid-Atlantic, and north-central states (Lovett et al. 2006). Currently, the gypsy moth’s range extends from Maine to North Carolina and west to Wisconsin (Tobin et al. 2004, Johnson et al. 2006). In spite of intermittent introductions, gypsy moth populations have not yet become established in Kentucky; however, they are established in the adjoining states of Virginia, West Virginia, Ohio, and Indiana (APHIS 2003, Lovett et al. 2006). High fecundity, eruptive populations, and extreme polyphagy give the gypsy moth its status as one of the most ecologically and economically significant North American forest pests (Drooz 1985, Elkinton and Liebhold 1990). More than 500 trees and shrubs can serve as hosts, with oaks (Quercus spp.) preferred (Liebhold et al. 1995). Apple, sweetgum, basswood, gray and white birch, poplar, willow, and hawthorn are also favored trees for all instars, whereas only older larvae feed on hemlock, pines, and spruce (Elkinton 1982, McManus et al. 1989, Douce et al. 1994, Liebhold et al. 1995, APHIS 2003). Since 1924, more than 32.8 million forested ha have been defoliated, and since 1970, more than 4.9 million ha have been treated to suppress gypsy moth populations (USDA 1995). In 1981, a record 5.2 million ha were defoliated (APHIS 2003). An area of West Virginia directly east of Kentucky had record defoliations from 2000 to 2002 totaling more than 428,000 ha (Haynes et al. 2005). Average sawtimber and pulpwood volume losses in West Virginia were ~20% each, with oaks making up 94.2% of the volume lost (Haynes et al. 2005). The estimated value for timber killed on the 22,906 ha that were heavily defoliated twice in West Virginia during this 3-yr period was more than $18 million (Haynes et al. 2005). The economic impacts associated with ecological effects of gypsy moth defoliation are less tangible, but include losses in revenue associated with recreation, tourism, hunting, and angling. In the United States, ~126 million forested ha are at risk of defoliation by gypsy moth, in addition to thousands of hectares of urban and rural forested areas (Powell et al. 1993). Adult females are flightless, and wind-borne dispersal of newly hatched larvae results in annual range expansions of 2–3 km (Liebhold et al. 1992). However, from 1960 to 1990, populations demonstrated an alarming spread rate averaging
Is Diglossa (?Thraupinae) Monophyletic?

The currently recognized genus of Neotropical flowerpiercers, Diglossa (TThraupinae), is polyphyletic as shown primarily by the structure of the corneous tongue. The species caerulescens, cyanea and glauca constitute the genus Diglossopis Sclater 1856, whereas the remaining species form the restricted genus Diglossa Wagler 1832. These genera are not closely related to one another within the New World nine-primaried oscines and have acquired their frilled tongue and other nectar feeding adaptations independently. Similarities in the flower-piercing nectarivorous habits and the bill structures of the two genera are examples of convergent evolution. RESUMEN. El genero actualmente reconocido para mieleros, Diglossa (TThraupinae), tiene su origen en varios linajes ("polyphyletic") tal como lo muestra principalmente la estructura de la lengua cornea. Las especies caerulescens, cyanea y glauca constituyen el genero Diglossopis Sclater 1856, mientras que las restantes especies, el genero restringido Diglossa Wagler 1832. Estos generos no estan cercanamente relacionados entre si con los oscines de nueve primarias del Nuevo Mundo y han adquirido su lengua escarolada y otras adaptaciones para su alimentation de nectar, de manera independiente. Las similaridades en los habitos nectarivoros de picar flores y en la estructura del pico de los dos generos son ejemplos de evolution
Briefly Noted

469 chronic HD patients with hypertension, treatment with an angiotensin receptor blocker (olmesartan) conferred no benefits (mortality, cardiovascular endpoints) over other classes of antihypertensives (ACE inhibitors not included) (1). Over a mean 3.5 years of follow-up, all-cause death occurred in 16.2% of the olmesartan group and in 16.7% of the control patients; BP control did not differ in the groups.
SUBKLONING DAN ISOLASI GEN PENYANDI MIKRONEMA 3 (MIC-3) Toxoplasma gondii ISOLAT LOKAL

Microneme protein (MIC) is one of proteins that belongs to excretory-secretory antigens (ESAs) of Toxoplasma gondii . Microneme 3 protein (MIC-3) is the protein that plays an important role in the invasion proccess during cell infection as a mediator attachment parasite to the host cell. The aim of this research is to clone mic3 (gene encoding for MIC-3) of T. gondii from local isolate using recombinant DNA technology by cloning mic3 in an expression vector. Deoxyribonucleic acid (DNA) from T. gondii tachyzoites was amplified by PuRe Taq RTG-PCR Beads using mic3 specific primers. Amplified DNA was double digested using Eco RV and Hind III restriction endonucleases and then purified using EZ-10 spin coloumn purification kit . The mic 3 DNA was ligated into pET-32a(+) expression vector and transformated into Escherichia coli BL21. The results showed that recombinant mic3 gene 4.2 kDa has been successfully performed by cloning gene encoding for MIC-3 protein of T . gondii local isolate into pET-32a(+) and transformed to E. coli BL21.
A Coupled Field and Modeling Approach for the Analysis of Nitrogen Cycling in Streams

The stable isotope stream tracer model (SISTM) calculates the expected <sup>15</sup>N content in various stream ecosystem N compartments over distance and time during and after <sup>15</sup>N additions to streams. SISTM is a steady state compartment model that predicts δ <sup>15</sup>N values based on N stocks and fluxes and the experimental rate of <sup>15</sup>N addition. Predicted δ <sup>15</sup>N values are compared with observed δ <sup>15</sup>N values from a field tracer addition to evaluate our understanding of the N cycle. We demonstrated the use of this tool with information collected from field measurements and a 6-wk <sup>15</sup>N-NH<sub>4</sub><sup>+</sup> addition to the Kuparuk River, Alaska, during the summer of 1991. SISTM was used to run a series of model calibrations that reflected increased information as the experiment progressed. Results of an a priori calibration (using pre-1991 data) yielded a predicted NH<sub>4</sub><sup>+</sup> uptake length (S<sub>w</sub>) of 5.2 km compared with the observed S<sub>w</sub> of 0.84 km, and underestimated the δ <sup>15</sup>N values of biota in all cases. When discharge and NH<sub>4</sub><sup>+</sup> concentrations measured during the 1991 experiment were added (model calibration Update 1), the predicted S<sub>w</sub> dropped to 0.44 km, indicating that the modeled fluxes overestimated the rate of NH<sub>4</sub><sup>+</sup> removal by the stream bottom. Adding N stocks and fluxes measured during the tracer addition (Update 2) did not improve predicted S<sub>w</sub>, indicating faulty assumptions in our a priori calibration. The observed isotope data were used to estimate the form (NH<sub>4</sub><sup>+</sup> vs NO<sub>3</sub><sup>-</sup>) of N taken up by primary producers and to improve our representation of the epilithon compartment (Update 3). Including this information brought the predicted S<sub>w</sub> to 0.71 km compared with the observed 0.84 km, and resulted in a reasonable correspondence between predicted and observed δ <sup>15</sup>N values over the 6-wk addition. SISTM can be used as a framework to 1) summarize N-cycle information prior to a tracer addition, 2) generate testable predictions for field isotope studies, 3) improve our understanding of the N cycle using the field isotope data as constraints on flux estimates, and 4) explore hypothetical N-cycle characteristics. The combined modeling and field tracer experiment approach efficiently provided a synoptic view of the N cycle in streams and rivers.