Role of Melatonin and the Biological Clock in Regulating Lactation in Seasonal Sheep

Impact of light on animal behavior has been known for a long time—from 1925, Rowan [30] showed that lighting conditions influence gonad activity in birds and the related processes are controlled not only by means of intraorganic signals. Studies carried out in subsequent years have established that, also in mammals, the gland reacting to changes in light conditions is the pineal gland, producing a substance called melatonin. Biosynthesis of melatonin in most animals studied to date occurs at a rhythm dependent on the photocycle. The highest concentrations of this hormone—often called “the hormone of darkness”—are recorded at night. Seasonal changes in melatonin secretion conditioned by activity of the biological clock, known also as “biochemical calendar”, are the key signals in the annual reproductive cycles of animals exhibiting seasonality of reproduction. Seasonality in sheep refers not only to the reproduction itself but also to lactation. One of the main hormones conditioning initiation and maintenance of lactation, synthesis of milk proteins, fat and immunoglobulins is prolactin (PRL), secreted primarily by lactotrophic cells in the adenohypophysis. Prolactin is also produced locally by the mammary gland—the hormone of this origin is identical to prolactin secreted by the pituitary gland. Until now, it was considered that the level of milk production in mammals is determined by both genetic and environmental factors. However, in recent years, many studies focused on the role of light as a modulator of prolactin levels. In livestock, changes in light-period length play a very important role as this determines their productivity and milk yield. Photoperiod is particularly important in short-day breeder animals (sheep), for which the length of light period is associated with changes in melatonin level. The modulating effect of melatonin on secretion of prolactin may take place via two different mechanisms. One is associated with the circadian rhythm, wherein—directly or through the medium of a factor popularly termed “tuberalin”—melatonin stimulates the release of prolactin. However, this effect is short-lived and is most likely applicable only to prolactin stored in lactotrophic cells of the pituitary. The second mechanism regulating the secretion of melatonin and prolactin is associated with the annual rhythms of secretion—melatonin, due to its lipophilic characteristics, has a direct effect on the secretion of prolactin. Under natural conditions, the maximum concentration of prolactin in the blood of sheep is observed over the long-day period, during which the melatonin level decreases. The lowest prolactin concentration is observed over the short-day period, where melatonin levels are at their highest. Changes in secretion of prolactin during lactation in sheep undoubtedly affect the amount of milk produced

Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation

Hearing loss caused by the death of cochlear hair cells (HCs) might be restored through regeneration from supporting cells (SCs) via dedifferentiation and proliferation, as observed in birds. In a previous report, ERBB2 activation in a subset of cochlear SCs promoted widespread down-regulation of SOX2 in neighboring cells, proliferation, and the differentiation of HC-like cells. Here we analyze single cell transcriptomes from neonatal mouse cochlear SCs with activated ERBB2, with the goal of identifying potential secreted effectors. ERBB2 induction in vivo generated a new population of cells with de novo expression of a gene network. Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs), these ligands and their regulators can alter NOTCH signaling and promote cell survival, proliferation, and differentiation in other systems. We validated mRNA expression of network members, and then extended our analysis to older stages. ERBB2 signaling in young adult SCs also promoted protein expression of gene network members. Furthermore, we found proliferating cochlear cell aggregates in the organ of Corti. Our results suggest that ectopic activation of ERBB2 signaling in cochlear SCs can alter the microenvironment, promoting proliferation and cell rearrangements. Together these results suggest a novel mechanism for inducing stem cell-like activity in the adult mammalian cochlea

Effect of long-term proton pump inhibitor therapy on complete blood count parameters and selected trace elements : a pilot study

Introduction: Proton pump inhibitors (PPIs) are widely prescribed for several gastrointestinal conditions, often as long-term therapy. The effects of long-term PPI use have not been fully elucidated. Objectives: We aimed to determine the association between long-term PPI use and complete blood count parameters, particularly red blood cell (RBC) count, white blood cell (WBC) count, and hemoglobin concentrations, as well as serum levels of selected micronutrients such as selenium (Se), iron (Fe), copper (Cu), and zinc (Zn). Patients and methods: We enrolled 37 patients on long-term PPI therapy (mean [SD] age, 57.1 [15.4] years) and 30 healthy controls (mean [SD] age, 39.3 [11.8] years). In each group, complete blood count, and serum Fe levels were performed, and serum Cu, Zn, and Se levels were measured using atomic absorption spectrometry. Results: Red blood cell and WBC counts were lower in the PPI group compared with controls (mean [SD], 4.24 [0.55]×106/μl vs 4.7 [0.4]×106/μl; P <0.001 and 6.13 [1.44]×103/μl vs 7.3 [1.28]×103/μl; P <0.001, respectively). Hemoglobin and serum Fe concentrations were also lower in the PPI group (mean [SD], 12.5 [1.8] g/dl vs 14.3 [0.8] g/dl; P <0.001 and 16.3 [5.4] μmol/l vs 23.4 [2.7] μmol/l; P <0.001, respectively). Serum Zn and Cu concentrations were higher in PPI users than in controls. Conclusions: Long-term PPI therapy may reduce RBC and WBC counts as well as hemoglobin levels, leading to iron deficiency. It may also affect concentrations of some micronutrients, although the underlying mechanism of this association is not fully clear

Increased central auditory gain in 5xFAD Alzheimer’s disease mice as an early biomarker candidate for Alzheimer’s disease diagnosis

Alzheimer’s Disease (AD) is a neurodegenerative illness without a cure. All current therapies require an accurate diagnosis and staging of AD to ensure appropriate care. Central auditory processing disorders (CAPDs) and hearing loss have been associated with AD, and may precede the onset of Alzheimer’s dementia. Therefore, CAPD is a possible biomarker candidate for AD diagnosis. However, little is known about how CAPD and AD pathological changes are correlated. In the present study, we investigated auditory changes in AD using transgenic amyloidosis mouse models. AD mouse models were bred to a mouse strain commonly used for auditory experiments, to compensate for the recessive accelerated hearing loss on the parent background. Auditory brainstem response (ABR) recordings revealed significant hearing loss, a reduced ABR wave I amplitude, and increased central gain in 5xFAD mice. In comparison, these effects were milder or reversed in APP/PS1 mice. Longitudinal analyses revealed that in 5xFAD mice, central gain increase preceded ABR wave I amplitude reduction and hearing loss, suggesting that it may originate from lesions in the central nervous system rather than the peripheral loss. Pharmacologically facilitating cholinergic signaling with donepezil reversed the central gain in 5xFAD mice. After the central gain increased, aging 5xFAD mice developed deficits for hearing sound pips in the presence of noise, consistent with CAPD-like symptoms of AD patients. Histological analysis revealed that amyloid plaques were deposited in the auditory cortex of both mouse strains. However, in 5xFAD but not APP/PS1 mice, plaque was observed in the upper auditory brainstem, specifically the inferior colliculus (IC) and the medial geniculate body (MGB). This plaque distribution parallels histological findings from human subjects with AD and correlates in age with central gain increase. Overall, we conclude that auditory alterations in amyloidosis mouse models correlate with amyloid deposits in the auditory brainstem and may be reversed initially through enhanced cholinergic signaling. The alteration of ABR recording related to the increase in central gain prior to AD-related hearing disorders suggests that it could potentially be used as an early biomarker of AD diagnosis

The ICNP® terms cross-mapping on the example of nursing care of patient with rheumatoid arthritis

Introduction. Infectious mononucleosis is a disease caused by the Ebstein-Barr virus (EBV) belonging to the Herpes virus group. It causes infections in all age groups, most often in young children, adolescents and young adults. Symptoms include pharyngitis, fever and enlarged lymph nodes. There is a proven link between EBV infection and malignant tumors. Mononucleosis diagnosis is based on the laboratory tests (full blood count) and transaminases. The aim. The aim of the study was to present a nursing care plan for a child with infectious mononucleosis using classic terminology and concepts from ICNP®. Materials and methods. The work uses the method of literature analysis devoted to the issues of child care with infectious mononucleosis and the case study. The terms describing nursing practice were taken from the ICNP® dictionary. Results and conclusions. The care plan presented is an example of the ICNP® classification use for the needs of nursing practice documentation.Wstęp. Mononukleoza zakaźna jest chorobą wywoływaną przez wirus Ebsteina-Barr (EBV) należącego do grupy wirusów Herpes. Wywołuje zakażenia w każdej grupie wiekowej, najczęściej u małych dzieci, nastolatków i młodych dorosłych. Objawy charakterystyczne to zapalenie gardła, gorączka i limfadenopatia. Udowodniono także związek pomiędzy zakażeniem EBV a nowotworami złośliwymi. Mononukleozę diagnozuje się na podstawie morfologii krwi obwodowej z rozmazem i aktywności aminotransferaz. Cel. Celem pracy było zaprezentowanie planu opieki pielęgniarskiej nad dzieckiem z mononukleozą zakaźną z zastosowaniem klasycznej terminologii oraz pojęć z ICNP®. Materiały i metody. W pracy wykorzystano metodę analizy literatury poświęconej zagadnieniom opieki nad dziećmi z mononukleozą zakaźną oraz metodę studium przypadku. Terminy opisujące praktykę pielęgniarską zaczerpnięto ze słownika ICNP®. Podsumowanie. Zaprezentowany w pracy plan opieki stanowi propozycję korzystania z klasyfikacji ICNP® dla potrzeb dokumentowania praktyki pielęgniarskiej

Acetylation regulates DNA repair mechanisms in human cells

The p300-mediated acetylation of enzymes involved in DNA repair and replication has been previously shown to stimulate or inhibit their activities in reconstituted systems. To explore the role of acetylation on DNA repair in cells we constructed plasmid substrates carrying inactivating damages in the EGFP reporter gene, which should be repaired in cells through DNA mismatch repair (MMR) or base excision repair (BER) mechanisms. We analyzed efficiency of repair within these plasmid substrates in cells exposed to deacetylase and acetyltransferase inhibitors, and also in cells deficient in p300 acetyltransferase. Our results indicate that protein acetylation improves DNA mismatch repair in MMR-proficient HeLa cells and also in MMR-deficient HCT116 cells. Moreover, results suggest that stimulated repair of mismatches in MMR-deficient HCT116 cells is done though a strand-displacement synthesis mechanism described previously for Okazaki fragments maturation and also for the EXOI-independent pathway of MMR. Loss of p300 reduced repair of mismatches in MMR-deficient cells, but did not have evident effects on BER mechanisms, including the long patch BER pathway. Hypoacetylation of the cells in the presence of acetyltransferase inhibitor, garcinol generally reduced efficiency of BER of 8-oxoG damage, indicating that some steps in the pathway are stimulated by acetylation