The carboxyl terminal mutational hotspot of the ciliary disease protein RPGRORF15 (retinitis pigmentosa GTPase regulator) is glutamylated in vivo

Mutations inRPGR(ORF15)(retinitis pigmentosa GTPase regulator) are a major cause of inherited retinal degenerative diseases. RPGR(ORF15)(1152 residues) is a ciliary protein involved in regulating the composition and function of photoreceptor cilia. The mutational hotspot in RPGR(ORF15)is an unusual C-terminal domain encoded by exon ORF15, which is rich in polyglutamates and glycine residues (Glu-Gly domain) followed by a short stretch of basic amino acid residues (RPGR(C2)domain; residues 1072-1152). However, the properties of the ORF15-encoded domain and its involvement in the pathogenesis of the disease are unclear. Here we show that RPGR(ORF15)is glutamylated at the C-terminus, as determined by binding to GT335, which recognizes glutamylated substrates. This reactivity is lost in two mouse mutants ofRpgr, which do not express RPGR(ORF15)due to disease-causing mutations in exon ORF15. Our results indicate that RPGR(ORF15)is posttranslationally glutamylated in the Glu-Gly domain and that the GT335 antibody predominantly recognizes RPGR(ORF15)in photoreceptor cilia

Ablation of retinal ciliopathy protein RPGR results in altered photoreceptor ciliary composition

Cilia regulate several developmental and homeostatic pathways that are critical to survival. Sensory cilia of photoreceptors regulate phototransduction cascade for visual processing. Mutations in the ciliary protein RPGR (retinitis pigmentosa GTPase regulator) are a prominent cause of severe blindness disorders due to degeneration of mature photoreceptors. However, precise function of RPGR is still unclear. Here we studied the involvement of RPGR in ciliary trafficking by analyzing the composition of photoreceptor sensory cilia (PSC) in Rpgr(ko) retina. Using tandem mass spectrometry analysis followed by immunoblotting, we detected few alterations in levels of proteins involved in proteasomal function and vesicular trafficking in Rpgr(ko) PSC, prior to onset of degeneration. We also found alterations in the levels of high molecular weight soluble proteins in Rpgr(ko) PSC. Our data indicate RPGR regulates entry or retention of soluble proteins in photoreceptor cilia but spares the trafficking of key structural and phototransduction-associated proteins. Given a frequent occurrence of RPGR mutations in severe photoreceptor degeneration due to ciliary disorders, our results provide insights into pathways resulting in altered mature cilia function in ciliopathies

Prenylated retinal ciliopathy protein RPGR regulates ciliary localization of Joubert Syndrome-associated protein INPP5E in cooperation with PDE6

Ciliary dysfunction is an underlying cause of severe human disorders (collectively called ciliopathies), such as retinitis pigmentosa (RP), Joubert Syndrome (JBTS), and Bardet-Biedl Syndrome. Ciliary proteins form distinct functional networks for localization to cilia as well as regulation of ciliary function. However, not much is known about the mechanism of ciliary localization and function of RPGR (retinitis pigmentosa GTPase regulator), a ciliary protein frequently associated with RP worldwide. Using tandem mass spectrometry analysis, we show that RPGR interacts with two JBTS-associated proteins: PDE6Π (delta subunit of Phosphodiesterase; a prenyl-binding protein) and INPP5E (inositol polyphosphate-5-phosphatase 5E; a ciliary cargo). Whereas PDE6Π binds in a prenylation-dependent manner to the C-terminus of RPGR, INPP5E associates with the N-terminus of RPGR. Prenylation and interaction of RPGR with PDE6Π are critical for its localization to cilia. We further show that loss of RPGR results in reduced amount of INPP5E in cilia of fibroblasts and in photoreceptor outer segment, a modified sensory cilium. Overall, our results suggest that RPGR, in complex with PDE6D, regulates the trafficking of ciliary cargo INPP5E and implicate reduction in ciliary INPP5E in the pathogenesis of RPGR-ciliopathy

Quenching across quantum critical points in periodic systems: dependence of scaling laws on periodicity

We study the quenching dynamics of a many-body system in one dimension described by a Hamiltonian that has spatial periodicity. Specifically, we consider a spin-1/2 chain with equal xx and yy couplings and subject to a periodically varying magnetic field in the z direction or, equivalently, a tight-binding model of spinless fermions with a periodic local chemical potential, having period 2q, where q is a natural number. For a linear quench of the magnetic field strength (or potential strength) at rate 1/\tau across a quantum critical point, we find that the density of defects thereby produced scales as 1/\tau^{q/(q+1)}, deviating from the 1/\sqrt{\tau} scaling that is ubiquitous to a range of systems. We analyze this behavior by mapping the low-energy physics of the system to a set of fermionic two-level systems labeled by the lattice momentum k undergoing a non-linear quench as well as by performing numerical simulations. We also find that if the magnetic field is a superposition of different periods, the power law depends only on the smallest period for very large values of \tau although it may exhibit a cross-over at intermediate values of \tau. Finally, for the case where a zz coupling is also present in the spin chain, or equivalently, where interactions are present in the fermionic system, we argue that the power associated with the scaling law depends on a combination of q and interaction strength.Comment: 13 pages including 11 figure

Sensors Based Trash Can Using IOT

The main theme of our project is to develop a sensor based dustbin for a proper garbage management. This project depicts a worthy elucidation for maintaining green environment. The disposal of waste can be done efficiently by segregating between dry waste and wet waste. This system reduces the maintenance stress. A smart handling technology is used to avoid all such hazardous scenario and maintain cleanliness. The whole process is upheld by an embedded system integrated with microcontroller and sensors. The dustbin lid will automatically open when something is sensed within its boundary or limit. This project works on the basis of colour sensor. The sensor distinguishes the colour for efficient disposal of garbage. Thus the system is solution for environmental maintenance and reduces the work of human intervention in garbage maintenance

Maternal Manganese Restriction Increases Susceptibility to High-Fat Diet-Induced Dyslipidemia and Altered Adipose Function in WNIN Male Rat Offspring

Growth in utero is largely a reflection of nutrient and oxygen supply to the foetus. We studied the effects of Mn restriction per se, maternal Mn restriction, and postnatal high-fat feeding in modulating body composition, lipid metabolism and adipocyte function in Wistar/NIN (WNIN) rat offspring. Female weanling, WNIN rats received ad libitum for 4 months, a control or Mn-restricted diet and were mated with control males. Some restricted mothers were rehabilitated with control diet from conception (MnRC) or parturition (MnRP), and their offspring were raised on control diet. Some restricted offspring were weaned onto control diet (MnRW), while others continued on restricted diet throughout (MnR). A set of offspring from each group was fed high-fat diet from 9 months onwards. Body composition, adipocytes function, and lipid metabolism were monitored in male rat offspring at regular intervals. Maternal manganese restriction increased the susceptibility of the offspring to high-fat-induced adiposity, dyslipidaemia, and a proinflammatory state but did not affect their glycemic or insulin status

Maternal and fetal factors associated with stillbirth in singleton pregnancies in 13 hospitals across six states in India: a prospective cohort study

Methods: We conducted a secondary data analysis of a hospital-based cohort from the Maternal and Perinatal Health Research collaboration, India (MaatHRI), including pregnant women who gave birth between October 2018–September 2023. Data from 9823 singleton pregnancies recruited from 13 hospitals across six Indian states were included. Univariable and multivariable Poisson regression analysis were performed to examine the relationship between stillbirth and potential risk factors. Model prediction was assessed using the area under the receiver-operating characteristic (AUROC) curve. Results: There were 216 stillbirths (48 antepartum and 168 intrapartum) in the study population, representing an overall stillbirth rate of 22.0 per 1000 total births (95% confidence interval [CI]: 19.2–25.1). Modifiable risk factors for stillbirth were: receiving less than four antenatal check-ups (adjusted relative risk [aRR]: 1.75, 95% CI: 1.25–2.47), not taking any iron and folic acid supplementation during pregnancy (aRR: 7.23, 95% CI: 2.12–45.33) and having severe anemia in the third trimester (aRR: 3.37, 95% CI: 1.97–6.11). Having pregnancy/fetal complications such as hypertensive disorders of pregnancy (aRR: 1.59, 95% CI: 1.03–2.36), preterm birth (aRR: 4.41, 95% CI: 3.21–6.08) and birth weight below the 10th percentile for gestational age (aRR: 1.35, 95% CI: 1.02–1.79) were also associated with an increased risk of stillbirth. Identified risk factors explained 78.2% (95% CI: 75.0%–81.4%) of the risk of stillbirth in the population. Conclusion: Addressing potentially modifiable antenatal factors could reduce the risk of stillbirths in India

The complex relationship between iron status and anemia in pregnant and postpartum women in India: analysis of two Indian study cohorts of uncomplicated pregnancies

Low hemoglobin is widely used as an indicator of iron deficiency anemia in India and other low-and-middle income counties, but anemia need not accurately reflect iron deficiency. We examined the relationship between hemoglobin and biomarkers of iron status in antenatal and postnatal period. Secondary analysis of uncomplicated singleton pregnancies in two Indian study cohorts: 1132 antenatal women in third trimester and 837 postnatal women 12–72 h after childbirth. Associations of hemoglobin with ferritin in both data sets, and with sTfR, TSAT, and hepcidin in the postnatal cohort were examined using multivariable linear regression. Multinomial logistic regression was used to examine the association between severity of anemia and iron status. Regression models were adjusted for potential confounders. Over 55% of the women were anemic; 34% of antenatal and 40% of postnatal women had low ferritin, but 4% antenatal and 6% postnatal women had high ferritin. No evidence of association between hemoglobin and ferritin was observed (antenatal: adjusted coefficient [aCoef] −0.0004, 95% confidence interval [CI] −0.001, 0.001; postnatal: aCoef −0.0001, 95% CI −0.001, 0.001). We found a significant linear association of hemoglobin with sTfR (aCoef −0.04, 95% CI −0.07, −0.01), TSAT (aCoef −0.005, 95% CI −0.008, −0.002), and hepcidin (aCoef 0.02, 95% CI 0.02, 0.03) in postnatal women. Likelihood of low ferritin was more common in anemic than non-anemic women, but high ferritin was also more common in women with severe anemia in both cohorts. Causes of anemia in pregnant and postpartum women in India are multifactorial; low hemoglobin alone is not be a useful marker of iron deficiency

Facial Emotion Recognition

Emotion is a complex conscious that humans experience as a result of interactions with the environment. The project basically takes in the image, recognises the emotion by fragmenting the image with the deep learning technique using CNN. The tools and framework used here are keras and TensorFlow respectively. Here the facial feeling analysis refers to computing system that makes an attempt to mechanically analyse and recognise facial feeling and facial feature changes from visual data. The image being pre-processed helps for aiming a better quality of image and hence the emotion can be detected in a better way. This project can be used in many fields and one such field is mental health care centre. Patients with bipolar disorders should be treated by adhering the emotional behavior of patient and our project helps in doing the same

High Intensity Interval Exercise Does Not Influence Overnight GH Secretion in Overweight Sedentary Young Women

Exercise and sleep are the two major factors that influence growth hormone (GH) secretion and it has been well established that there is a strong positive relationship between exercise intensity and GH release. This dose-dependent response may also be correlated with the lactate response to exercise, with steady-state exercise intensities above the lactate threshold eliciting a greater GH pulse. It has yet to be determined, however, if high-intensity interval exercise (HIE) can influence overnight pulsatile GH secretion, which accounts for the majority of daily GH release. PURPOSE: To determine if HIE significantly increased overnight GH secretion compared to continuous moderate-intensity exercise (MOD), or no exercise (CON) in young women. METHODS: Five young, sedentary women (mean ± SD age: 22.6 ± 1.3 y; BMI: 27.4 ± 3.1 kg/m2; body fat: 39.2 ± 1.7 %; VO2max: 29.4 ± 5.7 mL/kg/min) were studied on three different occasions during the follicular phase of their menstrual cycle (CON: no exercise; MOD: 30-min of continuous cycling at 50% of peak power determined from the VO2max test; and HIE: 4 30-s “all-out” sprints at a resistance equal to 6.5% body mass with 4.5-min recovery. Each trial was randomly assigned and separated by a minimum of one month. For each visit, participants reported to the lab at 1700h, exercised from 1730h – 1800h, and remained in the lab until 0700h the following morning. The overnight GH secretory profile of each trial was determined from 10-min sampling of venous blood from 1730h – 0600h (12.5 h) using deconvolution analysis. RESULTS: Mean power output during MOD was 80.6 ± 6.3 W (68.2 ± 9.7 %VO2max). Estimated exercising energy expenditure for MOD (145.1 ± 11.2 kcal) was significantly lower than HIE (204.5 ± 15.5 kcal, P = 0.002). Peak lactate was significantly higher during MOD (4.7 ± 0.9 mmol/L) compared to CON (0.9 ± 0.2 mmol/L, P = 0.002) and was highest during HIE (11.2 ± 2.1 mmol/L) compared to MOD (P \u3c 0.001) and CON (P \u3c 0.001). Calculated GH AUC (0 – 120 min) was significantly greater in HIE (1018.2 ± 576.1 ng· min/mL) than CON (181.7 ± 138.9 ng· min/mL, P = 0.009), but not MOD (544.7 ± 160.7 ng· min/mL). Overnight GH production rate (ng/mL/min) determined by deconvolution analysis was not significantly different between CON (1040.3 ± 242.0), MOD (1429.2 ± 206.0), and HIE (1831.2 ± 873.8, P = 0.107). Other GH secretory variables: basal GH concentration (ng/mL), number of GH peaks, GH pulse amplitude and mass, and interpulse interval were not different between the three trials. CONCLUSION: For these untrained, overweight sedentary young women, a single bout of exercise was insufficient to significantly affect overnight pulsatile GH secretion. Adiposity is a negative determinant of GH secretion, and the GH response to exercise in these women was extremely variable. Aerobic fitness, prior training, as well as several metabolic factors associated with obesity (e.g., increased insulin and circulating free fatty acids) can also influence GH secretion and should be taken into account as potential mediators of the GH response to exercise