The Lys 280 → Gln mutation mimicking disease‐linked acetylation of Lys 280 in tau extends the structural core of fibrils and modulates their catalytic properties

Amyloid fibrillar aggregates isolated from the brains of patients with neurodegenerative diseases invariably have post‐translational modifications (PTMs). The roles that PTMs play in modulating the structures and polymorphism of amyloid aggregates, and hence their ability to catalyze the conversion of monomeric protein to their fibrillar structure is, however, poorly understood. This is particularly true in the case of tau aggregates, where specific folds of fibrillar tau have been implicated in specific tauopathies. Several PTMs, including acetylation at Lys 280, increase aggregation of tau in the brain, and increase neurodegeneration. In this study, tau‐K18 K280Q, in which the Lys 280 → Gln mutation is used to mimic acetylation at Lys 280, is shown, using HX‐MS measurements, to form fibrils with a structural core that is longer than that of tau‐K18 fibrils. Measurements of critical concentrations show that the binding affinity of monomeric tau‐K18 for its fibrillar counterpart is only marginally more than that of monomeric tau‐K18 K280Q for its fibrillar counterpart. Quantitative analysis of the kinetics of seeded aggregation, using a simple Michaelis–Menten‐like model, in which the monomer first binds and then undergoes conformational conversion to β‐strand, shows that the fibrils of tau‐K18 K280Q convert monomeric protein more slowly than do fibrils of tau‐K18. In contrast, monomeric tau‐K18 K280Q is converted faster to fibrils than is monomeric tau‐K18. Thus, the effect of Lys 280 acetylation on tau aggregate propagation in brain cells is expected to depend on the amount of acetylated tau present, and on whether the propagating seed is acetylated at Lys 280 or not.     

Cleavage of the PO glycoprotein of the rat peripheral nerve myelin: Tentative identification of cleavage site and evidence for the precursor-product relationship

The incubation of sciatic nerve slices in Krebs Ringer bicarbonate (KRB) buffer (pH 7.4) at 37°C, or the incubation of freshly isolated myelin in ammonium bicarbonate buffer (pH 8), resulted in the generation of a 24kDa protein with a concomitant decrease of PO protein. The conversion of PO into 24kDa protein was blocked by heating isolated myelin at 100°C for 5 min suggesting that the reaction is enzyme mediated. Inclusion of the protease inhibitors and chelating agent to isolated myelin did not prevent the formation of 24kDa protein. Similarly, addition of CaCl₂ to isolated myelin did not accentuate the formation of 24kDa protein suggesting that the conversion of PO into 24kDa protein may not be due to Ca²⁺ activated protease. It is postulated that the formation of 24kDa protein may be due to neutral protease and/or metalloproteinase associated with the PNS myelin. 24kDa protein was purified and characterized. The N-terminal sequence of 1–17 amino acid residues of 24kDa protein was identical to PO. 24kDa protein was immunostained and immunoprecipitated with anti-PO antiserum indicating the immunological similarities between PO and 24kDa protein. Labeling of 24kDa protein with [³⁵S]methionine provided evidence that PO may be in all probability cleaved between Met-168 and Met-193. Further studies were carried out to demonstrate that 24kDa protein was phosphorylated, glycosylated and acylated like PO. Phosphorylation of 24kDa protein in the nerve slices was increased five-fold by phorbol esters and phosphoserine was the only phosphoamino acid identified after partial acid hydrolysis of 24kDa protein. These results suggested that serine residue phosphorylated by protein kinase C may be located in amino acid residues 1-168. 24kDa protein was stained with periodic Schiff reagent. In addition, 24kDa protein was fucosylated and the fucosylation of 24kDa protein was inhibited (70%) by tunicamycin, providing evidence that it is N-glycosylated. Recently, it was demonstrated that both PO and 24kDa protein were fatty acylated with [³H]palmitic acid in the nerve slices and fatty acids are covalently linked to these proteins (Agrawal, H.C. and Agrawal, D. 1989, Biochem. J. 263:173–177). The time course of inhibition of acylation by cycloheximide of 24kDa protein was identical to PO. Cycloheximide inhibited acylation of PO and 24kDa protein by 61% and 58% respectively, whereas, monensin had little affect on the fatty acylation of these proteins. Less [³H]palmitic acid and¹⁴C-amino acids were incorporated into 24kDa protein when compared to PO between 5–30 min after incubation of the nerve slices. However, more radioactivity was incorporated into 24kDa protein after 60 min when compared to PO under identical conditions. These results provided evidence of a precursor-product relationship between PO and 24kDa protein. Therefore, PO may be cleaved into 24kDa protein in the myelin membrane following its acylation and glycosylation in the Schwann cells.     

New and Known Species of Pratylenchus Filipjev, 1936 (Nematoda: Pratylenchidae) from Haryana,India, with Remarks on Intraspecific Variations

Two new monosexual and one bisexual species Pratylenchus Filipjev, 1936 collected from Haryana state of India are described and illustrated. The primary distinguishing features of these species are Pratylenchus microstylus n. sp.: L = 331-458 μm, spear = 11 or 12 μm; Pratylenchus cruciferus n. sp.: L = 648-793 μm, central core of lateral fields with oblique lines, hemizonid 2-8 annules anterior to excretory pore; Pratylenchus ekrami n. sp.: spear = 11-13 μm, spermatheca oblong, post vulval uterine sac with differentiated cells, tail with 26-40 annules, males abundant. Studies on intraspecific variations of P. cruciferus, P. ekrami, and P. coffeae (Zimmermann, 1898) Goodey, 1951 revealed that spear length and value of ''V'' are the least variable characters. Body length and size of post vulval uterine sac varies to varying degrees in different species. Shape of median bulb in P. ekrami, number of incisures in P. coffeae, and tail shape in P. ekrami and P. coffeae exhibit the greatest amount of intraspecific variations. P. zeae Graham, 1936 and P. thornei Sher & Allen, 1953 are the other species collected during the present studies.     

Translocation t(22;22)(p11.1;q11.1) and NOR studies in a female with a history of repeated fetal loss.

A 32-year-old phenotypic female with a history of nine consecutive abortions each in the first trimester was referred for cytogenetic studies. She was found to have 45,XX,t(22;22) (p11.1;q11.1) chromosomal pattern. The Ag-NOR banding technique showed that the NORs of both the acrocentrics involved in the translocation were deleted and the loss suffered from the elimination was compensated by the increased NOR activity as well as presence of dNOR on other acrocentric chromosomes.     

Crystallographic,morphological and photoluminescent investigations of Tb3+-doped YAlO3 perovskites for lighting applications

Terbium(III)-doped yttrium aluminate perovskite (YAP:xTb³⁺) (x = 0.01–0.08 mol) was synthesized using a simple gel-combustion method. Structural elucidations were performed using X-ray diffraction (XRD) and Rietveld analysis. Fourier-transform infrared spectral studies validated the efficient synthesis of designed doped samples. Transmission electron microscopic images showed the agglomerated irregular dimensions of the synthesized nanocrystalline materials. When excited at 251 nm, a strong emissive line attributed to ⁵D₄ → ⁷F₅ electronic transition was observed at 545 nm (green emission). The maximum luminescence was found at the optimized concentration (0.05 mol) of Tb³⁺ ions; this emission was quenched by dipolar–dipolar (d–d) interactions. Chromaticity (x and y) and correlated colour temperature parameters were obtained by analysing the emission profiles. Finally, the colour coordinates of nanophosphors were closer to the National Television Standards Committee green coordinates, which replicates their potency in the design and architecture of R-G-B-based white LEDs.     

Eocyzicus spinifer sp. nov. (Conchostraca: Cyzicidae) from Iraq

A new Conchostracan species, Eocyzicus spinifer from Iraq is described. A table is given to distinguish the known species of the genus Eocyzicus.     

The human–primate interface in the New Normal: Challenges and opportunities for primatologists in the COVID-19 era and beyond

The emergence of SARS-CoV-2 in late 2019 and human responses to the resulting COVID-19 pandemic in early 2020 have rapidly changed many aspects of human behavior, including our interactions with wildlife. In this commentary, we identify challenges and opportunities at human–primate interfaces in light of COVID-19, focusing on examples from Asia, and make recommendations for researchers working with wild primates to reduce zoonosis risk and leverage research opportunities. First, we briefly review the evidence for zoonotic origins of SARS-CoV-2 and discuss risks of zoonosis at the human–primate interface. We then identify challenges that the pandemic has caused for primates, including reduced nutrition, increased intraspecific competition, and increased poaching risk, as well as challenges facing primatologists, including lost research opportunities. Subsequently, we highlight opportunities arising from pandemic-related lockdowns and public health messaging, including opportunities to reduce the intensity of problematic human–primate interfaces, opportunities to reduce the risk of zoonosis between humans and primates, opportunities to reduce legal and illegal trade in primates, new opportunities for research on human–primate interfaces, and opportunities for community education. Finally, we recommend specific actions that primatologists should take to reduce contact and aggression between humans and primates, to reduce demand for primates as pets, to reduce risks of zoonosis in the context of field research, and to improve understanding of human–primate interfaces. Reducing the risk of zoonosis and promoting the well-being of humans and primates at our interfaces will require substantial changes from “business as usual.” We encourage primatologists to help lead the way.     

Dhanwantaram kashayam,an Ayurvedic polyherbal formulation,reduces oxidative radicals and reverts lipids profile towards normal in diabetic rats

BackgroundHyperglycemia and hyper oxidative stress are indicators of diabetes mellitus which is also accompanied with decreased levels of antioxidant enzymes. While oxidative stress is important in increasing insulin secretion and controlling blood sugar level at the same time excess oxidative stress leads to the destruction of beta cells of pancreas resulting in to low insulin production and hyperglycemia. A balance between the levels of oxidative radicals and insulin production is needed, but is not defined yet. Hyperglycemia also leads to hyperlipidemia which can contribute to various health conditions like cardiovascular diseases.ObjectivesThis study was designed to study the oxidative stress and lipid levels in diabetic rats. This also was designed to elucidate the effect of Dhanwantaram Kashayam, an Ayurvedic polyphenolic derived from plants on lipid metabolism and oxidative radical scavenging in diabetic rats.MethodsRats were made diabetic by injecting streptozotocin. Different enzymes involved in oxidative radical scavenging and lipid profiles including triglycerides, total cholesterol, free fatty acids and phospholipids were estimated using standard methods reported elsewhere.ResultsLevel of antioxidant enzymes were lower in diabetic rats compared to normal controls. Administration of Dhanwantaram Kashayam restored the enzyme activity as well as reduced levels of different lipids in diabetic rats.ConclusionsAdministration of Dhanwantaram Kashayam increased the activity levels of antioxidant enzymes and reduced the levels of total cholesterol, phospholipids and triglycerides. The results of this study point to the possibility of developing Dhanwantaram Kashayam as a dietary supplement which can alleviate the complications associated with diabetes or prevent them altogether.