Structural basis for regulation of the Crk signaling protein by a proline switch

Proline switches, controlled by cis-trans isomerization, have emerged as a particularly effective regulatory mechanism in a wide range of biological processes. Here we report the structures of both the cis and trans conformers of a proline switch in the Crk signaling protein. Proline isomerization toggles Crk between two conformations: an autoinhibitory conformation, stabilized by the intramolecular association of two tandem SH3 domains in the cis form, and an uninhibited, activated conformation promoted by the trans form. In addition to acting as a structural switch, the heterogeneous proline recruits cyclophilin A, which accelerates the interconversion rate between the isomers, thereby regulating the kinetics of Crk activation. The data provide atomic insight into the mechanisms that underpin the functionality of this binary switch and elucidate its remarkable efficiency. The results also reveal new SH3 binding surfaces, highlighting the binding versatility and expanding the noncanonical ligand repertoire of this important signaling domain.     

Protein intake and stress levels in nurses and housewives of Pakistan

Stress has many biological effects on human daily life. In the present study, dietary protein intake was correlated with the investigated stress levels of nurses and housewives of the targeted urban population. Age group ranged from 30 to 45 years and both the groups belonged to middle socioeconomic status. After calculations of environmental, psychological and physiological stresses, it was observed that the levels of stress in housewives were significantly higher than those of nurses. Recommended dietary allowances, RDA and actual protein intakes, API were also compared in both the groups. The found protein intake was less in housewives as compared to that of nurses.     

Light and ultrastructural description of Meglitschia mylei n. sp. (myxozoa) from Myleus rubripinnis (Teleostei: Serrasalmidae) in the Amazon River system

Meglitschia mylei n. sp. found in the gall bladder of the teleostean fish Myleus rubripinnis (Serrasalmidae) from the middle Amazonian region of Brazil is described using light and transmission electron microscopy. The spores observed in the bile averaged 24.6±0.8 μm long, 8.7±0.4 μm wide and 5.1±0.3 μm thick and were strongly furcate and arcuate ∩-shaped composed of two symmetric equal-sized valves, up to ～70 nm thick. Each valve possessed one opposed tapering appendage, 20.1±0.7 μm long, oriented parallel towards the basal tip of the appendages and joined along a right suture line forming a thick strand. The strand goes around the central part of the spore, which in turn surrounds two equal and symmetric spherical polar capsules (PC), 2.1±0.3 μm in diameter, located at the same level. Each capsule contains a polar filament with five (rarely six) coils. The binucleate sporoplasm was irregular in shape, contained several sporoplasmosomes, ～175 nm in diameter and filled all the space of the two caudal appendages. Based on the arc shape of the spore with two tapering caudal appendages oriented to the basis of spores, on the number and position of the PC and of the polar filament coils and arrangements, and on the host specificity, we propose the name M. mylei n. sp. for this new myxozoan. Accordingly, this is the second described species of this genus.     

Deletion of UCP2 in iNOS deficient mice reduces the severity of the disease during experimental autoimmune encephalomyelitis

Uncoupling protein 2 is a member of the mitochondrial anion carrier family that is widely expressed in neurons and the immune cells of humans. Deletion of Ucp2 gene in mice pre-activates the immune system leading to higher resistance toward infection and to an increased susceptibility to develop chronic inflammatory diseases as previously exemplified with the Experimental Autoimmune Encephalomyelitis (EAE), a mouse model for multiple sclerosis. Given that oxidative stress is enhanced in Ucp2-/- mice and that nitric oxide (NO) also plays a critical function in redox balance and in chronic inflammation, we generated mice deficient for both Ucp2 and iNos genes and submitted them to EAE. Mice lacking iNos gene exhibited the highest clinical score (3.4+/-0.5 p<0.05). Surprisingly, mice deficient for both genes developed milder disease with reduced immune cell infiltration, cytokines and ROS production as compared to iNos-/- mice.     

Hepatocellular Damage and Severity of COVID-19 Infection in Iraqi Patients: A Biochemical Study

Background:Infection with COVID-19 can cause hepatic damages. Here, we aimed to examine the effect of COVID-19 infection on the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, and procalcitonin (PCT) concentrations as markers to evaluate the liver function.Methods:In this study, 56 patients infected with COVID- 19 and 28 healthy controls was recruited in Private Nursing Home Hospital of the Medical City, Baghdad. Patients were subdivided according to disease severity into severe and non-severe groups.Results:The results showed that the mean±SD value of serum AST activity and serum PCT concentrations were elevated significantly in severe group in comparison to healthy control, (p< 0.01, p< 0.001) respectively. Also, the mean ±SD value of serum ALT activity was higher in severe group compared to the healthy subjects and non-severe ones, significantly (p< 0.0001, p< 0.003) respectively. While the mean value of serum albumin concentration of severe patients and non-severe group were significantly decreased compared to healthy subjects. The receiver operating characteristic curve (ROC) revealed that ROC value of albumin (0.992) differentiates between non-severe infected patients and healthy subjects, while the ROC value of serum ALT activity (0.735) differentiates between severe COVID-19 patients and non- severe ones.Conclusion:Changes of liver function parameters in COVID-19 patients were mild to moderate and measurement of serum ALT activity is the best biomarker in differentiation between non-severe patients and severe ones and albumin concentration is excellent in discrimination between patients and controls.Key Words: Serum aminotransferase enzymes, Albumin, Procalcitonin     

Field evaluation of transgenic wheat plants stably expressing the HVA1 gene for drought tolerance

The barley HVA1 gene, encoding a member of the group 3 late embryogenesis abundant (LEA) proteins, has previously been introduced into spring wheat cv. Hi-Line to determine its effect on drought tolerance (Sivamani E, Bahieldin A, Wraith JM, Al-Niemi T, Dyer WE, Ho T-HD, Qu R (2000) Improved biomass productivity and water use efficiency under water deficit conditions in transgenic wheat constitutively expressing the barley HVA1 gene. Plant Sci 155, 1–9). T4 progeny from six independent transgenic events (lines 111/1, 1/1, 11/2, 84, 765 and 1201) were tested in nine field experiments over six cropping seasons. In the first two seasons, the total biomass per plot and the grain yield per plot of line 111/1 were higher than those of line 1/1, and higher than those of the wild-type control in the second season. The grain yield per plot of line 11/2 was significantly lower than that of the transgenic lines 111/1 and 1/1 in the third season, and this line was not tested further. In the fourth season, the plant height and grain yield per plot of line 111/1 were significantly higher than those of the wild-type control. Under dryland conditions in the fifth season, line 111/1 showed significantly greater plant height, total biomass per plot and grain yield per plot than the wild-type control in at least two of the four locations, as well as across locations. In the sixth season, newly developed transgenic lines 1201 and 765 significantly overyielded the two original transgenic lines 111/1 and 1/1, the non-expressing transgenic line 84 as well as the wild-type control in the three yield attributes and leaf water measurement, namely relative water content (RWC). This result coincided with the rate of HVA1 transgene expression of the different genotypes. Differences in total seed storage protein concentrations between the transgenic lines and the wild-type control within or across environmental conditions were insignificant. These field trials show that the HVA1 gene has the potential to confer drought stress protection in transgenic spring wheat.