Non-exploitative human disturbance provides shelter for prey from predator.

Human activities can influence behaviors of predators and prey, as well as predator-prey interactions. Using camera trap data, we investigated whether or to what extent human activities influenced behaviors of predators (tigers and leopards) and prey (sambar deer, spotted deer, wild boar, and barking deer), and predator-prey interactions in the Barandabhar Corridor Forest (BCF), Chitwan District, Nepal. A multispecies occupancy model revealed that the presence of humans altered the conditional occupancy of both prey and predator species.

Direct phosphorylation of proliferative and survival pathway proteins by RET.

Background: Gain-of-function mutations in the RET tyrosine kinase receptor cause the multiple endocrine neoplasia syndromes type 2a and 2b, and medullary thyroid cancer. We have previously shown that RET signals through focal adhesion kinase (FAK) in medullary thyroid cancer cells and that extracellular signal-regulated kinase (ERK) activity can be blocked by pp2, an inhibitor of both Src and RET. We hypothesized that RET could directly phosphorylate FAK and ERK.

RET signals through focal adhesion kinase in medullary thyroid cancer cells.

Background: The RET proto-oncogene is implicated in medullary thyroid cancer (MTC) and has been shown to signal indirectly to focal adhesion kinase (FAK) in cell types other than MTC. We have previously shown that FAK is phosphorylated in MTC cells. We hypothesized that inhibition of RET with pharmacologic inhibitors or by depletion with siRNA would decrease FAK phosphorylation in MTC cells, thereby implicating a RET-FAK signaling pathway.

Circumvention of nuclear factor kappaB-induced chemoresistance by cytoplasmic-targeted anthracyclines.

Nuclear factor kappaB (NF-kappaB) has been implicated in inducible chemoresistance against anthracyclines. In an effort to improve the cytotoxicity of anthracyclines while reducing their cardiotoxic effects, we have developed a novel class of extranuclear-localizing 14-O-acylanthracyclines that bind to the phorbol ester/diacylglycerol-binding C1b domain of conventional and novel protein kinase C (PKC) isoforms, thereby promoting an apoptotic response. Because PKCs have been shown to be involved in NF-kappaB activation, in this report, we determined the mechanism of NF-kappaB activation by N-benzyladriamycin-14-valerate (AD 198) and N-benzyladriamycin-14-pivalate (AD 445), two novel 14-O-acylanthracylines.

ATM and the catalytic subunit of DNA-dependent protein kinase activate NF-kappaB through a common MEK/extracellular signal-regulated kinase/p90(rsk) signaling pathway in response to distinct forms of DNA damage.

We have identified a novel pathway of ataxia telangiectasia mutated (ATM) and DNA-dependent protein kinase (DNA-PK) signaling that results in nuclear factor kappaB (NF-kappaB) activation and chemoresistance in response to DNA damage. We show that the anthracycline doxorubicin (DOX) and its congener N-benzyladriamycin (AD 288) selectively activate ATM and DNA-PK, respectively. Both ATM and DNA-PK promote sequential activation of the mitogen-activated protein kinase (MAPK)/p90(rsk) signaling cascade in a p53-independent fashion.

Inhibition of CK2 activity by TGF-beta1 promotes IkappaB-alpha protein stabilization and apoptosis of immortalized hepatocytes.

Nuclear factor kappaB (NF-kappaB) is an antiapoptotic factor involved in development, regeneration, and neoplastic progression of the liver. Previously, we have shown that stabilization of inhibitor kappaB (IkappaB)-alpha protein following treatment of hepatocytes with transforming growth factor (TGF)-beta1 promoted NF-kappaB repression, which then permitted induction of AP-1/SMAD-mediated liver cell death. Because basal IkappaB-alpha protein turnover is regulated by protein kinase CK2, here we have elucidated the regulation of CK2 kinase activity and its role in control of NF-kappaB levels following treatment with TGF-beta1.

Transient activation of NF-kappaB through a TAK1/IKK kinase pathway by TGF-beta1 inhibits AP-1/SMAD signaling and apoptosis: implications in liver tumor formation.

NF-kappaB has been implicated in the regulation of apoptosis, a key mechanism of normal and malignant growth control. Previously, we demonstrated that inhibition of NF-kappaB activity by TGF-beta1 leads directly to induction of apoptosis of murine B-cell lymphomas and hepatocytes. Thus, we were surprised to determine that NF-kappaB is transiently activated in response to TGF-beta1 treatment.