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AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca 2+ -impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission. Genetic variants in ionotropic glutamate receptors have been implicated in neurodevelopmental disorders. Here, the authors report heterozygous de novo mutations in the GRIA2 gene in 28 individuals with intellectual disability and neurodevelopmental abnormalities associated with reduced Ca 2+ transport and AMPAR currents.”

The speed of absorption of dietary amino acids by the gut varies according to the type of ingested dietary protein. This could affect postprandial protein synthesis, breakdown, and deposition. To test this hypothesis, two intrinsically 13C-leucine-labeled milk proteins, casein (CAS) and whey protein (WP), of different physicochemical properties were ingested as one single meal by healthy adults. Postprandial whole body leucine kinetics were assessed by using a dual tracer methodology. WP induced a dramatic but short increase of plasma amino acids. CAS induced a prolonged plateau of moderate hyperaminoacidemia, probably because of a slow gastric emptying. Whole body protein breakdown was inhibited by 34% after CAS ingestion but not after WP ingestion. Postprandial protein synthesis was stimulated by 68% with the WP meal and to a lesser extent (+31%) with the CAS meal. Postprandial whole body leucine oxidation over 7 h was lower with CAS (272 +/- 91 micromoles . kg-1) than with WP (373 +/- 56 micromoles . kg-1). Leucine intake was identical in both meals (380 micromoles . kg-1). Therefore, net leucine balance over the 7 h after the meal was more positive with CAS than with WP (P 0.05, WP vs. CAS). In conclusion, the speed of protein digestion and amino acid absorption from the gut has a major effect on whole body protein anabolism after one single meal. By analogy with carbohydrate metabolism, slow and fast proteins modulate the postprandial metabolic response, a concept to be applied to wasting situations

This book systematically describes the green engineering, chemistry and manufacture of bio-based polymers and composites derived from plants. This book gives a thorough introduction to bio-based material resources, availability, sustainability, bio-based polymer formation, extraction and refining technologies, and the need for integrated research and multi-disciplinary working teams. It provides an in-depth description of adhesives, resins, plastics, and composites derived from plant oils, proteins, starches, and natural fibers in terms of structures, properties, manufacturing, and product performance. This is an excellent book for scientists, engineers, graduate students and industrial researchers in the field of bio-based materials.

The ionic compound N-(2-hydroxyethyl)piperazinium chloride (HEPH)Cl, containing a piperazinium cation with a + 1 charge, was crystallized in the orthorhombic space group P 2 1 2 1 2 1 . The unit cell parameters were determined to be a  = 8.6083(3) Å, b  = 8.8523(3) Å, and c  = 10.7405(4) Å. The volume of the unit cell was found to be 818.46(5) ų, with a Z value of 4. Refinement yielded R [ F 2  > 2 σ ( F 2 )] = 0.018, wR ( F 2 ) = 0.028, and a goodness-of-fit parameter of S  = 1.77. The crystal structure reveals the presence of three hydrogen bonds: O1–H1o1···Cl1, N1–H1n1···N2, and N1–H2n1···Cl1, which contribute to the specific molecular arrangements within the crystal lattice.Electrochemical properties of (HEPH)Cl were examined by cyclic voltammetry (CV). Molecular docking experiments were conducted to assess the interactions of (HEPH)Cl with Mycobacterium tuberculosis DNA gyrase, coronavirus main protease, Plasmodium falciparum protein, and human serum albumin. Graphical Abstract N-(2-hydroxyethyl)piperazinium chloride cation uniquely adopts a chair conformation carrying a +1 charge, stabilized by crucial hydrogen bonding interactions that enhance molecular recognition and binding affinity observed in docking study.

Tobacco mosaic virus (TMV) derivatives that encode movement protein (MP) as a fusion to the green fluorescent protein (MP:GFP) were used in combination with antibody staining to identify host cell components to which MP and replicase accumulate in cells of infected Nicotiana benthamiana leaves and in infected BY-2 protoplasts. MP:GFP and replicase colocalized to the endoplasmic reticulum (ER; especially the cortical ER) and were present in large, irregularly shaped, ER-derived structures that may represent \"viral factories.\" The ER-derived structures required an intact cytoskeleton, and microtubules appeared to redistribute MP:GFP from these sites during late stages of infection. In leaves, MP:GFP accumulated in plasmodesmata, whereas in protoplasts, the MP:GFP was targeted to distinct, punctate sites near the plasma membrane. Treating protoplasts with cytochalasin D and brefeldin A at the time of inoculation prevented the accumulation of MP:GFP at these sites. It is proposed that the punctate sites anchor the cortical ER to plasma membrane and are related to sites at which plasmodesmata form in walled cells. Hairlike structures containing MP:GFP appeared on the surface of some of the infected protoplasts and are reminiscent of similar structures induced by other plant viruses. We present a model that postulates the role of the ER and cytoskeleton in targeting the MP and viral ribonucleoprotein from sites of virus synthesis to the plasmodesmata through which infection is spread.

Microtubules influence morphogenesis by forming distinct geometrical arrays in the cell cortex, which in turn affect the deposition of cellulose microfibrils. Although many chemical and physical factors affect microtubule orientation, it is unclear how cortical microtubules in elongating cells maintain their ordered transverse arrays and how they reorganize into new geometries. To visualize these reorientations in living cells, we constructed a microtubule reporter gene by fusing the microtubule binding domain of the mammalian microtubule-associated protein 4 (MAP4) gene with the green fluorescent protein (GFP) gene, and transient expression of the recombinant protein in epidermal cells of fava bean was induced. The reporter protein decorates microtubules in vivo and binds to microtubules in vitro. Confocal microscopy and time-course analysis of labeled cortical arrays along the outer epidermal wall revealed the lengthening, shortening, and movement of microtubules; localized microtubule reorientations; and global microtubule reorganizations. The global microtubule orientation in some cells fluctuates about the transverse axis and may be a result of a cyclic self-correcting mechanism to maintain a net transverse orientation during cellular elongation

In the highly concentrated environment of the cell, polypeptide chains are prone to aggregation during synthesis (as nascent chains await the emergence of the remainder of their folding domain), translocation, assembly, and exposure to stresses that cause previously folded proteins to unfold. A large and diverse group of proteins, known as chaperones, transiently associate with such folding intermediates to prevent aggregation, but in many cases the specific functions of individual chaperones are still not clear. In vivo, Hsp90 (heat shock protein 90) plays a role in the maturation of components of signal transduction pathways but also exhibits chaperone activity with diverse proteins in vitro, suggesting a more general function. We used a unique temperature-sensitive mutant of Hsp90 in Saccharomyces cerevisiae, which rapidly and completely loses activity on shift to high temperatures, to examine the breadth of Hsp90 functions in vivo. The data suggest that Hsp90 is not required for the de novo folding of most proteins, but it is required for a specific subset of proteins that have greater difficulty reaching their native conformations. Under conditions of stress, Hsp90 does not generally protect proteins from thermal inactivation but does enhance the rate at which a heat-damaged protein is reactivated. Thus, although Hsp90 is one of the most abundant chaperones in the cell, its in vivo functions are highly restricted

We determine the effects of the technology of obtaining potato protein preparation and of different variants of enzymatic hydrolysis on the chemical and amino acid compositions of the hydrolysates obtained. Potato protein concentrates obtained through their thermal coagulation in potato juice with calcium chloride, calcium lactate or without salt addition were subjected to enzymatic hydrolysis using two commercial hydrolytic enzymes: endopeptidase (Alcalase) and exopeptidase (Flavourzyme). Chemical (contents of ash, total and coagulable protein) and amino acid compositions of the hydrolysates obtained were determined. On the ground of the findings it was stated that the type of potato protein preparation used and conditions of enzymatic modification influenced on the properties of the hydrolysates obtained. Preparations obtained during the study were characterised by similar chemical and amino acid compositions, whereas the preparation obtained through thermal coagulation with the use of calcium lactate contained insignificantly more protein and essential amino acids. The least liable to enzymatic hydrolysis was the preparation obtained by using calcium chloride, particularly when only endopeptidase was used. The application of endopeptidase enzyme enabled to obtain 60% of proteolysis efficiency and the addition of the second enzyme (exopeptidase) to the protein solution insignificantly increased the proteolysis efficiency (to ca 70%), mainly when the preparation coagulated with the use of calcium chloride was hydrolysed. Proteolysis of the protein preparations obtained with the use of two enzymes was more favourable, particularly due to the quantity of free amino acids in and amino acids composition of the hydrolysates.

The PKC1-MPK1 pathway in yeast functions in the maintenance of cell wall integrity and in the stress response. We have identified a family of genes that are putative regulators of this pathway. WSC1, WSC2, and WSC3 encode predicted integral membrane proteins with a conserved cysteine motif and a WSC1-green fluorescence protein fusion protein localizes to the plasma membrane. Deletion of WSC results in phenotypes similar to mutants in the PKC1-MPK1 pathway and an increase in the activity of MPK1 upon a mild heat treatment is impaired in a wsc delta mutant. Genetic analysis places the function of WSC upstream of PKC1, suggesting that they play a role in its activation. We also find a genetic interaction between WSC and the RAS-cAMP pathway. The RAS-cAMP pathway is required for cell cycle progression and for the heat shock response. Overexpression of WSC suppresses the heat shock sensitivity of a strain in which RAS is hyperactivated and the heat shock sensitivity of a wsc delta strain is rescued by deletion of RAS2. The functional characteristics and cellular localization of WSC suggest that they may mediate intracellular responses to environmental stress in yeast