Linkage disequilibrium and functional analysis of PRE1 insertion together with SNPs in the promoter region of IGFBP7 gene in different pig breeds

Abstract

Polymorphisms in regions upstream of transcription initiation site may modify the transcriptional activity of target genes by changing promoter activity. This study aims to determine whether or not polymorphisms at porcine IGFBP7 promoter region affect gene expression. In this study, eight SNPs and one PRE1 insertion in this region were first confirmed. The PRE1 insertion was widespread in 20 Chinese indigenous breeds, but was not observed in three commercial breeds. A perfect linkage disequilibrium, consisting of six of those SNPs and a PRE1, was observed with two haplotypes (h1 and h2) in five pig breeds. The h1 haplotype had an overwhelming superiority distribution in Large White, Landrace, and Bama mini-pig; in turn, the h2 only existed in the PRE1 presence breeds. As the haplotypes and PRE1 were located at gene promoter regions, we further investigated the transfection of plasmids with three different fragments of IGFBP-7 promoter region (H1, H2, RF). The CMV promoter of the pEGFP-N1 was substituted by these three different fragments, respectively. Different transcriptional and translational activities of EGFP in PK-15 cells were observed in these three recombinant plasmids by quantitative real-time PCR and flow cytometric analysis. The results indicated that H1 had the higher transcriptional and translational activities of EGFP as compared to the H2 (P < 0.05, P < 0.05). As compared to the RF group, EGFP mRNA expression level was significantly higher in H1 groups (P < 0.05). The IGFBP-7 promoter polymorphisms detected in this study may be important functional variants and potential genetic markers for pig population genetic study.

from Genetics via xlomafota13 on Inoreader https://ift.tt/2DSPNgJ
via IFTTT

LEC1 (NF-YB9) directly interacts with LEC2 to control gene expression in seed

Publication date: Available online 24 March 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): C. Boulard, J. Thévenin, O. Tranquet, V. Laporte, L. Lepiniec, B. Dubreucq
The LAFL transcription factors LEC2, ABI3, FUS3 and LEC1 are master regulators of seed development. LEC2, ABI3 and FUS3 are closely related proteins that contain a B3-type DNA binding domain. We have previously shown that LEC1 (a NF-YB type protein) can increase LEC2 and ABI3 but not FUS3 activity. Interestingly, FUS3, LEC2 and ABI3 contain a B2 domain, the function of which remains elusive. We showed that LEC1 and LEC2 partially co-localised in the nucleus of developing embryos. By comparing protein sequences from various species, we identified within the B2 domains a set of highly conserved residues (i.e. TKxxARxxRxxAxxR). This domain directly interacts with LEC1 in yeast. Mutations of the conserved amino acids of the motif in the B2 domain abolished this interaction both in yeast and in moss protoplasts and did not alter the nuclear localisation of LEC2 in planta. Conversely, the mutations of key amino acids for the function of LEC1 in planta (D86K) prevented the interaction with LEC2. These results provide molecular evidences for the binding of LEC1 to B2-domain containing transcription factors, to form heteromers, involved in the control of gene expression.



from Genetics via xlomafota13 on Inoreader https://ift.tt/2GidUeb
via IFTTT

Phylogenetic relationship of a fossil macaque (Macaca cf. robusta) from the Korean Peninsula to extant species of macaques based on zygomaxillary morphology

Publication date: June 2018
Source:Journal of Human Evolution, Volume 119
Author(s): Tsuyoshi Ito, Yung-jo Lee, Takeshi D. Nishimura, Mikiko Tanaka, Jong-yoon Woo, Masanaru Takai
Little is known about the biogeographical and evolutionary histories of macaques (Macaca spp.) in East Asia because the phylogenetic positions of fossil species remain unclear. Here we examined the zygomaxillary remains of a fossil macaque (M. cf. robusta) from the Durubong Cave Complex, South Korea, that dates back to the late Middle to Late Pleistocene, to infer its phylogenetic relationship to extant species. We took 195 fixed- and semi-landmarks from the zygomaxillary regions of the fossil specimen and from 147 specimens belonging to 14 extant species. We then conducted a generalized Procrustes analysis followed by a multivariate statistical analysis to evaluate the phenetic affinities of the fossil to the extant species and reconstructed the most parsimonious phylogenetic tree using a phylogenetic morphometric approach. We found that the fossil was most similar to Macaca fuscata (Japanese macaque) in the zygomaxillary morphospace although it was at the limit of the range of variation for this species. The second closest in the morphospace was the continental Macaca mulatta (rhesus macaque). Parsimonious reconstruction confirmed that the fossil was most closely related to M. fuscata, even after controlling for the effects of allometry. These findings suggest that in the late Middle to Late Pleistocene, close relatives of M. fuscata that looked like the extant species were distributed on the Korean Peninsula, where no species of macaques are found today. Thus, some morphological characteristics of M. fuscata may have developed before its ancestor dispersed into the Japanese archipelago.



from Genetics via xlomafota13 on Inoreader https://ift.tt/2I1yWL9
via IFTTT

Woman recalls trying to save life of stranger hit by truck

Former corrections officer Faith Appelgren and a trauma nurse performed CPR on the victim in the middle of the road while responders were stuck in traffic

from EMS via xlomafota13 on Inoreader https://ift.tt/2I14zER
via IFTTT

Early life trauma: An exploratory study of effects on OXTR and NR3C1 gene expression and nurturing self-efficacy in mothers of infants

Publication date: Available online 24 March 2018
Source:International Journal of Psychophysiology
Author(s): Alysson E. Light, Julianne Holt-Lunstad, Chris L. Porter, Kathleen C. Light
BackgroundIn animals, adverse early experience alters oxytocinergic and glucocorticoid activity and maternal behavior in adulthood. This preliminary study explored associations among childhood trauma (loss of a parent or sexual abuse in childhood), maternal self-efficacy, and leukocyte gene expression (mRNA) of oxytocin and glucocorticoid receptors (OXTR and NR3C1) in mothers of infants.Methods62 mothers (20 with early life trauma) with healthy 3-month old infants reported maternal self-efficacy, depression, infant temperament, and overall social support; the effects of early trauma on these measures were assessed. Of these, 35 mothers (14 with early trauma) underwent blood draws after 2 infant feeding times; their OXTR and NR3C1 mRNA was compared to a control group of 25 no-infant women without early trauma, and also was examined for associations with self-efficacy.ResultsOXTR mRNA was increased in mothers of infants versus no-infant controls (p < 0.0003), and mothers with greatest prior maternal experience had higher OXTR than those with less experience (0–2 vs. 3+ older children, p < 0.033). Mothers with early trauma and less maternal experience had lower OXTR mRNA than no-trauma mothers (p < 0.029) and lower NR3C1 mRNA than controls (p < 0.004). Mothers with depression also had lower NR3C1 than other mothers (p < 0.003) but did not differ in OXTR. Mothers with early trauma also reported their support network to be less helpful and more upsetting and unpredictable than other mothers (p < 0.035–p < 0.005). Regarding maternal behavior, in mothers with early trauma, helpful support networks increased self-reported nurturing self-efficacy when babies were not fussy but decreased it with fussy babies (p < 0.05). Support was unrelated to self-efficacy in no-trauma mothers. Similarly, among mothers with low OXTR or NR3C1 (−1SD, most having early trauma and lower maternal experience), greater support was associated with lower self-efficacy (p < 0.05), while mothers with high OXTR or NR3C1 (+1SD) tended to have higher self-efficacy with greater support.ConclusionsThese preliminary findings need confirmation in a larger sample but suggest that childhood trauma influences maternal behavior and both OXTR and NR3C1 pathways in mothers of infants, and that both depression and prior maternal experience may be other important factors. Effects on maternal behavior appear to require more complex modeling.



from Physiology via xlomafota13 on Inoreader https://ift.tt/2G4ZxX3
via IFTTT

Neuromagnetic correlates of audiovisual word processing in the developing brain

Publication date: Available online 23 March 2018
Source:International Journal of Psychophysiology
Author(s): Samantha Dinga, Di Wu, Shuyang Huang, Caiyun Wu, Xiaoshan Wang, Jingping Shi, Yue Hu, Chun Liang, Fawen Zhang, Meng Lu, Kimberly Leiken, Jing Xiang
The brain undergoes enormous changes during childhood. Little is known about how the brain develops to serve word processing. The objective of the present study was to investigate the maturational changes of word processing in children and adolescents using magnetoencephalography (MEG). Responses to a word processing task were investigated in sixty healthy participants. Each participant was presented with simultaneous visual and auditory word pairs in "match" and "mismatch" conditions. The patterns of neuromagnetic activation from MEG recordings were analyzed at both sensor and source levels. Topography and source imaging revealed that word processing transitioned from bilateral connections to unilateral connections as age increased from 6 to 17 years old. Correlation analyses of language networks revealed that the path length of word processing networks negatively correlated with age (r = −0.833, p < 0.0001), while the connection strength (r = 0.541, p < 0.01) and the clustering coefficient (r = 0.705, p < 0.001) of word processing networks were positively correlated with age. In addition, males had more visual connections, whereas females had more auditory connections. The correlations between gender and path length, gender and connection strength, and gender and clustering coefficient demonstrated a developmental trend without reaching statistical significance. The results indicate that the developmental trajectory of word processing is gender specific. Since the neuromagnetic signatures of these gender-specific paths to adult word processing were determined using non-invasive, objective, and quantitative methods, the results may play a key role in understanding language impairments in pediatric patients in the future.



from Physiology via xlomafota13 on Inoreader https://ift.tt/2G0Nez1
via IFTTT

Different profiles of decision making and physiology under varying levels of stress in trained military personnel

Publication date: Available online 23 March 2018
Source:International Journal of Psychophysiology
Author(s): Katherine R. Gamble, Jean M. Vettel, Debra J. Patton, Marianna D. Eddy, F. Caroline Davis, Javier O. Garcia, Derek P. Spangler, Julian F. Thayer, Justin R. Brooks
Decision making is one of the most vital processes we use every day, ranging from mundane decisions about what to eat to life-threatening choices such as how to avoid a car collision. Thus, the context in which our decisions are made is critical, and our physiology enables adaptive responses that account for how environmental stress influences our performance. The relationship between stress and decision making can additionally be affected by one's expertise in making decisions in high-threat environments, where experts can develop an adaptive response that mitigates the negative impacts of stress. In the present study, 26 male military personnel made friend/foe discriminations in an environment where we manipulated the level of stress. In the high-stress condition, participants received a shock when they incorrectly shot a friend or missed shooting a foe; in the low-stress condition, participants received a vibration for an incorrect decision. We characterized performance using signal detection theory to investigate whether a participant changed their decision criterion to avoid making an error. Results showed that under high-stress, participants made more false alarms, mistaking friends as foes, and this co-occurred with increased high frequency heart rate variability. Finally, we examined the relationship between decision making and physiology, and found that participants exhibited adaptive behavioral and physiological profiles under different stress levels. We interpret this adaptive profile as a marker of an expert's ingrained training that does not require top down control, suggesting a way that expert training in high-stress environments helps to buffer negative impacts of stress on performance.



from Physiology via xlomafota13 on Inoreader https://ift.tt/2G5X9zm
via IFTTT

To die or not to die: death signaling in nonalcoholic fatty liver disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) is an emerging liver disease worldwide. In subset of patients, NAFLD progresses to its advanced form, nonalcoholic steatohepatitis (NASH), which is accompanied with inflammation and fibrosis. Saturated free fatty acid-induced hepatocyte apoptosis is a feature of NASH. Death signaling in NASH does not always result in apoptosis, but can alternatively lead to the survival of cells presenting signs of pro-inflammatory and pro-fibrotic signals. With the current lack of established treatments for NASH, it is important to understand the molecular mechanisms responsible for disease development and progression. This review focuses on the latest findings in hepatocyte death signaling and discusses possible targets for intervention, including caspases, death receptor and c-Jun N-terminal kinase 1 signaling, oxidative stress, and endoplasmic reticulum stress, as well as epigenomic factors.

from Gastroenterology via xlomafota13 on Inoreader https://ift.tt/2G5USEk
via IFTTT

Characterization and modelling of looming-sensitive neurons in the crab Neohelice

Abstract

Looming-sensitive neurons (LSNs) are motion-sensitive neurons tuned for detecting imminent collision. Their main characteristic is the selectivity to looming (a 2D representation of an object approach), rather than to receding stimuli. We studied a set of LSNs by performing surface extracellular recordings in the optic nerve of Neohelice granulata crabs, and characterized their response against computer-generated visual stimuli with different combinations of moving edges, highlighting different components of the optical flow. In addition to their selectivity to looming stimuli, we characterized other properties of these neurons, such as low directionality; reduced response to sustained excitement; and an inhibition phenomenon in response to visual stimuli with dense optical flow of expansion, contraction, and translation. To analyze the spatio-temporal processing of these LSNs, we proposed a biologically plausible computational model which was inspired by previous computational models of the locust lobula giant motion detector (LGMD) neuron. The videos seen by the animal during electrophysiological experiments were applied as an input to the model which produced a satisfactory fit to the measured responses, suggesting that the computation performed by LSNs in a decapod crustacean appears to be based on similar physiological processing previously described for the LGMD in insects.

from Physiology via xlomafota13 on Inoreader https://ift.tt/2IQW3cM
via IFTTT

Examining Mechanisms and Moderators of the Relationship Between Discriminatory Health Care Encounters and Attempted Suicide Among U.S. Transgender Help-Seekers

Abstract

This study examined how experiences of service denial and discrimination in three health care settings—doctors' offices, emergency rooms, and mental health clinics—might contribute to attempted suicide among transgender adults. Mechanisms of this relationship were examined, including treatment receipt and the use of substances to cope with mistreatment. Perceived emotional social support was also tested as a potential protective factor against the deleterious effects of service denial and discrimination on treatment receipt, substance use, and attempted suicide. The analysis included 4190 respondents from the National Transgender Discrimination Survey. Structural equation modeling was employed to test hypothesized relationships. Being denied a greater number of services and discriminated against in more settings were associated with lower levels of treatment receipt. Service denial was also correlated with increased rates of coping-motivated substance use and elevated rates of attempted suicide. Treatment receipt mediated the relationships between service denial/discrimination and substance use. Substance use mediated the relationship between treatment receipt and attempted suicide. Higher levels of support were protective to treatment receipt when denied services in one setting, but no longer retained protective effects when denied in two or three settings. Results have critical implications for service access and delivery and policies that protect transgender help-seekers in the health care system.

from Health via xlomafota13 on Inoreader https://ift.tt/2ufk7m6
via IFTTT

Factors Associated with Assignment of Therapeutic Homework in a Large Public Children’s Mental Health System

Abstract

Therapeutic homework is a fundamental skill-building component of the majority of evidence-based therapies and is associated with better treatment outcomes. However, it is rarely utilized in public mental health settings. To determine barriers to homework use and identify predictors of clinicians' assignment of homework, an online survey was administered to 267 clinicians in a large diverse public mental health system. Clinicians who were younger, licensed, whose supervisors asked about homework and whose clients completed their homework more frequently were predictors of greater homework utilization. The survey results are discussed and a novel idea to increase the use of homework is introduced.

from Health via xlomafota13 on Inoreader https://ift.tt/2IOMNWC
via IFTTT

Exercise Blood Pressure Guidelines: Time to Re-evaluate What is Normal and Exaggerated?

Abstract

Blood pressure responses to graded exercise testing can provide important diagnostic and prognostic information. While published guidelines outline what constitutes a "normal" and "abnormal" (i.e., exaggerated) blood pressure response to exercise testing, the widespread use of exaggerated blood pressure responses as a clinical tool is limited due to sparse and inconsistent data. A review of the original sources from these guidelines reveals an overall lack of empirical evidence to support both the normal blood pressure responses and their upper limits. In this current opinion, we critically evaluate the current exercise blood pressure guidelines including (1) the normal blood pressure responses to graded exercise testing; (2) the upper limits of this normal response; (3) the blood pressure criteria for test termination; and (4) the thresholds for exaggerated blood pressure responses. We provide evidence that exercise blood pressure responses vary according to subject characteristics, and subsequently a re-evaluation of what constitutes normal and abnormal responses is necessary to strengthen the clinical utility of this assessment.

from Sports Medicine via xlomafota13 on Inoreader https://ift.tt/2G0SYZV
via IFTTT

The putative leucine sensor Sestrin2 is hyperphosphorylated by acute resistance exercise but not protein ingestion in human skeletal muscle

Abstract

Purpose

Dietary protein and resistance exercise (RE) are both potent stimuli of the mammalian target of rapamycin complex 1 (mTORC1). Sestrins1, 2, 3 are multifunctional proteins that regulate mTORC1, stimulate autophagy and alleviate oxidative stress. Of this family, Sestrin2 is a putative leucine sensor implicated in mTORC1 and AMP-dependent protein kinase (AMPK) regulation. There is currently no data examining the responsiveness of Sestrin2 to dietary protein ingestion, with or without RE.

Methods

In Study 1, 16 males ingested either 10 or 20 g of milk protein concentrate (MPC) with muscle biopsies collected pre, 90 and 210 min post-beverage consumption. In Study 2, 20 males performed a bout of RE immediately followed by the consumption of 9 g of MPC or carbohydrate placebo. Analysis of Sestrins, AMPK and antioxidant responses was examined.

Results

Dietary protein ingestion did not result in Sestrin2 mobility shift. After RE, Sestrin2 phosphorylation state was significantly altered and was not further modified by post-exercise protein or carbohydrate ingestion. With RE, AMPK phosphorylation remained stable, while the mRNA expressions of several antioxidants were upregulated.

Conclusions

Dietary protein ingestion did not affect the signalling by the family of Sestrins. With RE, Sestrin2 was hyperphosphorylated, with no further evidence of a relationship to AMPK signalling.

from Physiology via xlomafota13 on Inoreader https://ift.tt/2G3WH4J
via IFTTT