Doxycycline alters metabolism and proliferation of human cell lines.

The tetracycline antibiotics are widely used in biomedical research as mediators of inducible gene expression systems. Despite many known effects of tetracyclines on mammalian cells-including inhibition of the mitochondrial ribosome-there have been few reports on potential off-target effects at concentrations commonly used in inducible systems. Here, we report that in human cell lines, commonly used concentrations of doxycycline change gene expression patterns and concomitantly shift metabolism towards a more glycolytic phenotype, evidenced by increased lactate secretion and reduced oxygen consumption. We also show that these concentrations are sufficient to slow proliferation. These findings suggest that researchers using doxycycline in inducible expression systems should design appropriate controls to account for potential confounding effects of the drug on cellular metabolism

Recent Decisions

Comments on recent decisions by John M. Sullivan, William G. Greif, Joseph F. MacKrell, William N. Antonis, Thomas Meaney, Jr., William J. Hurley, Joseph H. Harrison, Robert L. Berry, Robert F. McCoy, Edward Canary, Maynard R. Bissonnette, and Luke R. Morin

Ultralocality and Slow Contraction

We study the detailed process by which slow contraction smooths and flattens the universe using an improved numerical relativity code that accepts initial conditions with non-perturbative deviations from homogeneity and isotropy along two independent spatial directions. Contrary to common descriptions of the early universe, we find that the geometry first rapidly converges to an inhomogeneous, spatially-curved and anisotropic ultralocal state in which all spatial gradient contributions to the equations of motion decrease as an exponential in time to negligible values. This is followed by a second stage in which the geometry converges to a homogeneous, spatially flat and isotropic spacetime. In particular, the decay appears to follow the same history whether the entire spacetime or only parts of it are smoothed by the end of slow contraction.Comment: 27 pages, 10 figure

State Mandated Prenatal Human Immunodeficiency Virus Screening at a Large Community Hospital

Purpose: To describe the initial experience of state mandated prenatal HIV screening at a large community hospital.Methods: HIV screening was provided to all pregnant women as of October 1, 1999. All HIV-positive women identified received aggressive antiretroviral therapy to reduce the likelihood for vertical transmission. Neonates were screened for HIV at zero, six, and 12 months of age.Results: Seven pregnant women (0.3%) and two additional family members tested positive for HIV. All seven infants born to the identified HIV-positive women have tested negative for infection. We estimated that six of nine cases of HIV infection identified would have been missed under a policy of voluntary HIV screening.Conclusions: Universal screening for HIV in pregnancy is achievable and desirable and provides the best opportunity to minimize the number of new neonatal HIV infections

An analysis of sentence structure, capitalization and punctuation errors made by pupils in grades four, five, and six in free writing of sentences using given stimuli words.

Thesis (M.A.)--Boston Universit

Pioglitazone Treatment Following Spinal Cord Injury Maintains Acute Mitochondrial Integrity and Increases Chronic Tissue Sparing and Functional Recovery

Pioglitazone is an FDA-approved PPAR-γ agonist drug used to for treat diabetes, and it has demonstrated neuroprotective effects in multiple models of central nervous system (CNS) injury. Acute treatment after spinal cord injury (SCI) in rats is reported to suppress neuroinflammation, rescue injured tissues, and improve locomotor recovery. In the current study, we additionally assessed the protective efficacy of pioglitazone treatment on acute mitochondrial respiration, as well as functional and anatomical recovery after contusion SCI in adult male C57BL/6 mice. Mice received either vehicle or pioglitazone (10 mg/kg) at either 15 min or 3 hr after injury (75 kDyn at T9) followed by a booster at 24 hr post-injury. At 25 hr, mitochondria were isolated from spinal cord segments centered on the injury epicenters and assessed for their respiratory capacity. Results showed significantly compromised mitochondrial respiration 25 hr following SCI, but pioglitazone treatment that was initiated either at 15 min or 3 hr post-injury significantly maintained mitochondrial respiration rates near sham levels. A second cohort of injured mice received pioglitazone at 15 min post injury, then once a day for 5 days post-injury to assess locomotor recovery and tissue sparing over 4 weeks. Compared to vehicle, pioglitazone treatment resulted in significantly greater recovery of hind-limb function over time, as determined by serial locomotor BMS assessments and both terminal BMS subscores and gridwalk performance. Such improvements correlated with significantly increased grey and white matter tissue sparing, although pioglitazone treatment did not abrogate long-term injury-induced inflammatory microglia/macrophage responses. In sum, pioglitazone significantly increased functional neuroprotection that was associated with remarkable maintenance of acute mitochondrial bioenergetics after traumatic SCI. This sets the stage for dose-response and delayed administration studies to maximize pioglitazone’s efficacy for SCI while elucidating the precise role that mitochondria play in governing its neuroprotection; the ultimate goal to develop novel therapeutics that specifically target mitochondrial dysfunction

Differential Leukocyte and Platelet Profiles in Distinct Models of Traumatic Brain Injury

Traumatic brain injury (TBI) affects over 3 million individuals every year in the U.S. There is growing appreciation that TBI can produce systemic modifications, which are in part propagated through blood–brain barrier (BBB) dysfunction and blood–brain cell interactions. As such, platelets and leukocytes contribute to mechanisms of thromboinflammation after TBI. While these mechanisms have been investigated in experimental models of contusion brain injury, less is known regarding acute alterations following mild closed head injury. To investigate the role of platelet dynamics and bioenergetics after TBI, we employed two distinct, well-established models of TBI in mice: the controlled cortical impact (CCI) model of contusion brain injury and the closed head injury (CHI) model of mild diffuse brain injury. Hematology parameters, platelet-neutrophil aggregation, and platelet respirometry were assessed acutely after injury. CCI resulted in an early drop in blood leukocyte counts, while CHI increased blood leukocyte counts early after injury. Platelet-neutrophil aggregation was altered acutely after CCI compared to sham. Furthermore, platelet bioenergetic coupling efficiency was transiently reduced at 6 h and increased at 24 h post-CCI. After CHI, oxidative phosphorylation in intact platelets was reduced at 6 h and increased at 24 h compared to sham. Taken together, these data demonstrate that brain trauma initiates alterations in platelet-leukocyte dynamics and platelet metabolism, which may be time- and injury-dependent, providing evidence that platelets carry a peripheral signature of brain injury. The unique trend of platelet bioenergetics after two distinct types of TBI suggests the potential for utilization in prognosis

Sexual Signal Evolution Outpaces Ecological Divergence during Electric Fish Species Radiation

Natural selection arising from resource competition and environmental heterogeneity can drive adaptive radiation. Ecological opportunity facilitates this process, resulting in rapid divergence of ecological traits in many celebrated radiations. In other cases, sexual selection is thought to fuel divergence in mating signals ahead of ecological divergence. Comparing divergence rates between naturally and sexually selected traits can offer insights into processes underlying species radiations, but to date such comparisons have been largely qualitative. Here, we quantitatively compare divergence rates for four traits in African mormyrid fishes, which use an electrical communication system with few extrinsic constraints on divergence. We demonstrate rapid signal evolution in the Paramormyrops species flock compared to divergence in morphology, size, and trophic ecology. This disparity in the tempo of trait evolution suggests that sexual selection is an important early driver of species radiation in these mormyrids. We also found slight divergence in ecological traits among closely related species, consistent with a supporting role for natural selection in Paramormyrops diversification. Our results highlight the potential for sexual selection to drive explosive signal divergence when innovations in communication open new opportunities in signal space, suggesting that opportunity can catalyze species radiations through sexual selection, as well as natural selection