Lysosomal Trafficking and Degradation of Extracellular Proteins via Multivalent Small Molecule Ligand Display on Dextran Scaffolds.

Targeted protein degradation (TPD) marks a shift in drug development from conventional inhibition to the complete removal of pathological proteins. Traditional TPD technologies target intracellular proteins of interest (POIs) for degradation but are ineffective against extracellular cell surface and soluble proteins, a significant portion of the human proteome. Recent advances involve the formation of ternary complexes between a POI and a cell surface lysosomal trafficking receptor, directing POIs to lysosomes for degradation.

CO-DELIVERY of glutamic acid-extended peptide antigen and imidazoquinoline TLR7/8 agonist via ionizable lipid nanoparticles induces protective anti-tumor immunity.

Cancer vaccines aim at generating cytotoxic CD8 T cells that kill cancer cells and confer durable tumor regression. Hereto, CD8 peptide epitopes should be presented by antigen presenting cells to CD8 T cells in lymphoid tissue. Unfortunately, in unformulated soluble form, peptide antigens are poorly taken up by antigen presenting cells and do not efficiently reach lymph nodes.

Profiling Bacteria in the Lungs of Patients with Severe Influenza Versus COVID-19 with or without Aspergillosis.

The influence of the lung bacterial microbiome, including potential pathogens, in patients with influenza-associated pulmonary aspergillosis (IAPA) or coronavirus disease (COVID-19)-associated pulmonary aspergillosis (CAPA) has yet to be explored. To explore the composition of the lung bacterial microbiome and its association with viral and fungal infection, immunity, and outcome in severe influenza versus COVID-19 with or without aspergillosis. We performed a retrospective study in mechanically ventilated patients with influenza and COVID-19 with or without invasive aspergillosis in whom BAL for bacterial culture (with or without PCR) was obtained within 2 weeks after ICU admission.

Lipid Nanoparticle Delivery Alters the Adjuvanticity of the TLR9 Agonist CpG by Innate Immune Activation in Lymphoid Tissue.

Pharmacological strategies to activate innate immune cells are of great relevance in the context of vaccine design and anticancer immune therapy, to mount broad immune responses able to clear infection and malignant cells. Synthetic CpG oligodeoxynucleotides (CpG-ODNs) are short single-stranded DNA molecules containing unmethylated CpG dinucleotides and a phosphorothioate backbone. Class B CpG ODNs activate robust innate immune responses through a TLR9-dependent NF-κB signaling pathway.

High Burden of COVID-19-Associated Pulmonary Aspergillosis in Severely Immunocompromised Patients Requiring Mechanical Ventilation.

Background: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is a frequent superinfection in critically ill patients with COVID-19 and is associated with increased mortality rates. The increasing proportion of severely immunocompromised patients with COVID-19 who require mechanical ventilation warrants research into the incidence and impact of CAPA during the vaccination era.

Methods: We performed a retrospective, monocentric, observational study.

Cell-specific distribution of oestrogen receptor-alpha in the bovine ovary.

In this study, the expression of estrogen receptor alpha (ERalpha) in the bovine ovary is described. ERalpha was visualized by immunohistochemistry on paraffin sections of ovaries obtained from 11 non-pregnant and 2 pregnant animals. In general, ERalpha was not observed in cells of primordial, primary and secondary follicles, whereas weak expression was noticed in cells of healthy and arteric tertiary follicles.

A study of the ultrastructure and staining characteristics of the 'dental star' of equine incisors.

The objective of this study was to examine the diameter, extent, orientation and contents of dentinal tubules in order to validate the hypothesis of pigment penetration into the dental star of equine incisival occlusal surfaces. The time of appearance and the configuration of the dental star on the incisival occlusal surface are macroscopically visible features that, along with other more reliable parameters, are used for the determination of horses' age. Although dental stars are an integral part of the equine incisor occlusive surface, the exact nature and microstructure of the dental star are poorly documented.

Scanning electron microscopic changes of the canine uterine luminal surface during oestrus and late metoestrus.

In this study the endometrial morphology of four dogs in oestrus and 10 dogs in late metoestrus was investigated with scanning electron microscopy. In early oestrus the cells were slightly convex with fairly long microvilli and cell boundaries that were apparent but situated on a deeper level than the cell surface. In late oestrus the cells were clearly convex with long and numerous microvilli masking the cell boundaries.

Variation in the estrogen receptor content of canine uterine tissue throughout the estrous cycle.

The estrogen receptor (ER) was visualized immunohistochemically in paraffin sections of the canine uterus using a monoclonal antibody. The ER-expression was quantified by means of an immunohistochemical score. In the uterine horns highest scores were found during proestrus and lowest scores during early metestrus.

Scanning electron microscopic study of the posterior ciliary veins in domestic ungulates.

Vascular corrosion casts of 12 equine, 15 bovine and 50 porcine eyes were studied scanning electron microscopically for the presence of posterior ciliary veins. These veins drain a postequatorial segment of the choroid and emerge near the posterior bulbar pole. They complement the four vorticose veins that emerge near or at the equatorial zone of the eyeball and the slender choroidoretinal veins that drain the peridiscal area of the choroid.

The distribution of intratubular dentine in equine incisors: a scanning electron microscopic study.

The distribution of intratubular (peritubular) dentine was studied by scanning electron microscopy in 12 equine incisor teeth. High levels of intratubular dentine were found in the peripheral regions of the dentine. In these areas, a marked asymmetry occurred, as intratubular dentine was predominantly deposited onto the side of the dentinal tubular walls nearest to the dentino-enamel junction.

The dentinal structure of equine incisors: a light and scanning electron-microscopic study.

This paper gives an anatomical overview of the dentinal structure in equine incisor teeth with special reference to the three-dimensional organization, the number and the diameter of the dentinal tubules. The spatial arrangement of equine dentine was examined by scanning electron microscopy of occlusal surfaces and longitudinally fractured teeth and by light microscopy of both decalcified and ground sections. The dentinal tubules of the peripherally situated primary dentine were directly continuous with those of the circumpulpal secondary dentine.

Tubular contents of equine dentin: a scanning electron microscopic study.

The dentinal tubules of 20 permanent equine incisors were investigated by scanning electron microscopy. Occlusal surfaces and longitudinal fracture planes of both etched and undecalcified teeth were examined. Three different types of structure were observed inside the dentinal tubular lumen.

Immunohistochemical detection of the estrogen receptor-alpha and progesterone receptor in the canine pregnant uterus and placental labyrinth.

The presence of hormone receptors is as important as the amount of hormone to predict hormone action. Therefore, the presence of estrogen receptors of the alpha subtype (ER-alpha) and progesterone receptors (PR) was evaluated in six pregnant uteri including the placenta and in three postpartum uteri of dogs. This preliminary study is part of our immunohistochemical research project on steroid hormone receptor distribution in the canine female genital tract.

Immunohistochemical detection of progesterone receptors in the canine uterus and their relation to sex steroid hormone levels.

The aim of this immunohistochemical study is to describe the normal distribution of progesterone receptors in the various cell types of the canine uterine horns, body and cervix. The results can be used for research on uterine and endocrinological pathology, since the impact of progesterone on different uterine cell types is partly determined by the receptor availability. Nuclear staining for progesterone receptors was observed in epithelial cells of the surface epithelium, glandular ducts and basal glands of the endometrium, in endometrial stroma cells and in myometrial smooth muscle cells.

Immunohistochemical detection of estrogen receptors in the canine uterus and their relation to sex steroid hormone levels.

Cyclic changes in estrogen receptor expression in the uterine tissue of 60 female dogs were evaluated, using an immunohistochemical technique on formalin-fixed paraffin-embedded sections. The expression of estrogen receptors in the uterine horns, body and cervix was quantified by means of an immunohistochemical score. A negative correlation was found between staining scores in the uterine horns and serum progesterone levels.

Age-related morphometry of equine incisors.

In the present study the age-related morphological characteristics of 948 equine incisors were investigated. After extraction, total incisival length and root length were measured at the vestibular side of the teeth. Equine incisors reach their maximal length 2-3 years after eruption.

Age determination in mini-Shetland ponies and donkeys.

The accuracy of ageing mini-Shetland ponies and donkeys was assessed by correlating the appearance of specific dental features with the known ages of 106 mini-Shetland ponies and 63 donkeys. The ages of the animals ranged between 2 days and 26 years. In both species the eruption of the deciduous and permanent incisors occurred later than in horses.

Dental wear in horses in relation to the microhardness of enamel and dentine.

The microhardness of enamel, primary dentine and secondary dentine was determined in the incisor teeth of 39 horses of three different breeds, trotter horses, Belgian draft horses and Arab horses. Using a microhardness tester fitted with a Knoop diamond indenter, the overall Knoop Hardness Number was determined for each tissue, and the influence of breed and age on the hardness were evaluated. Enamel and secondary dentine were significantly harder in Arab horses than in trotters and Belgian draft horses, but there were no significant differences between draft horses and trotter horses in the hardness of their enamel and dentine.

Histological study of the innervation of the suspensory ligament of the forelimb of the horse.

The innervation pattern of the interosseus muscle of the forelimb was studied in two ponies and two horses. The nerves of the suspensory ligament were studied histologically after neurectomy of the ulnar and median nerve branches proximal to the carpal joint. The results demonstrated that the interosseus muscle is innervated by the deep branch of the lateral palmar nerve which emerges at the level of the midcarpal region and contains fibres from the ulnar and the median nerve.

Ageing Arab horses by their dentition.

The dentition of 170 Arab horses of known ages was examined and compared with the dental characteristics of trotter horses and Belgian draft horses of the same ages. The results indicated that inaccuracies in the determination of the age of horses by their dentition may result, at least partly, from differences between the breeds of horse involved because there were some major differences between the three breeds examined. These differences increased as the horses' true age increased.

Ageing draft and trotter horses by their dentition.

The accuracy of ageing horses by their dentition was assessed by comparing the dental features with the known dates of birth of 212 trotter horses and 189 Belgian draft horses. The horses ranged in age from two to 25 years. In both breeds it was observed that the shedding of the incisors and the appearance of the dental stars were the most reliable features for age determination.

Comparative morphology of the pectinate ligaments of domestic mammals, as observed under the dissecting microscope and the scanning electron microscope.

The pectinate ligaments of ten horses, two donkeys, five oxen, five sheep, ten goats, five dogs, five cats, thirty pigs and two rabbits were studied under the stereomicroscope and the scanning electron microscope. In the horse and the donkey, the pectinate ligament was very prominent and was characterized by sturdy interconnected strands and relatively small intertrabecular spaces. The pectinate ligaments of ruminants were composed of shorter strands, separated by relatively larger spaces.

Anatomy of the ocular arteries in the horse.

Orbital and intrabulbar arteries were studied in 20 equine eyes by means of latex injections and methylmethacrylate casts. The orbital branches of the external ophthalmic artery arise far caudal to the posterior pole of the eyeball and present a variable topographic arrangement. The intrabulbar arteries are supplied by ciliary and choroidoretinal arteries.