156 research outputs found
An improved lower bound for (1,<=2)-identifying codes in the king grid
We call a subset of vertices of a graph a -identifying
code if for all subsets of vertices with size at most , the sets
are distinct. The concept of
identifying codes was introduced in 1998 by Karpovsky, Chakrabarty and Levitin.
Identifying codes have been studied in various grids. In particular, it has
been shown that there exists a -identifying code in the king grid
with density 3/7 and that there are no such identifying codes with density
smaller than 5/12. Using a suitable frame and a discharging procedure, we
improve the lower bound by showing that any -identifying code of
the king grid has density at least 47/111
SIRT6 Promotes Hepatic Beta-Oxidation via Activation of PPARΞ±
The pro-longevity enzyme SIRT6 regulates various metabolic pathways. Gene expression analyses in SIRT6 heterozygotic mice identify significant decreases in PPARΞ± signaling, known to regulate multiple metabolic pathways. SIRT6 binds PPARΞ± and its response element within promoter regions and activates gene transcription. Sirt6+/β results in significantly reduced PPARΞ±-induced Ξ²-oxidation and its metabolites and reduced alanine and lactate levels, while inducing pyruvate oxidation. Reciprocally, starved SIRT6 transgenic mice show increased pyruvate, acetylcarnitine, and glycerol levels and significantly induce Ξ²-oxidation genes in a PPARΞ±-dependent manner. Furthermore, SIRT6 mediates PPARΞ± inhibition of SREBP-dependent cholesterol and triglyceride synthesis. Mechanistically, SIRT6 binds PPARΞ± coactivator NCOA2 and decreases liver NCOA2 K780 acetylation, which stimulates its activation of PPARΞ± in a SIRT6-dependent manner. These coordinated SIRT6 activities lead to regulation of whole-body respiratory exchange ratio and liver fat content, revealing the interactions whereby SIRT6 synchronizes various metabolic pathways, and suggest a mechanism by which SIRT6 maintains healthy liver
The Involvement of IL-17A in the Murine Response to Sub-Lethal Inhalational Infection with Francisella tularensis
Background: Francisella tularensis is an intercellular bacterium often causing fatal disease when inhaled. Previous reports have underlined the role of cell-mediated immunity and IFNc in the host response to Francisella tularensis infection. Methodology/Principal Findings: Here we provide evidence for the involvement of IL-17A in host defense to inhalational tularemia, using a mouse model of intranasal infection with the Live Vaccine Strain (LVS). We demonstrate the kinetics of IL-17A production in lavage fluids of infected lungs and identify the IL-17A-producing lymphocytes as pulmonary cd and Th17 cells. The peak of IL-17A production appears early during sub-lethal infection, it precedes the peak of immune activation and the nadir of the disease, and then subsides subsequently. Exogenous airway administration of IL-17A or of IL-23 had a limited yet consistent effect of delaying the onset of death from a lethal dose of LVS, implying that IL-17A may be involved in restraining the infection. The protective role for IL-17A was directly demonstrated by in vivo neutralization of IL-17A. Administration of anti IL-17A antibodies concomitantly to a sub-lethal airway infection with 0.16LD50 resulted in a fatal disease. Conclusion: In summary, these data characterize the involvement and underline the protective key role of the IL-17A axis in the lungs from inhalational tularemia
Dietary Restriction: Standing Up For Sirtuins
We believe that L. Fontana, L. Partridge, and V. D. Longo should have included a
discussion of sirtuins in their Review βExtending healthy life spanβFrom yeast to humansβ
(16 April, p. 321). We also believe that some of the references used are misleading.
The authors state that the purpose of their Review is to βconsider the role of nutrient-sensing
signaling pathways in mediating the beneficial effects of dietary restriction.β Yet there was
no mention of the sirtuins, a family of critically important nutrient-sensing proteins that
promote health span from yeast to mammals, as shown by more than 1000 peer-reviewed
publications from labs around the world. The authors state that β[i]t is unlikely that a single,
linear pathway mediates the effects of dietary restriction in any organism,β and we agree.
Indeed, the aging field now recognizes that healthy life span is under the influence of several
nutrient-sensing pathways, and there is at least as much evidence for the involvement of
sirtuins in the dietary restriction response as for any of the pathways discussed in the Review
The relationship between early neural responses to emotional faces at age 3 and later autism and anxiety symptoms in adolescents with autism
Both autism spectrum (ASD) and anxiety disorders are associated with atypical neural and attentional responses to emotional faces, differing in affective face processing from typically developing peers. Within a longitudinal study of children with ASD (23 male, 3 female), we hypothesized that early ERPs to emotional faces would predict concurrent and later ASD and anxiety symptoms. Greater response amplitude to fearful faces corresponded to greater social communication difficulties at age 3, and less improvement by age 14. Faster ERPs to neutral faces predicted greater ASD symptom improvement over time, lower ASD severity in adolescence, and lower anxiety in adolescence. Early individual differences in processing of emotional stimuli likely reflect a unique predictive contribution from social brain circuitry early in life
The Impact of Worry on Attention to Threat
Prior research has often linked anxiety to attentional vigilance for threat using the dot probe task, which presents probes in spatial locations that were or were not preceded by a putative threat stimulus. The present study investigated the impact of worry on threat vigilance by administering this task during a worry condition and during a mental arithmetic control condition to 56 undergraduate students scoring in the low normal range on a measure of chronic worry. The worry induction was associated with faster responses than arithmetic to probes in the attended location following threat words, indicating the combined influence of worry and threat in facilitating attention. Within the worry condition, responses to probes in the attended location were faster for trials containing threat words than for trials with only neutral words, whereas the converse pattern was observed for responses to probes in the unattended location. This connection between worry states and attentional capture by threat may be central to understanding the impact of hypervigilance on information processing in anxiety and its disorders
Cues for Early Social Skills: Direct Gaze Modulates Newborns' Recognition of Talking Faces
Previous studies showed that, from birth, speech and eye gaze are two important
cues in guiding early face processing and social cognition. These studies tested
the role of each cue independently; however, infants normally perceive speech
and eye gaze together. Using a familiarization-test procedure, we first
familiarized newborn infants (nβ=β24) with videos of
unfamiliar talking faces with either direct gaze or averted gaze. Newborns were
then tested with photographs of the previously seen face and of a new one. The
newborns looked longer at the face that previously talked to them, but only in
the direct gaze condition. These results highlight the importance of both speech
and eye gaze as socio-communicative cues by which infants identify others. They
suggest that gaze and infant-directed speech, experienced together, are powerful
cues for the development of early social skills
Do faces capture the attention of individuals with Williams syndrome or Autism? Evidence from tracking eye movements
The neuro-developmental disorders of Williams syndrome (WS) and autism can reveal key components of social cognition. Eyeβtracking techniques were applied in two tasks exploring attention to pictures containing faces. Images were i) scrambled pictures containing faces or ii) pictures of scenes with embedded faces. Compared to individuals who were developing typically, participants with WS and autism showed atypicalities of gaze behaviour. Individuals with WS showed prolonged face gaze across tasks, relating to the typical WS social phenotype. Participants with autism exhibited reduced face gaze, linking to a lack of interest in socially relevant information. The findings are interpreted in terms of wider issues regarding socioβcognition and attention mechanisms
Predicting In Vivo Efficacy of Potential Restenosis Therapies by Cell Culture Studies: Species-Dependent Susceptibility of Vascular Smooth Muscle Cells
Although drug-eluting stents (DES) are successfully utilized for restenosis therapy, the development of local and systemic therapeutic means including nanoparticles (NP) continues. Lack of correlation between in vitro and in vivo studies is one of the major drawbacks in developing new drug delivery systems. The present study was designed to examine the applicability of the arterial explant outgrowth model, and of smooth muscle cells (SMC) cultures for prescreening of possible drugs. Elucidation of different species sensitivity (rat, rabbit, porcine and human) to diverse drugs (tyrphostins, heparin and bisphsophonates) and a delivery system (nanoparticles) could provide a valuable screening tool for further in vivo studies. The anticipated sensitivity ranking from the explant outgrowth model and SMC mitotic rates (porcine>rat>>rabbit>human) do not correlate with the observed relative sensitivity of those animals to antiproliferative therapy in restenosis models (ratβ₯rabbit>porcine>human). Similarly, the inhibitory profile of the various antirestenotic drugs in SMC cultures (rabbit>porcine>rat>>human) do not correlate with animal studies, the rabbit- and porcine-derived SMC being highly sensitive. The validity of in vitro culture studies for the screening of controlled release delivery systems such as nanoparticles is limited. It is suggested that prescreening studies of possible drug candidates for restenosis therapy should include both SMC cell cultures of rat and human, appropriately designed with a suitable serum
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