Evidence for similar changes in offspring phenotype following either maternal undernutrition or overnutrition: potential impact on fetal epigenetic mechanisms

2012 ◽  
Vol 24 (1) ◽  
pp. 105 ◽  
Author(s):  
S. P. Ford ◽  
N. M. Long

The goal of this review is to shed light on the role of maternal malnutrition in inducing epigenetic changes in gene expression, leading to alterations in fetal growth and development, and to altered postnatal phenotype and the development of metabolic disease. We present evidence supporting the concept that both maternal undernutrition and overnutrition can induce the same cadre of fetal organ and tissue abnormalities and lead to the same postnatal metabolic changes in the resulting offspring. Furthermore, we present evidence that in both overnourished and undernourished ovine pregnancies, fetuses experience a period of nutrient restriction as a result of alterations in placental delivery of maternal nutrients into the fetal compartment. We argue that this bout of reduced fetal nutrition in undernourished and overnourished pregnancies leads to the development of a thrifty phenotype in which the fetus attempts to alter the function of its tissues and organs to maximise its chances of survival in a postnatal environment that is deficient in nutrients. Importantly, we present evidence to support the concept that these phenotypic changes in offspring quality resulting from maternal malnutrition are transmitted to subsequent generations, independent of their maternal nutritional inputs.

2018 ◽  
Author(s):  
Brett Buttliere

Over the last decade, there have been many suggestions to improve how scientists answer their questions, but far fewer attempt to improve the questions scientists are asking in the first place. The goal of the paper is then to examine and summarize synthesize the evidence on how to ask the best questions possible. First is a brief review of the philosophical and empirical literature on how the best science is done, which implicitly but not explicitly mentions the role of psychology and especially cognitive conflict. Then we more closely focus on the psychology of the scientist, finding that they are humans, engaged in a meaning making process, and that cognitive conflict is a necessary input for any learning or change in the system. The scientific method is, of course, a specialized meaning making process. We present evidence for this central role of cognitive conflict in science by examining the most discussed scientific papers between 2013 and 2017, which are, in general, controversial and about big problems (e.g., whether vaccines cause autism, how often doctors kill us with their mistakes). Toward the end we discuss the role of science in society, suggesting science itself is an uncertainty reducing and problem solving enterprise. From this basis we encourage scientists to take riskier stances on bigger topics, for the good of themselves and society generally.


Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 663
Author(s):  
Yu Yuan ◽  
Abdalla Adam ◽  
Chen Zhao ◽  
Honglei Chen

Release of immunoreactive negative regulatory factors such as immune checkpoint limits antitumor responses. PD-L1 as a significant immunosuppressive factor has been involved in resistance to therapies such as chemotherapy and target therapy in various cancers. Via interacting with PD-1, PD-L1 can regulate other factors or lead to immune evasion of cancer cells. Besides, immune checkpoint blockade targeting PD-1/PD-L1 has promising therapeutic efficacy in the different tumors, but a significant percentage of patients cannot benefit from this therapy due to primary and acquired resistance during treatment. In this review, we described the utility of PD-L1 expression levels for predicting poor prognosis in some tumors and present evidence for a role of PD-L1 in resistance to therapies through PD-1/PD-L1 pathway and other correlating signaling pathways. Afterwards, we elaborate the key mechanisms underlying resistance to PD-1/PD-L1 blockade in cancer immunotherapy. Furthermore, promising combination of therapeutic strategies for patients resistant to PD-1/PD-L1 blockade therapy or other therapies associated with PD-L1 expression was also summarized.


2008 ◽  
Vol 294 (3) ◽  
pp. H1183-H1187 ◽  
Author(s):  
Kristen M. Park ◽  
Mario Trucillo ◽  
Nicolas Serban ◽  
Richard A. Cohen ◽  
Victoria M. Bolotina

Store-operated channels (SOC) and store-operated Ca2+ entry are known to play a major role in agonist-induced constriction of smooth muscle cells (SMC) in conduit vessels. In microvessels the role of SOC remains uncertain, in as much as voltage-gated L-type Ca2+ (CaL2+) channels are thought to be fully responsible for agonist-induced Ca2+ influx and vasoconstriction. We present evidence that SOC and their activation via a Ca2+-independent phospholipase A2 (iPLA2)-mediated pathway play a crucial role in agonist-induced constriction of cerebral, mesenteric, and carotid arteries. Intracellular Ca2+ in SMC and intraluminal diameter were measured simultaneously in intact pressurized vessels in vitro. We demonstrated that 1) Ca2+ and contractile responses to phenylephrine (PE) in cerebral and carotid arteries were equally abolished by nimodipine (a CaL2+ inhibitor) and 2-aminoethyl diphenylborinate (an inhibitor of SOC), suggesting that SOC and CaL2+ channels may be involved in agonist-induced constriction of cerebral arteries, and 2) functional inhibition of iPLA2β totally inhibited PE-induced Ca2+ influx and constriction in cerebral, mesenteric, and carotid arteries, whereas K+-induced Ca2+ influx and vasoconstriction mediated by CaL2+ channels were not affected. Thus iPLA2-dependent activation of SOC is crucial for agonist-induced Ca2+ influx and vasoconstriction in cerebral, mesenteric, and carotid arteries. We propose that, on PE-induced depletion of Ca2+ stores, nonselective SOC are activated via an iPLA2-dependent pathway and may produce a depolarization of SMC, which could trigger a secondary activation of CaL2+ channels and lead to Ca2+ entry and vasoconstriction.


2014 ◽  
Vol 56 (3) ◽  
pp. 681-713 ◽  
Author(s):  
Katherine Bowie

AbstractDespite a growing literature revealing the presence of millenarian movements in both Theravada and Mahayana Buddhist societies, scholars have been remarkably reluctant to consider the role of messianic beliefs in Buddhist societies. Khruubaa Srivichai (1878–1938) is the most famous monk of northern Thailand and is widely revered as atonbun, or saint. Althoughtonbunhas been depoliticized in the modern context, the term also refers to a savior who is an incarnation of the coming Maitreya Buddha. In 1920 Srivichai was sent under arrest to the capital city of Bangkok to face eight charges. This essay focuses on the charge that he claimed to possess the god Indra's sword. Although this charge has been widely ignored, it was in fact a charge of treason. In this essay, I argue that the treason charge should be understood within the context of Buddhist millenarianism. I note the saint/savior tropes in Srivichai's mytho-biography, describe the prevalence of millenarianism in the region, and detail the political economy of the decade of the 1910s prior to Srivichai's detention. I present evidence to show that the decade was characterized by famine, dislocation, disease, and other disasters of both natural and social causes. Such hardships would have been consistent with apocalyptic omens in the Buddhist repertoire portending the advent of Maitreya. Understanding Srivichai in this millenarian context helps to explain both the hopes of the populace and the fears of the state during that tumultuous decade.


e-Neuroforum ◽  
2013 ◽  
Vol 19 (3) ◽  
Author(s):  
N. Sachser ◽  
K.-P. Lesch

AbstractIndividual differences in fear, anxiety, and the etiology of anxiety disorders develop dur­ing ontogeny. They are due to both genet­ic and environmental factors. With regard to the role of the environment, the organism is most susceptible to external influences dur­ing early development. Accordingly, stressors that impinge on the maternal organism dur­ing pregnancy evoke high levels of anxiety in the offspring later in life, as does an adverse early postnatal environment. However, anxi­ety-related circuits in the central nervous sys­tem retain their plasticity in adulthood, i.e., levels of anxiety can also be modified by ex­perience across the entire successive lifespan. Notably, the effects of external stressors on the individual’s level of anxiety are modulat­ed by genotype. Such genotype-by-environ­ment interactions are particularly well stud­ied in relation to genetic variants that modu­late the function of the serotonin transport­er. Thus, this review focuses on this candidate gene to elucidate the interplay of genotype and environment in the development of fear and anxiety.


2014 ◽  
Vol 307 (2) ◽  
pp. H134-H142 ◽  
Author(s):  
Praveen Shukla ◽  
Srinivas Ghatta ◽  
Nidhi Dubey ◽  
Caleb O. Lemley ◽  
Mary Lynn Johnson ◽  
...  

The mechanisms underlying developmental programming are poorly understood but may be associated with adaptations by the fetus in response to changes in the maternal environment during pregnancy. We hypothesized that maternal nutrient restriction during pregnancy alters vasodilator responses in fetal coronary arteries. Pregnant ewes were fed a control [100% U.S. National Research Council (NRC)] or nutrient-restricted (60% NRC) diet from days 50 to 130 of gestation (term = 145 days); fetal tissues were collected at day 130. In coronary arteries isolated from control fetal lambs, relaxation to bradykinin was unaffected by nitro-l-arginine (NLA). Iberiotoxin or contraction with KCl abolished the NLA-resistant response to bradykinin. In fetal coronary arteries from nutrient-restricted ewes, relaxation to bradykinin was fully suppressed by NLA. Large-conductance, calcium-activated potassium channel (BKCa) currents did not differ in coronary smooth muscle cells from control and nutrient-restricted animals. The BKCa openers, BMS 191011 and NS1619, and 14,15-epoxyeicosatrienoic acid [a putative endothelium-derived hyperpolarizing factor (EDHF)] each caused fetal coronary artery relaxation and BKCa current activation that was unaffected by maternal nutrient restriction. Expression of BKCa-channel subunits did not differ in fetal coronary arteries from control or undernourished ewes. The results indicate that maternal undernutrition during pregnancy results in loss of the EDHF-like pathway in fetal coronary arteries in response to bradykinin, an effect that cannot be explained by a decreased number or activity of BKCa channels or by decreased sensitivity to mediators that activate BKCa channels in vascular smooth muscle cells. Under these conditions, bradykinin-induced relaxation is completely dependent on nitric oxide, which may represent an adaptive response to compensate for the absence of the EDHF-like pathway.


2016 ◽  
pp. 79-108 ◽  
Author(s):  
Konrad Matyjaszek

The rules of the reservation. On the book Jewish Poland Revisited by Erica Lehrer The paper offers a review of Erica Lehrer’s Jewish Poland Revisited, a publication presenting outcomes of an anthropological research on Jewish-Polish memory projects in Cracow's former Jewish district of Kazimierz. In a discussion of the book's theses, the author critically analyses Lehrer's postulate of 'ethnography of possibility' and the resultant strategy of approval for contemporary Kazimierz as a 'space of encounter' alongside with its rules of participation, imposed by the Polish proprietors of the district on its visitors.The article focuses on two such rules that condition a visitor’s possibility of participation in shrinking public spaces of Kazimierz. First of these laws is discussed as an imperative of abandoning the immediacy of district's physical space and its histories signified by the surviving built environment. Instead, Lehrer introduces a conceptual division of "social" and "physical" spaces, which leads to silencing of otherwise immediately present evidence of the violent past. The second rule is analyzed as a requirement of accepting the contemporary Polish owners’ role of 'brokers" and "purveyors" of Jewish heritage, consequential with an approval of a doubtful legal and moral title to the appropriated spaces.Through focusing on these rules of participation that determine and perpetuate the conditionality of Jewish presence in the space of Kazimierz, the author argues for a necessity of questioning and re-defining the traditional divisions of disciplines that establish conceptual separations of "social" and "built" spaces, as well as for a necessity of a critical outlook on contemporary Central European understandings of "heritage". Such an inquiry is discussed as conditional for overcoming the largely avoided yet still present "heritages" in the history of Polish-Jewish relations: the traditions of violence and exclusion, either social and spatial. Regulamin rezerwatu. O książce Jewish Poland Revisited Eriki LehrerArtykuł stanowi recenzję książki Jewish Poland Revisited Eriki Lehrer, prezentującej wyniki antropologicznych badań na temat żydowsko-polskich projektów pamięci realizowanych w byłej dzielnicy żydowskiej na krakowskim Kazimierzu. Omawiając tezy pracy, autor poddaje krytycznej analizie proponowany przez Lehrer projekt etnografii możliwości i wynikającą z niego strategię akceptacji współczesnego Kazimierza jako przestrzeni spotkania, za którą idzie akceptacja zasad uczestnictwa narzuconych gościom przez polskich zarządców Kazimierza.W artykule rozpatrywane są dwie takie zasady, warunkujące możliwość uczestnictwa gościa w kurczącej się przestrzeni publicznej Kazimierza. Pierwszą z nich autor opisuje jako nakaz porzucenia bezpośrednio dostępnej, fizycznej przestrzeni dzielnicy i niesionych przez nią historii, których znakiem jest ocalała zabudowa. W to miejsce Lehrer wprowadza podział na przestrzeń społeczną i fizyczną, skutkiem czego stłumione zostają ślady brutalnej przeszłości, w przeciwnym razie bezpośrednio obecne. Drugą zasadę autor odtwarza jako wymóg akceptacji roli współczesnych polskich właścicieli jako brokerów i pośredników żydowskiego dziedzictwa, co w konsekwencji pociąga za sobą akceptację ich wątpliwych prawnie i moralnie roszczeń do zawłaszczonej przestrzeni.Skupienie uwagi na regulaminie uczestnictwa, który ustanawia i utrzymuje warunkowy charakter żydowskiej obecności w przestrzeni Kazimierza, prowadzi autora do wniosku o konieczności rewaluacji i redefinicji tradycyjnego rozdziału dyscyplin, który tworzy konceptualny podział na społeczne przestrzenie i architektoniczne obiekty, oraz do krytycznego namysłu nad obowiązującym obecnie w Europie Środkowo-Wschodniej rozumieniem pojęcia „dziedzictwo”. Tego rodzaju poszukiwanie uznaje autor za warunek przezwyciężenia ignorowanego zwykle, choć mimo wszystko obecnego w polsko-żydowskich stosunkach „dziedzictwa”: tradycji przemocy i wykluczenia, tak społecznego, jak i przestrzennego. 


Development ◽  
1996 ◽  
Vol 122 (8) ◽  
pp. 2395-2403 ◽  
Author(s):  
B. Grbic ◽  
A.B. Bleecker

In this paper, we describe a late-flowering ecotype of Arabidopsis, Sy-0, in which the axillary meristems maintain a prolonged vegetative phase, even though the primary shoot apical meristem has already converted to reproductive development. This novel heterochronic shift in the development of axillary meristems results in the formation of aerial rosettes of leaves at the nodes of the primary shoot axis. We present evidence that the aerial-rosette phenotype arises due to the interaction between dominant alleles of two genes: ART, aerial rosette gene (on chromosome 5) and EAR, enhancer of aerial rosette (on chromosome 4): EAR has been tentatively identified as a new allele of the FRI locus. The possible role of these two genes in the conversion of shoot apical meristems to reproductive development is discussed.


2020 ◽  
Vol 319 (3) ◽  
pp. R282-R287
Author(s):  
Maycon I. O. Milanez ◽  
Erika E. Nishi ◽  
Cássia T. Bergamaschi ◽  
Ruy R. Campos

The control of sympathetic vasomotor activity involves a complex network within the brain and spinal circuits. An extensive range of studies has indicated that sympathoexcitation is a common feature in several cardiovascular diseases and that strategies to reduce sympathetic vasomotor overactivity in such conditions can be beneficial. In the present mini-review, we present evidence supporting the spinal cord as a potential therapeutic target to mitigate sympathetic vasomotor overactivity in cardiovascular diseases, focusing mainly on the actions of spinal angiotensin II on the control of sympathetic preganglionic neuronal activity.


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