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Spatial restriction of alpha4 integrin phosphorylation regulates lamellipodial stability and alpha4beta1-dependent cell migration.
Integrins coordinate spatial signaling events essential for cell polarity and directed migration. Such signals from alpha4 integrins regulate cell migration in development and in leukocyte trafficking. Here, we report that efficient alpha4-mediated migration requires spatial control of alpha4 phosphorylation by protein kinase A, and hence localized inhibition of binding of the signaling adaptor, paxillin, to the integrin. In migrating cells, phosphorylated alpha4 accumulated along the leading edge. Blocking alpha4 phosphorylation by mutagenesis or by inhibition of protein kinase A drastically reduced alpha4-dependent migration and lamellipodial stability. alpha4 phosphorylation blocks paxillin binding in vitro; we now find that paxillin and phospho-alpha4 were in distinct clusters at the leading edge of migrating cells, whereas unphosphorylated alpha4 and paxillin colocalized along the lateral edges of those cells. Furthermore, enforced paxillin association with alpha4 inhibits migration and reduced lamellipodial stability. These results show that topographically specific integrin phosphorylation can control cell migration and polarization by spatial segregation of adaptor protein binding
Book Reviews
Reviews of the following books: Hardliners: A History of the Emery-Waterhouse Company by Edgar Allen Beem and Charles L. Hildreth, Jr.; L.L. Bean: The Making of an American Icon by Leon Gorman; Eminent Mainers: Succinct Biographies of Thousands of Amazing Mainers, Mostly Dead and a Few People from Away Who Have Done Something Useful Within the State Maine; Compiled by Arthur Douglas Stover and Maine: Downeast and Different: An Illustrated History by Neil Rolde; ; The Rangeley and Its Region: The Famous Boat and Lakes of Western Maine by Stephen A. Cole; Voyages: A Maine Franco-American Reader, edited by Nelson Madore and Barry Rodrigu
Spatial restriction of α4 integrin phosphorylation regulates lamellipodial stability and α4ÎČ1-dependent cell migration
Ăntegrins coordinate spatial signaling events essential for cell polarity and directed migration. Such signals from α4 integrins regulate cell migration in development and in leukocyte trafficking. Here, we report that efficient α4-mediated migration requires spatial control of α4 phosphorylation by protein kinase A, and hence localized inhibition of binding of the signaling adaptor, paxillin, to the integrin. In migrating cells, phosphorylated α4 accumulated along the leading edge. Blocking α4 phosphorylation by mutagenesis or by inhibition of protein kinase A drastically reduced α4-dependent migration and lamellipodial stability. α4 phosphorylation blocks paxillin binding in vitro; we now find that paxillin and phospho-α4 were in distinct clusters at the leading edge of migrating cells, whereas unphosphorylated α4 and paxillin colocalized along the lateral edges of those cells. Furthermore, enforced paxillin association with α4 inhibits migration and reduced lamellipodial stability. These results show that topographically specific integrin phosphorylation can control cell migration and polarization by spatial segregation of adaptor protein binding
Preventing farm land price inflation in the midwest
Both a recollection of the disastrous consequences of the inflationary land prices following World War I and recognition o f the possibility of a recurrence have stimulated public interest in information about the current farm real estate situation. This report has been prepared by the North Central Regional Land Tenure Committee for the purpose of presenting an appraisal of the current situation, stimulating discussion of the problems, and outlining the various possible lines of action most often suggested for curbing undesirable developments.
The North Central Regional Land Tenure Committee came into existence as the result o f an informal conference sponsored by the Farm Foundation in the spring of 1939 for land economists from the agricultural experiment stations in the Midwest. As an outgrowth of this and subsequent meetings, the director of each station appointed one of his staff to the Regional Land Tenure Committee which also includes representatives from the United States Department of Agriculture.
The major function of the committee is to develop an integrated long-time program of research that will lead to the improvement of farm tenure in the region. This report pertaining to land price inflation in the Midwest is the committeeâs second formal publication. The first was entitled âImproving Farm Tenure in the Midwestâ and was published as Illinois Agricultural Experiment Station Bulletin 502. The present bulletin is based not only on reports collected from sample counties but on observation and study of the situation by at least one representative from each of the participating states. It is impractical to cite specific land market material published by the several cooperating institutions, but such information is available upon request to the participating agencies
Diminished trk A receptor signaling reveals cholinergicâattentional vulnerability of aging
The cellular mechanisms underlying the exceptional vulnerability of the basal forebrain ( BF ) cholinergic neurons during pathological aging have remained elusive. Here we employed an adenoâassociated viral vectorâbased RNA interference ( AAV â RNA i) strategy to suppress the expression of tropomyosinârelated kinase A (trk A ) receptors by cholinergic neurons in the nucleus basalis of M eynert/substantia innominata ( nMB / SI ) of adult and aged rats. Suppression of trk A receptor expression impaired attentional performance selectively in aged rats. Performance correlated with trk A levels in the nMB / SI . trk A knockdown neither affected nMB / SI cholinergic cell counts nor the decrease in cholinergic cell size observed in aged rats. However, trk A suppression augmented an ageârelated decrease in the density of cortical cholinergic processes and attenuated the capacity of cholinergic neurons to release acetylcholine ( AC h). The capacity of cortical synapses to release AC h in vivo was also lower in aged/trk A â AAV âinfused rats than in aged or young controls, and it correlated with their attentional performance. Furthermore, ageârelated increases in cortical pro NGF and p75 receptor levels interacted with the vectorâinduced loss of trk A receptors to shift NGF signaling toward p75âmediated suppression of the cholinergic phenotype, thereby attenuating cholinergic function and impairing attentional performance. These effects model the abnormal trophic regulation of cholinergic neurons and cognitive impairments in patients with early A lzheimer's disease. This rat model is useful for identifying the mechanisms rendering aging cholinergic neurons vulnerable as well as for studying the neuropathological mechanisms that are triggered by disrupted trophic signaling. The cellular mechanisms underlying the exceptional vulnerability of the basal forebrain ( BF ) cholinergic neurons during pathological aging have remained elusive. Here we employed an adenoâassociated viral vectorâbased RNA interference ( AAV â RNA i) strategy to suppress the expression of trk A receptors by cholinergic neurons in the nucleus basalis of M eynert/substantia innominata (n MB / SI ) of adult and aged rats. This study provides novel evidence that reduced trkA receptors is not sufficient to trigger cholinergic dysfunction. Rather, aging interacts with disrupted trkA signaling to escalate the vulnerability of BF cholinergic neurons and the manifestation of ageârelated attentional impairments.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96365/1/ejn12090-sup-0001-SupportingInformation.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/96365/2/ejn12090.pd
Six-dimensional Supergravity and Projective Superfields
We propose a superspace formulation of N=(1,0) conformal supergravity in six
dimensions. The corresponding superspace constraints are invariant under
super-Weyl transformations generated by a real scalar parameter. The known
variant Weyl super-multiplet is recovered by coupling the geometry to a
super-3-form tensor multiplet. Isotwistor variables are introduced and used to
define projective superfields. We formulate a locally supersymmetric and
super-Weyl invariant action principle in projective superspace. Some families
of dynamical supergravity-matter systems are presented.Comment: 39 pages; v3: some modifications in section 2; equations (2.3),
(2.14b), (2.16) and (2.17) correcte
Interview with Dr. Charles Mullins, John Howe, Dr. James Guckian, Bill Cunningham, Nancy Payne, Anne Shepard, and Bob Shepard, 2023-08-04
https://scholarworks.utrgv.edu/somhi/1060/thumbnail.jp
The Relationship Between Socioeconomic Status and CV Risk Factors: The CRONICAS Cohort Study of Peruvian Adults.
BACKGROUND: Variations in the distribution of cardiovascular disease and risk factors by socioeconomic status (SES) have been described in affluent societies, yet a better understanding of these patterns is needed for most low- and middle-income countries. OBJECTIVE: This study sought to describe the relationship between cardiovascular risk factors and SES using monthly family income, educational attainment, and assets index, in 4 Peruvian sites. METHODS: Baseline data from an age- and sex-stratified random sample of participants, ages â„35 years, from 4 Peruvian sites (CRONICAS Cohort Study, 2010) were used. The SES indicators considered were monthly family income (n = 3,220), educational attainment (n = 3,598), and assets index (n = 3,601). Behavioral risk factors included current tobacco use, alcohol drinking, physical activity, daily intake of fruits and vegetables, and no control of salt intake. Cardiometabolic risk factors included obesity, elevated waist circumference, hypertension, insulin resistance, diabetes mellitus, low high-density lipoprotein cholesterol, and high triglyceride levels. RESULTS: In the overall population, 41.6% reported a monthly family income <US$198, and 45.6% had none or primary education. Important differences were noted between the socioeconomic indicators: for example, higher income and higher scores on an asset index were associated with greater risk of obesity, whereas higher levels of education were associated with lower risk of obesity. In contrast, higher SES according to all 3 indicators was associated with higher levels of triglycerides. CONCLUSIONS: The association between SES and cardiometabolic risk factors varies depending on the SES indicator used. These results highlight the need to contextualize risk factors by socioeconomic groups in Latin American settings
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