Publications by authors named "Pedro Bonilla"

The KRAS gene plays a pivotal role in numerous cancers by encoding a GTPase that upon association with the plasma membrane activates the MAPK pathway, promoting cellular proliferation. In our study, we investigated small molecules that disrupt KRAS's membrane interaction, hypothesizing that such disruption could in turn inhibit mutant RAS signaling. Native mass spectrometry screening of KRAS-FMe identified compounds with a preference for interacting with the hypervariable region (HVR), and surface plasmon resonance (SPR) further refined our selection to graveoline as a compound exhibiting preferential HVR binding.

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Fluorescence lifetime imaging performed under FRET conditions between two interacting molecules is a sensitive and robust way to quantify intermolecular interactions in cells. The fluorescence lifetime, an inherent property of the fluorophore, remains unaffected by factors such as concentration, laser intensity, and other photophysical artifacts. In the context of FLIM-FRET, the focus lies on measuring the fluorescence lifetime of the donor molecule, which diminishes upon interaction with a neighboring acceptor molecule.

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Article Synopsis
  • The N-terminal domain of STAT3 is a potential target for cancer therapy and immune response modulation, but it's hard to reach with therapeutic antibodies since STAT3 is found in different cell compartments.
  • This domain is considered "non-druggable" due to its surface structure lacking deep pockets for binding.
  • The study used advanced virtual screening methods on massive compound libraries to identify potential inhibitors, indicating that broader chemical libraries can aid in creating drugs for challenging intracellular targets.
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Objective: The authors present what is to their knowledge the first description of a model for longitudinal third-year medical student psychiatry education.

Method: A longitudinal, integrated psychiatric curriculum was developed, implemented, and sustained within the Harvard Medical School-Cambridge Integrated Clerkship. Curriculum elements include longitudinal mentoring by attending physicians in an outpatient psychiatry clinic, exposure to the major psychotherapies, psychopharmacology training, acute psychiatry "immersion" experiences, and a variety of clinical and didactic teaching sessions.

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This article reviews the principles and skills involved with psychosomatic medicine and their potential ability to improve global health care. New awareness of the escalating global public health impact of noncommunicable diseases, including chronic medical conditions and mental disorders, has stimulated interest in determining how best to organize health services. Home to the biopsychosocial model, the field of psychosomatic medicine is well-suited to inform such efforts by virtue of its emphasis on cross-disciplinary collaboration and specialized knowledge at the interface of medicine and psychiatry that takes into account individual and contextual influences on health.

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