Endocytic pathways of pathogenic protein aggregates in neurodegenerative diseases

Endocytosis is the fundamental uptake process through which cells internalize extracellular materials and species. Neurodegenerative diseases (NDs) are characterized by a progressive accumulation of intrinsically disordered protein species, leading to neuronal death. Misfolding in many proteins leads to various NDs such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and other disorders. Despite the significance of disordered protein species in neurodegeneration, their spread between cells and the cellular uptake of extracellular species is not entirely understood. This review discusses the major internalization mechanisms of the different conformer species of these proteins and their endocytic mechanisms. We briefly introduce the broad types of endocytic mechanisms found in cells and then summarize what is known about the endocytosis of monomeric, oligomeric and aggregated conformations of tau, Aβ, α-Syn, Huntingtin, Prions, SOD1, TDP-43 and other proteins associated with neurodegeneration. We also highlight the key players involved in internalizing these disordered proteins and the several techniques and approaches to identify their endocytic mechanisms. Finally, we discuss the obstacles involved in studying the endocytosis of these protein species and the need to develop better techniques to elucidate the uptake mechanisms of a particular disordered protein species.     

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.     

Synaptic repression at crayfish neuromuscular junctions. II. Evidence for calcium involvement

The inability of synaptic junctions to generate normalsized postsynaptic potentials under normal physiological conditions was studied at crayfish neuromuscular synapses. Synaptic repression in the superficial flexor muscle system of the crayfish was induced by surgery: the nerve was cut in the middle of the target field, and the lateral muscle fibers were removed. After this surgery, the remaining medial synapses were unable to generate normal-sized junction potentials (jp) over the medial muscle population. In an attempt to study the mechanism underlying this response, we varied the extracellular calcium concentration of the Ringers solution bathing the preparation, in both repressed and control animals, while monitoring the size of the same junction potential. The junction potential generated by the spontaneous activity of the nerve increased in size with increasing calcium concentrations in control animals, but failed to do so in repressed animals, that is, changes in external calcium concentrations did not affect repressed synapses. However, in the presence of the calcium ionophore A23187, control and repressed synapses both show an increase in the junction potential sizes they generate. Our data suggest that calcium is involved in the mechanisms that underlie synaptic repression in this crustacean neuromuscular system. © 1993 John Wiley & Sons, Inc.     

Fecundity of two hillstream fishes, Garra lamta (Ham.) and Garra gotyla gotyla (gray)

The fecundity of two hillstream fishes, Garra lamta and G. gotyla gotyla, is related to their total body length (L), total body weight (W), ovary length (X) and ovary weight (V). The relationships to L, W, X and V were all linear. The correlation coefficient values (r) showed that total body length and total body weight were the best indices in fecundity estimates in both fishes.     

Evaluation of anti-inflammatory activity of Vernonia cinerea Less. extract in rats.

The methanol extract of the whole plant of Vernonia cinerea Less. was evaluated for its anti-inflammatory activity in acute (carrageenin, histamine and serotonin induced rat paw edema) and a chronic model (cotton pouch induced granuloma). The methanol extract (250 and 500 mg/kg(-1) p.o.) exhibited significant activity (p < 0.001) against all phlogistic agents used in a dose dependant manner. In the chronic model (cotton pouch granuloma method) the methanol extract exhibited significant anti-inflammatory activity. All these effects were compared with standard drug phenylbutazone (100 mg/kg(-1) p.o.).     

Primary malignant melanoma of uterine cervix: a rare entity diagnosed on fine needle aspiration cytology – report of a case

Primary malignant melanoma of uterine cervix is a rare neoplasm. Its diagnosis on cervical fine needle aspiration cytology, a first of its kind in the literature, has been reported. Although cervix is a rare site for melanoma, cytopathologists should be familiar with it and be able to diagnose this entity on cervical cytology when pigment containing tumour cells are present. In a patient with visible growth on cervix, fine needle aspiration cytology may prove to be a useful diagnostic tool, especially when cervical smear/scrape cytology is non-diagnostic.     

The diagnostic value of fine needle aspiration cytology (FNAC) in the assessment of palpable supraclavicular lymph nodes: a study of 218 cases

The aim of this study was to evaluate the diagnostic value of fine needle aspiration cytology (FNAC) in the assessment of palpable supraclavicular lymph nodes. The material was analysed in 218 cases with enlarged supraclavicular lymph nodes in which FNAC was performed by the conventional method. In all cases cytological examination was performed on-site after staining the smears by the Papanicolaou method. In addition, air-dried smears, fixed smears, filter preparations from needle washings and cell blocks were studied. The FNAC diagnosis was supported by examining cell blocks which added the reliability of histological architecture; further support was obtained by tissue biopsy and/or comparison with the primary tumour in some of the cases. Eleven cases were diagnosed as inflammatory lesions and 41 cases were unsatisfactory because of scanty/acellular samples (despite two to three repeat samplings). However, in five of these, malignant tumours were later found on biopsy, which was done for persistent enlargement of the supraclavicular lymph node(s). Fifty-three cases were diagnosed as negative for malignancy (normal cellular elements, n=15; reactive elements, n=38) and 12 cases were suspicious of malignancy. In 11 cases a diagnosis of lymphoma was made on histology and in 90 cases metastatic tumours were diagnosed. The overall sensitivity was 92.7%, specificity 98.5%, positive predictive value 97.3% and the negative predictive value was 94.8%. Based on our study we feel that FNAC of palpable supraclavicular lymph nodes as a first line of investigation is a cost-effective procedure and is not only useful in the diagnosis of various lesions but can also help in deciding on appropriate management. Furthermore, the histological architecture from cell blocks can be correlated with cytology, and such material can be used for appropriate histochemical and immunomarker studies, which can be useful in enhancing the diagnosis.     

Short communication: Protoplast formation from the thermophilic fungus Malbranchea sulfurea,using the thermostable chitinase and laminarinase of Paecilomyces varioti

Two thermostable enzymes produced by the thermophilic fungus Paecilomyces varioti, a chitinase and laminarinase, were used to isolate protoplasts of a thermophilic fungus, Malbranchea sulfurea. The frequency of protoplast regeneration observed (35%) was considerably higher than that obtained using commercial lytic enzymes.     

Genetic fingerprinting of pigeonpea [Cajanus cajan (L.) Millsp.] and its wild relatives using RAPD markers

Randomly amplified polymorphic DNA (RAPD) markers were used for the identification of pigeonpea [Cajanus cajan (L.) Millsp.] cultivars and their related wild species. The use of single primers of arbitrary nucleotide sequence resulted in the selective amplification of DNA fragments that were unique to individual accessions. The level of polymorphism among the wild species was extremely high, while little polymorphism was detected within Cajanus cajan accessions. All of the cultivars and wild species under study could be easily distinguished with the help of different primers, thereby indicating the immense potential of RAPD in the genetic fingerprinting of pigeonpea. On the basis of our data the genetic relationship between pigeonpea cultivars and its wild species could be established.NCL Communication No. 6062