Fatal perinatal sarcocystosis in a lamb

A 3-wk-old lamb died because of neurological disease. The predominant microscopic lesions were in the brain and spinal cord and consisted of nonsuppurative encephalomyelitis with severe gliosis throughout the gray and white matter. Immature and mature schizonts, 15.7 x 10.6 microns (8-30 x 6-18 microns), occurred in capillaries and were structurally similar to those of Sarcocystis tenella.     

Expression of Mitochondrial Regulators PGC1α and TFAM as Putative Markers of Subtype and Chemoresistance in Epithelial Ovarian Carcinoma

Epithelial ovarian carcinoma (EOC), the major cause of gynaecological cancer death, is a heterogeneous disease classified into five subtypes. Each subtype has distinct clinical characteristics and is associated with different genetic risk factors and molecular events, but all are treated with surgery and platinum/taxane regimes. Tumour progression and chemoresistance is generally associated with major metabolic alterations, notably altered mitochondrial function(s). Here, we report for the first time that the expression of the mitochondrial regulators PGC1α and TFAM varies between EOC subtypes; furthermore, we have identified a profile in clear-cell carcinoma consisting of undetectability of PGC1α/TFAM, and low ERα/Ki-67. By contrast, high-grade serous carcinomas were characterised by a converse state of PGC1α/TFAM, ERα positivity and a high Ki-67 index. Interestingly, loss of PGC1α/TFAM and ERα was found also in a non-clear cell EOC cell line made highly resistant to platinum in vitro. Similar to clear-cell carcinomas, these resistant cells also showed accumulation of glycogen. Altogether, our data provide mechanistic insights into the chemoresistant nature of ovarian clear-cell carcinomas. Furthermore, these findings corroborate the need to take into account the diversity of EOC and to develop subtype specific treatment strategies.     

Optimized linker sequences for the expression of monomeric and dimeric bispecific single-chain diabodies.

Bispecific single-chain diabodies (scDb) consist of the variable heavy and light chain domains of two antibodies connected by three linkers. The structure of an scDb in the V(H)-V(L) orientation is V(H)A-linkerA-V(L)B-linkerM-V(H)B-linkerB-V(L)A, with linkers A and B routinely chosen to be 5-6 residues and linker M 15-20 residues. Here, we applied display of scDb on filamentous phage to analyse the composition of optimal linker sequences. The three linkers were randomized in length and sequence using degenerated triplets coding for only six hydrophilic or aliphatic amino acids (Thr, Ser, Asp, Asn, Gly, Ala). Antigen-binding clones were then isolated by one to two rounds of selection on the two different antigens recognized by the bispecific scDb. Using an scDb directed against carcinoembryonic antigen (CEA) and beta-galactosidase (Gal), we found that monomeric scDb had a preferred length of 15 or more amino acid residues for the middle linker M and of 3-6 residues for the linkers A and B. No obvious bias towards a preferred linker sequence was observed. Reduction of the middle linker below 13 residues led to the formation of dimeric scDb, which most likely results from interchain pairing between all the V(H) and V(L) domains. Dimeric scDb were also formed by fragments possessing a long linker M and linkers A and B of 0 or 1 residue. We assume that these dimeric scDb are formed by intrachain pairing of the central variable domains and interchain pairing of the flanking variable domains. Thus, the latter molecules represent a novel format of bispecific and tetravalent molecules. The described strategy allows for the isolation of both optimized and minimal linker sequences for the assembly of monomeric or dimeric single-chain diabodies.     

Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs

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Biochemical applications of a synchronously pumped krypton ion dye laser fluorescence system.

A synchronously pumped krypton ion dye laser fluorescence system is shown to provide tunable, polarized, subnanosecond pulses at high repetition rates, modest peak powers, and low energy. Such a source is uniquely suited to fluorescence investigations of biochemical mechanisms. Applications of this fluorescence excitation source to analysis, life-time determination, and depolarization effects are discussed.     

The effects of androgens on the β-glands of the tokay (Gekko gecko): Modification of an hypothesis

Study of the posterior abdominal epidermis in hypophysectomized/thyroidectomized male and female tokays following surgery, and subsequent androgen therapy, indicates that, contrary to a previous model, all aspects of β-gland differentiation are under direct androgenic control. On the other hand, another epidermal specialization, the digital foot-pad, shows a pattern of histogenesis directly comparable to that of β-glands, but is unaffected by androgens. These data are discussed with respect to the evolution of glandular epidermal specializations in gekkonid lizards and the possible role of androgens in modifying the control of cell differentiation in lizard epidermis.