We similarly compared the female proportion (F/(F + M), where F =

We similarly compared the female proportion (F/(F + M), where F = female counts and M = male counts) for impala, topi and giraffe computed by pooling all individuals of the same sex over all age classes and the 2003 and 2004 surveys, separately for each area. Results Comparative changes in herbivore density The details of differences in wildlife densities between the reserve and the APR-246 concentration ranches were complex and varied with species and season, but some consistent overall patterns were nevertheless evident. Small sized herbivores Most small herbivores CP673451 molecular weight were consistently

more abundant in the ranches than in the reserve in both seasons (Fig. 2a, e). Interestingly, warthog did not conform to this pattern and showed a preference for the reserve in the dry season but for the ranches in the wet season (Fig. 2d). https://www.selleckchem.com/products/gsk2126458.html Sheep and goats were more abundant in the ranches than in the reserve, and their numbers increased noticeably during 2000–2010 relative to earlier years (Fig. 2b; Tables S1, S2). Fig. 2 Comparative changes

in densities (number/km2) of small pure grazers and mixed gazer/browsers, a Thomson’s gazelle, b sheep and goats, c impala, d warthog and, e Grant’s gazelle between the Mara Reserve (light bars) and the adjoining Koyiaki pastoral ranch Akt inhibitor (dark bars) during the dry and wet seasons based on the DRSRS aerial surveys from 1977 to 2010. Vertical lines show the 95% pointwise confidence limits whereas stars indicate that the mean densities differed significantly between the reserve and Koyiaki Medium sized herbivores

Most medium-sized herbivores moved seasonally between the reserve and the ranches (Fig. 3a, f). However, hartebeest and waterbuck had slightly higher densities in the reserve during both seasons, but more especially in the wet season (Fig. 3c, d; Tables S1, S2). Topi, wildebeest and zebra had slightly higher densities in the reserve in the dry season when the migrants are present but somewhat higher densities in the ranches in the wet season (Fig. 3a, b, f; Tables S1, S2). More specifically, the resident wildebeest had lower densities in the ranches than in the reserve in the dry season but higher densities in the ranches than in the reserve in the wet season (Fig. 3b). Cattle were more abundant in the ranches than in the reserve in the dry season but more occurred in the reserve in the dry than in the wet season, and more recently (2000–2010) than in earlier years 1970–1999 (Fig. 3e; Tables S1, S2). Fig.

Several lines of evidence further support the role of so2426 in t

Several lines of evidence further support the role of so2426 in the regulation of iron acquisition in S. oneidensis MR-1. A recent study applying gene network reconstruction to MR-1 indicated that SO2426 clusters with iron acquisition genes in a distinct iron-responsive network system [14]. Within this iron acquisition gene network were a learn more number of members

of the SO2426 regulon proposed here, namely, so1188, so1190, so3025, so3030-3031-3032, so3063, and so4743 [14]. All of these genes, including so2426, were up-regulated under iron-depleted growth conditions compared to iron-replete conditions. Additionally, ACP-196 datasheet so3030 was up-regulated almost 14-fold in a fur mutant, while genes so3031-so3033 were up-regulated 4 to 11-fold [13]. A separate transcriptomic study with a fur deletion mutant revealed that the gene with the greatest expression change in the fur mutant ABT-737 compared to the MR-1 wild-type strain was so2426, which showed a 30- and 26-fold increase in expression at the transcript level under aerobic and anaerobic growth conditions, respectively [12]. In addition to the enhanced expression

of so2426 in a fur mutant, this gene has been shown to be up-regulated under chromate [15, 41] and strontium [42] stress. The presence of a putative Fur-binding sequence in the promoter region of so2426 suggests that expression of this response regulator may be subject to multiple levels of regulatory control. Identification of a Fur box immediately FER downstream of the -10 promoter element and up-regulation of so2426 expression in a fur deletion mutant are both consistent with repression of this gene by Fur under iron-sufficient conditions. Similarly, of those genes encoding transport and binding proteins, ftn, so1580, the so3030-3031-3032 operon, so4516, and so4743

are probable members of the Fur regulon based on their derepressed expression patterns in a S. oneidensis Δfur mutant and the presence of a putative Fur box in their respective upstream regions [12]. Collectively, these observations suggest cross-regulation of iron-responsive and other metal-responsive gene networks in S. oneidensis MR-1. SO2426 binds in region of predicted recognition site upstream of alcA Given the potential overlap in the response of S. oneidensis to iron and other metals, we chose to focus on the S. oneidensis siderophore biosynthesis operon in testing the interaction of two recombinant versions of the SO2426 protein with its predicted binding motif. The direct involvement of so3030-3031-3032 in the production of hydroxamate-type siderophores was recently demonstrated with deletion mutants within this gene cluster [43].

The changes in these

The changes in these proportions were significant by Fisher’s exact test (P = 0.033 for strain 11168; P = 0.004 for strain D0835; P = 0.031 for strain D2600). In previous experiments, the jejunum was colonized in 30–60% of mice infected for 28–35 days with unpassaged C. jejuni 11168 [40]. At the time of necropsy, levels of C. jejuni colonization in the cecum, the site where C. jejuni populations are highest and most consistent, were estimated on a semi-quantitative scale [40] and were similar check details for all

five colonizing strains in all passages (data not shown). In the first passage, all mice inoculated with all C. jejuni strains survived through the entire 30 days of SC79 mouse the experiment. In the second passage, some mice inoculated with strains 11168, D0835, and D2600 required early euthanasia due to severe Epigenetics inhibitor clinical disease (Figure 4). (For details of clinical scoring protocol, see Michigan State University

(MSU) Microbiology Research Unit Food and Waterborne Diseases Integrated Research Network-sponsored Animal Model Phenome Database website http://​www.​shigatox.​net/​cgi-bin/​mru/​mi004). In the third passage, some mice inoculated with these strains and with strain D2586 required early euthanasia. In addition, the time between inoculation and the development of severe clinical disease requiring euthanasia decreased steadily

over the second and third passages for strains 11168, D0835, and D2600. In all passages, all mice inoculated with strain NW survived for the full duration of the experiment (data not shown). Kaplan Meier log-rank survival analysis was conducted on the data for each strain from the four isothipendyl passages, although the number of animals (25) in each data set was low. Results were significant for strain D2600 (P = 0.028) but not for strains 11168, D2586, or D0835 (P = 0.264, 0.270, and 0.201, respectively). No mice infected with strain NW required early euthanasia. Figure 4 Decrease in mouse survival in four passages during adaptation by serial passage (experiment 2). Panel A, C. jejuni 11168; panel B, C. jejuni D0835; panel C, C. jejuni D2600; panel D, C. jejuni D2586. No control mice or mice infected with strain NW required early euthanasia (data not shown). All mice in all passages experienced a dietary shift from an ~12% fat diet to an ~6% fat diet 3 to 5 days prior to inoculation with C. jejuni. Passages 1, 2, and 3 had five infected mice each for each strain; passage four had 10 infected mice. Passage 1 had four sham inoculated control mice; passages 2 and 3 had five control mice each; passage four had 10 control mice.

Thus, insertion of 5 kb of foreign sequence (i e the T-DNA eleme

Thus, insertion of 5 kb of foreign sequence (i.e. the T-DNA element) into this region should disrupt promoter activity. OSU8 and the parent WU15 strain were grown to early

stationary phase and cell-free supernatants were prepared. To determine whether Cbp1 production was impaired in OSU8, we separated supernatant proteins by poly-acrylamide gel electrophoresis and visualized the proteins by silver staining. Supernatants from the CBP1(+) WU15 strain had a prominent 9-11 kD protein which was not detected in supernatants harvested from the OSU8 culture (Trichostatin A supplier Figure 5) indicating the cbp1::T-DNA insertion disrupts production of Cbp1 protein. The identity of this protein was confirmed click here as Cbp1 since supernatant from a strain in which Cbp1 was independently depleted by RNAi also specifically lacked this protein band. Thus, while the T-DNA insertion does not interrupt the coding region, insertion into the CBP1 promoter effectively prevents

production of Cbp1 in OSU8. Figure 5 The T-DNA insertion in CBP1 prevents production of the Cbp1 protein. Culture supernatants from the cbp1::T-DNA insertion (OSU8) lack the Cbp1 protein whereas culture supernatants from CBP1(+) yeast cells (WU15) show abundant production of Cbp1. Cell-free culture supernatants were prepared from late log/early stationary phase cultures of Histoplasma yeast and the major secreted proteins separated by electrophoresis. The Cbp1 protein runs as a 9-11 kD band. Positive identification of this band as Cbp1 was determined by loss of the 9-11 kD protein band from supernatants derived selleck products from a CBP1-RNAi strain (OSU38). A strain harboring a gfp-RNAi plasmid (OSU37) was used to show specific depletion of Cbp1 by CBP1-RNAi in OSU38. The secreted 20 kD protein produced by all strains was used to normalize supernatant loadings. Conclusion We have developed a reverse HSP90 genetics procedure employing random mutagenesis and PCR-based screening techniques to identify insertion mutants in a targeted gene in Histoplasma capsulatum

without regard to a mutant phenotype. Since the mutagen creates a large insertion, the majority of mutations should reflect the knock-out mutant phenotype. However, insertions within the promoter of a gene may allow some residual transcription resulting in hypomorphic but not null phenotypes. In such cases, as demonstrated by our cbp1:T-DNA mutant, delineation of the minimal promoter of a targeted gene could resolve what type of phenotype the insertion mutation would likely produce. Thus, the regions most likely to produce mutant phenotypes are the proximal promoter and the coding region of the targeted gene. Consequently, we routinely design our PCR screening primers at the 3′ end of the gene to amplify these regions in particular and maximize the targeted site for insertions.

ATCC 33277             Increased Decreased Unchanged Not detected

ATCC 33277             Increased Decreased Unchanged Not detected Total W83   396 248 622   1266 Increased 380 242 10 124 4   Decreased 235 5 140 79 11   Unchanged 570 93 75 345 57   Not detected   56 23 74     Total 1185           The numbers of proteins showing increased, decreased or unchanged abundance in the internalized state for each analysis are given. Entries indicate the number of proteins from each category in one analysis that are assigned to the categories in the other analysis, including proteins that are

not detected in a specific analysis. Whole cell proteomics measurements of this type are noisy and the trade off between quantitative selleckchem FDR (false discovery rate) and FNR (false negative rate) is made based on the informed judgment of the analyst, and often tends to be ad hoc and Ipatasertib datasheet arbitrary in practice [9, 14]. The q-value cut-off of 0.01 used here for statistical significance SN-38 solubility dmso based on formal hypothesis testing was in good agreement with experimentally derived error distributions, as illustrated by the two pseudo M/A plots given in Additional

file 1. The present findings serve to show the value of examining trends in groups of proteins, both as an end in itself with respect to biological questions and as feedback Methamphetamine in the determination of proper cut-off values for the quantitative significance testing of individual proteins. As proteomics technology improves and it becomes economically feasible to run a greater number of independent cultures (biological replicates) than what was possible here, the

overall noise issue in any one set of measurements will be less of a concern, and it will be easier to distinguish biological noise from deficiencies with respect to analytical repeatability, and thus identify biological trends that are truly significant rather than stochastically driven. Nonetheless, as in our previous work [9] the trends identified here are consistent with what we know about the behavior of the organism under intracellular conditions [3, 9, 16]. Comparison between W83 and ATCC 33277 annotations for proteomics As expected, the new analysis identified more proteins, 1266 proteins compared to 1185 in the previous analysis (Table 1). The number of proteins with statistically significant changes between internalized and medium incubated cells also increased, from 380 proteins with increased abundance to 396 proteins and from 235 proteins with decreased abundance to 248 proteins. This was a consequence of the higher number of proteolytic fragments detected across the proteome.

These cells have diverse functions within the host including phag

These cells have diverse functions Selleck MK 8931 within the host including phagocytosis of bacterial, fungal, parasitic and viral pathogens, cytokine and chemokine biosynthesis for inflammatory mediated responses to invading pathogens as well as regulation of cellular metabolic processes including fatty acid metabolism, iron reprocessing and mineral reabsorption [9–11]. In response to certain biological triggers, monocytes or macrophages form multinucleated giant cells (MNGCs), which

involves the fusion of adjacent cells and results in a multinucleated cell with a single cytoplasmic compartment [12]. MNGCs are a well characterized phenotype in tissue granuloma formation in response to bacterial infection, with the most notable being associated with Mycobacterium tuberculosis (Mtb). Using various animal, human, in vitro cell culture and explant tissue models of Mtb infection it has been demonstrated click here that monocytes develop into various MNGC types, which is essential in the confinement of Mtb within infectious granulomas [13–20]. Likewise,

monocyte and macrophage MNGC formation can be induced in vitro using various conditioned mediums containing exogenous cytokines, lectin, phorbol myristate acetate and even select antibodies [21–32]. The most notable cytokines associated with monocyte and macrophage differentiation into MNGCs are Interleukin-4 (IL-4) and Interferon gamma (IFN-γ). However, recent reports have also demonstrated that MNGC formation is dependent on diverse range of cellular proteins including CD36, TREM-2, E-cadherin, CCL2 TPCA-1 cost and Rac1, MMP9, DC-STAMP, E-cadherin and Syk; all of which are involved in intracellular signaling, cell surface communication, proteolysis, chemotaxis and cellular

transcription [28, 33–43]. A unique phenotypic characteristic of Bp infection, in addition to Burkholderia mallei (Bm) and Burkholderia thailandensis (Bt), is the ability to induce host cell Interleukin-3 receptor MNGC formation following cellular uptake, in both tissue culture cells (i.e. murine macrophages) and in primary human cells (patients with active melioidosis) [44–47]. MNGC formation has been demonstrated in both phagocytic and non-phagocytic cells in addition to patient tissue(s) with active melioidosis [46–54]. The importance of Bp-mediated MNGC formation during infection is currently unknown, but it is possible that cell to cell spread via MNGC allows the pathogen to avoid immune surveillance in vivo. The Bp genome encodes a diverse range of specialized protein secretion systems including three type III secretion systems (T3SS) and six type VI secretion systems (T6SS) [1, 55, 56]. Mutation of the Bp T3SS-3, which is homologous to the Shigella Mxi-Spa and Salmonella SPI-1 T3SSs, results in loss of Bp induced MNGC formation, inability of endosomal escape and loss of virulence in animal models of Bp infection [50, 53, 57].

Figure 3 Effects of TGF-β1 on expression of collagen III and fibr

Figure 3 Effects of TGF-β1 on expression of collagen III and fibronectin mRNA in HPMCs. Serum-starved HPMCs were incubated with TGF-β1 (2 or 10 ng/ml) for up to 72 h and RNA was then

isolated and subjected to semi-quantitative RT-PCR analysis of collagen III (A) and fibronectin (B). Expression of β-actin was used as a loading control. Figure 4 Western blot analysis of collagen III and fibronectin protein levels in HPMCs with or without TGF-β1 treatment. Serum-starved HPMCs were incubated with increasing concentrations of TGF-β1 for up to 72 h and total learn more cellular protein was extracted and subjected to western blot analysis. A, Dose response of collagen III expression. B, Time course of collagen III expression. C, Dose response of fibronectin expression. D, Time course of fibronectin expression. Figure 5 Confocal immunofluorescence of fibronectin expression in mesothelial cells. Serum-starved Tucidinostat chemical structure HPMCs were incubated with TGF-β1 for up to 72 h, and fixed mTOR inhibitor for immunostaining with a polyclonal antibody against fibronectin. Fibronectin was visualized by FITC (green), and nuclei were visualized by To-PRO-3 (blue) under immunofluorescence confocal microscopy.

A, Control cells. B, Mesothelial cells treated with TGF-β1 (5 ng/ml) for 72 h. All photos were obtained at 100× magnification. TGF-β1 induction of Smad 2 and 3 phosphorylation in HPMCs To determine how TGF-β1 regulates collagen III and fibronectin expression, we treated HPMCs with 5 ng/ml of TGF-β1; subsequent western blot analysis showed that TGF-β1 induced phosphorylation

of Smad 2 and 3 starting at 10 min post-treatment and reached a maximum between 30-60 min, but TGF-β1 did not affect the total Smad 2 and 3 expression levels (Figure 6). Figure 6 Effects of TGF-β1 on Smad 2 and 3 phosphorylation in the mesothelial cells. The MycoClean Mycoplasma Removal Kit HPMCs were grown in serum-free medium with or without 5 ng/mL TGF-β1 treatment for up to 24 h. Total cellular protein was then extracted and subjected to Western blot analysis. A, Expression of phosphorylated Smad 2 protein. B, Expression of phosphorylated Smad 3 protein. C, Total Smad 2/3 protein. Induction of gastric cancer cell adhesion to the mesothelial cells through peritoneal fibrosis We then assessed the role of peritoneal fibrosis and RGD (Arg-Gly-Asp sequences) in regulating the adhesion ability of gastric cancer cells to mesothelial cells. Through fluorescently examining the level of tumor cells adhering to mesothelial cells in response to TGF-β1 treatment, we found that peritoneal fibrosis appeared to be able to promote gastric cancer cell adherence to mesothelial cells in a TGF-β1 dose-dependent manner, as compared to the control (p < 0.05). RGD decreased the number of cancer cells to adhere to the mesothelial cells under TGF-β1 stimulation (Figure 7). The data on cancer cells obtained from ascites or no-ascites also showed similar results. Figure 7 Effects of TGF-β1 and RGD on adhesion of gastric cancer cells to mesothelial cells.

After that, the AsH3 flow was removed from the chamber, while TMS

After that, the AsH3 flow was removed from the chamber, while TMSb (6.75×10−5) and TMIn (4.5×10−6) flows were simultaneously introduced into the reactor chamber to initiate the growth of InSb NWs. The

InSb NWs were grown for 40 min and then cooled down with the protection of only hydrogen flow (TMIn and TMSb flows were removed from the reactor chamber during cooling). For comparison, InSb layers were also grown directly on Si (111) under the same growth conditions but without InAs seed layer. The morphology of InSb structures was characterized with field-emission scanning electron microscopy (FE-SEM; JSM-6700 F, JEOL, Akishima-shi, Japan)and transmission electron microscopy (TEM; Tecnai G20, 200 keV, FEI, Hillsboro, OR, USA). Raman scattering measurements were performed in a backscattering geometry at room temperature with a Jobin Yvon HR800 confocal micro-Raman spectrometer (HORIBA, #TGF-beta inhibitor randurls[1|1|,|CHEM1|]# LY3023414 datasheet Kyoto, Japan), in which a 514.5-nm line of an Ar-ion laser was used as the excitation source with the focus size around 1 μm and excitation power of 0.5 mW. Results and discussion Figure 1 shows the SEM images of InSb structures with and without InAs seed layer. Clearly, InSb NWs are formed in the sample

with InAs seed layer, while no InSb NWs are observed in the sample without InAs seed layer. For the latter case, as shown in Figure 1b, only particle-like morphology is observed, instead of NWs. This indicates that InAs seed layer plays an important role in growing InSb NWs. Epitaxial growth of InSb is not trivial due to its large lattice constant (a 0 =

0.648 nm) compared to other III-V-semiconductor materials. As reported in our previous work [11], vertical InAs NWs can be directly heteroepitaxially grown on Si substrates at about 550°C (Additional file 1: Figure S1 and Additional file 2: Figure S2). Therefore, the InAs seed layer deposited at 550°C can form InAs NWs, which provide a template for the subsequent growth very of InSb NWs. With the growth temperature being reduced to 440°C, TMIn and TMSb are introduced into the reactor chamber, and the InSb growth is initiated on the template provided by the InAs seed layer, which facilitates the formation of InSb NWs. This growth mechanism is confirmed by the chemical composition distribution along the InSb NWs, which will be discussed later. It should be noted that the parasitic growth of non-wire-like InSb material is also observed in the form of InSb structures with non-well-developed crystal faces [12]. All vertical InSb NWs are grown along the (111) direction perpendicular to Si substrate, as shown in Figure 1a. Figure 1 SEM images of InSb NWs grown on Si substrate. SEM image of the InSb NWs grown with (a) and without (b) InAs-seed-layer (tilt 45°); (c) side view of the InSb NWs showing a clear metallic droplet on their top.

Thus, the hole width does not depend on the HB mechanism, as long

Thus, the hole width does not depend on the HB mechanism, as long as the latter takes place at a time scale much larger than the dynamic process under study (Creemers et al. 1997; Koedijk et al. 1996). Experimental methods A hole-burning (HB) experiment consists of three steps, AZD0156 datasheet schematically shown in Fig. 2: Apoptosis Compound Library (1) the laser is scanned with low light intensity for a time t p over the wavelength range of interest to generate a baseline

in the absorption band; (2) a hole is burnt at a fixed wavelength for a time t b with a much higher laser intensity (typically a factor of 10–103); (3) the hole is probed for a time t p by scanning the laser with low intensity as in step (1). To obtain the hole profile, the difference CA3 is taken between the

signals in steps (1) and (3). To study spectral holes as a function of time (spectral diffusion), the delay time t d is varied. Every new hole is then burnt at a slightly different wavelength in a spectral region outside of the previous scan region (Creemers and Völker 2000; Den Hartog et al. 1999b; Völker 1989a, b). Fig. 2 Pulse sequence used in time-resolved hole-burning (HB) experiments. Top: Timing of the laser pulses with t p: probe time, t b: burn time and t d: delay time. Bottom: Frequency ramp and steps with Δν: change in laser frequency (Den Hartog et al. 1999b) Experimental set-up for continuous-wave hole burning The experimental set-up used in our laboratory to perform CW hole-burning experiments is depicted in Fig. 3a. A single-frequency,

CW titanium:sapphire ring laser (bandwidth ~0.5 MHz, tunable from ~700 to 1,000 nm) or a dye laser (bandwidth ~1 MHz, tunable between ~550 and 700 nm), both pumped by an Ar+ laser (2–15 W), is used. The intensity of the laser light is stabilized with a feedback loop consisting of an electro-optic modulator (EOM), a photodiode (PD) and control circuitry for Light-Intensity Stabilization (LIS). The wavelength of the laser is calibrated with a wavemeter (resolution Δλ/λ ~ 10−7) ADAMTS5 and the mode structure of the laser is monitored with a confocal Fabry–Perot (FP) etalon (free spectral range, FSR = 300 MHz, 1.5 GHz or 8 GHz). Burning power densities P/A (P is the power of the laser, and A is the area of the laser beam on the sample) between ~1 μW/cm2 and a few 100 μW/cm2, with burning times t b from ~5 to ~100 s, are generally used. Fig. 3 Top: a Set-up for CW hole burning. Either a CW (continuous wave), single-frequency titanium-sapphire (bandwidth 0.5 MHz) or a dye laser (bandwidth 1–2 MHz) was used.

Acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML),

Acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and non-Hodgkin Lymphoma (NHL) are common cancer in children and teenagers [1]. Current treatment approaches

are tailored according to the clinical characteristics of the host, genotype of the blasts, and early response to therapy [2]. Although these approaches have been successfully used in improving the outcome, several children with high risk acute leukemia and stage IV NHL still relapse. Cell drug resistance and cell-signaling pathways could be involved as important determinants of chemotherapy failure [3]. Programmed cell death, or apoptosis, has emerged as a common mechanism by which cells respond to cytotoxic drugs. However, the signaling mechanisms that mediate drug-induced apoptosis are still widely unknown. Mitogen-activated protein kinase (MAPK) signaling cascades trigger stimulus-specific responses in cells: in fact, Selleck Pitavastatin selleckchem ERK is associated to proliferation and differentiation of hematopoietic cells while C-Jun N-terminal kinases (JNKs) are involved in stress-induced apoptosis and are associated to T cell activation [4]. A recent study showed that the JNK inhibition, in T-cell and Hepatocellular

carcinoma cell lines, induces anti-tumor activity by JNK-IN-8 ic50 growth arrest and CD95-mediated apoptosis through a transcription-independent mechanism [5]. Upregulation of the Ras/Raf/Mek/Erk pathways and phosphorylation of the downstream target are frequently observed in adult ALL and AML specimens and are associated to worse prognosis. In addition, it has been reported that Erk1 activation may represent an independent prognostic factor for achievement of complete remission in ALL and AML patients [6, 7]. Another crucial cell mechanism involved in leukemogenesis

is an alterate DNA repair and cell cycle arrest. Gadd45 is one of several growth arrest, apoptosis and DNA-damage-inducible genes. Interestingly, recent reports have suggested that GADD45a and b proteins also function Protein tyrosine phosphatase in hematopoietic cell survival against genotoxic stress, in apparent contradiction to the role that GADD45 proteins family plays in apoptosis of epithelial and endothelial cells [8]. These data indicated that, conversely to the pro-apoptotic function of GADD45, in hematopoietic cells both Gadd45a and Gadd45b genes play a survival role. Induction of Gadd45 genes at the onset of myeloid differentiation suggested that Gadd45a protein plays a role in hematopoiesis [9]. Altered expression and activity of different components of the apoptotic pathway, including receptors, ligands, adaptors, and caspases, can contribute to malfunction of the apoptotic machinery and, ultimately, to a more malignant phenotype. The ability of cytotoxic agents to trigger caspase activation appears to be a crucial determinant of drug response [10, 11].